A large clinical study found that using women's genetic profiles to guide the type of hormone used in in-vitro fertilization could improve their chances of becoming pregnant and giving birth.
Researchers discovered that matching the type of follicle-stimulating hormone (FSH) to a woman’s FSH receptor (FSHR) N680S gene variant led to better outcomes compared with standard treatment protocols.
The researchers enrolled 475 women undergoing their first cycle of ovarian stimulation for in vitro fertilization (IVF). All of the participants were genotyped for the FSHR N680S variant, which affects response to two hormone types: recombinant FSH (rFSH) and urinary FSH (uFSH). Based on genetic results, rFSH was given to women with the NN genotype, whereas uFSH was given to those carrying the S allele (NS or SS genotypes).
An additional 991 women who weren't genotyped and received hormone therapy based on clinical routine served as the control group.
In the genotype-guided group, the cumulative pregnancy rate was 51% compared with 40% in controls. The live birth rate was 40% vs 29%, respectively. After adjusting for age, body mass index, and fertilization method, the rate of live birth was higher in the matched group (adjusted odds ratio = 1.55, 95% confidence interval = 1.23–1.96, P < .001).
The researchers also evaluated ovarian response. Among the women with the NN genotype, those who received rFSH had 33% more oocytes retrieved compared with those who received uFSH. In contrast, S-allele carriers had improved pregnancy outcomes with uFSH, though the number of oocytes retrieved didn't significantly differ by hormone type.
To confirm these findings at the molecular level, the team conducted in vitro experiments using genetically modified cells expressing either the N or S variant of the FSH receptor. Stimulation with uFSH led to significantly higher cAMP production in S-variant cells compared with 'with rFSH' (10 IU: 176 vs 39 pmol/mg, P = .002), supporting the clinical results.
“This genetic variant can be utilized in the choice of hormone type prior to IVF,” said lead study author Ida Hjelmér, of Lund University in Malmö, Sweden, and colleagues.
The miscarriage rate in the genotype-guided group was 7%, compared with 10% in controls. The incidence of severe ovarian hyperstimulation syndrome was 0.6%. The study excluded women with conditions such as polycystic ovary syndrome or endometriosis. The researchers noted that the results may not generalize to those populations.
The findings supported a precision medicine approach in fertility care. A low-cost genetic test could optimize hormone selection, potentially reducing the number of IVF cycles required and improving overall success rates.
With demand for assisted reproduction continuing to rise, even modest improvements in birth rates could translate into thousands of additional live births annually, the researchers concluded.
Full disclosures can be found in the published study.
Source: Frontiers in Endocrinology