FSH treatment of male idiopathic infertility: Time for a paradigm change

Abstract

Follicle-stimulating hormone (FSH) has been used in inconclusive clinical trials for male idiopathic infertility in the past. FSH is sometimes prescribed empirically for male idiopathic infertility, showing some improvement in sperm parameters in about half of the patients. In this opinion article, we briefly analyze the pathophysiological evidences in favor of a more aggressive approach in planning future studies on pharmacological FSH use in male infertility, in analogy with the FSH use for multiple follicular growth in women undergoing ovarian stimulation for assisted reproduction. There is sufficient evidence that spermatogenesis does not run at its top in the primate and that some extra FSH can stimulate spermatogenesis over its baseline.Existing data suggest that the pharmacological regimens applied so far were insufficient, both in dosage and in duration, to elicit this response in about half of the patients. A paradigm change is needed now: We should move away from the classical, endocrinological approach, which simply applied the substitutive, therapeutic regimen used in hypogonadotropic hypogonadism, toward testing a 'testicular hyperstimulation' scheme for a time sufficient to cover more than only one spermatogenic cycle, a concept to be verified in an appropriately controlled, prospective, randomized clinical trial. K E Y W O R D SFSH, follicle-stimulating hormone, male infertility

Follicle-Stimulating Hormone (FSH) Action on Spermatogenesis: A Focus on Physiological and Therapeutic Roles

“…A recent Italian nation-wide survey evaluated the idiopathic male infertility management, detecting an FSH prescription rate of 55% [5]. Although this study was not designed to detect FSH efficacy in male infertility, it showed a slight increase in semen parameters in about half of the treated men, confirming the need for properly designed larger clinical trials in this setting [5,52].…”

“…However, qualitatively and quantitatively adequate spermatogenesis requires FSH action and high intratesticular testosterone levels, acting in additive and synergistic ways [51]. These data provide new perspectives in the therapeutic approaches to male infertility, similar to what is currently done in women undergoing ART [52].…”

“…On the other hand, most favorable genetic haplotypes could be sufficiently stimulated with the current empirical FSH therapeutic regimens. Thus, new, comprehensive approaches, connecting the genetic background to spermatogenesis and treatment response, are required [52].…”

FSH for the Treatment of Male Infertility

“…Moreover, this approach has the limitation of relatively high costs and off-label usage [114], so that only limited clinical data are available [112,113]. To date, seventeen clinical trials evaluated FSH use in idiopathic infertile men and were listed in an opinion article [115], obtaining different results. These data were recently meta-analyzed and suggested that the use of FSH may increase overall pregnancy rates, which, however, was never considered as the primary end point in the original studies [116,117].…”

The effect of rhFSH on Sperm DNA Fragmentation and sperm parameters in Oligozoospermia Infertile Men

“…A semen sample will be taken from 50 infertile men that referred to highly specialized infertility treatment center of ACECR (academic center of education, culture, and research, Qom Branch). The inclusion criteria were the low level of FSH (<1.7 mIU/mL), aged 25-45 years, history of infertility for at least 2 years, sperm concentration <15×106 (oligozoospermia) according to 2010 World Health Organization criteria [13,14]. Under the supervision of a urologist, all enrolled patients received subcutaneous recombinant FSH (Gonal-f) treatment, 75 IU every other day, starting from Visit 1, for three months, three times a week.…”