Variants Ala307Ala and Ser680Ser of 307 and 680 FSHr polymorphisms negatively influence on assisted reproductive techniques outcome and determine high probability of non-pregnancy in Caucasian patients

J Assist Reprod Genet. 2021 Oct;38(10):2769-2779. doi: 10.1007/s10815-021-02276-0. Epub 2021 Aug 3.

Abstract

Purpose: To determine the influence of different genotypes of Ala307Thr and Asn680Ser FSHr polymorphisms on controlled ovarian stimulation (COS) outcome and pregnancy.

Methods: This study collected blood and physiological and clinical parameters of 517 Caucasian patients (Statistical power ≥ 80%) that underwent COS treatment. Genotypes of Ala307Thr and Asn680Ser polymorphisms were determined using PCR amplification followed by Bsu36I and BsrI digestion, respectively.

Results: Ala307Ala and Ser680Ser genotypes associated to worse parameters of COS outcome (preovulatory follicles P = 0.05, in both), justifying their lower pregnancy rate than Non-Ala307Ala, P = 0.01 and Non-Ser680Ser, P = 0.004, respectively or together, (P = 0.003). Within the Non-Ala307Ala group, Thr307Thr genotype showed higher number of fertilized oocytes (P = 0.04) and embryos (P = 0.01) than Non-Thr307Thr, but no influence on pregnancy rate. Ala307Ala and Ser680Ser patients doubled probability of non-pregnancy than Non-Ala307Ala (odds ratio = 2.0) and Non-Ser680Ser (odds ratio = 2.11), respectively. Ala307Ala and Ser680Ser genotypes tend to appear together (P < 0.0001), which increases the probability of non-pregnancy.

Conclusions: Ala307Ala and Ser680Ser genotypes of 307 and 680 FSHr polymorphisms associate to worse COS outcome than its respective Non-Ala307Ala and Non-Ser680Ser. Within the Non-Ala307Ala genotypes, Thr307Thr, although shows higher Fertilized Oocytes and Embryos, do not influence on pregnancy rate. Ala307Ala and Ser680Ser genotypes double the probability of Non-Pregnancy than their respective Non-Ala307Ala and Non-Ser680Ser genotypes. Furthermore, the strong tendency of these genotypes to appear together worsens the probability of pregnancy in these patients.

Keywords: Ala307Thr polymorphism;; Asn680Ser polymorphism; Assisted reproductive techniques;; Controlled ovarian stimulation (COS);; FSHr polymorphisms;.

MeSH terms

  • Adult
  • Female
  • Humans
  • Infertility, Female / genetics
  • Infertility, Female / pathology
  • Infertility, Female / therapy*
  • Ovulation Induction / statistics & numerical data*
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Pregnancy Rate*
  • Receptors, FSH / genetics*
  • Reproductive Techniques, Assisted / adverse effects*

Substances

  • FSHR protein, human
  • Receptors, FSH