{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T07:17:32Z","timestamp":1774768652497,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:00:00Z","timestamp":1694131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Testis stimulation with follicle-stimulating hormone (FSH) is one of the empirical treatments proposed for male idiopathic infertility, although reliable markers to predict its efficacy are still lacking. This study aimed to identify parameters able to predict FSH efficacy in terms of pregnancy achievement. A real-world study was conducted, enrolling idiopathic infertile men treated with FSH 150IU three times weekly. Patients were treated until pregnancy achievement or for a maximum of two years and two visits were considered: V0 (baseline) and V1 (end of FSH treatment). Primary endpoints were the V1-V0 percentage change in sperm concentration, total sperm count, and total motile sperm number. In total, 48 pregnancies were recorded (27.7%) among 173 men (age 37.9 \u00b1 6.2 years). All three endpoints increased after FSH administration, and only the V1-V0 percentage of sperm concentration significantly predicted pregnancy (p = 0.007). A V1-V0 sperm concentration of 30.8% predicted pregnancy, and the sperm concentration V1-V0 percentage (Y) required to obtain a pregnancy was predicted according to its baseline values (x): Y = 9.8433x2 \u2212 203.67x + 958.29. A higher number of pregnancies was reached in men with baseline sperm concentration below 7.3 million\/mL. Thus, the percentage of sperm concentration increasing after FSH administration could predict the treatment efficacy in terms of pregnancy. At the dosage used, the efficacy was significantly higher in patients with a starting sperm concentration &lt; 7.3 mill\/mL. Mathematical analyses identified a function able to predict the sperm concentration increase required to obtain a pregnancy in relation to the baseline sperm number.<\/jats:p>","DOI":"10.3390\/cells12182236","type":"journal-article","created":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T07:57:17Z","timestamp":1694159837000},"page":"2236","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sperm Concentration Improvement May Be a Parameter Predicting Efficacy of FSH Therapy of Male Idiopathic Infertility"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6607-7105","authenticated-orcid":false,"given":"Daniele","family":"Santi","sequence":"first","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41122 Modena, Italy"},{"name":"Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, 41122 Modena, Italy"},{"name":"Unit of Andrology and Sexual Medicine of the Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, 41122 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"Spaggiari","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, 41122 Modena, Italy"},{"name":"Unit of Andrology and Sexual Medicine of the Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, 41122 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"Dalla Valentina","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41122 Modena, Italy"},{"name":"Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, 41122 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilina","family":"Romeo","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41122 Modena, Italy"},{"name":"Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, 41122 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Nuzzo","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41122 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Serlenga","sequence":"additional","affiliation":[{"name":"Willis Towers Watson, Willis Holdings plc, London EC3M 7DQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Roli","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Azienda USL of Modena, 41122 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Cristina","family":"De Santis","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Azienda USL of Modena, 41122 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommaso","family":"Trenti","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Azienda USL of Modena, 41122 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio R. M.","family":"Granata","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, 41122 Modena, Italy"},{"name":"Unit of Andrology and Sexual Medicine of the Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, 41122 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2133-4304","authenticated-orcid":false,"given":"Manuela","family":"Simoni","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41122 Modena, Italy"},{"name":"Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, 41122 Modena, Italy"},{"name":"Unit of Andrology and Sexual Medicine of the Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, 41122 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1111\/andr.12673","article-title":"The present crisis in male reproductive health: An urgent need for a political, social, and research roadmap","volume":"7","author":"Barratt","year":"2019","journal-title":"Andrology"},{"key":"ref_2","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"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1111\/andr.262","article-title":"Factors affecting spermatogenesis upon gonadotropin-replacement therapy: A meta-analytic study","volume":"2","author":"Rastrelli","year":"2014","journal-title":"Andrology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Simoni, M., and Huhtaniemi, I. (2017). Endocrinology of the Testis and Male Reproduction, Springer.","DOI":"10.1007\/978-3-319-44441-3"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1007\/s40618-018-0843-y","article-title":"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)","volume":"41","author":"Barbonetti","year":"2018","journal-title":"J. Endocrinol. