Patrice Wendling

CHICAGO – Oral antibiotics alone or in combination with mechanical bowel preparation were independently associated with reduced surgical site infections after elective colorectal resection in a large national patient sample.

Oral antibiotics (OA) alone significantly reduced the rate of any surgical site infection (SSI) by 44% (odds ratio, 0.56; 95% confidence interval, 0.36-0.87) and wound SSI by 59% (OR, 0.41; 95% CI, 0.23-0.72), compared with no bowel preparation in propensity-adjusted multivariate analysis.

Patrice Wendling/Frontline Medical News

OA combined with mechanical bowel preparation (MBP) was independently associated with significant reductions of 54%, 58%, and 41%, respectively, for any SSI (OR, 0.46; 95% CI, 0.38-0.55), wound SSI (OR, 0.42; 95% CI, 0.33-0.53), and organ space SSI (OR, 0.59; 95% CI, 0.44-0.78).

In contrast, MBP, which was used in 40.8% of cases, was not independently associated with reduced rates of any SSI (OR, 0.95; 95% CI, 0.82-1.10), wound SSI (OR, 0.91; 95% CI, 0.76-1.09), or organ space SSI (OR, 1.0; 95% CI, 0.79-1.27), according to Dr. Sarah Koller of Temple University Hospital in Philadelphia and her associates.

A limitation of the study was the lack of information on type of OA or MBP used, patient compliance, and use of parenteral antibiotic prophylaxis.

“Randomized clinical trials are needed to determine the true benefits of oral antibiotics alone versus combined oral antibiotics and mechanical bowel prep prior to elective colorectal resection,” Dr. Koller said at the American College of Surgeons/National Surgery Quality Improvement Program National Conference.

Session comoderator Dr. E. Patchen Dellinger, of the University of Washington in Seattle, commented, “Logically, it’s hard for me to believe that oral antibiotics would affect a couple of kilograms of stool in the colon and yet here are these tantalizing data. So we do need the prospective trial you mention.

Patrice Wendling/Frontline Medical News

“But, the other thing that blows my mind every time I see these data is 49% of people getting a mechanical bowel prep without oral antibiotics, which has conclusively been shown to be useless for anything but torture of the patient.”

Significant variability in the use of bowel preparation exists within the surgical community, with a recent survey of colorectal surgeons revealing that 76% routinely used MBP and only 36% routinely used oral antibiotics, Dr. Koller observed.

In the current analysis, just 3.3% of patients received OA, 30.4% OA plus MBP, 40.8% MBP, and 25.5% no bowel preparation.

Physicians have been slow to abandon MBP, despite multiple studies showing that MBP alone does not reduce SSIs in elective colon and rectal surgery. There also have been reports of higher rates of anastomotic leak, increased cardiac or metabolic complications, and a slower return of bowel function with MBP.

Several studies, including a recent Cochrane Database Review, have shown that oral or intravenous antibiotic prophylaxis reduces surgical wound infection after colorectal surgery. The comparison groups are not uniform across the studies, however, and the controversy persists as to which type of bowel prep best reduces SSI after colorectal surgery, she said.

To explore this issue, the investigators identified all patients who underwent elective, nonemergent colorectal resections in both the ACS NSQIP Participant Use Data File (PUF) and the Procedure Targeted PUF for colectomy from 2012 to 2013. The cohort included 19,372 patients with complete preoperative bowel preparation data. Patients who were ventilator dependent or had infections or open wounds at the time of surgery were excluded.

The overall rates of any SSI, wound SSI (superficial and/or deep), and organ space SSI were 9.5%, 6.4%, and 3.5%, respectively.

With regard to adverse outcomes cited in previous studies, only OA plus MBP was shown to independently reduce anastomotic leak (OR, 0.57; 95% CI, 0.42-0.78) and postoperative ileus (OR, 0.79; 95% CI, 0.68-0.92), compared with no bowel prep, Dr. Koller reported.

Both OA and OA plus MBP, however, decreased length of stay by 0.83 days.

None of the bowel preparations were independently associated with increased rates of cardiac or renal complications, she said.

The investigators were not able to track rates of Clostridium difficile colitis after administration of the oral antibiotics. Dr. Koller acknowledged this is a concern when using oral antibiotics and may contribute to why they aren’t used frequently.

Dr. Koller reported having no conflicts of interest. A coauthor disclosed consulting for Intuitive Surgical.

[email protected]

CHICAGO – Oral antibiotics alone or in combination with mechanical bowel preparation were independently associated with reduced surgical site infections after elective colorectal resection in a large national patient sample.

Oral antibiotics (OA) alone significantly reduced the rate of any surgical site infection (SSI) by 44% (odds ratio, 0.56; 95% confidence interval, 0.36-0.87) and wound SSI by 59% (OR, 0.41; 95% CI, 0.23-0.72), compared with no bowel preparation in propensity-adjusted multivariate analysis.

Patrice Wendling/Frontline Medical News

OA combined with mechanical bowel preparation (MBP) was independently associated with significant reductions of 54%, 58%, and 41%, respectively, for any SSI (OR, 0.46; 95% CI, 0.38-0.55), wound SSI (OR, 0.42; 95% CI, 0.33-0.53), and organ space SSI (OR, 0.59; 95% CI, 0.44-0.78).

In contrast, MBP, which was used in 40.8% of cases, was not independently associated with reduced rates of any SSI (OR, 0.95; 95% CI, 0.82-1.10), wound SSI (OR, 0.91; 95% CI, 0.76-1.09), or organ space SSI (OR, 1.0; 95% CI, 0.79-1.27), according to Dr. Sarah Koller of Temple University Hospital in Philadelphia and her associates.

A limitation of the study was the lack of information on type of OA or MBP used, patient compliance, and use of parenteral antibiotic prophylaxis.

“Randomized clinical trials are needed to determine the true benefits of oral antibiotics alone versus combined oral antibiotics and mechanical bowel prep prior to elective colorectal resection,” Dr. Koller said at the American College of Surgeons/National Surgery Quality Improvement Program National Conference.

Session comoderator Dr. E. Patchen Dellinger, of the University of Washington in Seattle, commented, “Logically, it’s hard for me to believe that oral antibiotics would affect a couple of kilograms of stool in the colon and yet here are these tantalizing data. So we do need the prospective trial you mention.

Patrice Wendling/Frontline Medical News

“But, the other thing that blows my mind every time I see these data is 49% of people getting a mechanical bowel prep without oral antibiotics, which has conclusively been shown to be useless for anything but torture of the patient.”

Significant variability in the use of bowel preparation exists within the surgical community, with a recent survey of colorectal surgeons revealing that 76% routinely used MBP and only 36% routinely used oral antibiotics, Dr. Koller observed.

In the current analysis, just 3.3% of patients received OA, 30.4% OA plus MBP, 40.8% MBP, and 25.5% no bowel preparation.

Physicians have been slow to abandon MBP, despite multiple studies showing that MBP alone does not reduce SSIs in elective colon and rectal surgery. There also have been reports of higher rates of anastomotic leak, increased cardiac or metabolic complications, and a slower return of bowel function with MBP.

Several studies, including a recent Cochrane Database Review, have shown that oral or intravenous antibiotic prophylaxis reduces surgical wound infection after colorectal surgery. The comparison groups are not uniform across the studies, however, and the controversy persists as to which type of bowel prep best reduces SSI after colorectal surgery, she said.

To explore this issue, the investigators identified all patients who underwent elective, nonemergent colorectal resections in both the ACS NSQIP Participant Use Data File (PUF) and the Procedure Targeted PUF for colectomy from 2012 to 2013. The cohort included 19,372 patients with complete preoperative bowel preparation data. Patients who were ventilator dependent or had infections or open wounds at the time of surgery were excluded.

The overall rates of any SSI, wound SSI (superficial and/or deep), and organ space SSI were 9.5%, 6.4%, and 3.5%, respectively.

With regard to adverse outcomes cited in previous studies, only OA plus MBP was shown to independently reduce anastomotic leak (OR, 0.57; 95% CI, 0.42-0.78) and postoperative ileus (OR, 0.79; 95% CI, 0.68-0.92), compared with no bowel prep, Dr. Koller reported.

Both OA and OA plus MBP, however, decreased length of stay by 0.83 days.

None of the bowel preparations were independently associated with increased rates of cardiac or renal complications, she said.

The investigators were not able to track rates of Clostridium difficile colitis after administration of the oral antibiotics. Dr. Koller acknowledged this is a concern when using oral antibiotics and may contribute to why they aren’t used frequently.

Dr. Koller reported having no conflicts of interest. A coauthor disclosed consulting for Intuitive Surgical.

[email protected]

CHICAGO – Oral antibiotics alone or in combination with mechanical bowel preparation were independently associated with reduced surgical site infections after elective colorectal resection in a large national patient sample.

Oral antibiotics (OA) alone significantly reduced the rate of any surgical site infection (SSI) by 44% (odds ratio, 0.56; 95% confidence interval, 0.36-0.87) and wound SSI by 59% (OR, 0.41; 95% CI, 0.23-0.72), compared with no bowel preparation in propensity-adjusted multivariate analysis.

Patrice Wendling/Frontline Medical News

OA combined with mechanical bowel preparation (MBP) was independently associated with significant reductions of 54%, 58%, and 41%, respectively, for any SSI (OR, 0.46; 95% CI, 0.38-0.55), wound SSI (OR, 0.42; 95% CI, 0.33-0.53), and organ space SSI (OR, 0.59; 95% CI, 0.44-0.78).

In contrast, MBP, which was used in 40.8% of cases, was not independently associated with reduced rates of any SSI (OR, 0.95; 95% CI, 0.82-1.10), wound SSI (OR, 0.91; 95% CI, 0.76-1.09), or organ space SSI (OR, 1.0; 95% CI, 0.79-1.27), according to Dr. Sarah Koller of Temple University Hospital in Philadelphia and her associates.

A limitation of the study was the lack of information on type of OA or MBP used, patient compliance, and use of parenteral antibiotic prophylaxis.

“Randomized clinical trials are needed to determine the true benefits of oral antibiotics alone versus combined oral antibiotics and mechanical bowel prep prior to elective colorectal resection,” Dr. Koller said at the American College of Surgeons/National Surgery Quality Improvement Program National Conference.

Session comoderator Dr. E. Patchen Dellinger, of the University of Washington in Seattle, commented, “Logically, it’s hard for me to believe that oral antibiotics would affect a couple of kilograms of stool in the colon and yet here are these tantalizing data. So we do need the prospective trial you mention.

Patrice Wendling/Frontline Medical News

“But, the other thing that blows my mind every time I see these data is 49% of people getting a mechanical bowel prep without oral antibiotics, which has conclusively been shown to be useless for anything but torture of the patient.”

