Santi Daniele, Scafa Raffaele, Spaggiari Giorgia, Grande Giuseppe, Romeo Marilina, Dalla Valentina Leonardo, Graziani Andrea, Granata Antonio Raffaele Michele, Garolla Andrea, Simoni Manuela, Ferlin Alberto
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 Endocrinol Invest. 2025 Sep;48(9):2187-2196. doi: 10.1007/s40618-025-02614-4. Epub 2025 Aug 5.
Follicle-stimulating hormone (FSH) therapy improves spermatogenesis, sperm quality, and reproductive outcomes. However, variability in patients' response and limited data on pregnancy rate complicate its extensive application in male idiopathic infertility. The aim of the study was to identify predictors of FSH efficacy in male idiopathic infertility in terms of pregnancy.
A retrospective, observational study was conducted at two Italian clinics from 2019 to 2024, enrolling men with idiopathic infertility, serum FSH < 8 IU/L, treated with FSH. Data were collected at baseline (V0) and at the final follow-up visit (V1) when FSH treatment was discontinued. Different, putative "testicular indexes" (TI) were calculated. Pregnancy rate was defined at ultrasound confirmation of fetus heartbeat.
A total of 84 achieved pregnancy (19%) on 443 patients were recorded. One TI ((FSH + Total testosterone)/bi-testicular volume) was directly related to V0-semen parameters. Significant improvements in sperm concentration (p < 0.001), count (p < 0.001) and motility (p = 0.003) were observed following FSH treatment regardless of pregnancy achievement. Men who achieved pregnancy had lower baseline TI (p = 0.001), larger testicular volume (p = 0.001), and lower FSH concentrations (p = 0.001). Multivariate analysis identified patients' age (B=-0.14, standard error (SE) = 0.05, p = 0.014) and TI (B=-1.51, SE = 0.62, p = 0.015) as significant predictors of pregnancy success.
This real-life study identified a novel TI that predicts response to exogenous FSH stimulation. TI assesses the interstitial compartment function (indicated by testosterone concentrations), spermatogenic potential (FSH concentrations), and target tissue amount (testicular volume). Low baseline TI correlates with a higher likelihood of achieving pregnancy through exogenous FSH stimulation.
促卵泡生成素（FSH）治疗可改善精子发生、精子质量和生殖结局。然而，患者反应的变异性以及妊娠率数据有限，使其在男性特发性不育症中的广泛应用变得复杂。本研究的目的是确定男性特发性不育症中FSH疗效在妊娠方面的预测因素。
2019年至2024年在两家意大利诊所进行了一项回顾性观察研究，纳入患有特发性不育症、血清FSH<8 IU/L且接受FSH治疗的男性。在基线（V0）和停止FSH治疗的最终随访就诊时（V1）收集数据。计算了不同的假定“睾丸指数”（TI）。妊娠率定义为超声确认胎儿心跳时的妊娠率。
在443例患者中，共记录到84例（19%）成功妊娠。一种TI（（FSH+总睾酮）/双侧睾丸体积）与V0精液参数直接相关。无论是否成功妊娠，FSH治疗后精子浓度（p<0.001）、计数（p<0.001）和活力（p=0.003）均有显著改善。成功妊娠的男性基线TI较低（p=0.001）、睾丸体积较大（p=0.001）且FSH浓度较低（p=0.001）。多变量分析确定患者年龄（B=-0.14，标准误（SE）=0.05，p=0.014）和TI（B=-1.51，SE=0.62，p=0.015）是妊娠成功的显著预测因素。
这项真实世界研究确定了一种新的TI，可预测对外源性FSH刺激的反应。TI评估间质功能（以睾酮浓度表示）、生精潜能（FSH浓度）和靶组织量（睾丸体积）。低基线TI与通过外源性FSH刺激实现妊娠的较高可能性相关。
