Amy Karon

SALT LAKE CITY – Certain nonsurgical biomarkers appear to accurately identify chronic endometriosis, and might soon spare patients from years of misdiagnosis and the costs and burden of diagnostic surgery, according to experts at the annual meeting of the American Society for Reproductive Medicine.

Most notably, expression levels of three microRNAs, 125-b-5p, 451a, and 3613-5p, correctly distinguished patients with chronic endometriosis from healthy controls, said Hugh S. Taylor, MD, of Yale University in New Haven, Conn.

Patients may go up to 12 years and see five or more physicians before they are diagnosed. Clinicians tend to rely on surgical diagnosis, but “there is a reluctance to perform surgery unless there is severe disease,” he added. “The lack of nonsurgical biomarkers contributes significantly to delays in diagnosis and timely intervention.”

These concerns prompted Dr. Taylor and his associates to study microRNAs – the short, noncoding, functional RNAs that promote messenger RNA breakdown or repress its translation. MicroRNA expression varies by tissue type and disease status, and occurs in a variety of body fluids, giving them real potential as nonsurgical biomarkers, Dr. Taylor said. To examine their role in endometriosis, he and his associates performed microarray profiling and confirmatory quantitative real-time polymerase chain reaction testing of serum samples from 24 women with chronic endometriosis and 24 healthy women who served as controls (Fertil Steril. 2016 Aug;106[2]:402-9).

MicroRNA 125b-5p was upregulated the most in endometriosis patients and distinguished patients from controls with a “giant” area under the receiver operating characteristic curve value of 0.974, Dr. Taylor said. Remarkably, this value rose to 1 – meaning that sensitivity and specificity both were 100% – when the researchers added another upregulated microRNA (451a) and a downregulated microRNA (3613-5p) to the model. More work is underway to understand how a test for these microRNAs would perform in larger populations, Dr. Taylor said.

MicroRNAs also are likely to play functional roles in chronic endometriosis and may mediate treatment response, he noted. For example, the microRNA 125b-5p, which is upregulated in endometriosis, increases the expression of inflammatory cytokines and tumor necrosis factor alpha in macrophages, and the aromatase inhibitor letrozole, which reduces pelvic pain in the disease, increases the expression of let-7 microRNAs, with corresponding decreases in the migration of endometrial cells (Fertil Steril. 2016 Sep 1;106[3]:673-80). “Maybe these microRNAs are changing metabolism. Maybe they are changing immune cell activity,” Dr. Taylor said. “I think they are doing a lot more than sitting around waiting for us to discover them.”

None of the 24 patients with endometriosis in his study had taken oral contraceptives in the 3 months prior to serum sampling, Dr. Taylor noted. “We need to look at oral contraception as a potential confounder,” he acknowledged. “If something is independent of the menstrual cycle phase, that is much better than a marker that is dependent on cycle phase.”

Menstrual cycle phase and oral contraceptives are just two of many potential confounders of biomarkers in chronic endometriosis, according to Linda Giudice, MD, PhD, of the University of California, San Francisco. Disease severity, as well as the type, number, and location of lesions and the presence or absence of coexisting inflammatory disorders all can potentially affect the sensitivity and specificity of a marker, she said. Consequently, “there is no single biomarker for chronic endometriosis,” but there are several candidates besides microRNAs, she added. For example, studies show that menstrual blood is readily distinguishable from peripheral blood, and closely resembles the immune environment of the uterus. Another study found that urinary peptides distinguished patients with moderate to severe endometriosis from healthy controls, and mild disease from severe disease, with sensitivities and specificities ranging from 72% to 88% (Fertil Steril. 2011 Mar 15;95[4]:1261-6).

Other potential sources of diagnostic tests include the endometrial proteome, transcriptome, and methylome, as well as endometrial stem cells, Dr. Giudice said. But for now, surgical diagnosis remains the gold standard, and the World Endometriosis Research Foundation is working to homogenize recording of surgical phenotypic information and laparoscopic specimens to improve data quality, she added.

Dr. Taylor did not report funding sources. He disclosed financial ties to Pfizer, OvaScience AbbVie, Bayer, and Euroscreen. Dr. Giudice acknowledged support from the National Institutes of Health and the UCSF NIH Human Endometrial Tissue and DNA Bank. She disclosed ties to Merck, Pfizer, NextGen Jane, AbbVie, and Juniper Pharmaceuticals.

SALT LAKE CITY – Certain nonsurgical biomarkers appear to accurately identify chronic endometriosis, and might soon spare patients from years of misdiagnosis and the costs and burden of diagnostic surgery, according to experts at the annual meeting of the American Society for Reproductive Medicine.

Most notably, expression levels of three microRNAs, 125-b-5p, 451a, and 3613-5p, correctly distinguished patients with chronic endometriosis from healthy controls, said Hugh S. Taylor, MD, of Yale University in New Haven, Conn.

Patients may go up to 12 years and see five or more physicians before they are diagnosed. Clinicians tend to rely on surgical diagnosis, but “there is a reluctance to perform surgery unless there is severe disease,” he added. “The lack of nonsurgical biomarkers contributes significantly to delays in diagnosis and timely intervention.”

These concerns prompted Dr. Taylor and his associates to study microRNAs – the short, noncoding, functional RNAs that promote messenger RNA breakdown or repress its translation. MicroRNA expression varies by tissue type and disease status, and occurs in a variety of body fluids, giving them real potential as nonsurgical biomarkers, Dr. Taylor said. To examine their role in endometriosis, he and his associates performed microarray profiling and confirmatory quantitative real-time polymerase chain reaction testing of serum samples from 24 women with chronic endometriosis and 24 healthy women who served as controls (Fertil Steril. 2016 Aug;106[2]:402-9).

MicroRNA 125b-5p was upregulated the most in endometriosis patients and distinguished patients from controls with a “giant” area under the receiver operating characteristic curve value of 0.974, Dr. Taylor said. Remarkably, this value rose to 1 – meaning that sensitivity and specificity both were 100% – when the researchers added another upregulated microRNA (451a) and a downregulated microRNA (3613-5p) to the model. More work is underway to understand how a test for these microRNAs would perform in larger populations, Dr. Taylor said.

MicroRNAs also are likely to play functional roles in chronic endometriosis and may mediate treatment response, he noted. For example, the microRNA 125b-5p, which is upregulated in endometriosis, increases the expression of inflammatory cytokines and tumor necrosis factor alpha in macrophages, and the aromatase inhibitor letrozole, which reduces pelvic pain in the disease, increases the expression of let-7 microRNAs, with corresponding decreases in the migration of endometrial cells (Fertil Steril. 2016 Sep 1;106[3]:673-80). “Maybe these microRNAs are changing metabolism. Maybe they are changing immune cell activity,” Dr. Taylor said. “I think they are doing a lot more than sitting around waiting for us to discover them.”

None of the 24 patients with endometriosis in his study had taken oral contraceptives in the 3 months prior to serum sampling, Dr. Taylor noted. “We need to look at oral contraception as a potential confounder,” he acknowledged. “If something is independent of the menstrual cycle phase, that is much better than a marker that is dependent on cycle phase.”

Menstrual cycle phase and oral contraceptives are just two of many potential confounders of biomarkers in chronic endometriosis, according to Linda Giudice, MD, PhD, of the University of California, San Francisco. Disease severity, as well as the type, number, and location of lesions and the presence or absence of coexisting inflammatory disorders all can potentially affect the sensitivity and specificity of a marker, she said. Consequently, “there is no single biomarker for chronic endometriosis,” but there are several candidates besides microRNAs, she added. For example, studies show that menstrual blood is readily distinguishable from peripheral blood, and closely resembles the immune environment of the uterus. Another study found that urinary peptides distinguished patients with moderate to severe endometriosis from healthy controls, and mild disease from severe disease, with sensitivities and specificities ranging from 72% to 88% (Fertil Steril. 2011 Mar 15;95[4]:1261-6).

Other potential sources of diagnostic tests include the endometrial proteome, transcriptome, and methylome, as well as endometrial stem cells, Dr. Giudice said. But for now, surgical diagnosis remains the gold standard, and the World Endometriosis Research Foundation is working to homogenize recording of surgical phenotypic information and laparoscopic specimens to improve data quality, she added.

Dr. Taylor did not report funding sources. He disclosed financial ties to Pfizer, OvaScience AbbVie, Bayer, and Euroscreen. Dr. Giudice acknowledged support from the National Institutes of Health and the UCSF NIH Human Endometrial Tissue and DNA Bank. She disclosed ties to Merck, Pfizer, NextGen Jane, AbbVie, and Juniper Pharmaceuticals.

SALT LAKE CITY – Certain nonsurgical biomarkers appear to accurately identify chronic endometriosis, and might soon spare patients from years of misdiagnosis and the costs and burden of diagnostic surgery, according to experts at the annual meeting of the American Society for Reproductive Medicine.

