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IVF & Preterm Birth: 4.24X higher odds of landing in the delivery room, too soon

Updated: Jan 11

Preterm birth (PTB), birth before 37 weeks gestation, representing 8% of Canadian births [1]. PTB is associated with significant risks for the infant including respiratory problems, neurological impairments, gastrointestinal complications, and even death. Costs are real for the infant, the family and the public healthcare system. In turn, understanding the factors that may increase the odds of preterm delivery is critical.[2]


ART and Preterm Birth

A retrospective cohort study examined the association between ART fertility treatments and preterm birth  [3] (Sanders et al.(2022). A cohort of 490 women with a history of primary subfertility were recruited at the University of Utah between 2010-2012, investigating whether ART fertility treatments like IVF and IUI increased odds of preterm birth among women with subfertility.


Fertility treatment patients accessing in vitro fertilization (IVF), intrauterine insemination (IUI) with ovulation induction drugs, and ovulation induction drugs alone were followed. The outcome of interest was preterm birth before 37 weeks. By comparing preterm birth (PTB) rates between women who underwent fertility treatments to those who did not, this study aimed to assess whether fertility treatments increase the risk of preterm delivery.

Young mother and healthy young baby is a medical safety net provided by less invasive infertility care
Trouble conceiving? Less invasive fertility treatments might reduce risk of preterm birth.

Study Summary

- Participants included in retrospective cohort study were 490 women with history of primary subfertility recruited at University of Utah between 2010-2012


Findings Summary: Increased Preterm Birth odds from ART

IVF = 4.24 X higher odds of PTB

IUI = 3.17 X higher odds PTB

Ovulation drugs alone = 2.17 X higher odds PTB.


ART Carries Risks


The study found significantly increased odds of preterm birth associated with fertility treatments including IVF, IUI, and ovulation induction medications. However, the mechanisms explaining this association were not clear. Higher risk odds published in an earlier longitudinal cohort study reflected a similar trend [5] Declercq et al., 2015) Several factors related to ART based fertility treatments could potentially contribute to increased preterm birth risk.


Multiple embryo transfers leading to higher order multiple pregnancies (twins, triplets, etc) that increase risk for preterm birth have been well documented for over 20 years. The natural rate of twins is under 2 %. In Canada, IVF multiple rates were 29% for twin and 7% for triplets and higher in 2006. The rate of multiple pregnancies after IUI with COS was estimated to be about 21% to 29%. [4]


Realizing the size of the problem to the Canadian healthcare system and danger to neonates, multiples from IVF in Canada dropped to 13% by 2015 (outside of Quebec, who was at that time funding IVF in order to enforce single embryo transfer to reduce these high multiples rates). [8] (Canadian Fertility and Andrology Society, n.d.)

However, this study found increased risk even for singleton IVF pregnancies, suggesting the treatments themselves may confer risk beyond just multiple gestations.[4]


The type and dosing of exogenous hormones used for ovarian stimulation may play a role, for instance ovarian hyperstimulation syndrome occurs in 1 to 10% of IVF patients and may have an effect on PTB rates. The procedures involved in IVF and IUI could also have an impact - for example, the process of egg retrieval in IVF requires a needle puncturing the vaginal wall to access the ovaries, with possible resultant inflammation or physical trauma that could lead to PTB. [4]


Better understanding the drivers of increased preterm birth risk might allow development of enhanced IVF and IUI protocols to minimize harm. The simplest of these is to limit multiple embryo transfers to protect child health [4].


In the meantime, patients pursuing fertility treatment should be counseled about potential risks. Suggesting less invasive medical options that optimize ovulation and physical health is another avenue that can be accessed.



“The treating physician has the obligatory role of suggesting the most effective treatment paradigm with the least risk and least expense.”

-Dr. Jerome Check [6]



Important Study Limitations

As a retrospective cohort study [3] this research has obvious limitations in establishing causality between fertility treatments and preterm birth.


  • The retrospective design means that women were not randomized to treatment groups. There may have been underlying differences between the groups that account for the differences in preterm birth.

  • The study was a single academic center, which may limit generalizability of the findings. Women who seek care at an academic fertility center may differ from the broader population in ways that affect preterm birth risk.


Overall, while this study identified increased odds of preterm birth associated with fertility treatments, the retrospective design while novel, means causation cannot be proven.


Key Study Takeaways


This retrospective cohort study (Sanders et al., 2022, Reprod Health.) provides important evidence on the association between fertility treatments and preterm birth. Findings:

- IVF 4.24 X increase odds of PTB

- IUI with ovulation stimulation drugs 3.17 X increase odds of PTB

- Ovulation stimulation drugs alone 2.17 X increase odds of PTB

- More intensive fertility treatments carry greater preterm birth risk.


For those who are having trouble conceiving, trying less invasive treatments to achieve pregnancy might reduce their risk of preterm birth.


For patients and doctors, these findings should be considered when weighing up risks and benefits of pursuing invasive fertility treatment and patients at higher baseline risk may wish to avoid the most intensive ART treatments if possible.


Written by Carolyn Plican, Creighton Model FertilityCare Practitioner

Reviewed by Dr. Mary Ellen Haggerty, Restorative Reproductive Medicine Clinician


Referenced:

  1. Statistics Canada. (2023). Live births, by weeks of gestation (Table 13-10-0425-01). Retrieved from https://www150.statcan.gc.ca/t1/tbl1/en/tv.action?pid=1310042501

  2. Canadian Institute for Health Information. (2009). Too Early, Too Small: A Profile of Small Babies Across Canada. https://secure.cihi.ca/free_products/too_early_too_small_en.pdf

  3. Sanders JN, Simonsen SE, Porucznik CA, Hammoud AO, Smith KR, Stanford JB. Fertility treatments and the risk of preterm birth among women with subfertility: a linked-data retrospective cohort study. Reprod Health. 2022 Mar 29;19(1):83. doi: 10.1186/s12978-022-01363-4. PMID: 35351163; PMCID: PMC8966354.

  4. Medical Advisory Secretariat. In vitro fertilization and multiple pregnancies: an evidence-based analysis. Ont Health Technol Assess Ser. 2006;6(18):1-63. Epub 2006 Oct 1. PMID: 23074488; PMCID: PMC3379537.

  5. Declercq E, Luke B, Belanoff C, Cabral H, Diop H, Gopal D, et al. Perinatal outcomes associated with assisted reproductive technology: the Massachusetts Outcomes Study of Assisted Reproductive Technologies (MOSART) Fertil Steril. 2015;103(4):888–895

  6. Carp, H., & Carp, H.J.A. (Eds.). (2014). Recurrent Pregnancy Loss: Causes, Controversies, and Treatment, Second Edition (2nd ed.). CRC Press. https://doi.org/10.1201/b17855

  7. Canadian Fertility and Andrology Society. Canadian ART Register. Retrieved [1.8.2024], from https://cfas.ca/canadian-art-register.html

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