Women's Health

NEW ORLEANS — Postmenopausal women with osteoporosis may not be receiving all the recommended tests to rule out secondary causes of bone loss prior to treatment initiation, new research found.

In a single-center chart review of 150 postmenopausal women who had been diagnosed and treated for osteoporosis, most had received a complete blood cell count, basic metabolic panel, thyroid screening, and vitamin D testing. However, one in four had not been tested for a parathyroid hormone (PTH) level, and in nearly two thirds, a 24-hour urine calcium collection had not been ordered.

Overall, less than a third had received the complete workup for secondary osteoporosis causes as recommended by the American Association of Clinical Endocrinologists (AACE) and the Endocrine Society.

“An appropriate evaluation for secondary causes of osteoporosis is essential because it impacts different treatment options and modalities. We discovered low rates of complete testing for secondary causes of osteoporosis in our patient population prior to treatment initiation,” said Kajol Manglani, MD, an internal medicine resident at Georgetown University/MedStar Washington Hospital Center, Washington, DC, and colleagues, in a poster at the American Association of Clinical Endocrinology (AACE) annual meeting held on May 9-12, 2024.

First author Sheetal Bulchandani, MD, said in an interview, “It depends a lot on clinical judgment, but there are certain things that everybody with osteoporosis should be evaluated for. We looked for the things that all the guidelines recommend.”

Studies have suggested that up to 30% of postmenopausal women with osteoporosis have secondary causes, noted Dr. Bulchandani, who conducted the study as a postdoctoral fellow with colleagues at Georgetown University/MedStar Washington Hospital and is now in private endocrine practice in Petersburg, Virginia.

“It’s important not to assume that every woman who walks in with osteoporosis has postmenopausal osteoporosis. I think it would be appropriate to at least discuss with the patients what would warrant certain kinds of clinical workup. … If you don’t figure out if there is an underlying cause, you may end up using an unnecessary medication,” Dr. Bulchandani said.
 

Are You Missing Something Treatable?

For example, she said, if the patient has underlying hyperparathyroidism and is treated with osteoporosis medications, “you might not see the desired or expected outcome in their bone density.”

Asked to comment, Rachel Pessah-Pollack, MD, clinical associate professor at the Holman Division of Endocrinology, Diabetes, and Metabolism at New York University School of Medicine, New York City, told this news organization, “Certainly, if you have patients who have osteoporosis, it’s important to take a good history and consider secondary causes of bone loss because you may find a treatable etiology that actually can improve their bone density without even starting on a medication.”

Dr. Pessah-Pollack, who was an author of the 2020 AACE/American College of Endocrinology 2020 Clinical Practice Guidelines for the Diagnosis and Treatment of Osteoporosis, said a 24-hour urine calcium collection, not a spot calcium check, is “super important because you’re looking to see if there’s any evidence of hypercalciuria or malabsorption that may be associated with higher rates of bone loss. … These may be a little more cumbersome and harder to get patients to do and more logistics to arrange. But clearly, if you pick up hypercalciuria, that is a potentially treatable etiology and can improve bone density as well.”

Another example, Dr. Pessah-Pollack said, is “if they have a low serum calcium level and high PTH, that would be a real reason to look for celiac disease. By not getting that PTH level, you may be missing that potential diagnosis. There is a wide range of additional causes of osteoporosis ranging from common conditions such as hyperthyroidism to rare conditions such as Cushing disease.”
 

Differences in Ordering Found Across Specialties

The 150 postmenopausal women were all receiving treatment with either alendronate, denosumab, or zoledronic acid. Their average age was 64.7 years, and 63% were seeing an endocrinologist.

Complete workups as per AACE and Endocrine Society guidelines had been performed in just 28% of those who saw an endocrinologist and 12.5% of patients seen by a rheumatologist, in contrast to 84% of those who saw the head of the hospital’s fracture prevention program.

Overall, across all specialties, just 28.67% had the complete recommended workup for secondary osteoporosis causes.

The most missed test was a 24-hour urine calcium collection, ordered for just 38% of the patients, while PTH was ordered for 73% and phosphorus for 80%. The rest were more commonly ordered: Thyroid-stimulating hormone level for 92.7%, complete blood cell count for 91.3%, basic metabolic panel for 100%, and vitamin D level for 96%.

The high rate of vitamin D testing is noteworthy, Dr. Pessah-Pollack said. “The fact that 96% of women are having vitamin D levels checked as part of an osteoporosis evaluation means that everybody’s aware about vitamin D deficiency, and people want to know what their vitamin D levels are. … That’s good because we want to identify vitamin D deficiency in our osteoporosis patients.”

But the low rate of complete secondary screening even by endocrinologists is concerning. “I look at this study as an opportunity for education that we can reinforce the importance of a secondary evaluation for our osteoporosis patients and really tailor which additional tests should be ordered for the individual patient,” Dr. Pessah-Pollack said.

In the poster, Dr. Bulchandani and colleagues wrote, “Further intervention will be aimed to ensure physicians undertake adequate evaluation before considering further treatment directions.” Possibilities that have been discussed include electronic health record alerts and educational materials for primary care providers, she told this news organization.

Dr. Manglani and Dr. Bulchandani had no disclosures. Dr. Pessah-Pollack is an advisor for Boehringer Ingelheim and Eli Lilly.

A version of this article appeared on Medscape.com.

NEW ORLEANS — Postmenopausal women with osteoporosis may not be receiving all the recommended tests to rule out secondary causes of bone loss prior to treatment initiation, new research found.

In a single-center chart review of 150 postmenopausal women who had been diagnosed and treated for osteoporosis, most had received a complete blood cell count, basic metabolic panel, thyroid screening, and vitamin D testing. However, one in four had not been tested for a parathyroid hormone (PTH) level, and in nearly two thirds, a 24-hour urine calcium collection had not been ordered.

Overall, less than a third had received the complete workup for secondary osteoporosis causes as recommended by the American Association of Clinical Endocrinologists (AACE) and the Endocrine Society.

“An appropriate evaluation for secondary causes of osteoporosis is essential because it impacts different treatment options and modalities. We discovered low rates of complete testing for secondary causes of osteoporosis in our patient population prior to treatment initiation,” said Kajol Manglani, MD, an internal medicine resident at Georgetown University/MedStar Washington Hospital Center, Washington, DC, and colleagues, in a poster at the American Association of Clinical Endocrinology (AACE) annual meeting held on May 9-12, 2024.

First author Sheetal Bulchandani, MD, said in an interview, “It depends a lot on clinical judgment, but there are certain things that everybody with osteoporosis should be evaluated for. We looked for the things that all the guidelines recommend.”

Studies have suggested that up to 30% of postmenopausal women with osteoporosis have secondary causes, noted Dr. Bulchandani, who conducted the study as a postdoctoral fellow with colleagues at Georgetown University/MedStar Washington Hospital and is now in private endocrine practice in Petersburg, Virginia.

“It’s important not to assume that every woman who walks in with osteoporosis has postmenopausal osteoporosis. I think it would be appropriate to at least discuss with the patients what would warrant certain kinds of clinical workup. … If you don’t figure out if there is an underlying cause, you may end up using an unnecessary medication,” Dr. Bulchandani said.
 

Are You Missing Something Treatable?

For example, she said, if the patient has underlying hyperparathyroidism and is treated with osteoporosis medications, “you might not see the desired or expected outcome in their bone density.”

Asked to comment, Rachel Pessah-Pollack, MD, clinical associate professor at the Holman Division of Endocrinology, Diabetes, and Metabolism at New York University School of Medicine, New York City, told this news organization, “Certainly, if you have patients who have osteoporosis, it’s important to take a good history and consider secondary causes of bone loss because you may find a treatable etiology that actually can improve their bone density without even starting on a medication.”

Dr. Pessah-Pollack, who was an author of the 2020 AACE/American College of Endocrinology 2020 Clinical Practice Guidelines for the Diagnosis and Treatment of Osteoporosis, said a 24-hour urine calcium collection, not a spot calcium check, is “super important because you’re looking to see if there’s any evidence of hypercalciuria or malabsorption that may be associated with higher rates of bone loss. … These may be a little more cumbersome and harder to get patients to do and more logistics to arrange. But clearly, if you pick up hypercalciuria, that is a potentially treatable etiology and can improve bone density as well.”

Another example, Dr. Pessah-Pollack said, is “if they have a low serum calcium level and high PTH, that would be a real reason to look for celiac disease. By not getting that PTH level, you may be missing that potential diagnosis. There is a wide range of additional causes of osteoporosis ranging from common conditions such as hyperthyroidism to rare conditions such as Cushing disease.”
 

Differences in Ordering Found Across Specialties

The 150 postmenopausal women were all receiving treatment with either alendronate, denosumab, or zoledronic acid. Their average age was 64.7 years, and 63% were seeing an endocrinologist.

Complete workups as per AACE and Endocrine Society guidelines had been performed in just 28% of those who saw an endocrinologist and 12.5% of patients seen by a rheumatologist, in contrast to 84% of those who saw the head of the hospital’s fracture prevention program.

Overall, across all specialties, just 28.67% had the complete recommended workup for secondary osteoporosis causes.

The most missed test was a 24-hour urine calcium collection, ordered for just 38% of the patients, while PTH was ordered for 73% and phosphorus for 80%. The rest were more commonly ordered: Thyroid-stimulating hormone level for 92.7%, complete blood cell count for 91.3%, basic metabolic panel for 100%, and vitamin D level for 96%.

The high rate of vitamin D testing is noteworthy, Dr. Pessah-Pollack said. “The fact that 96% of women are having vitamin D levels checked as part of an osteoporosis evaluation means that everybody’s aware about vitamin D deficiency, and people want to know what their vitamin D levels are. … That’s good because we want to identify vitamin D deficiency in our osteoporosis patients.”

But the low rate of complete secondary screening even by endocrinologists is concerning. “I look at this study as an opportunity for education that we can reinforce the importance of a secondary evaluation for our osteoporosis patients and really tailor which additional tests should be ordered for the individual patient,” Dr. Pessah-Pollack said.

In the poster, Dr. Bulchandani and colleagues wrote, “Further intervention will be aimed to ensure physicians undertake adequate evaluation before considering further treatment directions.” Possibilities that have been discussed include electronic health record alerts and educational materials for primary care providers, she told this news organization.

Dr. Manglani and Dr. Bulchandani had no disclosures. Dr. Pessah-Pollack is an advisor for Boehringer Ingelheim and Eli Lilly.

A version of this article appeared on Medscape.com.

NEW ORLEANS — Postmenopausal women with osteoporosis may not be receiving all the recommended tests to rule out secondary causes of bone loss prior to treatment initiation, new research found.

In a single-center chart review of 150 postmenopausal women who had been diagnosed and treated for osteoporosis, most had received a complete blood cell count, basic metabolic panel, thyroid screening, and vitamin D testing. However, one in four had not been tested for a parathyroid hormone (PTH) level, and in nearly two thirds, a 24-hour urine calcium collection had not been ordered.

Overall, less than a third had received the complete workup for secondary osteoporosis causes as recommended by the American Association of Clinical Endocrinologists (AACE) and the Endocrine Society.

“An appropriate evaluation for secondary causes of osteoporosis is essential because it impacts different treatment options and modalities. We discovered low rates of complete testing for secondary causes of osteoporosis in our patient population prior to treatment initiation,” said Kajol Manglani, MD, an internal medicine resident at Georgetown University/MedStar Washington Hospital Center, Washington, DC, and colleagues, in a poster at the American Association of Clinical Endocrinology (AACE) annual meeting held on May 9-12, 2024.

First author Sheetal Bulchandani, MD, said in an interview, “It depends a lot on clinical judgment, but there are certain things that everybody with osteoporosis should be evaluated for. We looked for the things that all the guidelines recommend.”

Studies have suggested that up to 30% of postmenopausal women with osteoporosis have secondary causes, noted Dr. Bulchandani, who conducted the study as a postdoctoral fellow with colleagues at Georgetown University/MedStar Washington Hospital and is now in private endocrine practice in Petersburg, Virginia.

“It’s important not to assume that every woman who walks in with osteoporosis has postmenopausal osteoporosis. I think it would be appropriate to at least discuss with the patients what would warrant certain kinds of clinical workup. … If you don’t figure out if there is an underlying cause, you may end up using an unnecessary medication,” Dr. Bulchandani said.
 

Are You Missing Something Treatable?

For example, she said, if the patient has underlying hyperparathyroidism and is treated with osteoporosis medications, “you might not see the desired or expected outcome in their bone density.”

Asked to comment, Rachel Pessah-Pollack, MD, clinical associate professor at the Holman Division of Endocrinology, Diabetes, and Metabolism at New York University School of Medicine, New York City, told this news organization, “Certainly, if you have patients who have osteoporosis, it’s important to take a good history and consider secondary causes of bone loss because you may find a treatable etiology that actually can improve their bone density without even starting on a medication.”

Dr. Pessah-Pollack, who was an author of the 2020 AACE/American College of Endocrinology 2020 Clinical Practice Guidelines for the Diagnosis and Treatment of Osteoporosis, said a 24-hour urine calcium collection, not a spot calcium check, is “super important because you’re looking to see if there’s any evidence of hypercalciuria or malabsorption that may be associated with higher rates of bone loss. … These may be a little more cumbersome and harder to get patients to do and more logistics to arrange. But clearly, if you pick up hypercalciuria, that is a potentially treatable etiology and can improve bone density as well.”

Another example, Dr. Pessah-Pollack said, is “if they have a low serum calcium level and high PTH, that would be a real reason to look for celiac disease. By not getting that PTH level, you may be missing that potential diagnosis. There is a wide range of additional causes of osteoporosis ranging from common conditions such as hyperthyroidism to rare conditions such as Cushing disease.”
 

Differences in Ordering Found Across Specialties

The 150 postmenopausal women were all receiving treatment with either alendronate, denosumab, or zoledronic acid. Their average age was 64.7 years, and 63% were seeing an endocrinologist.

Complete workups as per AACE and Endocrine Society guidelines had been performed in just 28% of those who saw an endocrinologist and 12.5% of patients seen by a rheumatologist, in contrast to 84% of those who saw the head of the hospital’s fracture prevention program.

Overall, across all specialties, just 28.67% had the complete recommended workup for secondary osteoporosis causes.

The most missed test was a 24-hour urine calcium collection, ordered for just 38% of the patients, while PTH was ordered for 73% and phosphorus for 80%. The rest were more commonly ordered: Thyroid-stimulating hormone level for 92.7%, complete blood cell count for 91.3%, basic metabolic panel for 100%, and vitamin D level for 96%.

The high rate of vitamin D testing is noteworthy, Dr. Pessah-Pollack said. “The fact that 96% of women are having vitamin D levels checked as part of an osteoporosis evaluation means that everybody’s aware about vitamin D deficiency, and people want to know what their vitamin D levels are. … That’s good because we want to identify vitamin D deficiency in our osteoporosis patients.”

But the low rate of complete secondary screening even by endocrinologists is concerning. “I look at this study as an opportunity for education that we can reinforce the importance of a secondary evaluation for our osteoporosis patients and really tailor which additional tests should be ordered for the individual patient,” Dr. Pessah-Pollack said.

In the poster, Dr. Bulchandani and colleagues wrote, “Further intervention will be aimed to ensure physicians undertake adequate evaluation before considering further treatment directions.” Possibilities that have been discussed include electronic health record alerts and educational materials for primary care providers, she told this news organization.

Dr. Manglani and Dr. Bulchandani had no disclosures. Dr. Pessah-Pollack is an advisor for Boehringer Ingelheim and Eli Lilly.

A version of this article appeared on Medscape.com.

Five experts discussed research that they considered to be highlights of the European Society of Medical Oncology (ESMO) Breast Cancer annual congress during a “Key Takeaways” session at the meeting.

Among the topics the speakers addressed were breast cancer prevention, early breast cancer, advanced breast cancer, and supportive care.

In recent years, the way clinicians look at carcinogenesis in breast cancer has changed, and many new targets for potential early detection and prevention have emerged, said Suzette Delaloge, MD, of Gustave Roussy, Paris, France, in her presentation at the meeting.

Instant risk assessment at different time points could potentially intercept cancer among high-risk individuals, she said.

A study by Mikael Eriksson, PhD, and colleagues focused on external validation of the Profound AI tool to identify breast cancer risk in the general population. The researchers showed an area under the curve of 0.72 in their AI risk model, which has the potential to be clinically meaningful, although it must be prospectively validated, Dr. Delaloge said in her presentation.

She also reviewed two studies on the use of genes to further refine breast cancer risk among carriers. One of these, a prospective study presented in a session by Kelly-Anne Phillips, MD, of Peter MacCallum Cancer Center, Melbourne, Australia, used the CANRISK online risk assessment tool and validated increased breast cancer risk in BRCA1 and BRCA2 carriers, with AUCs of 0.79 and 0.78, respectively. The other study, which was by Maria Rezqallah Aron, MD, and colleagues examined polygenic scores as a way to refine breast cancer risk stratification among carriers of the ALM and PALB2 genes as well. These genes might be useful in identifying individuals who could benefit from early intervention, including surgery, Dr. Delaloge said.
 

Translational Research

“Preparing my talk, I felt like a kid in a candy store,” because of the amount of new translational research presented, including several studies of endocrine treatment–based approaches to therapy, said Marleen Kok, MD, of the Netherlands Cancer Institute, Amsterdam.

In her presentation, Dr. Kok highlighted findings from an analysis of patients in the monarchE study (a trial of high-risk patients) showing a consistent improvement in invasive disease-free survival for the subset of patients with germline BRCA1 and BRCA2 mutations who received abemaciclib plus endocrine therapy.

The value of tumor-infiltrating lymphocytes (TILs) on patients who are not receiving chemotherapy is important because of the focus on prognosis, and prospective trials are underway, she said.

A poster on the impact of chemotherapy and stromal tumor-infiltrating lymphocytes (sTILs) in stage I triple-negative breast cancer showed no association between chemotherapy and better outcomes regardless of sTILs in patients who did and did not receive chemotherapy, which has implications for potential treatment sparing in this population, Dr. Kok noted.

Artificial Intelligence (AI) was the subject of several posters at the meeting, and Dr. Kok identified a multisite European study of an automated HER2 scoring system as notable for its size and accuracy. In the study, the accuracy among pathologists was much higher with the assistance of AI, she said. Using AI for more complex analysis has shown success, she said.

Dr. Kok ended her talk with a poster that surveyed breast cancer patients about their understanding of their disease. The results showed that less than half (44%) of patients reported that their healthcare providers had given them enough information to learn about their breast cancer type, and less than one third could recall terminology about biomarkers; the study is important because it shows that clinicians need to do better in explaining these terms to patients, Dr. Kok said.
 

Early Breast Cancer

Right-sizing therapy, meaning identifying the right treatment for every patient, is a key element of new research in early breast cancer, said Erika Hamilton, MD, of the Sarah Cannon Research Institute, Nashville, Tenn.

She highlighted safety and treatment duration updates from the NATALEE study, which compared adjuvant ribociclib plus nonsteroidal aromatase inhibitor (NSAI) to NSAI alone for ER+/HER2- breast cancer. The current analysis presented at the meeting showed significant benefits with the addition of ribociclib and no evidence of new safety signals or adverse event exacerbations at 3 years, she said. Dose modifications had no significant impact on efficacy, she added.

The findings of no impact of dose reduction on efficacy in both the NATALEE and monarchE studies provide important information on whether dosage can be reduced in patients, which will increase the odds that patients will tolerate extended therapy with good outcomes and stay on their prescribed therapies, Dr. Hamilton emphasized.

The CARABELA study, a phase 2 trial of neoadjuvant letrozole plus abemaciclib vs adriamycin and cyclophosphamide (AC), showed clinically similar response rates but did not meet its endpoint for residual cancer burden (RCB) scores. These data add to results from other studies and show that it is too soon to universally replace neoadjuvant chemotherapy as first-line treatment for highly proliferative ER+ breast cancer, Dr. Hamilton said in her presentation.
 

Advanced Breast Cancer

Take-home messages about advanced breast cancer include growing evidence for the potential benefits of antibody drug conjugates (ADCs), said Eva Ciruelos, MD, of University Hospital, Madrid, Spain. The TROPION-BREAST01 study, a phase 3 randomized trial, showed significant and clinically meaningful improvement in progression-free survival in patients with previously treated, inoperable, or metastatic HR+/HER2- breast cancer who received datopotamab deruxtecan (Dato-DXd) compared with those who received chemotherapy.

