The Effect of the Allelics of Ser680Asn Polymorphisms of Follicle-Stimulating Hormone Receptor Gene in IVF/ICSI Cycles: a Systematic Review and Meta-analysis

A significant number of single-nucleotide polymorphisms (SNPs) of the follicle-stimulating hormone receptor (FSHr) can modify the response to exogenous FSH administration. A significant diversity in response to controlled ovarian stimulation (COS) in assisted reproductive technologies (ART) according to the type of allelic has been reported. We aimed to evaluate the relation between the Asn680Ser allelics and COS. A total of 4 electronic databases were searched for articles published up to August 2021. Prospective and retrospective comparative studies which reported outcomes after COS in patients who underwent genotyping for the detection of FSHr polymorphisms were considered eligible. A total of 11 studies including 4343 patients with Asn680Ser polymorphisms of the FSHr were included. Patients carrying the Asn/Asn allelic provide elevated E2 on the day of human chorionic gonadotropin (hCG) administration (1549 patients MD 262.39 pg/ml, p = 0.0007), but less transferrable embryos as compared with Ser/Ser genotype (283 patients MD - 0.11 embryos, p = 0.04). Ans/Ser versus Ser/Ser genotypes showed a higher E2 on the day of hCG administration (1799 patients, MD 207.86 pg/ml, p = 0.02). Pregnancy rates were similar in all combination of genotypes. There is currently no strong evidence suggesting that the examination of one gene in relation to genotypes can be effectively used as single tool to improve COS. However, polygenic analysis of different polymorphisms by analyzing the genetic profile of each individual could be useful. Further research is warranted to develop an algorithm that will enable simultaneous analysis of many genes, which combined with hormonal profile could promote treatment individualization.