Hostname: page-component-89b8bd64d-r6c6k Total loading time: 0 Render date: 2026-05-05T05:26:56.079Z Has data issue: false hasContentIssue false
  • English
  • Français

Assisted reproductive technologies: a hierarchy of risks for conception, pregnancy outcomes and treatment decisions

Part of: DOHAD & IVF

Published online by Cambridge University Press:  19 July 2017

M. J. Davies ,
A. R. Rumbold  and
V. M. Moore
M. J. Davies*
Affiliation:
Lifecourse and Intergenerational Health, The Robinson Institute, University of Adelaide, Adelaide, Australia
A. R. Rumbold
Affiliation:
Lifecourse and Intergenerational Health, The Robinson Institute, University of Adelaide, Adelaide, Australia
V. M. Moore
Affiliation:
Lifecourse and Intergenerational Health, The Robinson Institute, University of Adelaide, Adelaide, Australia Discipline of Public Health, University of Adelaide, Adelaide, Australia
*
*Address for correspondence: M. Davies, Lifecourse and Intergenerational Health, The Robinson Institute, The University of Adelaide, Level 8 Hughes Building, Adelaide, 5006, South Australia. (Email michael.davies@adelaide.edu.au)
Get access Rights & Permissions [Opens in a new window]

Abstract

The use of assisted reproductive technologies (ART) for the treatment of infertility has grown exponentially over the last 20 years, and now accounts for 4% of all births in Australia, and over 1 m births annually around the globe. There is consistent reporting of increased risk of adverse perinatal outcomes and birth defects following infertility treatment. However, change in practice has been stymied by critical knowledge gaps with regards to (a) the relative contribution of patient and treatment factors to adverse outcomes, (b) the independent contribution of specific contemporary treatments and treatment combinations to outcomes, (c) the impact of innovations in laboratory and clinical practice on treatment success and observed risk and (d) changes over time in patient characteristics. Here we summarize key findings from the South Australian Birth Cohort, which is a whole-of-population cohort of over 300,000 births from 1986 to 2002. Relative to spontaneous conceptions, singletons from assisted conception were more likely to be stillborn [odds ratio (OR)=1.82; 95% confidence interval (CI) 1.34–2.48], while survivors as a group were comprehensively disadvantaged at birth, including lower birth weight (OR=2109 g; 95% CI 2129–289), very low birth weight (OR=2.74; 95% CI 2.19–3.43), very preterm birth (OR=2.30; 95% CI 1.82–2.90) and neonatal death (OR=2.04; 95% CI 1.27–3.26). Major birth defects, including cardiac, urogenital and musculoskeletal defects are doubled after fresh ICSI cycles, which is a particular concern as ICSI now accounts for 70% of all treatment cycles globally. Future study is needed to provide contemporary, precise evidence to inform patient and clinic decision making, and generate knowledge for future innovation in ART laboratory methods and clinical practice, thereby optimizing treatment and health outcomes while reducing adverse events.

Keywords

developmental stagefetus/fetushumanpregnancy

Information

Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 8 , Issue 4: Themed Issue: Assisted Reproductive Treatments (ART) and DOHAD , August 2017 , pp. 443 - 447
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

