Impact of FSHR -29 (G>A) Polymorphism on Ovarian Response and Pregnancy Outcomes in PCOD Patients Undergoing ART
DOI:
https://doi.org/10.52783/jns.v14.2579Keywords:
FSHR-29 polymorphism, PCOD, ovarian response, assisted reproductive technology, in vitro fertilization, genetic markers, reproductive successAbstract
Background: Polycystic ovary disease (PCOD) is a leading cause of anovulatory infertility, often requiring assisted reproductive technology (ART) for successful conception. Genetic polymorphisms, particularly in the follicle-stimulating hormone receptor (FSHR) gene, may influence ovarian response and reproductive outcomes. This study investigates the association of FSHR-29 (rs1394205) polymorphism with ovarian stimulation parameters, gonadotropin sensitivity, and pregnancy outcomes in PCOD patients undergoing ART.
Methods: A retrospective cohort study was conducted at Krishna IVF Clinic, Visakhapatnam, analyzing 224 PCOD patients undergoing ART between July 2015 and December 2020. Participants were stratified into three genotypic groups: GG (n=107, 47.77%), GA (n=85,37.95%), and AA (n=32, 14.29%). Ovarian response, hormone administration levels, embryo quality, clinical pregnancy rates, and live birth rates were assessed. Statistical analysis included ANOVA, Kruskal-Wallis, and logistic regression models, with GG as the reference genotype.
Results: AA genotype carriers exhibited higher gonadotropin requirements for ovarian stimulation (p=0.074), suggesting reduced FSH receptor expression. Despite comparable antral follicle count (AFC) and oocyte yield across genotypes, clinical pregnancy rates were highest in GG (49.53%), followed by GA (47.06%) and AA (37.50%). AA carriers also demonstrated the lowest live birth rates (21.8%) and highest rates of negative pregnancy outcomes (62.5%). However, statistical significance was not established for pregnancy or live birth outcomes.
Conclusion: FSHR-29 polymorphism may influence ovarian response and reproductive success in PCOD patients undergoing ART. While AA genotype carriers required higher FSH doses, exhibited lower pregnancy rates, and had poorer live birth outcomes, the findings warrant further investigation with larger cohorts to validate clinical significance.
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Achrekar, S. K., Modi, D. N., Desai, S. K., Mangoli, V. S., Mangoli, R. V., & Mahale, S. D. (2009). Poor ovarian response to gonadotrophin stimulation is associated with FSH receptor polymorphism. Reproductive Biomedicine Online, 18(4), 509–515. https://doi.org/10.1016/S1472-6483(10)60127-7
Allegra, A., Marino, A., Raimondo, S., Maiorana, A., Gullo, S., Scaglione, P., ... & Alessandro, R. (2017). The carriers of the A/GG/G allelic combination of the c. 2039 A> G and c.-29 G> A FSH receptor polymorphisms retrieve the highest number of oocytes in IVF/ICSI cycles. Journal of assisted reproduction and genetics, 34, 263-273. https://doi.org/10.1007/s10815-016-0835-9
Alviggi, C., Humaidan, P., & Ezcurra, D. (2012). Hormonal, functional and genetic biomarkers in controlled ovarian stimulation: Tools for matching patients and protocols. Reproductive Biology and Endocrinology, 10(1), 1–9. https://doi.org/10.1186/1477-7827-10-9
Alviggi, C., Longobardi, S., Papaleo, E., Santi, D., Alfano, S., Vanni, V. S., ... & Conforti, A. (2023). Genetic variants of gonadotropins and their receptors could influence controlled ovarian stimulation: IVF data from a prospective multicenter study. Genes, 14(6), 1269. https://doi.org/10.3390/genes14061269
Camp, T. A., Rahal, J. O., & Mayo, K. E. (1991). Cellular localization and hormonal regulation of follicle-stimulating hormone and luteinizing hormone receptor messenger RNAs in the rat ovary. Molecular Endocrinology, 5(10), 1405–1417.https:/ doi.org/ 10.1210/mend-5-10-1405
Catteau-Jonard, S., Jamin, S. P., Leclerc, A., Gonzalès, J., Dewailly, D., & Di Clemente, N. (2008). Anti-Mullerian hormone, its receptor, FSH receptor, and androgen receptor genes are overexpressed by granulosa cells from stimulated follicles in women with polycystic ovary syndrome. The Journal of Clinical Endocrinology & Metabolism, 93(11), 4456-4461.2008;93(11):4456-61. https://doi.org/ 10.1210 /jc.2008-1231
Desai, S. S., Achrekar, S. K., Pathak, B. R., Desai, S. K., Mangoli, V. S., Mangoli, R. V., & Mahale, S. D. (2011). Follicle-stimulating hormone receptor polymorphism (G− 29A) is associated with altered level of receptor expression in granulosa cells. The Journal of Clinical Endocrinology & Metabolism, 96(9), 2805-2812. https:// doi.org/10.1210/jc.2011-1064
Ga, R., Cheemakurthi, R., Kalagara, M., Prathigudupu, K., Balabomma, K. L., Mahapatro, P., ... & Muvvala, S. P. R. (2021). Effect of LHCGR gene polymorphism (rs2293275) on LH supplementation protocol outcomes in second IVF cycles: A retrospective study. Frontiers in Endocrinology, 12, 628169. https://doi.org /10.3389/fendo.2021.628169
Govind, A., Obhrai, M. S., & Clayton, R. N. (1999). Polycystic ovaries are inherited as an autosomal dominant trait: analysis of 29 polycystic ovary syndrome and 10 control families. The Journal of Clinical Endocrinology & Metabolism, 84(1), 38-43. https://doi.org/10.1210/jcem.84.1.5382
McNeilly, A. S., Picton, H. M., Campbell, B. K., & Baird, D. T. (1991). Gonadotrophic control of follicle growth in the ewe. Journal of Reproduction and Fertility Supplement, 43, 177–186. PMID: 1843339.
