目的:尽管一些研究报道了亚甲基四氢叶酸还原酶(MTHFR)多态性对控制性卵巢刺激(COS)的潜在影响,结果仍然存在争议。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。
方法:PubMed,WebofScience,Embase,截至2020年12月2日,搜索了Cochrane中央对照试验登记册数据库。包括基于基因多态性的COS临床结果。两个审阅者独立地提取数据。主要结果是回收的卵母细胞数量。次要结果是中期II(MII)卵母细胞的数量,刺激持续时间,基础卵泡刺激素(FSH)水平,FSH用量,妊娠试验阳性,持续怀孕率,临床妊娠率,流产率,和活产率。使用ReviewMan5.3.5的固定效应模型或随机效应模型进行Meta分析。计算连续结局的平均差(MD)和95%置信区间(95CIs)。纳入研究的质量评价采用纽卡斯尔-渥太华量表进行评价。
结果:系统评价包括11项研究,和7项2015年参与者的研究纳入荟萃分析.CC纯合子的基础FSH水平显着低于TT纯合子(四项研究,867名与会者,MD-0.54,95CI-0.85至-0.23,P=0.0006;I2=0%)的MTHFR(rs1801133)。与CT异质性相比,CC纯合子的FSH剂量明显较少(三项研究,949名与会者,MD-75.78,95CI-135.23至-16.33,P=0.01;I2=32%)或CT/TT模型(三项研究,1097名参与者,MD-80.18,95CI-135.54至-24.81,P=0.005;I2=42%)。回收的卵母细胞和刺激持续时间的差异微不足道。MTHFR(rs1801133)和MTHFR(rs1801131)的基因变异在持续妊娠率中报道,临床妊娠率,和活产率。
结论:迄今为止的研究表明,MTHFR的多态性可能影响基础FSH水平和FSH剂量。该结果可用于促进COS方案的临床实践。需要进一步的研究来评估多基因组合对COS的临床相关性。
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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; I2 = 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; I2 = 32%) or CT/TT model (three studies, 1097 participants, MD - 80.18, 95%CI - 135.54 to - 24.81, P = 0.005; I2 = 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.
CONCLUSIONS: 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.