title: Risk assessment of medically assisted reproduction and advanced maternal ages in the development of Prader-Willi syndrome due to UPD(15)mat.
abstract: 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.
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.|Department of Pediatrics, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsubara
authors.affiliation: Department of Pediatrics, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Murakami
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fukami
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kagami
authors.affiliation: Department of Pediatrics, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.|Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ogata
mesh_terms: D000328:Adult; D000367:Age Factors; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008423:Maternal Age; D008875:Middle Aged; D009865:Oocytes / Q000378:metabolism; D010331:Paternal Age; D011218:Prader-Willi Syndrome / Q000209:etiology / Q000235:genetics*; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects / Q000706:statistics & numerical data*; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D024182:Uniparental Disomy; D055815:Young Adult
keywords: Prader-Willi syndrome; UPD(15)mat; advanced maternal age; assisted reproductive technology; controlled ovarian stimulation; medically assisted reproduction; trisomy rescue