Fertility issues and pregnancy outcomes in females with partial X-chromosome deletions: a retrospective observational...

To investigate fertility challenges, factors influencing spontaneous pregnancy, and pregnancy outcomes in females with partial X-chromosome deletions, and to provide evidence for genetic counseling.

A retrospective analysis of 101,018 individuals who underwent peripheral blood karyotype analysis was performed; females with partial X-deletions or 45,X karyotype were identified. Follow-up was conducted for females aged ≥ 15 years as of 2025. Clinical phenotypes were compared between females with partial X-deletions and those with homozygous 45,X karyotype. Females with partial X-deletions were stratified into spontaneous pregnancy and non-spontaneous pregnancy groups to identify predictive factors. Pregnancy outcomes were compared with 130 pregnant women with normal karyotype, with postnatal infant follow-up conducted.

68 partial X-deletion and 55 45,X cases were followed up. It revealed significantly higher rates of spontaneous menarche, normal uterine/ovarian ultrasound findings, and conception probability in partial X-deletion group (p < 0.05/p < 0.01). Among 68 females with partial X-deletions, 23 successfully delivered. Spontaneous pregnancy was significantly associated with earlier menarche and normal ultrasound findings (p < 0.05), while mosaicism without normal karyotypes and increased infertility-related gene deletions were adverse factors (p < 0.001). Compared with pregnant women with normal karyotypes, elevated rates of assisted reproductive technology utilization and cesarean section were observed (p < 0.05), with significantly increased abnormal fetal screening results (p < 0.001). Postnatally, 15 of 27 fetuses (55.6%) inherited maternal chromosomal abnormalities; 10 exhibited clinical phenotypes including one severe case.

This study is a preliminary exploration focusing on reproductive issues in females with partial X-chromosome deletions. These females face significant reproductive challenges, with infertility being the primary one. However, they have a significantly higher probability of spontaneous conception compared with females with a homozygous 45,X karyotype. Their offspring have a high probability of inheriting the maternal abnormal X-chromosome and often present with clinical phenotypes of varying severity. Larger cohort validation and long-term follow-up are necessary to further validate these findings.