International Journal of Reproductive BioMedicine

ISSN: 2476-3772

The latest discoveries in all areas of reproduction and reproductive technology.

 

Significance of FSHR and LHCGR gene polymorphisms on clinical outcomes in gonadotropin-releasing hormone antagonist protocol with freeze-all strategy: A case-control study

Published date: Sep 03 2024

Journal Title: International Journal of Reproductive BioMedicine

Issue title: International Journal of Reproductive BioMedicine (IJRM): Volume 22, Issue No. 7

Pages: 539–552

DOI: 10.18502/ijrm.v22i7.16962

Authors:

Jayesh Amin - drjayeshamin8@gmail.com

Naga Sandhya Alle

Ami Patel

Bansi Prajapathi

Paresh Makwana

Jaya Prakash

Kota Murali Krishna

Abstract:

Background: Follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/choriogonadotropin receptor (LHCGR) are integral to ovarian function, facilitating follicle development and maturation through their respective hormonal interactions. The influence of receptor polymorphisms on the outcomes of freeze-all cycles remains unclear.

Objective: This study investigates the impact of FSHR N680S and LHCGR N312S polymorphisms on clinical outcomes in freeze-all cycles.

Materials and Methods: Women undergoing controlled ovarian stimulation for assisted reproductive technology participated in this study. They were administered a gonadotropin-releasing hormone antagonist protocol, with recombinant folliclestimulating hormone (rFSH) dosages adjusted according to age, body mass index, antral follicle count, and individual hormonal responses. Additionally, human menopausal gonadotropin dosages were tailored based on the LHCGR N312S genetic variant.

Results: Analysis revealed no significant differences in age, body mass index, antral follicle count, or marital status across the genotypes of FSHR N680S and LHCGR N312S. However, notable differences were observed in the rFSH dosage required daily and in total among the FSHR polymorphism genotypes. Genotypes of the LHCGR polymorphism correlated with fewer stimulation days. A significant interaction was observed between the 2 polymorphisms concerning total rFSH dosage.

Conclusion: The presence of serine in the FSHR polymorphism was associated with higher rFSH dosage requirements. Both FSHR N680S and LHCGR N312S polymorphisms significantly influenced clinical pregnancy and live birth outcomes in freeze-all cycles, underscoring the potential of a pharmacogenomic approach to optimize hormone supplementation in controlled ovarian stimulation protocols during assisted reproductive technology treatments.

Key words: LHCGR, FSHR, Polymorphism.

References:

[1] Borumandnia N, Alavi Majd H, Khadembashi N, Alaii H. Worldwide trend analysis of primary and secondary infertility rates over past decades: A cross-sectional study. Int J Reprod BioMed 2022; 20: 37–46.

[2] Cox CM, Thoma ME, Tchangalova N, Mburu G, Bornstein MJ, Johnson CL, et al. Infertility prevalence and the methods of estimation from 1990 to 2021: A systematic review and meta-analysis. Hum Reprod Open 2022; 2022: hoac051.

[3] Racca A, Drakopoulos P, Neves AR, Polyzos NP. Current therapeutic options for controlled ovarian stimulation in assisted reproductive technology. Drugs 2020; 80: 973–994.

[4] Fatemi H, Bilger W, Denis D, Griesinger G, La Marca A, Longobardi S, et al. Dose adjustment of folliclestimulating hormone (FSH) during ovarian stimulation as part of medically-assisted reproduction in clinical studies: A systematic review covering 10 years (2007– 2017). Reprod Biol Endocrinol 2021; 11: 68.

[5] Alviggi C, Longobardi S, Papaleo E, Santi D, Alfano S, Vanni VS, et al. Genetic variants of gonadotropins and their receptors could influence controlled ovarian stimulation: IVF data from a prospective multicenter study. Genes 2023; 14: 1269.

[6] Conforti A, Tuettelmann F, Alviggi C, Behre HM, Fischer R, Hu L, et al. Effect of genetic variants of gonadotropins and their receptors on ovarian stimulation outcomes: A delphi consensus. Front Endocrinol 2022; 12: 797365.

[7] Ga R, Cheemakurthi R, Kalagara M, Prathigudupu K, Balabomma KL, Mahapatro P, et al. Effect of LHCGR gene polymorphism (rs2293275) on LH supplementation protocol outcomes in second IVF cycles: A retrospective study. Front Endocrinol 2012; 12: 628169.

[8] Polyzos NP, Neves AR, Drakopoulos P, Spits C, Alvaro Mercadal B, Garcia S, et al. The effect of polymorphisms in FSHR and FSHB genes on ovarian response: A prospective multicenter multinational study in Europe and Asia. Hum Reprod 2021; 36: 1711–1721.

[9] Meireles AJ, Bilibio JP, Lorenzzoni PL, De Conto E, do Nascimento FC, da Cunha-Filho JS. Association of FSHR, LH, LHR, BMP15, GDF9, AMH, and AMHR polymorphisms with poor ovarian response in patients undergoing in vitro fertilization. JBRA Assist Reprod 2021; 25: 439.

