Genetic predictors of controlled ovarian hyperstimulation: where do we stand today?

Hum Reprod Update. 2011 Nov-Dec;17(6):813-28. doi: 10.1093/humupd/dmr034. Epub 2011 Aug 23.

Abstract

Background: Nowadays, the use of IVF has improved the prospects of infertility treatment. The expected outcome of IVF depends greatly on the effectiveness of controlled ovarian hyperstimulation (COH), where exogenous gonadotrophins are used to induce folliculogenesis. The response to stimulation varies substantially among women and is difficult to predict. Several predictive markers of COH outcome have been proposed (e.g. maternal age and ovarian reserve), but the search for optimal predictors is ongoing. Pharmacogenetic studies demonstrate the effects of individual genetic variability on COH outcome and the potential for customizing therapy based on the patient's genome.

Methods: MEDLINE, EMBASE, DARE, CINAHL and the Cochrane Library, and references from relevant articles were investigated up to February 2011 regarding any common genetic variation and COH/IVF outcome.

Results: Several polymorphisms in genes involved in FSH signalling, estrogen biosynthesis, folliculogenesis, folate metabolism and other aspects influence the response to exogenous gonadotrophin administration, resulting in differences in COH and IVF outcomes. Nevertheless, the most studied polymorphism FSHR Asn680Ser is practically the only genetic marker, together with ESR1 PvuII T/C, that could be applied in clinical tests.

Conclusions: Although data are accumulating with evidence suggesting that the ovarian response to COH is mediated by various polymorphisms, the optimal biomarkers and the efficacy of the tests still remain to be evaluated.

Publication types

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

MeSH terms

  • Aromatase / genetics
  • Cholesterol Side-Chain Cleavage Enzyme / genetics
  • Female
  • Fertilization in Vitro / methods
  • Folic Acid / metabolism
  • Genetic Markers
  • Genome-Wide Association Study
  • Humans
  • Infertility, Female / genetics
  • Infertility, Female / metabolism
  • Infertility, Female / therapy
  • Luteinizing Hormone, beta Subunit / genetics
  • Metabolic Networks and Pathways / genetics
  • Ovulation Induction / methods*
  • Pharmacogenetics
  • Polymorphism, Genetic
  • Pregnancy
  • Receptors, Estrogen / genetics
  • Receptors, FSH / genetics
  • Receptors, LH / genetics
  • Receptors, Progesterone / genetics
  • Transforming Growth Factor beta / genetics

Substances

  • Genetic Markers
  • Luteinizing Hormone, beta Subunit
  • Receptors, Estrogen
  • Receptors, FSH
  • Receptors, LH
  • Receptors, Progesterone
  • Transforming Growth Factor beta
  • Folic Acid
  • Aromatase
  • Cholesterol Side-Chain Cleavage Enzyme