Risk assessment of medically assisted reproduction and advanced maternal ages in the development of Prader–Willi syndrome due to UPD(15)mat

Recent studies have suggested that disomic oocyte‐mediated uniparental disomy 15 ( UPD (15)mat) is increased in patients with Prader–Willi syndrome ( PWS ) born after medically assisted reproduction ( MAR ). However, it remains unknown whether the increase is primarily due to MAR procedure itself or advanced maternal childbearing ages as a predisposing factor for the disomic oocyte production. To examine this matter, we studied 122 naturally conceived PWS patients ( PWS‐NC group) and 13 MAR ‐conceived patients ( PWS‐MAR group). The relative frequency of disomic oocyte‐mediated UPD (15)mat was significantly higher in PWS‐MAR group than in PWS‐NC group (7/13 vs 20/122, p = 0.0045), and the maternal childbearing ages were significantly higher in PWS‐MAR group than in PWS‐NC group [median (range), 38 (26–45) vs 30 (19–42), p = 0.0015]. However, the logistic regression analysis revealed no significant association between the occurrence of disomic oocyte‐mediated UPD (15)mat and MAR , after adjusting for childbearing age (p = 0.25). Consistent with this, while the frequency of assisted reproductive technology ( ART )‐conceived livebirths was higher in the PWS patients than in the Japanese general population (6.4% vs 1.1%, p = 0.00018), the distribution of childbearing ages was significantly skewed to the increased ages in the PWS patients (p < 2.2 × 10 −16 ). These results argue against a positive association of MAR procedure itself with the development of UPD (15)mat.