Data from an additional safety analysis were presented at the meeting; although Dato-DXd, a trophoblast cell-surface antigen 2 (TROP2)–directed antibody-drug conjugate, was well-tolerated, it is important to remain aware of toxicities, notably oral mucositis, which occurred in 55.6% of the patients in the study across all grades, and ocular surface toxicity, which occurred in 40% of patients across all grades, Dr. Ciruelos emphasized.

Key research in the area of advanced triple-negative breast cancer included data from the IMPASSION 132 study. This study is “specifically centered on early relapsers,” a population often excluded from other trials, Dr. Ciruelos said. In this study, patients with advanced triple-negative breast cancer were randomized to chemotherapy with or without atezolizumab, and the study showed no benefits with atezolizumab for overall survival, progression-free survival, or overall response rate, she said. “This is something to work with, because this is a very refractory population,” Dr. Ciruelos noted.

New immunotherapy combinations are needed to improve survival in advanced breast cancer patients, Dr. Ciruelos said. At the meeting, researchers presented interim data from a subset of patients in the MORPHEUS-pan breast cancer trial, a phase 1B/2 study involving multiple treatment combinations in locally advanced/metastatic breast cancer patients.

The interim analysis included 18-week data from triple-negative breast cancer patients and compared outcomes for patients randomized to atezolizumab with or without sacituzumab govitecan (SG).

The study was small, with only 31 patients in the combination arm and 11 controls, but the results were promising, with an overall response rate of 76.7% in the combination arm vs 66.7% in the control arm, Dr. Ciruelos said.

Supportive Care

Key supportive care takeaways included data on pregnancy in young breast cancer survivors and the safety of vaginal estrogen therapy in breast cancer patients with genitourinary symptoms, said Anne May, MD, of the University Medical Center Utrecht, Utrecht, Netherlands.

A study previously published in JAMA including nearly 5000 BRCA carriers who were diagnosed with invasive breast cancer at age 40 years or younger showed no association between pregnancy after breast cancer and adverse maternal or fetal outcomes, and pregnancy had no significant impact on overall survival. The authors presented new data on the safety of assisted reproductive techniques (ART) based on the 543 pregnancies in the original study, at the meeting. Of these, 436 conceived naturally, and 107 used ART. After a median of 9.1 years, ART had no effect on disease-free survival compared to natural conception (hazard ratio [HR], 0.64). Based on these findings, fertility preservation should be offered to all women who receive a breast cancer diagnosis and are interested in future fertility, Dr. May said.

Conceiving after breast cancer treatment and follow-up should not be contraindicated for young BRCA carriers, she added.No trial data are available for the effects of vaginal estrogen therapy (VET) on disease-free survival in breast cancer survivors with genitourinary symptoms caused by declining estrogen levels, Dr. May said. However, researchers in France and Switzerland conducted an emulation of a hypothetical target trial using data from the French National social security system for more than 130,000 individuals. Although VET therapy had no impact on disease-free survival in most breast cancer survivors overall, it did have a negative impact in a subset of patients with HR-positive and HR-negative tumors who were treated with aromatase inhibitors. The study was hypothetical, but important because the results suggest that clinicians can safely propose VTE to patients who report genitourinary symptoms after treatment for early-stage breast cancer with tamoxifen, but VTE should be avoided in patients treated with aromatase inhibitors, Dr. May said.

Dr. Delaloge disclosed research support to her institution from AstraZeneca, MSD, Bristol Myers Squibb, Sanofi, Taiho, Novartis, European Commission, INCa, Banque des Territoires, and Fondation Philanthropia. She also disclosed honoraria to her institution from AstraZeneca, Gilead, Novartis, Elsan, Besins, Sanofi, Exact Sciences, and Lilly, as well as travel support from Novartis.

Dr. Kok disclosed research funding from AstraZeneca, Bristol Myers Squibb, Daichi, and Roche, and advisory board membership/speaker’s fees from Alderaan Biotechnology, BIONTECH, Domain Therapeutics, AstraZeneca, Daichi, Bristol Myers Squibb, Gilead, Medscape, MSD, and Roche.

Dr. Hamilton disclosed a consulting advisory role (to her institution) for Accutar Biotechology, AstraZeneca, Daiichi Sankyo, Ellipses Pharma, Entos, Forsum Pharma, Gilead Sciences, Greenwich LifeSciences, Jazz Pharmaceuticals, Lilly, Medical Pharma Services, Mersana, Novartis, Olema Pharmaceuticals, Orum Therapeutics, Roche/Genentech, Stemline Therapeutics, ands others. She also disclosed contracted research/grant support to her institution only from Abbvie, Acerta Pharma, Accutar Biotechnology , ADC Therapeutics, AKESOBIO Australia , Amgen, Aravive, ArQule, Artios, Arvinas, AstraZeneca, AtlasMedx, BeiGene, Black Diamond and others.

Dr. Ciruelos disclosed serving as an external advisor for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, and Lilly, as well as serving as a speaker for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, Lilly, and Pierre Fabre. She also disclosed travel grants from Roche, Pfizer, and AstraZeneca, and research grants from Seagen and Roche.

Dr. May had no financial conflicts to disclose.

Five experts discussed research that they considered to be highlights of the European Society of Medical Oncology (ESMO) Breast Cancer annual congress during a “Key Takeaways” session at the meeting.

Among the topics the speakers addressed were breast cancer prevention, early breast cancer, advanced breast cancer, and supportive care.

In recent years, the way clinicians look at carcinogenesis in breast cancer has changed, and many new targets for potential early detection and prevention have emerged, said Suzette Delaloge, MD, of Gustave Roussy, Paris, France, in her presentation at the meeting.

Instant risk assessment at different time points could potentially intercept cancer among high-risk individuals, she said.

A study by Mikael Eriksson, PhD, and colleagues focused on external validation of the Profound AI tool to identify breast cancer risk in the general population. The researchers showed an area under the curve of 0.72 in their AI risk model, which has the potential to be clinically meaningful, although it must be prospectively validated, Dr. Delaloge said in her presentation.

She also reviewed two studies on the use of genes to further refine breast cancer risk among carriers. One of these, a prospective study presented in a session by Kelly-Anne Phillips, MD, of Peter MacCallum Cancer Center, Melbourne, Australia, used the CANRISK online risk assessment tool and validated increased breast cancer risk in BRCA1 and BRCA2 carriers, with AUCs of 0.79 and 0.78, respectively. The other study, which was by Maria Rezqallah Aron, MD, and colleagues examined polygenic scores as a way to refine breast cancer risk stratification among carriers of the ALM and PALB2 genes as well. These genes might be useful in identifying individuals who could benefit from early intervention, including surgery, Dr. Delaloge said.
 

Translational Research

“Preparing my talk, I felt like a kid in a candy store,” because of the amount of new translational research presented, including several studies of endocrine treatment–based approaches to therapy, said Marleen Kok, MD, of the Netherlands Cancer Institute, Amsterdam.

In her presentation, Dr. Kok highlighted findings from an analysis of patients in the monarchE study (a trial of high-risk patients) showing a consistent improvement in invasive disease-free survival for the subset of patients with germline BRCA1 and BRCA2 mutations who received abemaciclib plus endocrine therapy.

The value of tumor-infiltrating lymphocytes (TILs) on patients who are not receiving chemotherapy is important because of the focus on prognosis, and prospective trials are underway, she said.

A poster on the impact of chemotherapy and stromal tumor-infiltrating lymphocytes (sTILs) in stage I triple-negative breast cancer showed no association between chemotherapy and better outcomes regardless of sTILs in patients who did and did not receive chemotherapy, which has implications for potential treatment sparing in this population, Dr. Kok noted.

Artificial Intelligence (AI) was the subject of several posters at the meeting, and Dr. Kok identified a multisite European study of an automated HER2 scoring system as notable for its size and accuracy. In the study, the accuracy among pathologists was much higher with the assistance of AI, she said. Using AI for more complex analysis has shown success, she said.

Dr. Kok ended her talk with a poster that surveyed breast cancer patients about their understanding of their disease. The results showed that less than half (44%) of patients reported that their healthcare providers had given them enough information to learn about their breast cancer type, and less than one third could recall terminology about biomarkers; the study is important because it shows that clinicians need to do better in explaining these terms to patients, Dr. Kok said.
 

Early Breast Cancer

Right-sizing therapy, meaning identifying the right treatment for every patient, is a key element of new research in early breast cancer, said Erika Hamilton, MD, of the Sarah Cannon Research Institute, Nashville, Tenn.

She highlighted safety and treatment duration updates from the NATALEE study, which compared adjuvant ribociclib plus nonsteroidal aromatase inhibitor (NSAI) to NSAI alone for ER+/HER2- breast cancer. The current analysis presented at the meeting showed significant benefits with the addition of ribociclib and no evidence of new safety signals or adverse event exacerbations at 3 years, she said. Dose modifications had no significant impact on efficacy, she added.

The findings of no impact of dose reduction on efficacy in both the NATALEE and monarchE studies provide important information on whether dosage can be reduced in patients, which will increase the odds that patients will tolerate extended therapy with good outcomes and stay on their prescribed therapies, Dr. Hamilton emphasized.

The CARABELA study, a phase 2 trial of neoadjuvant letrozole plus abemaciclib vs adriamycin and cyclophosphamide (AC), showed clinically similar response rates but did not meet its endpoint for residual cancer burden (RCB) scores. These data add to results from other studies and show that it is too soon to universally replace neoadjuvant chemotherapy as first-line treatment for highly proliferative ER+ breast cancer, Dr. Hamilton said in her presentation.
 

Advanced Breast Cancer

Take-home messages about advanced breast cancer include growing evidence for the potential benefits of antibody drug conjugates (ADCs), said Eva Ciruelos, MD, of University Hospital, Madrid, Spain. The TROPION-BREAST01 study, a phase 3 randomized trial, showed significant and clinically meaningful improvement in progression-free survival in patients with previously treated, inoperable, or metastatic HR+/HER2- breast cancer who received datopotamab deruxtecan (Dato-DXd) compared with those who received chemotherapy.

Data from an additional safety analysis were presented at the meeting; although Dato-DXd, a trophoblast cell-surface antigen 2 (TROP2)–directed antibody-drug conjugate, was well-tolerated, it is important to remain aware of toxicities, notably oral mucositis, which occurred in 55.6% of the patients in the study across all grades, and ocular surface toxicity, which occurred in 40% of patients across all grades, Dr. Ciruelos emphasized.

Key research in the area of advanced triple-negative breast cancer included data from the IMPASSION 132 study. This study is “specifically centered on early relapsers,” a population often excluded from other trials, Dr. Ciruelos said. In this study, patients with advanced triple-negative breast cancer were randomized to chemotherapy with or without atezolizumab, and the study showed no benefits with atezolizumab for overall survival, progression-free survival, or overall response rate, she said. “This is something to work with, because this is a very refractory population,” Dr. Ciruelos noted.

New immunotherapy combinations are needed to improve survival in advanced breast cancer patients, Dr. Ciruelos said. At the meeting, researchers presented interim data from a subset of patients in the MORPHEUS-pan breast cancer trial, a phase 1B/2 study involving multiple treatment combinations in locally advanced/metastatic breast cancer patients.

The interim analysis included 18-week data from triple-negative breast cancer patients and compared outcomes for patients randomized to atezolizumab with or without sacituzumab govitecan (SG).

The study was small, with only 31 patients in the combination arm and 11 controls, but the results were promising, with an overall response rate of 76.7% in the combination arm vs 66.7% in the control arm, Dr. Ciruelos said.

Supportive Care

Key supportive care takeaways included data on pregnancy in young breast cancer survivors and the safety of vaginal estrogen therapy in breast cancer patients with genitourinary symptoms, said Anne May, MD, of the University Medical Center Utrecht, Utrecht, Netherlands.

A study previously published in JAMA including nearly 5000 BRCA carriers who were diagnosed with invasive breast cancer at age 40 years or younger showed no association between pregnancy after breast cancer and adverse maternal or fetal outcomes, and pregnancy had no significant impact on overall survival. The authors presented new data on the safety of assisted reproductive techniques (ART) based on the 543 pregnancies in the original study, at the meeting. Of these, 436 conceived naturally, and 107 used ART. After a median of 9.1 years, ART had no effect on disease-free survival compared to natural conception (hazard ratio [HR], 0.64). Based on these findings, fertility preservation should be offered to all women who receive a breast cancer diagnosis and are interested in future fertility, Dr. May said.

Conceiving after breast cancer treatment and follow-up should not be contraindicated for young BRCA carriers, she added.No trial data are available for the effects of vaginal estrogen therapy (VET) on disease-free survival in breast cancer survivors with genitourinary symptoms caused by declining estrogen levels, Dr. May said. However, researchers in France and Switzerland conducted an emulation of a hypothetical target trial using data from the French National social security system for more than 130,000 individuals. Although VET therapy had no impact on disease-free survival in most breast cancer survivors overall, it did have a negative impact in a subset of patients with HR-positive and HR-negative tumors who were treated with aromatase inhibitors. The study was hypothetical, but important because the results suggest that clinicians can safely propose VTE to patients who report genitourinary symptoms after treatment for early-stage breast cancer with tamoxifen, but VTE should be avoided in patients treated with aromatase inhibitors, Dr. May said.

Dr. Delaloge disclosed research support to her institution from AstraZeneca, MSD, Bristol Myers Squibb, Sanofi, Taiho, Novartis, European Commission, INCa, Banque des Territoires, and Fondation Philanthropia. She also disclosed honoraria to her institution from AstraZeneca, Gilead, Novartis, Elsan, Besins, Sanofi, Exact Sciences, and Lilly, as well as travel support from Novartis.

Dr. Kok disclosed research funding from AstraZeneca, Bristol Myers Squibb, Daichi, and Roche, and advisory board membership/speaker’s fees from Alderaan Biotechnology, BIONTECH, Domain Therapeutics, AstraZeneca, Daichi, Bristol Myers Squibb, Gilead, Medscape, MSD, and Roche.

Dr. Hamilton disclosed a consulting advisory role (to her institution) for Accutar Biotechology, AstraZeneca, Daiichi Sankyo, Ellipses Pharma, Entos, Forsum Pharma, Gilead Sciences, Greenwich LifeSciences, Jazz Pharmaceuticals, Lilly, Medical Pharma Services, Mersana, Novartis, Olema Pharmaceuticals, Orum Therapeutics, Roche/Genentech, Stemline Therapeutics, ands others. She also disclosed contracted research/grant support to her institution only from Abbvie, Acerta Pharma, Accutar Biotechnology , ADC Therapeutics, AKESOBIO Australia , Amgen, Aravive, ArQule, Artios, Arvinas, AstraZeneca, AtlasMedx, BeiGene, Black Diamond and others.

Dr. Ciruelos disclosed serving as an external advisor for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, and Lilly, as well as serving as a speaker for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, Lilly, and Pierre Fabre. She also disclosed travel grants from Roche, Pfizer, and AstraZeneca, and research grants from Seagen and Roche.

Dr. May had no financial conflicts to disclose.

Five experts discussed research that they considered to be highlights of the European Society of Medical Oncology (ESMO) Breast Cancer annual congress during a “Key Takeaways” session at the meeting.

Among the topics the speakers addressed were breast cancer prevention, early breast cancer, advanced breast cancer, and supportive care.

In recent years, the way clinicians look at carcinogenesis in breast cancer has changed, and many new targets for potential early detection and prevention have emerged, said Suzette Delaloge, MD, of Gustave Roussy, Paris, France, in her presentation at the meeting.

Instant risk assessment at different time points could potentially intercept cancer among high-risk individuals, she said.

A study by Mikael Eriksson, PhD, and colleagues focused on external validation of the Profound AI tool to identify breast cancer risk in the general population. The researchers showed an area under the curve of 0.72 in their AI risk model, which has the potential to be clinically meaningful, although it must be prospectively validated, Dr. Delaloge said in her presentation.

She also reviewed two studies on the use of genes to further refine breast cancer risk among carriers. One of these, a prospective study presented in a session by Kelly-Anne Phillips, MD, of Peter MacCallum Cancer Center, Melbourne, Australia, used the CANRISK online risk assessment tool and validated increased breast cancer risk in BRCA1 and BRCA2 carriers, with AUCs of 0.79 and 0.78, respectively. The other study, which was by Maria Rezqallah Aron, MD, and colleagues examined polygenic scores as a way to refine breast cancer risk stratification among carriers of the ALM and PALB2 genes as well. These genes might be useful in identifying individuals who could benefit from early intervention, including surgery, Dr. Delaloge said.
 

Translational Research

“Preparing my talk, I felt like a kid in a candy store,” because of the amount of new translational research presented, including several studies of endocrine treatment–based approaches to therapy, said Marleen Kok, MD, of the Netherlands Cancer Institute, Amsterdam.

In her presentation, Dr. Kok highlighted findings from an analysis of patients in the monarchE study (a trial of high-risk patients) showing a consistent improvement in invasive disease-free survival for the subset of patients with germline BRCA1 and BRCA2 mutations who received abemaciclib plus endocrine therapy.

The value of tumor-infiltrating lymphocytes (TILs) on patients who are not receiving chemotherapy is important because of the focus on prognosis, and prospective trials are underway, she said.

A poster on the impact of chemotherapy and stromal tumor-infiltrating lymphocytes (sTILs) in stage I triple-negative breast cancer showed no association between chemotherapy and better outcomes regardless of sTILs in patients who did and did not receive chemotherapy, which has implications for potential treatment sparing in this population, Dr. Kok noted.

Artificial Intelligence (AI) was the subject of several posters at the meeting, and Dr. Kok identified a multisite European study of an automated HER2 scoring system as notable for its size and accuracy. In the study, the accuracy among pathologists was much higher with the assistance of AI, she said. Using AI for more complex analysis has shown success, she said.

Dr. Kok ended her talk with a poster that surveyed breast cancer patients about their understanding of their disease. The results showed that less than half (44%) of patients reported that their healthcare providers had given them enough information to learn about their breast cancer type, and less than one third could recall terminology about biomarkers; the study is important because it shows that clinicians need to do better in explaining these terms to patients, Dr. Kok said.
 

Early Breast Cancer

Right-sizing therapy, meaning identifying the right treatment for every patient, is a key element of new research in early breast cancer, said Erika Hamilton, MD, of the Sarah Cannon Research Institute, Nashville, Tenn.

She highlighted safety and treatment duration updates from the NATALEE study, which compared adjuvant ribociclib plus nonsteroidal aromatase inhibitor (NSAI) to NSAI alone for ER+/HER2- breast cancer. The current analysis presented at the meeting showed significant benefits with the addition of ribociclib and no evidence of new safety signals or adverse event exacerbations at 3 years, she said. Dose modifications had no significant impact on efficacy, she added.

The findings of no impact of dose reduction on efficacy in both the NATALEE and monarchE studies provide important information on whether dosage can be reduced in patients, which will increase the odds that patients will tolerate extended therapy with good outcomes and stay on their prescribed therapies, Dr. Hamilton emphasized.

The CARABELA study, a phase 2 trial of neoadjuvant letrozole plus abemaciclib vs adriamycin and cyclophosphamide (AC), showed clinically similar response rates but did not meet its endpoint for residual cancer burden (RCB) scores. These data add to results from other studies and show that it is too soon to universally replace neoadjuvant chemotherapy as first-line treatment for highly proliferative ER+ breast cancer, Dr. Hamilton said in her presentation.
 

Advanced Breast Cancer

Take-home messages about advanced breast cancer include growing evidence for the potential benefits of antibody drug conjugates (ADCs), said Eva Ciruelos, MD, of University Hospital, Madrid, Spain. The TROPION-BREAST01 study, a phase 3 randomized trial, showed significant and clinically meaningful improvement in progression-free survival in patients with previously treated, inoperable, or metastatic HR+/HER2- breast cancer who received datopotamab deruxtecan (Dato-DXd) compared with those who received chemotherapy.

Data from an additional safety analysis were presented at the meeting; although Dato-DXd, a trophoblast cell-surface antigen 2 (TROP2)–directed antibody-drug conjugate, was well-tolerated, it is important to remain aware of toxicities, notably oral mucositis, which occurred in 55.6% of the patients in the study across all grades, and ocular surface toxicity, which occurred in 40% of patients across all grades, Dr. Ciruelos emphasized.

