PurposeGenetic variation may influence women’s response to ovarian stimulation therapy. The purpose of this study was to investigate any effects of genetic variants in the anti-Müllerian hormone (AMH) and AMH type II receptor genes on ovarian response/treatment outcomes and on current markers of ovarian reserve in individuals undergoing in vitro fertilisation (IVF) treatment.MethodsIn this prospective observational study, we genotyped the AMH c.146G>T, p.(Ile49Ser) and AMHR2 -482A>G variants in 603 unrelated women undergoing their first cycle of controlled ovarian stimulation for IVF and ICSI (intracytoplasmic sperm injection) using gonadotrophins at a tertiary referral centre for reproductive medicine. Pelvic ultrasound and blood hormone levels were taken on days 2–3 of the cycle. Genotypes were determined using TaqMan allelic discrimination assay. Regression analysis was performed to assess the relationship between the genotypes and the ovarian reserve markers (FSH, AMH, antral follicle count) and the early outcomes of response (number of oocytes retrieved and gonadotropin dose) as well as the treatment outcome (live birth).ResultsThere were no significant associations between the variants AMH c.146G>T and AMHR2 -482A>G with ovarian response in terms of number of oocytes retrieved (p = 0.08 and p = 0.64, respectively), live births (p = 0.28 and p = 0.52) and/or markers of ovarian reserve.ConclusionsGenotyping of the AMH c.146G>T and AMHR2 -482A>G polymorphisms does not provide additional useful information as a predictor of ovarian reserve or ovarian response and treatment outcomes.

Perrault syndrome (PS) is a genetically heterogeneous disorder characterized by primary ovarian insufficiency (POI) in females and sensorineural hearing loss in males and females. In many PS subjects, causative variants have not been found in the five reported PS genes. The objective of this study was to identify the genetic cause of PS in an extended consanguineous family with six deaf individuals. Whole exome sequencing (WES) was completed on four affected members of a large family, and variants and co-segregation was confirmed by Sanger sequencing. All hearing impaired individuals, including the proband, are homozygous for a pathogenic variant of CLDN14, but this only explains the deafness. The PS proband is also homozygous for a frameshift variant (c.1453_1454delGA, p.Glu485Lysfs*5) in exon 7 of SGO2 encoding shugoshin 2, which is the likely cause of her concurrent ovarian insufficiency. In mouse, Sgol2a encoding shugoshin-like 2a is necessary during meiosis in both sexes to maintain the integrity of the cohesin complex that tethers sister chromatids. Human SGO2 has not previously been implicated in any disorder, but in this case of POI and perhaps others, it is a candidate for unexplained infertility.

Previous studies have suggested an association between a variant in the promoter region of the FSHR gene and diminished response to controlled ovarian hyperstimulation (COH) in women undergoing assisted reproduction. FSHR -29G>A was genotyped in 559 women undergoing their first cycle of COH for IVF/intracytoplasmic sperm injection (ICSI) using TaqMan allelic discrimination assay. Correlation and regression analysis was performed to assess the relationship between FSHR promoter genotypes and markers of ovarian reserve and measures of response to COH, including the number of oocytes retrieved, gonadotrophin dose used and the live-birth rate. There were no statistically significant differences between the genotype frequencies and the markers of ovarian reserve or the early measures of response to COH. However, the live-birth rate was higher for women carrying the variant A allele (odds ratio [OR] 1.37; 95% confidence interval [CI] 1.02-1.84 per allele). This relationship did not reach statistical significance after adjustment for the number of embryos transferred (OR 1.33; 95% CI 0.98-1.83 per allele). Results from this study do not provide evidence that the FSHR -29G>A variant can be used in the individualization of the treatment protocol for women undergoing IVF/ICSI.