POs of asymptomatic women with similar age, ethnicity, residency, educational background, and harmful habits of populations in the intact cervix group (ICG) vs. cervical conization group (CCG) with its subsets after the adjustment for the USCL (SCLG and STCG), and depending on PTB prevention modes (PAG vs PPG) were retrospectively analyzed. Medical records of women with somatic diseases, obesity, and severe pregnancy pathologies were excluded to limit comorbidity factors of the PTB and focus on the impact of the CCS and USCL changes on POs.
Cervical conizations followed by pregnancies were performed mostly among asymptomatic women in their late twenties which is the age of the population with the peak incidence of severe dysplasia.53 There was a significantly higher nulliparous proportion among women who underwent cervical conization in comparison to that of women without cervical conization (p < 0.0001), supporting the physicians’ decisions to avoid cervical conizations in nulliparous women.
The Cesarean section and vaginal birth rates, as well as rupture of the amniotic membranes, were similar between compared populations. Our findings contradicted the literature data showing the increased amniotic membrane ruptures among women with cervical conizations than without54–55 and an association of the amniotic membrane ruptures with the impending preterm birth.56 The delivery prolongation was significantly decreased among women with cervical conization independently of their CL (P < 0.0001) compared to that of the population with the intact cervix, which contradicts the data showing the prolonged duration of delivery time in women with cervical conizations than without.18
Our comparisons of the PTB rates and pregnancy duration in women without and with cervical conization in the 1st cohort, when the USCL was not adjusted, were similar to the literature data showing no difference between these populations24,26,29 Besides, the PTB rates of women with sufficient CL (> 25 mm) were also similar to those of women without cervical conization, whereas the PTB rate significantly increased in women with a short cervix (≤ 25) in comparison with women without cervical conization, cervical conization in total and sufficient CL (P < 0.001). Subsequently, we confirm that the results of studies demonstrating controversial impacts of cervical electrosurgical procedures on the PTB rates11,12 in comparison to POs in population or internal controls were dependent on the volume of the CCS20,56−59 and the USCL adjustment.12,13,60
The proportion remaining pregnant in the survival curve was significantly lower among women with a short cervix between 32–37 weeks of gestation than in other groups with and without cervical conizations by the Gehan-Breslow-Wilcoxon test (P < 0.0001). The survival curve demonstrating the pregnancy duration among women with the short cervix in this study was similar to findings of Iams et al 13 who compared two groups adjusted for USCL ≤ 25 vs > 25 mm. We found similar findings with literature when the increased PTB rates in women with short cervix after cervical conization were remaining with adjusting for maternal age, parity, and smoking61, and prior PTB history.62 These results showed that the CL is the cornerstone in the POs after cervical electrosurgical procedures, therefore changes of USCL before and during pregnancy were thoroughly analyzed. The USCL values before pregnancy were similar in all groups, whereas during pregnancy this parameter significantly changed between all comparisons adjusted without and with cervical conization, as well as sufficient and short cervix (P < 0.0001). In turn, the USCL during pregnancy was remained non changed only among women with sufficient CL, whereas in women without cervical conization become significantly longer, and in contrast among women with cervical conization it was shorter, and in women, with a short cervix, this parameter extremely shortened (P < 0.0001). In our work, we describe for the first time findings of the USCL changes, monitored before and after conization in non-pregnant women and during pregnancy supplemented with the simple method of the CCS assessment, in addition, the short cervix after cervical conization was observed mostly among the nulliparous population, whereas the sufficient CL in women with the prior parity.