Key research in the area of advanced triple-negative breast cancer included data from the IMPASSION 132 study. This study is “specifically centered on early relapsers,” a population often excluded from other trials, Dr. Ciruelos said. In this study, patients with advanced triple-negative breast cancer were randomized to chemotherapy with or without atezolizumab, and the study showed no benefits with atezolizumab for overall survival, progression-free survival, or overall response rate, she said. “This is something to work with, because this is a very refractory population,” Dr. Ciruelos noted.

New immunotherapy combinations are needed to improve survival in advanced breast cancer patients, Dr. Ciruelos said. At the meeting, researchers presented interim data from a subset of patients in the MORPHEUS-pan breast cancer trial, a phase 1B/2 study involving multiple treatment combinations in locally advanced/metastatic breast cancer patients.

The interim analysis included 18-week data from triple-negative breast cancer patients and compared outcomes for patients randomized to atezolizumab with or without sacituzumab govitecan (SG).

The study was small, with only 31 patients in the combination arm and 11 controls, but the results were promising, with an overall response rate of 76.7% in the combination arm vs 66.7% in the control arm, Dr. Ciruelos said.

Supportive Care

Key supportive care takeaways included data on pregnancy in young breast cancer survivors and the safety of vaginal estrogen therapy in breast cancer patients with genitourinary symptoms, said Anne May, MD, of the University Medical Center Utrecht, Utrecht, Netherlands.

A study previously published in JAMA including nearly 5000 BRCA carriers who were diagnosed with invasive breast cancer at age 40 years or younger showed no association between pregnancy after breast cancer and adverse maternal or fetal outcomes, and pregnancy had no significant impact on overall survival. The authors presented new data on the safety of assisted reproductive techniques (ART) based on the 543 pregnancies in the original study, at the meeting. Of these, 436 conceived naturally, and 107 used ART. After a median of 9.1 years, ART had no effect on disease-free survival compared to natural conception (hazard ratio [HR], 0.64). Based on these findings, fertility preservation should be offered to all women who receive a breast cancer diagnosis and are interested in future fertility, Dr. May said.

Conceiving after breast cancer treatment and follow-up should not be contraindicated for young BRCA carriers, she added.No trial data are available for the effects of vaginal estrogen therapy (VET) on disease-free survival in breast cancer survivors with genitourinary symptoms caused by declining estrogen levels, Dr. May said. However, researchers in France and Switzerland conducted an emulation of a hypothetical target trial using data from the French National social security system for more than 130,000 individuals. Although VET therapy had no impact on disease-free survival in most breast cancer survivors overall, it did have a negative impact in a subset of patients with HR-positive and HR-negative tumors who were treated with aromatase inhibitors. The study was hypothetical, but important because the results suggest that clinicians can safely propose VTE to patients who report genitourinary symptoms after treatment for early-stage breast cancer with tamoxifen, but VTE should be avoided in patients treated with aromatase inhibitors, Dr. May said.

Dr. Delaloge disclosed research support to her institution from AstraZeneca, MSD, Bristol Myers Squibb, Sanofi, Taiho, Novartis, European Commission, INCa, Banque des Territoires, and Fondation Philanthropia. She also disclosed honoraria to her institution from AstraZeneca, Gilead, Novartis, Elsan, Besins, Sanofi, Exact Sciences, and Lilly, as well as travel support from Novartis.

Dr. Kok disclosed research funding from AstraZeneca, Bristol Myers Squibb, Daichi, and Roche, and advisory board membership/speaker’s fees from Alderaan Biotechnology, BIONTECH, Domain Therapeutics, AstraZeneca, Daichi, Bristol Myers Squibb, Gilead, Medscape, MSD, and Roche.

Dr. Hamilton disclosed a consulting advisory role (to her institution) for Accutar Biotechology, AstraZeneca, Daiichi Sankyo, Ellipses Pharma, Entos, Forsum Pharma, Gilead Sciences, Greenwich LifeSciences, Jazz Pharmaceuticals, Lilly, Medical Pharma Services, Mersana, Novartis, Olema Pharmaceuticals, Orum Therapeutics, Roche/Genentech, Stemline Therapeutics, ands others. She also disclosed contracted research/grant support to her institution only from Abbvie, Acerta Pharma, Accutar Biotechnology , ADC Therapeutics, AKESOBIO Australia , Amgen, Aravive, ArQule, Artios, Arvinas, AstraZeneca, AtlasMedx, BeiGene, Black Diamond and others.

Dr. Ciruelos disclosed serving as an external advisor for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, and Lilly, as well as serving as a speaker for Roche, MSD, Gilead, AstraZeneca, Daichii Sankyo, Reveal Genomics, Pfizer, Novartis, Lilly, and Pierre Fabre. She also disclosed travel grants from Roche, Pfizer, and AstraZeneca, and research grants from Seagen and Roche.

Dr. May had no financial conflicts to disclose.

SAN FRANCISCO — Patients with a low-lying placenta who underwent cesarean deliveries were at higher risk for multiple complications even if they did not have placenta previa, according to data presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Rates of preterm delivery, postpartum hemorrhage, placenta accreta, and need for hysterectomy and transfusion were all significantly higher in patients with low-lying placenta than in patients without, Jacob Thomas, MD, of Advocate Aurora Health in Chicago, Illinois, and Ascension Illinois St. Alexius Medical Center in Hoffman Estates, reported at the meeting.

A low-lying placenta is defined as a placental edge less than 20 mm from the internal os but not covering it. Most studies looking at low-lying placentas, however, group them with placenta previa, making it difficult to know if there are differences in risk of adverse outcomes for those who don’t have placenta previa.

“These are not necessarily shocking findings, but it shows that even low-lying placentas have significant morbidity in and of themselves, not just when they’re lumped with placenta previas,” Dr. Thomas said in an interview. “This means, if you’re doing a C-section for a low-lying placenta, you probably want to treat it a lot like you would treat a placenta previa. You may have blood ready, whether or not you’re going to give it, and you’re going to be more prepared for those complications.”

Noting that approximately 30% of patients with low-lying placenta had preterm deliveries, Dr. Thomas added that these patients might need to be counseled differently as well. The researchers did not have data on how preterm the deliveries were — many could have been 35-37 weeks, for example — but “how you prepare those patients is different,” he said.

Breanna Bolivar, MD, MPH, an obgyn hospitalist at MAHEC Ob/Gyn Specialists in Asheville, North Carolina, said the findings confirm her experience in practice.

“Low-lying placentas are treated very similarly to placenta previas and the results seem similar to patients that have placenta previas,” Dr. Bolivar said in an interview. “In my practice, I treat patients with low-lying placenta the same as I do with placenta previa. I have the same risk factors in mind, and I prepare in the same way.”

The researchers conducted a retrospective analysis of all patients who underwent a cesarean delivery in the National Inpatient Sample from 2017 to 2019 through the Healthcare Cost and Utilization Project from the Agency for Healthcare Research and Quality. After excluding patients with placenta previa, the researchers compared outcomes among patients with ICD-10 codes for low-lying placenta to those of patients without low-lying placenta. The researchers specifically looked at preterm delivery, hemorrhage, hysterectomy, placenta accreta spectrum (PAS), sepsis, shock, disseminated intravascular coagulation, and blood transfusion.

Among 700,635 patients with cesarean deliveries in the database, 0.4% had low-lying placenta. These patients were more likely to be older, to be anemic, and to deliver at a large or urban teaching hospital. They were less likely to have public insurance or a previous cesarean.

After controlling for confounders that differed between the two populations, the researchers found a higher likelihood of all adverse maternal outcomes studied in patients with low-lying placenta (P < .05). These patients had three times greater risk for preterm delivery (adjusted odds ratio [aOR], 3.07; 95% CI, 2.81-3.35) and nearly three times greater risk for shock (aOR 2.55; 95% CI, 1.44-4.52), and transfusion (aOR, 2.56; 95% CI, 2.14-3.06).

Compared to those without low-lying placenta, risk for patients with low-lying placenta was even higher for hemorrhage (aOR, 8.87; 95% CI, 8.10-9.73), hysterectomy (aOR, 9.42; 95% CI, 7.11-12.47), and PAS (aOR, 13.41; 95% CI, 10.34-17.39).

Within the group with low-lying placenta, older patients were modestly, but significantly, more likely to have hemorrhage, hysterectomy, and PAS (aOR, 1.06 for all). The risk was more elevated and significant in patients with tobacco use for hemorrhage (aOR, 1.43), hysterectomy (aOR, 1.40), and PAS (aOR, 1.40). Patients with anemia were also significantly more likely to experience PAS (aOR, 1.34).

“Interestingly, in this population, prior cesarean was not associated with increased rates of hemorrhage or hysterectomy,” the researchers reported. The findings can also “help guide research in terms of questions for the future,” Dr. Thomas said, such as looking at complication rates for vaginal deliveries in people with low-lying placenta.

No external funding was noted, and the authors all had no disclosures. Dr. Bolivar had no disclosures.

SAN FRANCISCO — Patients with a low-lying placenta who underwent cesarean deliveries were at higher risk for multiple complications even if they did not have placenta previa, according to data presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Rates of preterm delivery, postpartum hemorrhage, placenta accreta, and need for hysterectomy and transfusion were all significantly higher in patients with low-lying placenta than in patients without, Jacob Thomas, MD, of Advocate Aurora Health in Chicago, Illinois, and Ascension Illinois St. Alexius Medical Center in Hoffman Estates, reported at the meeting.

A low-lying placenta is defined as a placental edge less than 20 mm from the internal os but not covering it. Most studies looking at low-lying placentas, however, group them with placenta previa, making it difficult to know if there are differences in risk of adverse outcomes for those who don’t have placenta previa.

“These are not necessarily shocking findings, but it shows that even low-lying placentas have significant morbidity in and of themselves, not just when they’re lumped with placenta previas,” Dr. Thomas said in an interview. “This means, if you’re doing a C-section for a low-lying placenta, you probably want to treat it a lot like you would treat a placenta previa. You may have blood ready, whether or not you’re going to give it, and you’re going to be more prepared for those complications.”

Noting that approximately 30% of patients with low-lying placenta had preterm deliveries, Dr. Thomas added that these patients might need to be counseled differently as well. The researchers did not have data on how preterm the deliveries were — many could have been 35-37 weeks, for example — but “how you prepare those patients is different,” he said.

Breanna Bolivar, MD, MPH, an obgyn hospitalist at MAHEC Ob/Gyn Specialists in Asheville, North Carolina, said the findings confirm her experience in practice.

“Low-lying placentas are treated very similarly to placenta previas and the results seem similar to patients that have placenta previas,” Dr. Bolivar said in an interview. “In my practice, I treat patients with low-lying placenta the same as I do with placenta previa. I have the same risk factors in mind, and I prepare in the same way.”

The researchers conducted a retrospective analysis of all patients who underwent a cesarean delivery in the National Inpatient Sample from 2017 to 2019 through the Healthcare Cost and Utilization Project from the Agency for Healthcare Research and Quality. After excluding patients with placenta previa, the researchers compared outcomes among patients with ICD-10 codes for low-lying placenta to those of patients without low-lying placenta. The researchers specifically looked at preterm delivery, hemorrhage, hysterectomy, placenta accreta spectrum (PAS), sepsis, shock, disseminated intravascular coagulation, and blood transfusion.

Among 700,635 patients with cesarean deliveries in the database, 0.4% had low-lying placenta. These patients were more likely to be older, to be anemic, and to deliver at a large or urban teaching hospital. They were less likely to have public insurance or a previous cesarean.

After controlling for confounders that differed between the two populations, the researchers found a higher likelihood of all adverse maternal outcomes studied in patients with low-lying placenta (P < .05). These patients had three times greater risk for preterm delivery (adjusted odds ratio [aOR], 3.07; 95% CI, 2.81-3.35) and nearly three times greater risk for shock (aOR 2.55; 95% CI, 1.44-4.52), and transfusion (aOR, 2.56; 95% CI, 2.14-3.06).

Compared to those without low-lying placenta, risk for patients with low-lying placenta was even higher for hemorrhage (aOR, 8.87; 95% CI, 8.10-9.73), hysterectomy (aOR, 9.42; 95% CI, 7.11-12.47), and PAS (aOR, 13.41; 95% CI, 10.34-17.39).

Within the group with low-lying placenta, older patients were modestly, but significantly, more likely to have hemorrhage, hysterectomy, and PAS (aOR, 1.06 for all). The risk was more elevated and significant in patients with tobacco use for hemorrhage (aOR, 1.43), hysterectomy (aOR, 1.40), and PAS (aOR, 1.40). Patients with anemia were also significantly more likely to experience PAS (aOR, 1.34).

“Interestingly, in this population, prior cesarean was not associated with increased rates of hemorrhage or hysterectomy,” the researchers reported. The findings can also “help guide research in terms of questions for the future,” Dr. Thomas said, such as looking at complication rates for vaginal deliveries in people with low-lying placenta.

No external funding was noted, and the authors all had no disclosures. Dr. Bolivar had no disclosures.

SAN FRANCISCO — Patients with a low-lying placenta who underwent cesarean deliveries were at higher risk for multiple complications even if they did not have placenta previa, according to data presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Rates of preterm delivery, postpartum hemorrhage, placenta accreta, and need for hysterectomy and transfusion were all significantly higher in patients with low-lying placenta than in patients without, Jacob Thomas, MD, of Advocate Aurora Health in Chicago, Illinois, and Ascension Illinois St. Alexius Medical Center in Hoffman Estates, reported at the meeting.

A low-lying placenta is defined as a placental edge less than 20 mm from the internal os but not covering it. Most studies looking at low-lying placentas, however, group them with placenta previa, making it difficult to know if there are differences in risk of adverse outcomes for those who don’t have placenta previa.

“These are not necessarily shocking findings, but it shows that even low-lying placentas have significant morbidity in and of themselves, not just when they’re lumped with placenta previas,” Dr. Thomas said in an interview. “This means, if you’re doing a C-section for a low-lying placenta, you probably want to treat it a lot like you would treat a placenta previa. You may have blood ready, whether or not you’re going to give it, and you’re going to be more prepared for those complications.”

Noting that approximately 30% of patients with low-lying placenta had preterm deliveries, Dr. Thomas added that these patients might need to be counseled differently as well. The researchers did not have data on how preterm the deliveries were — many could have been 35-37 weeks, for example — but “how you prepare those patients is different,” he said.

Breanna Bolivar, MD, MPH, an obgyn hospitalist at MAHEC Ob/Gyn Specialists in Asheville, North Carolina, said the findings confirm her experience in practice.

“Low-lying placentas are treated very similarly to placenta previas and the results seem similar to patients that have placenta previas,” Dr. Bolivar said in an interview. “In my practice, I treat patients with low-lying placenta the same as I do with placenta previa. I have the same risk factors in mind, and I prepare in the same way.”

The researchers conducted a retrospective analysis of all patients who underwent a cesarean delivery in the National Inpatient Sample from 2017 to 2019 through the Healthcare Cost and Utilization Project from the Agency for Healthcare Research and Quality. After excluding patients with placenta previa, the researchers compared outcomes among patients with ICD-10 codes for low-lying placenta to those of patients without low-lying placenta. The researchers specifically looked at preterm delivery, hemorrhage, hysterectomy, placenta accreta spectrum (PAS), sepsis, shock, disseminated intravascular coagulation, and blood transfusion.

Among 700,635 patients with cesarean deliveries in the database, 0.4% had low-lying placenta. These patients were more likely to be older, to be anemic, and to deliver at a large or urban teaching hospital. They were less likely to have public insurance or a previous cesarean.

After controlling for confounders that differed between the two populations, the researchers found a higher likelihood of all adverse maternal outcomes studied in patients with low-lying placenta (P < .05). These patients had three times greater risk for preterm delivery (adjusted odds ratio [aOR], 3.07; 95% CI, 2.81-3.35) and nearly three times greater risk for shock (aOR 2.55; 95% CI, 1.44-4.52), and transfusion (aOR, 2.56; 95% CI, 2.14-3.06).

Compared to those without low-lying placenta, risk for patients with low-lying placenta was even higher for hemorrhage (aOR, 8.87; 95% CI, 8.10-9.73), hysterectomy (aOR, 9.42; 95% CI, 7.11-12.47), and PAS (aOR, 13.41; 95% CI, 10.34-17.39).

Within the group with low-lying placenta, older patients were modestly, but significantly, more likely to have hemorrhage, hysterectomy, and PAS (aOR, 1.06 for all). The risk was more elevated and significant in patients with tobacco use for hemorrhage (aOR, 1.43), hysterectomy (aOR, 1.40), and PAS (aOR, 1.40). Patients with anemia were also significantly more likely to experience PAS (aOR, 1.34).

“Interestingly, in this population, prior cesarean was not associated with increased rates of hemorrhage or hysterectomy,” the researchers reported. The findings can also “help guide research in terms of questions for the future,” Dr. Thomas said, such as looking at complication rates for vaginal deliveries in people with low-lying placenta.

No external funding was noted, and the authors all had no disclosures. Dr. Bolivar had no disclosures.

TOPLINE:

Individuals with severe maternal morbidity (SMM) are at an increased risk for mental health condition–related hospitalization or emergency department (ED) visits up to 13 years after delivery.

METHODOLOGY:

• This retrospective cohort study compared mental health hospitalizations and ED visits in postpartum individuals with and without SMM over 13 years after delivery from April 2008 to March 2021.
• The study analyzed 1,579,392 individuals aged 18-55 years with a first recorded liveborn or stillborn delivery from a pregnancy lasting 20-43 weeks, of which 35,825 (2.3%) had exposure to SMM.
• The SMM exposure was analyzed for events occurring after 20 weeks’ gestation and up to 42 days after delivery hospital discharge in the first recorded birth; those without SMM were considered unexposed.
• The main outcome was a combination of mental health hospitalizations or ED visits occurring at least 43 days after the index birth hospitalization.

TAKEAWAY:

• Individuals with SMM had a 1.3-fold increased risk of mental health hospitalizations or ED visits.
• The hospital or ED visits per 10,000 person-years were 59.2 for mood and anxiety disorders, 17.1 for substance abuse and related disorders, 4.8 for suicidality or self-harm, and 4.1 for schizophrenia spectrum or other psychotic disorders.
• Following SMM, an elevated risk was observed for all mental health outcomes except one (schizophrenia spectrum and other psychotic disorders), with the highest risk seen for suicidality and self-harm (aHR, 1.54).

IN PRACTICE:

“Knowledge of the short- and long-term risks of serious mental health conditions after SMM and its subtypes could inform the need for enhanced postpartum supportive resources,” the authors wrote.

SOURCE:

This study was led by Asia Blackman, MSc, Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec, Canada. It was published online in JAMA Network Open.

LIMITATIONS:

The study is limited by its observational design, missing data, and misclassification bias.

DISCLOSURES:

This study was supported by funding from the Canadian Institutes of Health Research. Three authors reported receiving personal fees or grants outside the submitted work. No other conflicts of interest were reported.

A version of this article first appeared on Medscape.com.

TOPLINE:

Individuals with severe maternal morbidity (SMM) are at an increased risk for mental health condition–related hospitalization or emergency department (ED) visits up to 13 years after delivery.

METHODOLOGY:

• This retrospective cohort study compared mental health hospitalizations and ED visits in postpartum individuals with and without SMM over 13 years after delivery from April 2008 to March 2021.
• The study analyzed 1,579,392 individuals aged 18-55 years with a first recorded liveborn or stillborn delivery from a pregnancy lasting 20-43 weeks, of which 35,825 (2.3%) had exposure to SMM.
• The SMM exposure was analyzed for events occurring after 20 weeks’ gestation and up to 42 days after delivery hospital discharge in the first recorded birth; those without SMM were considered unexposed.
• The main outcome was a combination of mental health hospitalizations or ED visits occurring at least 43 days after the index birth hospitalization.

TAKEAWAY:

• Individuals with SMM had a 1.3-fold increased risk of mental health hospitalizations or ED visits.
• The hospital or ED visits per 10,000 person-years were 59.2 for mood and anxiety disorders, 17.1 for substance abuse and related disorders, 4.8 for suicidality or self-harm, and 4.1 for schizophrenia spectrum or other psychotic disorders.
• Following SMM, an elevated risk was observed for all mental health outcomes except one (schizophrenia spectrum and other psychotic disorders), with the highest risk seen for suicidality and self-harm (aHR, 1.54).

