Interpretation
Cervical incompetence (CI) along with unexplained factor accounted for
the majority of LMs in this study, and were associated with the
recurrence. This is consistent with the findings of a retrospective
study by Joubert et al. to evaluate the causes of LM(21). It has been also reported that CI is a
well-known risk factor for preterm birth, which contributes to 70% of
neonatal death and pregnancy complications (22, 23).
Cervical cerclage is considered as a safe and effective procedure
resulting in almost 90% of successful vaginal deliveries without
maternal or fetal complications (22). Prior studies
demonstrated that women were supposed to be performed therapeutic
cervical
cerclage after the diagnosis of cervical shortening or dilatation so as
to elevate the live birth rate (24, 25). However, the
specific amounts of women who underwent cervical cerclage during their
subsequent pregnancy after one ceLM was unknown in our study, due to the
inadequate follow-up system in our reproductive center ten years ago.
Hence, we could not determine whether cervical cerclage had helped
reduce the recurrence of LM and occurrence of preterm birth in women
with a ceLM. Nevertheless, our study suggests that
serial
surveillance for cervical length and maturity during second and third
trimester is of great importance for pregnant women with a history of
ceLM, even only once.
Unexplained LM might be caused by maternal
thrombophilic
states, immunological factors, infection factors, or uncontrolled
illnesses (26, 27). Our study found that women with
one unexplained LM would have a significant higher risk of EM, which was
consistent with the findings reported by Egerup et al.(13) and by Ni et al.(14). Thrombotic
and
immunological
factors may play an important role in this association. Women with
threatened LM had significant higher levels of amniotic immune
biomarkers (IL2β receptor, IL6, IL8, IL10, IL1β, and TNFα) and specific
biomarkers for thrombophilia, such as factor V Leiden or prothrombin
G20210A or lupus anticoagulants (LA), which also significantly
correlated with EM (8, 28, 29). On the other hand,
Cicinelli et al verified that the chronic endometritis due to common
bacteria were associated with the recurrence of spontaneous miscarriage
and
antibiotic
prophylaxis in subsequent pregnancies seems to help improve reproductive
outcome (30). All these findings above suggest that
women with a unLM might be in a chronic pro-inflammatory or
pro-thromboembolic state, which may increase the risk of embryonal or
fetal death in all stages of pregnancy. It’s undeniable that the
etiological
examination for women with only one unLM was largely ignored in clinics.
Additionally, we found that the interval between the occurrence of unLM
and subsequent embryo transfer was the shortest, which can partly
explain the higher risk of EM in women with a unLM. Therefore, women
with a previous unLM should be informed of the risk of adverse pregnancy
outcomes, and more attention should be paid during the subsequent
pregnancy.
Previous studies ascertained that trauma is one of common contributors
to maternal and fetal morbidity and mortality (31),
and
trLM
accounts for 5.22% of all types of LM in our study. The underlying
etiology between trauma and LM includes the subclinical chronic
abruptions secondary to trauma which may lead to placental
insufficiency, and poor fetal tolerance to maternal physiologic stress
from trauma (32). Notably, we found that the
recurrence risk of LM was significantly higher after one trLM,
which
highlights the need to enhance education in trauma prevention during
pregnancy. However, the sample size in this subgroup was small and the
association between trLM and its recurrence along with the potential
mechanisms warrants further investigation.
Several studies have suggested that PCOS was associated with an
increased risk of some pregnancy complications, such as miscarriage and
preterm delivery (20, 33). PCOS women often combine
with a higher BMI as well as hyperandrogenism and serum testosterone is
significantly correlated with the disease severity of PCOS(34). In our study, women with a LM were more likely
to be diagnosed with PCOS than general IVF population. Further
regression analysis demonstrated that the diagnosis of PCOS had a
moderate correlation with the recurrence of LM, while no association
with the subsequent live birth, which has been considered as a
confounder and has been adjusted.