Neonatal characteristics of children conceived with in vitro fertilization or intrauterine insemination compared with sibling births from unassisted conceptions

Matthew R Reeder; Joseph B Stanford; Christina A Porucznik; Karen C Schliep; Erica Johnstone; Lorenzo D Botto; James Hotaling

doi:10.1016/j.fertnstert.2025.08.027

Assisted Reproduction · Safety and Risks

Neonatal characteristics of children conceived with in vitro fertilization or intrauterine insemination compared with sibling births from unassisted conceptions

Reeder MR, Stanford JB, Porucznik CA, Schliep KC, Johnstone E, Botto LD, Hotaling J

Published February 2026 Fertility and sterility, 125(2), 326-337

DOI 10.1016/j.fertnstert.2025.08.027 PMID 40876723 PMC PMC13188690

RRM Academy Synopsis

IVF singletons faced more preterm birth than their siblings

Singleton babies conceived with IVF were born preterm more often than their siblings. In a Utah sibling cohort, about 11 out of 100 IVF singletons arrived early, against about 7 out of 100 siblings conceived without treatment. The study drew on one clinic and counted 460 IVF singletons, 666 IUI singletons and 1,579 siblings.

Preterm birth: Unassisted siblings, 6.8 in 100; IVF singletons, 11.1 in 100. Source: Reeder MR et al., 2026, PMID 40876723.

Study at a glance, Retrospective sibling cohort: IVF singletons faced more preterm birth than their siblings — Study at a glance, Retrospective sibling cohort of 460 IVF singletons: IVF singletons faced more preterm birth than their siblings. Source: Reeder MR et al., 2026, PMID 40876723.

Key Findings

Preterm birth affected 11.1% of IVF singletons, 8.7% of IUI singletons and 6.8% of unassisted siblings.
Adjusted for maternal age, sex, birth year, earlier pregnancies and birth order, IVF singletons had a preterm risk ratio of 1.6 (95% CI, 1.2–2.2), an absolute difference of 4.3%.
Among IVF singletons, large for gestational age had an adjusted risk ratio of 1.8 (95% CI, 1.2–2.5; 3.2% absolute difference) and major congenital anomalies 1.9 (95% CI, 1.0–3.8; 2.3% absolute difference).
IVF singletons arrived nearly half a week earlier (95% CI, −0.6 to −0.3) and weighed 72.1 g less at birth (95% CI, −118.8 to −25.4) than their siblings.
IUI singletons weighed 55.8 g less than siblings (95% CI, −95.6 to −15.9), and their preterm risk ratio was 1.2 (95% CI, 0.9–1.7).

Interpretation

Researchers compared each couple's treatment births with that couple's own births without treatment, which helps control for many shared family factors. The design shows associations. Data came from one Utah fertility clinic and a predominantly white, non-Hispanic cohort. Most IVF singleton births with known transfer details followed multiple embryo transfer (372/439, 85%), so current single embryo transfer may give different results. The authors write that treatment-related factors may contribute beyond the couple's own fertility problems. They call the gaps in absolute terms small and possibly of limited clinical significance. Anomaly records covered 1995 through 2015.

RRM Context

IVF bypasses the reproductive system without resolving why conception fails. Restorative reproductive medicine evaluates both partners to find and treat that cause. The sibling design holds the couple constant, so it speaks to a long-running question: does added risk come from the couple's fertility problems or from the procedure? The authors report that treatment-related factors may contribute.

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

Abstract

Objective

To examine birth outcomes between children conceived with in vitro fertilization (IVF) or intrauterine insemination (IUI) and sibling births from unassisted conceptions.

Design

Retrospective sibling cohort.

Subjects

Live born children conceived via IVF, with or without intracytoplasmic sperm injection, or IUI at the Utah Center for Reproductive Medicine, 1999-2018, and sibling births from unassisted conceptions (born 1985-2018). The main analysis included singleton births (460 IVF, 666 IUI, and 1,579 unassisted siblings).

Exposure

In vitro fertilization, with or without intracytoplasmic sperm injection, or IUI.

Main Outcome Measures

Preterm birth, low birth weight, small for gestational age, large for gestational age (LGA), and major congenital anomalies.

Results

Compared with unassisted siblings, singleton children conceived via IVF had gestational ages shorter by nearly half a week (95% confidence interval [CI], -0.6 to -0.3), birth weights of 72.1 g lower (95% CI, -118.8 to -25.4), and higher proportions of preterm birth (IVF, 11.1%; IUI, 8.7%; unassisted siblings, 6.8%), LGA (IVF, 9.1%; IUI, 4.5%; unassisted siblings, 5.9%), and major congenital anomalies (IVF, 3.7%; IUI, 2.0%; unassisted siblings, 1.4%). Models adjusted for maternal age, infant sex, infant birth year, previous pregnancy, and birth order showed that children conceived via IVF were more likely to be preterm (adjusted risk ratio [aRR], 1.6; 95% CI, 1.2-2.2; absolute difference, 4.3%) and LGA (aRR, 1.8; 95% CI, 1.2-2.5; absolute difference, 3.2%). Children conceived via IVF had a higher risk of major congenital anomalies than unassisted siblings adjusted for maternal age, infant sex, and birth order (aRR, 1.9; 95% CI, 1.0-3.8; absolute difference, 2.3%). Children conceived via IUI had birth weights 55.8 g lower (95% CI, -95.6 to -15.9) than unassisted siblings.

Conclusion

We observed an increased risk of preterm birth, low birth weight, LGA, and major congenital anomalies among singleton children conceived with IVF compared with that among unassisted siblings; however, absolute differences remain small. For children conceived via IUI, lower birth weights were observed. These results suggest that treatment-related factors in addition to underlying subfertility may contribute to adverse birth outcomes.

Topics

Assisted Reproduction › Safety and Risks › Neonatal and Birth Outcomes · Pregnancy › Neonatal Outcomes › Neonatal Morbidity

Matthew R Reeder, Joseph B Stanford, Christina A Porucznik, Karen C Schliep, Erica Johnstone, Lorenzo D Botto, James Hotaling

Matt Reeder, M Reeder, Joe Stanford, Joey Stanford, J Stanford, C Porucznik, K Schliep, E Johnstone, L Botto, Jim Hotaling, Jimmy Hotaling, J Hotaling

PMID 40876723 40876723 DOI 10.1016/j.fertnstert.2025.08.027 10.1016/j.fertnstert.2025.08.027 Reeder et al. 2026, Reeder 2026

Neonatal characteristics of children conceived with in vitro fertilization or intrauterine insemination compared with sibling births from unassisted conceptions

IVF singletons faced more preterm birth than their siblings

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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