Ana Raquel Neves, Sandra Garcia, Lan TN Vuong, Christophe Blockeel, Gemma Arroyo, Claudia Spits, Toan D Pham, Tuong M Ho, Herman Tournaye, Nikolaos P Polyzos
Published: 26 January, 2023
Author information
Department of Obstetrics, Gynecology and Reproductive Medicine, Dexeus University Hospital, 08028 Barcelona, Spain
IVFMD and HOPE Research Center, My Duc Hospital, Ho Chi Minh City, Vietnam
University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, Brussels, Belgium
Research Group Reproduction and Genetics, Vrije Universiteit Brussel, Brussels, Belgium
Abstract
Highlights
- c.919A>G genotypes AG/GG are associated with higher CPR versus genotype AA
- c.919A>G genotypes AG/GG are associated with higher LBR versus genotype AA
- c.2039A>G genotype GG is associated with lower CLBR versus genotype AA
Reseach question
Is there an association between FSHR sequence variants and reproductive outcomes following IVF in predicted normoresponders?Design
Multicentre prospective cohort study conducted from November 2016 to June 2019 in Vietnam, Belgium and Spain including patients aged <38 years, and undergoing IVF with a predicted normal response with fixed-dose 150 IU rFSH in an antagonist protocol. Genotyping was performed for three FSHR (c.919A>G, c.2039A>G, c.-29G>A) and one FSHB sequence variants (c.-211G>T). Clinical pregnancy rate (CPR), live birth rate (LBR) and miscarriage rate in the first embryo transfer and cumulative live birth rate (CLBR) were compared between the different genotypes.
Results
A total of 351 patients underwent at least one embryo transfer. Genetic model analysis that adjusted for patient age, body mass index, ethnicity, type of embryo transfer, embryo stage and number of top-quality embryos transferred revealed a higher CPR for homozygous patients for the variant allele G of c.919A>G when compared to patients with genotype AA (60.3% versus 46.3%, adjusted odds ratio [ORadj] 1.96, 95% confidence interval [CI] 1.09–3.53). Also, c.919A>G genotypes AG and GG presented a higher CPR and LBR when compared with genotype AA (59.1% versus 46.3%, ORadj 1.80, 95% CI 1.08–3.00, and 51.3% versus 39.0%, ORadj 1.69, 95% CI 1.01–2.80, respectively). Cox regression models revealed a statistically significantly lower CLBR for c.2039A>G genotype GG in the codominant model (hazard ratio [HR] 0.66, 95% CI 0.43–0.99).
Conclusion
These results demonstrate a previously unreported association between variant c.919A>G genotype GG and higher CPR and LBR in infertile patients and reinforce a potential role for genetic background in predicting the reproductive prognosis following IVF.
Keywords
Clinical pregnancy rate, Cumulative live birth rate, FSH receptor, Live birth rate, Sequence variants