Association of methylene tetrahydrofolate reductase polymorphisms with cycle day two hormonal characteristics

Authors

  • Rabab Al-yasiry Department of Anatomy, and Histology, College of Medicine / Babylon University, Babylon / Iraq
  • Mufeda AL-Ammar The High Institute for Infertility Diagnosis and Assisted Reproductive Technologies https://orcid.org/0000-0002-7995-6755
  • Muayad S. Abbood The High Institute for Infertility Diagnosis and Assisted Reproductive Technologies https://orcid.org/0000-0002-7995-6755

DOI:

https://doi.org/10.28969/IJEIR.v13.i2.r7.23

Abstract

The 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme is a key
methionine and folate metabolism enzyme that is found in oocytes and
embryos in preimplantation stages and plays a vital role in female
reproduction.To assess the impact of MTHFR genetic polymorphisms
(C677T and A1298C) on follicular stimulating hormone (FSH), luteinizing
hormone(LH), Estradiol (E2), progesterone and antimullerian hormone
(AMH) in female receiving intracytoplasmic sperm injection (ICSI), 85
infertile women undergoing ICSI treatment at the High Institute of Infertility
Diagnosis and Assisted Reproductive Technologies in Baghdad, Iraq, were
recruited. These patients had their MTHFR polymorphism genotypes
examined, FSH, LH, E2, progesterone, and AMH levels were compared
between groups. Furthermore, all demographic characteristics as well as ICSI
outcomes were compared between pregnant and non-pregnant women. The
research revealed no discernible variation between the means of FSH, LH, E2
and AMH with respect to the 219A>C(rs1801131) (A1298C) genotypes (p >
0.05). Progesterone level was significantly differed with high level found in
CC followed by AA and AC. There was no statistically significant variation
in hormonal features between CC, CT, and TT for A1298C,
219A>C(rs1801133). The demographic features (age, duration, type of
infertility, cause of infertility and previous trial) were not notably different
between women who were pregnant and those who were not. In women
undergoing ICSI, the maternal MTHFR polymorphisms is not related to FSH,
LH, E2 and AMH. MTHFR polymorphisms therefore don't offer useful
information regarding the hormonal levels in our groups

References

Lu YJ, Li Q, Chen LX, Tian T, Kang J, Hao YX, Zhou JS, Wang YY, Yan LY, Li R, Chang L. Association between maternal MTHFR C677T/A1298C combination polymorphisms and IVF/ICSI outcomes: a retrospective cohort study. Human Reproduction Open. 2023 Jan 1;2023(1):hoac055. https://doi.org/10.1093/hropen/hoac055.

Cariati F, D’Argenio V, Tomaiuolo R. The evolving role of genetic tests in reproductive medicine. Journal of translational medicine. 2019 Dec;17:1-33. https://doi.org/10.1186/s12967-019-2019-8.

Panera N, Mandato C, Crudele A, Bertrando S, Vajro P, Alisi A. Genetics, epigenetics and transgenerational transmission of obesity in children. Frontiers in Endocrinology. 2022 Nov 14;13:1006008. https://doi.org/10.3389/fendo.2022.1006008.

Simkanin E. 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.

Clément, A., Menezo, Y., Cohen, M., Cornet, D. and Clément, P., 2020. 5-Methyltetrahydrofolate reduces blood homocysteine level significantly in C677T methyltetrahydrofolate reductase single-nucleotide polymorphism carriers consulting for infertility. Journal of Gynecology Obstetrics and Human Reproduction, 49(1), p.101622. https://doi.org/10.1016/j.jogoh.2019.08.005.

Yan R, Gu C, You D, Huang Z, Qian J, Yang Q, Cheng X, Zhang L, Wang H, Wang P, Guo F. Decoding dynamic epigenetic landscapes in human oocytes using single-cell multi-omics sequencing. Cell Stem Cell. 2021 Sep 2;28(9):1641-56. https://doi.org/10.1016/j.stem.2021.04.012.

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. Reproductive biomedicine online. 2014 Jun 1;28(6):733-8. https://doi.org/10.1016/j.rbmo.2014.02.005.

Xu Y, Ban Y, Ran L, Yu Y, Zhai S, Sun Z, Zhang J, Zhang M, Hong T, Liu R, Ren L. Relationship between unexplained recurrent pregnancy loss and 5, 10-methylenetetrahydrofolate reductase) polymorphisms. Fertility and sterility. 2019 Mar 1;111(3):597-603. https://doi.org/10.1016/j.fertnstert.2018.11.011.

Bulloch RE, Wall CR, McCowan LM, Taylor RS, Roberts CT, Thompson JM. The Effect of interactions between folic acid supplementation and one carbon metabolism gene variants on small-for-gestational-age births in the Screening for Pregnancy Endpoints (SCOPE) cohort study. Nutrients. 2020 Jun 4;12(6):1677. https://doi.org/10.3390/nu12061677.

He HR, Chen SY, You HS, Hu SS, Sun JY, Dong YL, Lu J. Association between methylenetetrahydrofolate reductase polymorphisms and the relapse of acute lymphoblastic leukemia: a meta-analysis. The Pharmacogenomics Journal. 2014 Oct;14(5):432-8. https://doi.org/10.1038/tpj.2014.10.

MURTO T, KALLAK TK, HOAS A, ALTMÄE S, SALUMETS A. Folic acid supplementation and methylenetetrahydrofolate reductase (MTHFR) gene variations in relation to IVF pregnancy outcome. https://doi:10.1111/aogs.12522.