Significant variability in the use of bowel preparation exists within the surgical community, with a recent survey of colorectal surgeons revealing that 76% routinely used MBP and only 36% routinely used oral antibiotics, Dr. Koller observed.

In the current analysis, just 3.3% of patients received OA, 30.4% OA plus MBP, 40.8% MBP, and 25.5% no bowel preparation.

Physicians have been slow to abandon MBP, despite multiple studies showing that MBP alone does not reduce SSIs in elective colon and rectal surgery. There also have been reports of higher rates of anastomotic leak, increased cardiac or metabolic complications, and a slower return of bowel function with MBP.

Several studies, including a recent Cochrane Database Review, have shown that oral or intravenous antibiotic prophylaxis reduces surgical wound infection after colorectal surgery. The comparison groups are not uniform across the studies, however, and the controversy persists as to which type of bowel prep best reduces SSI after colorectal surgery, she said.

To explore this issue, the investigators identified all patients who underwent elective, nonemergent colorectal resections in both the ACS NSQIP Participant Use Data File (PUF) and the Procedure Targeted PUF for colectomy from 2012 to 2013. The cohort included 19,372 patients with complete preoperative bowel preparation data. Patients who were ventilator dependent or had infections or open wounds at the time of surgery were excluded.

The overall rates of any SSI, wound SSI (superficial and/or deep), and organ space SSI were 9.5%, 6.4%, and 3.5%, respectively.

With regard to adverse outcomes cited in previous studies, only OA plus MBP was shown to independently reduce anastomotic leak (OR, 0.57; 95% CI, 0.42-0.78) and postoperative ileus (OR, 0.79; 95% CI, 0.68-0.92), compared with no bowel prep, Dr. Koller reported.

Both OA and OA plus MBP, however, decreased length of stay by 0.83 days.

None of the bowel preparations were independently associated with increased rates of cardiac or renal complications, she said.

The investigators were not able to track rates of Clostridium difficile colitis after administration of the oral antibiotics. Dr. Koller acknowledged this is a concern when using oral antibiotics and may contribute to why they aren’t used frequently.

Dr. Koller reported having no conflicts of interest. A coauthor disclosed consulting for Intuitive Surgical.

[email protected]

CHICAGO – Implementing an enhanced recovery after surgery (ERAS) protocol at Canada’s second largest hospital significantly reduced morbidity and surgical site infections after elective colorectal surgery.

Rates of postoperative morbidity declined 48.7% from 27.3% before implementation to 14% after full ERAS implementation (P less than .05), while total surgical site infections fell 45% (20.2% vs. 11%; P less than .05).

Nonsignificant reductions were also seen in superficial surgical site infections (11.1% vs. 7.3%), deep SSIs (2% vs. 0.6%), and organ space SSIs (7.1% vs. 3.4%).

“Our results illustrate that using a multidisciplinary team, with attention to details and small multiple changes, aggregation of marginal gains can result in dramatic improvements in patient outcomes,” primary author Tracey Hong, R.N., said at the American College of Surgeons/National Surgical Quality Improvement Program National Conference.

The ERAS protocol was implemented at Vancouver General Hospital, after ACS NSQIP risk-adjusted reports showed the 743-bed hospital had a high odds ratio of 1.50 for colorectal operative mortality.

Patrice Wendling/Frontline Medical News

“We had a problem,” Ms. Hong, the hospital’s quality and patient safety coordinator, said.

ERAS documents were developed, staff were educated on the protocol, intraoperative components were implemented and audited, and the full protocol was initiated in November 2013.

To explore the effects of ERAS implementation, chart reviews were conducted on 278 general surgery patients undergoing elective colorectal surgery: 99 patients before ERAS implementation (July 2011 through June 2013) and 179 patients in the first 10 months after full implementation (November 2013 through August 2014).

Laparoscopic colon resections were performed in 53% of the pre-ERAS group and 62% of the post-ERAS group, laparoscopic anterior and abdominoperineal resections in 10% and 23%, and open anterior and abdominoperineal resections in 23% and 18%, respectively. The median American Society of Anesthesiologists classification in both groups was 2.

After ERAS implementation, there was a trend for less postoperative pneumonia, unplanned intubation, ventilator use greater than 48 hours, and urinary tract infections (data not presented).

The median length of stay was reduced from 7 to 5 days, while readmissions increased from 7.1% to 11.7% (both changes were nonsignificant), according to Ms. Hong, who won the conference’s 2015 Surgical Clinical Reviewers Abstract Competition.

The reason for the increased readmissions is unclear, but opportunities to avoid preventable readmissions have been identified and are currently being worked on, she said.

Process measures showed that the goal of achieving a minimum 80% compliance from August 2014 to March 2015 was met within 4 months and sustained for the preoperative and intraoperative ERAS components, in aggregate. The aggregate postoperative components, which include early oral nutrition, early ambulation, early catheter removal, use of chewing gum, and defined discharge criteria, were the slowest to change, but are trending in the right direction, Ms. Hong said.

The key to achieving better outcomes with ERAS lies in involving a multidisciplinary team in all stages of planning and implementation, ongoing communication and sharing of results with stakeholders to foster commitment and ownership, and real-time auditing and use of plan-do-study-act cycles to enhance the rate of improvement, she said.

“It takes time to change culture; tenacity is important,” Ms. Hong added.

In a separate poster presentation, Ms. Hong and her colleagues reported compliance of ERAS components under the control of the anesthesiologist. The highest rate of compliance was seen in practices with few barriers to implementation such as active pre- and intraoperative warming (96%) and appropriate admission of antibiotics (92%) and antiemetics (86%). Conversely, rates were lower for multimodal analgesia (72%) and goal-directed fluid therapy (50%), which can be more labor intensive. Also, there is controversy around goal-directed fluid therapy’s benefit in low-risk patients, which may contribute to the lower compliance rates, the study authors noted. Overall, just under three-quarters of patients received at least four out of five components in their care.

On the basis of the success of the protocol, ERAS is now used for patients undergoing radical cystectomy, with plans to expand its use to all emergent and urgent cases within general surgery at Vancouver General as well as bariatric surgery at Richmond Hospital, also a member of Vancouver Coastal Health, Andrea Bisaillon, operations director of surgical services at Vancouver General Hospital, said in an interview.

“We’re rolling out ERAS to all the surgical patients because it’s best practice for all of surgery, not just colorectal surgery anymore,” she said.

[email protected]

CHICAGO – Implementing an enhanced recovery after surgery (ERAS) protocol at Canada’s second largest hospital significantly reduced morbidity and surgical site infections after elective colorectal surgery.

Rates of postoperative morbidity declined 48.7% from 27.3% before implementation to 14% after full ERAS implementation (P less than .05), while total surgical site infections fell 45% (20.2% vs. 11%; P less than .05).

Nonsignificant reductions were also seen in superficial surgical site infections (11.1% vs. 7.3%), deep SSIs (2% vs. 0.6%), and organ space SSIs (7.1% vs. 3.4%).

“Our results illustrate that using a multidisciplinary team, with attention to details and small multiple changes, aggregation of marginal gains can result in dramatic improvements in patient outcomes,” primary author Tracey Hong, R.N., said at the American College of Surgeons/National Surgical Quality Improvement Program National Conference.

The ERAS protocol was implemented at Vancouver General Hospital, after ACS NSQIP risk-adjusted reports showed the 743-bed hospital had a high odds ratio of 1.50 for colorectal operative mortality.

Patrice Wendling/Frontline Medical News

“We had a problem,” Ms. Hong, the hospital’s quality and patient safety coordinator, said.

ERAS documents were developed, staff were educated on the protocol, intraoperative components were implemented and audited, and the full protocol was initiated in November 2013.

To explore the effects of ERAS implementation, chart reviews were conducted on 278 general surgery patients undergoing elective colorectal surgery: 99 patients before ERAS implementation (July 2011 through June 2013) and 179 patients in the first 10 months after full implementation (November 2013 through August 2014).

Laparoscopic colon resections were performed in 53% of the pre-ERAS group and 62% of the post-ERAS group, laparoscopic anterior and abdominoperineal resections in 10% and 23%, and open anterior and abdominoperineal resections in 23% and 18%, respectively. The median American Society of Anesthesiologists classification in both groups was 2.

After ERAS implementation, there was a trend for less postoperative pneumonia, unplanned intubation, ventilator use greater than 48 hours, and urinary tract infections (data not presented).

The median length of stay was reduced from 7 to 5 days, while readmissions increased from 7.1% to 11.7% (both changes were nonsignificant), according to Ms. Hong, who won the conference’s 2015 Surgical Clinical Reviewers Abstract Competition.

The reason for the increased readmissions is unclear, but opportunities to avoid preventable readmissions have been identified and are currently being worked on, she said.

Process measures showed that the goal of achieving a minimum 80% compliance from August 2014 to March 2015 was met within 4 months and sustained for the preoperative and intraoperative ERAS components, in aggregate. The aggregate postoperative components, which include early oral nutrition, early ambulation, early catheter removal, use of chewing gum, and defined discharge criteria, were the slowest to change, but are trending in the right direction, Ms. Hong said.

The key to achieving better outcomes with ERAS lies in involving a multidisciplinary team in all stages of planning and implementation, ongoing communication and sharing of results with stakeholders to foster commitment and ownership, and real-time auditing and use of plan-do-study-act cycles to enhance the rate of improvement, she said.

“It takes time to change culture; tenacity is important,” Ms. Hong added.

In a separate poster presentation, Ms. Hong and her colleagues reported compliance of ERAS components under the control of the anesthesiologist. The highest rate of compliance was seen in practices with few barriers to implementation such as active pre- and intraoperative warming (96%) and appropriate admission of antibiotics (92%) and antiemetics (86%). Conversely, rates were lower for multimodal analgesia (72%) and goal-directed fluid therapy (50%), which can be more labor intensive. Also, there is controversy around goal-directed fluid therapy’s benefit in low-risk patients, which may contribute to the lower compliance rates, the study authors noted. Overall, just under three-quarters of patients received at least four out of five components in their care.

On the basis of the success of the protocol, ERAS is now used for patients undergoing radical cystectomy, with plans to expand its use to all emergent and urgent cases within general surgery at Vancouver General as well as bariatric surgery at Richmond Hospital, also a member of Vancouver Coastal Health, Andrea Bisaillon, operations director of surgical services at Vancouver General Hospital, said in an interview.

“We’re rolling out ERAS to all the surgical patients because it’s best practice for all of surgery, not just colorectal surgery anymore,” she said.

[email protected]

CHICAGO – Implementing an enhanced recovery after surgery (ERAS) protocol at Canada’s second largest hospital significantly reduced morbidity and surgical site infections after elective colorectal surgery.

