Association of Methylenetetrahydrofolate Reductase Gene Polymorphism C677T with Oocyte Number and Embryo Quality in Iraqi Infertile Women Undergoing Intracytoplasmic Sperm Injection
DOI:
https://doi.org/10.54133/ajms.v6i1.421Keywords:
Infertility, Intracytoplasmic sperm injection, Methylene tetrahydrofolate reductase, Single nucleotide polymorphismAbstract
Background: Methylenetetrahydrofolate reductase (MTHFR) C677T is a single nucleotide polymorphism (SNP) that affects the production of 5-methyltetrahydrofolate (5-MTHF), the active folate that enables the recycling of homocysteine (Hcy) to methionine. Objective: to investigate the association between the MTHFR (C677T) polymorphism and the outcomes of intracytoplasmic sperm injection (ICSI). Methods: A prospective cohort study included 85 infertile women undergoing ICSI treatment at the High Institute of Infertility Diagnosis and Assisted Reproductive Technologies in Baghdad, Iraq. The study period extended from January 2022 to September 2023. The MTHFR C677T polymorphism genotyping was evaluated in these patients, and they were classified into three groups according to genotyping results: normal (CC), heterozygote mutated (CT), and mutated homozygote (TT). In addition, we conducted a comparative analysis of oocyte, embryo and pregnancy rates among these three groups. Results: In comparison to the CT and TT genotypes, the total number of oocytes, total embryos, mature oocytes, good-quality embryos, and pregnancy rate were all found to be significantly higher (p<0.05) in the CC genotype. Compared to the CC group, the proportion of immature oocytes and poor-quality embryos was significantly higher in the TT and CT groups (p<0.05). The rate of fertilization was comparable among the study groups. Conclusions: The maternal MTHFR C677T polymorphism is linked to oocyte number, maturity, total embryo, embryo quality, and pregnancy in ICSI. In light of this, MTHFR polymorphism in our community offers useful data regarding the success of ICSI.
Downloads
References
Mani S, Ghosh J, Coutifaris C, Sapienza C, Mainigi M. Epigenetic changes and assisted reproductive technologies. Epigenetics. 2020;15(1-2):12-25. doi: 10.1080/15592294.2019.1646572.
Gleicher N, Barad DH. Assessing in-vitro fertilization at age 40 years. Lancet. 2019;393(10177):1181-1183. doi: 10.1016/S0140-6736(18)32070-1.
Gernand AD, Schulze KJ, Stewart CP, West Jr KP, Christian P. Micronutrient deficiencies in pregnancy worldwide: health effects and prevention. Nature Rev Endocrinol. 2016;12(5):274-289. doi: 10.1038/nrendo.2016.37.
Ducker GS, Rabinowitz JD. One-carbon metabolism in health and disease. Cell Metab. 2017;25(1):27-42. doi: 10.1016/j.cmet.2016.08.009.
Simkanin E. Thesis. Effects that the methylenetetrahydrofolate gene mutation (both the C677T and A1298C polymorphisms) have on both men and women’s fertility abilities and subsequent fetal development, as well as what nutritional changes can possibly do to aid in reversing these supposed negative effects. The University of Akron in Akron, Ohio, USA; 2023.
Guo J, Hao X, Wang R, Lian K, Jiang J, Chen N, Feng Z, Rao Y. MTHFR polymorphism's influence on the clinical features and therapeutic effects in patients with migraine: An observational study. Front Neurol. 2022;13:1074857. doi: 10.3389/fneur.2022.1074857.
Mallhi TH, Shahid M, Rehman K, Khan YH, Alanazi AS, Alotaibi NH, et al. Biochemical association of MTHFR C677T polymorphism with myocardial infarction in the presence of diabetes mellitus as a risk factor. Metabolites. 2023;13(2):251. doi: 10.3390/metabo13020251.
Abood ES, Naser MS, Naser RJ. MTHFR 677 C< T and 1298 A> C polymorphisms increases the risk of recurrent abortion in the Iraqi woman. Research Square. 2023. Pre-print. doi: 10.21203/rs.3.rs-480746/v1.
Ye F, Zhang S, Qi Q, Zhou J, Du Y, Wang L. Association of MTHFR 677C> T polymorphism with pregnancy outcomes in IVF/ICSI-ET recipients with adequate synthetic folic acid supplementation. BioScience Trends. 2022;16(4):282-290. doi: 10.5582/bst.2021.01306.
Liu L, Lin Z, Lin P, Jiang Z. Association between serum homocysteine level and unexplained infertility in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI): A retrospective, hospital‐based, case‐control study. J Clin Lab Anal. 2020;34(5):e23167. doi: 10.1002/jcla.23167.
Servy EJ, Jacquesson-Fournols L, Cohen M, Menezo YJ. MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series. J Assist Reprod Genetics. 2018;35:1431-1435. doi: 10.1007/s10815-018-1225-2.
Zeng H, Liu Z, Zhang L, Liu N. MTHFR 677TT is associated with decreased number of embryos and cumulative live birth rate in patients undergoing GnRHa short protocol: a retrospective study. BMC Preg Childbirth. 2022;22(1):170. doi: 10.1186/s12884-022-04506-4.
Chen L, Chen H, Wang X, Wei B, Wu Z, Chen S, et al. Association of homocysteine with IVF/ICSI outcomes stratified by MTHFR C677T polymorphisms: a prospective cohort study. Reprod Biomed Online. 2021;43(1):52-61. doi: 10.1016/j.rbmo.2021.04.009.
Dobson AT, Davis RM, Rosen MP, Shen S, Rinaudo PF, Chan J, et al. Methylenetetrahydrofolate reductase C677T and A1298C variants do not affect ongoing pregnancy rates following IVF. Human Reprod. 2007;22(2):450-456. doi: 10.1093/humrep/del396.