IN PRACTICE:

“Knowledge of the short- and long-term risks of serious mental health conditions after SMM and its subtypes could inform the need for enhanced postpartum supportive resources,” the authors wrote.

SOURCE:

This study was led by Asia Blackman, MSc, Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec, Canada. It was published online in JAMA Network Open.

LIMITATIONS:

The study is limited by its observational design, missing data, and misclassification bias.

DISCLOSURES:

This study was supported by funding from the Canadian Institutes of Health Research. Three authors reported receiving personal fees or grants outside the submitted work. No other conflicts of interest were reported.

A version of this article first appeared on Medscape.com.

TOPLINE:

Individuals with severe maternal morbidity (SMM) are at an increased risk for mental health condition–related hospitalization or emergency department (ED) visits up to 13 years after delivery.

METHODOLOGY:

• This retrospective cohort study compared mental health hospitalizations and ED visits in postpartum individuals with and without SMM over 13 years after delivery from April 2008 to March 2021.
• The study analyzed 1,579,392 individuals aged 18-55 years with a first recorded liveborn or stillborn delivery from a pregnancy lasting 20-43 weeks, of which 35,825 (2.3%) had exposure to SMM.
• The SMM exposure was analyzed for events occurring after 20 weeks’ gestation and up to 42 days after delivery hospital discharge in the first recorded birth; those without SMM were considered unexposed.
• The main outcome was a combination of mental health hospitalizations or ED visits occurring at least 43 days after the index birth hospitalization.

TAKEAWAY:

• Individuals with SMM had a 1.3-fold increased risk of mental health hospitalizations or ED visits.
• The hospital or ED visits per 10,000 person-years were 59.2 for mood and anxiety disorders, 17.1 for substance abuse and related disorders, 4.8 for suicidality or self-harm, and 4.1 for schizophrenia spectrum or other psychotic disorders.
• Following SMM, an elevated risk was observed for all mental health outcomes except one (schizophrenia spectrum and other psychotic disorders), with the highest risk seen for suicidality and self-harm (aHR, 1.54).

IN PRACTICE:

“Knowledge of the short- and long-term risks of serious mental health conditions after SMM and its subtypes could inform the need for enhanced postpartum supportive resources,” the authors wrote.

SOURCE:

This study was led by Asia Blackman, MSc, Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec, Canada. It was published online in JAMA Network Open.

LIMITATIONS:

The study is limited by its observational design, missing data, and misclassification bias.

DISCLOSURES:

This study was supported by funding from the Canadian Institutes of Health Research. Three authors reported receiving personal fees or grants outside the submitted work. No other conflicts of interest were reported.

A version of this article first appeared on Medscape.com.

The number of Americans seeking permanent forms of contraception has surged in the nearly 2 years since the Dobbs v. Jackson Women’s Health Organization Supreme Court decision that overturned a federal right to abortion, according to a study presented on May 5 at the annual meeting of the American Urological Association (AUA) (abstract PD40-03). Several other studies at the conference reported similar findings.

Rates of vasectomy and tubal ligation have increased in states where abortion became illegal after the court’s June 2022 ruling, researchers found. Rates of tubal sterilization had already been higher in states where abortion was illegal compared with those where access to the procedure remained available and was expected to remain so, but the difference widened after the decision. 

“Our study showed trends of increasing utilization of permanent contraception post-Dobbs, with a significant increase in patients less than 30 years old pursuing any type of permanent contraception post-Dobbs,” Jessica N. Schardein, MD, MS, of University of Utah Health in Salt Lake City, told attendees. “Reproductive autonomy is important for people of all genders and may be influenced by legal climate. Understanding the relationship between state-level abortion laws and trends in permanent contraception is crucial for us to determine how to best allocate resources for education and services to ensure reproductive rights for all patients.”

Dr. Schardein told this news organization the increase in vasectomies post-Dobbs was consistent across most states regardless of legal climate, showing that “reproductive health matters to all people,” both women and men.

“We should continue to offer permanent contraception to patients who are not interested in future fertility, regardless of their age or marital status, to ensure reproductive autonomy for those patients,” Dr. Schardein said. “Patients may need increased access to these procedures if the increased rates continue over time.”

Dr. Schardein’s study investigated national trends in the use of permanent contraception before and after the Dobbs ruling. She and her colleagues analyzed data from the Epic Cosmos database of more than 217 million patients from an estimated 27,000 clinics and 1260 hospitals nationwide. The researchers identified all adults who underwent a vasectomy or tubal ligation from July to December 2021 and then from July to December 2022, in the 5 months following the decision.

Among adults aged 18-30 years, rates of vasectomy were 1.59 times higher and rates of tubal ligation were 1.29 times higher after the Dobbs ruling than before it (P < .001). Although overall rates of tubal ligation among single women did not change after Dobbs, rates of vasectomy in single men were 1.13 times higher (P < .001).

States were categorized as not hostile to abortion access (abortion access remained available), hostile (access was restricted or might become illegal), or illegal on the basis of information from the Center for Reproductive Rights. Vasectomies increased in most states, with the biggest gain in Tennessee, where abortions are illegal. 

The increase in vasectomy rates was similar across nonhostile (incidence rate ratio [IRR], 1.43), hostile (IRR, 1.46), and illegal (IRR, 1.41) states (P < .001). Although the rate of increase was similar regardless of legal climate, the rate of vasectomies was higher in hostile and illegal states than in nonhostile states both before and after the Dobbs ruling, according to the researchers.

Rates of tubal ligation did not change as substantially across the United States after Dobbs, remaining unchanged in states hostile to abortion access and rising slightly in nonhostile states (IRR, 1.06) and in states where abortion is now illegal (IRR, 1.12; P < .001 for both).

However, when the researchers looked at tubal ligation in nonhostile states and hostile or illegal states, they found that rates of the procedure were nearly double in the hostile or illegal states both before and after Dobbs, with a bigger increase after Dobbs in illegal states. Tubal ligation rates were 1.85 times higher in illegal states than in nonhostile states after Dobbs, compared with being 1.76 times higher than in nonhostile states before Dobbs.
 

Other Studies Support the Findings 

Another study assessed the change in the volume of vasectomy consultations at six US academic medical centers in the 17 months before and 5 months after Dobbs (abstract PD40-02). The researchers reported that the rate was roughly 7% higher after the ruling than before (143 vs 134 cases per month, respectively). Again, the men seeking vasectomies after Dobbs were younger than those who sought the procedure before Dobbs (median age, 38 vs 39 years; P < .001). Post-Dobbs patients were also significantly more likely to be non-Hispanic White, English-speaking, and privately insured. 

“Younger, childless people are choosing vasectomies as permanent method of birth control,” lead author Kara L. Watts, MD, associate professor of urology at Montefiore Medical Center in Bronx, New York, told attendees. “The impact of this decision is likely to be long-lasting, requiring urologists and medical centers to adjust practice patterns to account for the increased demand.”

Twice as many childless married men underwent vasectomies after Dobbs than before the ruling (11% vs 5%, respectively; P = .001), but substantially more childless single men had the procedure after Dobbs than before it (36% vs 21%; P = .003). Those seeking vasectomies after Dobbs had to wait a median of 8 days longer between consult and procedure (59 vs 51 days pre-Dobbs; P < .001). Several of the same researchers had identified an increase in online searches about vasectomies in the months just after the Dobbs decision.

“We’ve been trying to get men to take more responsibility” for their role in unplanned pregnancies, Ajay K. Nangia, MD, MBBS, professor and vice chair of urology at University of Kansas Medical Center in Overland Park, told this news organization. Dr. Nangia, who helped conduct the study of vasectomy consultations and has spent years on research related to pharmaceutical contraception options for men, said the sudden increase in interest in vasectomies can be ethically fraught. Only 25% of vasectomies can be reversed, and some patients who seek the surgery may not have permanently ruled out having children.

“They’re going into this with their eyes wide open, knowing that it’s not 100% going to be reversible with a vasectomy,” he said. But fear of not having abortion access for their partners is part of their motivation, which creates tension for providers in balancing ethical counseling with the potential paternalism of advising against a vasectomy if they’re not certain that they don’t want children. 

“What happens in that situation, when it’s a political decision making you change your medical decision?” Dr. Nangia said. “I worry about that ethically.”

Dr. Nangia noted that the findings of his study cannot show that the Dobbs decision was the cause of the increase in vasectomies. However, in another abstract from the same session (PD40-01), researchers at The Ohio State University College of Medicine in Columbus presented findings from a survey of 57 men who underwent vasectomies in the preceding 2 years. Those results revealed that abortion access had been a factor among some of the 47% of patients whose procedures were performed after Dobbs. Post-Dobbs patients were significantly more likely to say they sought a vasectomy because of concerns about not being able to get abortion (P = .026) and because they didn’t want “to bring children into the current political climate” (P = .002). 

A study presented on May 6 (abstract MP76-06) involved a retrospective review of all 631 patients who underwent a vasectomy consult at UC San Diego Medical Center from June 2021 to June 2023. More vasectomy consults occurred after the Dobbs decision than before it (56% vs 44%). The gap for vasectomy consults was slightly wider for partnerless patients after vs before Dobbs (58% vs 42%) and substantially larger for childless patients post-Dobbs compared with pre-Dobbs (63% vs 37%). The childless men undergoing vasectomies after Dobbs also were significantly younger than those who had had this procedure before the ruling (mean, 36.4 vs 39.8 years; P <.001). 

“Patients should be counseled on the permanent nature of this procedure, underscoring need for effective and reversible male contraception,” the authors concluded.

Dr. Schardein and Dr. Watts reported no relevant financial conflicts of interest. Dr. Nangia is conducting an idiopathic infertility study with funding from Ferring Pharmaceuticals. None of the studies reported external funding.

A version of this article first appeared on Medscape.com.

The number of Americans seeking permanent forms of contraception has surged in the nearly 2 years since the Dobbs v. Jackson Women’s Health Organization Supreme Court decision that overturned a federal right to abortion, according to a study presented on May 5 at the annual meeting of the American Urological Association (AUA) (abstract PD40-03). Several other studies at the conference reported similar findings.

Rates of vasectomy and tubal ligation have increased in states where abortion became illegal after the court’s June 2022 ruling, researchers found. Rates of tubal sterilization had already been higher in states where abortion was illegal compared with those where access to the procedure remained available and was expected to remain so, but the difference widened after the decision. 

“Our study showed trends of increasing utilization of permanent contraception post-Dobbs, with a significant increase in patients less than 30 years old pursuing any type of permanent contraception post-Dobbs,” Jessica N. Schardein, MD, MS, of University of Utah Health in Salt Lake City, told attendees. “Reproductive autonomy is important for people of all genders and may be influenced by legal climate. Understanding the relationship between state-level abortion laws and trends in permanent contraception is crucial for us to determine how to best allocate resources for education and services to ensure reproductive rights for all patients.”

Dr. Schardein told this news organization the increase in vasectomies post-Dobbs was consistent across most states regardless of legal climate, showing that “reproductive health matters to all people,” both women and men.

“We should continue to offer permanent contraception to patients who are not interested in future fertility, regardless of their age or marital status, to ensure reproductive autonomy for those patients,” Dr. Schardein said. “Patients may need increased access to these procedures if the increased rates continue over time.”

Dr. Schardein’s study investigated national trends in the use of permanent contraception before and after the Dobbs ruling. She and her colleagues analyzed data from the Epic Cosmos database of more than 217 million patients from an estimated 27,000 clinics and 1260 hospitals nationwide. The researchers identified all adults who underwent a vasectomy or tubal ligation from July to December 2021 and then from July to December 2022, in the 5 months following the decision.

Among adults aged 18-30 years, rates of vasectomy were 1.59 times higher and rates of tubal ligation were 1.29 times higher after the Dobbs ruling than before it (P < .001). Although overall rates of tubal ligation among single women did not change after Dobbs, rates of vasectomy in single men were 1.13 times higher (P < .001).

States were categorized as not hostile to abortion access (abortion access remained available), hostile (access was restricted or might become illegal), or illegal on the basis of information from the Center for Reproductive Rights. Vasectomies increased in most states, with the biggest gain in Tennessee, where abortions are illegal. 

The increase in vasectomy rates was similar across nonhostile (incidence rate ratio [IRR], 1.43), hostile (IRR, 1.46), and illegal (IRR, 1.41) states (P < .001). Although the rate of increase was similar regardless of legal climate, the rate of vasectomies was higher in hostile and illegal states than in nonhostile states both before and after the Dobbs ruling, according to the researchers.

Rates of tubal ligation did not change as substantially across the United States after Dobbs, remaining unchanged in states hostile to abortion access and rising slightly in nonhostile states (IRR, 1.06) and in states where abortion is now illegal (IRR, 1.12; P < .001 for both).

However, when the researchers looked at tubal ligation in nonhostile states and hostile or illegal states, they found that rates of the procedure were nearly double in the hostile or illegal states both before and after Dobbs, with a bigger increase after Dobbs in illegal states. Tubal ligation rates were 1.85 times higher in illegal states than in nonhostile states after Dobbs, compared with being 1.76 times higher than in nonhostile states before Dobbs.
 

Other Studies Support the Findings 

Another study assessed the change in the volume of vasectomy consultations at six US academic medical centers in the 17 months before and 5 months after Dobbs (abstract PD40-02). The researchers reported that the rate was roughly 7% higher after the ruling than before (143 vs 134 cases per month, respectively). Again, the men seeking vasectomies after Dobbs were younger than those who sought the procedure before Dobbs (median age, 38 vs 39 years; P < .001). Post-Dobbs patients were also significantly more likely to be non-Hispanic White, English-speaking, and privately insured. 

“Younger, childless people are choosing vasectomies as permanent method of birth control,” lead author Kara L. Watts, MD, associate professor of urology at Montefiore Medical Center in Bronx, New York, told attendees. “The impact of this decision is likely to be long-lasting, requiring urologists and medical centers to adjust practice patterns to account for the increased demand.”

Twice as many childless married men underwent vasectomies after Dobbs than before the ruling (11% vs 5%, respectively; P = .001), but substantially more childless single men had the procedure after Dobbs than before it (36% vs 21%; P = .003). Those seeking vasectomies after Dobbs had to wait a median of 8 days longer between consult and procedure (59 vs 51 days pre-Dobbs; P < .001). Several of the same researchers had identified an increase in online searches about vasectomies in the months just after the Dobbs decision.

“We’ve been trying to get men to take more responsibility” for their role in unplanned pregnancies, Ajay K. Nangia, MD, MBBS, professor and vice chair of urology at University of Kansas Medical Center in Overland Park, told this news organization. Dr. Nangia, who helped conduct the study of vasectomy consultations and has spent years on research related to pharmaceutical contraception options for men, said the sudden increase in interest in vasectomies can be ethically fraught. Only 25% of vasectomies can be reversed, and some patients who seek the surgery may not have permanently ruled out having children.

“They’re going into this with their eyes wide open, knowing that it’s not 100% going to be reversible with a vasectomy,” he said. But fear of not having abortion access for their partners is part of their motivation, which creates tension for providers in balancing ethical counseling with the potential paternalism of advising against a vasectomy if they’re not certain that they don’t want children. 

“What happens in that situation, when it’s a political decision making you change your medical decision?” Dr. Nangia said. “I worry about that ethically.”

Dr. Nangia noted that the findings of his study cannot show that the Dobbs decision was the cause of the increase in vasectomies. However, in another abstract from the same session (PD40-01), researchers at The Ohio State University College of Medicine in Columbus presented findings from a survey of 57 men who underwent vasectomies in the preceding 2 years. Those results revealed that abortion access had been a factor among some of the 47% of patients whose procedures were performed after Dobbs. Post-Dobbs patients were significantly more likely to say they sought a vasectomy because of concerns about not being able to get abortion (P = .026) and because they didn’t want “to bring children into the current political climate” (P = .002). 

A study presented on May 6 (abstract MP76-06) involved a retrospective review of all 631 patients who underwent a vasectomy consult at UC San Diego Medical Center from June 2021 to June 2023. More vasectomy consults occurred after the Dobbs decision than before it (56% vs 44%). The gap for vasectomy consults was slightly wider for partnerless patients after vs before Dobbs (58% vs 42%) and substantially larger for childless patients post-Dobbs compared with pre-Dobbs (63% vs 37%). The childless men undergoing vasectomies after Dobbs also were significantly younger than those who had had this procedure before the ruling (mean, 36.4 vs 39.8 years; P <.001). 

“Patients should be counseled on the permanent nature of this procedure, underscoring need for effective and reversible male contraception,” the authors concluded.

Dr. Schardein and Dr. Watts reported no relevant financial conflicts of interest. Dr. Nangia is conducting an idiopathic infertility study with funding from Ferring Pharmaceuticals. None of the studies reported external funding.

A version of this article first appeared on Medscape.com.

The number of Americans seeking permanent forms of contraception has surged in the nearly 2 years since the Dobbs v. Jackson Women’s Health Organization Supreme Court decision that overturned a federal right to abortion, according to a study presented on May 5 at the annual meeting of the American Urological Association (AUA) (abstract PD40-03). Several other studies at the conference reported similar findings.

Rates of vasectomy and tubal ligation have increased in states where abortion became illegal after the court’s June 2022 ruling, researchers found. Rates of tubal sterilization had already been higher in states where abortion was illegal compared with those where access to the procedure remained available and was expected to remain so, but the difference widened after the decision. 

“Our study showed trends of increasing utilization of permanent contraception post-Dobbs, with a significant increase in patients less than 30 years old pursuing any type of permanent contraception post-Dobbs,” Jessica N. Schardein, MD, MS, of University of Utah Health in Salt Lake City, told attendees. “Reproductive autonomy is important for people of all genders and may be influenced by legal climate. Understanding the relationship between state-level abortion laws and trends in permanent contraception is crucial for us to determine how to best allocate resources for education and services to ensure reproductive rights for all patients.”

Dr. Schardein told this news organization the increase in vasectomies post-Dobbs was consistent across most states regardless of legal climate, showing that “reproductive health matters to all people,” both women and men.

“We should continue to offer permanent contraception to patients who are not interested in future fertility, regardless of their age or marital status, to ensure reproductive autonomy for those patients,” Dr. Schardein said. “Patients may need increased access to these procedures if the increased rates continue over time.”

Dr. Schardein’s study investigated national trends in the use of permanent contraception before and after the Dobbs ruling. She and her colleagues analyzed data from the Epic Cosmos database of more than 217 million patients from an estimated 27,000 clinics and 1260 hospitals nationwide. The researchers identified all adults who underwent a vasectomy or tubal ligation from July to December 2021 and then from July to December 2022, in the 5 months following the decision.

Among adults aged 18-30 years, rates of vasectomy were 1.59 times higher and rates of tubal ligation were 1.29 times higher after the Dobbs ruling than before it (P < .001). Although overall rates of tubal ligation among single women did not change after Dobbs, rates of vasectomy in single men were 1.13 times higher (P < .001).

States were categorized as not hostile to abortion access (abortion access remained available), hostile (access was restricted or might become illegal), or illegal on the basis of information from the Center for Reproductive Rights. Vasectomies increased in most states, with the biggest gain in Tennessee, where abortions are illegal. 

The increase in vasectomy rates was similar across nonhostile (incidence rate ratio [IRR], 1.43), hostile (IRR, 1.46), and illegal (IRR, 1.41) states (P < .001). Although the rate of increase was similar regardless of legal climate, the rate of vasectomies was higher in hostile and illegal states than in nonhostile states both before and after the Dobbs ruling, according to the researchers.

Rates of tubal ligation did not change as substantially across the United States after Dobbs, remaining unchanged in states hostile to abortion access and rising slightly in nonhostile states (IRR, 1.06) and in states where abortion is now illegal (IRR, 1.12; P < .001 for both).

However, when the researchers looked at tubal ligation in nonhostile states and hostile or illegal states, they found that rates of the procedure were nearly double in the hostile or illegal states both before and after Dobbs, with a bigger increase after Dobbs in illegal states. Tubal ligation rates were 1.85 times higher in illegal states than in nonhostile states after Dobbs, compared with being 1.76 times higher than in nonhostile states before Dobbs.
 

