Does metformin affect the ovarian response to gonadotropins for in vitro fertilization treatment in patients with polycystic ovary syndrome and reduced ovarian reserve? A randomized controlled trial

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].…”

“…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.…”

Assisted Reproduction

“…A prospective, randomized placebo-controlled trial of 120 PCO patients treated with metformin 500 mg three times per day during IVF treatment with a long GnRH agonist protocol until menses or a positive pregnancy test revealed that the relative risk of ovarian hyperstimulation was 0.28 (95% CI 0.11 to 0.67) with metformin use. The metformin arm also used somewhat more gonadotropins ( 108,109 For women with hypothalamic amenorrhea, as with PCO, treatment with IVF avoids a high risk of multiple gestation that is in turn associated with multiple follicular development with gonadotropins (see Chapter 30).…”

Advances in Treatment Options for Polycystic Ovary Syndrome

“…52 More recently, concerns have been raised regarding a blunted ovarian response to exogenous gonadotropin therapy in women with PCOS and evidence of borderline ovarian reserve who were being treated with metformin. 54 While the mechanisms were not entirely evident, the authors implied that women with PCOS and compromised ovarian reserve may benefit from discontinuation of metformin therapy prior to the start of controlled ovarian hyperstimulation.…”