Assisted Reproduction Safety and Risks

Assisted Reproductive Technology or Infertility: What underlies adverse outcomes? Lessons from the Massachusetts Outcome Study of Assisted Reproductive Technology

Stern JE, Farland LV, Hwang SS, Dukhovny D, Coddington CC, Cabral HJ, Missmer SA, Declercq E, Diop H

Published October 2022 F&S reviews
DOI 10.1016/j.xfnr.2022.06.003 PMID 36505962 PMC PMC9733832

RRM Academy Synopsis

Infertility and ART are each linked to higher preterm birth risk

Singleton preterm birth risk was higher with infertility, and higher again with ART. The Massachusetts study team (MOSART) reviews its own cohort studies of just over one million births. The groups were ART (IVF and related technologies), women with signs of infertility, and fertile women.

Key Findings

  • Adjusted odds of preterm birth (under 37 weeks) in singletons, against fertile women: 1.24 (95% CI 1.12–1.38) for the subfertile group and 1.53 (1.40–1.67) for ART. ART against subfertile: 1.23 (1.08–1.41).
  • Adjusted odds of low birthweight (under 2,500 grams): 1.20 (1.06–1.36) for the subfertile group and 1.51 (1.37–1.67) for ART, both against fertile women. ART against subfertile: 1.26 (1.08–1.47).
  • Severe maternal morbidity after singleton deliveries had adjusted odds of 2.27 (95% CI 1.78–2.88) with ART against the fertile group. The subfertile group showed no significant increase.
  • Placental problems mediated 16% of the ART effect on late preterm birth and 32% on early preterm birth. For unassisted subfertility, mediation was 7% for late and 12% for early preterm birth.
  • Early Intervention enrollment among 318,305 singleton children was 18.7% after ART, 17.4% in the subfertile group, and 16.5% in the fertile group (P<0.001).

Interpretation

The paper is a narrative review by the MOSART team of its own retrospective cohort studies. The results show association and cannot prove cause. The data come from one state and cover only live births and stillbirths, so miscarriages and time to pregnancy are missing. Records defined the subfertile group (women with signs of infertility), so some infertile women sit in the fertile group. The authors acknowledge that ART patients may have more severe infertility. Sibling comparisons and placental findings lead them to propose that ART itself adds risk.

RRM Context

Restorative reproductive medicine starts with the causes of infertility. The review lists endometriosis, ovulation problems, and tubal, uterine, and male factor diagnoses. It adds high blood pressure, diabetes, and thyroid problems that persisted after adjusting for age. ART bypasses these causes and leaves unresolved why conception fails. In these data, ART was associated with some pregnancy and delivery risks beyond those seen with infertility alone.

Abstract

Numerous studies have demonstrated that assisted reproductive technology (ART: defined here as including only in vitro fertilization and related technologies) is associated with increased adverse pregnancy, neonatal, and childhood developmental outcomes, even in singletons. The comparison group for many had often been a fertile population that conceived without assistance. The Massachusetts Outcome Study of Assisted Reproductive Technology (MOSART) was initiated to define a subfertile population with which to compare ART outcomes. Over more than 10 years, we have used the MOSART database to study pregnancy abnormalities and delivery complications but also to evaluate ongoing health of women, infants, and children. This article will review studies from MOSART in the context of how they compare with those of other investigations. We will present MOSART studies that identified the influence of ART and subfertility/infertility on adverse pregnancy (pregnancy hypertensive disorder, gestational diabetes, placental abnormality) and delivery (preterm birth, low birthweight) outcomes as well as on maternal and child hospitalizations. We will provide evidence that although subfertility/infertility increases the risk of adverse outcomes, there is additional risk associated with the use of ART. Studies exploring the contribution of placental abnormalities as one factor adding to this increased ART-associated risk will be described.

Topics

By this author

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Assisted Reproduction › Safety and Risks › Procedure-Attributable Risk · Pregnancy › Pregnancy Complications › Hypertensive Disorders · Birth and Delivery › Birth Outcomes › Maternal Morbidity
Judy E Stern, Leslie V Farland, Sunah S Hwang, Dmitry Dukhovny, Charles C Coddington, Howard J Cabral, Stacey A Missmer, Eugene Declercq, Hafsatou Diop
J Stern, L Farland, S Hwang, D Dukhovny, Charlie Coddington, Chuck Coddington, C Coddington, H Cabral, S Missmer, E Declercq, H Diop
PMID 36505962 36505962 DOI 10.1016/j.xfnr.2022.06.003 10.1016/j.xfnr.2022.06.003 Stern et al. 2022, Stern 2022