Role of gene polymorphisms related to progesterone elevation in women undergoing long GnRH agonist protocols

Can single-nucleotide polymorphisms (SNP) of genes related to progesterone synthesis predict the risk of premature serum progesterone elevation in women undergoing gonadotrophin-releasing hormone agonist protocols for ovarian stimulation?

A total of 765 women were divided into high progesterone and normal progesterone groups according to progesterone concentration on the day of human chorionic gonadotrophin (HCG) administration, with the 75th percentile as the threshold between the group. Associations were analysed of genetic information from whole exome sequencing and the clinical characteristics of the two groups to identify the relationship between SNP, haplotypes and serum progesterone elevation.

Among 40 common SNP of eight genes (FSHR, LHCGR, ESR1, ESR2, PGR, HSD3B1, CYP11A1 and CYP17A1), no statistical significance between the high and normal progesterone groups was identified in the distribution of genotypes and allele frequencies after multiple test correction to adjust the false discovery rate (P_FDR > 0.05). When compared with the most common haplotypes of each gene, haplotype GAAG in CYP17A1 was associated with a 1.44-fold increased risk of progesterone elevation (95% confidence interval [CI] 1.22-1.69, P_FDR < 0.001), while haplotypes of the following genes showed a decreased risk of progesterone elevation: haplotype CC in FSHR and LHCGR (0.66-fold, P_FDR = 0.020, and 0.64-fold, P_FDR < 0.001, respectively), CA in ESR1 (0.90-fold, P_FDR < 0.001), TCTGG in ESR2 (0.92-fold, P_FDR = 0.007) and GAACC in HSD3B1 (0.42-fold, P_FDR < 0.001).

Polymorphism in genes involved in enzymes or hormone receptors in the progesterone synthesis pathway may have a role in modifying risk of serum progesterone elevation.