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The Additive Effect of Combinations of FSH Receptor Gene Variants in Ovarian Response to Stimulation

  • Reproductive Biology: Original Article
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Abstract

To analyze whether combinations of polymorphisms within FSHR gene influence ovarian response (OR) to stimulation. A multicenter prospective cohort study was conducted from 11/2016–06/2019 in Europe and Asia including predicted normo-responders under 38y. Patients underwent ovarian stimulation using fixed-dose 150 IU rFSH in a GnRH antagonist protocol. FSHR variants rs6165, rs6166 and rs1394205 were genotyped and combined in diplotypes. OR was compared following multivariable regression. rs6165/rs6166 genotype AG/AG exhibited more hypo-response (33.1% vs. 24%,adjOR 1.77 [95%CI 1.08–2.90]) and lower Follicle to Oocyte Index (FOI) compared with other diplotypes (EMD -11.72 [95%CI -20.89;-2.55]). Genotype GG/AA showed less hypo-response (19.1% vs. 31%, adjOR 0.48 [95%CI 0.24–0.96]), while AA/AA had higher FOI (EMD 20.04 [95%CI 4.51;35.56]). Concerning rs6165/rs1394205, less oocytes (EMD -1.99 [95%CI -3.57;-0.42]) and lower FOI (EMD -12.07 [95%CI -23.09;-1.05]) were retrieved with genotype AG/AG and higher FORT with genotype AA/AG (EMD 17.88 [95%CI 3.77;31.98]). Regarding rs6166/rs1394205, less hypo-response (16.3% vs. 29.5%,adjOR 0.42 [95%CI 0.19–0.97]), more oocytes (EMD 3.45 [95%CI 1.57;5.34]) and higher FOI (EMD 17.57 [95%CI 4.41;30.73) were found with genotype AA/GG. Genotype AA/AG presented higher FORT (EMD 13.47 [95%CI 2.51,24.42]), while more hypo-response (56.3% vs. 26.4%,adjOR 6.30 [95%CI 1.88;21.08]) and lower FOI (EMD -23.51 [95%CI -45.04;-1.97]) was reported with AG/AA. In accordance with our previous studies, FSHR polymorphisms have a statistically significant impact on OR, both individually and in association. However, only rs6166/rs1394205 genotype AA/GG seems to have a clinically significant effect, with a decrease in the prevalence of hypo-response, higher oocyte yield and increase in FOI.

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Acknowledgements

This study was supported by an unrestricted grant by Merck Sharp & Dohme (MSD).

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Authors and Affiliations

  1. IVI-RMA Lisboa, 1-9ª, Av. Infante Dom Henrique 333 H, Lisbon, Portugal

    Ana Raquel Neves

  2. Dexeus Fertility, Dexeus University Hospital, 08028, Barcelona, Spain

    Ana Raquel Neves, Sandra Garcia & Nikolaos P. Polyzos

  3. Autonomous University of Barcelona, Cerdanyola del Vallès, 08193, Barcelona, Spain

    Ana Raquel Neves

  4. University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam

    Lan N. Vuong

  5. IVFMD and HOPE Research Center, My Duc Hospital, Ho Chi Minh City, Vietnam

    Lan N. Vuong

  6. Brussels IVF, Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, Brussels, Belgium

    Christophe Blockeel

  7. Department of Obstetrics and Gynecology, University of Zagreb-School of Medicine, Šalata 3, Zagreb, Croatia

    Christophe Blockeel

  8. Research Group Genetics Reproduction and Development, Vrije Universiteit Brussel, Brussels, Belgium

    Christophe Blockeel & Claudia Spits

  9. Faculty of Medicine and Health Sciences, Ghent University (UZ Gent), 9000 Gent, Belgium

    Nikolaos P. Polyzos

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  1. Ana Raquel Neves
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Correspondence to Ana Raquel Neves.

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Conflict of Interests/Competing Interests

C.B discloses honoraria for lectures from Abbott, Ferring, Organon, Merck, IBSA and Cook. LNV discloses grants from Merck Sharpe and Dohme as well as speaker and conference fees from Merck, Merck Sharpe and Dohme and Ferring and participation on a scientific board from Ferring. NPP reports grants from Merck Serono, Organon, Ferring Pharmaceutical, Roche Diagnostics, Theramex, IBSA, Gedeon Richter and Besins Healthcare; consulting fees from Merck Serono, Besins Healthcare, Organon and IBSA; honoraria from Merck Serono, Theramex, IBSA, Organon, Gedeon Richter, Besins Healthcare, Ferring Pharmaceuticals and Roche Diagnostics. ARN, SG and CS have no conflict of interests to disclose.

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Neves, A.R., Garcia, S., Vuong, L.N. et al. The Additive Effect of Combinations of FSH Receptor Gene Variants in Ovarian Response to Stimulation. Reprod. Sci. 31, 3560–3568 (2024). https://doi.org/10.1007/s43032-024-01700-x

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