臨床婦人科産科65巻6号

2011年06月発行

今月の臨床 ART─いま何が問題か

ARTによる出生児の問題

1．生後発育と先天異常

著者： 平原史樹¹

所属機関： ¹横浜市立大学大学院医学研究科生殖生育病態医学（産婦人科学）

ページ範囲：P.764 - P.769

文献概要

はじめに

　人類初の体外受精を成功させたケンブリッジ大学名誉教授エドワード博士と産婦人科医ステプトー博士は1978年に世界初のいわゆる“試験管ベビー”としてルイーズ・ブラウンさんを誕生させた．その後ルイーズさんは自然に妊娠し健児を得ている．生殖補助医療（assisted reproductive technology：ART）による出産児数はいまや年間1万出生を大きく超え，新生児の50～60名に一人はARTによる出産児といわれている．いままでにも児の健康や先天異常とARTとの関係を論じた報告が数多くあるが，最近の報告では，不妊として診療を受ける医学的理由が背景にあることから，やはり，若干の問題点の存在が指摘されている．しかしながらその背景には，複雑な要因の介在が示唆されてきている．本稿ではそれらの各論を論じることとする．

参考文献

1）三春範夫，本田奈央：配偶子や受精卵の染色体異常．産婦人科世界56：増刊277-283，2004

2）Westergaard HB, Johansen AM, Erb K, et al：Danish National In-Vitro Fertilization Registry 1994 and 1995：a controlled study of births, malformations and cytogenetic findings. Hum Reprod 14：1896-1902, 1999

3）Bonduelle M, Liebaers I, Deketelaere V, et al：Neonatal data on a cohort of 2889 infants born after ICSI（1991～1999）and of 2995 infants born after IVF（1983～1999）. Hum Reprod 17：671-694, 2002

4）Kunej T, Zorn B, Peterlin B：Y chromosome microdeletions in infertile men with cryptorchidism. Fertil Steril 79 Suppl：1559-1565, 2003

5）Lewis-Jones I, Aziz N, Seshadri S, et al：Sperm chromosomal abnormalities are linked to sperm morphologic deformities. Fertil Steril 79：212-215, 2003

6）Zenzes MT, Wang P, Casper RF：Chromosome status of untransferred（spare）embryos and probability of pregnancy after in-vitro fertilisation. Lancet 15：391-394, 1992

7）Samli H, Solak M, Imirzalioglu N, et al：Fetal chromosomal analysis of pregnancies following intracytoplasmic sperm injection with amniotic tissue culture. Prenat Diagn 23：847-850, 2003

8）Mastroiacovo P, Castilla EE, Arpino C, et al：Congenital malformations in twins：an international study. Am J Med Genet 83：117-124, 1999

9）Wennerholm UB, Bergh C, Hamberger L, et al：Incidence of congenital malformations in children born after ICSI. Hum Reprod 15：944-948, 2000

10）Hansen M, Kurinczuk JJ, Bower C, et al：The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med 346：725-730, 2002

11）Reefhuis J, Honein MA, Schieve LA, et al：National Birth Defects Prevention Study Assisted reproductive technology and major structural birth defects in the United States. Hum Reprod 24：360-366, 2009

12）Wen SW, Leader A, White RR, et al：A comprehensive assessment of outcomes in pregnancies conceived by in vitro fertilization／intracytoplasmic sperm injection. Eur J Obstet Gynecol Reprod Biol 150：160-165, 2010

13）Gosden R, Trasler J, Lucifero D, et al：Rare congenital disorders, imprinted genes, and assisted reproductive technology. Lancet 3611：975-977, 2003

14）Sutcliffe AG, Peters CJ, Bowdin S, et al：Assisted reproductive therapies and imprinting disorders--a preliminary British survey. Hum Reprod 21：1009-1011, 2006

15）Shiota K, Yamada S：Intrauterine environment-genome interaction and children's development（3）: Assisted reproductive technologies and developmental disorders. J Toxicol Sci 34 Suppl 2：SP287-291, 2009

16）ESHRE PGD Consortium Steering Committee.：ESHRE Preimplantation Genetic Diagnosis Consortium：data collection III（May 2001）. Hum Reprod 17：233-246, 2002

17）Young LE, Fernandes K, McEvoy TG, Butterwith SC, Gutierrez CG, Carolan C, Broadbent PJ, Robinson JJ, Wilmut I, et al：Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat Genet 27：153-154, 2001

18）森　崇英，中村幸雄，他：日本受精着床学会実態調査委員会報告　平成9年度実施の生殖補助医療による出生児の生後発育に関する調査報告　日本受精着床誌23：1-18，2006

19）Leunens L, Celestin-Westreich S, Bonduelle M, et al：Follow-up of cognitive and motor development of 10-year-old singleton children born after ICSI compared with spontaneously conceived children. Hum Reprod 23：105-111, 2008

20）Ludwig A, Katalinic A, Thyen U, et al：Neuromotor development and mental health at 5.5 years of age of singletons born at term after intracytoplasmatic sperm injection ICSI：results of a prospective controlled single-blinded study in Germany. Fertil Steril 91：125-132, 2009

21）Ericson A, Nygren KG, Olausson PO, et al：Hospital care utilization of infants born after IVF. Hum Reprod 17：929-932, 2002

22）Bonduelle M, Wennerholm UB, Loft A, et al：A multi-centre cohort study of the physical health of 5-year-old children conceived after intracytoplasmic sperm injection, in vitro fertilization and natural conception. Hum Reprod 20：413-419, 2005

23）Moll AC, Imhof SM, Cruysberg JR, et al：Incidence of retinoblastoma in children born after in-vitro fertilisation. Lancet 361：309-310, 2003

24）Ludwig AK, Katalinic A, Thyen U et al：Physical health at 5.5 years of age of term-born singletons after intracytoplasmic sperm injection：results of a prospective, controlled, single-blinded study. Fertil Steril 91：115-124, 2009

25）Fortunato A, Tosti E：The impact of in vitro fertilization on health of the children：an update. Eur J Obstet Gynecol Reprod Biol 154：125-129, 2011

26）Klemetti R, Sevón T, Gissler M, et al：Health of children born after ovulation induction. Fertil Steril 93：1157-1168, 2010

27）Brinton LA, Krüger Kjaer S, Thomsen BL et al：Childhood tumor risk after treatment with ovulation-stimulating drugs. Fertil Steril 81：1083-1091, 2004

28）Souter VL, Kapur RP, Nyholt DR, et al：A report of dizygous monochorionic twins. N Engl J Med 349：154-158, 2003