Rates of postoperative morbidity declined 48.7% from 27.3% before implementation to 14% after full ERAS implementation (P less than .05), while total surgical site infections fell 45% (20.2% vs. 11%; P less than .05).

Nonsignificant reductions were also seen in superficial surgical site infections (11.1% vs. 7.3%), deep SSIs (2% vs. 0.6%), and organ space SSIs (7.1% vs. 3.4%).

“Our results illustrate that using a multidisciplinary team, with attention to details and small multiple changes, aggregation of marginal gains can result in dramatic improvements in patient outcomes,” primary author Tracey Hong, R.N., said at the American College of Surgeons/National Surgical Quality Improvement Program National Conference.

The ERAS protocol was implemented at Vancouver General Hospital, after ACS NSQIP risk-adjusted reports showed the 743-bed hospital had a high odds ratio of 1.50 for colorectal operative mortality.

Patrice Wendling/Frontline Medical News

“We had a problem,” Ms. Hong, the hospital’s quality and patient safety coordinator, said.

ERAS documents were developed, staff were educated on the protocol, intraoperative components were implemented and audited, and the full protocol was initiated in November 2013.

To explore the effects of ERAS implementation, chart reviews were conducted on 278 general surgery patients undergoing elective colorectal surgery: 99 patients before ERAS implementation (July 2011 through June 2013) and 179 patients in the first 10 months after full implementation (November 2013 through August 2014).

Laparoscopic colon resections were performed in 53% of the pre-ERAS group and 62% of the post-ERAS group, laparoscopic anterior and abdominoperineal resections in 10% and 23%, and open anterior and abdominoperineal resections in 23% and 18%, respectively. The median American Society of Anesthesiologists classification in both groups was 2.

After ERAS implementation, there was a trend for less postoperative pneumonia, unplanned intubation, ventilator use greater than 48 hours, and urinary tract infections (data not presented).

The median length of stay was reduced from 7 to 5 days, while readmissions increased from 7.1% to 11.7% (both changes were nonsignificant), according to Ms. Hong, who won the conference’s 2015 Surgical Clinical Reviewers Abstract Competition.

The reason for the increased readmissions is unclear, but opportunities to avoid preventable readmissions have been identified and are currently being worked on, she said.

Process measures showed that the goal of achieving a minimum 80% compliance from August 2014 to March 2015 was met within 4 months and sustained for the preoperative and intraoperative ERAS components, in aggregate. The aggregate postoperative components, which include early oral nutrition, early ambulation, early catheter removal, use of chewing gum, and defined discharge criteria, were the slowest to change, but are trending in the right direction, Ms. Hong said.

The key to achieving better outcomes with ERAS lies in involving a multidisciplinary team in all stages of planning and implementation, ongoing communication and sharing of results with stakeholders to foster commitment and ownership, and real-time auditing and use of plan-do-study-act cycles to enhance the rate of improvement, she said.

“It takes time to change culture; tenacity is important,” Ms. Hong added.

In a separate poster presentation, Ms. Hong and her colleagues reported compliance of ERAS components under the control of the anesthesiologist. The highest rate of compliance was seen in practices with few barriers to implementation such as active pre- and intraoperative warming (96%) and appropriate admission of antibiotics (92%) and antiemetics (86%). Conversely, rates were lower for multimodal analgesia (72%) and goal-directed fluid therapy (50%), which can be more labor intensive. Also, there is controversy around goal-directed fluid therapy’s benefit in low-risk patients, which may contribute to the lower compliance rates, the study authors noted. Overall, just under three-quarters of patients received at least four out of five components in their care.

On the basis of the success of the protocol, ERAS is now used for patients undergoing radical cystectomy, with plans to expand its use to all emergent and urgent cases within general surgery at Vancouver General as well as bariatric surgery at Richmond Hospital, also a member of Vancouver Coastal Health, Andrea Bisaillon, operations director of surgical services at Vancouver General Hospital, said in an interview.

“We’re rolling out ERAS to all the surgical patients because it’s best practice for all of surgery, not just colorectal surgery anymore,” she said.

[email protected]

LISBON – Melatonin supplementation during ovarian stimulation improved oocyte and embryo quality but not clinical pregnancy rates in older women undergoing in vitro fertilization in a double-blind, randomized trial.

© Wjeger/Thinkstockphotos.com

“In clinical pregnancy, we did not find a statistical difference, even if we can see a higher proportion of pregnant patients,”said Dr. Arianna Pacchiarotti, director of the IVF Center Praxi Provita, Rome.

Melatonin is secreted by the pineal gland and declines in middle age after peaking in early childhood. The powerful free-radical scavenger and antioxidant has been shown to protect the testis and ovary from oxidative stress, stimulates the secretion of progesterone, and inhibits the synthesis of prostaglandins, she said.

In a recent study, fertilization rates nearly doubled, and the rate of good quality embryos increased from 48% to 65.6% following at least 2 weeks of oral melatonin 3 mg/day in all women undergoing in vitro fertilization (Gynecol. Endocrinol. 2014;30:359-62).

The current study involved 358 women, aged 38-42 years, who were undergoing their first IVF treatment comprised of a short down regulation protocol with a gonadotropin-releasing hormone analogue and combined stimulation with urinary and recombinant follicle stimulating hormone. Patients were randomly assigned in a double-blind fashion to 4 mg of melatonin 1 month before starting stimulation or no pretreatment.

The 165 evaluable patients treated with melatonin and the 166 evaluable controls were similar in age, body mass index, cycle length, duration of sterility, or primary and secondary sterility.

Following supplementation, the melatonin group had significantly higher progesterone concentration in follicular fluid than did controls (10.4 ng/mL vs. 4.3 ng/mL; P = .001), more mature oocytes (48.2% vs. 35%; P = .008), and more grade 1 embryos (45.7% vs. 30.4%; P = .0045), Dr. Pacchiarotti reported at the annual meeting of the European Society of Human Reproduction and Embryology.

The study also demonstrated a significant reduction of oxygen free radicals in the melatonin group (190 Carratelli units vs. 388 CARR U; P = .014) and therefore higher concentrations of intrafollicular melatonin (213 pg/mL vs. 69 pg/mL; P = .0013), she said.

Antioxidative capacity was also significantly higher with melatonin supplementation (1.76 vs. 0.89; P = 018).

“This hypothesizes an important scavenger role of melatonin, which results in better oocyte and embryo quality in aged women and IVF outcome,” Dr. Pacchiarotti concluded.

No significant differences were observed between the melatonin group and controls in endometrial thickness on the day of human chorionic gonadotropin administration (10.8 mm vs. 11.2 mm), total oocytes retrieved (5.1 vs. 5.2), implantation rates (13.8% vs. 12.2%), abortion rates (10.8% vs. 8.6%), and twin pregnancies (20.8% vs. 20%).

Audience members questioned how the investigators arrived at the melatonin dose and whether the study was underpowered to identify an effect of melatonin on pregnancy. A prior study evaluating melatonin 2 mg showed no difference in outcomes, while a 5-mg dose has been shown to be effective in cancer prevention, Dr. Pacchiarotti said. The study had 80% power to detect a 20% difference with 50 evaluable patients per group.

[email protected]

LISBON – Melatonin supplementation during ovarian stimulation improved oocyte and embryo quality but not clinical pregnancy rates in older women undergoing in vitro fertilization in a double-blind, randomized trial.

© Wjeger/Thinkstockphotos.com

“In clinical pregnancy, we did not find a statistical difference, even if we can see a higher proportion of pregnant patients,”said Dr. Arianna Pacchiarotti, director of the IVF Center Praxi Provita, Rome.

Melatonin is secreted by the pineal gland and declines in middle age after peaking in early childhood. The powerful free-radical scavenger and antioxidant has been shown to protect the testis and ovary from oxidative stress, stimulates the secretion of progesterone, and inhibits the synthesis of prostaglandins, she said.

In a recent study, fertilization rates nearly doubled, and the rate of good quality embryos increased from 48% to 65.6% following at least 2 weeks of oral melatonin 3 mg/day in all women undergoing in vitro fertilization (Gynecol. Endocrinol. 2014;30:359-62).

The current study involved 358 women, aged 38-42 years, who were undergoing their first IVF treatment comprised of a short down regulation protocol with a gonadotropin-releasing hormone analogue and combined stimulation with urinary and recombinant follicle stimulating hormone. Patients were randomly assigned in a double-blind fashion to 4 mg of melatonin 1 month before starting stimulation or no pretreatment.

The 165 evaluable patients treated with melatonin and the 166 evaluable controls were similar in age, body mass index, cycle length, duration of sterility, or primary and secondary sterility.

Following supplementation, the melatonin group had significantly higher progesterone concentration in follicular fluid than did controls (10.4 ng/mL vs. 4.3 ng/mL; P = .001), more mature oocytes (48.2% vs. 35%; P = .008), and more grade 1 embryos (45.7% vs. 30.4%; P = .0045), Dr. Pacchiarotti reported at the annual meeting of the European Society of Human Reproduction and Embryology.

The study also demonstrated a significant reduction of oxygen free radicals in the melatonin group (190 Carratelli units vs. 388 CARR U; P = .014) and therefore higher concentrations of intrafollicular melatonin (213 pg/mL vs. 69 pg/mL; P = .0013), she said.

Antioxidative capacity was also significantly higher with melatonin supplementation (1.76 vs. 0.89; P = 018).

“This hypothesizes an important scavenger role of melatonin, which results in better oocyte and embryo quality in aged women and IVF outcome,” Dr. Pacchiarotti concluded.

No significant differences were observed between the melatonin group and controls in endometrial thickness on the day of human chorionic gonadotropin administration (10.8 mm vs. 11.2 mm), total oocytes retrieved (5.1 vs. 5.2), implantation rates (13.8% vs. 12.2%), abortion rates (10.8% vs. 8.6%), and twin pregnancies (20.8% vs. 20%).

Audience members questioned how the investigators arrived at the melatonin dose and whether the study was underpowered to identify an effect of melatonin on pregnancy. A prior study evaluating melatonin 2 mg showed no difference in outcomes, while a 5-mg dose has been shown to be effective in cancer prevention, Dr. Pacchiarotti said. The study had 80% power to detect a 20% difference with 50 evaluable patients per group.

[email protected]

LISBON – Melatonin supplementation during ovarian stimulation improved oocyte and embryo quality but not clinical pregnancy rates in older women undergoing in vitro fertilization in a double-blind, randomized trial.

© Wjeger/Thinkstockphotos.com

“In clinical pregnancy, we did not find a statistical difference, even if we can see a higher proportion of pregnant patients,”said Dr. Arianna Pacchiarotti, director of the IVF Center Praxi Provita, Rome.