Most notably, expression levels of three microRNAs, 125-b-5p, 451a, and 3613-5p, correctly distinguished patients with chronic endometriosis from healthy controls, said Hugh S. Taylor, MD, of Yale University in New Haven, Conn.

Patients may go up to 12 years and see five or more physicians before they are diagnosed. Clinicians tend to rely on surgical diagnosis, but “there is a reluctance to perform surgery unless there is severe disease,” he added. “The lack of nonsurgical biomarkers contributes significantly to delays in diagnosis and timely intervention.”

These concerns prompted Dr. Taylor and his associates to study microRNAs – the short, noncoding, functional RNAs that promote messenger RNA breakdown or repress its translation. MicroRNA expression varies by tissue type and disease status, and occurs in a variety of body fluids, giving them real potential as nonsurgical biomarkers, Dr. Taylor said. To examine their role in endometriosis, he and his associates performed microarray profiling and confirmatory quantitative real-time polymerase chain reaction testing of serum samples from 24 women with chronic endometriosis and 24 healthy women who served as controls (Fertil Steril. 2016 Aug;106[2]:402-9).

MicroRNA 125b-5p was upregulated the most in endometriosis patients and distinguished patients from controls with a “giant” area under the receiver operating characteristic curve value of 0.974, Dr. Taylor said. Remarkably, this value rose to 1 – meaning that sensitivity and specificity both were 100% – when the researchers added another upregulated microRNA (451a) and a downregulated microRNA (3613-5p) to the model. More work is underway to understand how a test for these microRNAs would perform in larger populations, Dr. Taylor said.

MicroRNAs also are likely to play functional roles in chronic endometriosis and may mediate treatment response, he noted. For example, the microRNA 125b-5p, which is upregulated in endometriosis, increases the expression of inflammatory cytokines and tumor necrosis factor alpha in macrophages, and the aromatase inhibitor letrozole, which reduces pelvic pain in the disease, increases the expression of let-7 microRNAs, with corresponding decreases in the migration of endometrial cells (Fertil Steril. 2016 Sep 1;106[3]:673-80). “Maybe these microRNAs are changing metabolism. Maybe they are changing immune cell activity,” Dr. Taylor said. “I think they are doing a lot more than sitting around waiting for us to discover them.”

None of the 24 patients with endometriosis in his study had taken oral contraceptives in the 3 months prior to serum sampling, Dr. Taylor noted. “We need to look at oral contraception as a potential confounder,” he acknowledged. “If something is independent of the menstrual cycle phase, that is much better than a marker that is dependent on cycle phase.”

Menstrual cycle phase and oral contraceptives are just two of many potential confounders of biomarkers in chronic endometriosis, according to Linda Giudice, MD, PhD, of the University of California, San Francisco. Disease severity, as well as the type, number, and location of lesions and the presence or absence of coexisting inflammatory disorders all can potentially affect the sensitivity and specificity of a marker, she said. Consequently, “there is no single biomarker for chronic endometriosis,” but there are several candidates besides microRNAs, she added. For example, studies show that menstrual blood is readily distinguishable from peripheral blood, and closely resembles the immune environment of the uterus. Another study found that urinary peptides distinguished patients with moderate to severe endometriosis from healthy controls, and mild disease from severe disease, with sensitivities and specificities ranging from 72% to 88% (Fertil Steril. 2011 Mar 15;95[4]:1261-6).

Other potential sources of diagnostic tests include the endometrial proteome, transcriptome, and methylome, as well as endometrial stem cells, Dr. Giudice said. But for now, surgical diagnosis remains the gold standard, and the World Endometriosis Research Foundation is working to homogenize recording of surgical phenotypic information and laparoscopic specimens to improve data quality, she added.

Dr. Taylor did not report funding sources. He disclosed financial ties to Pfizer, OvaScience AbbVie, Bayer, and Euroscreen. Dr. Giudice acknowledged support from the National Institutes of Health and the UCSF NIH Human Endometrial Tissue and DNA Bank. She disclosed ties to Merck, Pfizer, NextGen Jane, AbbVie, and Juniper Pharmaceuticals.

SALT LAKE CITY – An aspiring mother calls the sperm bank she has arranged to work with for insemination. “We can ship sperm across state lines,” she is told – until the clinic learns she has a wife and reverses its policy.

This is just one of many experiences faced by lesbian, gay, bisexual, and transgender (LGBT) individuals on the road to parenthood, Sarah R. Holley, PhD, in the psychology department bat San Francisco (Calif.) State University, said at the annual meeting of the American Society of Reproductive Medicine.

Such experiences harm LGBT persons seeking ART and convince them that clinics only care about their money, according to Dr. Holley. So how to do better? “In order to combat heteronormative bias, we first need to get out of problem-solving mode and offer emotional understanding,” she said. For example, providers should never assume that the uteri and eggs of two female partners are interchangeable, or that a woman who is infertile should not grieve, simply because her wife can conceive.

Providers also should be ready to discuss the downsides of tandem pregnancy with lesbian couples, said Angela K. Lawson, PhD, a psychologist at Northwestern University in Chicago. While few studies have examined specific outcomes, “Each woman has a different chance of a successful pregnancy,” she said. “What if one or both women have complications, or a medically challenged child, or they don’t get pregnant at same time?” By taking turns at IVF, couples can better cope with these potential outcomes, she suggested.

Increasingly, lesbian couples are pursuing “reciprocal in vitro fertilization,” in which one woman contributes her ovum for embryo formation, and her partner undergoes implantation. The correct terms here are “genetic mother” and “gestational mother,” not “egg donor” and “gestational carrier,” which have completely different emotional and legal implications, Dr. Lawson emphasized.

That difference makes it imperative for ART clinics to use properly worded consent forms, said Colleen M. Quinn, JD, of the Adoption and Surrogacy Law Center at Locke & Quinn in Richmond, Va. The U.S. Supreme Court decision recognizing same-sex marriage did not clarify legal parental status; birth certificates do not grant legal parental status or rescind the rights of sperm donors, she said. As a result, lesbian couples who separated have won or lost custody battles based on the wording of ART consent forms, she added. Clinics are ethically obligated to advise their LGBT clients to seek legal counsel and create their own agreements about intended parenthood, she emphasized.

For their own protection, clinics also should insist that couples create a legal property disposition agreement between themselves before creating or storing embryos on their behalf, Ms. Quinn said. “An informed consent document is not sufficient,” she added. “Neither is a disposition agreement with the clinic.”

Prospective transgender parents also merit empathic consideration, said Dr. Lawson. Self-identified women who are biologically male may face “profound sadness” because they cannot carry a pregnancy. Conversely, transgender men who become pregnant in order to fulfill dreams of children may nonetheless experience intense gender dysphoria. In at least one case, a transgender male secluded himself at home throughout his pregnancy to avoid public scrutiny, Dr. Lawson said. In all cases, it helps to identify local sources of support and information and refer patients appropriately, Dr. Holley noted.

The experts also briefly covered prospective gay male fathers, who may pay upward of $100,000 to work with a gestational carrier from an agency, they said. Couples who cannot afford to do so may work with a female friend or seek a gestational carrier in another country, each of which raises questions about parental involvement and legal rights. When same-sex male partners are both donating sperm for embryo formation, “One of the biggest controversies is what to do if only one embryo implants,” Dr. Lawson said. “Will the fathers pursue DNA testing of that child? This gets us into issues of intentional unknowing and secrecy, and we know that secrecy can destroy families, whereas privacy typically doesn’t. It’s in the best interest of children to know the story of their parentage.”

None of the experts acknowledged funding sources. Ms. Quinn had no disclosures.

SALT LAKE CITY – An aspiring mother calls the sperm bank she has arranged to work with for insemination. “We can ship sperm across state lines,” she is told – until the clinic learns she has a wife and reverses its policy.

This is just one of many experiences faced by lesbian, gay, bisexual, and transgender (LGBT) individuals on the road to parenthood, Sarah R. Holley, PhD, in the psychology department bat San Francisco (Calif.) State University, said at the annual meeting of the American Society of Reproductive Medicine.

Such experiences harm LGBT persons seeking ART and convince them that clinics only care about their money, according to Dr. Holley. So how to do better? “In order to combat heteronormative bias, we first need to get out of problem-solving mode and offer emotional understanding,” she said. For example, providers should never assume that the uteri and eggs of two female partners are interchangeable, or that a woman who is infertile should not grieve, simply because her wife can conceive.

Providers also should be ready to discuss the downsides of tandem pregnancy with lesbian couples, said Angela K. Lawson, PhD, a psychologist at Northwestern University in Chicago. While few studies have examined specific outcomes, “Each woman has a different chance of a successful pregnancy,” she said. “What if one or both women have complications, or a medically challenged child, or they don’t get pregnant at same time?” By taking turns at IVF, couples can better cope with these potential outcomes, she suggested.

