Endocrine DOI 10.1007/s12020-016-1037-z ORIGINAL ARTICLE FSH treatment in infertile males candidate to assisted reproduction improved sperm DNA fragmentation and pregnancy rate Andrea Garolla 1 ● Marco Ghezzi 1 ● Ilaria Cosci 1 ● Barbara Sartini 1 ● Alberto Bottacin 1 ● Bruno Engl 2 ● Andrea Di Nisio 1 ● Carlo Foresta 1 Received: 3 May 2016 / Accepted: 23 June 2016 © Springer Science+Business Media New York 2016 Abstract 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 treat- ment (cases) and 82 refused treatment (controls). Semen parameters, sexual hormones, and sperm nucleus (fluores- cence 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 fragmenta- tion 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. Keywords FSH treatment ● IVF/ICSI outcome ● Male Infertility ● Sperm DNA damage Introduction A multicentre study on couple infertility found that in 20 % of cases the problem was predominantly male and in 27 % abnormalities were found in both partners [1]. Since the introduction of assisted reproduction techniques (ARTs), such as intrauterine insemination (IUI) and in-vitro fertili- zation (IVF), it has been possible to successfully treat couples with mild or severe male factor infertility. How- ever, despite many years of technological improvements, both clinical pregnancy and live birth rates remain relatively low at ~35 and 25 % per started cycle, respectively [2]. In particular, it has been frequently reported that ARTs have * Andrea Garolla andrea.garolla@unipd.it 1 Unit of Andrology and Reproductive Medicine, Department of Medicine, University of Padova, via Modena 9, Padova 35121, Italy 2 Obstetrics and Gynecology Unit, Azienda Sanitaria Alto Adige, via Ospedale 11, Brunico 39031, Italy Electronic supplementary material The online version of this article (doi:10.1007/s12020-016-1037-z) contains supplementary material, which is available to authorized users.