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/S0015-0282(99)00322-2","article-title":"The role of purified follicle stimulating hormone therapy in the male partner before intracytoplasmic sperm injection","volume":"72","author":"Ashkenazi","year":"1999","journal-title":"Fertil. Steril."},{"key":"ref_7","first-page":"133","article-title":"Effect of follicle-stimulating hormone on sperm quality and pregnancy rate","volume":"6","author":"Baccetti","year":"2004","journal-title":"Asian J. Androl."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/S0015-0282(99)00461-6","article-title":"Follicle-stimulating hormone treatment for men with idiopathic oligoteratoasthenozoospermia before in vitro fertilization: The impact on sperm microstructure and fertilization potential","volume":"73","author":"Farhi","year":"2000","journal-title":"Fertil. Steril."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/S0015-0282(03)02202-7","article-title":"Recombinant human follicle-stimulating hormone as a pretreatment for idiopathic oligoasthenoteratozoospermic patients undergoing intracytoplasmic sperm injection","volume":"80","author":"Caroppo","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1111\/cen.12770","article-title":"Treatment of idiopathic oligozoospermia with recombinant human follicle-stimulating hormone: A prospective, randomized, double-blind, placebo-controlled clinical study in Chinese population","volume":"83","author":"Ding","year":"2015","journal-title":"Clin. Endocrinol."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1093\/humrep\/13.3.596","article-title":"Recombinant human follicle stimulating hormone for treatment of male idiopathic infertility: A randomized, double-blind, placebo-controlled, clinical trial","volume":"13","author":"Kamischke","year":"1998","journal-title":"Hum. Reprod."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.fertnstert.2006.02.087","article-title":"Effects of high doses of recombinant human follicle-stimulating hormone in the treatment of male factor infertility: Results of a pilot study","volume":"86","author":"Paradisi","year":"2006","journal-title":"Fertil. Steril."},{"key":"ref_17","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_18","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_19","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/j.fertnstert.2008.07.1766","article-title":"Gonadotropin administration after gonadotropin-releasing-hormone agonist: A therapeutic option in severe testiculopathies","volume":"92","author":"Foresta","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1210\/jcem-65-6-1081","article-title":"Treatment of severe oligospermia with human chorionic gonadotropin\/human menopausal gonadotropin: A placebo-controlled, double blind trial","volume":"65","author":"Knuth","year":"1987","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","first-page":"1","article-title":"The Effect of Recombinant Human Follicle-Stimulating Hormone on Sperm Quality, Chromatin Status and Clinical Outcomes of Infertile Oligozoospermic Men Candidate for Intracytoplasmic Sperm Injection: A Randomized Clinical Trial","volume":"15","author":"Verdi","year":"2021","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"69","DOI":"10.4103\/UA.UA_37_19","article-title":"Efficacy of follicle-stimulating hormone as a treatment of severe idiopathic oligospermia: A retrospective study","volume":"12","author":"Aljuhayman","year":"2020","journal-title":"Urol. Ann."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/j.fertnstert.2011.09.034","article-title":"Toward a pharmacogenetic approach to male infertility: Polymorphism of follicle-stimulating hormone beta-subunit promoter","volume":"96","author":"Ferlin","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0303-7207(99)00228-2","article-title":"FSH in the treatment of oligozoospermia","volume":"161","author":"Foresta","year":"2000","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"R46","DOI":"10.1530\/EC-15-0050","article-title":"Follicle-stimulating hormone treatment of male idiopathic infertility improves pregnancy rate: A meta-analysis","volume":"4","author":"Santi","year":"2015","journal-title":"Endocr. Connect."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/andr.12746","article-title":"FSH Treatment of male idiopathic infertility: Time for a paradigm change","volume":"8","author":"Simoni","year":"2019","journal-title":"Andrology"},{"key":"ref_28","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":"2019","journal-title":"Asian J. Androl."