Other Studies Support the Findings 

Another study assessed the change in the volume of vasectomy consultations at six US academic medical centers in the 17 months before and 5 months after Dobbs (abstract PD40-02). The researchers reported that the rate was roughly 7% higher after the ruling than before (143 vs 134 cases per month, respectively). Again, the men seeking vasectomies after Dobbs were younger than those who sought the procedure before Dobbs (median age, 38 vs 39 years; P < .001). Post-Dobbs patients were also significantly more likely to be non-Hispanic White, English-speaking, and privately insured. 

“Younger, childless people are choosing vasectomies as permanent method of birth control,” lead author Kara L. Watts, MD, associate professor of urology at Montefiore Medical Center in Bronx, New York, told attendees. “The impact of this decision is likely to be long-lasting, requiring urologists and medical centers to adjust practice patterns to account for the increased demand.”

Twice as many childless married men underwent vasectomies after Dobbs than before the ruling (11% vs 5%, respectively; P = .001), but substantially more childless single men had the procedure after Dobbs than before it (36% vs 21%; P = .003). Those seeking vasectomies after Dobbs had to wait a median of 8 days longer between consult and procedure (59 vs 51 days pre-Dobbs; P < .001). Several of the same researchers had identified an increase in online searches about vasectomies in the months just after the Dobbs decision.

“We’ve been trying to get men to take more responsibility” for their role in unplanned pregnancies, Ajay K. Nangia, MD, MBBS, professor and vice chair of urology at University of Kansas Medical Center in Overland Park, told this news organization. Dr. Nangia, who helped conduct the study of vasectomy consultations and has spent years on research related to pharmaceutical contraception options for men, said the sudden increase in interest in vasectomies can be ethically fraught. Only 25% of vasectomies can be reversed, and some patients who seek the surgery may not have permanently ruled out having children.

“They’re going into this with their eyes wide open, knowing that it’s not 100% going to be reversible with a vasectomy,” he said. But fear of not having abortion access for their partners is part of their motivation, which creates tension for providers in balancing ethical counseling with the potential paternalism of advising against a vasectomy if they’re not certain that they don’t want children. 

“What happens in that situation, when it’s a political decision making you change your medical decision?” Dr. Nangia said. “I worry about that ethically.”

Dr. Nangia noted that the findings of his study cannot show that the Dobbs decision was the cause of the increase in vasectomies. However, in another abstract from the same session (PD40-01), researchers at The Ohio State University College of Medicine in Columbus presented findings from a survey of 57 men who underwent vasectomies in the preceding 2 years. Those results revealed that abortion access had been a factor among some of the 47% of patients whose procedures were performed after Dobbs. Post-Dobbs patients were significantly more likely to say they sought a vasectomy because of concerns about not being able to get abortion (P = .026) and because they didn’t want “to bring children into the current political climate” (P = .002). 

A study presented on May 6 (abstract MP76-06) involved a retrospective review of all 631 patients who underwent a vasectomy consult at UC San Diego Medical Center from June 2021 to June 2023. More vasectomy consults occurred after the Dobbs decision than before it (56% vs 44%). The gap for vasectomy consults was slightly wider for partnerless patients after vs before Dobbs (58% vs 42%) and substantially larger for childless patients post-Dobbs compared with pre-Dobbs (63% vs 37%). The childless men undergoing vasectomies after Dobbs also were significantly younger than those who had had this procedure before the ruling (mean, 36.4 vs 39.8 years; P <.001). 

“Patients should be counseled on the permanent nature of this procedure, underscoring need for effective and reversible male contraception,” the authors concluded.

Dr. Schardein and Dr. Watts reported no relevant financial conflicts of interest. Dr. Nangia is conducting an idiopathic infertility study with funding from Ferring Pharmaceuticals. None of the studies reported external funding.

A version of this article first appeared on Medscape.com.

New expert guidance to help clinicians manage the treatment of patients with epilepsy during pregnancy has been released.

Issued by the American Academy of Neurology, the American Epilepsy Society, and the Society for Maternal-Fetal Medicine, the new practice guideline covers the use of antiseizure medications (ASMs) and folic acid supplementation before conception and during pregnancy.

“Most children born to people with epilepsy are healthy, but there is a small risk of pregnancy-related problems, partly due to seizures and partly due to the effects of antiseizure medications,” the guidelines’ lead author Alison M. Pack, MD, MPH, professor of neurology and chief of the Epilepsy and Sleep Division, Columbia University, New York City, said in a news release.

“This guideline provides recommendations regarding the effects of antiseizure medications and folic acid supplementation on malformations at birth and the development of children during pregnancy, so that doctors and people with epilepsy can determine which treatments may be best for them,” she added. 

The guideline was published online in Neurology.
 

Why Now? 

The new guideline updates the 2009 guidance on epilepsy management during pregnancy. Since then, Dr. Pack told this news organization, there has been a wealth of new data on differential effects of different ASMs — notably, lamotrigine and levetiracetam — the most commonly prescribed medications in this population.

“In this guideline, we were able to assess differential effects of different ASMs on outcomes of interest, including major congenital malformations [MCMs], perinatal outcomes, and neurodevelopmental outcomes. In addition, we looked at the effect of folic acid supplementation on each of these outcomes,” she said.

The overarching goals of care for patients are to “optimize health outcomes both for individuals and their future offspring,” the authors wrote. Shared decision-making, they add, leads to better decision-making by providing a better understanding of the available treatment options and their potential risks, resulting in enhanced decision-making that aligns with personal values.

Clinicians should recommend ASMs that optimize seizure control and fetal outcomes, in the event of a pregnancy, at the earliest possible preconception time, the guideline authors note.

“Overall, treating clinicians need to balance treating the person with epilepsy to control convulsive seizures (generalized tonic-clonic seizures and focal-to-bilateral tonic-clonic seizures) to minimize potential risks to the birth parent and the possible risks of certain ASMs on the fetus if pregnancy occurs,” they wrote.

If a patient is already pregnant, the experts recommend that clinicians “exercise caution” in removing or replacing an ASM that controls convulsive seizures, even if it’s “not an optimal choice” for the fetus. 

In addition, they advise that ASM levels should be monitored throughout the pregnancy, guided by individual ASM pharmacokinetics and an individual patient’s clinical presentation. ASM dose, they note, should be adjusted during pregnancy in response to decreasing serum ASM levels or worsening seizure control.

The authors point out that there are limited data on “pregnancy-related outcomes with respect to acetazolamide, eslicarbazepine, ethosuximide, lacosamide, nitrazepam, perampanel, piracetam, pregabalin, rufinamide, stiripentol, tiagabine, and vigabatrin.”

Patients should be informed that the birth prevalence of any major congenital malformation in the general population ranges between 2.4% and 2.9%.
 

If Feasible, Avoid Valproic Acid 

“One of the most important take-home messages is that valproic acid has the highest unadjusted birth prevalence of all major congenital malformations — 9.7% — and the highest unadjusted birth prevalence of neural tube defects at 1.4%,” Dr. Pack said. As a result, the guideline authors advise against using valproic acid, if clinically feasible.

Valproic acid also has the highest prevalence of negative neurodevelopmental outcomes, including a reduction in global IQ and an increased prevalence of autism spectrum disorder (ASD). Patients should be counseled accordingly and advised of the increased risk for ASD and decreased IQ resulting from valproic acid.

Clinicians should consider using lamotrigine, levetiracetam, or oxcarbazepine when appropriate. Serum concentrations of most ASMs have a “defined therapeutic window” for effective seizure control and that concentration may decrease during pregnancy, particularly with lamotrigine and levetiracetam, the authors note.

Phenobarbital, topiramate, and valproic acid should because of the increased risk for cardiac malformations, oral clefts, and urogenital and renal malformations.

Fetal screening for major congenital malformations is recommended to enable early detection and timely intervention in patients treated with any ASM during pregnancy Patients receiving phenobarbital during pregnancy should also undergo fetal cardiac screenings.

Valproic acid and topiramate are also associated with children who are small for their gestational age. To enable early identification of fetal growth restriction, patients taking valproic acid or topiramate should be monitored. In addition, children exposed to these medications in utero should be monitored during childhood to ensure they are meeting age-appropriate developmental milestones. 

Folic acid taken during pregnancy can reduce the prevalence of negative neurodevelopment outcomes, but not major congenital malformations, Dr. Pack noted. 

“Due to limited available data, we were unable to define an optimal dose of folic acid supplementation beyond at least 0.4 mg/d,” Dr. Pack said. “Future studies, preferably randomized clinical trials, are needed to better define the optimal dose.”

She emphasized that epilepsy is one of the most common neurologic disorders, and 1 in 5 of those affected are people of childbearing potential. Understanding the effects of ASMs on pregnancy outcomes is critical for physicians who manage these patients.
 

Uncertainty Remains 

Commenting for this news organization, Kimford Meador, MD, a professor in the Department of Neurology and Neurological Sciences at Stanford University School of Medicine , Stanford Neuroscience Health Center, Palo Alto, California, noted that the new guidelines reflect the gains in knowledge since 2009 and that the recommendations are “reasonable, based on available data.”

However, “one very important point is how much remains unknown,” said Dr. Meador, who was not involved in writing the current guideline. “Many ASMs have no data, and several have estimates based on small samples or a single observational study.” Thus, “the risks for the majority of ASMs are uncertain.”

Given that randomized trials “are not possible in this population, and that all observational studies are subject to residual confounding, a reliable signal across multiple studies in humans is required to be certain of findings,” he stated.

This practice guideline was developed with financial support from the American Academy of Neurology. Dr. Pack serves on the editorial board for the journal Epilepsy Currents, receives royalties from UpToDate, receives funding from the National Institutes of Health for serving as coinvestigator and site principal investigator for the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, and receives funding from Bayer for serving as a co-investigator on a study on women with epilepsy initiating a progestin intrauterine device. One of Dr. Pack’s immediate family members has received personal compensation for serving as an employee of REGENEXBIO. The other authors’ disclosures are listed on the original paper. Dr. Meador has received research support from the National Institutes of Health, Veterans Administration, Eisai, Inc, and Suno Medtronic Navigation, Inc, and the Epilepsy Study Consortium pays Dr. Meador’s university for his research on the Human Epilepsy Project and consultant time related to Eisai, UCB Pharma, and Xenon.

A version of this article first appeared on Medscape.com.

New expert guidance to help clinicians manage the treatment of patients with epilepsy during pregnancy has been released.

Issued by the American Academy of Neurology, the American Epilepsy Society, and the Society for Maternal-Fetal Medicine, the new practice guideline covers the use of antiseizure medications (ASMs) and folic acid supplementation before conception and during pregnancy.

“Most children born to people with epilepsy are healthy, but there is a small risk of pregnancy-related problems, partly due to seizures and partly due to the effects of antiseizure medications,” the guidelines’ lead author Alison M. Pack, MD, MPH, professor of neurology and chief of the Epilepsy and Sleep Division, Columbia University, New York City, said in a news release.

“This guideline provides recommendations regarding the effects of antiseizure medications and folic acid supplementation on malformations at birth and the development of children during pregnancy, so that doctors and people with epilepsy can determine which treatments may be best for them,” she added. 

The guideline was published online in Neurology.
 

Why Now? 

The new guideline updates the 2009 guidance on epilepsy management during pregnancy. Since then, Dr. Pack told this news organization, there has been a wealth of new data on differential effects of different ASMs — notably, lamotrigine and levetiracetam — the most commonly prescribed medications in this population.

“In this guideline, we were able to assess differential effects of different ASMs on outcomes of interest, including major congenital malformations [MCMs], perinatal outcomes, and neurodevelopmental outcomes. In addition, we looked at the effect of folic acid supplementation on each of these outcomes,” she said.

The overarching goals of care for patients are to “optimize health outcomes both for individuals and their future offspring,” the authors wrote. Shared decision-making, they add, leads to better decision-making by providing a better understanding of the available treatment options and their potential risks, resulting in enhanced decision-making that aligns with personal values.

Clinicians should recommend ASMs that optimize seizure control and fetal outcomes, in the event of a pregnancy, at the earliest possible preconception time, the guideline authors note.

“Overall, treating clinicians need to balance treating the person with epilepsy to control convulsive seizures (generalized tonic-clonic seizures and focal-to-bilateral tonic-clonic seizures) to minimize potential risks to the birth parent and the possible risks of certain ASMs on the fetus if pregnancy occurs,” they wrote.

If a patient is already pregnant, the experts recommend that clinicians “exercise caution” in removing or replacing an ASM that controls convulsive seizures, even if it’s “not an optimal choice” for the fetus. 

In addition, they advise that ASM levels should be monitored throughout the pregnancy, guided by individual ASM pharmacokinetics and an individual patient’s clinical presentation. ASM dose, they note, should be adjusted during pregnancy in response to decreasing serum ASM levels or worsening seizure control.

The authors point out that there are limited data on “pregnancy-related outcomes with respect to acetazolamide, eslicarbazepine, ethosuximide, lacosamide, nitrazepam, perampanel, piracetam, pregabalin, rufinamide, stiripentol, tiagabine, and vigabatrin.”

Patients should be informed that the birth prevalence of any major congenital malformation in the general population ranges between 2.4% and 2.9%.
 

If Feasible, Avoid Valproic Acid 

“One of the most important take-home messages is that valproic acid has the highest unadjusted birth prevalence of all major congenital malformations — 9.7% — and the highest unadjusted birth prevalence of neural tube defects at 1.4%,” Dr. Pack said. As a result, the guideline authors advise against using valproic acid, if clinically feasible.

Valproic acid also has the highest prevalence of negative neurodevelopmental outcomes, including a reduction in global IQ and an increased prevalence of autism spectrum disorder (ASD). Patients should be counseled accordingly and advised of the increased risk for ASD and decreased IQ resulting from valproic acid.

Clinicians should consider using lamotrigine, levetiracetam, or oxcarbazepine when appropriate. Serum concentrations of most ASMs have a “defined therapeutic window” for effective seizure control and that concentration may decrease during pregnancy, particularly with lamotrigine and levetiracetam, the authors note.

Phenobarbital, topiramate, and valproic acid should because of the increased risk for cardiac malformations, oral clefts, and urogenital and renal malformations.

Fetal screening for major congenital malformations is recommended to enable early detection and timely intervention in patients treated with any ASM during pregnancy Patients receiving phenobarbital during pregnancy should also undergo fetal cardiac screenings.

Valproic acid and topiramate are also associated with children who are small for their gestational age. To enable early identification of fetal growth restriction, patients taking valproic acid or topiramate should be monitored. In addition, children exposed to these medications in utero should be monitored during childhood to ensure they are meeting age-appropriate developmental milestones. 

Folic acid taken during pregnancy can reduce the prevalence of negative neurodevelopment outcomes, but not major congenital malformations, Dr. Pack noted. 

“Due to limited available data, we were unable to define an optimal dose of folic acid supplementation beyond at least 0.4 mg/d,” Dr. Pack said. “Future studies, preferably randomized clinical trials, are needed to better define the optimal dose.”

She emphasized that epilepsy is one of the most common neurologic disorders, and 1 in 5 of those affected are people of childbearing potential. Understanding the effects of ASMs on pregnancy outcomes is critical for physicians who manage these patients.
 

Uncertainty Remains 

Commenting for this news organization, Kimford Meador, MD, a professor in the Department of Neurology and Neurological Sciences at Stanford University School of Medicine , Stanford Neuroscience Health Center, Palo Alto, California, noted that the new guidelines reflect the gains in knowledge since 2009 and that the recommendations are “reasonable, based on available data.”

However, “one very important point is how much remains unknown,” said Dr. Meador, who was not involved in writing the current guideline. “Many ASMs have no data, and several have estimates based on small samples or a single observational study.” Thus, “the risks for the majority of ASMs are uncertain.”

Given that randomized trials “are not possible in this population, and that all observational studies are subject to residual confounding, a reliable signal across multiple studies in humans is required to be certain of findings,” he stated.

This practice guideline was developed with financial support from the American Academy of Neurology. Dr. Pack serves on the editorial board for the journal Epilepsy Currents, receives royalties from UpToDate, receives funding from the National Institutes of Health for serving as coinvestigator and site principal investigator for the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, and receives funding from Bayer for serving as a co-investigator on a study on women with epilepsy initiating a progestin intrauterine device. One of Dr. Pack’s immediate family members has received personal compensation for serving as an employee of REGENEXBIO. The other authors’ disclosures are listed on the original paper. Dr. Meador has received research support from the National Institutes of Health, Veterans Administration, Eisai, Inc, and Suno Medtronic Navigation, Inc, and the Epilepsy Study Consortium pays Dr. Meador’s university for his research on the Human Epilepsy Project and consultant time related to Eisai, UCB Pharma, and Xenon.

A version of this article first appeared on Medscape.com.

New expert guidance to help clinicians manage the treatment of patients with epilepsy during pregnancy has been released.

Issued by the American Academy of Neurology, the American Epilepsy Society, and the Society for Maternal-Fetal Medicine, the new practice guideline covers the use of antiseizure medications (ASMs) and folic acid supplementation before conception and during pregnancy.

“Most children born to people with epilepsy are healthy, but there is a small risk of pregnancy-related problems, partly due to seizures and partly due to the effects of antiseizure medications,” the guidelines’ lead author Alison M. Pack, MD, MPH, professor of neurology and chief of the Epilepsy and Sleep Division, Columbia University, New York City, said in a news release.

“This guideline provides recommendations regarding the effects of antiseizure medications and folic acid supplementation on malformations at birth and the development of children during pregnancy, so that doctors and people with epilepsy can determine which treatments may be best for them,” she added. 

The guideline was published online in Neurology.
 

Why Now? 

The new guideline updates the 2009 guidance on epilepsy management during pregnancy. Since then, Dr. Pack told this news organization, there has been a wealth of new data on differential effects of different ASMs — notably, lamotrigine and levetiracetam — the most commonly prescribed medications in this population.

“In this guideline, we were able to assess differential effects of different ASMs on outcomes of interest, including major congenital malformations [MCMs], perinatal outcomes, and neurodevelopmental outcomes. In addition, we looked at the effect of folic acid supplementation on each of these outcomes,” she said.

The overarching goals of care for patients are to “optimize health outcomes both for individuals and their future offspring,” the authors wrote. Shared decision-making, they add, leads to better decision-making by providing a better understanding of the available treatment options and their potential risks, resulting in enhanced decision-making that aligns with personal values.

Clinicians should recommend ASMs that optimize seizure control and fetal outcomes, in the event of a pregnancy, at the earliest possible preconception time, the guideline authors note.

“Overall, treating clinicians need to balance treating the person with epilepsy to control convulsive seizures (generalized tonic-clonic seizures and focal-to-bilateral tonic-clonic seizures) to minimize potential risks to the birth parent and the possible risks of certain ASMs on the fetus if pregnancy occurs,” they wrote.

If a patient is already pregnant, the experts recommend that clinicians “exercise caution” in removing or replacing an ASM that controls convulsive seizures, even if it’s “not an optimal choice” for the fetus. 

In addition, they advise that ASM levels should be monitored throughout the pregnancy, guided by individual ASM pharmacokinetics and an individual patient’s clinical presentation. ASM dose, they note, should be adjusted during pregnancy in response to decreasing serum ASM levels or worsening seizure control.

The authors point out that there are limited data on “pregnancy-related outcomes with respect to acetazolamide, eslicarbazepine, ethosuximide, lacosamide, nitrazepam, perampanel, piracetam, pregabalin, rufinamide, stiripentol, tiagabine, and vigabatrin.”

Patients should be informed that the birth prevalence of any major congenital malformation in the general population ranges between 2.4% and 2.9%.
 

If Feasible, Avoid Valproic Acid 

“One of the most important take-home messages is that valproic acid has the highest unadjusted birth prevalence of all major congenital malformations — 9.7% — and the highest unadjusted birth prevalence of neural tube defects at 1.4%,” Dr. Pack said. As a result, the guideline authors advise against using valproic acid, if clinically feasible.

Valproic acid also has the highest prevalence of negative neurodevelopmental outcomes, including a reduction in global IQ and an increased prevalence of autism spectrum disorder (ASD). Patients should be counseled accordingly and advised of the increased risk for ASD and decreased IQ resulting from valproic acid.

Clinicians should consider using lamotrigine, levetiracetam, or oxcarbazepine when appropriate. Serum concentrations of most ASMs have a “defined therapeutic window” for effective seizure control and that concentration may decrease during pregnancy, particularly with lamotrigine and levetiracetam, the authors note.

