09.25.2015

by Jeff Minerd
Contributing Writer, MedPage Today

Losing weight improved ovulation rates in overweight and obese women with infertility due to polycystic ovary syndrome (PCOS), according to a clinical trial published in the Journal of Clinical Endocrinology & Metabolism.

Weight loss was also associated with a trend toward more live births, reported lead investigator Richard Legro, MD, of the Penn State College of Medicine in Hershey, Pa., and colleagues.

When used in combination with a short course of oral contraceptive pills (OCPs) — a standard preconception treatment to boost ovulation — the weight loss regimen mitigated the negative metabolic effects of the OCPs, in addition to enhancing fertility, Legro and colleagues said.

“Lifestyle modification is recommended in women with polycystic ovary syndrome prior to conception but there are few randomized trials to support its implementation or benefit,” the investigators wrote.

The study also has implications for women with PCOS who are not trying to get pregnant and are taking OCPs to regulate their menstrual cycle and hormones, Legro said in an interview with MedPage Today.

“The birth control pills exacerbate metabolic abnormalities, but with a concurrent lifestyle modification plan the metabolic effects are ameliorated and you get the benefit of hormonal suppression and menstrual control,” Legro said.

The study included 149 overweight or obese women ages 18-40 with infertility due to PCOS. They were randomized to one of three preconception interventions:

• The OCP group received 16 weeks of daily oral contraceptive (ethinyl estradiol 20 mcg/ 1 mg norethindrone acetate).

• The lifestyle group underwent a 16-week intervention consisting of caloric restriction, increased physical activity, and a weight loss medication (sibutramine or orlistat) for those with a body-mass index of 30 or higher.

• The combination group received both interventions.

Key outcomes included weight loss, ovulation rates, live births, and aspects of the metabolic syndrome including lipid and glucose measurements.

Mean weight loss from baseline was slightly more than 6% of body weight in the lifestyle and combination groups, compared with 1% in the OCP group (P<0.001).

Ovulation rates were 46% in the OCP group, 60% in the lifestyle group, and 67% in the combination group (P<0.05).

Live birth rates were 12% in the OCP group, 26% in the lifestyle group, and 24% in the combination group (P=0.13).

“The primary weakness is that our study was underpowered to detect a difference in live birth between the two lifestyle modification groups,” the researchers said. “Nevertheless, the trend toward benefit supports the epidemiologic association of lower maternal weight with better birth outcome and cardiovascular risk and thus, the health changes are relevant to all women with PCOS.”

The study “provides strong clinical trial evidence to encourage lifestyle modification and weight loss prior to infertility treatment in obese women with PCOS. These observations provide critical evidence to expert opinion recommending weight loss to improve reproductive and metabolic abnormalities,” the investigators concluded.

“For clinicians, this is level 1 evidence that lifestyle modification is better than oral contraceptive pills,” Legro told MedPage Today.

“The lifestyle modification not only resulted in weight loss but in improved metabolic health and a better chance for ovulation and pregnancy,” Legro said. “That’s a win-win scenario.”

One strength of the study was that a primary outcome was live birth, said Esther Eisenberg, MD, a reproductive endocrinologist with the National Institute of Child Health and Human Development, which sponsored the study.

“Oftentimes, an intermediary outcome, like ovulation, or conception is the main outcome,” Eisenberg told MedPage Today via email, “but the outcome the couple is interested in is whether there is a live birth.”

“This study also showed that preconceptual treatment with oral contraceptives may worsen the metabolic profile of an obese woman with PCOS,” she said.

“Oral contraceptives have been used in clinical practice to reduce hyperandrogenism in women with PCOS prior to ovarian stimulation treatment, with the theoretical notion that this would improve ovulation rates in response to treatment. However, this study calls into question this practice. This is my opinion, not that of the NIH,” Eisenberg wrote.