14-05-2025
Genotype-Based FSH Choice Boosts IVF Outcomes
Follicle-stimulating hormone receptor (FSHR) N680S–genotyped women treated with either recombinant FSH or urinary FSH had higher pregnancy rates of 51% vs 40% in non-genotyped control individuals. This personalized approach also improved cumulative live birth rates to 40% vs 29% in non-genotyped control individuals.
METHODOLOGY:
A total of 475 women undergoing in vitro fertilization (IVF) were randomized to receive either recombinant FSH or urinary FSH for ovarian stimulation, with their FSHR N680S variant analyzed afterward.
Researchers compared outcomes between 221 optimally treated women (based on FSHR genotype) and 991 non-genotyped control individuals, with adjustment for age, body mass index, and fertilization method.
Clinical data were supported by laboratory experiments where COS-1 cells were transfected with homozygous FSHR variants and stimulated with either urinary FSH or recombinant FSH to evaluate receptor activity.
Primary outcomes were cumulative pregnancy rates and clinical live birth rates for all treatments related to the first ovarian stimulation cycle.
TAKEAWAY:
Women who underwent genotype-guided FSH selection showed significantly higher pregnancy rates (51% vs 40%; odds ratio [OR], 1.40; 95% CI, 1.12-1.75; P = .003) and live birth rates (40% vs 29%; OR, 1.55; 95% CI, 1.23-1.96; P < .001) than non-genotyped control individuals.
= .003) and live birth rates (40% vs 29%; OR, 1.55; 95% CI, 1.23-1.96; < .001) than non-genotyped control individuals. Urinary FSH proved optimal for S-allele carriers, while recombinant FSH showed better results for asparagine homozygous carriers, with 33% more oocytes retrieved in NN-genotype women treated with recombinant FSH.
In vitro experiments revealed the S variant displayed higher extracellular cyclic adenosine monophosphate when stimulated with urinary FSH vs recombinant FSH (10 IU: 176 vs 39 pmol/mg; P = .002; 90 IU: 227 vs 58 pmol/mg; P = .007).
IN PRACTICE:
'In the context of applying precision medicine to OS [ovarian stimulation] prior to IVF, the most important finding was an 11% higher CLBR [cumulative life birth rate] in the first OS cycle in women who had been treated with the type of FSH that best matched their FSHR N680S genotype as compared to non-genotyped controls,' the authors of the study wrote.
SOURCE:
The study was led by Ida Hjelmér, Department of Translational Medicine, Lund University, Malmö, Sweden. It was published online in Frontiers in Endocrinology .
LIMITATIONS:
The study was not sufficiently powered to evaluate the effect of the precision medicine concept on miscarriage or ovarian hyperstimulation syndrome risk. Results cannot be extrapolated to women with polycystic ovary syndrome, endometriosis, or other excluded conditions. The study comprised only women undergoing their first ovarian stimulation cycle, limiting its applicability to those requiring multiple treatments.
DISCLOSURES:
The study was funded by EU Interreg NYPS 20201846 and an ALF government grant. Aleksander Giwercman reported receiving an unrestricted grant from Ferring Pharmaceuticals to the ReproUnion research network and a lecture fee from Merck Serono. Additional disclosures are noted in the original article.
