{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T19:32:03Z","timestamp":1775071923190,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T00:00:00Z","timestamp":1591056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Scientific evidence shows that the administration of follicle-stimulating hormone (FSH) to infertile patients with normal serum FSH concentrations improves sperm parameters in oligozoospermic men. The aim of this study was to evaluate the effects of highly purified urofollitropin (hpFSH) on conventional and bio-functional sperm parameters and on oxidative stress indices in patients with idiopathic infertility. We also evaluated the response to hpFSH on these parameters in relationship to FSHR c. 2039 A\/G and FSHR c. -29 G\/A genotypes. A prospective longitudinal study was conducted on 42 patients with idiopathic male infertility, 23 of whom underwent to FSHR c. 2039 A\/G and FSHR c. -29 G\/A genotyping. Each patient was asked to collect two semen samples before and after administration of 150 IU hpFSH three times a week for 16 weeks. Patients were divided into responders or non-responders based on whether their total sperm count had at least doubled or was less than double at the end of treatment, respectively. Responders showed a significantly higher semen volume, sperm concentration, spermatids, and leukocytes. Non-responders had a significant decrease of the percentage of spermatozoa in early apoptosis after hpFSH administration. Oxidative stress indexes did not differ significantly after FSH administration in both groups. Conventional and bio-functional sperm parameters did not differ in patients with FSHR c. 2039 GG and AA genotypes, and FSHR c. -29 GG genotype both before and after FSH administration. The FSHR c. 2039 and FSHR -29 G\/A genotypes and allelic distribution did not differ between responders and non-responders. FSH showed to be capable of ameliorating sperm parameters in about half patients treated, therefore it may be helpful in patients with idiopathic infertility.<\/jats:p>","DOI":"10.3390\/jcm9061690","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T09:19:27Z","timestamp":1591089567000},"page":"1690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Follicle-Stimulating Hormone Treatment and Male Idiopathic Infertility: Effects on Sperm Parameters and Oxidative Stress Indices according to FSHR c. 2039 A\/G and c. -29 G\/A Genotypes"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2341-0996","authenticated-orcid":false,"given":"Laura M.","family":"Mongio\u00ec","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, Via S. Sofia 78, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5217-9343","authenticated-orcid":false,"given":"Rosita A.","family":"Condorelli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, Via S. Sofia 78, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Alamo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, Via S. Sofia 78, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4599-8487","authenticated-orcid":false,"given":"Rossella","family":"Cannarella","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, Via S. Sofia 78, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2451-1158","authenticated-orcid":false,"given":"Nicol\u00f2","family":"Musso","sequence":"additional","affiliation":[{"name":"Bio-Nanotech Research and Innovation Tower (BRIT), University of Catania, Via S. Sofia 78, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7113-2372","authenticated-orcid":false,"given":"Sandro","family":"La Vignera","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, Via S. Sofia 78, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6950-335X","authenticated-orcid":false,"given":"Aldo E.","family":"Calogero","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, Via S. Sofia 78, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/S0015-0282(16)54367-2","article-title":"Possible role of pure human follicle-stimulating hormone in the treatment of severe male-factor infertility by assisted reproduction: Preliminary report","volume":"55","author":"Acosta","year":"1991","journal-title":"Fertil. Steril."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1093\/oxfordjournals.humrep.a137794","article-title":"Pure human follicle stimulating hormone has a role in the treatment of severe male infertility by assisted reproduction: Norfolk\u2019s total experience","volume":"7","author":"Acosta","year":"1992","journal-title":"Hum. Reprod."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"R46","DOI":"10.1530\/EC-15-0050","article-title":"FSH treatment of male idiopathic infertility improves pregnancy rate: A meta-analysis","volume":"4","author":"Santi","year":"2015","journal-title":"Endocr. Connect."