Fertility treatments and the risk of preterm birth among women with subfertility:  a linked-data retrospective cohort study

Jessica N Sanders; Sara E Simonsen; Christina A Porucznik; Ahmad O Hammoud; Ken R Smith; Joseph B Stanford

doi:10.1186/s12978-022-01363-4

Assisted Reproduction · Safety and Risks

Fertility treatments and the risk of preterm birth among women with subfertility: a linked-data retrospective cohort study

Sanders JN, Simonsen SE, Porucznik CA, Hammoud AO, Smith KR, Stanford JB

Published March 29, 2022 Reproductive Health, 19(1), 83

DOI 10.1186/s12978-022-01363-4 PMID 35351163 PMC PMC8966354

RRM Academy Synopsis

IVF and IUI were linked to higher preterm birth odds in infertility

In a retrospective cohort of 490 first births to Utah women with trouble getting pregnant, IVF conception was linked to 4.24 times the odds of preterm birth versus no treatment. IUI was linked to 3.17 times the odds. Accounting for multiple births, no fertility treatment showed a clear link to preterm birth in this sample.

Key Findings

Among 490 linked first births to women with trouble getting pregnant, 92 (18.8%) were preterm, meaning before 37 weeks.
Adjusted odds of preterm birth against no treatment in the conception month: ovulation drugs 2.17 (95% CI 0.99, 4.75), IUI 3.17 (95% CI 1.40, 7.19), IVF 4.24 (95% CI 2.05, 8.77).
Twins made up 6.6% of births after no treatment, 19% after ovulation drugs, 10.9% after IUI and 30% after IVF.
With multiple gestation in the model, odds ratios were 1.34 (95% CI 0.52, 3.45) for ovulation drugs, 2.16 (0.82, 5.69) for IUI and 1.46 (0.59, 3.58) for IVF.

Interpretation

The retrospective cohort matched self-reported treatment to birth certificates. It shows association and cannot show that a treatment caused early birth. The authors note that treatment intensity may mark how hard conceiving was. Participants all lived in Utah, nearly all were white and most were Latter-day Saints. The authors say the sample was too small to detect a smaller effect among singleton births. Gestational age came from birth certificates, and the study did not separate spontaneous from induced early labor.

RRM Context

The authors report that preterm risk across the whole group, untreated controls included, ran markedly above population rates. They read this as a link between the underlying cause and preterm birth, alongside treatment. A reported female factor diagnosis had its own independent association. Restorative reproductive medicine looks for why conception is not happening, in both partners, before treating. IVF bypasses that question.

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

Abstract

Background

In vitro fertilization (IVF) births contribute to a considerable proportion of preterm birth (PTB) each year. However, there is no formal surveillance of adverse perinatal outcomes for less invasive fertility treatments. The study objective was to describe associations between fertility treatment (in vitro fertilization, intrauterine insemination, usually with ovulation drugs (IUI), or ovulation drugs alone) and preterm birth, compared to no treatment in subfertile women.

Methods

The Fertility Experiences Study (FES) is a retrospective cohort study conducted at the University of Utah between April 2010 and September 2012. Women with a history of primary subfertility self-reported treatment data via survey and interviews. Participant data were linked to birth certificates and fetal death records to asses for perinatal outcomes, particularly preterm birth.

Results

A total 487 birth certificates and 3 fetal death records were linked as first births for study participants who completed questionnaires. Among linked births, 19% had a PTB. After adjustment for maternal age, paternal age, maternal education, annual income, religious affiliation, female or male fertility diagnosis, and duration of subfertility, the odds ratios and 95% confidence intervals (CI) for PTB were 2.17 (CI 0.99, 4.75) for births conceived using ovulation drugs, 3.17 (CI 1.4, 7.19) for neonates conceived using IUI and 4.24 (CI 2.05, 8.77) for neonates conceived by IVF, compared to women with subfertility who used no treatment during the month of conception. A reported diagnosis of female factor infertility increased the adjusted odds of having a PTB 2.99 (CI 1.5, 5.97). Duration of pregnancy attempt was not independently associated with PTB. In restricting analyses to singleton gestation, odds ratios were not significant for any type of treatment.

Conclusion

IVF, IUI, and ovulation drugs were all associated with a higher incidence of preterm birth and low birth weight, predominantly related to multiple gestation births.

Topics

Assisted Reproduction › Safety and Risks › Neonatal and Birth Outcomes · Pregnancy › Preterm Birth › Prediction · Birth and Delivery › Birth Outcomes › Maternal Morbidity

Jessica N Sanders, Sara E Simonsen, Christina A Porucznik, Ahmad O Hammoud, Ken R Smith, Joseph B Stanford

Jess Sanders, J Sanders, S Simonsen, C Porucznik, A Hammoud, Kenneth Smith, K Smith, Joe Stanford, Joey Stanford, J Stanford

PMID 35351163 35351163 DOI 10.1186/s12978-022-01363-4 10.1186/s12978-022-01363-4 Sanders et al. 2022, Sanders 2022