Effect of polymorphisms of MTHFR in controlled ovarian stimulation: a systematic review and meta-analysis

Wang, Xinrui; Sun, Xiaoying; Tang, Borui; Feng, Xin

doi:10.1007/s10815-021-02236-8

Cited by 3 publications

(1 citation statement)

References 46 publications

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“…Some studies have suggested that variation at the MTHFR 677 locus is associated with fewer oocytes retrieved ( Thaler et al , 2006 ; Pavlik et al , 2011 ), a lower oocyte maturation rate ( D'Elia et al , 2014 ), a lower fertilization rate ( Marci et al , 2012 ), a higher miscarriage rate ( Nair et al , 2012 ; Xu et al , 2019 ) or a higher risk of small for gestational age ( Bulloch et al , 2020 ), while other studies have not confirmed such associations ( Dobson et al , 2007 ; Rosen et al , 2007 ; Marci et al , 2012 ; D'Elia et al , 2014 ; Aguilar-Lacasaña et al , 2021 ; Wang et al , 2021 ) or even yielded opposite results ( Laanpere et al , 2011 ). Also, previous studies have yielded conflicting results on the correlation between A1298C polymorphism and reproductive outcomes ( Haggarty et al , 2006 ; Dobson et al , 2007 ; Rosen et al , 2007 ; Laanpere et al , 2011 ; D'Elia et al , 2014 ; Xu et al , 2019 ; Bulloch et al , 2020 ; Wang et al , 2021 ). Thereby, there is currently no consistent and convincing conclusion on the relationship between MTHFR polymorphisms and reproductive outcomes.…”

Section: Introductionmentioning

confidence: 99%

Association between maternal MTHFR C677T/A1298C combination polymorphisms and IVF/ICSI outcomes: a retrospective cohort study

Chen

et al. 2022

Human Reproduction Open

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Study question What are the roles of maternal 5,10-Methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C combination polymorphisms on the embryological and clinical outcomes of IVF/ICSI? Summary answer Our study reveals for the first time that the oocyte maturation potential gradually decreases with a reduction of maternal MTHFR activity determined by combined C677T/A1298C polymorphisms, while embryo quality was worse in women with intermediate MTHFR activity. What is known already Although many previous studies have explored the association between MTHFR polymorphisms and IVF/ICSI outcomes, the results remain contradictory due to inadequate samples, no adjustment for potential confounders, and/or the study of C677T and A1298C separately. Few studies have systematically investigated the exact role of MTHFR activity determined by combined C677T/A1298C polymorphisms on the embryological and clinical outcomes of IVF/ICSI. Study design, size, duration This is a retrospective cohort study investigating 1,160 women who were referred for MTHFR genotyping and IVF/ICSI treatment at Peking University Third Hospital from May 2017 to May 2020. Participants/materials, setting, methods Women who were referred for MTHFR genotyping and their first IVF/ICSI treatment at our hospital were included and those undergoing preimplantation genetic testing (PGT) cycles were excluded. The included women were divided into different cohorts according to their C677T, A1298C and combined C677T/A1298C genotypes, respectively. The embryological outcomes, including oocytes retrieved, metaphase II (MII) oocytes, oocyte maturation rate, normal fertilization rate, and transplantable embryo rate, were evaluated by generalized linear regression models. The clinical outcomes, including biochemical pregnancy rate, clinical pregnancy rate, and live birth rate, were evaluated by log-binomial regression models. All outcomes were adjusted for potential confounders. Main results and the role of chance Women with the combined 677TT/1298AA genotype (hereafter abbreviated as TT/AA, as with other combined genotypes), whose enzyme activity was the lowest, had a lower oocyte maturation rate compared with those with the wild-type genotype (P = 0.007). Moreover, the oocyte maturation rate decreased linearly with the decline in MTHFR enzyme activity determined by combined C677T/A1298C genotypes (P-trend = 0.001). The combined CC/AC, CC/CC&CT/AA, and CT/AC genotypes with intermediate enzyme activity were associated with a lower transplantable embryo rate (P = 0.013, 0.030, and 0.039, respectively). The differences in clinical outcomes between women with wild-type genotype and combined C677T/A1298C variant genotypes were not significant. Limitations, reasons for caution Our study population had comparable embryological outcomes but worse clinical outcomes than other women undergoing IVF/ICSI treatment at our hospital. Therefore, the results related to the clinical outcomes should be generalized with caution. In addition, we did not detect the folate concentration of each patient during pregnancy. However, this might not have much influence on our results because almost all of our study participants took sufficient folic acid around pregnancy. Wider implications of the findings We provide a holistic view of the effect of MTHFR C677T and A1298C polymorphisms on the IVF/ICSI outcomes, which can contribute to providing reasonable folic acid supplementation suggestions for women with different MTHFR genotypes, especially for those with a low oocyte maturation rate and/or low embryo quality. Study funding/competing interest(s) This work was funded by the National Natural Science Foundation of China (31871447, 81730038, 82101677), the National Key Research and Development Program (2019YFA0801400), and the Natural Science Foundation of Beijing Municipality (7202226). The authors declare that they have no competing interests. Trial registration number N/A

