2. Interpretation
(1) History of multiple pregnancy and assisted reproductive technology
This study found that 7.66% of CI patients had a previous history of multiple pregnancies. The RCOG clinical guidelines consider multiple pregnancies as a risk factor for CI; therefore, whether women with previous multiple pregnancies increased the risk of CI in a singleton pregnancy was considered. Eventually, the results showed that a previous history of multiple pregnancies increased the risk of CI by 17.51-fold. Recent studies haven’t mentioned the effect of previous multiple pregnancies in the occurrence of CI. These points should be further explored and confirmed in subsequent studies, which may also guide our future research to a certain extent. This study also demonstrated a 3.26-fold increased risk of CI via IVF-ET/ovulation induction pregnancy. A population-based study in 2007 showed that ART increased the risk of CI by 6-fold;8 two retrospective cohort studies in 2010 and 2012 showed that the risk of CI was higher in women treated with ART than in women with spontaneous pregnancy.11, 12 Meanwhile, a study of 4710 women who became pregnant after IVF/ICSI treatment in 2021 found that a high proportion of patients (2.31%) were diagnosed with CI.9 In anovulation-related infertility patients, the formation of CI has been shown to be related to ovarian stimulation with gonadotropin and clomiphene citrate, and the use of other reproductive technologies.13 Hence, attention should be given to the management of pregnancy and timely ultrasound monitoring during continuous pregnancy in patients undergoing assisted reproductive conception. Furthermore, focus should be given to the relationship between CI and infertility in clinical and scientific research.
(2)GDM/PGDM and PCOS
This study showed that diabetes (most patients are GDM) incidence was 41.21% among CI patients and approximately 18.39% among non-CI population. However, literature showed that the total incidence of GDM in mainland China was 14.8%,14 indicating that the incidence of diabetes in the CI population of this study was significantly increased, while the incidence in the non-CI population was similar to the total incidence in mainland China. A history of diabetes mellitus was identified to be a predictor of CI in 2010,15 and few studies have been published since then. The present multivariate analysis showed that GDM/PGDM increased the risk of CI by 2.88-fold. Pregnant women with diabetes are known to have a higher risk of adverse pregnancy outcomes, however, no systematic study exists pertaining to the relationship between diabetes and CI, while the association between the two may be explored by searching for a common pathogenesis. Insulin resistance and chronic subclinical inflammatory processes are considered to be the main factors leading to the development of GDM, which may be related to the development of CI.16-18 The association and mechanism between the two should be further explored via basic experiments. This study also showed that about 10.55% of CI patients had PCOS, which increased the risk of CI by 8.72 times. This was consistent with SOGC clinical guidelines attributing PCOS to risk factors for CI. PCOS is a disease characterized by abnormal menstruation, hirsutism and acne, affecting about 6% -10% of women of childbearing age. PCOS patients have an increased risk of infertility, endometrial hyperplasia, and abnormal glucose metabolism.19 According to literature, CI patients with PCOS have worse pregnancy outcomes than those without PCOS.20, 21 Therefore, more attention should be given to the clinical management of such patients as well as the possible intercorrelation between PCOS and CI. Furthermore, supervision of pregnancy and the management of patients should be carried out adequately.
(3)Müllerian anomalies and uterine malformations
Müllerian anomaly is a known risk factor for congenital CI. Abnormalities that occur during development can range from uterine and vaginal agenesis to congenital uterine malformations.22, 23 In 2011, the prevalence of congenital uterine malformations was reported to be about 5.5% in the general population, 8.0% in the infertile population, and 13.3% in the recurrent miscarriage population.24 Meanwhile, in 2013, the prevalence of congenital uterine malformations was reported to be about 1.8–37.6% in the recurrent miscarriage population, which largely depended on the choice of methods and diagnostic criteria.25 According to this study, uterine malformations accounted for about 1.44% in the non-CI population and 4% in CI patients. The incidence of uterine malformations was found to be slightly different from that reported in literature, which may be related to diagnostic methods, racial differences and chronological differences. According to literature, the incidence of CI is about 3.6% -30% in patients with uterine malformation.26-28 The present study showed that patients with uterine malformations had a 4.00-fold increased risk of CI, which is in line with studies reporting that Mullerian abnormalities may increase the risk of CI by 6.19-fold.28 Therefore, when encountering cases with congenital uterine malformations, CI may also be associated; hence, the cervical status of these patients must be assessed by serial ultrasonography in the second trimester.
(4)BMI
Regarding the effect of BMI on CI, a study conducted by German scholars in 2011 showed that gestational obesity accounted for 7.9% of primiparous women, which reduced the risk of CI and preterm delivery. Although this study had a large sample size, it was conducted 10 years ago;6 In 2015, Chinese scholars pointed out that for each unit increase in BMI, the risk of CI increased by 1.296 times; however, due to its small sample size, its conclusions still need to be verified by studies with a large sample size.5 A retrospective study with a large sample size done by Yang et al in 2020 showed that BMI≥25 kg/m2 increased the risk of CI 3.87 times.21 Meanwhile, 2 of the three studies in 2017 and 2020 had moderate sample sizes, while one had a large sample size, all suggesting that higher BMI may be related to longer cervical length.29-31 In this study, although patients in the CI group had a larger mean pre-pregnancy BMI in the univariate analysis, and those with BMI of 24 kg/m2 and above accounted for more, the multivariate analysis did not find that high BMI was associated with the occurrence of CI. In recent years, few studies have been conducted on the association between BMI and CI with no consistent conclusions. This study’s conclusions also require a larger sample size to be further verified.