Impact of follicle stimulating hormone receptor variants in fertility

Genetic variation plays a crucial role in modification of normal or disease pathophysiology. Follicle stimulating hormone receptor (FSHR) signaling is necessary for normal development and function of the ovaries and testes. Here, we review the associations between FSHR polymorphisms and fertility or subfertility.

FSHR polymorphisms consist of single nucleotide changes within the coding and regulatory regions and/or alternatively spliced products. Most of the investigations focused on two single nucleotide polymorphisms (SNPs) in the coding region of the receptor, which result in amino acid changes (p.307Thr/Ala, p.680Asn/Ser). In women, these SNPs were associated with variable response to ovarian stimulation with FSH during infertility treatment. Not all studies revealed an association, and those that did showed a small effect. Alternative splice variants of the receptor affecting the extracellular domain without causing a frameshift have been found in women undergoing ovarian stimulation, and in infertile men. Associations with polycystic ovary syndrome, premature ovarian failure, osteoporosis, and cancer found small effect.

The identification of FSHR variants in a select infertility patient population has significant clinical implications in demonstrating a possible genetic cause to female infertility and improves our understanding of the genetic basis of infertility as a whole. Pharmacogenomics is a new field aiming to devise individualized treatments for disorders based on the genetic signature of the patients.