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Semin Reprod Med 2012; 30(02): 123-130
DOI: 10.1055/s-0032-1307420
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Long-Term Outcomes in Children Born after Assisted Conception

Esther Eisenberg
1   Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee
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Publication History

Publication Date:
27 April 2012 (online)

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Abstract

Millions of children have been born worldwide through assisted reproductive technology (ART), and access is increasing yearly. Our current knowledge and understanding of the long-term risks and/or benefits to the children conceived is incomplete. Investigations of the health, disease, cognitive, developmental, and behavioral outcomes are often confounded by other factors, including multiple gestations, prematurity, and low birthweight. Reports of the long-term health and psychosocial adjustment of children conceived with ART show generally good outcomes. Many of the major long-term problems observed in the children may be associated with multiple gestations, preterm delivery, and low birthweight or with subfertility of the parents. Evidence in the male infants conceived with the aid of intracytoplasmic sperm injection suggests an increased risk of reproductive tract anomalies such as hypospadias. Outcome data on health of children born after cryopreservation of cleavage stage embryos are reassuring. Measuring long-term outcomes is the first step to improving and optimizing health in the offspring conceived with medical and technological assistance.

Keywords

assisted reproductive technology (ART) - ovarian stimulation - gamete manipulation - birth outcomes - male reproductive tract anomalies - cerebral palsy - neurodevelopmental outcomes - psychosocial outcomes
 

