Embryological and Clinical Outcomes in Couples With Autosomal Dominant Polycystic Kidney Disease Undergoing PGT‐M: A Retrospective Cohort Study

BACKGROUND: Male reproductive abnormalities have been reported in autosomal dominant polycystic kidney disease (ADPKD), but their impact on embryo development and clinical outcomes after preimplantation genetic testing remains unclear. OBJECTIVES: This study aimed to evaluate the association of male and female ADPKD with embryologic and clinical outcomes in preimplantation genetic testing for monogenic disorder (PGT-M) cycles, and to explore whether progressive sperm motility modifies the association between male ADPKD and embryo developmental outcomes. MATERIALS/METHODS: This retrospective cohort study included 490 PGT-M cycles performed between January 2012 and December 2024, comprising 137 cycles with male ADPKD, 51 cycles with female ADPKD, and 302 non-ADPKD control cycles for other monogenic disorders. Embryologic and clinical outcomes were analyzed using denominator-aware generalized linear mixed models and logistic regression. Sensitivity, mediation, and interaction analyses were performed to explore the role of progressive sperm motility. RESULTS: Compared with controls, male ADPKD was associated with a lower Day 3 high-quality embryo rate (adjusted odds ratio [OR] 0.55, 95% confidence interval [CI]: 0.34-0.90, p = 0.017) and clinical pregnancy rate per embryo transfer (adjusted OR 0.46, 95% CI: 0.28-0.74, p = 0.002). In the primary analysis, the live birth rate per embryo transfer did not differ statistically (adjusted OR 0.62, 95% CI: 0.39-1.00, p = 0.052). The association with blastocyst formation was not statistically significant after adjustment for semen parameters (adjusted OR 0.76, 95% CI: 0.55-1.04, p = 0.090), but became significant when progressive sperm motility was omitted from the model (OR 0.67, 95% CI: 0.51-0.89, p = 0.005). An exploratory interaction was detected between male ADPKD and progressive sperm motility (interaction OR 1.81, 95% CI: 1.23-2.66, p = 0.003). No significant differences in the primary embryologic or clinical outcomes were observed between female ADPKD and control cycles. DISCUSSION: Associations with Day 3 embryo morphology and clinical pregnancy were not accompanied by a statistically significant difference in live birth in the primary analysis. Because semen quality differed substantially between groups and no non-ADPKD group with comparably severe asthenozoospermia was included, these analyses do not establish an ADPKD-specific effect on embryo development or overall PGT-M success. CONCLUSION: The findings identify associations with selected intermediate outcomes, but do not demonstrate that male ADPKD independently impairs clinically definitive PGT-M outcomes. The sperm motility analyses should be considered exploratory and hypothesis-generating.