Prospects for FSH Treatment of Male Infertility

Context: Despite the new opportunities provided by assisted reproductive technology (ART), 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 follicle-stimulating hormone (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 ART 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 treatment plans for male infertility have been borrowed from hypogonadism, without daring to overstimulate, as is done in women undergoing ART. FSH effectiveness depends not only on its serum levels, but also on individual genetic variants able to determine hormonal levels, activity, and receptor response. Single-nucleotide polymorphisms in the follicle- stimulating hormone subunit beta (FSHB) and follicle-stimulating hormone receptor (FSHR) genes have been described, with some of them affecting testicular volume and sperm output. The FSHR p.N680S and the FSHB –211G>T variants could be genetic markers 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 the FSHB-FSHR haplotype, are needed to define the most effective dosage, the best treatment length, and the criteria to select candidate responder patients.