Zeng S, Wang X, Wang Y, Xu Z, Zhang J, Liu W, et al. MTHFR C677T polymorphism is associated with follicle-stimulating hormone levels and controlled ovarian hyperstimulation response: a retrospective study from the clinical database. Fertil Steril. 2019;111(5):982-990. doi: 10.1016/j.fertnstert.2019.01.016.
Deryabin PI, Ivanova JS, Borodkina AV. Senescence of stromal cells contributes to endometrium dysfunction and embryo implantation failure. BioRxiv. 2021;2021-07. doi: 10.1101/2021.07.19.452880.
Coulam CB, Jeyendran RS, Fishel LA, Roussev R. Multiple thrombophilic gene mutations are risk factors for implantation failure. Reprod Biomed Online. 2006;12(3):322-327. doi: 10.1016/S1472-6483(10)61004-8.
Enciso M, Sarasa J, Xanthopoulou L, Bristow S, Bowles M, Fragouli E, et al. Polymorphisms in the MTHFR gene influence embryo viability and the incidence of aneuploidy. Human Genetics. 2016;135:555-568. doi: 10.1007/s00439-016-1652-z.
Harton GL, Munné S, Surrey M, Grifo J, Kaplan B, McCulloh DH, et al. Diminished effect of maternal age on implantation after preimplantation genetic diagnosis with array comparative genomic hybridization. Fertil Steril. 2013;100(6):1695-1703. doi: 10.1016/j.fertnstert.2013.07.2002.
Shahrokhi SZ, Kazerouni F, Ghaffari F, Rahimipour A, Omrani MD, Arabipoor A, et al. The relationship between the MTHFR C677T genotypes to serum anti-Müllerian hormone concentrations and in vitro fertilization/intracytoplasmic sperm injection outcome. Clin Lab. 2017;63(5):927-934. doi: 10.7754/clin.lab.2016.161104.
Pavlik R, Hecht S, Ochsenkühn R, Noss U, Lohse P, Thaler CJ. Divergent effects of the 677C> T mutation of the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene on ovarian responsiveness and anti-Müllerian hormone concentrations. Fertil Steril. 2011;95(7):2257-2262. doi: 10.1016/j.fertnstert.2011.03.023.
Thaler CJ, Budiman H, Ruebsamen H, Nagel D, Lohse P. Effects of the common 677C> T mutation of the 5, 10‐methylenetetrahydrofolate reductase (MTHFR) gene on ovarian responsiveness to recombinant follicle‐stimulating hormone. Am J Reprod Immunol. 2006;55(4):251-258. doi: 10.1111/j.1600-0897.2005.00357.
D’Elia PQ, dos Santos AA, Bianco B, Barbosa CP, Christofolini DM, Aoki T. MTHFR polymorphisms C677T and A1298C and associations with IVF outcomes in Brazilian women. Reprod Biomed Online. 2014;28(6):733-738. doi: 10.1016/j.rbmo.2014.02.005.
Altmäe S, Hovatta O, Stavreus-Evers A, Salumets A. Genetic predictors of controlled ovarian hyperstimulation: where do we stand today? Human Reprod Update. 2011;17(6):813-828. doi: 10.1093/humupd/dmr034.
Rosen MP, Shen S, McCulloch CE, Rinaudo PF, Cedars MI, Dobson AT. Methylenetetrahydrofolate reductase (MTHFR) is associated with ovarian follicular activity. Fertil Steril. 2007;88(3):632-638. doi: 10.1016/j.fertnstert.2006.11.165.
Lu YJ, Li Q, Chen LX, Tian T, Kang J, Hao YX, et al. Association between maternal MTHFR C677T/A1298C combination polymorphisms and IVF/ICSI outcomes: a retrospective cohort study. Human Reprod Open. 2023;2023(1):055. doi: 10.1093/hropen/hoac055.
Ledowsky CJ, Schloss J, Steel A. Variations in folate prescriptions for patients with the MTHFR genetic polymorphisms: A case series study. Explor Res Clin Soc Pharm. 2023;10:100277. doi: 10.1016/j.rcsop.2023.100277.
Jukam D, Shariati SA, Skotheim JM. Zygotic genome activation in vertebrates. Devel Cell. 2017;42(4):316-332. doi: 10.1016/j.devcel.2017.07.026.
Sendžikaitė G, Kelsey G. The role and mechanisms of DNA methylation in the oocyte. Essays Biochem. 2019;63(6):691-705. doi: 10.1042/EBC20190043.
Zhou F, Wang R, Yuan P, Ren Y, Mao Y, Li R, et al. Reconstituting the transcriptome and DNA methylome landscapes of human implantation. Nature. 2019;572(7771):660-664. doi: 10.1038/s41586-019-1500-0.
Yan R, Gu C, You D, Huang Z, Qian J, Yang Q, et al. Decoding dynamic epigenetic landscapes in human oocytes using single-cell multi-omics sequencing. Cell Stem Cell. 2021;28(9):1641-1656. doi: 10.1016/j.stem.2021.04.012.
Razi Y, Eftekhar M, Fesahat F, Dehghani Firouzabadi R, Razi N, et al. Concentrations of homocysteine in follicular fluid and embryo quality and oocyte maturity in infertile women: a prospective cohort. J Obstet Gynecol. 2021;41(4):588-593. doi: 10.1080/01443615.2020.1785409.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 )
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Published by Al-Rafidain University College. This is an open access journal issued under the CC BY-NC-SA 4.0 license (https://creativecommons.org/licenses/by-nc-sa/4.0/).