Melatonin is secreted by the pineal gland and declines in middle age after peaking in early childhood. The powerful free-radical scavenger and antioxidant has been shown to protect the testis and ovary from oxidative stress, stimulates the secretion of progesterone, and inhibits the synthesis of prostaglandins, she said.

In a recent study, fertilization rates nearly doubled, and the rate of good quality embryos increased from 48% to 65.6% following at least 2 weeks of oral melatonin 3 mg/day in all women undergoing in vitro fertilization (Gynecol. Endocrinol. 2014;30:359-62).

The current study involved 358 women, aged 38-42 years, who were undergoing their first IVF treatment comprised of a short down regulation protocol with a gonadotropin-releasing hormone analogue and combined stimulation with urinary and recombinant follicle stimulating hormone. Patients were randomly assigned in a double-blind fashion to 4 mg of melatonin 1 month before starting stimulation or no pretreatment.

The 165 evaluable patients treated with melatonin and the 166 evaluable controls were similar in age, body mass index, cycle length, duration of sterility, or primary and secondary sterility.

Following supplementation, the melatonin group had significantly higher progesterone concentration in follicular fluid than did controls (10.4 ng/mL vs. 4.3 ng/mL; P = .001), more mature oocytes (48.2% vs. 35%; P = .008), and more grade 1 embryos (45.7% vs. 30.4%; P = .0045), Dr. Pacchiarotti reported at the annual meeting of the European Society of Human Reproduction and Embryology.

The study also demonstrated a significant reduction of oxygen free radicals in the melatonin group (190 Carratelli units vs. 388 CARR U; P = .014) and therefore higher concentrations of intrafollicular melatonin (213 pg/mL vs. 69 pg/mL; P = .0013), she said.

Antioxidative capacity was also significantly higher with melatonin supplementation (1.76 vs. 0.89; P = 018).

“This hypothesizes an important scavenger role of melatonin, which results in better oocyte and embryo quality in aged women and IVF outcome,” Dr. Pacchiarotti concluded.

No significant differences were observed between the melatonin group and controls in endometrial thickness on the day of human chorionic gonadotropin administration (10.8 mm vs. 11.2 mm), total oocytes retrieved (5.1 vs. 5.2), implantation rates (13.8% vs. 12.2%), abortion rates (10.8% vs. 8.6%), and twin pregnancies (20.8% vs. 20%).

Audience members questioned how the investigators arrived at the melatonin dose and whether the study was underpowered to identify an effect of melatonin on pregnancy. A prior study evaluating melatonin 2 mg showed no difference in outcomes, while a 5-mg dose has been shown to be effective in cancer prevention, Dr. Pacchiarotti said. The study had 80% power to detect a 20% difference with 50 evaluable patients per group.

[email protected]

LISBON – Singletons born after frozen embryo transfer are at significantly increased risk for being born large for gestational age, results of a retrospective, case-matched cohort study confirm.

Frozen embryo transfer (FET) was found to be a significant independent risk factor for LGA among FET singletons (odds ratio, 1.697; P = .032) on par with multiparity (OR, 1.615; P = .039) and maternal body mass index (BMI) between 25 kg/m² and 30 kg/m² (OR, 1.85; P = .026).

BMI greater than 30 kg/m² tripled LGA risk (OR, 3.12; P = .002).Fresh embryo transfer (ET) and intra-cytoplasmic sperm injection had no effect on LGA occurrence, whereas double embryo transfer insignificantly reduced the LGA risk, study author Sara Korosec, Ph.D., of University Medical Centre Ljubljana (Slovenia), reported.

The logistic regression model included smoking, hypertension, multiparity, BMI^, gestational diabetes, and in vitro fertilization (IVF)/intra-cytoplasmic sperm injection.

“It appears we are running out of the most obvious maternal and IVF reasons for this phenomenon,” Dr. Korosec said at the annual meeting of the European Society of Human Reproduction and Embryology.

The findings are consistent with prior research demonstrating an increased risk for LGA in FET singletons, suggesting that the freezing and thawing procedures per se are partly to blame.

A recent Danish national cohort study (Hum. Reprod. 2014;29:618-27) reported adjusted odds ratios of 1.34 and 1.91 for LGA and macrosomia in FET singletons vs. singletons conceived after fresh ET. This increased risk was confirmed in a sibling cohort, where one singleton was born after FET and the next after fresh ET, or vice versa.

Danish study author Dr. Anja Pinborg of the University of Copenhagen rose from the audience to acknowledge that adjustment for BMI as a possible confounder was not possible in their study and applauded the inclusion of BMI and diabetes in the current analysis.

“I really congratulate you on your findings and it’s nice to see that after controlling for these factors, it’s still there,” she said.

Several audience members agreed with the investigators that further research is needed to identify possible reasons for higher LGA rates in FET babies now that the “low-hanging fruit,” including maternal diabetes and BMI, are being excluded. Other factors to consider include placental differences between fresh and frozen embryo pregnancies, embryo selection using vitrification vs. slow freezing, and “the thing we are all most afraid of, underlying epigenetic disturbances,” Dr. Korosec said.

Dr. Korosec and her associates identified 4,508 singleton pregnancies and births (211 after FET and 916 after fresh ET) conceived as a result of IVF at the university between 2004 and 2011 and 3,381 naturally conceived controls in the National Perinatal Data System. There were 3 controls for each IVF pregnancy, matched by maternal age, parity, and maternity hospital.

LGA, defined as a birth weight above the 90th percentile, occurred in 14.7% of FET singletons vs. 8.7% of FET controls (P = .017) and in 9.4% of fresh ET singletons vs. 9.1% of fresh controls (P = .791), Dr. Korosec reported.

LGA above the 95th percentile was reported in 10% of FET singletons vs. 4.9% of FET controls (P = .012) and in 4.9% of fresh ET vs. 5.1% of fresh controls (P = .862).

Significant LGA risk factors among fresh ET singletons were multiparity (OR, 1.61; P = .001), BMI 25-30 kg/m² (OR 1.70; P = .000), and BMI greater than 30 kg/m² (OR, 1.93; P = .0001), she said.

Dr. Korosec reported no conflicting interests.

[email protected]

LISBON – Singletons born after frozen embryo transfer are at significantly increased risk for being born large for gestational age, results of a retrospective, case-matched cohort study confirm.

Frozen embryo transfer (FET) was found to be a significant independent risk factor for LGA among FET singletons (odds ratio, 1.697; P = .032) on par with multiparity (OR, 1.615; P = .039) and maternal body mass index (BMI) between 25 kg/m² and 30 kg/m² (OR, 1.85; P = .026).

BMI greater than 30 kg/m² tripled LGA risk (OR, 3.12; P = .002).Fresh embryo transfer (ET) and intra-cytoplasmic sperm injection had no effect on LGA occurrence, whereas double embryo transfer insignificantly reduced the LGA risk, study author Sara Korosec, Ph.D., of University Medical Centre Ljubljana (Slovenia), reported.

The logistic regression model included smoking, hypertension, multiparity, BMI^, gestational diabetes, and in vitro fertilization (IVF)/intra-cytoplasmic sperm injection.

“It appears we are running out of the most obvious maternal and IVF reasons for this phenomenon,” Dr. Korosec said at the annual meeting of the European Society of Human Reproduction and Embryology.

The findings are consistent with prior research demonstrating an increased risk for LGA in FET singletons, suggesting that the freezing and thawing procedures per se are partly to blame.

A recent Danish national cohort study (Hum. Reprod. 2014;29:618-27) reported adjusted odds ratios of 1.34 and 1.91 for LGA and macrosomia in FET singletons vs. singletons conceived after fresh ET. This increased risk was confirmed in a sibling cohort, where one singleton was born after FET and the next after fresh ET, or vice versa.

Danish study author Dr. Anja Pinborg of the University of Copenhagen rose from the audience to acknowledge that adjustment for BMI as a possible confounder was not possible in their study and applauded the inclusion of BMI and diabetes in the current analysis.

“I really congratulate you on your findings and it’s nice to see that after controlling for these factors, it’s still there,” she said.

Several audience members agreed with the investigators that further research is needed to identify possible reasons for higher LGA rates in FET babies now that the “low-hanging fruit,” including maternal diabetes and BMI, are being excluded. Other factors to consider include placental differences between fresh and frozen embryo pregnancies, embryo selection using vitrification vs. slow freezing, and “the thing we are all most afraid of, underlying epigenetic disturbances,” Dr. Korosec said.

Dr. Korosec and her associates identified 4,508 singleton pregnancies and births (211 after FET and 916 after fresh ET) conceived as a result of IVF at the university between 2004 and 2011 and 3,381 naturally conceived controls in the National Perinatal Data System. There were 3 controls for each IVF pregnancy, matched by maternal age, parity, and maternity hospital.

LGA, defined as a birth weight above the 90th percentile, occurred in 14.7% of FET singletons vs. 8.7% of FET controls (P = .017) and in 9.4% of fresh ET singletons vs. 9.1% of fresh controls (P = .791), Dr. Korosec reported.

LGA above the 95th percentile was reported in 10% of FET singletons vs. 4.9% of FET controls (P = .012) and in 4.9% of fresh ET vs. 5.1% of fresh controls (P = .862).

Significant LGA risk factors among fresh ET singletons were multiparity (OR, 1.61; P = .001), BMI 25-30 kg/m² (OR 1.70; P = .000), and BMI greater than 30 kg/m² (OR, 1.93; P = .0001), she said.

Dr. Korosec reported no conflicting interests.

[email protected]

LISBON – Singletons born after frozen embryo transfer are at significantly increased risk for being born large for gestational age, results of a retrospective, case-matched cohort study confirm.

Frozen embryo transfer (FET) was found to be a significant independent risk factor for LGA among FET singletons (odds ratio, 1.697; P = .032) on par with multiparity (OR, 1.615; P = .039) and maternal body mass index (BMI) between 25 kg/m² and 30 kg/m² (OR, 1.85; P = .026).

BMI greater than 30 kg/m² tripled LGA risk (OR, 3.12; P = .002).Fresh embryo transfer (ET) and intra-cytoplasmic sperm injection had no effect on LGA occurrence, whereas double embryo transfer insignificantly reduced the LGA risk, study author Sara Korosec, Ph.D., of University Medical Centre Ljubljana (Slovenia), reported.

The logistic regression model included smoking, hypertension, multiparity, BMI^, gestational diabetes, and in vitro fertilization (IVF)/intra-cytoplasmic sperm injection.

“It appears we are running out of the most obvious maternal and IVF reasons for this phenomenon,” Dr. Korosec said at the annual meeting of the European Society of Human Reproduction and Embryology.

The findings are consistent with prior research demonstrating an increased risk for LGA in FET singletons, suggesting that the freezing and thawing procedures per se are partly to blame.