Phenobarbital, topiramate, and valproic acid should because of the increased risk for cardiac malformations, oral clefts, and urogenital and renal malformations.

Fetal screening for major congenital malformations is recommended to enable early detection and timely intervention in patients treated with any ASM during pregnancy Patients receiving phenobarbital during pregnancy should also undergo fetal cardiac screenings.

Valproic acid and topiramate are also associated with children who are small for their gestational age. To enable early identification of fetal growth restriction, patients taking valproic acid or topiramate should be monitored. In addition, children exposed to these medications in utero should be monitored during childhood to ensure they are meeting age-appropriate developmental milestones. 

Folic acid taken during pregnancy can reduce the prevalence of negative neurodevelopment outcomes, but not major congenital malformations, Dr. Pack noted. 

“Due to limited available data, we were unable to define an optimal dose of folic acid supplementation beyond at least 0.4 mg/d,” Dr. Pack said. “Future studies, preferably randomized clinical trials, are needed to better define the optimal dose.”

She emphasized that epilepsy is one of the most common neurologic disorders, and 1 in 5 of those affected are people of childbearing potential. Understanding the effects of ASMs on pregnancy outcomes is critical for physicians who manage these patients.
 

Uncertainty Remains 

Commenting for this news organization, Kimford Meador, MD, a professor in the Department of Neurology and Neurological Sciences at Stanford University School of Medicine , Stanford Neuroscience Health Center, Palo Alto, California, noted that the new guidelines reflect the gains in knowledge since 2009 and that the recommendations are “reasonable, based on available data.”

However, “one very important point is how much remains unknown,” said Dr. Meador, who was not involved in writing the current guideline. “Many ASMs have no data, and several have estimates based on small samples or a single observational study.” Thus, “the risks for the majority of ASMs are uncertain.”

Given that randomized trials “are not possible in this population, and that all observational studies are subject to residual confounding, a reliable signal across multiple studies in humans is required to be certain of findings,” he stated.

This practice guideline was developed with financial support from the American Academy of Neurology. Dr. Pack serves on the editorial board for the journal Epilepsy Currents, receives royalties from UpToDate, receives funding from the National Institutes of Health for serving as coinvestigator and site principal investigator for the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, and receives funding from Bayer for serving as a co-investigator on a study on women with epilepsy initiating a progestin intrauterine device. One of Dr. Pack’s immediate family members has received personal compensation for serving as an employee of REGENEXBIO. The other authors’ disclosures are listed on the original paper. Dr. Meador has received research support from the National Institutes of Health, Veterans Administration, Eisai, Inc, and Suno Medtronic Navigation, Inc, and the Epilepsy Study Consortium pays Dr. Meador’s university for his research on the Human Epilepsy Project and consultant time related to Eisai, UCB Pharma, and Xenon.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO — Discussion of gestational weight gain occurred in only half of first-time obstetric visits, most often brought up by the provider, according to data presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“Weight can be a challenging and sensitive topic at a healthcare visit,” Malini Harinath, an undergraduate research assistant at Magee-Women’s Research Institute at University of Pittsburgh Medical Center, told attendees. “Providers discussed weight gain recommendations in less than half of conversations.”

The researchers analyzed an existing dataset of audio-recorded first obstetric visits to find out how often gestational weight gain was brought up, who initiated the discussion, whether ACOG guidelines were discussed, and what the provider’s comments were.

Among 150 visits, half (50%) involved discussion of weight, with patients bringing it up 24% of the time and providers bringing it up 72% of the time. In the other 3% of visits, it was brought up by a third party, such as a partner or other family member with the patient.

Only two of those visits mentioned body mass index (BMI) specifically, and ACOG guidelines on gestational weight gain were brought up in only six visits (8% of the visits where weight was mentioned). However, mention of recommendations on gestational weight gain was more frequent, coming up in nearly half (46.7%) of the visits where weight was mentioned, though that was still just 23% of all visits.

Concern about weight was brought up in 25.3% of visits where weight was discussed, and the provider’s reassurance to the patient occurred in about a third (32%) of those visits. General comments about the patient’s body occurred in 16% of visits, such as a clinician saying, “Usually we start trying [to find the heartbeat] at about 15 weeks, but you are so skinny we might be able to find it now.”

Ms. Harinath intends to look in future research at whether patient race or BMI are associated with the frequency and content of gestational weight gain conversations and to explore how patients react to different ways that discussion of weight is brought up.

Katherine Kaak, MD, a second-year resident at the University of Tennessee Graduate School of Medicine in Knoxville, was surprised that weight was brought up in only half of the visits. “The clinical takeaway is just how important counseling in the prenatal time is and how a lot of this discussion is preventive medicine,” Dr. Kaak said. “Even though we think of those visits as being quick, it’s good to keep in mind that we need to really take our time and make sure we counsel the patient as best we can.”

There’s a fair amount of research suggesting that existing recommendations on gestational weight gain are not very good because they’re very generic, Jill Maples, PhD, associate professor of ob.gyn. research at the University of Tennessee Graduate School of Medicine, said in an interview. For example, the guidelines are generally the same for everyone with a BMI over 30, but a person with a BMI of 30 is very different from someone with a BMI of 50, she said.

“There’s not even a lot of clarity on what is appropriate weight gain for that group because some people have seen good outcomes on the lower end of gestational weight gain,” Dr. Maples said. She said it’s important that clinicians not forget about the importance of these discussions, however, because lifestyle habits and gestational weight gain are related to maternal and neonatal outcomes.

The authors, Dr. Kaak, and Dr. Maples had no disclosures. The research was funded by the National Institute on Drug Abuse.

SAN FRANCISCO — Discussion of gestational weight gain occurred in only half of first-time obstetric visits, most often brought up by the provider, according to data presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“Weight can be a challenging and sensitive topic at a healthcare visit,” Malini Harinath, an undergraduate research assistant at Magee-Women’s Research Institute at University of Pittsburgh Medical Center, told attendees. “Providers discussed weight gain recommendations in less than half of conversations.”

The researchers analyzed an existing dataset of audio-recorded first obstetric visits to find out how often gestational weight gain was brought up, who initiated the discussion, whether ACOG guidelines were discussed, and what the provider’s comments were.

Among 150 visits, half (50%) involved discussion of weight, with patients bringing it up 24% of the time and providers bringing it up 72% of the time. In the other 3% of visits, it was brought up by a third party, such as a partner or other family member with the patient.

Only two of those visits mentioned body mass index (BMI) specifically, and ACOG guidelines on gestational weight gain were brought up in only six visits (8% of the visits where weight was mentioned). However, mention of recommendations on gestational weight gain was more frequent, coming up in nearly half (46.7%) of the visits where weight was mentioned, though that was still just 23% of all visits.

Concern about weight was brought up in 25.3% of visits where weight was discussed, and the provider’s reassurance to the patient occurred in about a third (32%) of those visits. General comments about the patient’s body occurred in 16% of visits, such as a clinician saying, “Usually we start trying [to find the heartbeat] at about 15 weeks, but you are so skinny we might be able to find it now.”

Ms. Harinath intends to look in future research at whether patient race or BMI are associated with the frequency and content of gestational weight gain conversations and to explore how patients react to different ways that discussion of weight is brought up.

Katherine Kaak, MD, a second-year resident at the University of Tennessee Graduate School of Medicine in Knoxville, was surprised that weight was brought up in only half of the visits. “The clinical takeaway is just how important counseling in the prenatal time is and how a lot of this discussion is preventive medicine,” Dr. Kaak said. “Even though we think of those visits as being quick, it’s good to keep in mind that we need to really take our time and make sure we counsel the patient as best we can.”

There’s a fair amount of research suggesting that existing recommendations on gestational weight gain are not very good because they’re very generic, Jill Maples, PhD, associate professor of ob.gyn. research at the University of Tennessee Graduate School of Medicine, said in an interview. For example, the guidelines are generally the same for everyone with a BMI over 30, but a person with a BMI of 30 is very different from someone with a BMI of 50, she said.

“There’s not even a lot of clarity on what is appropriate weight gain for that group because some people have seen good outcomes on the lower end of gestational weight gain,” Dr. Maples said. She said it’s important that clinicians not forget about the importance of these discussions, however, because lifestyle habits and gestational weight gain are related to maternal and neonatal outcomes.

The authors, Dr. Kaak, and Dr. Maples had no disclosures. The research was funded by the National Institute on Drug Abuse.

SAN FRANCISCO — Discussion of gestational weight gain occurred in only half of first-time obstetric visits, most often brought up by the provider, according to data presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“Weight can be a challenging and sensitive topic at a healthcare visit,” Malini Harinath, an undergraduate research assistant at Magee-Women’s Research Institute at University of Pittsburgh Medical Center, told attendees. “Providers discussed weight gain recommendations in less than half of conversations.”

The researchers analyzed an existing dataset of audio-recorded first obstetric visits to find out how often gestational weight gain was brought up, who initiated the discussion, whether ACOG guidelines were discussed, and what the provider’s comments were.

Among 150 visits, half (50%) involved discussion of weight, with patients bringing it up 24% of the time and providers bringing it up 72% of the time. In the other 3% of visits, it was brought up by a third party, such as a partner or other family member with the patient.

Only two of those visits mentioned body mass index (BMI) specifically, and ACOG guidelines on gestational weight gain were brought up in only six visits (8% of the visits where weight was mentioned). However, mention of recommendations on gestational weight gain was more frequent, coming up in nearly half (46.7%) of the visits where weight was mentioned, though that was still just 23% of all visits.

Concern about weight was brought up in 25.3% of visits where weight was discussed, and the provider’s reassurance to the patient occurred in about a third (32%) of those visits. General comments about the patient’s body occurred in 16% of visits, such as a clinician saying, “Usually we start trying [to find the heartbeat] at about 15 weeks, but you are so skinny we might be able to find it now.”

Ms. Harinath intends to look in future research at whether patient race or BMI are associated with the frequency and content of gestational weight gain conversations and to explore how patients react to different ways that discussion of weight is brought up.

Katherine Kaak, MD, a second-year resident at the University of Tennessee Graduate School of Medicine in Knoxville, was surprised that weight was brought up in only half of the visits. “The clinical takeaway is just how important counseling in the prenatal time is and how a lot of this discussion is preventive medicine,” Dr. Kaak said. “Even though we think of those visits as being quick, it’s good to keep in mind that we need to really take our time and make sure we counsel the patient as best we can.”

There’s a fair amount of research suggesting that existing recommendations on gestational weight gain are not very good because they’re very generic, Jill Maples, PhD, associate professor of ob.gyn. research at the University of Tennessee Graduate School of Medicine, said in an interview. For example, the guidelines are generally the same for everyone with a BMI over 30, but a person with a BMI of 30 is very different from someone with a BMI of 50, she said.

“There’s not even a lot of clarity on what is appropriate weight gain for that group because some people have seen good outcomes on the lower end of gestational weight gain,” Dr. Maples said. She said it’s important that clinicians not forget about the importance of these discussions, however, because lifestyle habits and gestational weight gain are related to maternal and neonatal outcomes.

The authors, Dr. Kaak, and Dr. Maples had no disclosures. The research was funded by the National Institute on Drug Abuse.

SAN FRANCISCO — Women who used marijuana during pregnancy were significantly less likely to view it as risky even in a state where it was not legalized, according to prospectively collected data presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. But most of those women had not received any counseling about stopping its use, and more than half wanted more information about its effects on pregnancy complications.

“The biggest thing we recognized was that our counseling in prenatal visits was lower than what it really should have been,” Abigail M. Ramseyer, DO, of University of Michigan Health– Sparrow in Lansing, said in an interview. She said doctors really need to be asking their patients about marijuana use and having a conversation about the risks of its use during pregnancy.

An estimated 3%-30% of pregnant women use marijuana, depending on the population, but prevalence has been rising as more states legalize its use. Yet research has shown an association between marijuana use during pregnancy and multiple neonatal complications, including fetal growth restriction and low birth weight.

Pregnant women at a single center in Arkansas were invited during their prenatal visits to complete a 35-question, anonymous survey electronically or on paper. Of the 460 approached, 88.7% completed the survey and 11.8% of those women reported use of marijuana during pregnancy. Among those who used it while pregnant, 50% reported using it 2-3 times a week, 27% reported using it once weekly, and 18.8% reported using it daily.

The women who used it while pregnant were less likely to have a college degree and half (50%) were aged 18-24, with use declining with increasing age. A third of those who use it were White (33.3%), 52.1% were Black, and 6.3% were Hispanic.

More than half of the women (52.7%) who used marijuana during pregnancy reported that there had not been any discussion about substance use during pregnancy at the prenatal visit, and 82.4% said they had not received any counseling about stopping its use during pregnancy. Yet 54% of them wanted more information about pregnancy complications linked to cannabis use.

The other questions asked respondents on a 5-point Likert scale how much they agreed or disagreed with various statements related to perceptions of marijuana, its use during pregnancy, and its risks.

Most respondents strongly agreed that “marijuana isn’t as bad as other drugs like heroin, cocaine or meth,” but average agreement was higher among those who used marijuana (4.88) than who didn’t (4.02, P < .001).

Respondents largely neither agreed nor disagreed with its being okay to use marijuana during pregnancy with a prescription, but agreement was still higher among those who used it (3.68) than didn’t use it (2.82, P < .001). Those who used marijuana were more likely to agree that it’s “a natural substance and not a drug” (4.67 vs. 3.38, P < .001); to believe “marijuana has minimal health risks during and outside of pregnancy” (4.15 vs. 2.96, P < .001); and to believe “marijuana has less risk for treating symptoms in pregnancy than prescription medication from my provider” (4.19 vs. 3.01, P < .001).

It was not surprising that patients using marijuana would have more favorable opinions toward legalizing it, Dr. Ramseyer said, but it was interesting that the respondents’ attitude overall, regardless of use, was positive in a fairly conservative state where it was still illegal. She said her research group has data they are starting to analyze about the perceptions of patients’ partners and family members regarding marijuana use during pregnancy.

Animesh Upadhyay, MD, a resident at Yale–New Haven Medical Center in Connecticut, was also surprised by how positive the attitudes toward marijuana use and legalization were in a state where it’s illegal.

“The thing that disturbs me is that nobody has spoken about the risks of marijuana in pregnancy” to many of the respondents, said Dr. Upadhyay, who was not involved in the study. Based on the findings, Dr. Upadhyay said he would definitely begin asking patients more about their use of marijuana and their beliefs about it.

In a separate poster, Sarah Dzubay, BS, of Oregon Health & Science University, Portland, presented data examining potential associations between cannabis use and fertility. Previous research has suggested an association, but the cross-sectional analysis by Ms. Dzubay identified only a nonsignificant trend toward an association.

The researchers analyzed data from the 2013-2018 National Health and Nutrition Examination Study (NHANES) for woman aged 20-49 based on self-reported use of cannabis. Among 3166 women, 51% reported never using cannabis, 29% reported irregular use, and 20% reported regular use at least monthly.

“Women reporting regular use were younger, of lower income and educational attainment, and more likely to be single,” Ms. Dzubay reported. Those reporting irregular use, meanwhile, were more likely to be college graduates.

More of the women who used cannabis regularly (15.4%) reported an inability to conceive within one year than women who used cannabis irregularly (10.8%) or never (12.6%). The higher odds ratio of infertility among those using cannabis regularly (OR 1.47) compared to never using it was not statistically significant, however, nor was the reduced odds ratio among those using it irregularly (OR 0.83).

Because the results were not significant, the possibility of a link to infertility is “something to keep in mind,” Ms. Dzubay said, but “a lot more data has to be collected about this question before we can definitively say there’s a risk.”

The authors and Dr. Upadhyay had no disclosures. Neither study noted any external funding.

SAN FRANCISCO — Women who used marijuana during pregnancy were significantly less likely to view it as risky even in a state where it was not legalized, according to prospectively collected data presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. But most of those women had not received any counseling about stopping its use, and more than half wanted more information about its effects on pregnancy complications.

“The biggest thing we recognized was that our counseling in prenatal visits was lower than what it really should have been,” Abigail M. Ramseyer, DO, of University of Michigan Health– Sparrow in Lansing, said in an interview. She said doctors really need to be asking their patients about marijuana use and having a conversation about the risks of its use during pregnancy.

An estimated 3%-30% of pregnant women use marijuana, depending on the population, but prevalence has been rising as more states legalize its use. Yet research has shown an association between marijuana use during pregnancy and multiple neonatal complications, including fetal growth restriction and low birth weight.

Pregnant women at a single center in Arkansas were invited during their prenatal visits to complete a 35-question, anonymous survey electronically or on paper. Of the 460 approached, 88.7% completed the survey and 11.8% of those women reported use of marijuana during pregnancy. Among those who used it while pregnant, 50% reported using it 2-3 times a week, 27% reported using it once weekly, and 18.8% reported using it daily.

The women who used it while pregnant were less likely to have a college degree and half (50%) were aged 18-24, with use declining with increasing age. A third of those who use it were White (33.3%), 52.1% were Black, and 6.3% were Hispanic.

More than half of the women (52.7%) who used marijuana during pregnancy reported that there had not been any discussion about substance use during pregnancy at the prenatal visit, and 82.4% said they had not received any counseling about stopping its use during pregnancy. Yet 54% of them wanted more information about pregnancy complications linked to cannabis use.

The other questions asked respondents on a 5-point Likert scale how much they agreed or disagreed with various statements related to perceptions of marijuana, its use during pregnancy, and its risks.

Most respondents strongly agreed that “marijuana isn’t as bad as other drugs like heroin, cocaine or meth,” but average agreement was higher among those who used marijuana (4.88) than who didn’t (4.02, P < .001).

Respondents largely neither agreed nor disagreed with its being okay to use marijuana during pregnancy with a prescription, but agreement was still higher among those who used it (3.68) than didn’t use it (2.82, P < .001). Those who used marijuana were more likely to agree that it’s “a natural substance and not a drug” (4.67 vs. 3.38, P < .001); to believe “marijuana has minimal health risks during and outside of pregnancy” (4.15 vs. 2.96, P < .001); and to believe “marijuana has less risk for treating symptoms in pregnancy than prescription medication from my provider” (4.19 vs. 3.01, P < .001).

It was not surprising that patients using marijuana would have more favorable opinions toward legalizing it, Dr. Ramseyer said, but it was interesting that the respondents’ attitude overall, regardless of use, was positive in a fairly conservative state where it was still illegal. She said her research group has data they are starting to analyze about the perceptions of patients’ partners and family members regarding marijuana use during pregnancy.

Animesh Upadhyay, MD, a resident at Yale–New Haven Medical Center in Connecticut, was also surprised by how positive the attitudes toward marijuana use and legalization were in a state where it’s illegal.

“The thing that disturbs me is that nobody has spoken about the risks of marijuana in pregnancy” to many of the respondents, said Dr. Upadhyay, who was not involved in the study. Based on the findings, Dr. Upadhyay said he would definitely begin asking patients more about their use of marijuana and their beliefs about it.

In a separate poster, Sarah Dzubay, BS, of Oregon Health & Science University, Portland, presented data examining potential associations between cannabis use and fertility. Previous research has suggested an association, but the cross-sectional analysis by Ms. Dzubay identified only a nonsignificant trend toward an association.

The researchers analyzed data from the 2013-2018 National Health and Nutrition Examination Study (NHANES) for woman aged 20-49 based on self-reported use of cannabis. Among 3166 women, 51% reported never using cannabis, 29% reported irregular use, and 20% reported regular use at least monthly.

“Women reporting regular use were younger, of lower income and educational attainment, and more likely to be single,” Ms. Dzubay reported. Those reporting irregular use, meanwhile, were more likely to be college graduates.

More of the women who used cannabis regularly (15.4%) reported an inability to conceive within one year than women who used cannabis irregularly (10.8%) or never (12.6%). The higher odds ratio of infertility among those using cannabis regularly (OR 1.47) compared to never using it was not statistically significant, however, nor was the reduced odds ratio among those using it irregularly (OR 0.83).

Because the results were not significant, the possibility of a link to infertility is “something to keep in mind,” Ms. Dzubay said, but “a lot more data has to be collected about this question before we can definitively say there’s a risk.”

The authors and Dr. Upadhyay had no disclosures. Neither study noted any external funding.

SAN FRANCISCO — Women who used marijuana during pregnancy were significantly less likely to view it as risky even in a state where it was not legalized, according to prospectively collected data presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. But most of those women had not received any counseling about stopping its use, and more than half wanted more information about its effects on pregnancy complications.

