Several studies have shown a relationship between the FSHR or FSHB genotype and the response to medication with rFSH in ovarian stimulation treatments, suggesting a possible effect of individual genetic variability on ovarian stimulation. However, the evidence from these studies is inconsistent, due to the inclusion of patients with variable ovarian reserve, the use of different starting gonadotropin doses, and the possibility of dose adjustments during treatment. For this reason, a group of researchers, led by Dr Nikolaos Polyzos, head of the Reproductive Medicine Service of Dexeus Mujer, has carried out a large prospective multinational and multicentre study in a homogeneous population treated with the same fixed protocol in order to provide information of interest on this aspect.

A total of 368 patients <38 years of age with normal ovarian reserve were included, from Vietnam, Belgium and Spain (168 from Europe and 200 from Asia), and the study was conducted between November 2016 and June 2019. All patients underwent ovarian stimulation followed by oocyte retrieval in an antagonistic protocol with a fixed daily dose of 150 IU of rFSH until the puncture. Blood sampling and DNA extraction were performed before oocyte retrieval, followed by genotyping of four FSHR (rs6165, rs6166, rs1394205) and FSHB (rs10835638) SNPs.

Based on the results obtained, the presence of FSHR SNPs (rs6165, rs6166, rs1394205) has a statistically significant impact on ovarian response, although this effect is of minimal clinical relevance in normal responders treated with a fixed dose of 150 IU of rFSH. According to the authors, genotyping of FSHB SNPs rs6165, rs6166, rs1394205, and SNP rs10835638 should not be recommended before initiating ovarian stimulation with rFSH in expected normal responders, considering the minimal clinical impact of such information in this population. Future research could focus on other populations and other genes related to folliculogenesis or steroidogenesis.

Reference article:

The effect of polymorphisms in FSHR and FSHB genes on ovarian response: a prospective multicenter multinational study in Europe and Asia
Nikolaos P Polyzos, A R Neves, P Drakopoulos, C Spits, B Alvaro Mercadal, S Garcia, P Q M Ma, L H Le, M T Ho, J Mertens, D Stoop, H Tournaye, N L Vuong.
Hum Reprod. 2021 May 17;36(6):1711-1721. doi: 10.1093/humrep/deab068.