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.