Dados do Trabalho

Title

Association between genetic polymorphisms of the FSHR gene and infertility in women undergoing hormonal stimulation: a systematic review.

Objective

To investigate, based on the existing literature, the genetic polymorphism of the follicle-stimulating hormone receptor (FSHR) gene and its association with infertility in women undergoing hormonal stimulation.

Methods

Using the PRISMA guidelines, a search was performed in the PubMed/Medline and BVS databases in June 2023, restricted to articles published between 2013 and 2023, in English. The DeCS/MeSH descriptors “FSH receptor”, “polymorphism” and “female infertility” were used, excluding systematic reviews. As inclusion criteria, this systematic review used all studies that: 1) mapped genetic polymorphisms of the gene for the Follicle-Stimulating Hormone Receptor (FSHR); 2) in infertile women due to any etiologies; 3) evaluated the patients according to their ovarian responses to different methods of hormonal stimulation; and 4) performed statistical correlation analysis between the gene present for FSHR and the ovarian response found for a given hormonal stimulation. Data from the articles were collected independently by the authors and extracted using an extraction table developed in the Google Docs tool.

Results

After searching the electronic databases, 95 published full articles were found. Of the total results, after applying the inclusion and exclusion criteria, as well as removing duplicates, 18 publications remained for analysis.
The total population (N) found consisted of N = 7032 women evaluated according to the type of genetic polymorphism found for the FSHR gene, being 6111 infertile patients, who integrate the study groups, and 921 fertile women, who form the control groups.
The most cited method of assisted reproduction was in vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI) present in 8 articles, followed by conventional IVF, present in 5 articles. 6 articles do not specify whether conventional IVF or with ICSI was performed. Furthermore, in relation to ovarian stimulation, 5 articles commented on the adoption of a GnRH agonist protocol, 5 articles used the GnRH antagonist protocol, 10 studies pointed to the use of exogenous FSH, 3 articles cited the use of hMG and 1 article mentions the administration of clomiphene citrate. 6 articles do not cite the methods adopted at this stage of the process.
Three polymorphisms for the FSHR gene were established in the total female population: 15 studies addressed the polymorphism at position c.2039G>A (rs6166:C>T, p.Ser680Asn), 9 articles studied the polymorphism at position c.919G>A (rs6165:C>T, p.Ala307Thr) and 5 served the polymorphism at position c. -29G>A (rs1394205). As for the statistical analysis, the allelic variations of the c.2039G>A gene (rs6166:C>T, p.Ser680Asn) were related as a potential infertility factor in 11 of the 15 articles (73.3%) that study it. The alleles of the c.919G>A gene (rs6165:C>T, p.Ala307Thr) were classified as a possible infertility factor in all 9 articles (100%) that analyzed it. The different alleles of the c. -29G>A (rs1394205) exciting statistical link to fertility in only 2 of 5 papers (40%) describing it.
Overall, the presence of at least one genetic polymorphism was considered statistically relevant in 15 articles of the 18 studies (83%) that make up the present systematic review, while in 3 publications (17%) it was considered statistically irrelevant.

Conclusion

In women undergoing hormonal stimulation, the presence of at least one genetic polymorphism for the FSHR gene seems to be related to infertility.

Keywords

Infertility; Polymorphism; FSH receptor.