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Consensus reached for treatment of infertility associated with PCOS
Recommendation based on consensus conference held last March.
WASHINGTON — The American Society for Reproductive Medicine and the European Society for Human Reproduction and Embryology have issued a consensus statement on the treatment of infertility due to polycystic ovary syndrome.
Richard S. Legro, MD, professor of the department of obstetrics and gynecology at Penn State University College of Medicine in Hershey, Pa., and Basil C. Tarlatzis, MD, PhD, unit of human reproduction, 1st department of obstetrics and gynecology at Aristotle University of Thessaloniki, Papageorgiou Hospital, in Greece, presented the recommendations at the American Society for Reproductive Medicine’s 63rd Annual Meeting.
Legro and Tarlatzis addressed reproductive issues including possible treatment algorithms for women with infertility and PCOS and counseling of patients with infertility. The consensus statement is based on results of studies presented at a preliminary meeting held last March.
“Our goal was to provide clinicians with a summary of what is known to be effective in the treatment of infertility and what is not,” Legro told Endocrine Today. “For instance, metformin has been disappointing in large multicenter trials and aromatase inhibitors show promise in small studies, but their efficacy and risk–benefit ratio has not been established in properly designed trials.”
Possible treatments for PCOS
Legro discussed possible treatment options including lifestyle modifications, treatment with clomiphene citrate, aromatase inhibitors and treatment with clomiphene citrate plus metformin.
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“There are data showing that obesity adversely affects reproduction and is associated with anovulating and pregnancy loss and late pregnancy complication,” he said. “Further, there is exhaustive literature that obesity is almost always a negative predictive factor for success no matter what you use to treat infertility due to PCOS; therefore, logically based on these associations, weight loss prior to infertility treatment improves ovulation rates in women with PCOS.”
Legro cited various studies that examined weight loss and infertility. A critical aspect of the Diabetes Prevention Program study was that patients who were previously inactive became active and maintained activity for up to five years, according to Legro. A comprehensive lifestyle program from Australia called Fertility Fitness examined different professional diets, weight loss and exercise.
“Weight loss is recommended as a first line of therapy in obese women with PCOS seeking pregnancy,” he said. “The available literature supports the use of bariatric surgery and pharmacologic weight loss for the treatment of obesity in PCOS, although large clinical trials are needed.”
The recommended dose for clomiphene citrate is 50 mg a day for five days and the maximum dose is 150 mg a day for up to six cycles. There are insufficient data to warrant the addition of metformin during pregnancy, according to Legro.
“Although uncontrolled trials and case reports suggest that metformin is safe during pregnancy, it would be prudent to discontinue metformin if pregnancy is confirmed for anyone with PCOS,” he said. “Although there have been suggestions that metformin treatment during pregnancy may be protective against complications, currently such use should take place only in a research context.”
There are multiple theoretical reasons for the use of aromatase inhibitors including lower multiple pregnancy, but the trials to date are not of adequate power or design to make a recommendation, according to Legro.
“There is still work to be done in helping women with PCOS lose weight and establish when assisted reproductive techniques should be instituted,” he said.
“The available evidence does not justify the routine use of gonadotropin releasing hormone agonists during ovulation induction with gonadatropins in PCOS patients; however, these data are derived from only four studies and a limited number of participants. Therefore, we need more randomized controlled trials to evaluate this medication,” Tarlatzis said during a presentation.
“The best estimate indicates that no major differences appear to exist between agonists and antagonists except for a shorter duration of stimulation with the antagonist; therefore, their use and value in ovulation induction is still questionable.”
Lines of treatment
For ovarian ovulation induction, the initial gonadatropin dosage recommendation is 37.5 IU to 50.0 IU per day. Duration should not exceed six ovulatory cycles, according to Tarlatzis.
When clomiphene citrate phase will result in pregnancy or ovulation second line treatment is either gonadatropins or laparoscopic ovarian surgery. “Both have distinct advantages and drawbacks, so choices should be made on an individual basis while taking many things into account,” he said.
Overall, ovulation induction with clomiphene citrate and gonadatropins was reported to be highly effective with a live birth rate of 72%, according to study data cited by Tarlatzis. In vitro fertilization is the recommended third line of treatment.
“More patient-tailored approaches should be developed for ovulation induction,” Tarlatzis said. “We need to identify predictors of response and predictors of achievement of pregnancy that will help clinicians choose the best treatment and choose the best dose to achieve pregnancy.” – by Christen Haigh
For more information:
- Legro RS, Tarlatzis BC. ASRM/ESHRE consensus on treatment of PCOS for infertility. Presented at: the American Society for Reproductive Medicine 63rd Annual Meeting; Oct. 13-17, 2007; Washington.