Effects of Metformin in Women with PCOS using Assisted Reproductive Technologies

Dan Zhang, MD, PhD

Results of a new study indicate metformin treatment could reduce ovarian hyperstimulation syndrome in women with polycystic ovarian syndrome undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection and embryo transfer (ICSI-ET).

The study, which analyzed data from a dozen randomized clinical trials, concluded metformin treatment was associated with reductions in ovarian hyperstimulation syndrome but did not improve overall clinical pregnancy or live birth rate among these women.

With no clear consensus based on evidence-based data on the appropriateness of m metformin use in women with PCOS using assisted reproductive technologies, Dan Zhang, MD, PhD, of the Zhejiang University School of Medicine, and a team of investigators sought to determine associations between metformin use and outcomes among women in this patient population using a systematic review and meta-analysis. For inclusion in the current study, articles needed to be designed as randomized clinical trials, enroll women with polycystic ovary syndrome undergoing infertility treatment with IVF/ICSI-ET, and report at least 1 outcome of IVF/ICSI-ET.

Through a search of PubMed, Embase, and Cochrane databases from inception through January 2020, investigators identified nearly 100 articles. Further inclusion criteria included patients being between the ages of 20-45 years and needed to include metformin as an intervention.

After exclusion of duplicates and application of inclusion criteria, a group of 12 trials were included in the analysis. From these 12 trials, investigators obtained data related to 1123 women with polycystic ovary syndrome. Of these 1123, 564 were receiving metformin and 559 were considered controls for the current analysis.

For the purpose of their analysis, investigators chose ovarian hyperstimulation syndrome, clinical pregnancy rate, and live birth rate as outcome measures.

Among 11 studies detailing ovarian hyperstimulation rates, 10 used the long gonadotropin-releasing hormone–agonist stimulation protocol and the other used gonadotropin-releasing hormone–antagonist protocol. Upon analysis, women in the metformin group had lower odds of ovarian hyperstimulation syndrome than those in the control group (OR, 0.43; 95% CI, 0.24-0.78; I2=38%; P=.005).

To further examining the potential effect, investigators assessed outcomes based on BMI—those with a BMI less than 26 and 26 or above, respectively. Results of this analysis indicated those with a BMI of 26 or more saw a greater effect on ovary hyperstimulation syndrome (6 RCTs with 482 participants; OR, 0.25; 95% CI, 0.12-0.51; I2=0%; P <.001) and this effect was not present in those with a BMI of less than 26 (4 RCTs with 425 participants; OR, 0.67; 95% CI, 0.30-1.51; I2=44%; P=.34).

In 11 studies examining clinical pregnancy rate, metformin was not associated with clinical pregnancy rate (OR, 1.24; 95% CI, 0.82-1.86; I2=55%; P=.31). In 8 studies examining live birth rate, investigators found no evidence between birth rate between the metformin and control groups (OR, 1.23; 95% CI, 0.74-2.04; I2=62%; P=.42). Investigators pointed out 4 studies including 388 women were used in an analysis assessing miscarriage rates. In this analysis, investigators found no difference in miscarriage rate based on metformin use (OR, 0.58; 95% CI, 0.24-1.39; I2=0%; P=.22).

“Metformin treatment should be carefully considered for women with PCOS undergoing IVF/ICSI-ET and may be more preferred for women with a body mass index greater than 26,” investigators wrote.

This study, “Association of Metformin With Pregnancy Outcomes in Women With Polycystic Ovarian Syndrome Undergoing In Vitro Fertilization,” was published in JAMA Network Open.