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Assisted Reproduction · Safety and Risks

The Association of Assisted Reproductive Technology with Placental and Umbilical Abnormalities

Siargkas A, Tsakiridis I, Giouleka S, Chaveeva P, Mar Gil M, Plasencia W, De Paco Matallana C, Kolibianakis EM, Dagklis T

Published April 27, 2025 Journal of personalized medicine, 15(5)
DOI 10.3390/jpm15050176 PMID 40423048 PMC PMC12113098

RRM Academy Synopsis

IVF pregnancies were associated with some placenta and cord problems

In a retrospective cohort of 13,854 single-baby pregnancies in Greece, IVF or ICSI pregnancies were linked to higher odds of seven placenta and cord abnormalities. Researchers compared 647 assisted reproductive technology (ART) pregnancies with spontaneous ones. They adjusted for factors like age, BMI and smoking.

Key Findings

  • Placenta previa had an adjusted odds ratio (aOR) of 1.99 (95% CI 1.10–3.61) and low-lying placenta an aOR of 1.71 (95% CI 1.38–2.11) in ART pregnancies.
  • In ART pregnancies, bilobate placenta had an aOR of 2.81 (95% CI 1.92–4.11), velamentous cord insertion 3.13 (95% CI 1.98–4.95) and marginal cord insertion 1.63 (95% CI 1.32–2.01).
  • In ART pregnancies, vasa previa had an aOR of 5.51 (95% CI 1.28–23.76) and single umbilical artery an aOR of 2.62 (95% CI 1.02–6.72).
  • After propensity score matching, five of the seven associations stayed significant, among them bilobate placenta (aOR 2.85, 95% CI 1.72–4.73) and velamentous cord insertion (aOR 2.08, 95% CI 1.13–3.83).
  • After matching, the associations with single umbilical artery (an aOR of 1.63, 95% CI 0.54–4.86) and with vasa previa (an aOR of 3.61, 95% CI 0.65–19.91) were no longer statistically significant.

Interpretation

The study is a retrospective cohort from one Greek hospital department, and the authors report associations observed in that setting. ICSI means injecting a single sperm into an egg. The authors state that other factors may still distort the results, especially the cause of infertility and the exact ART method. Multiple statistical comparisons raise the chance of a false-positive result, which the authors put at approximately 40%. Vasa previa is rare, and its wide confidence intervals limit how firm the result is.

RRM Context

Restorative reproductive medicine treats the cause of infertility and aims for conception in vivo. IVF bypasses the reproductive system and leaves the reason for infertility unresolved. The authors list the cause of infertility among the factors they could not fully adjust for. Placental outcomes belong in the record next to the live birth rate for any response to infertility.

Our editorial summary of this paper, not the article's abstract.

Abstract

Objective

Global utilization of assisted reproductive technology (ART) is increasing; however, it is associated with adverse perinatal outcomes. Placental and umbilical cord abnormalities contribute significantly to these negative outcomes. However, it remains unclear whether ART independently increases the risk of such abnormalities. This study aimed to investigate the association between ART and key umbilico-placental abnormalities, after adjustment for confounders.

Methods

In this retrospective cohort study, singleton pregnancies receiving routine antenatal care (January 2015 to June 2024) at the 3rd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Greece, were analyzed. Pregnancies conceived via ART were compared to those conceived spontaneously. To investigate placental and cord anomalies, this study employed multiple logistic regression. This approach adjusted for various confounders, including maternal age, BMI, parity, smoking status, history of previous cesarean section, diabetes mellitus, and thyroid disease.

Results

This study included a total of 13,854 singleton pregnancies, of which 647 were conceived via ART. ART was significantly associated with an increased risk of placenta previa (aOR 1.99, 95% CI 1.10-3.61), low-lying placenta (aOR 1.71, 95% CI 1.38-2.11), bilobate placenta (aOR 2.81, 95% CI 1.92-4.11), single umbilical artery (aOR 2.62, 95% CI 1.022-6.715), marginal (aOR 1.63, 95% CI 1.32-2.01) and velamentous cord insertion (aOR 3.13, 95% CI 1.98-4.95), and vasa previa (aOR 5.51, 95% CI 1.28-23.76).

Conclusions

ART-conceived pregnancies appear to carry a higher risk for certain placental and umbilical cord abnormalities, potentially contributing to adverse perinatal outcomes. Further studies are required to investigate the pathophysiology underlying these associations.

Topics

By this author

Related research

Assisted Reproduction › Safety and Risks › Procedure-Attributable Risk
Antonios Siargkas, Ioannis Tsakiridis, Sonia Giouleka, Petya Chaveeva, Maria Mar Gil, Walter Plasencia, Catalina De Paco Matallana, Efstratios M Kolibianakis, Themistoklis Dagklis
A Siargkas, I Tsakiridis, S Giouleka, P Chaveeva, M Gil, W Plasencia, C Matallana, E Kolibianakis, T Dagklis
PMID 40423048 40423048 DOI 10.3390/jpm15050176 10.3390/jpm15050176 Siargkas et al. 2025, Siargkas 2025

Keywords

assisted reproductive technology, bilobate placenta, in vitro fertilization, low-lying placenta, placenta previa, single umbilical artery, vasa previa, velamentous cord insertion

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