“The biggest thing we recognized was that our counseling in prenatal visits was lower than what it really should have been,” Abigail M. Ramseyer, DO, of University of Michigan Health– Sparrow in Lansing, said in an interview. She said doctors really need to be asking their patients about marijuana use and having a conversation about the risks of its use during pregnancy.

An estimated 3%-30% of pregnant women use marijuana, depending on the population, but prevalence has been rising as more states legalize its use. Yet research has shown an association between marijuana use during pregnancy and multiple neonatal complications, including fetal growth restriction and low birth weight.

Pregnant women at a single center in Arkansas were invited during their prenatal visits to complete a 35-question, anonymous survey electronically or on paper. Of the 460 approached, 88.7% completed the survey and 11.8% of those women reported use of marijuana during pregnancy. Among those who used it while pregnant, 50% reported using it 2-3 times a week, 27% reported using it once weekly, and 18.8% reported using it daily.

The women who used it while pregnant were less likely to have a college degree and half (50%) were aged 18-24, with use declining with increasing age. A third of those who use it were White (33.3%), 52.1% were Black, and 6.3% were Hispanic.

More than half of the women (52.7%) who used marijuana during pregnancy reported that there had not been any discussion about substance use during pregnancy at the prenatal visit, and 82.4% said they had not received any counseling about stopping its use during pregnancy. Yet 54% of them wanted more information about pregnancy complications linked to cannabis use.

The other questions asked respondents on a 5-point Likert scale how much they agreed or disagreed with various statements related to perceptions of marijuana, its use during pregnancy, and its risks.

Most respondents strongly agreed that “marijuana isn’t as bad as other drugs like heroin, cocaine or meth,” but average agreement was higher among those who used marijuana (4.88) than who didn’t (4.02, P < .001).

Respondents largely neither agreed nor disagreed with its being okay to use marijuana during pregnancy with a prescription, but agreement was still higher among those who used it (3.68) than didn’t use it (2.82, P < .001). Those who used marijuana were more likely to agree that it’s “a natural substance and not a drug” (4.67 vs. 3.38, P < .001); to believe “marijuana has minimal health risks during and outside of pregnancy” (4.15 vs. 2.96, P < .001); and to believe “marijuana has less risk for treating symptoms in pregnancy than prescription medication from my provider” (4.19 vs. 3.01, P < .001).

It was not surprising that patients using marijuana would have more favorable opinions toward legalizing it, Dr. Ramseyer said, but it was interesting that the respondents’ attitude overall, regardless of use, was positive in a fairly conservative state where it was still illegal. She said her research group has data they are starting to analyze about the perceptions of patients’ partners and family members regarding marijuana use during pregnancy.

Animesh Upadhyay, MD, a resident at Yale–New Haven Medical Center in Connecticut, was also surprised by how positive the attitudes toward marijuana use and legalization were in a state where it’s illegal.

“The thing that disturbs me is that nobody has spoken about the risks of marijuana in pregnancy” to many of the respondents, said Dr. Upadhyay, who was not involved in the study. Based on the findings, Dr. Upadhyay said he would definitely begin asking patients more about their use of marijuana and their beliefs about it.

In a separate poster, Sarah Dzubay, BS, of Oregon Health & Science University, Portland, presented data examining potential associations between cannabis use and fertility. Previous research has suggested an association, but the cross-sectional analysis by Ms. Dzubay identified only a nonsignificant trend toward an association.

The researchers analyzed data from the 2013-2018 National Health and Nutrition Examination Study (NHANES) for woman aged 20-49 based on self-reported use of cannabis. Among 3166 women, 51% reported never using cannabis, 29% reported irregular use, and 20% reported regular use at least monthly.

“Women reporting regular use were younger, of lower income and educational attainment, and more likely to be single,” Ms. Dzubay reported. Those reporting irregular use, meanwhile, were more likely to be college graduates.

More of the women who used cannabis regularly (15.4%) reported an inability to conceive within one year than women who used cannabis irregularly (10.8%) or never (12.6%). The higher odds ratio of infertility among those using cannabis regularly (OR 1.47) compared to never using it was not statistically significant, however, nor was the reduced odds ratio among those using it irregularly (OR 0.83).

Because the results were not significant, the possibility of a link to infertility is “something to keep in mind,” Ms. Dzubay said, but “a lot more data has to be collected about this question before we can definitively say there’s a risk.”

The authors and Dr. Upadhyay had no disclosures. Neither study noted any external funding.

For breast cancer survivors harboring BRCA1/2 gene mutations, the prospect of future pregnancy often raises concerns because of limited data on the safety of assisted reproductive techniques (ART) in this population. However, results from a large international study presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress provide reassuring evidence that ART, such as in vitro fertilization, can be safely used by BRCA1/2 mutation carriers previously treated for breast cancer.

“Our primary aim was to evaluate the safety profile of ART in this high-risk population by comparing maternal and fetal outcomes between those who conceived spontaneously versus those using ART,” explained Matteo Lambertini, MD, PhD, during his talk at the conference. “We found no statistically significant differences in pregnancy complications or fetal abnormalities.” Dr. Lambertini is an associate professor and medical oncologist at the University of Genova and IRCCS Policlinico San Martino Hospital, Genova, Italy.
 

Unmet Fertility Needs for Women With Breast Cancer

With the rising rates of early-onset breast cancer and improved survival outcomes with new therapies, the number of long-term breast cancer survivors is increasing. Fertility preservation and future reproductive choices are important considerations for young patients with breast cancer, especially for high-risk patients carrying pathogenic BRCA1/2 mutations. During his talk, Dr. Lambertini explained that defects in DNA damage repair due to BRCA1/2 mutations, in addition to chemotherapy after breast cancer diagnosis, can lead to premature menopause.

According to Dr. Lambertini, physicians face challenges in counseling these patients regarding the potential risks and benefits of pursuing pregnancy after cancer treatment because of the limited evidence available on the safety of ART in BRCA1/2 mutation carriers.

“Clinicians have to counsel BRCA carriers based on very limited data about the safety of pursuing pregnancy with ART after a breast cancer diagnosis,” he said during his presentation.
 

Study Design and Patient Population

The retrospective cohort study pooled data from 78 centers worldwide to explore ART outcomes in BRCA1/2 mutation carriers. The analysis included 4732 women diagnosed with stage I-III breast cancer at age 40 years or younger, all harboring a pathogenic BRCA1 or BRCA2 variant.

Among these high-risk patients, 543 became pregnant after completing cancer treatment; of these, 436 conceived naturally and 107 used ART. In the ART group, 45.5% underwent oocyte or embryo cryopreservation at breast cancer diagnosis, 33.3% underwent ovarian stimulation for in vitro fertilization after cancer treatment, and 21.2% underwent embryo transfer following oocyte donation.

Dr. Janice Tsang, MD, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, highlighted that this is the largest study focusing on ART safety in young patients with BRCA1/2 mutations. “With over 500 BRCA1/2 mutation carriers studied across nearly 80 sites, the cohort analysis had sufficient statistical power and global representation to detect potential safety signals with ART utilization, unlike prior smaller studies,” she said. Dr. Tsang, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, served as a discussant, providing her expert opinion on the findings presented by Dr. Lambertini.
 

No Increased Risks for Pregnancy and Fetal Outcomes

Although women using ART had slightly higher miscarriage rates (11.3% versus 8.8%) and lower rates of induced abortion (0.9% versus 8.3%) than women with spontaneous conceptions, the analysis revealed no statistically significant differences in the frequency of pregnancy complications, delivery complications, or congenital abnormalities between those who received ART and those who conceived naturally.

Dr. Lambertini explained that variations in baseline characteristics, such as age, may have contributed to differences in miscarriage rates.

“Patients in the ART group tended to be older at the time of conception, with a median age of 37.1 years, compared with 34.3 years in the spontaneous pregnancy group,” he said, during his presentation. Women in the ART group also more frequently had hormone receptor–positive breast cancer (43.4% versus 30.8%) and longer median time from diagnosis to conception (4.2 versus 3.3 years).
 

No Adverse Effects on Breast Cancer Prognosis

At a median follow-up of 5.2 years from conception, there was no detrimental effect of ART on disease-free survival for carriers of pathogenic BRCA1/2 variants who were treated for breast cancer. The ART group showed 13 (13.1%) recurrence events, compared with 118 (27.1%) recurrences in the spontaneous pregnancy group (adjusted hazard ratio, 0.72; 95% CI, 0.38-1.33; P = .147).

“The risk of cancer recurrence was comparable between those using and not using ART to become pregnant after their breast cancer diagnosis and treatment, and the small number of recurrence events in the ART group mostly involved locoregional recurrences,” Dr. Lambertini noted during his talk.

Moreover, breast cancer–specific survival and overall survival appeared to be similar between the two groups, although the small number of deaths precluded the conduction of formal analysis.

“These survival data suggest that utilizing ART does not appear to negatively impact the prognosis or course of the underlying breast cancer,” Dr. Lambertini said during the discussion.
 

Clinical Implications and Future Work

According to Dr. Lambertini, these results are incredibly valuable for clinicians counseling young breast cancer survivors with pathogenic BRCA1/2 mutations who wish to have biological children.

“Given the interest of patients in having their own family and for some of them in avoiding the transmission of the BRCA1/2 pathogenic variants, our results are critical in improving the oncofertility counseling of young women with breast cancer,” said Dr. Lambertini during his presentation. “We can reassure patients that pursuing ART does not appear to worsen their cancer prognosis or compromise pregnancy outcomes compared to spontaneous conceptions.”

During her discussion session, Dr. Tsang echoed the clinical implications of these findings, emphasizing that, by incorporating this evidence into clinical practice, healthcare providers can better support patients in making informed choices regarding fertility preservation and family planning after cancer treatment.

“Though this study is [retrospective] with a relatively small number, these real-world findings make a major contribution to our limited evidence base on ART safety for cancer survivors carrying BRCA1/2 mutations,” she said.

She cautioned, however, that there remain several unanswered questions and uncertainties. “We need prospective data with a larger sample size to confirm the safety of ART in this population, as well as studies to assess whether different types of ART have different safety profiles.”

Dr. Lambertini concluded his talk by saying, “While waiting for prospective studies to confirm our results, fertility preservation at diagnosis of early breast cancer should be offered to all women interested in future fertility, including BRCA carriers.”

Dr. Lambertini reported financial relationships with Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Pierre Fabre, and Menarini (consulting or advisory roles); Takeda, Roche, Lilly, Novartis, Pfizer, AstraZeneca, Sandoz, Ipsen, Libbs, Knight, Dalichi Sankyo, Gilead, Menarini (honoraria); Gilead, Daiichi Sankyo, and Roche (travel support); and Gilead (research funding to the institution). Dr. Tsang reported financial relationships with AstraZeneca, Amgen, Daichi Sankyo, Eisai, Gilead, Lilly, Lucence, Novartis, Pfizer, and Veracyte (honoraria); De Novo (consulting or advisory roles); and Pfizer (grant panel reviewer).

For breast cancer survivors harboring BRCA1/2 gene mutations, the prospect of future pregnancy often raises concerns because of limited data on the safety of assisted reproductive techniques (ART) in this population. However, results from a large international study presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress provide reassuring evidence that ART, such as in vitro fertilization, can be safely used by BRCA1/2 mutation carriers previously treated for breast cancer.

“Our primary aim was to evaluate the safety profile of ART in this high-risk population by comparing maternal and fetal outcomes between those who conceived spontaneously versus those using ART,” explained Matteo Lambertini, MD, PhD, during his talk at the conference. “We found no statistically significant differences in pregnancy complications or fetal abnormalities.” Dr. Lambertini is an associate professor and medical oncologist at the University of Genova and IRCCS Policlinico San Martino Hospital, Genova, Italy.
 

Unmet Fertility Needs for Women With Breast Cancer

With the rising rates of early-onset breast cancer and improved survival outcomes with new therapies, the number of long-term breast cancer survivors is increasing. Fertility preservation and future reproductive choices are important considerations for young patients with breast cancer, especially for high-risk patients carrying pathogenic BRCA1/2 mutations. During his talk, Dr. Lambertini explained that defects in DNA damage repair due to BRCA1/2 mutations, in addition to chemotherapy after breast cancer diagnosis, can lead to premature menopause.

According to Dr. Lambertini, physicians face challenges in counseling these patients regarding the potential risks and benefits of pursuing pregnancy after cancer treatment because of the limited evidence available on the safety of ART in BRCA1/2 mutation carriers.

“Clinicians have to counsel BRCA carriers based on very limited data about the safety of pursuing pregnancy with ART after a breast cancer diagnosis,” he said during his presentation.
 

Study Design and Patient Population

The retrospective cohort study pooled data from 78 centers worldwide to explore ART outcomes in BRCA1/2 mutation carriers. The analysis included 4732 women diagnosed with stage I-III breast cancer at age 40 years or younger, all harboring a pathogenic BRCA1 or BRCA2 variant.

Among these high-risk patients, 543 became pregnant after completing cancer treatment; of these, 436 conceived naturally and 107 used ART. In the ART group, 45.5% underwent oocyte or embryo cryopreservation at breast cancer diagnosis, 33.3% underwent ovarian stimulation for in vitro fertilization after cancer treatment, and 21.2% underwent embryo transfer following oocyte donation.

Dr. Janice Tsang, MD, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, highlighted that this is the largest study focusing on ART safety in young patients with BRCA1/2 mutations. “With over 500 BRCA1/2 mutation carriers studied across nearly 80 sites, the cohort analysis had sufficient statistical power and global representation to detect potential safety signals with ART utilization, unlike prior smaller studies,” she said. Dr. Tsang, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, served as a discussant, providing her expert opinion on the findings presented by Dr. Lambertini.
 

No Increased Risks for Pregnancy and Fetal Outcomes

Although women using ART had slightly higher miscarriage rates (11.3% versus 8.8%) and lower rates of induced abortion (0.9% versus 8.3%) than women with spontaneous conceptions, the analysis revealed no statistically significant differences in the frequency of pregnancy complications, delivery complications, or congenital abnormalities between those who received ART and those who conceived naturally.

Dr. Lambertini explained that variations in baseline characteristics, such as age, may have contributed to differences in miscarriage rates.

“Patients in the ART group tended to be older at the time of conception, with a median age of 37.1 years, compared with 34.3 years in the spontaneous pregnancy group,” he said, during his presentation. Women in the ART group also more frequently had hormone receptor–positive breast cancer (43.4% versus 30.8%) and longer median time from diagnosis to conception (4.2 versus 3.3 years).
 

No Adverse Effects on Breast Cancer Prognosis

At a median follow-up of 5.2 years from conception, there was no detrimental effect of ART on disease-free survival for carriers of pathogenic BRCA1/2 variants who were treated for breast cancer. The ART group showed 13 (13.1%) recurrence events, compared with 118 (27.1%) recurrences in the spontaneous pregnancy group (adjusted hazard ratio, 0.72; 95% CI, 0.38-1.33; P = .147).

“The risk of cancer recurrence was comparable between those using and not using ART to become pregnant after their breast cancer diagnosis and treatment, and the small number of recurrence events in the ART group mostly involved locoregional recurrences,” Dr. Lambertini noted during his talk.

Moreover, breast cancer–specific survival and overall survival appeared to be similar between the two groups, although the small number of deaths precluded the conduction of formal analysis.

“These survival data suggest that utilizing ART does not appear to negatively impact the prognosis or course of the underlying breast cancer,” Dr. Lambertini said during the discussion.
 

Clinical Implications and Future Work

According to Dr. Lambertini, these results are incredibly valuable for clinicians counseling young breast cancer survivors with pathogenic BRCA1/2 mutations who wish to have biological children.

“Given the interest of patients in having their own family and for some of them in avoiding the transmission of the BRCA1/2 pathogenic variants, our results are critical in improving the oncofertility counseling of young women with breast cancer,” said Dr. Lambertini during his presentation. “We can reassure patients that pursuing ART does not appear to worsen their cancer prognosis or compromise pregnancy outcomes compared to spontaneous conceptions.”

During her discussion session, Dr. Tsang echoed the clinical implications of these findings, emphasizing that, by incorporating this evidence into clinical practice, healthcare providers can better support patients in making informed choices regarding fertility preservation and family planning after cancer treatment.

“Though this study is [retrospective] with a relatively small number, these real-world findings make a major contribution to our limited evidence base on ART safety for cancer survivors carrying BRCA1/2 mutations,” she said.

She cautioned, however, that there remain several unanswered questions and uncertainties. “We need prospective data with a larger sample size to confirm the safety of ART in this population, as well as studies to assess whether different types of ART have different safety profiles.”

Dr. Lambertini concluded his talk by saying, “While waiting for prospective studies to confirm our results, fertility preservation at diagnosis of early breast cancer should be offered to all women interested in future fertility, including BRCA carriers.”

Dr. Lambertini reported financial relationships with Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Pierre Fabre, and Menarini (consulting or advisory roles); Takeda, Roche, Lilly, Novartis, Pfizer, AstraZeneca, Sandoz, Ipsen, Libbs, Knight, Dalichi Sankyo, Gilead, Menarini (honoraria); Gilead, Daiichi Sankyo, and Roche (travel support); and Gilead (research funding to the institution). Dr. Tsang reported financial relationships with AstraZeneca, Amgen, Daichi Sankyo, Eisai, Gilead, Lilly, Lucence, Novartis, Pfizer, and Veracyte (honoraria); De Novo (consulting or advisory roles); and Pfizer (grant panel reviewer).

For breast cancer survivors harboring BRCA1/2 gene mutations, the prospect of future pregnancy often raises concerns because of limited data on the safety of assisted reproductive techniques (ART) in this population. However, results from a large international study presented at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress provide reassuring evidence that ART, such as in vitro fertilization, can be safely used by BRCA1/2 mutation carriers previously treated for breast cancer.

“Our primary aim was to evaluate the safety profile of ART in this high-risk population by comparing maternal and fetal outcomes between those who conceived spontaneously versus those using ART,” explained Matteo Lambertini, MD, PhD, during his talk at the conference. “We found no statistically significant differences in pregnancy complications or fetal abnormalities.” Dr. Lambertini is an associate professor and medical oncologist at the University of Genova and IRCCS Policlinico San Martino Hospital, Genova, Italy.
 

Unmet Fertility Needs for Women With Breast Cancer

With the rising rates of early-onset breast cancer and improved survival outcomes with new therapies, the number of long-term breast cancer survivors is increasing. Fertility preservation and future reproductive choices are important considerations for young patients with breast cancer, especially for high-risk patients carrying pathogenic BRCA1/2 mutations. During his talk, Dr. Lambertini explained that defects in DNA damage repair due to BRCA1/2 mutations, in addition to chemotherapy after breast cancer diagnosis, can lead to premature menopause.

According to Dr. Lambertini, physicians face challenges in counseling these patients regarding the potential risks and benefits of pursuing pregnancy after cancer treatment because of the limited evidence available on the safety of ART in BRCA1/2 mutation carriers.

“Clinicians have to counsel BRCA carriers based on very limited data about the safety of pursuing pregnancy with ART after a breast cancer diagnosis,” he said during his presentation.
 

Study Design and Patient Population

The retrospective cohort study pooled data from 78 centers worldwide to explore ART outcomes in BRCA1/2 mutation carriers. The analysis included 4732 women diagnosed with stage I-III breast cancer at age 40 years or younger, all harboring a pathogenic BRCA1 or BRCA2 variant.

Among these high-risk patients, 543 became pregnant after completing cancer treatment; of these, 436 conceived naturally and 107 used ART. In the ART group, 45.5% underwent oocyte or embryo cryopreservation at breast cancer diagnosis, 33.3% underwent ovarian stimulation for in vitro fertilization after cancer treatment, and 21.2% underwent embryo transfer following oocyte donation.

Dr. Janice Tsang, MD, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, highlighted that this is the largest study focusing on ART safety in young patients with BRCA1/2 mutations. “With over 500 BRCA1/2 mutation carriers studied across nearly 80 sites, the cohort analysis had sufficient statistical power and global representation to detect potential safety signals with ART utilization, unlike prior smaller studies,” she said. Dr. Tsang, a clinical oncology specialist and assistant professor at the University of Hong Kong who was not involved in this study, served as a discussant, providing her expert opinion on the findings presented by Dr. Lambertini.
 

