In the present study, we found that the length/volume of original cervix and the cone length/volume and the proportions of cone length/volume varied substantially between individuals. We confirmed that the length of cervical cone, the volume of cervical cone, the proportion of cervical length excised, the proportion of cervical volume excised significantly correlated SAB and SPTB in multivariate logistic regression models, respectively (P < 0.05), but the proportion of the cervical volume excised has the best predictive value for SAB and SPTB (AUC 0.700,95% CI 0.634–0.765). And the risk of SAB and SPTB increased with the proportion of the cervical volume excised increasing (OR 19.704, 95% CI 4.646–83.568). When the proportion of the cervical volume excised is more than19.5% (sensitivity 0.635; specificity 0.655), it means that women are at high risk for SAB and SPTB in subsequent pregnancy.
Our study further complements and extends the relationship between cone dimensions and preterm birth. Nevertheless, we cannot be certain that the observed association is causal. However, even if the association is not causal, our results are of prognostic value to obstetricians[6]. In addition, the dimensions of cervix were measured using two-dimensional transvaginal sonography (2D-TVS). Although MRI is thought to be optimally accurate, both two-dimensional and three-dimensional (3D) transvaginal ultrasounds are reported to be imaging methods with a high accuracy in evaluating cervical volume[16, 17].
Furthermore, the excisional procedures were performed using a standardized technique. The data on cone dimensions relied on retrospective data recorded in histopathology reports of formalin-fixed samples, with limitations. Future research should aim to correlate outcomes with precise prospective cone depth and cervical measurements. Moreover, the retrospective data collected are at known risk of recall bias and incomplete outcome data, which could be a potential limitation. However, the meticulous gathering of data through medical chart review enabled the collection of data involving multiple confounding factors and decreased recall bias.
In line with previously published data[12], the present study indicated that the proportion of the cone volume was the best predictor for SAB and SPTB. And Papoutsis et al. found that cervical regeneration at 6 months after excision was dependent on the proportion of cervical volume excised[16]. And our findings showed that the proportion of the cervix removed and the dimensions of the cervix pretreatment varied substantially, which were also consistent with the previous studies[12]. We confirmed that the proportion of the cervix removed more accurately reflected the effect of treatment on the cervix than the absolute cone dimensions; and identical cone sizes represented different proportions of excision in different patients.
The results from our study demonstrated consistency with previous studies, which found that cone dimensions including cone length or volume were associated with preterm birth[4, 9, 10, 15, 18]. However, we also found a significant negative correlation of pregnancy duration with cone length (P = 0.007, r = − 0.153), but not with cone volume (P = 0.062), which was in contrast with Kyrgiou et al.[12],but in line with Carlo et al[15]. In our study, the cone length seemed to play a more important role in preterm labor than the cone volume. In fact, the results of the studies reflected that the effects of cone volume/length on pregnancy duration did not consider the effects of original cervical dimensions.
In fact, whether the safe cone dimensions exist below which the risk of preterm labor is not increased is unclear. We have shown that a woman is at risk for SAB and SPTB after conization when cone volume is more than 2.85cm3 or more than 19.5% of the initial cervical volume and cone length is more than 1.45cm or more than 48.5% of the initial cervical length, which have covered the optimal cutoff of cone parameters for margin negativity[19].
However, there are some discordant results in other studies, which did not show any relationship between cone volume /depth or conization and preterm birth[14, 20–22]. In fact, the exact pathogenetic link between cervical excisional treatments and risk of prematurity has not yet been fully elucidated. The causes could be mainly explained that removed tissues might significantly influence the restoration of anatomy and function of cervix following surgery and as a result lead to compromise the integrity of the cervical stroma and a lack of effective mechanical support in subsequent pregnancies[3, 5, 10, 23, 24].
Other factors may be also important. Infection with HPV changes normal cervicovaginal flora environment[1]. Immunological factors are altered during the process of the cervical lesions[5]. The recent study reported that CIN itself had a baseline risk for prematurity[4, 18, 25]. These factors play a very important role by promoting the persistence of HPV, thus favouring the development of frequent ascending infections and consequent abortion and prematurity. The recent study suggested that maternal HPV infection may be an upstream cause of preterm delivery that acts through a variety of downstream causes, including preterm premature rupture of membranes (PPROM)[26].