Impact of low-level sex chromosome mosaicism (<10%) on clinical outcomes of first fresh embryo transfer: a propensity score-matched retrospective cohort study.

BACKGROUND

Low-level sex chromosome mosaicism (SCM; abnormal cell proportion <10%) is frequently detected during preconception karyotype screening, yet its clinical relevance in assisted reproductive technology (ART) remains controversial. This study aimed to determine whether low-level SCM affects clinical outcomes in the first fresh embryo transfer cycle.

METHODS

This single-center retrospective cohort study included 3,216 infertile patients undergoing their first in vitro fertilization (IVF) or intracytoplasmic sperm injection and embryo transfer (ICSI-ET) cycle between January 2015 and December 2024 (261 in the SCM group and 2,955 in the control group). A 1:4 nearest-neighbor propensity score matching (PSM) was performed to balance comprehensive baseline demographic, ovarian reserve, and stimulation parameters. After matching, 221 SCM patients were paired with 881 controls. The primary outcome was live birth rate; secondary outcomes included clinical pregnancy rate and early miscarriage rate. Multivariable logistic regression was applied to the entire cohort to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs), with age-stratified analysis to assess interaction effects.

RESULTS

After PSM, the vast majority of covariates achieved excellent balance with standardized mean differences (SMD) < 0.1. No significant differences were observed between the SCM and control groups in live birth rate (34.39% vs. 40.75%), clinical pregnancy rate (45.25% vs. 49.72%), or early miscarriage rate (20.00% vs. 16.44%). Multivariable logistic regression showed no independent association between SCM status and live birth (aOR 0.890, 95% CI 0.633-1.252, P = 0.503) or clinical pregnancy (aOR 0.915, 95% CI 0.661-1.266, P = 0.591). Female age was the only consistently significant predictor: each additional year reduced live birth odds by 12.8% (aOR 0.872, 95% CI 0.824-0.923, P < 0.001) and clinical pregnancy odds by 9.7% (aOR 0.903, 95% CI 0.856-0.952, P < 0.001). Age-stratified analysis across four subgroups (<35, 35-37, 38-40, and >40 years) demonstrated consistent null results, with absolute differences remaining below 5 percentage points and parallel declining trends across strata.

CONCLUSION

Low-level sex chromosome mosaicism (<10%) does not significantly affect live birth rate, clinical pregnancy rate, or early miscarriage rate in the first fresh ART transfer cycle, with consistent null findings across all age strata. Female age remains the predominant determinant of ART outcomes. These findings provide robust evidence-based guidance for clinical management and genetic counseling of infertile patients with low-level sex chromosome mosaicism.