Rosen MP, Shen S, McCulloch CE, Rinaudo PF, Cedars MI, Dobson AT. Methylenetetrahydrofolate reductase (MTHFR) is associated with ovarian follicular activity. Fertility and sterility. 2007 Sep 1;88(3):632-8. https://doi.org/10.1016/j.fertnstert.2006.11.165.

Enciso M, Sarasa J, Xanthopoulou L, Bristow S, Bowles M, Fragouli E, Delhanty J, Wells D. Polymorphisms in the MTHFR gene influence embryo viability and the incidence of aneuploidy. Human genetics. 2016 May;135:555-68. https://doi.org/10.1007/s00439-016-1652-z.

Pierson HE, Invik J, Meriano J, Pierson RA. A novel system for rapid conversion of Gardner embryo grades to linear scale numeric variables. Reproductive BioMedicine Online. 2023 May 1;46(5):808-18. https://doi.org/10.1016/j.rbmo.2023.01.008.

Ledowsky C, Steel A, Schloss J. Methylenetetrahydrofolate Reductase (MTHFR) genetic polymorphisms and the risk of infertility in couples accessing Assisted Reproductive technologies: a systematic review. Advances in Integrative Medicine. 2021 Sep 1;8(3):220-9. https://doi.org/10.1016/j.aimed.2021.05.004.

Guo KM, Tian RH, Wang HL. Relationship of MTHFR gene polymorphisms with infertility. National Journal of Andrology. 2016:171-4.

Shahrokhi SZ, Kazerouni F, Ghaffari F, Hadizadeh M, Zolfaghary Z. The effect of A1298c polymorphism of the MTHFR gene on anti‐Müllerian hormone levels: experimental and Web‐based analysis. Journal of Clinical Laboratory Analysis. 2021 Sep;35(9):e23948. https://doi.org/10.1002/jcla.23948.

Undas A, Chojnowski K, Klukowska A, Łętowska M, Mital A, Młynarski WM, Musiał J, Podolak-Dawidziak M, Sąsiadek M, Treliński J, Urasiński T. Determination and interpretation of" MTHFR" gene mutations in gynecology and internal medicine. Polskie Archiwum Medycyny Wewnętrznej= Polish Archives of Internal Medicine. 2019;129(10). https://doi.org/10.20452/pamw.15039.

Shahrokhi SZ, Kazerouni F, Ghaffari F, Rahimipour A, Omrani MD, Arabipoor A, Lak R, Ghane ET. The Relationship Between the MTHFR C677T Genotypes to Serum Anti-Müllerian Hormone Concentrations and In Vitro Fertilization/Intracytoplasmic Sperm Injection Outcome. Clinical laboratory. 2017 May 1;63(5):927-34. https://doi.org/10.7754/clin.lab.2016.161104.

Zeng S, Wang X, Wang Y, Xu Z, Zhang J, Liu W, Qian L, Chen X, Wei J, Yang X, Gong Z. MTHFR C677T polymorphism is associated with follicle-stimulating hormone levels and controlled ovarian hyperstimulation response: a retrospective study from the clinical database. Fertility and sterility. 2019 May 1;111(5):982-90. https://doi.org/10.1016/j.fertnstert.2019.01.016.

Cai Q, Wan F, Huang K, Zhang H. Does the number of oocytes retrieved influence pregnancy after fresh embryo transfer?. PloS one. 2013 Feb 15;8(2):e56189. https://doi.org/10.1371/journal.pone.0056189.

Van Loendersloot LL, Van Wely M, Limpens J, Bossuyt PM, Repping S, Van Der Veen F. Predictive factors in in vitro fertilization (IVF): a systematic review and meta-analysis. Human reproduction update. 2010 Nov 1;16(6):577-89. https://doi.org/10.1093/humupd/dmq015.

Edan BJ, Al-Katib SR, AlGhazali BS. Embryo Grade I is The Most Important ICSI Parameters That Predict Intracytoplasmic Sperm Injection (ICSI) Outcome. Medical Journal of Babylon. 2015;12(1).

Hsu MI, Wang CW, Chen CH, Tzeng CR. Impact of the number of retrieved oocytes on pregnancy outcome in in vitro fertilization. Taiwanese Journal of Obstetrics and Gynecology. 2016 Dec 1;55(6):821-5. https://doi.org/10.1016/j.tjog.2015.05.009.

Berger DS, Zapantis A, Merhi Z, Younger J, Polotsky AJ, Jindal SK. Embryo quality but not pronuclear score is associated with clinical pregnancy following IVF. Journal of assisted reproduction and genetics. 2014 Mar;31:279-83. https://doi.org/10.1007/s10815-013-0162-3.

Kumar P, Adiga SK. Evaluation of Oxidative Stress and Antioxidants in Serum and Follicular Fluid of Women Undergoing Invitro Fertilization. International Journal of Basic and Life Sciences. 2014;2(2):1-0.

Shim YJ, Hong YH, Kim SK, Jee BC. Optimal numbers of mature oocytes to produce at least one or multiple top-quality day-3 embryos in normal responders. Clinical and Experimental Reproductive Medicine. 2020 Sep;47(3):221. https://doi.org/10.5653%2Fcerm.2019.03377.

Published

2023-11-08

How to Cite

1.
Al-yasiry R, AL-Ammar M, S. Abbood M. Association of methylene tetrahydrofolate reductase polymorphisms with cycle day two hormonal characteristics. IJEIR [Internet]. 2023 Nov. 8 [cited 2024 Apr. 20];13(2):78-9. Available from: https://ijeir.net/index.php/ijeir/article/view/144

Most read articles by the same author(s)