Use of Metformin Decreases Oocyte Retrieval Rates in Some Women With PCOS

Short-term treatment with metformin can decrease the number of oocytes retrieved in women with polycystic ovary syndrome (PCOS) who are overweight or obese, according to results from a prospective study. However, metformin did not otherwise adversely affect outcomes of in vitro fertilization (IVF) in these women.

Osama Abdalmageed, MBBCh, of the Duke Fertility Center, presented results from the prospective cohort study at the Scientific Congress & Expo of the American Society for Reproductive Medicine held October 15 to 19, 2016, in Salt Lake City, UT. William W. Hurd, MD, professor and director of the Division of Reproductive Endocrinology and Infertility at Duke University Medical Center and clinical director of the Duke Fertility Center, was a coinvestigator on the study.

PCOS is the most common endocrine disorder among reproductive-age women. Metformin and other insulin-sensitizing agents are used to improve insulin sensitivity and reduce hyperinsulinemia in women with PCOS, resulting in beneficial downstream effects on ovarian hyperandrogenism. The current prospective cohort study was designed to gain a better understanding of the effects of metformin on women with PCOS undergoing IVF.

The study enrolled 102 women who were overweight or obese (body mass index [BMI] > 24 kg/m²) with PCOS and undergoing their first fresh autologous IVF cycle with intracytoplasmic sperm injection and embryo transfer. Of these, 51 women (50%) received metformin 1000 mg/day starting from the onset of ovarian stimulation and continuing until the day of the pregnancy test. Women with a positive pregnancy test continued daily metformin treatment until the end of the twelfth week of gestation. Those in the control group (n = 51) did not receive metformin during the IVF cycle.

Study end points included the number of retrieved oocytes, the number of fertilized 2-pronuclei (2-PN) oocytes, and additional outcomes defined as follows:

  • Fertilization rate: proportion of 2-PN oocytes per total retrieved oocytes
  • Implantation rate: proportion of embryo sacs per total embryo transfers
  • Clinical pregnancy rate: proportion of clinical pregnancies diagnosed by sac on ultrasonography per initiated IVF cycle
  • Spontaneous abortion rate: proportion of spontaneous abortions per clinical pregnancy
  • Multiple pregnancy rate: proportion of multiple pregnancies per initiated IVF cycle
  • Live birth rate: proportion of at least 1 live birth per initiated IVF cycle

Baseline characteristics were similar in both groups in terms of patient age, BMI, duration of fertility, basal follicle-stimulating hormone level, and antral follicle count.

Treatment with metformin during the IVF cycle was associated with significant reductions in the numbers of retrieved oocytes and 2-PN oocytes (Table).

Table. Effects of Metformin on IVF Outcomes in Women With PCOS

Variable Metformin (n = 51) Control (n = 51) P Value
Mean oocytes retrieved, n 9.06 16.86 < .01
Mean 2-PN oocytes retrieved, n 5.65 9.00 < .01
Fertilization rate, % 62.3 55.4 .10
Clinical pregnancy rate, % 33.0 27.5 .52
Implantation rate, % 15.7 11.7 .32
Spontaneous abortion rate, % 23.5 35.7 .46
Multiple pregnancy rate, % 13.4 3.9 .08
Live birth rate, % 25.5 17.7 .34

2-PN = 2 pronuclei, IVF = in vitro fertilization, PCOS = polycystic ovary syndrome.

However, no statistically significant differences were observed between the metformin and control groups in rates of fertilization, implantation, multiple pregnancies, spontaneous abortions, or live births. No cases of ovarian hyperstimulation syndrome were reported in either group.

These findings suggest an adverse effect of short-term metformin therapy on oocyte retrieval rates, but no corresponding reduction in pregnancy and live birth rates were observed among overweight/obese women with PCOS undergoing IVF. Future studies will be necessary to fully characterize the relationship between metformin and IVF outcomes in this patient population.

Source: Abdalmageed OS, Farghaly TA, Ismail AM, Hurd WW. Impact of metformin on in vitro fertilization outcomes in overweight and obese polycystic ovary syndrome women: a prospective cohort study. Presented at: American Society for Reproductive Medicine 2016 Scientific Congress & Expo; October 15-19, 2016; Salt Lake City, UT. Abstract P-415.