No Increased Risks for Pregnancy and Fetal Outcomes

Although women using ART had slightly higher miscarriage rates (11.3% versus 8.8%) and lower rates of induced abortion (0.9% versus 8.3%) than women with spontaneous conceptions, the analysis revealed no statistically significant differences in the frequency of pregnancy complications, delivery complications, or congenital abnormalities between those who received ART and those who conceived naturally.

Dr. Lambertini explained that variations in baseline characteristics, such as age, may have contributed to differences in miscarriage rates.

“Patients in the ART group tended to be older at the time of conception, with a median age of 37.1 years, compared with 34.3 years in the spontaneous pregnancy group,” he said, during his presentation. Women in the ART group also more frequently had hormone receptor–positive breast cancer (43.4% versus 30.8%) and longer median time from diagnosis to conception (4.2 versus 3.3 years).
 

No Adverse Effects on Breast Cancer Prognosis

At a median follow-up of 5.2 years from conception, there was no detrimental effect of ART on disease-free survival for carriers of pathogenic BRCA1/2 variants who were treated for breast cancer. The ART group showed 13 (13.1%) recurrence events, compared with 118 (27.1%) recurrences in the spontaneous pregnancy group (adjusted hazard ratio, 0.72; 95% CI, 0.38-1.33; P = .147).

“The risk of cancer recurrence was comparable between those using and not using ART to become pregnant after their breast cancer diagnosis and treatment, and the small number of recurrence events in the ART group mostly involved locoregional recurrences,” Dr. Lambertini noted during his talk.

Moreover, breast cancer–specific survival and overall survival appeared to be similar between the two groups, although the small number of deaths precluded the conduction of formal analysis.

“These survival data suggest that utilizing ART does not appear to negatively impact the prognosis or course of the underlying breast cancer,” Dr. Lambertini said during the discussion.
 

Clinical Implications and Future Work

According to Dr. Lambertini, these results are incredibly valuable for clinicians counseling young breast cancer survivors with pathogenic BRCA1/2 mutations who wish to have biological children.

“Given the interest of patients in having their own family and for some of them in avoiding the transmission of the BRCA1/2 pathogenic variants, our results are critical in improving the oncofertility counseling of young women with breast cancer,” said Dr. Lambertini during his presentation. “We can reassure patients that pursuing ART does not appear to worsen their cancer prognosis or compromise pregnancy outcomes compared to spontaneous conceptions.”

During her discussion session, Dr. Tsang echoed the clinical implications of these findings, emphasizing that, by incorporating this evidence into clinical practice, healthcare providers can better support patients in making informed choices regarding fertility preservation and family planning after cancer treatment.

“Though this study is [retrospective] with a relatively small number, these real-world findings make a major contribution to our limited evidence base on ART safety for cancer survivors carrying BRCA1/2 mutations,” she said.

She cautioned, however, that there remain several unanswered questions and uncertainties. “We need prospective data with a larger sample size to confirm the safety of ART in this population, as well as studies to assess whether different types of ART have different safety profiles.”

Dr. Lambertini concluded his talk by saying, “While waiting for prospective studies to confirm our results, fertility preservation at diagnosis of early breast cancer should be offered to all women interested in future fertility, including BRCA carriers.”

Dr. Lambertini reported financial relationships with Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Pierre Fabre, and Menarini (consulting or advisory roles); Takeda, Roche, Lilly, Novartis, Pfizer, AstraZeneca, Sandoz, Ipsen, Libbs, Knight, Dalichi Sankyo, Gilead, Menarini (honoraria); Gilead, Daiichi Sankyo, and Roche (travel support); and Gilead (research funding to the institution). Dr. Tsang reported financial relationships with AstraZeneca, Amgen, Daichi Sankyo, Eisai, Gilead, Lilly, Lucence, Novartis, Pfizer, and Veracyte (honoraria); De Novo (consulting or advisory roles); and Pfizer (grant panel reviewer).

For years, scientists have sought to create a human artificial ovary, restoring fertility in patients without other options. The first cellular map of a human ovary, recently developed at the University of Michigan, Ann Arbor, represents a big leap forward in that quest.

“You cannot build something if you don’t have the blueprint,” said biomedical engineer Ariella Shikanov, PhD, associate professor at University of Michigan, who helped create what she and colleagues call an atlas of the ovary. “By creating a map or an atlas, we can now follow what nature created and engineer the building blocks of an ovary — and build a nature-like structure.”

So far, the concept of an artificial ovary has been successful only in mice, with the development of a 3D-printed prosthetic ovary that enabled sterilized mice to have pups. Researchers hope that artificial human ovary technology could someday help women left infertile after cancer treatment, as well as patients who don›t respond to fertility treatments and those with premature ovarian failure.

But Dr. Shikanov believes this research will go even further, providing a valuable resource to scientists studying diseases and other conditions related to the ovary.

“Whenever people think about the ovary, if they think about it at all, they usually think about fertility,” said Dr. Shikanov. The ovary is so much more.

Besides producing and carrying a woman’s unfertilized eggs during her lifetime, the ovary is also responsible for endocrine function — the production of estrogen and progesterone, which in addition to supporting reproductive health, help maintain a woman’s cardiovascular, bone, and mental health.

“We don’t really understand everything that is happening in the ovary yet,” Dr. Shikanov said. “But we know it is an important organ.”
 

Mapping the Ovary

Because people don’t typically donate their ovaries, there are not many available for research, especially from younger reproductive age women, said Dr. Shikanov. So, the scientists set out to build a resource. They described their work in Science Advances.

To create their atlas, the researchers studied two premenopausal donor ovaries, profiling 18,000 genes in 257 regions. From three additional donor ovaries, they also generated single-cell RNA sequencing data for 21,198 cells.

“We identified four major cell types and four immune cell subtypes in the ovary,” said Dr. Shikanov. Taking samples from different areas of the ovary revealed distinct gene activities for oocytes, theca cells, and granulosa cells — expanding scientists’ understanding of the molecular programs driving ovarian follicle development.

What’s unique about their work is the focus on both single cell and spatial analysis, said study coauthor Jun Z. Li, PhD, associate chair of the University of Michigan’s department of computational medicine and bioinformatics. Specifically, they used a relatively new method called spatial transcriptomics, which allows them to see which genes are being activated and where.

“We are constructing the spatial arrangement of the cells in the ovary,” said Dr. Li. “This spatial analysis is like saying, ‘Let me look at where you are and who your neighbor is.’ ”

Their findings are built on other genetic and cellular research in the field, Dr. Li noted. Biomedical engineers in other areas of medicine are applying similar technologies to other organs including the heart, the breast, and bone — part of a larger project called the Human Cell Atlas.
 

Advancing Women’s Health Research

Historically, women’s health research has been underfunded and underrepresented, but the authors believe their atlas of the ovary is a significant step forward.

“There are a lot of biological questions that we don’t know the answers to about the ovary,” said Dr. Shikanov.

One of the biggest mysteries is why so many eggs never become fertilizable. Each human female is born with about one to two million ovarian follicles. Each follicle carries one immature egg. Around puberty, two thirds of these follicles die off. And most that are left never develop into fertilizable eggs.

“The majority of these follicles either just grow and secrete hormones or undergo atresia,” Dr. Shikanov said. “One question that we wanted to understand is, what determines an egg that can grow, ovulate, and become a fertilizable egg and potentially develop into a new human being from one that does not?”

Another big question researchers have is, what’s happening with other types of cells in the ovary — the supporting cells that produce endocrine hormones? Where are they located and what proteins and RNA are they making? Their research begins to unravel some of these questions and lays a foundation for future studies.

“We wanted to analyze the transcriptional signatures from specific regions and then do bioinformatical analysis and really combine structure, function, and transcriptional signatures,” Dr. Shikanov said.

Knowing the transcriptional signatures can help researchers understand disease mechanisms and then go on to develop treatments for these diseases.

Winifred Mak, MD, PhD, a reproductive endocrinologist and infertility specialist at Dell Medical School, University of Texas, Austin, studies cancer fertility preservation. “For me, it is interesting to see that there are so many different clusters of cells in the ovary that have been identified by this study that we were not necessarily aware of before,” said Dr. Mak, who is not involved in the new research. “Also, the identification of new genes not previously studied in the human ovary.”
 

What’s Next

Dozens of scientists who study reproductive health are already reaching out to the researchers about their work, Dr. Shikanov said.

“We get contacted almost every day from researchers all around the world asking for data sets or asking for details from this paper,” she said, “from people who study ovarian cancer, for example.”

Dr. Mak said having a map of a normal ovary could also help researchers who study premature ovarian insufficiency — why the ovary sometimes goes into premature menopause — and polycystic ovarian syndrome.

Another big area of research interest is ovarian aging. “Women live so much longer now, but we still reach menopause at the age of 50,” Dr. Shikanov said. “So, there are efforts going toward understanding ovarian aging and maybe preventing it to extend ovarian longevity.”

Dr. Mak said it will enable scientists to “look at different age women and see what genes change across the reproductive lifespan.”

The atlas may also eventually lead to treatments that help restore fertility in individuals who had and were treated for cancer as children, people who undergo sex transitions, and those whose reproductive organs have been impacted by trauma in conflict settings or accidents, Dr. Li said.

The applications are numerous and exciting, Dr. Shikanov said. “Our atlas is like a benchmark. Now researchers can collect ovaries from individuals with these diseases and conditions and try to compare what’s different.”

A version of this article appeared on Medscape.com.

For years, scientists have sought to create a human artificial ovary, restoring fertility in patients without other options. The first cellular map of a human ovary, recently developed at the University of Michigan, Ann Arbor, represents a big leap forward in that quest.

“You cannot build something if you don’t have the blueprint,” said biomedical engineer Ariella Shikanov, PhD, associate professor at University of Michigan, who helped create what she and colleagues call an atlas of the ovary. “By creating a map or an atlas, we can now follow what nature created and engineer the building blocks of an ovary — and build a nature-like structure.”

So far, the concept of an artificial ovary has been successful only in mice, with the development of a 3D-printed prosthetic ovary that enabled sterilized mice to have pups. Researchers hope that artificial human ovary technology could someday help women left infertile after cancer treatment, as well as patients who don›t respond to fertility treatments and those with premature ovarian failure.

But Dr. Shikanov believes this research will go even further, providing a valuable resource to scientists studying diseases and other conditions related to the ovary.

“Whenever people think about the ovary, if they think about it at all, they usually think about fertility,” said Dr. Shikanov. The ovary is so much more.

Besides producing and carrying a woman’s unfertilized eggs during her lifetime, the ovary is also responsible for endocrine function — the production of estrogen and progesterone, which in addition to supporting reproductive health, help maintain a woman’s cardiovascular, bone, and mental health.

“We don’t really understand everything that is happening in the ovary yet,” Dr. Shikanov said. “But we know it is an important organ.”
 

Mapping the Ovary

Because people don’t typically donate their ovaries, there are not many available for research, especially from younger reproductive age women, said Dr. Shikanov. So, the scientists set out to build a resource. They described their work in Science Advances.

To create their atlas, the researchers studied two premenopausal donor ovaries, profiling 18,000 genes in 257 regions. From three additional donor ovaries, they also generated single-cell RNA sequencing data for 21,198 cells.

“We identified four major cell types and four immune cell subtypes in the ovary,” said Dr. Shikanov. Taking samples from different areas of the ovary revealed distinct gene activities for oocytes, theca cells, and granulosa cells — expanding scientists’ understanding of the molecular programs driving ovarian follicle development.

What’s unique about their work is the focus on both single cell and spatial analysis, said study coauthor Jun Z. Li, PhD, associate chair of the University of Michigan’s department of computational medicine and bioinformatics. Specifically, they used a relatively new method called spatial transcriptomics, which allows them to see which genes are being activated and where.

“We are constructing the spatial arrangement of the cells in the ovary,” said Dr. Li. “This spatial analysis is like saying, ‘Let me look at where you are and who your neighbor is.’ ”

Their findings are built on other genetic and cellular research in the field, Dr. Li noted. Biomedical engineers in other areas of medicine are applying similar technologies to other organs including the heart, the breast, and bone — part of a larger project called the Human Cell Atlas.
 

Advancing Women’s Health Research

Historically, women’s health research has been underfunded and underrepresented, but the authors believe their atlas of the ovary is a significant step forward.

“There are a lot of biological questions that we don’t know the answers to about the ovary,” said Dr. Shikanov.

One of the biggest mysteries is why so many eggs never become fertilizable. Each human female is born with about one to two million ovarian follicles. Each follicle carries one immature egg. Around puberty, two thirds of these follicles die off. And most that are left never develop into fertilizable eggs.

“The majority of these follicles either just grow and secrete hormones or undergo atresia,” Dr. Shikanov said. “One question that we wanted to understand is, what determines an egg that can grow, ovulate, and become a fertilizable egg and potentially develop into a new human being from one that does not?”

Another big question researchers have is, what’s happening with other types of cells in the ovary — the supporting cells that produce endocrine hormones? Where are they located and what proteins and RNA are they making? Their research begins to unravel some of these questions and lays a foundation for future studies.

“We wanted to analyze the transcriptional signatures from specific regions and then do bioinformatical analysis and really combine structure, function, and transcriptional signatures,” Dr. Shikanov said.

Knowing the transcriptional signatures can help researchers understand disease mechanisms and then go on to develop treatments for these diseases.

Winifred Mak, MD, PhD, a reproductive endocrinologist and infertility specialist at Dell Medical School, University of Texas, Austin, studies cancer fertility preservation. “For me, it is interesting to see that there are so many different clusters of cells in the ovary that have been identified by this study that we were not necessarily aware of before,” said Dr. Mak, who is not involved in the new research. “Also, the identification of new genes not previously studied in the human ovary.”
 

What’s Next

Dozens of scientists who study reproductive health are already reaching out to the researchers about their work, Dr. Shikanov said.

“We get contacted almost every day from researchers all around the world asking for data sets or asking for details from this paper,” she said, “from people who study ovarian cancer, for example.”

Dr. Mak said having a map of a normal ovary could also help researchers who study premature ovarian insufficiency — why the ovary sometimes goes into premature menopause — and polycystic ovarian syndrome.

Another big area of research interest is ovarian aging. “Women live so much longer now, but we still reach menopause at the age of 50,” Dr. Shikanov said. “So, there are efforts going toward understanding ovarian aging and maybe preventing it to extend ovarian longevity.”

Dr. Mak said it will enable scientists to “look at different age women and see what genes change across the reproductive lifespan.”

The atlas may also eventually lead to treatments that help restore fertility in individuals who had and were treated for cancer as children, people who undergo sex transitions, and those whose reproductive organs have been impacted by trauma in conflict settings or accidents, Dr. Li said.

The applications are numerous and exciting, Dr. Shikanov said. “Our atlas is like a benchmark. Now researchers can collect ovaries from individuals with these diseases and conditions and try to compare what’s different.”

A version of this article appeared on Medscape.com.

For years, scientists have sought to create a human artificial ovary, restoring fertility in patients without other options. The first cellular map of a human ovary, recently developed at the University of Michigan, Ann Arbor, represents a big leap forward in that quest.

“You cannot build something if you don’t have the blueprint,” said biomedical engineer Ariella Shikanov, PhD, associate professor at University of Michigan, who helped create what she and colleagues call an atlas of the ovary. “By creating a map or an atlas, we can now follow what nature created and engineer the building blocks of an ovary — and build a nature-like structure.”

So far, the concept of an artificial ovary has been successful only in mice, with the development of a 3D-printed prosthetic ovary that enabled sterilized mice to have pups. Researchers hope that artificial human ovary technology could someday help women left infertile after cancer treatment, as well as patients who don›t respond to fertility treatments and those with premature ovarian failure.

But Dr. Shikanov believes this research will go even further, providing a valuable resource to scientists studying diseases and other conditions related to the ovary.

“Whenever people think about the ovary, if they think about it at all, they usually think about fertility,” said Dr. Shikanov. The ovary is so much more.

Besides producing and carrying a woman’s unfertilized eggs during her lifetime, the ovary is also responsible for endocrine function — the production of estrogen and progesterone, which in addition to supporting reproductive health, help maintain a woman’s cardiovascular, bone, and mental health.

“We don’t really understand everything that is happening in the ovary yet,” Dr. Shikanov said. “But we know it is an important organ.”
 

Mapping the Ovary

Because people don’t typically donate their ovaries, there are not many available for research, especially from younger reproductive age women, said Dr. Shikanov. So, the scientists set out to build a resource. They described their work in Science Advances.

To create their atlas, the researchers studied two premenopausal donor ovaries, profiling 18,000 genes in 257 regions. From three additional donor ovaries, they also generated single-cell RNA sequencing data for 21,198 cells.

“We identified four major cell types and four immune cell subtypes in the ovary,” said Dr. Shikanov. Taking samples from different areas of the ovary revealed distinct gene activities for oocytes, theca cells, and granulosa cells — expanding scientists’ understanding of the molecular programs driving ovarian follicle development.

What’s unique about their work is the focus on both single cell and spatial analysis, said study coauthor Jun Z. Li, PhD, associate chair of the University of Michigan’s department of computational medicine and bioinformatics. Specifically, they used a relatively new method called spatial transcriptomics, which allows them to see which genes are being activated and where.

“We are constructing the spatial arrangement of the cells in the ovary,” said Dr. Li. “This spatial analysis is like saying, ‘Let me look at where you are and who your neighbor is.’ ”

Their findings are built on other genetic and cellular research in the field, Dr. Li noted. Biomedical engineers in other areas of medicine are applying similar technologies to other organs including the heart, the breast, and bone — part of a larger project called the Human Cell Atlas.
 

Advancing Women’s Health Research

Historically, women’s health research has been underfunded and underrepresented, but the authors believe their atlas of the ovary is a significant step forward.

“There are a lot of biological questions that we don’t know the answers to about the ovary,” said Dr. Shikanov.

One of the biggest mysteries is why so many eggs never become fertilizable. Each human female is born with about one to two million ovarian follicles. Each follicle carries one immature egg. Around puberty, two thirds of these follicles die off. And most that are left never develop into fertilizable eggs.

“The majority of these follicles either just grow and secrete hormones or undergo atresia,” Dr. Shikanov said. “One question that we wanted to understand is, what determines an egg that can grow, ovulate, and become a fertilizable egg and potentially develop into a new human being from one that does not?”

Another big question researchers have is, what’s happening with other types of cells in the ovary — the supporting cells that produce endocrine hormones? Where are they located and what proteins and RNA are they making? Their research begins to unravel some of these questions and lays a foundation for future studies.

“We wanted to analyze the transcriptional signatures from specific regions and then do bioinformatical analysis and really combine structure, function, and transcriptional signatures,” Dr. Shikanov said.

Knowing the transcriptional signatures can help researchers understand disease mechanisms and then go on to develop treatments for these diseases.

Winifred Mak, MD, PhD, a reproductive endocrinologist and infertility specialist at Dell Medical School, University of Texas, Austin, studies cancer fertility preservation. “For me, it is interesting to see that there are so many different clusters of cells in the ovary that have been identified by this study that we were not necessarily aware of before,” said Dr. Mak, who is not involved in the new research. “Also, the identification of new genes not previously studied in the human ovary.”
 

What’s Next

Dozens of scientists who study reproductive health are already reaching out to the researchers about their work, Dr. Shikanov said.

“We get contacted almost every day from researchers all around the world asking for data sets or asking for details from this paper,” she said, “from people who study ovarian cancer, for example.”

Dr. Mak said having a map of a normal ovary could also help researchers who study premature ovarian insufficiency — why the ovary sometimes goes into premature menopause — and polycystic ovarian syndrome.

Another big area of research interest is ovarian aging. “Women live so much longer now, but we still reach menopause at the age of 50,” Dr. Shikanov said. “So, there are efforts going toward understanding ovarian aging and maybe preventing it to extend ovarian longevity.”

Dr. Mak said it will enable scientists to “look at different age women and see what genes change across the reproductive lifespan.”

The atlas may also eventually lead to treatments that help restore fertility in individuals who had and were treated for cancer as children, people who undergo sex transitions, and those whose reproductive organs have been impacted by trauma in conflict settings or accidents, Dr. Li said.

The applications are numerous and exciting, Dr. Shikanov said. “Our atlas is like a benchmark. Now researchers can collect ovaries from individuals with these diseases and conditions and try to compare what’s different.”

A version of this article appeared on Medscape.com.