Department of Gynaecology and Obstetrics, Fertility Clinic, Trondheim University Hospital, 7030 Trondheim, Norway.
Hum Reprod. 2011 Aug;26(8):2045-53. doi: 10.1093/humrep/der154. Epub 2011 May 23.
To study the effect of metformin before and during assisted reproductive technology (ART) on the clinical pregnancy rate (CPR) in non-obese women with polycystic ovary syndrome (PCOS).
A multi-centre, prospective, randomized, double-blind study was conducted in eight IVF clinics in four Nordic countries. We enrolled 150 PCOS women with a body mass index <28 kg/m(2), and treated them with 2000 mg/day metformin or identical placebo tablets for ≥ 12 weeks prior to and during long protocol IVF or ICSI and until the day of pregnancy testing. The primary outcome measure was CPR. Secondary outcome measures included spontaneous pregnancy rates during the pretreatment period, and the live birth rate (LBR).
Among IVF treated women (n = 112), biochemical pregnancy rates were identical in both groups (42.9%), and there were no significant differences in the metformin versus the placebo group in CPR [39.3 versus 30.4%; 95% confidence interval (CI): -8.6 to 26.5]. The LBR was 37.5 versus 28.6% (95% CI: -8.4 to 26.3). However, prior to IVF there were 15 (20.3%) spontaneous pregnancies in the metformin group and eight (10.7%) in the placebo group (95% CI: -1.9 to 21.1; P = 0.1047). According to intention to treat analyses (n = 149); significantly higher overall CPR were observed in the metformin versus placebo group (50.0 versus 33.3%; 95% CI: -1.1 to 32.3; P = 0.0391). LBR was also significantly higher with use of metformin versus placebo (48.6 versus 32.0; 95% CI: 1.1 to 32.2; P = 0.0383). No major unexpected safety issues or multiple births were reported. More gastrointestinal side effects occurred in the metformin group (41 versus 12%; 95% CI: 0.15 to 0.42; P < 0.001).
Metformin treatment for 12 weeks before and during IVF or ICSI in non-obese women with PCOS significantly increases pregnancy and LBRs compared with placebo. However, there was no effect on the outcome of ART per se.
ClinicalTrials.gov Identifier: NCT00159575.
研究二甲双胍在辅助生殖技术（ART）前和期间对非肥胖多囊卵巢综合征（PCOS）妇女临床妊娠率（CPR）的影响。
在北欧四国的八家 IVF 诊所进行了一项多中心、前瞻性、随机、双盲研究。我们招募了 150 名 BMI<28kg/m2 的 PCOS 妇女，她们在长方案 IVF 或 ICSI 前和期间接受 2000mg/天二甲双胍或相同的安慰剂治疗≥12 周，直至妊娠试验日。主要结局指标是 CPR。次要结局指标包括治疗前期间的自发妊娠率和活产率（LBR）。
在接受 IVF 治疗的妇女（n=112）中，两组的生化妊娠率相同（42.9%），在 CPR 方面，二甲双胍组与安慰剂组无显著差异[39.3 与 30.4%；95%置信区间（CI）：-8.6 至 26.5]。LBR 为 37.5 与 28.6%（95%CI：-8.4 至 26.3）。然而，在 IVF 之前，二甲双胍组有 15 例（20.3%）自发妊娠，安慰剂组有 8 例（10.7%）（95%CI：-1.9 至 21.1；P=0.1047）。根据意向治疗分析（n=149）；与安慰剂组相比，二甲双胍组的总体 CPR 显著升高（50.0 与 33.3%；95%CI：-1.1 至 32.3；P=0.0391）。使用二甲双胍与安慰剂相比，LBR 也显著升高（48.6 与 32.0；95%CI：1.1 至 32.2；P=0.0383）。未报告主要意外安全问题或多胎妊娠。二甲双胍组胃肠道副作用发生率较高（41 与 12%；95%CI：0.15 至 0.42；P<0.001）。
在非肥胖 PCOS 妇女中，二甲双胍在 IVF 或 ICSI 前和期间治疗 12 周，与安慰剂相比，显著增加妊娠和 LBR。然而，对 ART 的结局本身没有影响。
ClinicalTrials.gov 标识符：NCT00159575。
