Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy.
J Clin Endocrinol Metab. 2020 Jul 1;105(7). doi: 10.1210/clinem/dgaa243.
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.
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.
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.
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.
尽管辅助生殖技术（ART）提供了新的机会，但男性不育症的治疗还远未得到优化。一种可能性是基于病理生理学证据，用促性腺激素刺激生精。
我们对截至 2020 年 1 月评估卵泡刺激素（FSH）作用的遗传基础、FSH 在生精中的作用以及其在男性不育中的给药效果的研究进行了全面的系统PubMed 文献综述。只要相关，我们还评估了遗传多态性和 FSH 给药在接受 ART 的女性中的作用的文献。
FSH 治疗已成功用于促性腺激素低下性性腺功能减退症，但在特发性男性不育症中的效果存在疑问。这种方法的局限性在于，男性不育症的治疗方案是从性腺功能减退症中借鉴而来的，而不敢像在接受 ART 的女性中那样过度刺激。FSH 的有效性不仅取决于其血清水平，还取决于能够确定激素水平、活性和受体反应的个体遗传变异。已经描述了卵泡刺激素亚基β（FSHB）和卵泡刺激素受体（FSHR）基因中的单核苷酸多态性，其中一些多态性影响睾丸体积和精子输出。FSHR p.N680S 和 FSHB-211G>T 变体可能是预测 FSH 反应的遗传标志物。
FSH 可能有助于增加不育男性的精子生成，即使推荐在这种情况下使用 FSH 的证据较弱。需要进行安慰剂对照临床试验，考虑到 FSHB-FSHR 单倍型，以确定最有效的剂量、最佳治疗长度以及选择候选反应者患者的标准。