Increasingly, lesbian couples are pursuing “reciprocal in vitro fertilization,” in which one woman contributes her ovum for embryo formation, and her partner undergoes implantation. The correct terms here are “genetic mother” and “gestational mother,” not “egg donor” and “gestational carrier,” which have completely different emotional and legal implications, Dr. Lawson emphasized.

That difference makes it imperative for ART clinics to use properly worded consent forms, said Colleen M. Quinn, JD, of the Adoption and Surrogacy Law Center at Locke & Quinn in Richmond, Va. The U.S. Supreme Court decision recognizing same-sex marriage did not clarify legal parental status; birth certificates do not grant legal parental status or rescind the rights of sperm donors, she said. As a result, lesbian couples who separated have won or lost custody battles based on the wording of ART consent forms, she added. Clinics are ethically obligated to advise their LGBT clients to seek legal counsel and create their own agreements about intended parenthood, she emphasized.

For their own protection, clinics also should insist that couples create a legal property disposition agreement between themselves before creating or storing embryos on their behalf, Ms. Quinn said. “An informed consent document is not sufficient,” she added. “Neither is a disposition agreement with the clinic.”

Prospective transgender parents also merit empathic consideration, said Dr. Lawson. Self-identified women who are biologically male may face “profound sadness” because they cannot carry a pregnancy. Conversely, transgender men who become pregnant in order to fulfill dreams of children may nonetheless experience intense gender dysphoria. In at least one case, a transgender male secluded himself at home throughout his pregnancy to avoid public scrutiny, Dr. Lawson said. In all cases, it helps to identify local sources of support and information and refer patients appropriately, Dr. Holley noted.

The experts also briefly covered prospective gay male fathers, who may pay upward of $100,000 to work with a gestational carrier from an agency, they said. Couples who cannot afford to do so may work with a female friend or seek a gestational carrier in another country, each of which raises questions about parental involvement and legal rights. When same-sex male partners are both donating sperm for embryo formation, “One of the biggest controversies is what to do if only one embryo implants,” Dr. Lawson said. “Will the fathers pursue DNA testing of that child? This gets us into issues of intentional unknowing and secrecy, and we know that secrecy can destroy families, whereas privacy typically doesn’t. It’s in the best interest of children to know the story of their parentage.”

None of the experts acknowledged funding sources. Ms. Quinn had no disclosures.

SALT LAKE CITY – An aspiring mother calls the sperm bank she has arranged to work with for insemination. “We can ship sperm across state lines,” she is told – until the clinic learns she has a wife and reverses its policy.

This is just one of many experiences faced by lesbian, gay, bisexual, and transgender (LGBT) individuals on the road to parenthood, Sarah R. Holley, PhD, in the psychology department bat San Francisco (Calif.) State University, said at the annual meeting of the American Society of Reproductive Medicine.

Such experiences harm LGBT persons seeking ART and convince them that clinics only care about their money, according to Dr. Holley. So how to do better? “In order to combat heteronormative bias, we first need to get out of problem-solving mode and offer emotional understanding,” she said. For example, providers should never assume that the uteri and eggs of two female partners are interchangeable, or that a woman who is infertile should not grieve, simply because her wife can conceive.

Providers also should be ready to discuss the downsides of tandem pregnancy with lesbian couples, said Angela K. Lawson, PhD, a psychologist at Northwestern University in Chicago. While few studies have examined specific outcomes, “Each woman has a different chance of a successful pregnancy,” she said. “What if one or both women have complications, or a medically challenged child, or they don’t get pregnant at same time?” By taking turns at IVF, couples can better cope with these potential outcomes, she suggested.

Increasingly, lesbian couples are pursuing “reciprocal in vitro fertilization,” in which one woman contributes her ovum for embryo formation, and her partner undergoes implantation. The correct terms here are “genetic mother” and “gestational mother,” not “egg donor” and “gestational carrier,” which have completely different emotional and legal implications, Dr. Lawson emphasized.

That difference makes it imperative for ART clinics to use properly worded consent forms, said Colleen M. Quinn, JD, of the Adoption and Surrogacy Law Center at Locke & Quinn in Richmond, Va. The U.S. Supreme Court decision recognizing same-sex marriage did not clarify legal parental status; birth certificates do not grant legal parental status or rescind the rights of sperm donors, she said. As a result, lesbian couples who separated have won or lost custody battles based on the wording of ART consent forms, she added. Clinics are ethically obligated to advise their LGBT clients to seek legal counsel and create their own agreements about intended parenthood, she emphasized.

For their own protection, clinics also should insist that couples create a legal property disposition agreement between themselves before creating or storing embryos on their behalf, Ms. Quinn said. “An informed consent document is not sufficient,” she added. “Neither is a disposition agreement with the clinic.”

Prospective transgender parents also merit empathic consideration, said Dr. Lawson. Self-identified women who are biologically male may face “profound sadness” because they cannot carry a pregnancy. Conversely, transgender men who become pregnant in order to fulfill dreams of children may nonetheless experience intense gender dysphoria. In at least one case, a transgender male secluded himself at home throughout his pregnancy to avoid public scrutiny, Dr. Lawson said. In all cases, it helps to identify local sources of support and information and refer patients appropriately, Dr. Holley noted.

The experts also briefly covered prospective gay male fathers, who may pay upward of $100,000 to work with a gestational carrier from an agency, they said. Couples who cannot afford to do so may work with a female friend or seek a gestational carrier in another country, each of which raises questions about parental involvement and legal rights. When same-sex male partners are both donating sperm for embryo formation, “One of the biggest controversies is what to do if only one embryo implants,” Dr. Lawson said. “Will the fathers pursue DNA testing of that child? This gets us into issues of intentional unknowing and secrecy, and we know that secrecy can destroy families, whereas privacy typically doesn’t. It’s in the best interest of children to know the story of their parentage.”

None of the experts acknowledged funding sources. Ms. Quinn had no disclosures.

SALT LAKE CITY – Women who are obese should receive more than 5,000 IU of human chorionic gonadotropin (HCG) to trigger final oocyte maturation during in vitro fertilization, findings of a retrospective cohort study suggest.

Fully 23% of obese women had low beta-HCG levels the day after receiving a 5,000 IU HCG trigger dose, compared with 1% of non-obese women (odds ratio, 21.4; 95% confidence interval, 15.0-30.4), reported Mohamad Irani, MD, and his associates from Cornell University, New York. In contrast, 10,000 IU HCG triggered adequate beta-HCG levels in 81% of obese patients with a BMI of 30-40 kg/m², and in 90% of those whose BMI exceeded 40 kg/m².

Low beta-HCG levels decreased the chances of oocyte maturation, fertilization, and live birth in the study. “Patients’ BMI should be taken into consideration when determining the dose of HCG trigger,” the investigators concluded in a poster presented at the annual meeting of the American Society for Reproductive Medicine.

Patients with hypothalamic amenorrhea or who are undergoing stimulation with a gonadotropin-releasing hormone (GnRH) agonist are not candidates for a GnRH-agonist trigger and therefore need to receive HCG instead, the researchers noted. To understand how the dose of HCG affects the chances of final oocyte maturation, they studied 19,084 HCG trigger recipients at their center between 2004 and 2013.

By protocol, patients received 10,000 IU HCG if their serum estradiol (E2) level was less than 1,500 pg/mL on the day of trigger; 5,000 IU if it measured 1,501-2,500 pg/mL; 4,000 IU if it was 2,501-3,000 pg/mL; and 3,300 IU if it exceeded 3,000 pg/mL.

The day after HCG trigger, 18,666 patients had beta-HCG levels of at least 50 mIU/mL, while 418 patients had low beta-HCG levels of less than 50 mIU/mL. A comparison of the two groups showed that low beta-HCG was associated with significantly lower rates of oocyte maturation (77% vs. 81%; P less than .001) and fertilization (63% vs. 72%; P less than .001). It was also associated with more than a 30% lower chance of a live birth (adjusted OR, 0.67; 95% CI, 0.5-0.8), even after accounting for age, and the stage and number of embryos transferred.

The researchers also examined response to HCG trigger among non-obese patients. Among patients who were overweight (BMI 25 to 30 kg/m²), the chances of a low beta-HCG level the day after trigger were 14% when the HCG dose was 3,300 IU, 12.5% when it was 4,000 IU, 4.3% when it was 5,000 IU, and 0.4% when it was 10,000 IU.

Among healthy-weight patients (BMI 18.5-25 kg/m²), low beta-HCG levels occurred 3.6% of the time when the HCG dose was 3,300 IU, 2.3% of the time when it was 4,000 IU, 0.6% of the time when it was 5,000 IU, and 0.08% of the time when it was 10,000 IU. Notably, these same doses triggered adequate beta-HCG levels in all 660 patients who were underweight (BMI less than 18.5 kg/m²), the researchers reported.

