{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:53:44Z","timestamp":1790142824878,"version":"4.0.1"},"reference-count":38,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"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>Background\/Objectives: Hypogonadotropic hypogonadism (HH) is an uncommon but treatable cause of non-obstructive azoospermia (NOA). Fertility can often be restored with gonadotropin therapy. This study evaluated spermatogenic and reproductive outcomes in men with HH-related NOA managed by stepwise gonadotropin therapy, microdissection testicular sperm extraction (microTESE) for persistent azoospermia, and assisted reproduction when indicated. Methods: A retrospective cohort study included 35 men treated between 2010 and 2022. Human chorionic gonadotropin (hCG), with or without follicle-stimulating hormone (FSH), was administered to induce spermatogenesis. Outcomes included sperm appearance in the ejaculate, microTESE sperm retrieval rate in persistent azoospermia, and pregnancy and live birth outcomes after natural conception or in vitro fertilization with intracytoplasmic sperm injection (IVF-ICSI) when required. Results: Mean gonadotropin therapy duration was 12.0 months (range 6\u201324). Sperm appeared in the ejaculate in 27\/35 men (77%). The remaining 8\/35 (23%) underwent microTESE, with sperm retrieved in 7\/8 (88%). Seven couples proceeded to IVF-ICSI, undergoing 11 cycles that yielded 6 clinical pregnancies (55% per cycle) and 5 live birth deliveries, including 2 twin pregnancies. Among responders, 13 natural pregnancies occurred, resulting in 13 live birth deliveries, including 2 twin pregnancies. Overall, 18\/35 men (51%) achieved biological fatherhood, corresponding to 18 live birth delivery events (4 twin and 14 singleton deliveries) and 22 newborns. Conclusions: In men with HH-related NOA, exogenous gonadotropin therapy is expected to induce spermatogenesis in most patients. MicroTESE provides high sperm retrieval rates for those without ejaculatory sperm. Through an integrated approach of hormonal induction, microsurgical sperm retrieval, and assisted reproduction, approximately half of patients may ultimately achieve biological fatherhood in longer-term follow-up, depending on baseline severity and partner factors.<\/jats:p>","DOI":"10.3390\/jcm15031204","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T16:46:28Z","timestamp":1770137188000},"page":"1204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Fertility Outcomes in Men with Nonobstructive Azoospermia Due to Hypogonadotropic Hypogonadism After Gonadotropin Therapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5287-4450","authenticated-orcid":false,"given":"Athanasios","family":"Zachariou","sequence":"first","affiliation":[{"name":"Laboratory of Spermatology, Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9553-6803","authenticated-orcid":false,"given":"Athanasios","family":"Zikopoulos","sequence":"additional","affiliation":[{"name":"Royal Cornwall Hospitals NHS Treliske Truro, Foundation Trust UK, Truro TR1 3LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleftheria","family":"Markou","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University Hospital of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9257-126X","authenticated-orcid":false,"given":"Sotirios","family":"Koukos","sequence":"additional","affiliation":[{"name":"Laboratory of Spermatology, Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0207-3395","authenticated-orcid":false,"given":"Grigorios","family":"Daligaros","sequence":"additional","affiliation":[{"name":"Laboratory of Spermatology, Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotirios","family":"Skouros","sequence":"additional","affiliation":[{"name":"Laboratory of Spermatology, Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1198-9144","authenticated-orcid":false,"given":"Fotios","family":"Dimitriadis","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Chrisofos","sequence":"additional","affiliation":[{"name":"Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Sofikitis","sequence":"additional","affiliation":[{"name":"Laboratory of Spermatology, Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4651-312X","authenticated-orcid":false,"given":"Aris","family":"Kaltsas","sequence":"additional","affiliation":[{"name":"Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"ref_1","unstructured":"Leslie, S.W., Soon-Sutton, T.L., and Khan, M.A.B. 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