The PLART study: incidence of preterm labor and adverse pregnancy outcomes after assisted reproductive techniques—a retrospective cohort study

  • Erica SantiEmail author
  • Giulia Nencini
  • Angelica Cerni
  • Pantaleo Greco
  • Federico Spelzini
  • Beniamino Tormettino
  • Marco Scioscia
Maternal-Fetal Medicine


Key message

Even though assisted reproductive techniques represent one of the greatest achievements in modern medicine, the risk of preterm birth related to these pregnancies is about twice as high. This must be highlighted and further investigated to optimize the management of both mothers and newborns.


The purpose of this study was to compare adverse pregnancy outcomes after assisted reproductive techniques (ART) and spontaneous conceptions, focusing on the incidence of preterm births (PTB) and distinguishing between iatrogenic and spontaneous events.


This retrospective cohort study analyzed single births of one Italian hospital. The incidence of PTBs in ART pregnancies, divided into iatrogenic procedures, spontaneous preterm labors and preterm premature ruptures of the membranes (pPROMs), was compared with the non-ART control group. The incidence of other adverse pregnancy outcomes and the types of delivery were also reported and compared.


Of the 11,769 single births included, 2.39% were conceived by ART. The incidence of PTBs was 4.74% for spontaneous pregnancies and 12.8% for ART pregnancies (aOR 1.93; 95% CI 1.29–2.88). The percentage of iatrogenic procedures was 27.78% in the ART-PTBs’ group and 30.88% in the non-ART-PTBs’ controls. ART pregnancies showed an increased incidence of pPROMs (6.40% versus 2.41%), preterm labors (2.85% versus 0.93%), hypertensive disorders of the pregnancy (8.19% versus 2.32%), placenta previa (3.20% versus 0.59%), cesarean sections (28.47% versus 16.27%) and vacuum extractions (10.32% versus 5.19%).


Singleton ART pregnancies have a higher risk of PTB which is mostly linked to a higher incidence of pPROMs and spontaneous preterm labor. The concurrency of a demonstrated higher risk of hypertensive gestational disorders and placenta previa suggests that placental development plays an important role in the pathogenesis of PTB.


Assisted reproductive techniques Preterm birth Preterm labor Preterm premature rupture of membranes Gestational hypertension Placenta previa 



Adverse pregnancy outcome


Assisted reproductive techniques


Body mass index


Preterm labor after assisted reproductive techniques


Preterm birth


Preterm premature rupture of the membranes



The authors thank Dr. Elisabetta Fabbri for her assistance with statistics and for the great availability.

Author contributions

We certify that all authors equally contributed to the realization of the study. In particular: AC data collection. PG, FS and BT project development. GN manuscript writing. ES data collection and manuscript writing. MS manuscript editing.

Compliance with ethical standards

Conflict of interest

All authors declare that there is no conflict of interest.

Ethical approval

Given its retrospective design, this article does not contain any studies with human participants or animals performed by any of the authors. All data were collected and analyzed keeping anonymity, according to European laws on privacy. The study was approved by the Local Ethics Committee (Comitato Etico di Area Vasta Romagna) in February 2018. According to the Italian Authorisation of the Guarantor n.9/2016 and taking into account the logistic impossibility to reach out to all the women included in the study, given the large number of the sample, the investigators were exonerated from the request of informed consents.