Dr. Irani reported having no relevant financial disclosures.
 

SALT LAKE CITY – Women who are obese should receive more than 5,000 IU of human chorionic gonadotropin (HCG) to trigger final oocyte maturation during in vitro fertilization, findings of a retrospective cohort study suggest.

Fully 23% of obese women had low beta-HCG levels the day after receiving a 5,000 IU HCG trigger dose, compared with 1% of non-obese women (odds ratio, 21.4; 95% confidence interval, 15.0-30.4), reported Mohamad Irani, MD, and his associates from Cornell University, New York. In contrast, 10,000 IU HCG triggered adequate beta-HCG levels in 81% of obese patients with a BMI of 30-40 kg/m², and in 90% of those whose BMI exceeded 40 kg/m².

Low beta-HCG levels decreased the chances of oocyte maturation, fertilization, and live birth in the study. “Patients’ BMI should be taken into consideration when determining the dose of HCG trigger,” the investigators concluded in a poster presented at the annual meeting of the American Society for Reproductive Medicine.

Patients with hypothalamic amenorrhea or who are undergoing stimulation with a gonadotropin-releasing hormone (GnRH) agonist are not candidates for a GnRH-agonist trigger and therefore need to receive HCG instead, the researchers noted. To understand how the dose of HCG affects the chances of final oocyte maturation, they studied 19,084 HCG trigger recipients at their center between 2004 and 2013.

By protocol, patients received 10,000 IU HCG if their serum estradiol (E2) level was less than 1,500 pg/mL on the day of trigger; 5,000 IU if it measured 1,501-2,500 pg/mL; 4,000 IU if it was 2,501-3,000 pg/mL; and 3,300 IU if it exceeded 3,000 pg/mL.

The day after HCG trigger, 18,666 patients had beta-HCG levels of at least 50 mIU/mL, while 418 patients had low beta-HCG levels of less than 50 mIU/mL. A comparison of the two groups showed that low beta-HCG was associated with significantly lower rates of oocyte maturation (77% vs. 81%; P less than .001) and fertilization (63% vs. 72%; P less than .001). It was also associated with more than a 30% lower chance of a live birth (adjusted OR, 0.67; 95% CI, 0.5-0.8), even after accounting for age, and the stage and number of embryos transferred.

The researchers also examined response to HCG trigger among non-obese patients. Among patients who were overweight (BMI 25 to 30 kg/m²), the chances of a low beta-HCG level the day after trigger were 14% when the HCG dose was 3,300 IU, 12.5% when it was 4,000 IU, 4.3% when it was 5,000 IU, and 0.4% when it was 10,000 IU.

Among healthy-weight patients (BMI 18.5-25 kg/m²), low beta-HCG levels occurred 3.6% of the time when the HCG dose was 3,300 IU, 2.3% of the time when it was 4,000 IU, 0.6% of the time when it was 5,000 IU, and 0.08% of the time when it was 10,000 IU. Notably, these same doses triggered adequate beta-HCG levels in all 660 patients who were underweight (BMI less than 18.5 kg/m²), the researchers reported.

Dr. Irani reported having no relevant financial disclosures.
 

SALT LAKE CITY – Women who are obese should receive more than 5,000 IU of human chorionic gonadotropin (HCG) to trigger final oocyte maturation during in vitro fertilization, findings of a retrospective cohort study suggest.

Fully 23% of obese women had low beta-HCG levels the day after receiving a 5,000 IU HCG trigger dose, compared with 1% of non-obese women (odds ratio, 21.4; 95% confidence interval, 15.0-30.4), reported Mohamad Irani, MD, and his associates from Cornell University, New York. In contrast, 10,000 IU HCG triggered adequate beta-HCG levels in 81% of obese patients with a BMI of 30-40 kg/m², and in 90% of those whose BMI exceeded 40 kg/m².

Low beta-HCG levels decreased the chances of oocyte maturation, fertilization, and live birth in the study. “Patients’ BMI should be taken into consideration when determining the dose of HCG trigger,” the investigators concluded in a poster presented at the annual meeting of the American Society for Reproductive Medicine.

Patients with hypothalamic amenorrhea or who are undergoing stimulation with a gonadotropin-releasing hormone (GnRH) agonist are not candidates for a GnRH-agonist trigger and therefore need to receive HCG instead, the researchers noted. To understand how the dose of HCG affects the chances of final oocyte maturation, they studied 19,084 HCG trigger recipients at their center between 2004 and 2013.

By protocol, patients received 10,000 IU HCG if their serum estradiol (E2) level was less than 1,500 pg/mL on the day of trigger; 5,000 IU if it measured 1,501-2,500 pg/mL; 4,000 IU if it was 2,501-3,000 pg/mL; and 3,300 IU if it exceeded 3,000 pg/mL.

The day after HCG trigger, 18,666 patients had beta-HCG levels of at least 50 mIU/mL, while 418 patients had low beta-HCG levels of less than 50 mIU/mL. A comparison of the two groups showed that low beta-HCG was associated with significantly lower rates of oocyte maturation (77% vs. 81%; P less than .001) and fertilization (63% vs. 72%; P less than .001). It was also associated with more than a 30% lower chance of a live birth (adjusted OR, 0.67; 95% CI, 0.5-0.8), even after accounting for age, and the stage and number of embryos transferred.

The researchers also examined response to HCG trigger among non-obese patients. Among patients who were overweight (BMI 25 to 30 kg/m²), the chances of a low beta-HCG level the day after trigger were 14% when the HCG dose was 3,300 IU, 12.5% when it was 4,000 IU, 4.3% when it was 5,000 IU, and 0.4% when it was 10,000 IU.

Among healthy-weight patients (BMI 18.5-25 kg/m²), low beta-HCG levels occurred 3.6% of the time when the HCG dose was 3,300 IU, 2.3% of the time when it was 4,000 IU, 0.6% of the time when it was 5,000 IU, and 0.08% of the time when it was 10,000 IU. Notably, these same doses triggered adequate beta-HCG levels in all 660 patients who were underweight (BMI less than 18.5 kg/m²), the researchers reported.

Dr. Irani reported having no relevant financial disclosures.
 

SALT LAKE CITY – The selective progesterone receptor modulator ulipristal acetate significantly reduced bleeding associated with fibroids in VENUS-I, a pivotal phase III trial of 147 premenopausal women.

A total of 58% of patients who took 10 mg ulipristal acetate per day had no bleeding except spotting during the last 35 days of treatment, compared with 2% of the placebo group (P less than .0001), James Simon, MD, said at the annual meeting of the American Society for Reproductive Medicine. Forty-seven percent of patients who took 5 mg ulipristal acetate per day also met the primary endpoint (P less than .0001, compared with placebo), he said.

The most common treatment-related adverse effect was hypertension, which affected 8% of women in the 10-mg group and 4% of women in the 5-mg group, he added during the late-breaking oral presentation.

Courtesy Wikimedia Commons/Hic et nunc/CC BY-SA 3.0

SALT LAKE CITY – The selective progesterone receptor modulator ulipristal acetate significantly reduced bleeding associated with fibroids in VENUS-I, a pivotal phase III trial of 147 premenopausal women.

A total of 58% of patients who took 10 mg ulipristal acetate per day had no bleeding except spotting during the last 35 days of treatment, compared with 2% of the placebo group (P less than .0001), James Simon, MD, said at the annual meeting of the American Society for Reproductive Medicine. Forty-seven percent of patients who took 5 mg ulipristal acetate per day also met the primary endpoint (P less than .0001, compared with placebo), he said.

The most common treatment-related adverse effect was hypertension, which affected 8% of women in the 10-mg group and 4% of women in the 5-mg group, he added during the late-breaking oral presentation.

Courtesy Wikimedia Commons/Hic et nunc/CC BY-SA 3.0

SALT LAKE CITY – The selective progesterone receptor modulator ulipristal acetate significantly reduced bleeding associated with fibroids in VENUS-I, a pivotal phase III trial of 147 premenopausal women.

A total of 58% of patients who took 10 mg ulipristal acetate per day had no bleeding except spotting during the last 35 days of treatment, compared with 2% of the placebo group (P less than .0001), James Simon, MD, said at the annual meeting of the American Society for Reproductive Medicine. Forty-seven percent of patients who took 5 mg ulipristal acetate per day also met the primary endpoint (P less than .0001, compared with placebo), he said.

The most common treatment-related adverse effect was hypertension, which affected 8% of women in the 10-mg group and 4% of women in the 5-mg group, he added during the late-breaking oral presentation.

Courtesy Wikimedia Commons/Hic et nunc/CC BY-SA 3.0

Metabolic syndrome was associated with a fourfold rise in cardiovascular events among patients with chronic hepatitis B virus infection, according to a prospective cohort study published in Hepatology.

