Outcomes of preterm infants conceived with in vitro fertilization

Article metrics



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.


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.


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 18.

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

  19. 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.

  20. 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.

  21. 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.

  22. 22.

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

  23. 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.

  24. 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.

  25. 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.

  26. 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.

  27. 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.

  28. 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.

  29. 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.

  30. 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.

  31. 31.

    Robbins ME, Dakhlallah D, Marsh CB, Rogers LK, Tipple TE. Of mice and men: correlations between microRNA-1792 cluster expression and promoter methylation in severe bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol. 2016;311:L981–4.

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

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

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) doi:10.1038/s41372-019-0332-y

Download citation

Further reading