{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T09:58:15Z","timestamp":1773827895299,"version":"3.50.1"},"reference-count":22,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: To evaluate the diagnostic yield of phenotype-guided cytogenetic and targeted molecular genetic testing in patients referred for infertility and reproductive disorders within a tertiary medical genetics referral pathway. Methods: This retrospective study included 900 consecutive patients (473 males, 427 females) referred to a tertiary medical genetics center between January 2020 and December 2024. Conventional karyotyping was performed in all patients. Additional targeted molecular tests were applied based on clinical indication: Y chromosome microdeletion analysis in azoospermia or oligospermia, CFTR sequencing in suspected congenital bilateral absence of the vas deferens, and F2\/F5 genotyping in recurrent pregnancy loss (RPL). Diagnostic yield was analyzed in a predefined subgroup of 566 patients with RPL, unexplained infertility, azoospermia, or oligospermia; remaining referrals were included in descriptive cytogenetic analyses only. Results: Chromosomal abnormalities were identified in 3.22% (29\/900) of the total cohort and in 5.12% (29\/566) of the diagnostic-yield cohort. Targeted testing yields were 3.75% (6\/160) for Y chromosome microdeletions, 9.38% (3\/32) for CFTR variants, and 3.31% (4\/121) for F2\/F5 variants. Diagnostic yield varied markedly by phenotype, being highest in azoospermia (33.3%), followed by oligospermia (6.6%), RPL (5.3%), and unexplained infertility (3.1%). In unexplained infertility, all chromosomal abnormalities were detected in female patients. Conclusions: In a tertiary referral setting, phenotype-guided genetic testing provides the greatest diagnostic value in well-defined infertility phenotypes, particularly azoospermia. Lower yields in other referral groups support a targeted, indication-based approach to genetic evaluation and highlight the need for advanced genomic strategies in persistently unexplained cases.<\/jats:p>","DOI":"10.3390\/diagnostics16060896","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:35:08Z","timestamp":1773819308000},"page":"896","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic Yield of Phenotype-Guided Genetic Testing in Infertility: A Five-Year Retrospective Study from a Tertiary Referral Cohort"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8341-3781","authenticated-orcid":false,"given":"Kristina","family":"Aleknavi\u010dien\u0117","sequence":"first","affiliation":[{"name":"Department of Genetics and Molecular Medicine, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius","family":"\u0160ukys","sequence":"additional","affiliation":[{"name":"Department of Genetics and Molecular Medicine, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u017divil\u0117","family":"\u017demeckien\u0117","sequence":"additional","affiliation":[{"name":"Department of Genetics and Molecular Medicine, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birut\u0117","family":"\u017dilaitien\u0117","sequence":"additional","affiliation":[{"name":"Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rasa","family":"Ugenskien\u0117","sequence":"additional","affiliation":[{"name":"Department of Genetics and Molecular Medicine, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"hoac051","DOI":"10.1093\/hropen\/hoac051","article-title":"Infertility prevalence and the methods of estimation from 1990 to 2021: A systematic review and meta-analysis","volume":"2022","author":"Cox","year":"2022","journal-title":"Hum. 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