A recent Danish national cohort study (Hum. Reprod. 2014;29:618-27) reported adjusted odds ratios of 1.34 and 1.91 for LGA and macrosomia in FET singletons vs. singletons conceived after fresh ET. This increased risk was confirmed in a sibling cohort, where one singleton was born after FET and the next after fresh ET, or vice versa.

Danish study author Dr. Anja Pinborg of the University of Copenhagen rose from the audience to acknowledge that adjustment for BMI as a possible confounder was not possible in their study and applauded the inclusion of BMI and diabetes in the current analysis.

“I really congratulate you on your findings and it’s nice to see that after controlling for these factors, it’s still there,” she said.

Several audience members agreed with the investigators that further research is needed to identify possible reasons for higher LGA rates in FET babies now that the “low-hanging fruit,” including maternal diabetes and BMI, are being excluded. Other factors to consider include placental differences between fresh and frozen embryo pregnancies, embryo selection using vitrification vs. slow freezing, and “the thing we are all most afraid of, underlying epigenetic disturbances,” Dr. Korosec said.

Dr. Korosec and her associates identified 4,508 singleton pregnancies and births (211 after FET and 916 after fresh ET) conceived as a result of IVF at the university between 2004 and 2011 and 3,381 naturally conceived controls in the National Perinatal Data System. There were 3 controls for each IVF pregnancy, matched by maternal age, parity, and maternity hospital.

LGA, defined as a birth weight above the 90th percentile, occurred in 14.7% of FET singletons vs. 8.7% of FET controls (P = .017) and in 9.4% of fresh ET singletons vs. 9.1% of fresh controls (P = .791), Dr. Korosec reported.

LGA above the 95th percentile was reported in 10% of FET singletons vs. 4.9% of FET controls (P = .012) and in 4.9% of fresh ET vs. 5.1% of fresh controls (P = .862).

Significant LGA risk factors among fresh ET singletons were multiparity (OR, 1.61; P = .001), BMI 25-30 kg/m² (OR 1.70; P = .000), and BMI greater than 30 kg/m² (OR, 1.93; P = .0001), she said.

Dr. Korosec reported no conflicting interests.

[email protected]

LISBON – Dehydroepiandrosterone supplementation was no match for the powerful effects of ovarian aging in women with diminished ovarian reserve in the DITTO trial.

Women who received oral dehydroepiandrosterone (DHEA) for at least 12 weeks prior to ovarian stimulation had a median of four oocytes retrieved, the same number as those given placebo.

Adjunct DHEA was also no better than placebo with regard to clinical pregnancy (28.6% vs. 36.0%; relative risk, 0.79) and live birth (25% vs. 32%; RR, 0.78) rates.

There were three miscarriages in each group, Dr. Kanna Jayaprakasan reported to an overflow crowd at the annual meeting of the European Society of Human Reproduction and Embryology.

The double-blind, randomized pilot trial was designed to test whether DHEA supplementation would improve in vitro fertilization (IVF) outcomes in women predicted to have poor ovarian response and to evaluate the feasibility of conducting a large multicenter DHEA trial.

“Successful recruitment for this pilot trial suggests a large definitive trial is feasible, but the lack of effect on IVF outcome – not even a trend – suggests it is a low priority,” Dr. Jayaprakasan of Royal Derby (England) Hospital and the University of Nottingham (England), said.

An animal study by the same investigators suggested that DHEA, a weak androgenic steroid secreted by the adrenal glands as well as the ovaries, might be a useful therapy to delay the effects of ovarian aging (Hum. Reprod. 2014;29:146-54).

Data from randomized controlled trials (RCTs) supporting its efficacy in humans, however, are limited, he said.

DHEA supplementation was associated with fewer miscarriages and significantly more live births in infertile women with normal ovarian reserve in a recent blinded RCT (Reprod. Biol. Endocrinol. 2015;13:18.).

Results were mixed, however, in a nonblinded RCT involving poor responders (Hum. Reprod. 2010;25:2496-500) in which DHEA 75 mg daily for at least 6 weeks (mean, 13.5 weeks) before ovulation induction had no impact on the number of oocytes retrieved, but more than quadrupled the live birth rate, compared with no pretreatment after two cycles (23% vs. 4%; P = .05).

The DITTO (Dehydroepiandrosterone Intervention to Treat Ovarian Aging) study used the same 75-mg daily dose of DHEA for up to 16 weeks (median, 12 weeks) before egg collection in 60 women, aged 23-43 years, with diminished ovarian reserve (antral follicle count <10 or serum Mullerian hormone level <5 pmol/L).All patients underwent a standard long downregulation protocol using human gonadotropin 300 IU/day. Seven women did not start the trial medication, leaving 28 DHEA patients and 25 patients allocated to matched placebo capsules evaluable for analysis.

DHEA levels were similar at baseline in the DHEA and control groups (9.4 vs. 7.5 ng/mL). Compliance was good, with DHEA levels significantly higher at the prestimulation stage in the study group than in controls (16.3 vs. 11.1 ng/mL; P <.01), Dr. Jayaprakasan said.Meeting attendees questioned whether longer DHEA supplementation might improve IVF outcomes, perhaps by affecting the gonadotropin-responsive follicle pool. While it is difficult to know whether prolonged DHEA would result in an improved outcome, it is less likely, he said.

As for whether the DITTO results nix further DHEA supplementation in poor responders, but leave the door open in normal responders, Dr. Jayaprakasan said, “I think there is no evidence to support its routine use in predicted poor or normal responders currently, and its use should be restricted to randomized controlled studies rather than a blanket approach.” The University of Nottingham supported the research. The authors reported having no relevant financial disclosures.

[email protected]

LISBON – Dehydroepiandrosterone supplementation was no match for the powerful effects of ovarian aging in women with diminished ovarian reserve in the DITTO trial.

Women who received oral dehydroepiandrosterone (DHEA) for at least 12 weeks prior to ovarian stimulation had a median of four oocytes retrieved, the same number as those given placebo.

Adjunct DHEA was also no better than placebo with regard to clinical pregnancy (28.6% vs. 36.0%; relative risk, 0.79) and live birth (25% vs. 32%; RR, 0.78) rates.

There were three miscarriages in each group, Dr. Kanna Jayaprakasan reported to an overflow crowd at the annual meeting of the European Society of Human Reproduction and Embryology.

The double-blind, randomized pilot trial was designed to test whether DHEA supplementation would improve in vitro fertilization (IVF) outcomes in women predicted to have poor ovarian response and to evaluate the feasibility of conducting a large multicenter DHEA trial.

“Successful recruitment for this pilot trial suggests a large definitive trial is feasible, but the lack of effect on IVF outcome – not even a trend – suggests it is a low priority,” Dr. Jayaprakasan of Royal Derby (England) Hospital and the University of Nottingham (England), said.

An animal study by the same investigators suggested that DHEA, a weak androgenic steroid secreted by the adrenal glands as well as the ovaries, might be a useful therapy to delay the effects of ovarian aging (Hum. Reprod. 2014;29:146-54).

Data from randomized controlled trials (RCTs) supporting its efficacy in humans, however, are limited, he said.

DHEA supplementation was associated with fewer miscarriages and significantly more live births in infertile women with normal ovarian reserve in a recent blinded RCT (Reprod. Biol. Endocrinol. 2015;13:18.).

Results were mixed, however, in a nonblinded RCT involving poor responders (Hum. Reprod. 2010;25:2496-500) in which DHEA 75 mg daily for at least 6 weeks (mean, 13.5 weeks) before ovulation induction had no impact on the number of oocytes retrieved, but more than quadrupled the live birth rate, compared with no pretreatment after two cycles (23% vs. 4%; P = .05).

The DITTO (Dehydroepiandrosterone Intervention to Treat Ovarian Aging) study used the same 75-mg daily dose of DHEA for up to 16 weeks (median, 12 weeks) before egg collection in 60 women, aged 23-43 years, with diminished ovarian reserve (antral follicle count <10 or serum Mullerian hormone level <5 pmol/L).All patients underwent a standard long downregulation protocol using human gonadotropin 300 IU/day. Seven women did not start the trial medication, leaving 28 DHEA patients and 25 patients allocated to matched placebo capsules evaluable for analysis.

DHEA levels were similar at baseline in the DHEA and control groups (9.4 vs. 7.5 ng/mL). Compliance was good, with DHEA levels significantly higher at the prestimulation stage in the study group than in controls (16.3 vs. 11.1 ng/mL; P <.01), Dr. Jayaprakasan said.Meeting attendees questioned whether longer DHEA supplementation might improve IVF outcomes, perhaps by affecting the gonadotropin-responsive follicle pool. While it is difficult to know whether prolonged DHEA would result in an improved outcome, it is less likely, he said.

As for whether the DITTO results nix further DHEA supplementation in poor responders, but leave the door open in normal responders, Dr. Jayaprakasan said, “I think there is no evidence to support its routine use in predicted poor or normal responders currently, and its use should be restricted to randomized controlled studies rather than a blanket approach.” The University of Nottingham supported the research. The authors reported having no relevant financial disclosures.

[email protected]

LISBON – Dehydroepiandrosterone supplementation was no match for the powerful effects of ovarian aging in women with diminished ovarian reserve in the DITTO trial.

Women who received oral dehydroepiandrosterone (DHEA) for at least 12 weeks prior to ovarian stimulation had a median of four oocytes retrieved, the same number as those given placebo.

Adjunct DHEA was also no better than placebo with regard to clinical pregnancy (28.6% vs. 36.0%; relative risk, 0.79) and live birth (25% vs. 32%; RR, 0.78) rates.

There were three miscarriages in each group, Dr. Kanna Jayaprakasan reported to an overflow crowd at the annual meeting of the European Society of Human Reproduction and Embryology.

The double-blind, randomized pilot trial was designed to test whether DHEA supplementation would improve in vitro fertilization (IVF) outcomes in women predicted to have poor ovarian response and to evaluate the feasibility of conducting a large multicenter DHEA trial.

“Successful recruitment for this pilot trial suggests a large definitive trial is feasible, but the lack of effect on IVF outcome – not even a trend – suggests it is a low priority,” Dr. Jayaprakasan of Royal Derby (England) Hospital and the University of Nottingham (England), said.

An animal study by the same investigators suggested that DHEA, a weak androgenic steroid secreted by the adrenal glands as well as the ovaries, might be a useful therapy to delay the effects of ovarian aging (Hum. Reprod. 2014;29:146-54).

Data from randomized controlled trials (RCTs) supporting its efficacy in humans, however, are limited, he said.

DHEA supplementation was associated with fewer miscarriages and significantly more live births in infertile women with normal ovarian reserve in a recent blinded RCT (Reprod. Biol. Endocrinol. 2015;13:18.).