1. Mansour, R, et al. International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted Reproductive Technology 2006. Hum Reprod. 2014; 29, 1536–1551.Google Scholar
2. Macaldowie, A, Wang, Y, Chughtai, A, Chambers, G. Australia’s Mothers and Babies 2012. Perinatal statistics series, 2014. AIHW National Perinatal Statistics Unit, Sydney, NSW.Google Scholar
3. Hart, R, Norman, RJ. The longer-term health outcomes for children born as a result of IVF treatment: Part I – general health outcomes. Hum Reprod Update. 2013; 19, 232–243.CrossRefGoogle ScholarPubMed
4. Davies, MJ, et al. Reproductive technologies and the risk of birth defects. New Engl J Med. 2012; 366, 1803–1813.Google Scholar
5. Petrou, S, Eddama, O, Mangham, L. A structured review of the recent literature on the economic consequences of preterm birth. Arch Dis Child Fetal Neonatal Ed. 2011; 96, F225–F232.Google Scholar
6. Marino, JL, et al. Perinatal outcomes by mode of assisted conception and sub-fertility in an Australian data linkage cohort. PLoS One. 2014; 9, e80398.Google Scholar
7. Pinborg, A, et al. Why do singletons conceived after assisted reproduction technology have adverse perinatal outcome? Systematic review and meta-analysis. Hum Reprod Update. 2013; 19, 87–104.Google Scholar
8. Lancaster, PA. Obstetric outcome. Clin Obstet Gynaecol. 1985; 12, 847–864.Google Scholar
9. Society of Obstetricians and Gynaecologists of Canada, Okun, N, Sierra, S. Pregnancy outcomes after assisted human reproduction. J Obstet Gynaecol Can. 2014; 36, 64–83.Google Scholar
10. Davies, MJ, et al. Maternal factors and the risk of birth defects after IVF and ICSI: a whole of population cohort study. BJOG. 2016.Google Scholar
11. Maheshwari, A, Pandey, S, Shetty, A, Hamilton, M, Bhattacharya, S. Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril. 2012; 98, 368–377.e361–369.Google Scholar
12. Hansen, M, Bower, C. The impact of assisted reproductive technologies on intra-uterine growth and birth defects in singletons. Semin Fetal Neonatal Med. 2014; 19, 228–233.CrossRefGoogle ScholarPubMed
13. Barnhart, KT. Assisted reproductive technologies and perinatal morbidity: interrogating the association. Fertil Steril. 2013; 99, 299–302.Google Scholar
14. Pinborg, A, et al. Large baby syndrome in singletons born after frozen embryo transfer (FET): is it due to maternal factors or the cryotechnique? Hum Reprod. 2014; 29, 618–627.CrossRefGoogle ScholarPubMed
15. Whitelaw, N, et al. Epigenetic status in the offspring of spontaneous and assisted conception. Hum Reprod. 2014.Google Scholar
16. Henningsen, AA, et al. Trends in perinatal health after assisted reproduction: a Nordic study from the CoNARTaS group. Hum Reprod. 2015.Google Scholar
17. Sazonova, A, Källen, K, Thurin-Kjellberg, A, Wennerholm, U-B, Bergh, C. Obstetric outcome in singletons after in vitro fertilization with cryopreserved/thawed embryos. Hum Reprod. 2012; 27, 1343–1350.Google Scholar
18. Assisted reproductive technology in Australia and New Zealand 2010. Cat. no. PER 55, 2012.Google Scholar
19. Boulet, SL, et al. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA. 2015; 313, 255–263.CrossRefGoogle ScholarPubMed
20. van Heesch, MM, et al. A comparison of perinatal outcomes in singletons and multiples born after in vitro fertilization or intracytoplasmic sperm injection stratified for neonatal risk criteria. Acta Obstet Gynecol Scand. 2014; 93, 277–286.Google Scholar
21. Toshimitsu, M, et al. Increased risk of pregnancy-induced hypertension and operative delivery after conception induced by in vitro fertilization/intracytoplasmic sperm injection in women aged 40 years and older. Fertil Steril. 2014.CrossRefGoogle Scholar
22. Pinborg, A, Lidegaard, O, Andersen, AN. The vanishing twin: a major determinant of infant outcome in IVF singleton births. Br J Hosp Med (Lond). 2006; 67, 417–420.Google Scholar
23. Davies, MJ, et al. Spontaneous loss of a co-twin and the risk of birth defects after assisted conception. J Dev Orig Health Dis. 2016; 7, 678–684.Google Scholar
24. Liu, SY, et al. Obstetric and neonatal outcomes after transfer of vitrified early cleavage embryos. Hum Reprod. 2013; 28, 2093–2100.CrossRefGoogle ScholarPubMed
25. Vega, M, Breborowicz, A, Moshier, EL, McGovern, PG, Keltz, MD. Blastulation rates decline in a linear fashion from euploid to aneuploid embryos with single versus multiple chromosomal errors. Fertil Steril. 2014; 102, 394–398.Google Scholar
26. Kanter, JR, Boulet, SL, Kawwass, JF, Jamieson, DJ, Kissin, DM. Trends and correlates of monozygotic twinning after single embryo transfer. Obstet Gynecol. 2015; 125, 111–117.Google Scholar
27. Wright, V, Schieve, LA, Vahratian, A, Reynolds, MA. Monozygotic twinning associated with day 5 embryo transfer in pregnancies conceived after IVF. Hum Reprod. 2004; 19, 1831–1836.CrossRefGoogle ScholarPubMed
28. Pinborg, A, Henningsen, AK, Malchau, SS, Loft, A. Congenital anomalies after assisted reproductive technology. Fertil Steril. 2013; 99, 327–332.CrossRefGoogle ScholarPubMed
29. Kallen, B, et al. Blastocyst versus cleavage stage transfer in in vitro fertilization: differences in neonatal outcome? Fertil Steril. 2010; 94, 1680–1683.Google Scholar
30. Gardner, DK. The impact of physiological oxygen during culture, and vitrification for cryopreservation, on the outcome of extended culture in human IVF. Reprod Biomed Online. 2016; 32, 137–141.Google Scholar
31. Chambers, GM, Chughtai, AA, Farquhar, CM, Wang, YA. Risk of preterm birth after blastocyst embryo transfer: a large population study using contemporary registry data from Australia and New Zealand. Fertil Steril. 2015; 104, 997–1003.CrossRefGoogle ScholarPubMed
32. Zander-Fox, D, Lane, M, Hamilton, H. Slow freezing and vitrification of mouse morula and early blastocysts. J Assist Reprod Genet. 2013; 30, 1091–1098.CrossRefGoogle ScholarPubMed
33. Banwell, KM, Lane, M, Russell, DL, Kind, KL, Thompson, JG. Oxygen concentration during mouse oocyte in vitro maturation affects embryo and fetal development. Hum Reprod. 2007; 22, 2768–2775.Google Scholar
34. Kleijkers, SH, et al. IVF culture medium affects post-natal weight in humans during the first 2 years of life. Hum Reprod. 2014.Google Scholar
35. Eskild, A, Monkerud, L, Tanbo, T. Birthweight and placental weight; do changes in culture media used for IVF matter? Comparisons with spontaneous pregnancies in the corresponding time periods. Hum Reprod. 2013; 28, 3207–3214.Google Scholar
36. Allen, VM, Wilson, RD, Cheung, A. Pregnancy outcomes after assisted reproductive technology. J Obstet Gynaecol Can. 2006; 28, 220–250.Google Scholar
37. Health Quality Ontario. In vitro fertilization and multiple pregnancies: an evidence-based analysis. Ont Health Technol Assess Ser. 2006; 6, 1–63.Google Scholar
38. Myers, ER, et al. Effectiveness of assisted reproductive technology (ART). Evid Rep Technol Assess. 2008; 1–195.Google Scholar