[10] Sindiani AM, Batiha O, Khadrawi S, Alsoukhni G, Alkofahi A, Alahmad NA, et al. Association of singlenucleotide polymorphisms in the ESR2 and FSHR genes with poor ovarian response in infertile Jordanian women. Clin Exp Reprod Med 2021; 48: 69.

[11] Tzoupis H, Nteli A, Androutsou ME, Tselios T. Gonadotropin-releasing hormone and GnRH receptor: Structure, function and drug development. Curr Med Chem 2020; 27: 6136–6158.

[12] Clément F, Yvinec R, Gallay N, Gagniac L, Guillou F, Crépieux P. The follicle-stimulating hormone signaling network in gonadal cells. In: Ulloa-Aguirre A, Conn PM. Cellular endocrinology in health and disease. USA: Academic Press; 2014.

[13] Oduwole OO, Huhtaniemi IT, Misrahi M. The roles of luteinizing hormone, follicle-stimulating hormone and testosterone in spermatogenesis and folliculogenesis revisited. Int J Mol Sci 2021; 22: 12735.

[14] Lindgren I, Nenonen H, Henic E, Bungum L, Prahl A, Bungum M, et al. Gonadotropin receptor variants are linked to cumulative live birth rate after in vitro fertilization. J Assist Reprod Genet 2019; 36: 29–38.

[15] Paschalidou C, Anagnostou E, Mavrogianni D, Raouasnte R, Klimis N, Drakakis P, et al. The effects of follicle-stimulating hormone receptor (FSHR)-29 and Ser680Asn polymorphisms in IVF/ICSI. Horm Mol Biol Clin Investig 2020; 41: 20190058.

[16] Althumairy D, Zhang X, Baez N, Barisas G, Roess DA, Bousfield GR, et al. Glycoprotein G-protein coupled receptors in disease: Luteinizing hormone receptors and follicle stimulating hormone receptors. Diseases 2020; 8: 35.

[17] Haldar S, Agrawal H, Saha S, Straughn AR, Roy P, Kakar SS. Overview of follicle stimulating hormone and its receptors in reproduction and in stem cells and cancer stem cells. Int J Biol Sci 2022; 18: 675–692.

[18] Themmen AP, Huhtaniemi IT. Mutations of gonadotropins and gonadotropin receptors: Elucidating the physiology and pathophysiology of pituitary-gonadal function. Endocr Rev 2000; 21: 551–583.

[19] Casarini L, Lazzaretti C, Paradiso E, Limoncella S, Riccetti L, Sperduti S, et al. Membrane estrogen receptor (GPER) and follicle-stimulating hormone receptor (FSHR) heteromeric complexes promote human ovarian follicle survival. Iscience 2020; 23: 101812.

[20] Tang H, Yan Y, Wang T, Zhang T, Shi W, Fan R, et al. Effect of follicle-stimulating hormone receptor Asn680Ser polymorphism on the outcomes of controlled ovarian hyperstimulation: An updated meta-analysis of 16 cohort studies. J Assist Reprod Genet 2015; 32: 1801–1810.

[21] König TE, van der Lee J, Schats R, Lambalk CB. The relationship between FSH receptor polymorphism status and IVF cycle outcome: A retrospective observational study. Reprod BioMed Online 2019; 39: 231–240.

[22] Guo C, Yu H, Feng G, Lv Q, Liu X, Liu X. Associations of FSHR and LHCGR gene variants with ovarian reserve and clinical pregnancy rates. Reprod BioMed Online 2021; 43: 561–569.

[23] Bianco B, Loureiro FA, Trevisan CM, Peluso C, Christofolini DM, Montagna E, et al. Effects of FSHR and FSHB variants on hormonal profile and reproductive outcomes of infertile women with endometriosis. Front Endocrinol 2021; 12: 760616.

[24] Jin H, Yang H, Zheng J, Zhou J, Yu R. Posttrigger luteinizing hormone concentration to positively predict oocyte yield in the antagonist protocol and its association with genetic variants of LHCGR. J Ovarian Res 2023; 16: 189.

[25] Peluso C, Oliveira RD, Laporta GZ, Christofolini DM, Fonseca FL, Laganà AS, et al. Are ovarian reserve tests reliable in predicting ovarian response? Results from a prospective, cross-sectional, single-center analysis. Gynecol Endocrinol 2021; 37: 358–366.

[26] Paffoni A, Cesana S, Corti L, Ballabio E, Salemi C, Kunderfranco A, et al. Pregnancy rate in IVF patients with unexpected poor response to ovarian stimulation. Gynecol Endocrinol 2022; 38: 736–741.

Download
HTML
Cite
Share
statistics

0 Abstract Views

14 PDF Downloads