Metformin in the treatment of clomiphene citrate-resistant women with polycystic ovary syndrome undergoingin vitrofertilisation treatment: A randomised controlled trial

Abstract

This study was conducted to determine the efficacy of metformin vs placebo in women with polycystic ovary syndrome (PCOS) undergoing IVF treatment. A total of 66 CC-resistant patients were studied prospectively. The women were randomly assigned to receive 850 mg of metformin (n = 34) or placebo (n = 32) twice daily that started 1 month before commencing the IVF treatment and continued to the day of the pregnancy test. Compared with the metformin-treated group, women who received a placebo had a significant increase in terms of days of stimulation with HMG, number of HMG ampoules, number of follicles >14 mm, number of oocytes retrieved, number of mature eggs, fertilisation rate and oestradiol level on the day of hCG administration. Similarly, women in the placebo group showed a significant increase in poor quality embryos, cancellation rate and the rate of ovarian hyperstimulation syndrome, as compared with the metformin-treated group. On the other hand, women who received metformin showed a significantly higher number of good quality embryos and implantation rate when compared with the placebo controls. Despite the transfer of a similar number of embryos, an insignificant increased in the pregnancy rate along with significant reduction in the abortion rate was observed in the metformin-treated group as compared with the placebo controls. No fetal abnormalities were encountered in the babies born in the metformin-treated group. It is concluded that metformin affects positively the quality of both oocytes and embryos without a significant increase in the pregnancy rate. It decreases significantly the rates of abortion and ovarian hyperstimulation syndrome.

Metformin use in patients undergoing in vitro fertilization treatment: results of a worldwide web-based survey

“…We reported that 87 % of cycles prescribe between 1500 and 2000 mg/day of metformin. Similar dose distribution was also demonstrated among various major randomized controlled trials, with the majority using between 1500 and 2000 mg/day of metformin [10][11][12][13][14][15][16][17][18][19]. Regardless, in Palombo's meta-analysis, when the studies were stratified by high dose (>1000 mg/day) and low dose (≤1000 mg/day) treatment regimens, there was no significant difference in reproductive outcomes in PCOS women [21].…”

“…However, analysis shows no significant effect on pregnancy and live birth rates among PCOS patients after these studies were categorized by long term pretreatment (>3 weeks), short term pretreatment (≤3 weeks), or no pretreatment, and by stopping time of metformin with hCG administration, oocyte retrieval and embryo transfer as endpoints [21]. A significant effect was observed when metformin was administered until 12 weeks of pregnancy, but the data was only obtained in one study [17,21]. Metformin dosages reported in our survey were similar to those used in current clinical research.…”

“…The two most common endpoints are a positive pregnancy test (35 %) and at 12 weeks gestational age (33 %). This trend in the variability of pretreatment (if any) and treatment duration seems to be mirrored by various major studies as well-ranging from≥16 weeks to the beginning of ovulation induction for the starting time of metformin, and from hCG administration to the 12th week of pregnancy for the stopping time [10][11][12][13][14][15][16][17][18][19]. However, analysis shows no significant effect on pregnancy and live birth rates among PCOS patients after these studies were categorized by long term pretreatment (>3 weeks), short term pretreatment (≤3 weeks), or no pretreatment, and by stopping time of metformin with hCG administration, oocyte retrieval and embryo transfer as endpoints [21].…”

“…Studies to date have demonstrated mixed results for metformin administration in PCOS patients undergoing IVF treatment with respect to reproductive outcomes. These studies displayed considerable heterogeneity in terms of patient characteristics, treatment protocols and study settings [8][9][10][11][12][13][14][15][16][17][18][19][20]. Thus, there is a currently a significant degree of uncertainty for the specific role of metformin in IVF therapy.…”

Strategies for improving outcome of assisted reproduction in women with polycystic ovary syndrome: systematic review and meta‐analysis

“…There was moderate‐quality evidence, from 13 studies involving 1551 women, that showed no significant difference in using antagonist or agonist protocols for ovarian stimulation (RR = 1.02 (95% CI, 0.91–1.15), I 2 = 7%). Low‐quality evidence, from 12 studies involving 1004 women, further suggested that the administration of metformin has a positive effect on clinical pregnancy compared with placebo or no metformin (RR = 1.26 (95% CI, 1.04–1.53), I 2 = 24%). Low‐quality evidence further suggested that there was no clinical difference between ovulation induction and estradiol for endometrial preparation for FET.…”