Results were mixed, however, in a nonblinded RCT involving poor responders (Hum. Reprod. 2010;25:2496-500) in which DHEA 75 mg daily for at least 6 weeks (mean, 13.5 weeks) before ovulation induction had no impact on the number of oocytes retrieved, but more than quadrupled the live birth rate, compared with no pretreatment after two cycles (23% vs. 4%; P = .05).

The DITTO (Dehydroepiandrosterone Intervention to Treat Ovarian Aging) study used the same 75-mg daily dose of DHEA for up to 16 weeks (median, 12 weeks) before egg collection in 60 women, aged 23-43 years, with diminished ovarian reserve (antral follicle count <10 or serum Mullerian hormone level <5 pmol/L).All patients underwent a standard long downregulation protocol using human gonadotropin 300 IU/day. Seven women did not start the trial medication, leaving 28 DHEA patients and 25 patients allocated to matched placebo capsules evaluable for analysis.

DHEA levels were similar at baseline in the DHEA and control groups (9.4 vs. 7.5 ng/mL). Compliance was good, with DHEA levels significantly higher at the prestimulation stage in the study group than in controls (16.3 vs. 11.1 ng/mL; P <.01), Dr. Jayaprakasan said.Meeting attendees questioned whether longer DHEA supplementation might improve IVF outcomes, perhaps by affecting the gonadotropin-responsive follicle pool. While it is difficult to know whether prolonged DHEA would result in an improved outcome, it is less likely, he said.

As for whether the DITTO results nix further DHEA supplementation in poor responders, but leave the door open in normal responders, Dr. Jayaprakasan said, “I think there is no evidence to support its routine use in predicted poor or normal responders currently, and its use should be restricted to randomized controlled studies rather than a blanket approach.” The University of Nottingham supported the research. The authors reported having no relevant financial disclosures.

[email protected]

The Food and Drug Administration has approved gefitinib (Iressa) for the initial treatment of metastatic epidermal growth factor receptor–positive (EGFR-positive) non–small-cell lung cancer (NSCLC) that carries exon 19 deletions or exon 21 substitution mutations.

Labeling expansion of a companion diagnostic test, therascreen EGFR RGQ PCR Kit, also was approved.

Courtesy Wikimedia Commons/ FitzColinGerald/Creative Commons License

“The approval of Iressa provides physicians and patients in the U.S. with a new choice of first-line treatment for metastatic non–small cell lung cancer,” Antoine Yver, head of oncology, global medicines development at AstraZeneca, said in a statement released July 13.

The oral EGFR tyrosine kinase inhibitor was approved based on the results of the single-arm, open-label, phase IV study [IFUM (Iressa Follow-Up Measure)] reporting a 50% response rate by independent review and 6-month median duration of response to once-daily gefitinib 250 mg in 106 treatment-naive patients with metastatic EGFR-positive NSCLC.

The efficacy results were supported by an exploratory analysis in a subset of patients with EGFR-positive metastatic adenocarcinoma NSCLC receiving first-line treatment in the pivotal IPASS (Iressa Pan-ASia Study). Among these 186 patients, the objective response rate (ORR) by independent review was 67% with a median duration of response of 9.6 months for gefitinib vs. an ORR of 41% and 5.5-month duration of response for carboplatin and paclitaxel (Abraxane). Median progression-free survival was 10.9 months and 7.4 months, respectively, according to the FDA statement.

Gefitinib gained initial approval in 2003 under the FDA’s accelerated approval process based on positive results in a randomized phase II trial in patients with advanced NSCLC failing two prior lines of chemotherapy. Gefitinib was withdrawn from the market in 2005, however, amid calls from the public, after failing to improve mortality in several trials including a phase III trial in patients failing first or second-line therapy.

In August 2014, gefitinib was granted orphan drug designation for the treatment of EGFR mutation-positive NSCLC.

For the current approval, the safety of gefitinib was evaluated in 1,129 patients in a double-blind randomized trial. The most common all-grade adverse events in order of decreasing frequency were skin reactions, increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, proteinuria, and diarrhea. The most common grade 3/4 adverse events were proteinuria, diarrhea, increased ALT, decreased appetite, increased AST, and skin reactions. About 5% of patients discontinued gefitinib because of an adverse event.

Serious and uncommon adverse drug reactions were also evaluated in 2,462 patients with NSCLC who received gefitinib monotherapy in three randomized trials. Significant adverse reactions were interstitial lung disease (1.3%), fatal hepatotoxicity (0.04%), and grade 3 ocular disorders (0.1%), according to the FDA.

The recommended dose of gefitinib is 250 mg once daily until disease progression or unacceptable toxicity. Full prescribing information is available here.

[email protected]

The Food and Drug Administration has approved gefitinib (Iressa) for the initial treatment of metastatic epidermal growth factor receptor–positive (EGFR-positive) non–small-cell lung cancer (NSCLC) that carries exon 19 deletions or exon 21 substitution mutations.

Labeling expansion of a companion diagnostic test, therascreen EGFR RGQ PCR Kit, also was approved.

Courtesy Wikimedia Commons/ FitzColinGerald/Creative Commons License

“The approval of Iressa provides physicians and patients in the U.S. with a new choice of first-line treatment for metastatic non–small cell lung cancer,” Antoine Yver, head of oncology, global medicines development at AstraZeneca, said in a statement released July 13.

The oral EGFR tyrosine kinase inhibitor was approved based on the results of the single-arm, open-label, phase IV study [IFUM (Iressa Follow-Up Measure)] reporting a 50% response rate by independent review and 6-month median duration of response to once-daily gefitinib 250 mg in 106 treatment-naive patients with metastatic EGFR-positive NSCLC.

The efficacy results were supported by an exploratory analysis in a subset of patients with EGFR-positive metastatic adenocarcinoma NSCLC receiving first-line treatment in the pivotal IPASS (Iressa Pan-ASia Study). Among these 186 patients, the objective response rate (ORR) by independent review was 67% with a median duration of response of 9.6 months for gefitinib vs. an ORR of 41% and 5.5-month duration of response for carboplatin and paclitaxel (Abraxane). Median progression-free survival was 10.9 months and 7.4 months, respectively, according to the FDA statement.

Gefitinib gained initial approval in 2003 under the FDA’s accelerated approval process based on positive results in a randomized phase II trial in patients with advanced NSCLC failing two prior lines of chemotherapy. Gefitinib was withdrawn from the market in 2005, however, amid calls from the public, after failing to improve mortality in several trials including a phase III trial in patients failing first or second-line therapy.

In August 2014, gefitinib was granted orphan drug designation for the treatment of EGFR mutation-positive NSCLC.

For the current approval, the safety of gefitinib was evaluated in 1,129 patients in a double-blind randomized trial. The most common all-grade adverse events in order of decreasing frequency were skin reactions, increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, proteinuria, and diarrhea. The most common grade 3/4 adverse events were proteinuria, diarrhea, increased ALT, decreased appetite, increased AST, and skin reactions. About 5% of patients discontinued gefitinib because of an adverse event.

Serious and uncommon adverse drug reactions were also evaluated in 2,462 patients with NSCLC who received gefitinib monotherapy in three randomized trials. Significant adverse reactions were interstitial lung disease (1.3%), fatal hepatotoxicity (0.04%), and grade 3 ocular disorders (0.1%), according to the FDA.

The recommended dose of gefitinib is 250 mg once daily until disease progression or unacceptable toxicity. Full prescribing information is available here.

[email protected]

The Food and Drug Administration has approved gefitinib (Iressa) for the initial treatment of metastatic epidermal growth factor receptor–positive (EGFR-positive) non–small-cell lung cancer (NSCLC) that carries exon 19 deletions or exon 21 substitution mutations.

Labeling expansion of a companion diagnostic test, therascreen EGFR RGQ PCR Kit, also was approved.

Courtesy Wikimedia Commons/ FitzColinGerald/Creative Commons License

“The approval of Iressa provides physicians and patients in the U.S. with a new choice of first-line treatment for metastatic non–small cell lung cancer,” Antoine Yver, head of oncology, global medicines development at AstraZeneca, said in a statement released July 13.

The oral EGFR tyrosine kinase inhibitor was approved based on the results of the single-arm, open-label, phase IV study [IFUM (Iressa Follow-Up Measure)] reporting a 50% response rate by independent review and 6-month median duration of response to once-daily gefitinib 250 mg in 106 treatment-naive patients with metastatic EGFR-positive NSCLC.

The efficacy results were supported by an exploratory analysis in a subset of patients with EGFR-positive metastatic adenocarcinoma NSCLC receiving first-line treatment in the pivotal IPASS (Iressa Pan-ASia Study). Among these 186 patients, the objective response rate (ORR) by independent review was 67% with a median duration of response of 9.6 months for gefitinib vs. an ORR of 41% and 5.5-month duration of response for carboplatin and paclitaxel (Abraxane). Median progression-free survival was 10.9 months and 7.4 months, respectively, according to the FDA statement.

Gefitinib gained initial approval in 2003 under the FDA’s accelerated approval process based on positive results in a randomized phase II trial in patients with advanced NSCLC failing two prior lines of chemotherapy. Gefitinib was withdrawn from the market in 2005, however, amid calls from the public, after failing to improve mortality in several trials including a phase III trial in patients failing first or second-line therapy.

In August 2014, gefitinib was granted orphan drug designation for the treatment of EGFR mutation-positive NSCLC.

For the current approval, the safety of gefitinib was evaluated in 1,129 patients in a double-blind randomized trial. The most common all-grade adverse events in order of decreasing frequency were skin reactions, increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, proteinuria, and diarrhea. The most common grade 3/4 adverse events were proteinuria, diarrhea, increased ALT, decreased appetite, increased AST, and skin reactions. About 5% of patients discontinued gefitinib because of an adverse event.

Serious and uncommon adverse drug reactions were also evaluated in 2,462 patients with NSCLC who received gefitinib monotherapy in three randomized trials. Significant adverse reactions were interstitial lung disease (1.3%), fatal hepatotoxicity (0.04%), and grade 3 ocular disorders (0.1%), according to the FDA.

The recommended dose of gefitinib is 250 mg once daily until disease progression or unacceptable toxicity. Full prescribing information is available here.

[email protected]

LISBON – Depression and emotional stress did not lead to poorer pregnancy outcomes 1 year after referral for recurrent pregnancy loss in a prospective, longitudinal study.

Among 287 women with recurrent pregnancy loss (RPL), 132 had a live birth or an ongoing pregnancy after 12 weeks gestation 1 year after referral to a tertiary RPL unit.

High scores on the PSS (Cohen Perceived Stress Scale) at referral were not associated with the chance of a subsequent live birth or ongoing pregnancy in unadjusted analysis (odds ratio, 1.012 ; 95% confidence interval 0.98-1.045) or after adjustment for maternal age and number of pregnancy losses prior to referral (OR, 1.015; CI 0.98-1.050).