Over a median of 7.3 years of follow-up, 8% of patients with metabolic syndrome developed ischemic or hemorrhagic stroke, acute coronary syndrome, or congestive heart failure, or underwent revascularization, compared with 2% of patients without metabolic syndrome (P less than .0001), reported Jenny Yeuk-Ki Cheng, MD, and her associates at The Chinese University of Hong Kong.

But it was liver stiffness measure (LSM), not metabolic syndrome, that predicted hepatic events (hazard ratio, 1.6; 95% confidence interval, 1.0 to 2.5) and death (HR, 1.9; 95% CI, 1.1 to 3.2), the investigators reported (Hepatology. 2016 Sep 29. doi: 10.1002/hep.28778).

Their study included 1,466 patients with chronic HBV infection who averaged 46 years of age, with an average baseline LSM of 8.4 kPa (standard deviation, 6.3 kPa). A total of 188 patients (12.8%) had metabolic syndrome at baseline, defined as at least three of the following five factors: central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension, and type 2 diabetes mellitus or fasting hyperglycemia.

©sarathsasidharan/Thinkstock

Metabolic syndrome was associated with a fourfold rise in cardiovascular events among patients with chronic hepatitis B virus infection, according to a prospective cohort study published in Hepatology.

Over a median of 7.3 years of follow-up, 8% of patients with metabolic syndrome developed ischemic or hemorrhagic stroke, acute coronary syndrome, or congestive heart failure, or underwent revascularization, compared with 2% of patients without metabolic syndrome (P less than .0001), reported Jenny Yeuk-Ki Cheng, MD, and her associates at The Chinese University of Hong Kong.

But it was liver stiffness measure (LSM), not metabolic syndrome, that predicted hepatic events (hazard ratio, 1.6; 95% confidence interval, 1.0 to 2.5) and death (HR, 1.9; 95% CI, 1.1 to 3.2), the investigators reported (Hepatology. 2016 Sep 29. doi: 10.1002/hep.28778).

Their study included 1,466 patients with chronic HBV infection who averaged 46 years of age, with an average baseline LSM of 8.4 kPa (standard deviation, 6.3 kPa). A total of 188 patients (12.8%) had metabolic syndrome at baseline, defined as at least three of the following five factors: central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension, and type 2 diabetes mellitus or fasting hyperglycemia.

©sarathsasidharan/Thinkstock

Metabolic syndrome was associated with a fourfold rise in cardiovascular events among patients with chronic hepatitis B virus infection, according to a prospective cohort study published in Hepatology.

Over a median of 7.3 years of follow-up, 8% of patients with metabolic syndrome developed ischemic or hemorrhagic stroke, acute coronary syndrome, or congestive heart failure, or underwent revascularization, compared with 2% of patients without metabolic syndrome (P less than .0001), reported Jenny Yeuk-Ki Cheng, MD, and her associates at The Chinese University of Hong Kong.

But it was liver stiffness measure (LSM), not metabolic syndrome, that predicted hepatic events (hazard ratio, 1.6; 95% confidence interval, 1.0 to 2.5) and death (HR, 1.9; 95% CI, 1.1 to 3.2), the investigators reported (Hepatology. 2016 Sep 29. doi: 10.1002/hep.28778).

Their study included 1,466 patients with chronic HBV infection who averaged 46 years of age, with an average baseline LSM of 8.4 kPa (standard deviation, 6.3 kPa). A total of 188 patients (12.8%) had metabolic syndrome at baseline, defined as at least three of the following five factors: central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension, and type 2 diabetes mellitus or fasting hyperglycemia.

©sarathsasidharan/Thinkstock

Healthy first-degree relatives of children and adolescents with inflammatory bowel disease had intestinal dysbiosis and an altered intestinal metabolome that correlated with one another and with the disease state, researchers reported in the November issue of Cellular and Molecular Gastroenterology and Hepatology.

These findings suggest the existence of a “high-risk microbiome/metabolome” that may increase susceptibility to inflammatory bowel disease (IBD), Jonathan Jacobs, MD, of the University of California, Los Angeles, reported with his associates. Among the healthy relatives with dysbiosis, nearly one-third also had elevated levels of fecal calprotectin, a marker of intestinal inflammation that has been previously reported in family members of patients with ulcerative colitis, the researchers noted. “If validated, prospective identification of [high-risk individuals] creates the opportunity to prevent disease development by targeting the dysbiosis and/or its metabolic consequences in the intestine,” they wrote.

selvanegra/thinkstockphotos.com

Healthy first-degree relatives of children and adolescents with inflammatory bowel disease had intestinal dysbiosis and an altered intestinal metabolome that correlated with one another and with the disease state, researchers reported in the November issue of Cellular and Molecular Gastroenterology and Hepatology.

These findings suggest the existence of a “high-risk microbiome/metabolome” that may increase susceptibility to inflammatory bowel disease (IBD), Jonathan Jacobs, MD, of the University of California, Los Angeles, reported with his associates. Among the healthy relatives with dysbiosis, nearly one-third also had elevated levels of fecal calprotectin, a marker of intestinal inflammation that has been previously reported in family members of patients with ulcerative colitis, the researchers noted. “If validated, prospective identification of [high-risk individuals] creates the opportunity to prevent disease development by targeting the dysbiosis and/or its metabolic consequences in the intestine,” they wrote.

selvanegra/thinkstockphotos.com

Healthy first-degree relatives of children and adolescents with inflammatory bowel disease had intestinal dysbiosis and an altered intestinal metabolome that correlated with one another and with the disease state, researchers reported in the November issue of Cellular and Molecular Gastroenterology and Hepatology.

These findings suggest the existence of a “high-risk microbiome/metabolome” that may increase susceptibility to inflammatory bowel disease (IBD), Jonathan Jacobs, MD, of the University of California, Los Angeles, reported with his associates. Among the healthy relatives with dysbiosis, nearly one-third also had elevated levels of fecal calprotectin, a marker of intestinal inflammation that has been previously reported in family members of patients with ulcerative colitis, the researchers noted. “If validated, prospective identification of [high-risk individuals] creates the opportunity to prevent disease development by targeting the dysbiosis and/or its metabolic consequences in the intestine,” they wrote.

selvanegra/thinkstockphotos.com

Interferon-free direct-acting antiviral (DAA) regimens for chronic hepatitis C virus (HCV) infection can cause reactivation of herpesvirus, said the authors of a multicenter case series published in the November issue of Clinical Gastroenterology and Hepatology.

Reactivation occurred in 10 of 576 (2%) patients treated at three hospitals in Spain, reported Dr. Christie Perello of Puerta de Hierro University Hospital in Madrid, together with her associates. Clinicians who treat HCV should maintain a high degree of clinical suspicion for latent herpesvirus infection, particularly when patients are older or have undergone liver transplantation, and should consider varicella zoster virus vaccination before beginning DAA therapy in nontransplant patients, they said.

Yale Rosen/Wikimedia Commons/Creative Commons Attribution-Share Alike 2.0 Generic

[email protected]

Interferon-free direct-acting antiviral (DAA) regimens for chronic hepatitis C virus (HCV) infection can cause reactivation of herpesvirus, said the authors of a multicenter case series published in the November issue of Clinical Gastroenterology and Hepatology.

Reactivation occurred in 10 of 576 (2%) patients treated at three hospitals in Spain, reported Dr. Christie Perello of Puerta de Hierro University Hospital in Madrid, together with her associates. Clinicians who treat HCV should maintain a high degree of clinical suspicion for latent herpesvirus infection, particularly when patients are older or have undergone liver transplantation, and should consider varicella zoster virus vaccination before beginning DAA therapy in nontransplant patients, they said.

Yale Rosen/Wikimedia Commons/Creative Commons Attribution-Share Alike 2.0 Generic

[email protected]

Interferon-free direct-acting antiviral (DAA) regimens for chronic hepatitis C virus (HCV) infection can cause reactivation of herpesvirus, said the authors of a multicenter case series published in the November issue of Clinical Gastroenterology and Hepatology.

Reactivation occurred in 10 of 576 (2%) patients treated at three hospitals in Spain, reported Dr. Christie Perello of Puerta de Hierro University Hospital in Madrid, together with her associates. Clinicians who treat HCV should maintain a high degree of clinical suspicion for latent herpesvirus infection, particularly when patients are older or have undergone liver transplantation, and should consider varicella zoster virus vaccination before beginning DAA therapy in nontransplant patients, they said.

Yale Rosen/Wikimedia Commons/Creative Commons Attribution-Share Alike 2.0 Generic

[email protected]

Interval colorectal cancers were proximally located and had DNA mismatch repair deficiency significantly more often than did colorectal cancers in colonoscopy-naive patients, researchers reported in the November issue of Gastroenterology.

