Metformin treatment before IVF/ICSI in women with polycystic ovary syndrome; a prospective, randomized, double blind study

• Published in: Human reproduction (Oxford) Vol. 19; no. 6; pp. 1315 - 1322
• Main Authors: Kjøtrød, S.B., von Düring, V., Carlsen, S.M.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.06.2004; Oxford Publishing Limited (England)
• Subjects: Adult; Biological and medical sciences; Double-Blind Method; Drug Administration Schedule; Embryology: invertebrates and vertebrates. Teratology; Female; Fertilization; Fertilization in Vitro; Fundamental and applied biological sciences. Psychology; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; IVF stimulation/insulin‐sensitizers/metformin/OHSS/polycystic ovary syndrome; Metformin - administration & dosage; Metformin - adverse effects; Metformin - therapeutic use; Polycystic Ovary Syndrome - drug therapy; Polycystic Ovary Syndrome - physiopathology; Pregnancy; Pregnancy Rate; Premedication; Prospective Studies; Sperm Injections, Intracytoplasmic; Weight Loss; IVF stimulation/insulin‐sensitizers/metformin/OHSS/polycystic ovary syndrome; IVF stimulation/insulin-sensitizers/metformin/OHSS/polycystic ovary syndrome; Female sterility; Polycystic ovary; Female genital diseases; Ovarian diseases; Vertebrata; Hypoglycemic agent; Biguanides; Mammalia; Treatment; Cyst; Double blind study; Female; Benign neoplasm; Metformin
• ISSN: 0268-1161; 1460-2350; 1460-2350
• DOI: 10.1093/humrep/deh248

BACKGROUND: Our aim was to investigate the effect of pre‐treatment with metformin in women with polycystic ovary syndrome (PCOS) scheduled for IVF stimulation. METHODS: Seventy‐three oligo/amenorrhoeic women with polycystic ovaries and at least one of the following criteria: hyperandrogenaemia, elevated LH/FSH ratio, hyperinsulinism, decreased SHBG levels or hirsutism, were studied. Normal weight and overweight patients were randomized separately in a prospective, randomized, double blind study. All patients were treated for at least 16 weeks with metformin (1000 mg bid) or placebo ending on the day of HCG injection. RESULTS: No differences were found in the primary end‐points: duration of FSH stimulation 14.4 (13.1–15.7) versus 14.2 (12.6–15.7) days or estradiol on the day of HCG injection 6.8 (5.3–8.2) versus 7.6 (5.6–9.6) nmol/l in the metformin and placebo groups, respectively. The secondary end‐points number of oocytes, fertilization rates, embryo quality, pregnancy rates and clinical pregnancy rates were equal. However, in the normal weight subgroup (BMI <28 kg/m2, n = 27), pregnancy rates following IVF were 0.71 (0.63–0.79) versus 0.23 (0.15–0.31) in the metformin and placebo groups, respectively (P = 0.04). Overall clinical pregnancy rates were equal: 0.51 (0.34–0.68) versus 0.44 (0.27–0.62) in the metformin and placebo groups, respectively. However, in the normal weight subgroup, clinical pregnancy rates were 0.67 (0.43–0.91) and 0.33 (0.06–0.60), respectively (P = 0.06). CONCLUSIONS: Pre‐treatment with metformin prior to conventional IVF/ICSI in women with PCOS does not improve stimulation or clinical outcome. However, among normal weight PCOS women, pre‐treatment with metformin tends to improve pregnancy rates. Further studies in subgroups of PCOS women are required.