Hormonal Treatment of Men with Nonobstructive Azoospermia: What Does the Evidence Suggest?

Abstract

Hormonal stimulation of spermatogenesis prior to surgery has been tested by some authors to maximize the sperm retrieval yield in patients with nonobstructive azoospermia. Although the rationale of such an approach is theoretically sound, studies have provided conflicting results, and there are unmet questions that need to be addressed. In the present narrative review, we reviewed the current knowledge about the hormonal control of spermatogenesis, the relationship between presurgical serum hormones levels and sperm retrieval rates, and the results of studies investigating the effect of hormonal treatments prior to microdissection testicular sperm extraction. We pooled the available data about sperm retrieval rate in patients with low vs. normal testosterone levels, and found that patients with normal testosterone levels had a significantly higher chance of successful sperm retrieval compared to those with subnormal T levels (OR 1.63, 95% CI 1.08–2.45, p = 0.02). These data suggest that hormonal treatment may be justified in patients with hypogonadism; on the other hand, the available evidence is insufficient to recommend hormonal therapy as standard clinical practice to improve the sperm retrieval rate in patients with nonobstructive azoospermia.

Differential Diagnosis of Azoospermia in Men with Infertility

“…Due to the high baseline levels of endogenous gonadotropins commonly seen in patient with NOA-STF, the relative amplitudes of FSH and LH are low, leading to a paradoxically weak stimulation of Leydig and Sertoli cells [35,83]. Therefore, there may be a potential role for pharmacotherapy in men with NOA [84,85]. Selective estrogen receptor modulators, aromatase inhibitors, human chorionic gonadotropin (hCG), and FSH have been used off-label to manipulate male reproductive hormones and optimize intratesticular testosterone production [5,84,[86][87][88].…”

“…Due to the high baseline levels of endogenous gonadotropins commonly seen in patient with NOA-STF, the relative amplitudes of FSH and LH are low, leading to a paradoxically weak stimulation of Leydig and Sertoli cells [ 35 , 83 ]. Therefore, there may be a potential role for pharmacotherapy in men with NOA [ 84 , 85 ].…”

“…The goals are to induce recovery of sperm to the ejaculate or improve surgical sperm retrieval rates. Case series and a few cohort studies suggested that these treatments might increase sperm retrieval rates, and in some cases, treatment was associated with the return of minimal numbers of sperm to the ejaculate [ 5 , 84 , 85 , 86 , 87 , 88 ]. Despite that, no randomized controlled trial exists, making it difficult to make clear recommendations on this matter.…”

The Novel Key Genes of Non-obstructive Azoospermia Affect Spermatogenesis: Transcriptomic Analysis Based on RNA-Seq and scRNA-Seq Data

“…; (2) the whole process of spermatogenesis and sperm kinetics of occurrence; (3) endocrine regulation of spermatogenesis; (4) testicular local regulation of spermatogenesis, etc. (Caroppo and Colpi, 2021;Park and Pang, 2021;Rodriguez-Casuriaga and Geisinger, 2021). Differentiating spermatogonia and early primary spermatocyte belong to the representative cells of spermatogenesis during meiosis, so the difference in the expression of these three genes is mainly reflected in the meiosis stage.…”

Endocrine Follow-Up of Men with Non-Obstructive Azoospermia Following Testicular Sperm Extraction

“…There is a lack of strong evidence concerning the superiority of one technique over the other in terms of sperm retrieval, pregnancy rates, and live birth rates. The results depend on NOA causes and testicular histology, the latter being a heterogeneous entity with distinct pathological patterns, ranging from hypospermatogenesis to Sertoli cell-only syndrome (SCOS) [ 5 , 6 , 7 , 8 ]. However, a recent meta-analysis indicates that mTESE has a 1.5 times higher sperm retrieval rate (SRR) compared with cTESE and 2 times higher rate compared with TESA.…”