Prospects for FSH Treatment of Male Infertility.

CONTEXT Despite the new opportunities provided by assisted reproduction techniques, male infertility treatment is far from being optimized. One possibility, based on pathophysiological evidence, is to stimulate spermatogenesis with gonadotropins. EVIDENCE ACQUISITION We conducted a comprehensive systematic PubMed literature review, up to January 2020, of studies evaluating the genetic basis of FSH action, the role of FSH in spermatogenesis, and the effects of its administration in male infertility. Manuscripts evaluating the role of genetic polymorphisms and FSH administration in women undergoing assisted reproduction were considered whenever relevant. EVIDENCE SYNTHESIS FSH treatment has been successfully used in hypogonadotropic hypogonadism, but with questionable results in idiopathic male infertility. A limitation of this approach is that schemes for male infertility have been borrowed from hypogonadism, without daring to overstimulate, as is done in women undergoing assisted reproduction. FSH effectiveness does not depend only on its serum levels, but also on individual, genetic variants able to determine hormonal levels, activity and receptor response. Single-nucleotide polymorphisms (SNPs) in FSHB and FSHR genes have been described, some of them impacting testicular volume and sperm output. The FSHR p.N680S and the FSHB -211G>T variants could be genetic marker to predict FSH response. CONCLUSIONS FSH may be helpful to increase sperm production in infertile men, even if the evidence to recommend the use of FSH in this setting is weak. Placebo-controlled clinical trials, considering FSHB-FSHR haplotype, are needed to define the most effective dosage, the best treatment length and the criteria to select candidate responder patients.