04-06-2012, 08:51 PM #1
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3 Months Metformin Pretreatment Benefits Obese Cysters Trying to Conceive
J Clin Endocrinol Metab. 2012 Mar 14.
Metformin Improves Pregnancy and Live-Birth Rates in Women with Polycystic Ovary Syndrome (PCOS): A Multicenter, Double-Blind, Placebo-Controlled Randomized Trial.
Morin-Papunen L, Rantala AS, Unkila-Kallio L, Tiitinen A, Hippeläinen M, Perheentupa A, Tinkanen H, Bloigu R, Puukka K, Ruokonen A, Tapanainen JS.
Departments of Obstetrics and Gynecology (L.M.-P., A.S.R., J.S.T.), and Clinical Chemistry (K.P., A.R.), Oulu University Hospital, FI-90029 Oys, Finland; Department of Obstetrics and Gynecology (L.U.-K., A.T., J.S.T.), Helsinki University Hospital, FI-00029 Helsinki, Finland; Department of Obstetrics and Gynecology (M.H.), Kuopio University Hospital, FI-70211 Kuopio, Finland; Department of Obstetrics and Gynecology (A.P.), Turku University Hospital, FI-20520 Turku, Finland; and Department of Obstetrics and Gynecology (H.T.), Tampere University Hospital, Tampere FI-33521, Finland; and Medical Informatic Group, University of Oulu (R.B.), FI-90220 Oulu, Finland.
Background:The role of metformin in the treatment of infertility in women with polycystic ovary syndrome (PCOS) is still controversial.
Objective and Outcomes:We investigated whether metformin decreases the early miscarriage rate and improves the pregnancy rates (PR) and live-birth rates (LBR) in PCOS.
Methods:This was a multicenter, randomized (1:1), double-blind, placebo-controlled study. Three hundred twenty women with PCOS and anovulatory infertility were randomized to metformin (n = 160, Diformin; obese women, 1000 mg two times daily; nonobese subjects, 500 mg + 1000 mg daily) or identical doses of placebo (n = 160). After 3 months' treatment, another appropriate infertility treatment was combined if necessary. If pregnancy occurred, metformin/placebo was continued up to the 12th week.
Miscarriage rates were low and similar in the two groups (metformin 15.2% vs. placebo 17.9%, P = 0.8). Intent-to-treat analysis showed that metformin significantly improved PR and LBR (vs. placebo) in the whole study population (PR: 53.6 vs. 40.4%, P = 0.006; LBR: 41.9 vs. 28.8%, P = 0.014) and PR in obese women (49.0 vs. 31.4%, P = 0.04), and there was a similar trend in nonobese (PR: 58.6 vs. 47.6%, P = 0.09; LBR: 46.7 vs. 34.5%, P = 0.09) and in obese women with regard to LBR (35.7 vs. 21.9%, P = 0.07). Cox regression analysis showed that metformin plus standard infertility treatment increased the chance of pregnancy 1.6 times (hazard rate 1.6, 95% confidence interval 1.13-2.27).
Obese women especially seem to benefit from 3 months' pretreatment with metformin and its combination thereafter with routine ovulation induction in anovulatory infertility.
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