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Assisted Reproduction · Safety and Risks

Complications and adverse outcomes in pregnancy and childbirth among women who conceived by assisted reproductive technologies: a nationwide birth cohort study of Japan environment and children's study

Nagata C, Yang L, Yamamoto-Hanada K, Mezawa H, Ayabe T, Ishizuka K, Konishi M, Ohya Y, Saito H, Sago H, Japan Environment & Children’s Study Group

Published February 20, 2019 BMC pregnancy and childbirth
DOI 10.1186/s12884-019-2213-y PMID 30786865 PMC PMC6381747

RRM Academy Synopsis

ART pregnancies had higher risks of placenta problems and transfusion

Women who conceived by ART had higher risks of blood transfusion and ICU admission. This Japanese nationwide birth cohort compared 1476 conventional IVF-ET pregnancies and 1671 ICSI pregnancies with 90,506 natural conceptions. Placenta previa, morbidly adherent placenta and preterm birth were also more likely after ART.

Key Findings

  • After conventional IVF-ET, adjusted odds ratios were: placenta previa 2.90 (95% CI 1.94 to 4.34), morbidly adherent placenta 6.85 (95% CI 3.88 to 12.13), pregnancy-induced hypertension 1.40 (95% CI 1.10 to 1.78).
  • After ICSI, adjusted odds ratios were: placental abruption 2.16 (95% CI 1.20 to 3.88), placenta previa 2.01 (95% CI 1.29 to 3.13), morbidly adherent placenta 7.81 (95% CI 4.56 to 13.38).
  • The adjusted odds ratio for blood transfusion was 3.85 (95% CI 2.52 to 5.88) after conventional IVF-ET and 3.76 (95% CI 2.49 to 5.66) after ICSI, with potential confounders controlled.
  • The adjusted odds ratio for ICU admission was 2.58 (95% CI 1.11 to 6.01) after conventional IVF-ET and 3.45 (95% CI 1.68 to 7.06) after ICSI.
  • For preterm birth, the adjusted odds ratio was 1.42 (95% CI 1.13 to 1.78) for babies conceived by conventional IVF-ET and 1.31 (95% CI 1.05 to 1.64) for babies conceived by ICSI.

Interpretation

The study is an observational birth cohort, so the results are associations. The authors say earlier studies have not settled why risk is higher. They name two candidates: the maternal characteristics that led to ART, and ART itself. Women reported their own mode of conception. The data had no detail on drugs or techniques, such as fresh or frozen embryo transfer. The cohort did not sample every expecting mother in its study areas, and the authors note that selection bias may have entered. In this study, morbidly adherent placenta was diagnosed clinically, irrespective of pathological examination. Ovulation induction without ART showed no significant increase after adjustment.

RRM Context

ART bypasses the reproductive problem that prevented conception and leaves its cause in place. The authors name underlying maternal characteristics, along with ART itself, as potential causes of the added risk. Restorative reproductive medicine begins with the question of what lies behind the infertility in each partner, and whether it can be treated. The authors also cite earlier work arguing that pregnancies after ART should be managed as high risk.

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

Abstract

Background

Although pregnancies conceived by assisted reproductive technology (ART) have a higher risk of maternal/perinatal complications, the overall risk of adverse outcomes necessitating advanced obstetric care has not been closely examined. The present study aimed to assess and compare the risk of maternal/perinatal complications and adverse outcomes in pregnancy and childbirth conceived by ART with those conceived naturally.

Methods

This study was conducted as a part of the Japan environment and children's study (JECS), an ongoing nationwide birth cohort study in Japan. The risk of maternal/perinatal complications and adverse outcomes was assessed by mode of conception (natural conception, ovulation induction [OI] without ART, conventional in vitro fertilization and embryo transfer [IVF-ET], or intracytoplasmic sperm injection [ICSI]) using logistic regression and generalized estimating equations controlling for potential confounders.

Results

The final dataset included women who conceived naturally (N = 90,506), by OI without ART (N = 3939), by conventional IVF-ET (N = 1476), and by ICSI (N = 1671). Compared with women who conceived naturally, those who conceived by conventional IVF-ET were at higher risk of placenta previa (adjusted OR 2.90 [95% CI 1.94, 4.34]), morbidly adherent placenta (6.85 [3.88, 12.13]), and pregnancy-induced hypertension (1.40 [1.10, 1.78]) whereas those who conceived by ICSI had a higher risk of placental abruption (2.16 [1.20, 3.88]) as well as placenta previa (2.01 [1.29, 3.13]) and morbidly adherent placenta (7.81 [4.56, 13.38]). Women who conceived by ART had a higher risk of blood transfusion (conventional IVF-ET: 3.85 [2.52, 5.88]; ICSI: 3.76 [2.49, 5.66]) and ICU admission (conventional IVF-ET: 2.58 [1.11, 6.01]; ICSI: 3.45 [1.68, 7.06]) even after controlling for potential confounders. Neonates conceived by ART had a higher risk of preterm birth (conventional IVF-ET: 1.42 [1.13, 1.78]; ICSI: 1.31 [1.05, 1.64]).

Conclusions

Women who conceived by ART had a higher risk of maternal/perinatal complications necessitating advanced obstetric care. Obstetricians should be aware of the increased risk of adverse outcomes among this population.

Topics

By this author

Related research

Assisted Reproduction › Safety and Risks › Maternal Complications · Birth and Delivery › Birth Outcomes › Maternal Morbidity · Pregnancy › Pregnancy Complications › Hypertensive Disorders
Chie Nagata, Limin Yang, Kiwako Yamamoto-Hanada, Hidetoshi Mezawa, Tadayuki Ayabe, Kazue Ishizuka, Mizuho Konishi, Yukihiro Ohya, Hirohisa Saito, Haruhiko Sago
C Nagata, L Yang, K Yamamoto-Hanada, H Mezawa, T Ayabe, K Ishizuka, M Konishi, Y Ohya, H Saito, H Sago
PMID 30786865 30786865 DOI 10.1186/s12884-019-2213-y 10.1186/s12884-019-2213-y Nagata et al. 2019, Nagata 2019

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