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

Amin J, Sandhya Alle N, Naga Sandhya Alle, Ami Patel, Patel A, Bansi Prajapathi, Prajapathi B, Paresh Makwana, Makwana P, Jaya Prakash, Prakash J, Murali Krishna K, Kota Murali Krishna
International journal of reproductive biomedicine · 2024 · vol. 22(7) , pp. 539–552 · doi:10.18502/ijrm.v22i7.16962 · PMID:39355311 · PMC11441282
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This case-control study found that FSHR N680S and LHCGR N312S polymorphisms influence gonadotropin dosage requirements, stimulation duration, and clinical pregnancy or live birth outcomes in freeze-all assisted reproductive technology cycles.

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This case-control study evaluated the impact of FSHR N680S and LHCGR N312S gene polymorphisms on clinical outcomes in 306 women undergoing gonadotropin-releasing hormone antagonist IVF cycles with a freeze-all strategy. The results indicated that women with the homozygous SS genotype for the FSHR gene required significantly higher doses of recombinant follicle-stimulating hormone compared to those with NN or NS genotypes, although differences in live birth rates were not statistically significant despite an observed trend toward higher success in the SS group. The authors note that while genetic variations influence stimulation requirements, they did not demonstrate a definitive statistical advantage in pregnancy or live birth outcomes within this specific protocol. Relevance to endometriosis: listed as one indication for GnRH antagonists, though the paper's main focus is uterine fibroids.

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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 follicle-stimulating 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.
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Jayesh Amin and Naga Sandhya Alle had complete access to all the data in the study and takes responsibility for both the integrity of the data and the accuracy of the data analysis, including the conceptualization and design of the study. Ami Patel, Bansi Prajapathi, and Paresh Makwana were responsible for the acquisition, analysis, and interpretation of the data. Kota Murali Krishna drafted the manuscript. Jaya Prakash and Kota Murali Krishna conducted statistical analysis. All authors contributed to the critical revision of the manuscript for significant intellectual content. Ami Patel and Kota Murali Krishna took care of the overall coordination and follow-up of the study.

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The authors declare that there is no conflict of interest.

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