Reproductive Medicine Center, Zhoushan Maternal and Child Health Care Hospital, Zhoushan, Zhejiang, China.
Laboratory for Reproductive Immunology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
Biosci Trends. 2022 Sep 17;16(4):282-290. doi: 10.5582/bst.2021.01306. Epub 2022 Jun 10.
Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphism rs1801133 (677C>T) will decrease the utilization of folate. Folate deficiency and its resulting homocysteine (HCY) accumulation can impair female fertility. Folic acid (FA) supplementation is necessary in pregnant women who are undergoing in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) - embryo transfer (ET), and especially in women with MTHFR rs1801133 C-to-T mutations. At present, affordable and accessible synthetic FA is mainly used. However, some studies have suggested that 5-methylenetetrahydrofolate (5-MTHF), a type of active FA, may be more suitable for women with the MTHFR 677C>T polymorphism, since it is safer and more effective. This retrospective study aimed to evaluate whether the MTHFR rs1801133 gene polymorphism is related to the pregnancy outcomes of IVF/ICSI-ET recipients after sufficient supplementation with FA instead of 5-MTHF. Data on 692 women undergoing IVF/ICSI-ET and taking adequate FA were collected. Participant characteristics were compared using the Kruskal-Wallis test and Pearson chi-square test. Logistic regressions were used to calculate the odds ratio (OR) and 95% confidence interval (95% CI), after adjusting for age, BMI, method of fertilization, method of embryo transfer and number of embryos transferred. An additive model (T/T vs. C/C), dominant model (C/T + T/T vs. C/C), and recessive model (T/T vs. C/T + C/C) were evaluated. Analysis revealed that MTHFR rs1801133 in IVF/ICSI-ET women with adequate FA supplementation was not associated with the pregnancy rate but with age (OR = 0.91, 95% CI = 0.88, 0.94, P < 0.001) and BMI (OR = 0.95, 95% CI = 0.90, 0.997, P = 0.037). In 349 clinically pregnant women, no association of the MTHFR 677C>T with pregnancy outcomes was found in the additive model, dominant model, or recessive model. Of the 273 women with positive pregnancy outcomes, 34 had a preterm delivery. MTHFR 677C>T was not associated with a preterm delivery after adjusting for age and BMI. The current results indicated that MTHFR polymorphism rs1801133 was not related to the pregnancy rate or pregnancy outcomes of women undergoing IVF/ICSI-ET with adequate synthetic FA supplementation, suggesting that simple supplementation with less expensive and readily available FA, rather than expensive 5-MTHF, appeared to be appropriate.
亚甲基四氢叶酸还原酶(MTHFR)基因多态性 rs1801133(677C>T)会降低叶酸的利用率。叶酸缺乏及其导致的同型半胱氨酸(HCY)积累会损害女性生育能力。在接受体外受精(IVF)/胞浆内单精子注射(ICSI)-胚胎移植(ET)的孕妇中,需要补充叶酸,尤其是在 MTHFR rs1801133 C 到 T 突变的女性中。目前,主要使用负担得起且可获得的合成叶酸。然而,一些研究表明,5-亚甲基四氢叶酸(5-MTHF),一种活性叶酸,可能更适合 MTHFR 677C>T 多态性的女性,因为它更安全、更有效。本回顾性研究旨在评估在充分补充 FA 而不是 5-MTHF 后,MTHFR rs1801133 基因多态性是否与 IVF/ICSI-ET 受者的妊娠结局相关。收集了 692 名接受 IVF/ICSI-ET 并服用足够 FA 的女性的数据。使用 Kruskal-Wallis 检验和 Pearson 卡方检验比较参与者特征。调整年龄、BMI、受精方式、胚胎移植方式和移植胚胎数量后,使用逻辑回归计算优势比(OR)和 95%置信区间(95%CI)。评估了加性模型(T/T 与 C/C)、显性模型(C/T+T/T 与 C/C)和隐性模型(T/T 与 C/T+C/C)。分析表明,在接受 IVF/ICSI-ET 并充分补充 FA 的女性中,MTHFR rs1801133 与妊娠率无关,但与年龄(OR=0.91,95%CI=0.88,0.94,P<0.001)和 BMI(OR=0.95,95%CI=0.90,0.997,P=0.037)有关。在 349 名临床妊娠的女性中,未发现 MTHFR 677C>T 与加性模型、显性模型或隐性模型的妊娠结局有关。在 273 名有阳性妊娠结局的女性中,有 34 名发生早产。调整年龄和 BMI 后,MTHFR 677C>T 与早产无关。目前的结果表明,MTHFR 多态性 rs1801133 与接受充分合成 FA 补充的 IVF/ICSI-ET 女性的妊娠率或妊娠结局无关,这表明简单补充更便宜且更容易获得的 FA,而不是昂贵的 5-MTHF,似乎是合适的。