Association between infertility and cervical insufficiency in nulliparous women- the contribution of fertility treatment.

Background: Pregnancies conceived through assisted reproduction have been associated with increased risks of adverse pregnancy and delivery outcomes, including cervical insufficiency (CI). Despite CI being a significant cause of late miscarriage or preterm birth, there are minimal published data on the associations of infertility (with or without fertility treatment) with CI. This study uses Swedish national health registers to examine the associations between infertility, assisted reproduction and CI in nulliparous women.

Methods: This population-based case-control study is based on data from Swedish national health registers. Using the information on parity and multiple gestation in the Medical Birth Register, singleton pregnancies of nulliparous women were extracted and linked to the National Patient Register and the National Quality Register for Assisted Reproduction. Using diagnostic codes for CI and procedural codes for cervical cerclage, a total of 2662 CI cases were identified for deliveries in the 21-year period, 1992-2012. A reference group of 26,620 controls were extracted from the population of non-cases using simple random sampling.. Infertility was classified using a woman's report of difficulty conceiving for at least one year. Fertility treatment was assessed through self-reported variables in the Medical Birth Register and fertility treatment registration in the National Quality Register for Assisted Reproduction.

Results: On adjusting for maternal characteristics and medical history, infertility was associated with CI, overall (adjusted odds ratio (aOR) ) 1.91 (1.53, 2.39) and in the subgroup of non-users of fertility treatment (aOR) 1.60 (1.21, 2.12), compared to women without infertility. Among women with infertility, pregnancies conceived with the aid of fertility treatment had higher risk of CI than naturally-conceived pregnancies (aOR 1.49 (1.05, 2.10). In the subgroup of women with infertility and no history of miscarriage, the use of fertility treatment was associated with CI (aOR 3.48 (2.02. 5.98)). No association was found between fertility treatment and CI in the pregnancies of women with infertility and a history of miscarriage.

Conclusions: From this study, we conclude that CI in nulliparous women is associated with both infertility and its treatment. For infertile women, the risk of CI following fertility treatment was seen only in those with no history of miscarriage, providing crucial information for improving risk assessment and management strategies for preterm birth prevention in populations availing of fertility treatment.