Department of Pharmacy, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, No. 17, Qi He Lou Street, Dongcheng District, Beijing, China.
Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, China.
J Assist Reprod Genet. 2021 Sep;38(9):2237-2249. doi: 10.1007/s10815-021-02236-8. Epub 2021 May 25.
Although several studies have reported a potential impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on controlled ovarian stimulation (COS), the results remain controversial. The aim of the systematic review and meta-analysis was to evaluate the effect of MTHFR polymorphism on COS outcomes.
PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials databases were searched up to December 2, 2020. COS clinical outcomes based on gene polymorphisms were included. Two reviewers independently extracted the data. The primary outcome was the number of oocytes retrieved. The secondary outcomes were the number of metaphase II (MII) oocytes, stimulation duration, basal follicle-stimulating hormone (FSH) level, FSH dosage, positive pregnancy test, ongoing pregnancy rate, clinical pregnancy rate, miscarriage rate, and live birth rate. Meta-analysis was performed using a fixed-effect model or random-effect model with Review Man 5.3.5. Mean difference (MD) with 95% confidence intervals (95%CIs) was calculated for continuous outcomes. The quality assessment of included studies was evaluated by using the Newcastle-Ottawa Scale.
Eleven studies were included in the systematic review, and seven studies with 2015 participants were included in the meta-analysis. Basal FSH level was significantly lower in CC homozygotes than TT homozygotes (four studies, 867 participants, MD - 0.54, 95%CI - 0.85 to - 0.23, P = 0.0006; I = 0%) of MTHFR (rs1801133). FSH dose was significantly fewer in CC homozygotes compared with CT heterogeneous (three studies, 949 participants, MD - 75.78, 95%CI - 135.23 to - 16.33, P = 0.01; I = 32%) or CT/TT model (three studies, 1097 participants, MD - 80.18, 95%CI - 135.54 to - 24.81, P = 0.005; I = 42%). Differences in the oocytes retrieved and stimulation duration were insignificant. Gene variants on MTHFR (rs1801133) and MTHFR (rs1801131) were reported in ongoing pregnancy rate, clinical pregnancy rate, and live birth rate.
Studies to date indicate that polymorphisms of MTHFR could influence basal FSH level and FSH dose. The results could be useful to promote clinical practice on COS protocols. Further studies are needed to evaluate the clinical relevance of the multigene combination on COS.
尽管已有多项研究报道亚甲基四氢叶酸还原酶（MTHFR）多态性可能对控制性卵巢刺激（COS）产生影响，但结果仍存在争议。本系统评价和荟萃分析的目的是评估 MTHFR 多态性对 COS 结局的影响。
检索PubMed、Web of Science、Embase 和 Cochrane 对照试验中心注册数据库，截至 2020 年 12 月 2 日。纳入基于基因多态性的 COS 临床结局研究。两位评审员独立提取数据。主要结局是获卵数。次要结局是获得的中期 II（MII）卵母细胞数、刺激持续时间、基础卵泡刺激素（FSH）水平、FSH 剂量、阳性妊娠试验、持续妊娠率、临床妊娠率、流产率和活产率。使用 Review Man 5.3.5 软件采用固定效应模型或随机效应模型进行荟萃分析。对于连续性结局，采用均数差（MD）及其 95%置信区间（95%CI）进行计算。采用纽卡斯尔-渥太华量表评估纳入研究的质量。
系统评价纳入 11 项研究，荟萃分析纳入 7 项研究共 2015 名参与者。MTHFR（rs1801133）的 CC 纯合子的基础 FSH 水平明显低于 TT 纯合子（四项研究，867 名参与者，MD-0.54，95%CI-0.85 至-0.23，P=0.0006；I=0%）。CC 纯合子的 FSH 剂量明显少于 CT 杂合子（三项研究，949 名参与者，MD-75.78，95%CI-135.23 至-16.33，P=0.01；I=32%）或 CT/TT 模型（三项研究，1097 名参与者，MD-80.18，95%CI-135.54 至-24.81，P=0.005；I=42%）。获卵数和刺激持续时间的差异无统计学意义。MTHFR（rs1801133）和 MTHFR（rs1801131）的基因变异与持续妊娠率、临床妊娠率和活产率有关。
目前的研究表明，MTHFR 多态性可能影响基础 FSH 水平和 FSH 剂量。这些结果可能有助于促进 COS 方案的临床实践。需要进一步研究评估多基因组合对 COS 的临床相关性。
