Exploring the correlation between homocysteine, red blood cell folate and MTHFRC677T genotypes with female infertility.

Aim: To investigate the association between serum homocysteine (HCY) levels, red blood cell folate (RCF) levels, methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and infertility.

& methods: Serum HCY and RCF levels and C677T polymorphism of MTHFR gene were analyzed in 149 infertile patients and 223 women of normal reproductive age with healthy childbirth history.

The HCY level of MTHFR C677T TT genotype infertility patients was higher than that of women of normal reproductive age, while the RCF level was not significantly different between the two groups.

Serum HCY levels increased in infertility patients, and the MTHFR C677T TT genotype in childbearing-aged women are associated with a higher risk of infertility. The results showed that HCY level and MTHFR C677T genotype were closely related to infertility. Red blood cell folate (RCF) levels serve as a more reliable indicator of folate status, and studies conducted in countries with folic acid fortification have underscored the prevalence of suboptimal RCF levels among many women of childbearing age. The methylenetetrahydrofolate reductase (MTHFR) C667T gene plays a pivotal role in regulating the metabolic pathway of folic acid, and extensive research has been conducted on its mutation over the past two decades. The findings of this study demonstrate a statistically significant disparity in serum homocysteine (HCY) levels between patients in the infertility group and those in the control group, indicating higher levels among the former. The results revealed that patients in the infertility group with the TT genotype exhibited elevated serum HCY levels compared with those in the control group. Additionally, the homozygous mutation rate of MTHFR C667T was higher in the infertility group (10.74%) than in the control group (4.04%), demonstrating a statistically significant difference (p < 0.05). Currently, there is a paucity of research investigating the levels of serum HCY, reproductive cytokines factor (RCF) and MTHFR in relation to infertility. The precise pathogenesis underlying unexplained infertility remains inadequately elucidated. We conducted a further analysis on the correlation between HCY and RCF levels in both groups of women, revealing no significant correlation between HCY and RCF levels (). These findings contradict the conclusions drawn by Paffoni et al. Therefore, for patients with the MTHFR C677T TT genotype, personalized extension of folic acid supplementation duration or an increase in folic acid dosage is recommended according to China's expert consensus on folic acid supplementation. Overall, there exists a significant association between HCY levels and the MTHFR C677T genotype with infertility, which represents a crucial risk factor in the context of reproductive health. Acknowledgments We would like to thank all the patients and family members who participated in this study for their cooperation and patience. Author contributions M Wu, Y Liu and H Yuan conceived and designed this study. B Yanga, S Huanga, Y Zoua, F Zhaoa and C Fenga collected and analyzed the data. H Laod collected the written informed consent. X You, Z Zhang and Y Xu wrote and revised the manuscript. All authors have read and agreed to the published version of the manuscript. Financial disclosure This study was supported by Jiangxi Provincial Key Laboratory of Birth Defect for Prevention and Control (No. 2024SSY06201 to Y Lu). Jiangxi Provincial Clinical Research Center for Birth Defects (No. 20223BCG74002 to Y Lu). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Competing interests disclosure The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Writing disclosure No writing assistance was utilized in the production of this manuscript. Ethical conduct of research The authors state that they have obtained appropriate institutional review board approval (Jiangxi Maternal and Child Health Hospital (NO.20200086)) and/or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved. Data availability statement The original contributions presented in the study are publicly available. This data can be found here: https://doi.org/10.6084/m9.figshare.26490526.