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Evidence summaries

Metformin Treatment Before and during Ivf or Icsi in Women with Polycystic Ovary Syndrome

Metformin treatment before and during assisted reproductive techniques (IVF or ICSI) or intrauterine insemination (IUS) may be effective in increasing live birth rate in infertile women with polycystic ovary syndrome, and it may reduce the risk of ovarian hyperstimulation syndrome. Level of evidence: "C"

A Cochrane review [Abstract] 1 included 13 studies with a total of 1132 subjects. Metformin treatment before or during assisted reproductive technique cycles (long protocol with GnRH-agonist ; in vitro fertilisation, IVF or intra-cytoplasmic sperm injection, ICSI) compared to placebo or no treatment did not clearly improve live birth rate (OR 1.30, 95% CI 0.94 to 1.79; 6 trials; n=651, I² 47%, low-quality evidence). This suggests that for a woman with a 28 % chance of achieving a live birth using placebo, the corresponding chance using metformin treatment would be between 27% and 51%. The risk of ovarian hyperstimulation syndrome was reduced with metformin (RR 0.46, 95% CI 0.29 to 0.72; 11 trials; n=1091; I² 38%). This suggests that for a woman with a 20% risk of having OHSS without metformin the corresponding chance using metformin treatment would be between 6% and 14%.

Another Cochrane review [Abstract] 2 included 5 studies with a total of 264 subjects comparing gonadotrophins plus metformin versus gonadotrophins. The gonadotrophin used was recombinant FSH in 4 studies and highly purified FSH in one study. Metformin plus FSH was associated with a higher cumulative live birth rate when compared with FSH (odds ratio (OR) 2.31, 95% CI 1.23 to 4.34; 2 RCTs, n=180). This suggests that if the chance of live birth after FSH is assumed to be 27%, then the chance after addition of metformin would be between 32% and 60%. Metformin use was associated with a higher ongoing pregnancy rate and a higher clinical pregnancy rate. Results showed no evidence of a difference in multiple pregnancy rates between metformin plus FSH and FSH (OR 0.55, 95% CI 0.15 to 1.95; 4 RCTs, n=232) and no evidence of a difference in rates of miscarriage or OHSS.

Comment: The quality of evidence is downgraded by several issues in study quality and by imprecise results (few patients and wide confidence intervals).

    References

    • Tso LO, Costello MF, Albuquerque LET et al. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev 2020;(12):CD006105. [PubMed]
    • Bordewijk EM, Nahuis M, Costello MF et al. Metformin during ovulation induction with gonadotrophins followed by timed intercourse or intrauterine insemination for subfertility associated with polycystic ovary syndrome. Cochrane Database Syst Rev 2017;(1):CD009090. [PubMed]

Primary/Secondary Keywords