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Barbonetti, A., Calogero, A.E., Balercia, G., Garolla, A., Krausz, C., La Vignera, S., Lombardo, F., Jannini, E.A., Maggi, M., and Lenzi, A. (2018). The use of follicle stimulating hormone (FSH) for the treatment of the infertile man: Position statement from the Italian Society of Andrology and Sexual Medicine (SIAMS). J. Endocrinol. Investig., 41.","DOI":"10.1007\/s40618-018-0843-y"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1093\/humrep\/12.9.1955","article-title":"The effect of follicle stimulating hormone therapy on human sperm structure (Notulaeseminologicae 11)","volume":"12","author":"Baccetti","year":"1997","journal-title":"Hum. Reprod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"588","DOI":"10.2164\/jandrol.111.013326","article-title":"Recombinant human FSH reduces sperm DNA fragmentation in men with idiopathic oligoasthenoteratozoospermia","volume":"33","author":"Colacurci","year":"2012","journal-title":"J. Androl."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1007\/s12020-016-1037-z","article-title":"FSH treatment in infertile males candidate to assisted reproduction improved sperm DNA fragmentation and pregnancy rate","volume":"56","author":"Garolla","year":"2017","journal-title":"Endocrine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1007\/s10815-017-0970-y","article-title":"The -29G\/A FSH receptor gene polymorphism is associated with higher FSH and LH levels in normozoospermic men","volume":"34","author":"Tamburino","year":"2017","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1007\/s10815-017-0896-4","article-title":"Impact of the FSHB gene -211G\/T polymorphism on male gonadal function","volume":"34","author":"Tamburino","year":"2017","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_10","first-page":"747","article-title":"Effects of highly purified follicle-stimulating hormone on sperm DNA damage in men with male idiopathic subfertility: A pilot study","volume":"34","author":"Palomba","year":"2011","journal-title":"J. Endocrinol. Investig."},{"key":"ref_11","unstructured":"WHO (2010). Laboratory Manual for the Examination and Processing of Human Semen, World Health Organization. [5th ed.]."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1177\/1358863X14532705","article-title":"ICAM-1 and SRD5A1 gene polymorphisms in symptomatic peripheral artery disease","volume":"19","author":"Barresi","year":"2014","journal-title":"Vasc. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.fertnstert.2005.03.055","article-title":"Treatment of male idiopathic infertility with recombinant human follicle-stimulating hormone: A prospective, controlled, randomized clinical study","volume":"84","author":"Foresta","year":"2005","journal-title":"Fertil. Steril."},{"key":"ref_14","first-page":"CD005071","article-title":"Gonadotrophins for idiopathic male factor subfertility","volume":"23","author":"Attia","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.rbmo.2014.02.014","article-title":"Spermatid count as a predictor of response to FSH therapy","volume":"29","author":"Garolla","year":"2014","journal-title":"Reprod. Biomed. Online"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"372060","DOI":"10.1155\/2014\/372060","article-title":"Reduced Seminal Concentration of CD45pos Cells after Follicle-Stimulating Hormone Treatment in Selected Patients with Idiopathic Oligoasthenoteratozoospermia","volume":"2014","author":"Condorelli","year":"2014","journal-title":"Int. J. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/S0015-0282(01)02966-1","article-title":"Use of recombinant human follicle-stimulating hormone in the treatment of male factor infertility","volume":"77","author":"Foresta","year":"2002","journal-title":"Fertil. Steril."},{"key":"ref_18","first-page":"7","article-title":"Relationship between gonadotrophin secretion, inhibin B and spermatogenesis in oligozoospermic men treated with highly purified urinary follicle-stimulating hormone (uFSH-HP): A preliminary report","volume":"107","author":"Cortes","year":"2003","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/andr.12333","article-title":"Short-term FSH treatment and sperm maturation: A prospective study in idiopathic infertile men","volume":"5","author":"Casamonti","year":"2017","journal-title":"Andrology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"309","DOI":"10.4103\/aja.aja_42_19","article-title":"FSH dosage effect on conventional sperm parameters: A meta-analysis of randomized controlled studies","volume":"22","author":"Cannarella","year":"2020","journal-title":"Asian J. Androl."