The findings underscore the need to effectively visualize the large colon to avoid missing lesions during colonoscopy, said Elena M. Stoffel, MD, MPH, of the University of Michigan Health System, Ann Arbor, and her associates. “Studies consistently show that colonoscopy affords less protection against proximal cancers, and DNA mismatch repair deficiency tumors are more frequent among proximal cancers,” they noted. But the proximal and distal colon also have different embryologic origins and gene expression profiles, “prompting some to suggest that these might be considered as two distinct organs. Whether the precursors of postcolonoscopy colorectal cancers are simply harder to detect or resect endoscopically, or whether their behavior differs on the basis of anatomic location or molecular subtype remains unclear,” they added.

Courtesy Wikimedia Commons/nephron/Creative Commons License

A variety of quality-related factors contribute to the risk of postcolonoscopy or interval colorectal cancer, as do clinical characteristics such as older age at diagnosis, proximal tumor location, family history of colorectal cancer, and previous polypectomy, the investigators noted. To further explore the clinical and molecular correlates of postcolonoscopy tumors, they conducted a cross-sectional study of 10,365 colorectal cancers diagnosed in Denmark between 2007 and 2011 (Gastroenterology. 2016 Jul 18. doi: 10.1053/j.gastro.2016.07.010). A total of 725 (7%) of the colorectal cancers occurred after colonoscopy, the researchers determined. These lesions were significantly more often located in the proximal colon (odds ratio, 2.34; 95% confidence interval, 1.90-2.89) and were more likely to have DNA mismatch repair deficiency (OR, 1.26; 95% CI, 1.00-59) when compared with colorectal cancers diagnosed in patients with no prior colonoscopy. However, they also were significantly less likely to be metastatic at presentation (OR, 0.65; 95% CI, 0.48-0.89). Interval colorectal cancers were particularly likely to be located in the proximal colon and/or to have DNA mismatch repair deficiency when diagnosed 3-6 years after colonoscopy, but the excess burden of these characteristics persisted up to 10 years after colonoscopy, the researchers said.

Molecular analyses of 85 postcolonoscopy colorectal cancers from one hospital indicated that 24% had DNA mismatch repair deficiency. When considering only those tumors diagnosed within 10 years after colonoscopy, 27% had KRAS/NRAS mutations, 19% had BRAF mutations, and 19% had PIK3CA mutations. The 7% of tumors with molecular features of Lynch syndrome all occurred within 10 years after index colonoscopy and accounted for a third of cases of DNA mismatch repair deficiency, reflecting the role of this mutation pathway in Lynch syndrome and its tendency to rapidly progress, the investigators said.

Notably, 38% of colorectal cancers diagnosed within a year after colonoscopy involved an incomplete examination, compared with only 16% of cases diagnosed within 1-10 years after colonoscopy, they also reported. This finding and the clinical and molecular correlates of the interval cancers “supports the popular assumption that many cancers diagnosed soon after colonoscopy result from missed lesions,” they concluded. “However, the heterogeneity in clinical and molecular features of cancers diagnosed at different time intervals suggests postcolonoscopy colorectal cancers are likely multifactorial in their etiology and clinical behavior.”

The study was supported by the Danish Cancer Society, the Lundbeck Foundation, the Novo Nordisk Foundation, the National Institutes of Health, M.D. Anderson Cancer Center, and a University of Texas Frederick Becker Distinguished University Chair in Cancer Research. The investigators had no disclosures.

Interval colorectal cancers were proximally located and had DNA mismatch repair deficiency significantly more often than did colorectal cancers in colonoscopy-naive patients, researchers reported in the November issue of Gastroenterology.

The findings underscore the need to effectively visualize the large colon to avoid missing lesions during colonoscopy, said Elena M. Stoffel, MD, MPH, of the University of Michigan Health System, Ann Arbor, and her associates. “Studies consistently show that colonoscopy affords less protection against proximal cancers, and DNA mismatch repair deficiency tumors are more frequent among proximal cancers,” they noted. But the proximal and distal colon also have different embryologic origins and gene expression profiles, “prompting some to suggest that these might be considered as two distinct organs. Whether the precursors of postcolonoscopy colorectal cancers are simply harder to detect or resect endoscopically, or whether their behavior differs on the basis of anatomic location or molecular subtype remains unclear,” they added.

Courtesy Wikimedia Commons/nephron/Creative Commons License

A variety of quality-related factors contribute to the risk of postcolonoscopy or interval colorectal cancer, as do clinical characteristics such as older age at diagnosis, proximal tumor location, family history of colorectal cancer, and previous polypectomy, the investigators noted. To further explore the clinical and molecular correlates of postcolonoscopy tumors, they conducted a cross-sectional study of 10,365 colorectal cancers diagnosed in Denmark between 2007 and 2011 (Gastroenterology. 2016 Jul 18. doi: 10.1053/j.gastro.2016.07.010). A total of 725 (7%) of the colorectal cancers occurred after colonoscopy, the researchers determined. These lesions were significantly more often located in the proximal colon (odds ratio, 2.34; 95% confidence interval, 1.90-2.89) and were more likely to have DNA mismatch repair deficiency (OR, 1.26; 95% CI, 1.00-59) when compared with colorectal cancers diagnosed in patients with no prior colonoscopy. However, they also were significantly less likely to be metastatic at presentation (OR, 0.65; 95% CI, 0.48-0.89). Interval colorectal cancers were particularly likely to be located in the proximal colon and/or to have DNA mismatch repair deficiency when diagnosed 3-6 years after colonoscopy, but the excess burden of these characteristics persisted up to 10 years after colonoscopy, the researchers said.

Molecular analyses of 85 postcolonoscopy colorectal cancers from one hospital indicated that 24% had DNA mismatch repair deficiency. When considering only those tumors diagnosed within 10 years after colonoscopy, 27% had KRAS/NRAS mutations, 19% had BRAF mutations, and 19% had PIK3CA mutations. The 7% of tumors with molecular features of Lynch syndrome all occurred within 10 years after index colonoscopy and accounted for a third of cases of DNA mismatch repair deficiency, reflecting the role of this mutation pathway in Lynch syndrome and its tendency to rapidly progress, the investigators said.

Notably, 38% of colorectal cancers diagnosed within a year after colonoscopy involved an incomplete examination, compared with only 16% of cases diagnosed within 1-10 years after colonoscopy, they also reported. This finding and the clinical and molecular correlates of the interval cancers “supports the popular assumption that many cancers diagnosed soon after colonoscopy result from missed lesions,” they concluded. “However, the heterogeneity in clinical and molecular features of cancers diagnosed at different time intervals suggests postcolonoscopy colorectal cancers are likely multifactorial in their etiology and clinical behavior.”

The study was supported by the Danish Cancer Society, the Lundbeck Foundation, the Novo Nordisk Foundation, the National Institutes of Health, M.D. Anderson Cancer Center, and a University of Texas Frederick Becker Distinguished University Chair in Cancer Research. The investigators had no disclosures.

Interval colorectal cancers were proximally located and had DNA mismatch repair deficiency significantly more often than did colorectal cancers in colonoscopy-naive patients, researchers reported in the November issue of Gastroenterology.

The findings underscore the need to effectively visualize the large colon to avoid missing lesions during colonoscopy, said Elena M. Stoffel, MD, MPH, of the University of Michigan Health System, Ann Arbor, and her associates. “Studies consistently show that colonoscopy affords less protection against proximal cancers, and DNA mismatch repair deficiency tumors are more frequent among proximal cancers,” they noted. But the proximal and distal colon also have different embryologic origins and gene expression profiles, “prompting some to suggest that these might be considered as two distinct organs. Whether the precursors of postcolonoscopy colorectal cancers are simply harder to detect or resect endoscopically, or whether their behavior differs on the basis of anatomic location or molecular subtype remains unclear,” they added.

Courtesy Wikimedia Commons/nephron/Creative Commons License

A variety of quality-related factors contribute to the risk of postcolonoscopy or interval colorectal cancer, as do clinical characteristics such as older age at diagnosis, proximal tumor location, family history of colorectal cancer, and previous polypectomy, the investigators noted. To further explore the clinical and molecular correlates of postcolonoscopy tumors, they conducted a cross-sectional study of 10,365 colorectal cancers diagnosed in Denmark between 2007 and 2011 (Gastroenterology. 2016 Jul 18. doi: 10.1053/j.gastro.2016.07.010). A total of 725 (7%) of the colorectal cancers occurred after colonoscopy, the researchers determined. These lesions were significantly more often located in the proximal colon (odds ratio, 2.34; 95% confidence interval, 1.90-2.89) and were more likely to have DNA mismatch repair deficiency (OR, 1.26; 95% CI, 1.00-59) when compared with colorectal cancers diagnosed in patients with no prior colonoscopy. However, they also were significantly less likely to be metastatic at presentation (OR, 0.65; 95% CI, 0.48-0.89). Interval colorectal cancers were particularly likely to be located in the proximal colon and/or to have DNA mismatch repair deficiency when diagnosed 3-6 years after colonoscopy, but the excess burden of these characteristics persisted up to 10 years after colonoscopy, the researchers said.