Moderate to severe depression on the Major Depression Inventory (MDI) also was not associated with the chance of either outcome in unadjusted (OR, 2.12; CI 0.91-4.93) or adjusted (OR, 1.86; CI 0.78-4.42) analyses.

Patrice Wendling/Frontline Medical News

“We did not find an association between emotional distress at referral and the chance for a positive pregnancy outcome,” study author Dr. Astrid Marie Kolte said at the annual meeting of the European Society of Human Reproduction and Embryology.

It is well-known that pregnancy loss is a significant major life event that can invoke grief similar to that after a neonatal death. Studies have also shown that depression and stress are highly prominent among women with RPL.

In a recent study by Dr. Kolte and her associates, moderate to severe depression was identified in 8.6% and high stress levels in 41.2% of 301 women with three or more pregnancy losses before 12 weeks gestation, compared with rates of 2.2% and 23.2%, respectively, among 1,813 women without RPL (Hum. Reprod. 2015;30:777-782).Other groups have found significantly higher prevalence rates of moderate to severe depression in RPL patients, in the range of 15% to 33%, Dr. Kolte of the RPL Unit, Copenhagen University Hospital Rigshospitalet, said.

Data are scarce and results mixed, however, on the impact of depression and stress on subsequent live birth rates, prompting the investigators to examine pregnancy outcomes among the 301 previously studied women.

A total of 185 participants completed a follow-up questionnaire at 1 year containing the same PSS and MDI filled out a referral, along with questions about their pregnancy. Reliable data was available for 102 pregnancies among the 116 nonrespondents, resulting in 287 patients in the current analysis.

Among these women, 82 had given birth to a live child within the first year after referral, 50 had an ongoing pregnancy after 12 weeks’ gestation, and 11 were pregnant at less than 12 weeks’ gestation.

Interestingly, women with a live birth or ongoing pregnancy after 12 weeks’ gestation had significantly lower MDI (13.59 vs. 10.12) and PSS (16.94 vs. 12.47) scores on follow-up. This was not the case for patients without a positive pregnancy outcome for either the MDI (12.65 vs. 12.92) or PSS (16.86 vs. 15.49), Dr. Kolte said.

She noted that the study may have been insufficiently powered because of the low prevalence (8.6%) of major depression at referral and remarkably similar perceived stress among patients with and without live births. However, the study used validated psychometric scales, had good obstetrical follow-up, and is by far the largest study of emotional stress and live birth/ongoing pregnancy to date, she said.

Dr. Kolte expressed frustration at providing the best care for these patients, observing that there is a severe lack of understanding of the pathophysiology of recurrent pregnancy loss and no evidence-based treatment for the majority of RPL patients.

“You can indeed discuss whether a cumulative live birth rate of 70% on average is a good prognosis, but this is still a distressing event for these patients and their partners,” she said.

All newly referred patients and their partners are now being screened for major depression and perceived stress in the Danish RPL Unit, but providers do not have the means to treat those patients with psychological morbidities and must refer them back to their general physician.

“In my opinion, this is an understudied and underprioritized area in early pregnancy management, at least in Denmark,” Dr. Kolte said.

Several attendees echoed this frustration and asked Dr. Kolte for advice. While not all women will need psychological medication, having a psychologist associated with a RPL program is essential, as is a good working relationship with a psychiatrist, she replied.

University Hospital Copenhagen Rigshospitalet funded the study. Dr. Kolte reported having no financial disclosures.

[email protected]

LISBON – Depression and emotional stress did not lead to poorer pregnancy outcomes 1 year after referral for recurrent pregnancy loss in a prospective, longitudinal study.

Among 287 women with recurrent pregnancy loss (RPL), 132 had a live birth or an ongoing pregnancy after 12 weeks gestation 1 year after referral to a tertiary RPL unit.

High scores on the PSS (Cohen Perceived Stress Scale) at referral were not associated with the chance of a subsequent live birth or ongoing pregnancy in unadjusted analysis (odds ratio, 1.012 ; 95% confidence interval 0.98-1.045) or after adjustment for maternal age and number of pregnancy losses prior to referral (OR, 1.015; CI 0.98-1.050).

Moderate to severe depression on the Major Depression Inventory (MDI) also was not associated with the chance of either outcome in unadjusted (OR, 2.12; CI 0.91-4.93) or adjusted (OR, 1.86; CI 0.78-4.42) analyses.

Patrice Wendling/Frontline Medical News

“We did not find an association between emotional distress at referral and the chance for a positive pregnancy outcome,” study author Dr. Astrid Marie Kolte said at the annual meeting of the European Society of Human Reproduction and Embryology.

It is well-known that pregnancy loss is a significant major life event that can invoke grief similar to that after a neonatal death. Studies have also shown that depression and stress are highly prominent among women with RPL.

In a recent study by Dr. Kolte and her associates, moderate to severe depression was identified in 8.6% and high stress levels in 41.2% of 301 women with three or more pregnancy losses before 12 weeks gestation, compared with rates of 2.2% and 23.2%, respectively, among 1,813 women without RPL (Hum. Reprod. 2015;30:777-782).Other groups have found significantly higher prevalence rates of moderate to severe depression in RPL patients, in the range of 15% to 33%, Dr. Kolte of the RPL Unit, Copenhagen University Hospital Rigshospitalet, said.

Data are scarce and results mixed, however, on the impact of depression and stress on subsequent live birth rates, prompting the investigators to examine pregnancy outcomes among the 301 previously studied women.

A total of 185 participants completed a follow-up questionnaire at 1 year containing the same PSS and MDI filled out a referral, along with questions about their pregnancy. Reliable data was available for 102 pregnancies among the 116 nonrespondents, resulting in 287 patients in the current analysis.

Among these women, 82 had given birth to a live child within the first year after referral, 50 had an ongoing pregnancy after 12 weeks’ gestation, and 11 were pregnant at less than 12 weeks’ gestation.

Interestingly, women with a live birth or ongoing pregnancy after 12 weeks’ gestation had significantly lower MDI (13.59 vs. 10.12) and PSS (16.94 vs. 12.47) scores on follow-up. This was not the case for patients without a positive pregnancy outcome for either the MDI (12.65 vs. 12.92) or PSS (16.86 vs. 15.49), Dr. Kolte said.

She noted that the study may have been insufficiently powered because of the low prevalence (8.6%) of major depression at referral and remarkably similar perceived stress among patients with and without live births. However, the study used validated psychometric scales, had good obstetrical follow-up, and is by far the largest study of emotional stress and live birth/ongoing pregnancy to date, she said.

Dr. Kolte expressed frustration at providing the best care for these patients, observing that there is a severe lack of understanding of the pathophysiology of recurrent pregnancy loss and no evidence-based treatment for the majority of RPL patients.

“You can indeed discuss whether a cumulative live birth rate of 70% on average is a good prognosis, but this is still a distressing event for these patients and their partners,” she said.

All newly referred patients and their partners are now being screened for major depression and perceived stress in the Danish RPL Unit, but providers do not have the means to treat those patients with psychological morbidities and must refer them back to their general physician.

“In my opinion, this is an understudied and underprioritized area in early pregnancy management, at least in Denmark,” Dr. Kolte said.

Several attendees echoed this frustration and asked Dr. Kolte for advice. While not all women will need psychological medication, having a psychologist associated with a RPL program is essential, as is a good working relationship with a psychiatrist, she replied.

University Hospital Copenhagen Rigshospitalet funded the study. Dr. Kolte reported having no financial disclosures.

[email protected]

LISBON – Depression and emotional stress did not lead to poorer pregnancy outcomes 1 year after referral for recurrent pregnancy loss in a prospective, longitudinal study.

Among 287 women with recurrent pregnancy loss (RPL), 132 had a live birth or an ongoing pregnancy after 12 weeks gestation 1 year after referral to a tertiary RPL unit.

High scores on the PSS (Cohen Perceived Stress Scale) at referral were not associated with the chance of a subsequent live birth or ongoing pregnancy in unadjusted analysis (odds ratio, 1.012 ; 95% confidence interval 0.98-1.045) or after adjustment for maternal age and number of pregnancy losses prior to referral (OR, 1.015; CI 0.98-1.050).

Moderate to severe depression on the Major Depression Inventory (MDI) also was not associated with the chance of either outcome in unadjusted (OR, 2.12; CI 0.91-4.93) or adjusted (OR, 1.86; CI 0.78-4.42) analyses.

Patrice Wendling/Frontline Medical News

“We did not find an association between emotional distress at referral and the chance for a positive pregnancy outcome,” study author Dr. Astrid Marie Kolte said at the annual meeting of the European Society of Human Reproduction and Embryology.

It is well-known that pregnancy loss is a significant major life event that can invoke grief similar to that after a neonatal death. Studies have also shown that depression and stress are highly prominent among women with RPL.

In a recent study by Dr. Kolte and her associates, moderate to severe depression was identified in 8.6% and high stress levels in 41.2% of 301 women with three or more pregnancy losses before 12 weeks gestation, compared with rates of 2.2% and 23.2%, respectively, among 1,813 women without RPL (Hum. Reprod. 2015;30:777-782).Other groups have found significantly higher prevalence rates of moderate to severe depression in RPL patients, in the range of 15% to 33%, Dr. Kolte of the RPL Unit, Copenhagen University Hospital Rigshospitalet, said.

Data are scarce and results mixed, however, on the impact of depression and stress on subsequent live birth rates, prompting the investigators to examine pregnancy outcomes among the 301 previously studied women.

A total of 185 participants completed a follow-up questionnaire at 1 year containing the same PSS and MDI filled out a referral, along with questions about their pregnancy. Reliable data was available for 102 pregnancies among the 116 nonrespondents, resulting in 287 patients in the current analysis.

Among these women, 82 had given birth to a live child within the first year after referral, 50 had an ongoing pregnancy after 12 weeks’ gestation, and 11 were pregnant at less than 12 weeks’ gestation.

Interestingly, women with a live birth or ongoing pregnancy after 12 weeks’ gestation had significantly lower MDI (13.59 vs. 10.12) and PSS (16.94 vs. 12.47) scores on follow-up. This was not the case for patients without a positive pregnancy outcome for either the MDI (12.65 vs. 12.92) or PSS (16.86 vs. 15.49), Dr. Kolte said.

She noted that the study may have been insufficiently powered because of the low prevalence (8.6%) of major depression at referral and remarkably similar perceived stress among patients with and without live births. However, the study used validated psychometric scales, had good obstetrical follow-up, and is by far the largest study of emotional stress and live birth/ongoing pregnancy to date, she said.