  • References

  • 1 Nygren KG, Sullivan E, Zegers-Hochschild F , et al. International Committee for Monitoring Assisted Reproductive Technology (ICMART) world report: assisted reproductive technology 2003. Fertil Steril 2011; 95 (7) 2209-2222 , 2222, e1–e17
    CrossrefPubMedSearch in Google Scholar
  • 2 Dapuzzo L, Seitz FE, Dodson WC, Stetter C, Kunselman AR, Legro RS. Incomplete and inconsistent reporting of maternal and fetal outcomes in infertility treatment trials. Fertil Steril 2011; 95 (8) 2527-2530
    CrossrefPubMedSearch in Google Scholar
  • 3 de Mouzon J, Goossens V, Bhattacharya S , et al; European IVF-monitoring (EIM) Consortium, for the European Society of Human Reproduction and Embryology (ESHRE). Assisted reproductive technology in Europe, 2006: results generated from European registers by ESHRE. Hum Reprod 2010; 25 (8) 1851-1862
    CrossrefPubMedSearch in Google Scholar
  • 4 Kalra SK, Barnhart KT. In vitro fertilization and adverse childhood outcomes: what we know, where we are going, and how we will get there. A glimpse into what lies behind and beckons ahead. Fertil Steril 2011; 95 (6) 1887-1889
    CrossrefPubMedSearch in Google Scholar
  • 5 Black M, Bhattacharya S. Epidemiology of multiple pregnancy and the effect of assisted conception. Semin Fetal Neonatal Med 2010; 15 (6) 306-312
    CrossrefPubMedSearch in Google Scholar
  • 6 Fauser BCJM, Devroey P, Macklon NS. Multiple birth resulting from ovarian stimulation for subfertility treatment. Lancet 2005; 365 (9473) 1807-1816
    CrossrefPubMedSearch in Google Scholar
  • 7 Fortunato A, Tosti E. The impact of in vitro fertilization on health of the children: an update. Eur J Obstet Gynecol Reprod Biol 2011; 154 (2) 125-129
    CrossrefPubMedSearch in Google Scholar
  • 8 McDonald SD, Han Z, Mulla S, Ohlsson A, Beyene J, Murphy KE ; Knowledge Synthesis Group. Preterm birth and low birth weight among in vitro fertilization twins: a systematic review and meta-analyses. Eur J Obstet Gynecol Reprod Biol 2010; 148 (2) 105-113
    CrossrefPubMedSearch in Google Scholar
  • 9 Messerschmidt A, Olischar M, Birnbacher R, Weber M, Pollak A, Leitich H. Perinatal outcome of preterm infants <1500 g after IVF pregnancies compared with natural conception. Arch Dis Child Fetal Neonatal Ed 2010; 95 (3) F225-F229
    CrossrefPubMedSearch in Google Scholar
  • 10 Pinborg A, Loft A, Aaris Henningsen AK, Rasmussen S, Andersen AN. Infant outcome of 957 singletons born after frozen embryo replacement: the Danish National Cohort Study 1995–2006. Fertil Steril 2010; 94 (4) 1320-1327
    CrossrefPubMedSearch in Google Scholar
  • 11 Källén B, Finnström O, Lindam A, Nilsson E, Nygren KG, Otterblad PO. Congenital malformations in infants born after in vitro fertilization in Sweden. Birth Defects Res A Clin Mol Teratol 2010; 88 (3) 137-143
    PubMedSearch in Google Scholar
  • 12 Funke S, Flach E, Kiss I , et al. Male reproductive tract abnormalities: more common after assisted reproduction?. Early Hum Dev 2010; 86 (9) 547-550
    CrossrefPubMedSearch in Google Scholar
  • 13 Reefhuis J, Honein MA, Schieve LA, Rasmussen SA ; National Birth Defects Prevention Study. Use of clomiphene citrate and birth defects, National Birth Defects Prevention Study, 1997–2005. Hum Reprod 2011; 26 (2) 451-457
    CrossrefPubMedSearch in Google Scholar
  • 14 Registry of pregnancies conceived following exposure to ovulation stimulation medications. Available at: http://clinicaltrials.gov/ct2/show/NCT00902382 . Accessed June 27, 2011
    PubMed
  • 15 SART national data summary. Clinic Summary Report. Available at: http://www.sartcorsonline.com . Accessed June 29, 2011
    PubMed
  • 16 Ludwig AK, Katalinic A, Thyen U, Sutcliffe AG, Diedrich K, Ludwig M. 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 2009; 91 (1) 115-124
    CrossrefPubMedSearch in Google Scholar
  • 17 Fedder J, Gabrielsen A, Humaidan P, Erb K, Ernst E, Loft A. Malformation rate and sex ratio in 412 children conceived with epididymal or testicular sperm. Hum Reprod 2007; 22 (4) 1080-1085
    CrossrefPubMedSearch in Google Scholar