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0015-0282(16)56653-9","article-title":"Sperm quality of subfertile males before and after treatment with human follicle-stimulating hormone","volume":"61","author":"Bartoov","year":"1994","journal-title":"Fertil. Steril."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1093\/humrep\/12.1.24","article-title":"Treatment of the male with follicle-stimulating hormone in intrauterine insemination with husband\u2019s spermatozoa: A randomized study","volume":"12","author":"Matorras","year":"1997","journal-title":"Hum. Reprod."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s10815-013-9951-y","article-title":"Lower sperm DNA fragmentation after r-FSH administration in functional hypogonadotropic hypogonadism","volume":"30","author":"Ruvolo","year":"2013","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1093\/humrep\/dew167","article-title":"Treatment with human, recombinant FSH improves sperm DNA fragmentation in idiopathic infertile men depending on the FSH receptor polymorphism p.N680S: A pharmacogenetic study","volume":"31","author":"Simoni","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S710","DOI":"10.21037\/tau.2017.06.21","article-title":"Sperm DNA fragmentation testing: A cross sectional survey on current practices of fertility specialists","volume":"6","author":"Majzoub","year":"2017","journal-title":"Transl. Androl. Urol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s10815-017-0912-8","article-title":"Free radical and superoxide reactivity detection in semen quality assessment: Past, present, and future","volume":"34","author":"Gosalvez","year":"2017","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1111\/j.1439-0272.2011.01228.x","article-title":"High levels of lipid peroxidation in semen of diabetic patients","volume":"44","author":"Condorelli","year":"2012","journal-title":"Andrologia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1095\/biolreprod41.1.183","article-title":"Generation of reactive oxygen species, lipid peroxidation, and human sperm function","volume":"41","author":"Aitken","year":"1989","journal-title":"Biol. Reprod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/humrep\/10.suppl_1.15","article-title":"Impact of reactive oxygen species on spermatozoa: A balancing act between beneficial and detrimental effects","volume":"10","author":"Gagnon","year":"1995","journal-title":"Hum. Reprod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1365-2605.1995.tb00388.x","article-title":"Superoxide anion production by human spermatozoa as a part of the ionophore-induced acrosome reaction process","volume":"18","author":"Griveau","year":"1995","journal-title":"Int. J. Androl."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/j.2047-2927.2012.00028.x","article-title":"Study in 1790 Baltic men: FSHR Asn680Ser polymorphism affects total testes volume","volume":"1","author":"Grigorova","year":"2013","journal-title":"Andrology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/j.1365-2605.2010.01086.x","article-title":"The response to FSH treatment in oligozoospermic men depends on FSH receptor gene polymorphisms","volume":"34","author":"Selice","year":"2011","journal-title":"Int. J. Androl."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.mce.2014.06.013","article-title":"FSHR polymorphism p.N680S mediates different responses to FSH in vitro","volume":"393","author":"Casarini","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1006\/geno.1996.0361","article-title":"The structure and organization of the human follicle-stimulating hormone receptor (FSHR) gene","volume":"35","author":"Gromoll","year":"1996","journal-title":"Genomics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1161\/01.HYP.0000233877.84343.d7","article-title":"Mutation of the follicle-stimulating hormone receptor gene 5\u2032-untranslated region associated with female hypertension","volume":"48","author":"Nakayama","year":"2006","journal-title":"Hypertension"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/andr.12502","article-title":"European Academy of Andrology guideline Management of oligo-astheno-teratozoospermia","volume":"6","author":"Colpi","year":"2018","journal-title":"Andrology"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/6\/1690\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:34:53Z","timestamp":1760175293000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/6\/1690"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,2]]},"references-count":36,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["jcm9061690"],"URL":"https:\/\/doi.org\/10.3390\/jcm9061690","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,2]]}}}