Metformin Use During in Vitro Fertilization in Polycystic Ovary Syndrome

描述(申请人提供)：多囊卵巢综合征(PCOS)，女性不孕的常见原因，在许多情况下与胰岛素抵抗有关。通常采用体外受精(IVF)治疗，但在IVF中，由于高胰岛素血症对卵母细胞质量和成功着床的影响，这些患者往往成功率很低。如果是这样的话，在多囊卵巢综合征患者的体外受精中使用二甲双胍将改善结局，降低多胎妊娠的风险，并将降低与这种生殖技术相关的成本。作为佛蒙特州大学生殖医学网络临床现场应用的一部分，这一概念方案假设，在PCOS患者的试管受精过程中，添加二甲双胍将提高卵母细胞成熟度、受精率、着床和妊娠率，并且在确定怀孕后，继续使用二甲双胍将减少胚胎损失率，以及妊娠后期的不良产科结果。为了解决这一问题，本申请提出了一项500名受试者的多中心、三臂、随机、盲法临床试验，在试管受精前3个月和试管受精周期中服用二甲双胍，并评估卵母细胞和胚胎质量。此外，该提案在妊娠的前12周继续服用二甲双胍或安慰剂，以评估减少胚胎丢失的潜在有益效果。如果这一假设被证明是真的，那么在体外受精中应用二甲双胍将代表着一种新的、廉价的优化多囊卵巢综合征患者体外受精周期的方法，从而减少成本和移植的胚胎数量，从而降低多胎妊娠率，同时增加这一程序的成功。这一概念协议的强度，以及本申请中概述的佛蒙特大学生殖医学努力的内在优势，说明了该机构作为生殖医学网络的临床站点的适用性。

DESCRIPTION (provided by applicant): Polycystic Ovarian Syndrome (PCOS), a common cause of female infertility, is in many cases associated with insulin resistance. It is often treated by In Vitro Fertilization (IVF), but at IVF, these patients frequently have poor success, because of the effects of hyperinsulinemia on oocyte quality and successful implantation. If so, metformin use at IVF in PCOS patients will improve outcome, with a reduced risk of multiple pregnancy, and will also decrease the costs associated with this reproductive technology. As part of the University of Vermont Reproductive Medicine Network clinical site application, this concept protocol hypothesizes that in PCOS patients, the addition of metformin to the process of IVF will improve oocyte maturity, fertilization rates, implantation and pregnancy rates, and after pregnancy is established, continued metformin use will reduce the rate of embryonic loss, as well as adverse obstetric outcomes later in gestation. To address this issue, this application proposes a 500 subject multicenter, three arm, and randomized, blinded clinical trial, giving metformin both for 3 months prior and during the IVF cycle, and assessing oocyte and embryo quality. Further, the proposal continues the metformin or placebo through the first 12 weeks of gestation to assess the potential beneficial effect reducing embryonic loss. If this hypothesis is proven true, metformin administration at IVF would represent a novel and inexpensive way of optimizing IVF cycles in PCOS patients, allowing for a reduction in costs and number of embryos transferred, thus decreasing multiple pregnancy rates, while increasing the success of this procedure The strength of this concept protocol, combined with the inherent strengths of the reproductive medicine endeavor at the University of Vermont, as outlined in this application, illustrate the suitability of this institution as a clinical site for the Reproductive Medicine Network.