Infertility and fertility treatment linked to cervical insufficiency risk

Infertility and fertility treatment linked to cervical insufficiency risk | Image Credit: © MedicalWorks – © MedicalWorks – stock.adobe.com.

Cervical insufficiency (CI) is associated with infertility and its treatment in nulliparous women, according to a recent study published in the American Journal of Obstetrics & Gynecology.¹

Risks of CI

CI, defined as a cervical ripening in the second trimester, has been listed as an underlying cause of late miscarriage and preterm birth. These adverse outcomes are more likely in infertile patients using assisted reproductive technology, which a Chinese study reported was more common in patients with CI.²

“Since women seeking fertility treatment will be mostly those in couples with fertility problems, it is of interest to investigate the role of the infertility and the actual fertility treatment in any increased risk of CI,” wrote investigators.¹

Study design and data sources

The population-based case-control study was conducted to determine the link between infertility and CI in singleton pregnancies. Stillbirths from week 22 onward were obtained from the Swedish Medical Birth Register (MBR), a record of pregnancies, deliveries, and neonatal information.

Diagnosis codes from the International Classification of Diseases (ICD) coding system were used to identify maternal and neonatal diagnoses. This allowed 2662 cases and 26,620 controls to be identified, with pregnancies with multiple gestation excluded from the analysis.

Defining infertility and miscarriage history

Infertility was identified from the MBR as the primary exposure, collected at enrollment to prenatal care by asking women if they have been involuntarily childless and how long they tried to conceive. Those with 1 year or longer of difficulty conceiving were considered infertile.

Subgroups among infertile women include using fertility treatment and not using fertility treatment, determined based on records in the MBR. Prior-miscarriage was reported as a binary variable and as a categorial variable. The 3 levels of miscarriage included none, sporadic, and recurrent.

Additional medical history such as gestational diabetes and polycystic ovary syndrome was assessed using ICD codes. Investigators also identified prior cervical procedures in patients. Covariates included height, body mass index, and age.

Increased risk of CI

The odds of CI were increased 2-fold among women with infertility, with an odds ratio (OR) of 2.05. Additionally, an OR of 2.53 was reported in women with infertility with the use of infertility treatment, indicating a further increase in odds.

CI risk was greatly increased among women with a previous miscarriage vs no miscarriage, with an OR of 6.49. This association was significantly higher among women with recurrent miscarriage, with an OR of 25.83.

Adjusted odds and impact of fertility treatment

When adjusting for maternal characteristics and medical history, the ORs for CI among women with infertility were 1.93 and 1.91, respectively, indicating no significant difference from the crude OR. A crude OR of 1.71 and adjusted OR of 1.61 were reported for women with infertility not using fertility treatment, highlighting a slight reduction.

Overall, an OR of 1.55 was reported for CI among infertile women with fertility treatment vs no fertility treatment. In women with no prior miscarriage, the ORs for CI when receiving fertility treatment vs no treatment ranged from 3.32 to 3.50, indicating an over 2-fold increase in risk.

No association was found in women with prior miscarriage. Overall, the results indicated a link to CI risk from infertility and fertility treatment among nulliparous women.

“Infertile women without a previous pregnancy should be monitored for change in cervical length during pregnancies conceived with the help of fertility treatment,” concluded investigators.

References

1. Meng L, Öberg S, Sandström A, et al. Association between infertility and cervical insufficiency in nulliparous women—the contribution of fertility treatment. Am J Obstet Gynecol. 2025;232:468.e1-9. doi:10.1016/j.ajog.2024.10.035
2. Liu Q, Wang J, Xu Q, Kong L, Wang J. A retrospective cohort study of obstetric complications and birth outcomes in women with polycystic ovarian syndrome. J Obstet Gynaecol. 2022;42(4):574-579. doi:10.1080/01443615.2021.1931066