  • 18 Belva F, De Schrijver F, Tournaye H , et al. Neonatal outcome of 724 children born after ICSI using non-ejaculated sperm. Hum Reprod 2011; 26 (7) 1752-1758
    CrossrefPubMedSearch in Google Scholar
  • 19 Woldringh GH, Horvers M, Janssen AJ , et al. Follow-up of children born after ICSI with epididymal spermatozoa. Hum Reprod 2011; 26 (7) 1759-1767
    CrossrefPubMedSearch in Google Scholar
  • 20 Rudick B, Opper N, Paulson R, Bendikson K, Chung K. The status of oocyte cryopreservation in the United States. Fertil Steril 2010; 94 (7) 2642-2646
    CrossrefPubMedSearch in Google Scholar
  • 21 Wennerholm UB, Söderström-Anttila V, Bergh C , et al. Children born after cryopreservation of embryos or oocytes: a systematic review of outcome data. Hum Reprod 2009; 24 (9) 2158-2172
    CrossrefPubMedSearch in Google Scholar
  • 22 Chian RC, Huang JY, Tan SL , et al. Obstetric and perinatal outcome in 200 infants conceived from vitrified oocytes. Reprod Biomed Online 2008; 16 (5) 608-610
    CrossrefPubMedSearch in Google Scholar
  • 23 Kansal Kalra S, Ratcliffe SJ, Milman L, Gracia CR, Coutifaris C, Barnhart KT. Perinatal morbidity after in vitro fertilization is lower with frozen embryo transfer. Fertil Steril 2011; 95 (2) 548-553
    CrossrefPubMedSearch in Google Scholar
  • 24 Henningsen AK, Pinborg A, Lidegaard O, Vestergaard C, Forman JL, Andersen AN. Perinatal outcome of singleton siblings born after assisted reproductive technology and spontaneous conception: Danish national sibling-cohort study. Fertil Steril 2011; 95 (3) 959-963
    CrossrefPubMedSearch in Google Scholar
  • 25 Li HZ, Qiao J, Chi HB, Chen XN, Liu P, Ma CH. Comparison of the major malformation rate of children conceived from cryopreserved embryos and fresh embryos. Chin Med J (Engl) 2010; 123 (14) 1893-1897
    PubMedSearch in Google Scholar
  • 26 Liebaers I, Desmyttere S, Verpoest W , et al. Report on a consecutive series of 581 children born after blastomere biopsy for preimplantation genetic diagnosis. Hum Reprod 2010; 25 (1) 275-282
    CrossrefPubMedSearch in Google Scholar
  • 27 Desmyttere S, De Schepper J, Nekkebroeck J , et al. Two-year auxological and medical outcome of singletons born after embryo biopsy applied in preimplantation genetic diagnosis or preimplantation genetic screening. Hum Reprod 2009; 24 (2) 470-476
    CrossrefPubMedSearch in Google Scholar
  • 28 Middelburg KJ, van der Heide M, Houtzager B , et al; PGS Follow-up Study Group. Mental, psychomotor, neurologic, and behavioral outcomes of 2-year-old children born after preimplantation genetic screening: follow-up of a randomized controlled trial. Fertil Steril 2011; 96 (1) 165-169
    CrossrefPubMedSearch in Google Scholar
  • 29 Källén B, Finnström O, Lindam A, Nilsson E, Nygren KG, Otterblad Olausson P. Trends in delivery and neonatal outcome after in vitro fertilization in Sweden: data for 25 years. Hum Reprod 2010; 25 (4) 1026-1034
    CrossrefPubMedSearch in Google Scholar
  • 30 Beydoun HA, Sicignano N, Beydoun MA , et al. A cross-sectional evaluation of the first cohort of young adults conceived by in vitro fertilization in the United States. Fertil Steril 2010; 94 (6) 2043-2049
    CrossrefPubMedSearch in Google Scholar
  • 31 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 2005; 20 (2) 413-419
    PubMedSearch in Google Scholar
  • 32 Bruinsma F, Venn A, Lancaster P, Speirs A, Healy D. Incidence of cancer in children born after in-vitro fertilization. Hum Reprod 2000; 15 (3) 604-607
    CrossrefPubMedSearch in Google Scholar
  • 33 Klip H, Burger CW, de Kraker J, van Leeuwen FE ; OMEGA-project group. Risk of cancer in the offspring of women who underwent ovarian stimulation for IVF. Hum Reprod 2001; 16 (11) 2451-2458
    PubMedSearch in Google Scholar
  • 34 Källén B, Finnström O, Lindam A, Nilsson E, Nygren KG, Olausson PO. Cancer risk in children and young adults conceived by in vitro fertilization. Pediatrics 2010; 126 (2) 270-276
    CrossrefPubMedSearch in Google Scholar
  • 35 Hvidtjørn D, Grove J, Schendel D , et al. Multiplicity and early gestational age contribute to an increased risk of cerebral palsy from assisted conception: a population-based cohort study. Hum Reprod 2010; 25 (8) 2115-2123