Molecular analyses of 85 postcolonoscopy colorectal cancers from one hospital indicated that 24% had DNA mismatch repair deficiency. When considering only those tumors diagnosed within 10 years after colonoscopy, 27% had KRAS/NRAS mutations, 19% had BRAF mutations, and 19% had PIK3CA mutations. The 7% of tumors with molecular features of Lynch syndrome all occurred within 10 years after index colonoscopy and accounted for a third of cases of DNA mismatch repair deficiency, reflecting the role of this mutation pathway in Lynch syndrome and its tendency to rapidly progress, the investigators said.

Notably, 38% of colorectal cancers diagnosed within a year after colonoscopy involved an incomplete examination, compared with only 16% of cases diagnosed within 1-10 years after colonoscopy, they also reported. This finding and the clinical and molecular correlates of the interval cancers “supports the popular assumption that many cancers diagnosed soon after colonoscopy result from missed lesions,” they concluded. “However, the heterogeneity in clinical and molecular features of cancers diagnosed at different time intervals suggests postcolonoscopy colorectal cancers are likely multifactorial in their etiology and clinical behavior.”

The study was supported by the Danish Cancer Society, the Lundbeck Foundation, the Novo Nordisk Foundation, the National Institutes of Health, M.D. Anderson Cancer Center, and a University of Texas Frederick Becker Distinguished University Chair in Cancer Research. The investigators had no disclosures.

Separate sampling of the duodenal bulb increased detection of celiac disease by only 0.1% when endoscopy patients had a low pretest probability of celiac disease, according to research published in the November issue of Clinical Gastroenterology and Hepatology.

Duodenal bulb histology did reveal other abnormal findings, such as chronic peptic duodenitis, gastric heterotopia, and Brunner gland hyperplasia, wrote Samantha Stoven, MD, of Mayo Clinic, Rochester, Minn., and her associates. These findings did not seem to impede the identification of celiac disease, but their clinical implications were unclear, the researchers noted.

©Monthian/Thinkstock

Most studies of the diagnostic yield of duodenal bulb specimens have been performed in patients with known celiac disease or positive serology. In past studies of these high-probability cohorts, duodenal bulb sampling increased the diagnostic yield of celiac disease anywhere from 1.8% to 18%, but whether and how that finding translates to low-probability cohorts is unclear, the researchers said. Therefore, they retrospectively analyzed data from 679 endoscopy patients who had both duodenal bulb and small bowel biopsies collected at three Mayo Clinic sites in 2011. These sites are “open access,” meaning that patients can be referred for endoscopy without the approval of a gastroenterologist.

The average age of the patients was 50 years, and 63% were female. They were most commonly referred for duodenal biopsy because of chronic dyspepsia (46% of patients), diarrhea (35%), or nausea (17%). Patients with either known celiac disease or positive serology were excluded from the study (Clin Gastroenterol Hepatol. 2016 Mar 7. doi: 10.1016/j.cgh.2016.02.026). A total of 265 patients (39%) had abnormal duodenal histology, which was most often diagnosed as chronic peptic duodenitis, the researchers said. Histologic abnormalities usually involved the duodenal bulb (36% of cases), not the distal duodenum (15%; P less than .0001). However, among the 16 patients (2%) found to have celiac disease, just one patient had disease only in the duodenal bulb. Thus, duodenal bulb sampling increased the diagnostic yield of celiac disease by only 0.1% when considering the overall cohort. The patient with celiac disease limited to the bulb was a 46-year-old female presenting with diarrhea and anemia who had normal serologies but a permissive human leukocyte antigen test. Her duodenal bulb had villous atrophy and more than 25 intraepithelial lymphocytes per 100 epithelial cells, while her distal duodenum was normal.

Among the 85% of patients who had normal distal duodenums, 28% had abnormal bulb histology, most often chronic peptic duodenitis, active chronic peptic duodenitis, or gastric heterotopia, the researchers said. Among the 59% of patients whose celiac serology before endoscopy was truly unknown, only two (0.5%) had histologic changes consistent with celiac disease, which in both cases were located in the distal duodenum.

SOURCE: American Gastroenterological Association

“Individual sampling of the duodenal bulb in patients with either negative or unknown celiac serologic status can be considered in practices where expert gastrointestinal pathologists are present and there is agreement that both samples can be submitted in the same bottle, or there is not a separate charge for the additional container. Further studies may be needed to assess the diagnostic yield of separate bulb biopsies for celiac detection in all comers.”

An American College of Gastroenterology Junior Faculty Development Award helped support the work. Senior author Joseph A. Murray, MD, disclosed ties to Alba Therapeutics, Alvine Pharmaceuticals, AMAG Pharmaceuticals, and several other corporate entities. The remaining authors had no disclosures.

Separate sampling of the duodenal bulb increased detection of celiac disease by only 0.1% when endoscopy patients had a low pretest probability of celiac disease, according to research published in the November issue of Clinical Gastroenterology and Hepatology.

Duodenal bulb histology did reveal other abnormal findings, such as chronic peptic duodenitis, gastric heterotopia, and Brunner gland hyperplasia, wrote Samantha Stoven, MD, of Mayo Clinic, Rochester, Minn., and her associates. These findings did not seem to impede the identification of celiac disease, but their clinical implications were unclear, the researchers noted.

©Monthian/Thinkstock

Most studies of the diagnostic yield of duodenal bulb specimens have been performed in patients with known celiac disease or positive serology. In past studies of these high-probability cohorts, duodenal bulb sampling increased the diagnostic yield of celiac disease anywhere from 1.8% to 18%, but whether and how that finding translates to low-probability cohorts is unclear, the researchers said. Therefore, they retrospectively analyzed data from 679 endoscopy patients who had both duodenal bulb and small bowel biopsies collected at three Mayo Clinic sites in 2011. These sites are “open access,” meaning that patients can be referred for endoscopy without the approval of a gastroenterologist.

The average age of the patients was 50 years, and 63% were female. They were most commonly referred for duodenal biopsy because of chronic dyspepsia (46% of patients), diarrhea (35%), or nausea (17%). Patients with either known celiac disease or positive serology were excluded from the study (Clin Gastroenterol Hepatol. 2016 Mar 7. doi: 10.1016/j.cgh.2016.02.026). A total of 265 patients (39%) had abnormal duodenal histology, which was most often diagnosed as chronic peptic duodenitis, the researchers said. Histologic abnormalities usually involved the duodenal bulb (36% of cases), not the distal duodenum (15%; P less than .0001). However, among the 16 patients (2%) found to have celiac disease, just one patient had disease only in the duodenal bulb. Thus, duodenal bulb sampling increased the diagnostic yield of celiac disease by only 0.1% when considering the overall cohort. The patient with celiac disease limited to the bulb was a 46-year-old female presenting with diarrhea and anemia who had normal serologies but a permissive human leukocyte antigen test. Her duodenal bulb had villous atrophy and more than 25 intraepithelial lymphocytes per 100 epithelial cells, while her distal duodenum was normal.

Among the 85% of patients who had normal distal duodenums, 28% had abnormal bulb histology, most often chronic peptic duodenitis, active chronic peptic duodenitis, or gastric heterotopia, the researchers said. Among the 59% of patients whose celiac serology before endoscopy was truly unknown, only two (0.5%) had histologic changes consistent with celiac disease, which in both cases were located in the distal duodenum.

SOURCE: American Gastroenterological Association

“Individual sampling of the duodenal bulb in patients with either negative or unknown celiac serologic status can be considered in practices where expert gastrointestinal pathologists are present and there is agreement that both samples can be submitted in the same bottle, or there is not a separate charge for the additional container. Further studies may be needed to assess the diagnostic yield of separate bulb biopsies for celiac detection in all comers.”

An American College of Gastroenterology Junior Faculty Development Award helped support the work. Senior author Joseph A. Murray, MD, disclosed ties to Alba Therapeutics, Alvine Pharmaceuticals, AMAG Pharmaceuticals, and several other corporate entities. The remaining authors had no disclosures.

Separate sampling of the duodenal bulb increased detection of celiac disease by only 0.1% when endoscopy patients had a low pretest probability of celiac disease, according to research published in the November issue of Clinical Gastroenterology and Hepatology.

Duodenal bulb histology did reveal other abnormal findings, such as chronic peptic duodenitis, gastric heterotopia, and Brunner gland hyperplasia, wrote Samantha Stoven, MD, of Mayo Clinic, Rochester, Minn., and her associates. These findings did not seem to impede the identification of celiac disease, but their clinical implications were unclear, the researchers noted.