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Section: Introductionmentioning

confidence: 99%

Association between maternal MTHFR C677T/A1298C combination polymorphisms and IVF/ICSI outcomes: a retrospective cohort study

Chen

et al. 2022

Human Reproduction Open

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The Value IRS-1 rs1801278G > A Polymorphism Testing in Evaluating Infertile Women with Polycystic Ovarian Syndrome: A Case-control Study

Raad Helmi,

Nori,

Ghani Zghair

2024

CWHR

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Background: Polycystic ovary syndrome (PCOS) is a leading cause of infertility. Insulin resistance is a key element in pathogenesis. The insulin receptor causes phosphorylation of the insulin receptor substrate (IRS); IRS-1 rs1801278G > A polymorphism variant is the most common genetic variant associated with IR and PCOS. Objective: We aimed to examine the frequency of IRS-1 rs1801278G > A polymorphism variant and test its value in evaluating infertile PCOS women. Methods: A case-control study recruited 140 age and body-mass-matched participants in the university hospital, subdivided according to Rotterdam criteria into PCOS cases (70/140) and healthy controls (70/140). We collected demographic data, ultrasonic [antral follicles and endometrial thickness], hormonal [FSH, LH, AMH, E2], and genetic data by polymerase chain reaction for analysis. Result: Wild GG SNP rs1801278 G was meaningfully higher among controls (58.57%, P<0.0001). Mutant AA SNP rs1801278 was significantly higher in PCOS women (37.14%, P-value =0.0001, an odds ratio of 20.50, 95% CI (9.42-28.63) to develop PCOS. Heterogenous GA gene SNP rs1801278 showed a trend of higher frequency in PCOS patients with 44.29%; OR of 3.91, 95% CI (1.37–7.55); P = 0.422. Upon correlating infertility parameters to SNP rs1801278 G>A polymorphism, statistical differences were found with AFC, LH/FSH ratio, and serum testosterone. As for the AMH, E2, and endometrial thickness, they failed to have a statistical value. Conclusion: The significant correlation of genetic polymorphism to infertility parameters among PCOS women opens a new therapeutic and prognostic avenue that helps gynecologists tailor manganate for a better and safer outcome.

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MTHFR as a Novel Candidate Marker for Litter Size in Rabbits

Yang,

Bao,

et al. 2024

Animals

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Litter size is a significant economic trait during animal reproduction. This current study attempted to decipher whether MTHFR promotes the apoptosis of granulosa cells (GCs) and inhibits their proliferation by investigating the effects of the MTHFR gene using flow cytometry and a Cell Counting Kit-8 (CCK-8) assay. MTHFR is linked with ovarian follicle development in the reproductive performance of 104 female New Zealand rabbits. We observed that MTHFR could regulate the mRNA of follicular development-related genes (TIMP1, CITED1, FSHR, GHR, HSD17B1, and STAR) with a qRT-PCR, and we observed the protein expression of CITED1 and GHR using a western blot (WB) analysis. The dual luciferase activity assays helped identify the core promoter region of the MTHFR gene, and the polymorphism of the MTHFR promoter region was studied using Sanger sequencing. The results indicated four single nucleotide polymorphisms (SNPs) within the core promoter region, among which the g.-680C>A locus was significantly associated with both the total and alive litter sizes. Additionally, the CC genotype was associated with the largest total and alive litter sizes, compared to the CA and AA genotypes (p < 0.05). In conclusion, this study investigated the effects of MTHFR on ovarian granulosa cells and its association with selected reproductive parameters in rabbits. The results provide a theoretical foundation for the use of MTHFR as a molecular marker in rabbits.

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Effect of polymorphisms of MTHFR in controlled ovarian stimulation: a systematic review and meta-analysis

Cited by 3 publications

References 46 publications

Association between maternal MTHFR C677T/A1298C combination polymorphisms and IVF/ICSI outcomes: a retrospective cohort study

Association between maternal MTHFR C677T/A1298C combination polymorphisms and IVF/ICSI outcomes: a retrospective cohort study

The Value IRS-1 rs1801278G > A Polymorphism Testing in Evaluating Infertile Women with Polycystic Ovarian Syndrome: A Case-control Study

MTHFR as a Novel Candidate Marker for Litter Size in Rabbits

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