Differences in sex development among individuals with a female phenotype and an absent uterus: Diagnostic approach

ObjectiveTo describe individuals with differences in sex development presenting with a female phenotype and an absent uterus and identify specific diagnostic characteristics that improve diagnostic accuracy and optimize patient care.Materials and MethodsThis descriptive comparative study included retrospective and prospective clinical data collected between 2023 and 2025 at the Reproductive Medicine Center "Universe," Tbilisi, Georgia. Among 233 individuals evaluated for primary amenorrhea, 26% with a female phenotype and an absent uterus who were evaluated for Complete Androgen Insensitivity Syndrome, Mayer-Rokitansky-Küster-Hauser syndrome, and ovotesticular disorder of sex development were included in the final sample. All participants underwent clinical, hormonal, genetic, and imaging assessment. Laparoscopy and histomorphological examination were performed when indicated.ResultsMayer-Rokitansky-Küster-Hauser syndrome accounted for 57.4%, Complete Androgen Insensitivity Syndrome for 37.7%, and ovotesticular disorder of sex development for 4.9% of the cases. Complete Androgen Insensitivity Syndrome patients exhibited preserved breast development with absent or sparse pubic hair, whereas Mayer-Rokitansky-Küster-Hauser syndrome and ovotesticular disorder of sex development patients exhibited normal pubic hair and breast development. Vaginal length was shortest in patients with Mayer-Rokitansky-Küster-Hauser, intermediate in those with complete androgen insensitivity syndrome, and variable in patients with ovotesticular disorder of sex development. Complete Androgen Insensitivity syndrome patients demonstrated male-range testosterone levels; Mayer-Rokitansky-Küster-Hauser patients exhibited female-range hormone profiles, and ovotesticular disorder of sex development patients were observed to have nonspecific endocrine patterns. Ovotesticular disorder of sex development was confirmed histomorphologically.ConclusionAn integrated diagnostic approach combining specific clinical features, hormonal profiles, imaging, karyotyping, and histomorphology enables accurate differentiation of Mayer-Rokitansky-Küster-Hauser, complete androgen insensitivity syndrome, and ovotesticular disorder of sex development.