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s12958-021-00744-x","article-title":"Dose adjustment of follicle-stimulating hormone (FSH) during ovarian stimulation as part of medically-assisted reproduction in clinical studies: A systematic review covering 10 years (2007\u20132017)","volume":"19","author":"Fatemi","year":"2021","journal-title":"Reprod. Biol. Endocrinol. RB&E"},{"key":"ref_30","first-page":"e15663","article-title":"Past, Present, and Future of Gonadotropin Use in Controlled Ovarian Stimulation During Assisted Reproductive Techniques","volume":"13","author":"Prodromidou","year":"2021","journal-title":"Cureus"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1007\/s40265-020-01324-w","article-title":"Current Therapeutic Options for Controlled Ovarian Stimulation in Assisted Reproductive Technology","volume":"80","author":"Racca","year":"2020","journal-title":"Drugs"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1111\/andr.13353","article-title":"Follicle-stimulating hormone effectiveness in male idiopathic infertility: What happens in daily practice?","volume":"11","author":"Romeo","year":"2022","journal-title":"Andrology"},{"key":"ref_33","unstructured":"(2023, March 31). AIFA: Note 74, Available online: http:\/\/www.agenziafarmaco.gov.it\/it\/content\/nota-74."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1111\/andr.12759","article-title":"The physician\u2019s gender influences the results of the diagnostic workup for erectile dysfunction","volume":"8","author":"Rastrelli","year":"2020","journal-title":"Andrology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1111\/andr.13225","article-title":"Qualitative and quantitative analysis of doctor-patient interactions during andrological consultations","volume":"10","author":"Santi","year":"2022","journal-title":"Andrology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1016\/S0140-6736(97)10514-1","article-title":"Relation between semen quality and fertility: A population-based study of 430 first-pregnancy planners","volume":"352","author":"Bonde","year":"1998","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1093\/humrep\/17.1.173","article-title":"Time to pregnancy in relation to semen quality assessed by CASA before and after sperm separation","volume":"17","author":"Andersen","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.fertnstert.2013.10.022","article-title":"Semen quality and time to pregnancy: The Longitudinal Investigation of Fertility and the Environment Study","volume":"101","author":"Sundaram","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Lamb, D.J., and Marinaro, J.A. (2023). Semen parameter prediction of pregnancy. Fertil. Steril., S0015-0282.","DOI":"10.1016\/j.fertnstert.2023.06.035"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/j.1939-4640.2000.tb03284.x","article-title":"Semen quality and human fertility: A prospective study with healthy couples","volume":"21","author":"Zinaman","year":"2000","journal-title":"J. Androl."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1093\/humrep\/deab133","article-title":"Semen parameter thresholds and time-to-conception in subfertile couples: How high is high enough?","volume":"36","author":"Keihani","year":"2021","journal-title":"Hum. Reprod."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1016\/j.fertnstert.2021.01.014","article-title":"Clarifying the relationship between total motile sperm counts and intrauterine insemination pregnancy rates","volume":"115","author":"Muthigi","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/andr.13123","article-title":"Are sperm parameters able to predict the success of assisted reproductive technologies? A retrospective analysis of over 22000 ART cycles","volume":"10","author":"Villani","year":"2021","journal-title":"Andrology"},{"key":"ref_44","first-page":"e14409","article-title":"The association of impaired semen quality and pregnancy rates in assisted reproduction technology cycles: Systematic review and meta-analysis","volume":"54","author":"Belladelli","year":"2022","journal-title":"Andrologia"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Casarini, L., Cr\u00e9pieux, P., Reiter, E., Lazzaretti, C., Paradiso, E., Rochira, V., Brigante, G., Santi, D., and Simoni, M. (2020). FSH for the Treatment of Male Infertility. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072270"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Lispi, M., Drakopoulos, P., Spaggiari, G., Caprio, F., Colacurci, N., Simoni, M., and Santi, D. (2022). Testosterone Serum Levels Are Related to Sperm DNA Fragmentation Index Reduction after FSH Administration in Males with Idiopathic Infertility. Biomedicines, 10.","DOI":"10.3390\/biomedicines10102599"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1093\/humrep\/deac189","article-title":"Standards in semen examination: Publishing reproducible and reliable data based on high-quality methodology","volume":"37","author":"Barratt","year":"2022","journal-title":"Hum. Reprod."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1080\/13685538.2019.1590696","article-title":"FSH therapy for idiopathic male infertility: Four schemes are better than one","volume":"23","author":"Condorelli","year":"2020","journal-title":"Aging Male Off. J. Int. Soc. Study Aging Male"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nrurol.2012.234","article-title":"Follicle-stimulating hormone treatment in normogonadotropic infertile men","volume":"10","author":"Valenti","year":"2013","journal-title":"Nat. Rev. Urol."},{"key":"ref_50","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"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/18\/2236\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:47:23Z","timestamp":1760129243000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/18\/2236"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,8]]},"references-count":50,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["cells12182236"],"URL":"https:\/\/doi.org\/10.3390\/cells12182236","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,8]]}}}