Assisted reproductive technology represents a possible risk factor for development of epimutation-mediated imprinting disorders for mothers aged ≥ 30 years

Table 2 Summary of the studies investigating the proportions of ART-conceived livebirths in imprinting disorders

IDs	Country	Number of patients	Number of patients with molecular analysis	Non-ART	ART (%)	Genetic causes found in ART-conceived IDs	Interventions of ART performed
Sutcliffe, 2006* [18]	UK
Total		317	12^a	295	22		IVF, ICSI
BWS		79	8	68	11 (13.9)	epi, 8^d; not doing genetic testing, 3
PWS		163	2	154	9 (5.5)	del, 2; not doing genetic testing, 7
AS		75	2	73	2 (2.7)	epi, 1; del, 1
Doornbos 2007* [19]	Netherlands
Total		220	11^a	206	14		IVF, ICSI,
BWS		71	6	65	6 (8.5)	epi, 6^d	COS, IUI
PWS		86	3	82	4 (4.7)	del, 3; not doing genetic testing, 1
AS		63	2	59	4 (6.3)	del, 2; not doing genetic testing, 2
Tenorio 2016* [20]	Spain
BWS		156	156^b	139	17 (10.9)	epi, 15^d; unknown, 2	IVF, AI, COS
Mussa, 2017* [21]	Italy
BWS		38	7^a	31	7 (18.4)	epi, 3^d; UPD, 2; unknown, 2	IVF, ICSI, IUI
Hattori, 2019* [14]	Japan
Total		931	556	888	43		IVF, ICSI
SRS		67	22^c	59	8 (11.9)	epi, 5; not doing genetic testing, 3
BWS		117	43	110	7 (6.0)	epi, 4^d; not doing genetic testing, 3
PWS		520	366	496	24 (4.6)	epi, 6; del, 6; UPD, 9; not doing genetic testing, 3
AS		227	147	223	4 (1.8)	del, 4
This study**	Japan
Total		136	136^b	114	22		IVF, ICSI, FET
SRS		77	77	65	12 (15.6)	epi, 12
BWS		31	31	23	8 (25.8)	epi, 8^e
KOS		5	5	5	0
TS14		4	4	3	1 (25.0)	epi, 1
PWS		4	4	4	0
AS		5	5	5	0
PHP1B		8	8	7	1 (12.5)	epi, 1
TNDM		2	2	2	0

IDs imprinting disorders, ART assisted reproductive technology, BWS Beckwith-Wiedemann syndrome, PWS Prader-Willi syndrome, AS Angelman syndrome, SRS Silver-Russell syndrome, KOS Kagami-Ogata syndrome, TS14 Temple syndrome, PHP1B pseudohypoparathyroidism 1B, TNDM transient neonatal diabetes mellitus, UK United Kingdom, epi epimutation, del deletion, UPD uniparental disomy, IVF in vitro fertilization, ICSI intracytoplasmic sperm injection, COS controlled ovarian stimulation, IUI intrauterine insemination, AI artificial insemination, FET frozen embryo transfer
*Patients with all genetic causes resulting in IDs were included
**Patients with only epimutation-mediated IDs were included
^aMolecular analysis was performed in patients with ART-conceived IDs only
^bMolecular analysis was performed in all patients
^cIncluding 10 patients from our study
^dAll patients had hypomethylated KCNQ1OT1:TSS-DMR
^ePatients had either hypomethylated KCNQ1OT1:TSS-DMR or hypermethylated H19/IGF2:IG-DMR

ISSN: 1868-7083