©Monthian/Thinkstock

Most studies of the diagnostic yield of duodenal bulb specimens have been performed in patients with known celiac disease or positive serology. In past studies of these high-probability cohorts, duodenal bulb sampling increased the diagnostic yield of celiac disease anywhere from 1.8% to 18%, but whether and how that finding translates to low-probability cohorts is unclear, the researchers said. Therefore, they retrospectively analyzed data from 679 endoscopy patients who had both duodenal bulb and small bowel biopsies collected at three Mayo Clinic sites in 2011. These sites are “open access,” meaning that patients can be referred for endoscopy without the approval of a gastroenterologist.

The average age of the patients was 50 years, and 63% were female. They were most commonly referred for duodenal biopsy because of chronic dyspepsia (46% of patients), diarrhea (35%), or nausea (17%). Patients with either known celiac disease or positive serology were excluded from the study (Clin Gastroenterol Hepatol. 2016 Mar 7. doi: 10.1016/j.cgh.2016.02.026). A total of 265 patients (39%) had abnormal duodenal histology, which was most often diagnosed as chronic peptic duodenitis, the researchers said. Histologic abnormalities usually involved the duodenal bulb (36% of cases), not the distal duodenum (15%; P less than .0001). However, among the 16 patients (2%) found to have celiac disease, just one patient had disease only in the duodenal bulb. Thus, duodenal bulb sampling increased the diagnostic yield of celiac disease by only 0.1% when considering the overall cohort. The patient with celiac disease limited to the bulb was a 46-year-old female presenting with diarrhea and anemia who had normal serologies but a permissive human leukocyte antigen test. Her duodenal bulb had villous atrophy and more than 25 intraepithelial lymphocytes per 100 epithelial cells, while her distal duodenum was normal.

Among the 85% of patients who had normal distal duodenums, 28% had abnormal bulb histology, most often chronic peptic duodenitis, active chronic peptic duodenitis, or gastric heterotopia, the researchers said. Among the 59% of patients whose celiac serology before endoscopy was truly unknown, only two (0.5%) had histologic changes consistent with celiac disease, which in both cases were located in the distal duodenum.

SOURCE: American Gastroenterological Association

“Individual sampling of the duodenal bulb in patients with either negative or unknown celiac serologic status can be considered in practices where expert gastrointestinal pathologists are present and there is agreement that both samples can be submitted in the same bottle, or there is not a separate charge for the additional container. Further studies may be needed to assess the diagnostic yield of separate bulb biopsies for celiac detection in all comers.”

An American College of Gastroenterology Junior Faculty Development Award helped support the work. Senior author Joseph A. Murray, MD, disclosed ties to Alba Therapeutics, Alvine Pharmaceuticals, AMAG Pharmaceuticals, and several other corporate entities. The remaining authors had no disclosures.

SALT LAKE CITY – Delaying cancer treatment to allow women to undergo fertility preservation did not affect long-term cancer outcomes, suggest the findings from a retrospective study of more than 500 patients.

Over a median of 3.7 years of follow-up, 2.3% of patients who elected fertility preservation developed recurrent cancer, compared with 5.3% of patients who did not undergo fertility preservation (P = .09), according to Molly Moravek, MD, of the University of Michigan, Ann Arbor, and her associates.

Survival rates were 97.7% for patients who underwent fertility preservation and 94.1% for those who did not (P = .05), the investigators reported in a poster at the annual meeting of the American Society for Reproductive Medicine.

“Pursuing fertility preservation results in minimal delays to initiation of cancer treatment and is unlikely to be clinically significant,” the investigators wrote. “There is no evidence of increased recurrence or mortality in fertility preservation patients versus controls, suggesting fertility preservation is safe for eligible cancer patients.”

Progress in cancer detection and survival has sharpened the focus on quality of life issues, including fertility preservation, the researchers said. But oncologists and patients themselves have raised concerns about postponing cancer treatment for this reason, and some have recommended shortening the delay by triggering ovarian stimulation regardless of the phase of the menstrual cycle – known as the “random start” protocol.

To explore these issues, the researchers reviewed the charts of all 553 cancer patients who had used the online patient navigator for fertility preservation at Northwestern University from 2006 to 2015.

A total of 213 patients pursued fertility preservation, while 340 did not. Undergoing fertility preservation postponed treatment of breast, hematologic, gynecologic, and other cancers by an average of 10 days, but this delay did not translate to worse recurrence rates or mortality, either overall or for any cancer subtype.

Cycle outcomes were similar between the 117 patients who underwent random-start protocols and the 23 patients underwent cycle-specific protocols, the investigators reported. Both protocols were associated with similar numbers of oocytes retrieved, numbers of mature oocytes, peak serum estradiol levels, days of stimulation, and times to cancer treatment.

The Northwestern Memorial Foundation supported the work. Dr. Moravek reported having no relevant financial disclosures.

SALT LAKE CITY – Delaying cancer treatment to allow women to undergo fertility preservation did not affect long-term cancer outcomes, suggest the findings from a retrospective study of more than 500 patients.

Over a median of 3.7 years of follow-up, 2.3% of patients who elected fertility preservation developed recurrent cancer, compared with 5.3% of patients who did not undergo fertility preservation (P = .09), according to Molly Moravek, MD, of the University of Michigan, Ann Arbor, and her associates.

Survival rates were 97.7% for patients who underwent fertility preservation and 94.1% for those who did not (P = .05), the investigators reported in a poster at the annual meeting of the American Society for Reproductive Medicine.

“Pursuing fertility preservation results in minimal delays to initiation of cancer treatment and is unlikely to be clinically significant,” the investigators wrote. “There is no evidence of increased recurrence or mortality in fertility preservation patients versus controls, suggesting fertility preservation is safe for eligible cancer patients.”

Progress in cancer detection and survival has sharpened the focus on quality of life issues, including fertility preservation, the researchers said. But oncologists and patients themselves have raised concerns about postponing cancer treatment for this reason, and some have recommended shortening the delay by triggering ovarian stimulation regardless of the phase of the menstrual cycle – known as the “random start” protocol.

To explore these issues, the researchers reviewed the charts of all 553 cancer patients who had used the online patient navigator for fertility preservation at Northwestern University from 2006 to 2015.

A total of 213 patients pursued fertility preservation, while 340 did not. Undergoing fertility preservation postponed treatment of breast, hematologic, gynecologic, and other cancers by an average of 10 days, but this delay did not translate to worse recurrence rates or mortality, either overall or for any cancer subtype.

Cycle outcomes were similar between the 117 patients who underwent random-start protocols and the 23 patients underwent cycle-specific protocols, the investigators reported. Both protocols were associated with similar numbers of oocytes retrieved, numbers of mature oocytes, peak serum estradiol levels, days of stimulation, and times to cancer treatment.

The Northwestern Memorial Foundation supported the work. Dr. Moravek reported having no relevant financial disclosures.

SALT LAKE CITY – Delaying cancer treatment to allow women to undergo fertility preservation did not affect long-term cancer outcomes, suggest the findings from a retrospective study of more than 500 patients.

Over a median of 3.7 years of follow-up, 2.3% of patients who elected fertility preservation developed recurrent cancer, compared with 5.3% of patients who did not undergo fertility preservation (P = .09), according to Molly Moravek, MD, of the University of Michigan, Ann Arbor, and her associates.

Survival rates were 97.7% for patients who underwent fertility preservation and 94.1% for those who did not (P = .05), the investigators reported in a poster at the annual meeting of the American Society for Reproductive Medicine.

“Pursuing fertility preservation results in minimal delays to initiation of cancer treatment and is unlikely to be clinically significant,” the investigators wrote. “There is no evidence of increased recurrence or mortality in fertility preservation patients versus controls, suggesting fertility preservation is safe for eligible cancer patients.”

Progress in cancer detection and survival has sharpened the focus on quality of life issues, including fertility preservation, the researchers said. But oncologists and patients themselves have raised concerns about postponing cancer treatment for this reason, and some have recommended shortening the delay by triggering ovarian stimulation regardless of the phase of the menstrual cycle – known as the “random start” protocol.

To explore these issues, the researchers reviewed the charts of all 553 cancer patients who had used the online patient navigator for fertility preservation at Northwestern University from 2006 to 2015.

A total of 213 patients pursued fertility preservation, while 340 did not. Undergoing fertility preservation postponed treatment of breast, hematologic, gynecologic, and other cancers by an average of 10 days, but this delay did not translate to worse recurrence rates or mortality, either overall or for any cancer subtype.

Cycle outcomes were similar between the 117 patients who underwent random-start protocols and the 23 patients underwent cycle-specific protocols, the investigators reported. Both protocols were associated with similar numbers of oocytes retrieved, numbers of mature oocytes, peak serum estradiol levels, days of stimulation, and times to cancer treatment.

The Northwestern Memorial Foundation supported the work. Dr. Moravek reported having no relevant financial disclosures.