Gynecology World Conference 2026

Abstract

Non-invasive prenatal testing has become an integral part of contemporary prenatal screening, offering high accuracy for common aneuploidies and fetal sex determination. Nevertheless, discordance between fetal sex predicted by NIPT and the sonographic appearance of fetal external genitalia, although rare, may represent the first indication of clinically significant chromosomal, developmental or placental abnormalities. Such findings introduce diagnostic uncertainty and require careful interpretation, confirmatory testing and sensitive parental counseling.

This presentation addresses the counseling challenges arising from two cytogenetically complex cases of fetal sex discordance identified in a retrospective cohort of 3320 pregnancies in which both NIPT and second-trimester ultrasound examination were performed. The observed discordance rate was 0.06%. In both cases, the discrepancy between genotypic sex suggested by NIPT and phenotypic sex assessed by ultrasound prompted referral for invasive prenatal diagnosis and multidisciplinary evaluation.

In the first case, NIPT indicated a low-risk female fetus with two X chromosomes. However, ultrasound examination at 15 weeks of gestation demonstrated male external genitalia and an enlarged cisterna magna. At 18 weeks, the posterior fossa finding was suggestive of an isolated Blake’s pouch cyst. Repeated NIPT confirmed the initial result. Amniocentesis followed by cytogenetic and FISH analysis revealed complex sex chromosome mosaicism involving multiple cell lines, including 45,X, 46,XY, 47,XYY and cell lines with an isodicentric Y chromosome. After genetic counseling, the parents opted for termination of pregnancy. Fetal autopsy confirmed male sex and normal testes.

In the second case, NIPT indicated a male fetus, whereas detailed 3D ultrasonography demonstrated female external genitalia with otherwise unremarkable fetal anatomy. Amniocentesis revealed a 45,X fetal karyotype, consistent with monosomy X. The pregnancy was continued, and a phenotypically female newborn was delivered at term with subtle clinical features compatible with Turner syndrome. Postnatal placental studies demonstrated mosaicism involving 45,X and 46,XY cell lines, supporting fetoplacental mosaicism as the most plausible explanation for the discordant NIPT result.

These cases illustrate that fetal sex discordance should not be dismissed as a technical inconsistency or isolated screening discrepancy. Instead, it should be approached as a potential marker of underlying sex chromosome mosaicism, differences of sex development, confined placental mosaicism or other complex biological mechanisms. Counseling in this setting must balance diagnostic uncertainty with clear communication regarding the limitations of screening, the role of ultrasound, the value of invasive testing and the possible implications for pregnancy outcome and postnatal care.

A structured multidisciplinary pathway involving fetal medicine specialists, clinical geneticists, cytogenetic laboratories, neonatologists and, when appropriate, pediatric endocrinologists is essential. Timely recognition and integrated counseling allow parents to make informed decisions and support individualized pregnancy management in these rare but clinically meaningful cases.