Involvement of single nucleotide polymorphisms in ovarian poor response

J Assist Reprod Genet. 2021 Sep;38(9):2405-2413. doi: 10.1007/s10815-021-02242-w. Epub 2021 May 29.


Purpose: Unpredictability in acquiring an adequate number of high-quality oocytes following ovarian stimulation is one of the major complications in controlled ovarian hyperstimulation (COH). Genetic predispositions of variations could alter the immunological profiles and consequently be implicated in the variability of ovarian response to the stimulation.

Design: Uncovering the influence of variations in AMHR2, LHCGR, MTHFR, PGR, and SERPINE1 genes with ovarian response to gonadotrophin stimulation in COH of infertile women.

Methods: Blood samples of the women with a good ovarian response (GOR) or with a poor ovarian response (POR) were collected. Genomic DNA was extracted, and gene variations were genotyped by TaqMan SNP Genotyping Assays using primer-probe sets or real-time PCR Kit.

Results: Except for PGR (rs10895068), allele distributions demonstrate that the majority of POR patients carried minor alleles of AMHR2 (rs2002555, G-allele), LHCGR (rs2293275, G-allele), MTHFR (rs1801131, C-allele, and rs1801133, T-allele), and SERPINE1 (rs1799889, 4G allele) genes compared to the GOR. Similarly, genotypes with a minor allele in AMHR2, LHCGR, MTHFR, and SERPINE1 genes had a higher prevalence among POR patients with the polymorphic genotypes. However, further genotype stratification indicated that the minor alleles of these genes are not associated with poor response. Multivariate logistic analysis of clinical-demographic factors and polymorphic genotypes demonstrated a correlation between FSH levels and polymorphic genotypes of SERPINE1 in poor response status.

Conclusions: Despite a higher prevalence of AMHR2, LHCGR, MTHFR, and SERPINE1 variations in the patients with poor ovarian response, it seems that these variations are not associated with the ovarian response.

Keywords: Assisted reproductive technology; Genetic variations; Infertility; Ovarian poor response.

MeSH terms

  • Adult
  • Female
  • Fertilization in Vitro
  • Genetic Predisposition to Disease
  • Genotype
  • Gonadotropins / pharmacology*
  • Humans
  • Infertility, Female / drug therapy
  • Infertility, Female / genetics
  • Infertility, Female / pathology*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Nuclear Proteins / genetics
  • Ovarian Hyperstimulation Syndrome / genetics
  • Ovarian Hyperstimulation Syndrome / physiopathology*
  • Ovarian Reserve / drug effects*
  • Ovulation Induction / statistics & numerical data*
  • Plasminogen Activator Inhibitor 1 / genetics
  • Polymorphism, Single Nucleotide*
  • RNA, Long Noncoding / genetics
  • Receptors, LH / genetics


  • Gonadotropins
  • Intracellular Signaling Peptides and Proteins
  • LHCGR protein, human
  • MRFAP1 protein, human
  • Nuclear Proteins
  • Plasminogen Activator Inhibitor 1
  • RNA, Long Noncoding
  • Receptors, LH
  • SERPINE1 protein, human
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)