Hussein Reda S, Elnashar Ihab, Amin Ahmed F, Zhao Yulian, Abdelmagied Ahmed M, Abbas Ahmed M, Abdelaleem Ahmed A, Farghaly Tarek A, Abdalmageed Osama S, Youssef Ahmed A, Badran Esraa, Abou-Taleb Hisham A
Department of Obstetrics and Gynecology, Faculty of Medicine, Assiut University, Assiut, Egypt.Email:
Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, USA.
Int J Fertil Steril. 2021 Apr;15(2):108-114. doi: 10.22074/IJFS.2020.134643. Epub 2021 Mar 11.
Premature luteinization (PL) is not unusual in fertilization (IVF) and could not be wholly avoided by using either gonadotropin-releasing hormone (GnRH) agonists or GnRH antagonist regimens. The study aims to evaluate metformin's efficacy in preventing PL in fresh GnRH antagonist intracytoplasmic sperm injection (ICSI) cycles with cleavage-stage embryo transfer.
This randomized, double-blind, placebo-controlled trial was conducted in a tertiary university IVF center. We recruited infertile women who were scheduled to perform their first or second ICSI trial. Eligible women were recruited and randomized in a 1:1 ratio into two groups. Metformin was administered in a dose of 1500 mg per day since the start of contraceptive pills in the cycle antecedent to stimulation cycle until the day of ovulation triggering, while women in the placebo group received a placebo for the same regimen and duration. The primary outcome was the incidence of PL, defined as serum progesterone (P) on the triggering day ≥1.5 ng/mL. Secondary outcomes comprised the live birth, ongoing pregnancy, implantation, and good-quality embryos rates.
The trial involved 320 eligible participants (n=160 in each group). Both groups had comparable stimulation days, endometrial thickness, peak estradiol levels, number of oocytes retrieved, and number of mature oocytes. Metformin group experienced lower level of serum P (P<0.001) and incidence of PL (10 vs. 23.6%, P=0.001). Moreover, lower progesterone/estradiol (P/E) ratio and progesterone to mature oocyte index (PMOI) (P=0.002 and P=0.002, respectively) were demonstrated in women receiving metformin. Metformin group generated a better rate of goodquality embryos (P=0.005) and ongoing pregnancy (43.8 vs. 31.8%, P=0.026). A similar trend, though of borderline significance, was observed in the live birth rate in favor of metformin administration (38.15 vs. 27.5%, P=0.04).
Metformin could be used in patients with potential PL to improve fresh cycle outcomes by preventing PL (Registration number: NCT03088631).
在体外受精（IVF）中，过早黄素化（PL）并不罕见，并且无论是使用促性腺激素释放激素（GnRH）激动剂方案还是GnRH拮抗剂方案，都无法完全避免。本研究旨在评估二甲双胍在预防新鲜GnRH拮抗剂卵胞浆内单精子注射（ICSI）周期并进行卵裂期胚胎移植时发生PL的疗效。
本随机、双盲、安慰剂对照试验在一所大学的三级IVF中心进行。我们招募了计划进行首次或第二次ICSI试验的不孕女性。符合条件的女性按1:1比例随机分为两组。从刺激周期前的避孕周期开始服用避孕药直至触发排卵日，二甲双胍的给药剂量为每日1500毫克，而安慰剂组的女性在相同的方案和持续时间内接受安慰剂。主要结局是PL的发生率，定义为触发日血清孕酮（P）≥1.5纳克/毫升。次要结局包括活产、持续妊娠、着床和优质胚胎率。
该试验纳入了320名符合条件的参与者（每组160名）。两组的刺激天数、子宫内膜厚度、雌二醇峰值水平、回收的卵母细胞数量和成熟卵母细胞数量具有可比性。二甲双胍组的血清P水平较低（P<0.001），PL发生率也较低（10%对23.6%，P=0.001）。此外，接受二甲双胍治疗的女性的孕酮/雌二醇（P/E）比值和孕酮与成熟卵母细胞指数（PMOI）较低（分别为P=0.002和P=0.002）。二甲双胍组产生了更好的优质胚胎率（P=0.005）和持续妊娠率（43.8%对31.8%，P=0.026）。在活产率方面也观察到了类似的趋势，有利于二甲双胍给药（38.15%对27.5%，P=0.04），尽管具有临界显著性。
二甲双胍可用于有潜在PL的患者，通过预防PL来改善新鲜周期结局（注册号：NCT03088631）。
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