  1. 1.
    Dunietz GL, Holzman C, McKane P, Li C, Boulet SL, Todem D et al (2015) Assisted reproductive technology and the risk of preterm birth among primiparas. Fertil Steril 103:974–979CrossRefGoogle Scholar
  2. 2.
    D’Angelo D, Whitehead N, Helms K, Barfield W, Ahluwalia I (2011) Birth outcomes of intended pregnancies among women who used assisted reproductive technology, ovulation stimulation, or no treatment. Fertil Steril 96:314–320CrossRefGoogle Scholar
  3. 3.
    Lane-Cordova AD, Khan SS, Grobman WA, Greenland P, Shah SJ (2019) Long-term cardiovascular risks associated with adverse pregnancy outcomes. J Am Coll Cardiol 73(16):2106–2116CrossRefGoogle Scholar
  4. 4.
    Das S, Blake D, Farquhar C, Seif M (2009) Assisted hatching on assisted conception (IVF and ICSI). Cochrane database Syst Rev. Google Scholar
  5. 5.
    Schieve L, Meikle S, Ferre C, Peterson H, Jeng G, Wilcox L (2002) Low and very low birth weight in infants conceived with use of assisted reproductive technology. N Engl J Med 346:731–737CrossRefGoogle Scholar
  6. 6.
    Messerlian C, Maclagan L, Basso O (2013) Infertility and the risk of adverse pregnancy outcomes: a systematic review and meta-analysis. Hum Reprod 28(1):125–137CrossRefGoogle Scholar
  7. 7.
    Jacques A, Amor D, Baker H, Healy D, Ukoumunne O, Breheny S et al (2010) Adverse obstetric and perinatal outcomes in subfertile women conceiving without assisted reproductive technologies. Fertil Steril 94(7):2674–2679CrossRefGoogle Scholar
  8. 8.
    Registro Nazionale Procreazione Medicalmente Assistita (2016). Available from: Accessed 12 Mar 2019
  9. 9.
    Sun L, Jiang L, Chen H (2017) Obstetric outcome of vanishing twins syndrome: a systematic review and meta-analysis. Arch Gynecol Obstet 295(3):559–567CrossRefGoogle Scholar
  10. 10.
    Jackson R, Gibson K, Wu Y, Croughan M (2004) Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet Gynecol 103:551–563CrossRefGoogle Scholar
  11. 11.
    Cavoretto P, Candiani M, Giorgione V, Inversetti A, Abu-Saba M, Tiberio F et al (2018) Risk of spontaneous preterm birth in singleton pregnancies conceived after IVF/ICSI treatment: meta-analysis of cohort studies. Ultrasound Obstet Gynecol 51(1):43–53CrossRefGoogle Scholar
  12. 12.
    Pandey S, Shetty A, Hamilton M, Bhattacharya S, Maheshwari A (2012) Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis. Hum Reprod Update 18:485–503CrossRefGoogle Scholar
  13. 13.
    McDonald S, Murphy K, Beyene J, Ohlsson A (2005) Perinatal outcomes of singleton pregnancies achieved by in vitro fertilization: a systematic review and meta-analysis. J Obstet Gynaecol Can 27:449–459CrossRefGoogle Scholar
  14. 14.
    Qin J, Liu X, Sheng X, Wang H, Gao S (2016) Assisted reproductive technology and the risk of pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies: a meta-analysis of cohort studies. Fertil Steril 105:73–85CrossRefGoogle Scholar
  15. 15.
    Capece A, Vasieva O, Meher S, Alfirevic Z, Alfirevic A (2014) Pathway analysis of genetic factors associated with spontaneous preterm birth and pre-labor preterm rupture of membranes. PLoS ONE 9:e108578CrossRefGoogle Scholar
  16. 16.
    Giminez L, Krupitzki H, Momany A, Gili J, Poletta F, Campana H et al (2016) Maternal and neonatal epidemiological features in clinical subtypes of preterm birth. J Matern Fetal Med 29:3153–3161CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Section of Obstetrics and Gynecology, Department of Morphology, Surgery and Experimental MedicineUniversity of Ferrara, Azienda Ospedaliero-Universitaria S. AnnaConaItaly
  2. 2.Department of Obstetrics and GynecologyOspedale Santa Maria della MisericordiaUrbinoItaly
  3. 3.Department of Obstetrics and GynecologyAUSL Romagna, Ospedale InfermiRiminiItaly
  4. 4.Section of Obstetrics and GynecologyPoliclinico Di Abano TermeAbano TermeItaly

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