Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Outcomes of preterm infants conceived with in vitro fertilization

Journal of Perinatology volume 39, pages 717–722 (2019)Cite this article

Subjects

Abstract

Objectives

To determine if there is increased risk of prematurity-related complications for in vitro fertilization (IVF)-conceived preterm infants compared to matched controls.

Study Design

Cohort study of 23–34 weeks’ preterm infants from 329 US NICUs discharged from 2009 to 2016. Each IVF patient was matched to three controls.

Results

We identified 6,756 IVF-conceived preterm infants who were matched with 20,268 controls. IVF-conceived infants had no increase in non-respiratory morbidities but had significantly higher rates of bronchopulmonary dysplasia (8.4% vs 7%, p < 0.001) and significantly greater exposure to common chronic respiratory medications.

Conclusions

In this large cohort of IVF-conceived preterm infants we found similar outcomes to controls with the exception of bronchopulmonary dysplasia and respiratory medication exposure. Further research is needed to explore the influence of in vitro fertilization on the development of neonatal respiratory disease.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Sullivan-Pyke CS, Senapati S, Mainigi MA, Barnhart KT. In vitro fertilization and adverse obstetric and perinatal outcomes. Semin Perinatol. 2017;41:345–53.

    Article  Google Scholar 

  2. Corchia C, Da Frè M, Di Lallo D, Gagliardi L, Macagno F, Carnielli V, et al. Mortality and major morbidities in very preterm infants born from assisted conception or naturally conceived: results of the area-based ACTION study. BMC Pregnancy Childbirth. 2014;14:307.

    Article  Google Scholar 

  3. Declercq E, Luke B, Belanoff C, Cabral H, Diop H, Gopal D, et al. Perinatal outcomes associated with assisted reproductive technology: the Massachusetts Outcomes Study of Assisted Reproductive Technologies (MOSART). Fertil Steril. 2015;103:888–95.

    Article  Google Scholar 

  4. Dunietz GL, Holzman C, McKane P, Li C, Boulet SL, Todem D, et al. Assisted reproductive technology and the risk of preterm birth among primiparas. Fertil Steril. 2015;103:974–.e1.

    Article  Google Scholar 

  5. Kondapalli LA, Perales-Puchalt A. Low birth weight: is it related to assisted reproductive technology or underlying infertility? Fertil Steril. 2013;99:303–10.

    Article  Google Scholar 

  6. Luke B, Stern JE, Kotelchuck M, Declercq ER, Cohen B, Diop H. Birth outcomes by infertility diagnosis analyses of the Massachusetts Outcomes Study of Assisted Reproductive Technologies (MOSART). J Reprod Med. 2015;60:480–90.

    PubMed  PubMed Central  Google Scholar 

  7. Shah V, Alwassia H, Shah K, Yoon W, Shah P. Neonatal outcomes among multiple births ≤32 weeks gestational age: does mode of conception have an impact? A cohort study. BMC Pediatr. 2011;11:54.

    Article  Google Scholar 

  8. Xu XK, Wang YA, Li Z, Lui K, Sullivan EA. Risk factors associated with preterm birth among singletons following assisted reproductive technology in Australia 2007–9—a population-based retrospective study. BMC Pregnancy Childbirth. 2014;14:406.

    Article  Google Scholar 

  9. Sabban H, Zakhari A, Patenaude V, Tulandi T, Abenhaim HA. Obstetrical and perinatal morbidity and mortality among in-vitro fertilization pregnancies: a population-based study. Arch Gynecol Obstet. 2017;296:107–13.

    Article  Google Scholar 

  10. Saunders K, Spensley J, Munro J, Halasz G. Growth and physical outcome of children conceived by in vitro fertilization. Pediatrics. 1996;97:688–92.

    CAS  PubMed  Google Scholar 

  11. Al-Hathlol K. Relationship between in vitro fertilization and neonatal outcomes in very low birth weight preterm infants. Am J Perinatol. 2018;35:1113–8.

    Article  Google Scholar 

  12. Koivurova S, Hartikainen A-L, Gissler M, Hemminki E, Sovio U, Järvelin M-R. Neonatal outcome and congenital malformations in children born after in-vitro fertilization. Hum Reprod. 2002;17:1391–8.

    Article  Google Scholar 

  13. Turker G, Doger E, Arısoy AE, Günlemez A, Gökalp AS. The effect of IVF pregnancies on mortality and morbidity in tertiary unit. Ital J Pediatr. 2013;39:17.

    Article  Google Scholar 

  14. Wang ET, Sundheimer LW, Spades C, Quant C, Simmons CF, Pisarska MD. Fertility treatment is associated with stay in the neonatal intensive care unit and respiratory support in late preterm infants. J Pediatr. 2017;187:309–12.

    Article  Google Scholar 

  15. Källén B, Finnström O, Nygren K-G, Otterblad Olausson P. Asthma in Swedish children conceived by in vitro fertilisation. Arch Dis Child. 2013;98:92–96.

    Article  Google Scholar 

  16. Koivurova S, Hartikainen A-L, Sovio U, Gissler M, Hemminki E, Järvelin M-R. Growth, psychomotor development and morbidity up to 3 years of age in children born after IVF. Hum Reprod. 2003;18:2328–36.

    Article  CAS  Google Scholar 

  17. Spitzer AR, Ellsbury DL, Handler D, Clark RH. The Pediatrix BabySteps Data Warehouse and the Pediatrix QualitySteps improvement project system—tools for ‘meaningful use’ in continuous quality improvement. Clin Perinatol. 2010;37:49–70.

    Article  Google Scholar 

  18. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163:1723–9.

