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.