Casamonti E, Vinci S, Serra E, Fino M G, Brilli S, Lotti F, Maggi M, Coccia M E, Forti G, Krausz C
Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
Center for Artificial Reproductive Techniques, University of Florence, Florence, Italy.
Andrology. 2017 May;5(3):414-422. doi: 10.1111/andr.12333. Epub 2017 Mar 15.
The standard FSH treatment is based on a 3 months period, after which both quantitative/qualitative improvement of sperm parameters and increased pregnancy rate were reported. In this prospective clinical trial, for the first time, we studied (i) Sperm hyaluronic acid binding capacity after highly purified FSH (hpFSH) treatment; (ii) the effect after short-term and standard treatment on this functional parameter. As secondary objective, we analyzed three SNPs on FSHβ and FSHR genes to define their potential predictive value for responsiveness. From a total of 210 consecutive patients, 40 oligo- and/or astheno- and/or teratozoospermic patients fulfilled the inclusion criteria. Treatment consisted in hpFSH 75 IU/L every other day for 3 months. To avoid potential biases derived from the lack of placebo, we analyzed each patient after 4-6 months of 'wash-out' period. After FSH treatment, we observed a statistically significant (p < 0.001) improvement of the percentage of hyaluronic acid bound spermatozoa from basal to T1 (after 1 month) and to T3 (after 3 months). Importantly, these values returned to near-baseline value after the wash-out. The same results were detected for total motile sperm count after 3 months with return to baseline after wash-out. Forty-two percent of patients responded to the therapy with increasing hyaluronic acid binding capacity above the double of the Intraindividual Variation (IV) while 24% of patients reached above the normal Sperm-Hyaluronan Binding Assay (HBA) value. Further increase in 'responders' was observed at T3. The responsiveness to treatment resulted independent from FSHR/FSHβ polymorphisms. The significant positive effect on sperm maturity after 1 month opens novel therapeutic perspectives. In view of both the high cost and the relative invasiveness of treatment, the short protocol (1 month) could represent a viable FSH treatment option prior Assisted Reproductive Techniques since FSH, by acting on sperm maturation, increases the proportion of functionally competent cells.
标准的促卵泡激素（FSH）治疗为期3个月，之后报告精子参数在数量和质量上均有所改善，妊娠率也有所提高。在这项前瞻性临床试验中，我们首次研究了：（i）高纯度FSH（hpFSH）治疗后精子透明质酸结合能力；（ii）短期和标准治疗对该功能参数的影响。作为次要目标，我们分析了FSHβ和FSHR基因上的三个单核苷酸多态性（SNP），以确定它们对反应性的潜在预测价值。在总共210例连续患者中，40例少精子症和/或弱精子症和/或畸形精子症患者符合纳入标准。治疗方案为每隔一天注射75 IU/L的hpFSH，持续3个月。为避免因缺乏安慰剂而产生潜在偏差，我们在“洗脱”期4至6个月后对每位患者进行了分析。FSH治疗后，我们观察到从基线到T1（1个月后）和T3（3个月后），透明质酸结合精子百分比有统计学意义的显著改善（p < 0.001）。重要的是，洗脱后这些值恢复到接近基线值。3个月后总活动精子数也得到了相同结果，洗脱后恢复到基线。42%的患者对治疗有反应，其透明质酸结合能力增加超过个体内变异（IV）的两倍，而24%的患者达到高于正常精子-透明质酸结合试验（HBA）值。在T3时观察到“反应者”进一步增加。治疗反应性与FSHR/FSHβ多态性无关。1个月后对精子成熟有显著的积极作用，这开辟了新的治疗前景。鉴于治疗成本高且具有相对侵入性，短疗程（1个月）可能是辅助生殖技术之前可行的FSH治疗选择，因为FSH通过作用于精子成熟，增加了功能正常细胞的比例。
