Garolla Andrea, Ghezzi Marco, Cosci Ilaria, Sartini Barbara, Bottacin Alberto, Engl Bruno, Di Nisio Andrea, Foresta Carlo
Unit of Andrology and Reproductive Medicine, Department of Medicine, University of Padova, via Modena 9, Padova, 35121, Italy.
Obstetrics and Gynecology Unit, Azienda Sanitaria Alto Adige, via Ospedale 11, Brunico, 39031, Italy.
Endocrine. 2017 May;56(2):416-425. doi: 10.1007/s12020-016-1037-z. Epub 2016 Jul 27.
The purpose of this study is to evaluate whether follicle-stimulating hormone treatment improves sperm DNA parameters and pregnancy outcome in infertile male candidates to in-vitro fertilization.Observational study in 166 infertile male partners of couples undergoing in-vitro fertilization. Eighty-four patients were receiving follicle-stimulating hormone treatment (cases) and 82 refused treatment (controls). Semen parameters, sexual hormones, and sperm nucleus (fluorescence in-situ hybridization, acridine orange, TUNEL, and γH2AX) were evaluated at baseline (T0) and after 3 months (T1), when all subjects underwent assisted reproduction techniques. Statistical analysis was performed by analysis of variance.Compared to baseline, cases showed significant improvements in seminal parameters and DNA fragmentation indexes after follicle-stimulating hormone therapy (all P < 0.05), whereas no changes were observed in controls. Within cases, follicle-stimulating hormone treatment allowed to perform intrauterine insemination in 35 patients with a pregnancy rate of 23.2 %. Intracytoplasmic sperm injection was performed in all controls and in 49 patients from cases, with pregnancy rates of 23.2 and 40.8 %, respectively (P < 0.05). After 3 months (T0 vs. T1) of follicle-stimulating hormone therapy, cases with positive outcome had reduced DNA fragmentation index and lower double strand breaks (P < 0.05 and P < 0.001 vs. negative outcome, respectively).In this observational study, we showed that follicle-stimulating hormone treatment improves sperm DNA fragmentation, which in turn leads to increased pregnancy rates in infertile males undergoing in-vitro fertilization. In particular, double strand breaks (measured with γH2AX test) emerged as the most sensible parameter to follicle-stimulating hormone treatment in predicting reproductive outcome.
本研究的目的是评估促卵泡激素治疗是否能改善体外受精男性不育候选者的精子DNA参数和妊娠结局。对166对接受体外受精夫妇的男性不育伴侣进行观察性研究。84例患者接受促卵泡激素治疗（病例组），82例拒绝治疗（对照组）。在基线时（T0）和3个月后（T1）评估精液参数、性激素和精子细胞核（荧光原位杂交、吖啶橙、TUNEL和γH2AX），此时所有受试者均接受辅助生殖技术。采用方差分析进行统计分析。与基线相比，病例组在促卵泡激素治疗后精液参数和DNA碎片化指数有显著改善（均P<0.05），而对照组未观察到变化。在病例组中，促卵泡激素治疗使35例患者能够进行宫内人工授精，妊娠率为23.2%。所有对照组和病例组中的49例患者进行了卵胞浆内单精子注射，妊娠率分别为23.2%和40.8%（P<0.05）。促卵泡激素治疗3个月后（T0与T1），妊娠结局为阳性的病例组DNA碎片化指数降低，双链断裂减少（分别与阴性结局相比，P<0.05和P<0.001）。在这项观察性研究中，我们表明促卵泡激素治疗可改善精子DNA碎片化，进而提高接受体外受精的男性不育者的妊娠率。特别是，双链断裂（用γH2AX试验测量）成为促卵泡激素治疗预测生殖结局最敏感的参数。