Dr. Kolte expressed frustration at providing the best care for these patients, observing that there is a severe lack of understanding of the pathophysiology of recurrent pregnancy loss and no evidence-based treatment for the majority of RPL patients.

“You can indeed discuss whether a cumulative live birth rate of 70% on average is a good prognosis, but this is still a distressing event for these patients and their partners,” she said.

All newly referred patients and their partners are now being screened for major depression and perceived stress in the Danish RPL Unit, but providers do not have the means to treat those patients with psychological morbidities and must refer them back to their general physician.

“In my opinion, this is an understudied and underprioritized area in early pregnancy management, at least in Denmark,” Dr. Kolte said.

Several attendees echoed this frustration and asked Dr. Kolte for advice. While not all women will need psychological medication, having a psychologist associated with a RPL program is essential, as is a good working relationship with a psychiatrist, she replied.

University Hospital Copenhagen Rigshospitalet funded the study. Dr. Kolte reported having no financial disclosures.

[email protected]

LISBON – A large observational study found no increased risk of preterm birth or low birth weight following in vitro fertilization within acceptable limits of ovarian stimulation compared with unstimulated IVF.

“These findings support that ovarian stimulation is safe for maximizing live birth rates when you use acceptable limits of ovarian stimulation such as less than 20 oocytes,” Dr. Sesh Kamal Sunkara said at the annual meeting of the European Society of Human Reproduction and Embryology.

Epigenetic modifications resulting from ovarian stimulation or embryo culture are under increasing scrutiny as possible contributory factors to adverse perinatal outcomes.

A recent analysis of almost 66,000 singleton births by Dr. Sunkara and her associates showed a significantly higher risk of preterm birth (PTB) and low birth weight (LBW) in women with an excessive response (> 20 oocytes) to ovarian stimulation versus those with a normal response (10-15 oocytes) (Hum. Reprod. 2015; 30:1473-80).

A 2013 systematic review and meta-analysis also identified a higher risk of PTB and early PTB among singletons born after blastocyst- versus cleavage-stage embryo transfer in IVF (Fertil. Steril. 2013; 100: 1615-21.e10).

Both of these confounding factors were taken into account in the current analysis, reported Dr. Sunkara, of Aberdeen Fertility Centre, Aberdeen Maternity Hospital, University of Aberdeen, Scotland.

Using the Human Fertilisation and Embryology Authority database, which includes data for all IVF cycles performed in the United Kingdom from 1991 to 2012, the investigators examined 719,220 fresh IVF stimulated cycles and 135,570 fresh IVF unstimulated cycles, resulting in 105,374 and 10,668 singleton live births, respectively. Surprisingly, most women in either group were aged 18-34 years at the time of treatment, Dr. Sunkara said.

A large proportion of the unstimulated cycles did not have any oocytes retrieved compared with the stimulated group (41.7% vs. ~7%).

The overall birth rate per cycle was significantly higher with stimulation than without stimulation (19.4% vs. 8%), as was the multiple birth rate (24.4% vs. 2.1%), she said.

In the unadjusted analyses, the stimulated versus unstimulated group had significantly higher rates of PTB (9.2% vs. 5.5%; odds ratio, 1.72; 95% confidence interval 1.58-1.88), early PTB (1.7% vs. 0.7%; OR, 2.36; CI, 1.88-2.96), LBW (9.3% vs. 5.1%; OR, 1.91; CI, 1.75-2.09), and very LBW (1.8% vs. 0.8%; OR, 2.23; CI, 1.80-2.77).

No significant differences were observed, however, for each outcome between stimulated and unstimulated cycles following logistic regression and adjustment for maternal age, year of treatment, previous IVF cycles, previous live birth, number of oocytes retrieved (≤ 20 or > 20), and day of embryo transfer (cleavage or blastocyst stage), Dr. Sunkara said.

The adjusted odds ratios were: PTB (aOR, 1.04; C.I. 0.60-1.80), early PTB (aOR, 1.60; C.I. 0.51-5.01), LBW (aOR, 1.93; C.I. 0.95-3.94), and very LBW (aOR, 1.01; C.I. 0.55-4.22).

“The results demonstrated that safe stimulation within acceptable limits does not increase the risk of PTB and LBW,” she said.

Dr. Sunkara reported no having no financial conflicts.

[email protected]

LISBON – A large observational study found no increased risk of preterm birth or low birth weight following in vitro fertilization within acceptable limits of ovarian stimulation compared with unstimulated IVF.

“These findings support that ovarian stimulation is safe for maximizing live birth rates when you use acceptable limits of ovarian stimulation such as less than 20 oocytes,” Dr. Sesh Kamal Sunkara said at the annual meeting of the European Society of Human Reproduction and Embryology.

Epigenetic modifications resulting from ovarian stimulation or embryo culture are under increasing scrutiny as possible contributory factors to adverse perinatal outcomes.

A recent analysis of almost 66,000 singleton births by Dr. Sunkara and her associates showed a significantly higher risk of preterm birth (PTB) and low birth weight (LBW) in women with an excessive response (> 20 oocytes) to ovarian stimulation versus those with a normal response (10-15 oocytes) (Hum. Reprod. 2015; 30:1473-80).

A 2013 systematic review and meta-analysis also identified a higher risk of PTB and early PTB among singletons born after blastocyst- versus cleavage-stage embryo transfer in IVF (Fertil. Steril. 2013; 100: 1615-21.e10).

Both of these confounding factors were taken into account in the current analysis, reported Dr. Sunkara, of Aberdeen Fertility Centre, Aberdeen Maternity Hospital, University of Aberdeen, Scotland.

Using the Human Fertilisation and Embryology Authority database, which includes data for all IVF cycles performed in the United Kingdom from 1991 to 2012, the investigators examined 719,220 fresh IVF stimulated cycles and 135,570 fresh IVF unstimulated cycles, resulting in 105,374 and 10,668 singleton live births, respectively. Surprisingly, most women in either group were aged 18-34 years at the time of treatment, Dr. Sunkara said.

A large proportion of the unstimulated cycles did not have any oocytes retrieved compared with the stimulated group (41.7% vs. ~7%).

The overall birth rate per cycle was significantly higher with stimulation than without stimulation (19.4% vs. 8%), as was the multiple birth rate (24.4% vs. 2.1%), she said.

In the unadjusted analyses, the stimulated versus unstimulated group had significantly higher rates of PTB (9.2% vs. 5.5%; odds ratio, 1.72; 95% confidence interval 1.58-1.88), early PTB (1.7% vs. 0.7%; OR, 2.36; CI, 1.88-2.96), LBW (9.3% vs. 5.1%; OR, 1.91; CI, 1.75-2.09), and very LBW (1.8% vs. 0.8%; OR, 2.23; CI, 1.80-2.77).

No significant differences were observed, however, for each outcome between stimulated and unstimulated cycles following logistic regression and adjustment for maternal age, year of treatment, previous IVF cycles, previous live birth, number of oocytes retrieved (≤ 20 or > 20), and day of embryo transfer (cleavage or blastocyst stage), Dr. Sunkara said.

The adjusted odds ratios were: PTB (aOR, 1.04; C.I. 0.60-1.80), early PTB (aOR, 1.60; C.I. 0.51-5.01), LBW (aOR, 1.93; C.I. 0.95-3.94), and very LBW (aOR, 1.01; C.I. 0.55-4.22).

“The results demonstrated that safe stimulation within acceptable limits does not increase the risk of PTB and LBW,” she said.

Dr. Sunkara reported no having no financial conflicts.

[email protected]

LISBON – A large observational study found no increased risk of preterm birth or low birth weight following in vitro fertilization within acceptable limits of ovarian stimulation compared with unstimulated IVF.

“These findings support that ovarian stimulation is safe for maximizing live birth rates when you use acceptable limits of ovarian stimulation such as less than 20 oocytes,” Dr. Sesh Kamal Sunkara said at the annual meeting of the European Society of Human Reproduction and Embryology.

Epigenetic modifications resulting from ovarian stimulation or embryo culture are under increasing scrutiny as possible contributory factors to adverse perinatal outcomes.

A recent analysis of almost 66,000 singleton births by Dr. Sunkara and her associates showed a significantly higher risk of preterm birth (PTB) and low birth weight (LBW) in women with an excessive response (> 20 oocytes) to ovarian stimulation versus those with a normal response (10-15 oocytes) (Hum. Reprod. 2015; 30:1473-80).

A 2013 systematic review and meta-analysis also identified a higher risk of PTB and early PTB among singletons born after blastocyst- versus cleavage-stage embryo transfer in IVF (Fertil. Steril. 2013; 100: 1615-21.e10).

Both of these confounding factors were taken into account in the current analysis, reported Dr. Sunkara, of Aberdeen Fertility Centre, Aberdeen Maternity Hospital, University of Aberdeen, Scotland.

Using the Human Fertilisation and Embryology Authority database, which includes data for all IVF cycles performed in the United Kingdom from 1991 to 2012, the investigators examined 719,220 fresh IVF stimulated cycles and 135,570 fresh IVF unstimulated cycles, resulting in 105,374 and 10,668 singleton live births, respectively. Surprisingly, most women in either group were aged 18-34 years at the time of treatment, Dr. Sunkara said.

A large proportion of the unstimulated cycles did not have any oocytes retrieved compared with the stimulated group (41.7% vs. ~7%).

The overall birth rate per cycle was significantly higher with stimulation than without stimulation (19.4% vs. 8%), as was the multiple birth rate (24.4% vs. 2.1%), she said.

In the unadjusted analyses, the stimulated versus unstimulated group had significantly higher rates of PTB (9.2% vs. 5.5%; odds ratio, 1.72; 95% confidence interval 1.58-1.88), early PTB (1.7% vs. 0.7%; OR, 2.36; CI, 1.88-2.96), LBW (9.3% vs. 5.1%; OR, 1.91; CI, 1.75-2.09), and very LBW (1.8% vs. 0.8%; OR, 2.23; CI, 1.80-2.77).

No significant differences were observed, however, for each outcome between stimulated and unstimulated cycles following logistic regression and adjustment for maternal age, year of treatment, previous IVF cycles, previous live birth, number of oocytes retrieved (≤ 20 or > 20), and day of embryo transfer (cleavage or blastocyst stage), Dr. Sunkara said.

The adjusted odds ratios were: PTB (aOR, 1.04; C.I. 0.60-1.80), early PTB (aOR, 1.60; C.I. 0.51-5.01), LBW (aOR, 1.93; C.I. 0.95-3.94), and very LBW (aOR, 1.01; C.I. 0.55-4.22).

“The results demonstrated that safe stimulation within acceptable limits does not increase the risk of PTB and LBW,” she said.

Dr. Sunkara reported no having no financial conflicts.

[email protected]