Functional genetic polymorphisms and female reproductive disorders: Part I: Polycystic ovary syndrome and ovarian response

Hum Reprod Update. 2008 Sep-Oct;14(5):459-84. doi: 10.1093/humupd/dmn024. Epub 2008 Jul 4.

Abstract

Background: The identification of polymorphisms associated with a disease can help to elucidate its pathogenesis, and this knowledge can be used to improve prognosis for women with a particular disorder, such as polycystic ovary syndrome (PCOS). Since an altered response to ovarian stimulation is also a characteristic of the disease, further knowledge about its aetiology could help in defining the parameters that determine the response of an individual to ovarian stimulation.

Methods: PubMed and EMBASE databases were systematically searched for gene association studies published until the end of August 2007, using search criteria relevant to PCOS and ovarian response to stimulation. Data from additional papers identified through hand searches were also included; 139 publications were reviewed.

Results: Several genes involved in ovarian function and metabolism are associated with increased susceptibility to PCOS, but none is strong enough to correlate alone with susceptibility to the disease, or response to therapy. A single-nucleotide polymorphism in exon 10 of the FSH receptor (FSHR) gene, FSHR p.N680S, was consistently identified as having a significant association with ovarian response to FSH.

Conclusions: No consistent association between gene polymorphism and PCOS could be identified. The FSHR gene may play a significant role in the success of ovarian stimulation, and can be used as a marker to predict differences in FSHR function and ovarian response to FSH. Genotyping the FSHR p.N680S polymorphism may provide a means of identifying a population of poor responders before in vitro fertilization procedures are initiated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cardiovascular Diseases / genetics
  • Chromosomes, Human, Pair 2
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Gonadal Steroid Hormones / blood
  • Gonadal Steroid Hormones / genetics
  • Gonadal Steroid Hormones / metabolism
  • Gonadotropins / pharmacology
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Menstrual Cycle / blood
  • Ovary / drug effects
  • Ovulation Induction
  • Polycystic Ovary Syndrome / enzymology
  • Polycystic Ovary Syndrome / epidemiology
  • Polycystic Ovary Syndrome / genetics*
  • Polymorphism, Genetic*
  • Pregnancy
  • Pregnancy Rate
  • Receptors, FSH / genetics

Substances

  • Gonadal Steroid Hormones
  • Gonadotropins
  • Intercellular Signaling Peptides and Proteins
  • Receptors, FSH