Means, A. R., MacDougall, E., Soderling, T. R., & Corbin, J. D. (1974). Testicular adenosine 3′:5′-monophosphate-dependent protein kinase: Regulation by folliclestimulating hormone. Journal of Biological Chemistry, 249(5), 1231–1238. DOI:10. 1016/S0021-9258(19)42965-7
Morón, F. J., & Ruiz, A. (2010). Pharmacogenetics of controlled ovarian hyperstimulation: Time to corroborate the clinical utility of FSH receptor genetic markers. Pharmacogenomics, 11(11), 1613–1618. https://doi.org/10.2217/pgs.10.156
Nakayama, T., Kuroi, N., Sano, M., Tabara, Y., Katsuya, T., Ogihara, T., Makita, Y., Hata, A., Yamada, M., Takahashi, N., & Hirawa, N. (2006). Mutation of the folliclestimulating hormone receptor gene 5′-untranslated region associated with female hypertension. Hypertension, 48(3), 512–518. https://doi.org/10.1161/01. HYP.0000233877.84343.d7
Nasiri, H., Forouzandeh, M., Rasaee, M. J., & Rahbarizadeh, F. (2005). Modified salting‐out method: high‐yield, high‐quality genomic DNA extraction from whole blood using laundry detergent. Journal of clinical laboratory analysis, 19(6), 229-232.
Nordhoff, V., Sonntag, B., von Tils, D., Götte, M., Schüring, A. N., Gromoll, J., Redmann, K., Casarini, L., & Simoni, M. (2011). Effects of the FSH receptor gene polymorphism p.N680S on cAMP and steroid production in cultured primary human granulosa cells. Reproductive Biomedicine Online, 23(2), 196–203. https://doi.org /10.1016/j.rbmo.2011.04.009
Perez Mayorga, M., Gromoll, J., Behre, H. M., Gassner, C., Nieschlag, E., & Simoni, M. (2000). Ovarian response to follicle-stimulating hormone (FSH) stimulation depends on the FSH receptor genotype. The Journal of Clinical Endocrinology & Metabolism, 85(9), 3365–3369.
Raju, G. A. R., Teng, S. C., Kavitha, P., Lakshmi, B. K., & Ravikrishna, C. (2012). Combination of recombinant follicle stimulating hormone with human menopausal gonadotrophin or recombinant luteinizing hormone in a long gonadotrophin-releasing hormone agonist protocol: a retrospective study. Reproductive medicine and biology, 11, 129-133.
Sacchi, S., Sena, P., Degli Esposti, C., Lui, J., & La Marca, A. (2018). Evidence for expression and functionality of FSH and LH/hCG receptors in human endometrium. Journal of Assisted Reproduction and Genetics, 35(10), 1703-1712. https://doi.org/ 10.1007/s10815-018-1248-8
Simoni, M., Gromoll, J., & Nieschlag, E. (1997). The follicle-stimulating hormone receptor: Biochemistry, molecular biology, physiology, and pathophysiology. Endocrine Reviews, 18(6), 739–773.
Simoni, M., Nieschlag, E., & Gromoll, J. (2002). Isoforms and single nucleotide polymorphisms of the FSH receptor gene: Implications for human reproduction. Human Reproduction Update, 8(5), 413–421.
Themmen, A. P., & Huhtaniemi, I. T. (2000). Mutations of gonadotropins and gonadotropin receptors: Elucidating the physiology and pathophysiology of pituitarygonadal function. Endocrine Reviews, 21(5), 551–583.
Thomas, R. M., Nechamen, C. A., Mazurkiewicz, J. E., Ulloa-Aguirre, A., & Dias, J. A. (2011). The adapter protein APPL1 links FSH receptor to inositol 1,4,5- trisphosphate production and is implicated in intracellular Ca²⁺ mobilization. Endocrinology, 152(5), 1691–1701.
Veeck, L. L. (1986). Atlas of the human oocyte and early conceptus.
Wong, P. C., Qiao, J., Ho, C., Ramaraju, G. A., Wiweko, B., Takehara, Y., ... & Vuong, T. N. L. (2011). Current opinion on use of luteinizing hormone supplementation in assisted reproduction therapy: an Asian perspective. Reproductive biomedicine online, 23(1), 81-90.
World Health Organization. (2000). WHO manual for the standardized investigation and diagnosis of the infertile couple. Cambridge University Press.
Wunsch, A., Ahda, Y., Banaz-Yaşar, F., Sonntag, B., Nieschlag, E., Simoni, M., & Gromoll, J. (2005). Single-nucleotide polymorphisms in the promoter region influence the expression of the human follicle-stimulating hormone receptor. Fertility and Sterility, 84(2), 446–453.
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