    Article  CAS  Google Scholar 

  19. Walsh MC, Yao Q, Gettner P, Hale E, Collins M, Hensman A, et al. Impact of a physiologic definition on bronchopulmonary dysplasia rates. Pediatrics. 2004;114:1305–11.

    Article  Google Scholar 

  20. Schimmel MS, Hammerman C, Lusky A, Reichman B. Very low-birth-weight-infants conceived by in vitro fertilization are not at higher risk for mortality and morbidity: a population-based study. Fertil Steril. 2006;85:907–12.

    Article  Google Scholar 

  21. Caserta D, Bordi G, Stegagno M, Filippini F, Podagrosi M, Roselli D, et al. Maternal and perinatal outcomes in spontaneous versus assisted conception twin pregnancies. Eur J Obstet Gynecol Reprod Biol. 2014;174:64–69.

    Article  CAS  Google Scholar 

  22. NICHD Neonatal Research Network. Neonatal BPD Outcome Estimator. https://neonatal.rti.org/index.cfm?fuseaction=bpdcalculator.start. Accessed 2018.

  23. Finnström O, Källén B, Lindam A, Nilsson E, Nygren K-G, Olausson PO. Maternal and child outcome after in vitro fertilization—a review of 25 years of population-based data from Sweden. Acta Obstet Gynecol Scand. 2011;90:494–500.

    Article  Google Scholar 

  24. Carson C, Sacker A, Kelly Y, Redshaw M, Kurinczuk JJ, Quigley MA. Asthma in children born after infertility treatment: findings from the UK Millennium Cohort Study. Hum Reprod. 2013;28:471–9.

    Article  CAS  Google Scholar 

  25. Guibas GV, Moschonis G, Xepapadaki P, Roumpedaki E, Androutsos O, Manios Y, et al. Conception via in vitro fertilization and delivery by Caesarean section are associated with paediatric asthma incidence. Clin Exp Allergy. 2013;43:1058–66.

    Article  CAS  Google Scholar 

  26. Stern JE, Luke B, Tobias M, Gopal D, Hornstein MD, Diop H. Adverse pregnancy and birth outcomes associated with underlying diagnosis with and without assisted reproductive technology treatment. Fertil Steril. 2015;103:1438–45.

    Article  Google Scholar 

  27. Wisborg K, Ingerslev HJ, Henriksen TB. In vitro fertilization and preterm delivery, low birth weight, and admission to the neonatal intensive care unit: a prospective follow-up study. Fertil Steril. 2010;94:2102–6.

    Article  Google Scholar 

  28. McGovern PG, Llorens AJ, Skurnick JH, Weiss G, Goldsmith LT. Increased risk of preterm birth in singleton pregnancies resulting from in vitro fertilization-embryo transfer or gamete intrafallopian transfer: a meta-analysis. Fertil Steril. 2004;82:1514–20.

    Article  Google Scholar 

  29. de Waal E, Vrooman LA, Fischer E, Ord T, Mainigi MA, Coutifaris C, et al. The cumulative effect of assisted reproduction procedures on placental development and epigenetic perturbations in a mouse model. Hum Mol Genet. 2015;24:6975–85.

    PubMed  PubMed Central  Google Scholar 

  30. Choux C, Binquet C, Carmignac V, Bruno C, Chapusot C, Barberet J et al. The epigenetic control of transposable elements and imprinted genes in newborns is affected by the mode of conception: ART versus spontaneous conception without underlying infertility. Hum Reprod. 2017. https://doi.org/10.1093/humrep/dex366.

    Article  Google Scholar 

  31. Robbins ME, Dakhlallah D, Marsh CB, Rogers LK, Tipple TE. Of mice and men: correlations between microRNA-17∼92 cluster expression and promoter methylation in severe bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol. 2016;311:L981–4.

    Article  Google Scholar 

Download references

Author contribution

KAA conceptualized and designed the study, analyzed and interpreted data, drafted the initial manuscript, and approved the final manuscript as submitted. PR, RHC, and VNT conceptualized and designed the study, analyzed and interpreted data, critically reviewed and revised the manuscript, and approved the final manuscript as written. CAC analyzed and interpreted data, critically reviewed and revised the manuscript, and approved the final manuscript as written. MMB carried out the data analyses, critically reviewed and revised the manuscript, and approved the final manuscript as written.

Author information

Authors and Affiliations

  1. Pediatrix Medical Group, San Antonio, TX, USA

    Kaashif Aqeeb Ahmad

  2. Department of Pediatrics, Baylor College of Medicine, San Antonio, TX, USA

    Kaashif Aqeeb Ahmad

  3. The Center for Research, Education, Quality and Safety, MEDNAX National Medical Group, Sunrise, FL, USA

    Kaashif Aqeeb Ahmad, C. Andrew Combs, Reese H. Clark & Veeral N. Tolia

  4. Center for Clinical Effectiveness, Baylor Scott & White Health, Dallas, TX, USA

    Monica M. Bennett

  5. Pediatrix Medical Group, Austin, TX, USA

    Polli Rayburn

  6. Pediatrix Medical Group, Dallas, TX, USA

    Veeral N. Tolia

  7. Department of Pediatrics, Baylor University Medical Center, Dallas, TX, USA

    Veeral N. Tolia

Authors
  1. Kaashif Aqeeb Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Monica M. Bennett
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Polli Rayburn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Andrew Combs
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Reese H. Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Veeral N. Tolia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kaashif Aqeeb Ahmad.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ahmad, K.A., Bennett, M.M., Rayburn, P. et al. Outcomes of preterm infants conceived with in vitro fertilization. J Perinatol 39, 717–722 (2019). https://doi.org/10.1038/s41372-019-0332-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-019-0332-y

This article is cited by

Search

Advanced search

Quick links