The 2nd cohort comparisons of the PTB prevention modes showed significantly increased PTB rates among women with a short cervix in both groups compared to that of the SCLG (P < 0.0001). Analogously pregnancy duration (the proportion remaining pregnant in the survival curve) was significantly shortened among women with a short cervix in PPG compared to that in SCLG (P < 0.0001). Our results of the PTB rates and the pregnancy duration among women with short cervix received vaginal progesterone alone were similar with findings39,40 and contradicted37,38,41, analogously combined progesterone and pessary application outcomes were in agreement49,52 and contradicted36,51,63 as well as pessary alone in accord45,47,48 and contradicted35,42,44 with findings of publications using analogous PTB prevention modes. Our observation concerning the efficient similarity of both PTB prevention modes in accord with the literature.49,64
The USCL values before and after conization were similar between all groups, although electrosurgical procedures substantially reduced the USCL among nonpregnant women. Interestingly, the USCL during pregnancy becomes significantly longer in women with sufficient CL (P < 0.0001), whereas in women with short cervix this parameter substantially shortened, in both PTB prevention groups, PAG (P < 0.0001) and PPG (P < 0.01). Analogously, during pregnancy in both PTB prevention groups the USCL was significantly reduced when compared to that of women in the SCLG (P < 0.0001). The biggest CCS was in women with the short cervix treated with progesterone-pessary and the smallest in women with sufficient CL (P < 0.0001), subsequently, short CL was associated with the volume of removed samples. These findings in accordance with analogous observations when the size (depth) of removed cervical tissue was taken into account to predict the PTB rates.21,22,57−59
Generally, significantly higher PTB rates were observed among women with short cervix groups (STCG, PAG, and PPG) in comparison to those of women without (ICG, p = 0.0001; 0.0073; 0.0068), and with (CCG, p = 0.0055; 0.0959; 0.0381) cervical conizations and sufficient cervical length (SCLG, p = 0.0001; 0.0029; 0.0036) (Table 2).
Analogously substantially increased risk ratios, such as relative risk and odds ratio of the PTB rates were found among women with a short cervix in comparison to women with sufficient CL as well as to those of both PTB prevention modalities. Both PTB risk ratios were also notably higher in women with short cervix compared to the intact cervix. The CL depending on the CCS is more critical in POs than the PTB prevention modes in our observations.
It seems that a combination of several factors such as the larger CCS and the shortened USCL at the 16–18 weeks of gestation depending on prior history of parity (nulliparous or women who given birth) plays a crucial role in PTB rate in asymptomatic women with singleton pregnancies. Such importance of the CCS in the PTB rates might be related to the high concentrations of neuropeptides, neurotransmitters, oxytocin, and other physiologically active substances in the cervical tissue and lower uterine segment than those of tissues in the upper part of the uterus.65,66 The cervix plays an important role during pregnancy and delivery through modification together with the part of the uterine body forming the lower uterine segment.67,68 Subsequently, we suggest that excessively cervical conization might lead to tissue insufficiency and impair the structure and function of the cervix.
Strengths
Singleton POs of similar populations in age, national compositions, residency, background education levels, and possessed bad habits (smoking) of asymptomatic women were retrospectively analyzed. All cervical electrosurgical procedures before pregnancy with measurement of the CCS and most USCL assessments were performed by trained professionals using the same equipment and instrumentation. Then the statistical analysis of all results was performed by the independent researcher. Medical records of women with somatic diseases, obesity, and severe pregnancy pathologies were excluded to limit comorbidity factors of the PTB and focus on the impact of conization size and cervical length changes on POs. Two-step statistics (1st and 2nd cohorts) enable us to demonstrate a significant value of the ultrasound cervical length measurements before and after cervical conization and during pregnancy as well as estimate efficiency of the PTB prevention modes, i.e., vaginal progesterone alone and its combination with pessary in women with short cervix adjusting the size of removed tissue, and the USCL changes before and during pregnancy. Observations of the USCL changes monitored before and after conization in non-pregnant women and during pregnancy with the simple method of physical volume (size) assessment of the removed part of the cervix, as well as findings with the highest proportion of the nulliparous women with a short cervix and contrary highest number of women who previously given birth with sufficient cervical length were described for the first time. These results added knowledge to the understanding of controversial PTB rates of the general population of women after cervical conization in comparison with control women without cervical conization before pregnancy and depending on the CCS and CL changes, as well as different PTB prevention modes. We suggest that the diagnostic and predicting value of the USCL assessment during pregnancy will be increased if take into account CCS.
Limitations
Our study has limitations due to the retrospective study design: a small number of patients in the group with combined application of progesterone and pessary, as well as using two models of pessaries, which could lead to decrease statistical power of our analysis. The comparison bodies of the PTB prevention modes were populations with an intact cervix, and with the cervical conization in total, and with sufficient CL adjusted during pregnancy, however, we could not provide the group with analogous short cervix without treatment, placebo, or used the only pessary because of an ethical reason and necessity to follow the PTB management guidelines by the Healthcare Ministry of the Russian Federation. Women had delivered in different maternity houses and medical centers in Moscow, but with relatively similar quality of services, although it might be considered as a limitation of our study. The retrospective nature of the study hampered our ability to collect data concerning newborns.