    CrossrefPubMedSearch in Google Scholar
  • 36 Källén AJ, Finnström OO, Lindam AP, Nilsson EM, Nygren KG, Olausson PM. Cerebral palsy in children born after in vitro fertilization. Is the risk decreasing?. Eur J Paediatr Neurol 2010; 14 (6) 526-530
    CrossrefPubMedSearch in Google Scholar
  • 37 Zhu JL, Hvidtjørn D, Basso O , et al. Parental infertility and cerebral palsy in children. Hum Reprod 2010; 25 (12) 3142-3145
    CrossrefPubMedSearch in Google Scholar
  • 38 Schendelaar P, Middelburg KJ, Bos AF, Heineman MJ, Jongbloed-Pereboom M, Hadders-Algra M. The Groningen ART cohort study: the effects of ovarian hyperstimulation and the IVF laboratory procedures on neurological condition at 2 years. Hum Reprod 2011; 26 (3) 703-712
    CrossrefPubMedSearch in Google Scholar
  • 39 Hvidtjørn D, Schieve L, Schendel D, Jacobsson B, Svaerke C, Thorsen P. Cerebral palsy, autism spectrum disorders, and developmental delay in children born after assisted conception: a systematic review and meta-analysis. Arch Pediatr Adolesc Med 2009; 163 (1) 72-83
    CrossrefPubMedSearch in Google Scholar
  • 40 Hvidtjørn D, Grove J, Schendel D , et al. Risk of autism spectrum disorders in children born after assisted conception: a population-based follow-up study. J Epidemiol Community Health 2011; 65 (6) 497-502
    CrossrefPubMedSearch in Google Scholar
  • 41 Wagenaar K, Huisman J, Cohen-Kettenis PT, Delemarre-van de Waal HA. An overview of studies on early development, cognition, and psychosocial well-being in children born after in vitro fertilization. J Dev Behav Pediatr 2008; 29 (3) 219-230
    CrossrefPubMedSearch in Google Scholar
  • 42 Olivennes F, Golombok S, Ramogida C, Rust J ; Follow-Up Team. Behavioral and cognitive development as well as family functioning of twins conceived by assisted reproduction: findings from a large population study. Fertil Steril 2005; 84 (3) 725-733
    CrossrefPubMedSearch in Google Scholar
  • 43 Mains L, Zimmerman M, Blaine J , et al. Achievement test performance in children conceived by IVF. Hum Reprod 2010; 25 (10) 2605-2611
    CrossrefPubMedSearch in Google Scholar
  • 44 Middelburg KJ, Heineman MJ, Bos AF, Hadders-Algra M. Neuromotor, cognitive, language and behavioural outcome in children born following IVF or ICSI—a systematic review. Hum Reprod Update 2008; 14 (3) 219-231
    CrossrefPubMedSearch in Google Scholar
  • 45 Leunens L, Celestin-Westreich S, Bonduelle M, Liebaers I, Ponjaert-Kristoffersen I. Follow-up of cognitive and motor development of 10-year-old singleton children born after ICSI compared with spontaneously conceived children. Hum Reprod 2008; 23 (1) 105-111
    CrossrefPubMedSearch in Google Scholar
  • 46 Wagenaar K, van Weissenbruch MM, Knol DL, Cohen-Kettenis PT, Delemarre-van de Waal HA, Huisman J. Behavior and socioemotional functioning in 9–18-year-old children born after in vitro fertilization. Fertil Steril 2009; 92 (6) 1907-1914
    CrossrefPubMedSearch in Google Scholar
  • 47 Golombok S, MacCallum F, Goodman E. The “test-tube” generation: parent-child relationships and the psychological well-being of in vitro fertilization children at adolescence. Child Dev 2001; 72 (2) 599-608
    CrossrefPubMedSearch in Google Scholar
  • 48 Barnes J, Sutcliffe AG, Kristoffersen I , et al; European Study. The influence of assisted reproduction on family functioning and children's socio-emotional development: results from a European study. Hum Reprod 2004; 19 (6) 1480-1487
    CrossrefPubMedSearch in Google Scholar
  • 49 Golombok S, Brewaeys A, Giavazzi MT, Guerra D, MacCallum F, Rust J. The European study of assisted reproduction families: the transition to adolescence. Hum Reprod 2002; 17 (3) 830-840
    Search in Google Scholar
  • 50 Wagenaar K, van Weissenbruch MM, van Leeuwen FE , et al. Self-reported behavioral and socioemotional functioning of 11- to 18-year-old adolescents conceived by in vitro fertilization. Fertil Steril 2011; 95 (2) 611-616
    CrossrefPubMedSearch in Google Scholar