Preterm birth (PTB), defined as delivery before 37 completed weeks of gestation, continues to be one of the most significant causes of neonatal morbidity and mortality globally.[1] In 2020, an estimated 13.4 million babies were born preterm, which is about 1 in every 10 live births worldwide.[2] The clinical and public-health impact of prematurity is high, with about 900,000 children under 5 years of age dying in 2019 due to complications of prematurity.[3]

One of the best predictors of recurrent preterm birth is a previous preterm birth, with women who had a previous preterm birth estimated to have anywhere from a 2- to 3-fold increased risk of preterm birth during a subsequent pregnancy.[4] This risk is even higher if a short cervix is

found during the second trimester.[5] The transvaginal cervical-length assessment is a proven technique for the detection of women who are at risk of spontaneous preterm delivery, and a short cervix is defined as a length of ≤25 mm in singleton pregnancies.[6] Previous spontaneous preterm birth and a short cervix are thus an important high-risk group where preventive intervention targeting this subgroup could make a significant impact on pregnancy and neonatal outcomes.[7]

Vaginal progesterone and cervical cerclage are two approaches that are used frequently to prevent a miscarriage.[8] Vaginal progesterone can help reduce cervical shortening and inhibit pathways that lead to premature cervical changes and uterine activity.[9] The American College of Obstetricians and Gynecologists (ACOG) now acknowledges the use of vaginal progesterone as a treatment option in women who have had a prior spontaneous preterm birth, a singleton pregnancy, and a short cervix, but acknowledges that this treatment has not been proven to benefit women who have had previous preterm births but do not have a short cervix.[10] In contrast, cervical cerclage strengthens the cervix and might be performed in women who have a short cervix and other significant risk factors for preterm delivery, such as a previous spontaneous preterm birth.[11]

Even with interventions available, optimal use of interventions for women with multiple episodes of preterm birth and a short cervix is clinically relevant and context-dependent.[12] Progesterone is non-invasive, comparatively easy to apply, and free from risks associated with surgery or anesthesia, while cerclage is a procedure that might offer a physical stop on cervical dilatation and shortening.[13] There is growing consensus that each patient should be treated individually based on cervical length, obstetric history, gestational age, and patient preference rather than using one surgical procedure that is always best.[14]

Findings from various populations and health systems might not necessarily be directly transferable to the context of women's health care in Pakistan due to variations in antenatal surveillance, referral practices, maternal characteristics, access to interventions, and resources for neonates. Hence, it is clinically relevant to assess the comparative effectiveness of these two approaches in a real-world scenario in a Pakistani hospital environment. A direct comparison between vaginal progesterone and cervical cerclage might clarify whether the less invasive method is equally effective, and might reveal differences in gestational age at delivery, recurrence of preterm birth, and outcomes for the newborns. In the present study, the pregnancy and neonatal outcomes were compared between women with a history of recurrent spontaneous preterm birth who were treated with cervical cerclage versus vaginal progesterone for a short cervix. The present study aimed to compare the maternal and neonatal outcomes of vaginal progesterone versus cervical cerclage for prevention of recurrent spontaneous preterm birth in women with a short cervix.

A prospective comparative cohort study was conducted in the Department of Obstetrics and Gynaecology at Federal General Hospital, Chak Shahzad, Islamabad. The study was carried out for six months, starting from 1st October, 2025 to 31st March, 2026. Study subjects were recruited over a period of time and followed from enrolment to delivery and early neonatal assessment. The sample size was calculated using OpenEpi version 3.01 based on an expected preterm birth rate of approximately 32% in the vaginal progesterone group and 14% in the cervical cerclage group was used for the calculation.[8] The minimum sample size per treatment group was calculated to be 85 participants for each treatment group, with a total sample size of 170 participants, for a 2-sided confidence level of 95%, a power of 80%, and an allocation ratio of 1:1 between the two treatment groups. The sample size was increased to 94 patients per group to account for a 10% dropout rate or missing outcome data. The final sample size was thus 188 pregnant women, including 94 women receiving vaginal progesterone and 94 women who had cervical cerclage. A consecutive sampling technique was used. Women were eligible when they were 18 years or older, had a singleton pregnancy, had a previous history of spontaneous preterm birth, and had a cervical length of < 25 mm on a sonographic measurement at mid-trimester. Women were included if treatment with either vaginal progesterone or cervical cerclage was clinically deemed appropriate and begun during the study period. The participants had to give informed consent and consent for follow-up until delivery. Women with multiple pregnancies, major fetal congenital anomalies, known fetal chromosomal abnormalities, current preterm labour, preterm prelabour rupture of membranes on recruitment, significant antepartum haemorrhage, clinically suspected intrauterine infection, or advanced cervical dilatation were excluded. Additionally, women who were spontaneously going into preterm labor but not otherwise indicated for preterm delivery were excluded because of severe pre-eclampsia, fetal growth restriction, or other maternal or foetal indications. Patients who had previously had a cerclage placed for cervical insufficiency, had a history of other uterine anomaly, or were undergoing another investigational procedure were excluded. Women who refused to participate or who were not likely to return for follow-up at the study hospital were also not included. Eligible women were approached after gaining ethical approval from the relevant institutional authority, and the purpose and procedures of the study were explained. All subjects participated in this study after receiving written informed consent. The demographic and clinical data was collected on a structured data collection form. Variables considered included maternal age, BMI, parity, gravidity, gestational age at entry to the study, number of previous preterm births and gestational age of previous preterm births, previous pregnancy outcomes, history of abortion, and pertinent maternal comorbidities. The length of the cervix was measured by transvaginal ultrasonography with a standardized method, and the minimum technically acceptable cervical length was determined. Cervical length ≤ 25 mm was defined as a short cervix.[15] Information on the preventive intervention was documented: treatment group, gestational age at start, progesterone dose and length of time in the progesterone group, type and gestational age at placement of cerclage in cerclage group. Procedure-related complications and adherence to the progesterone therapy were also reported. The participants were followed longitudinally during pregnancy. The main outcome was preterm delivery (before 37 completed weeks of gestation). Secondary obstetric outcomes were preterm birth (before 35 and 32 weeks) and gestational age at delivery, as well as premature rupture of membranes, mode of delivery, antenatal hospitalization, and maternal complications. Neonatal outcomes were birth weight, Apgar at 1 and 5 minutes, NPICU admission, respiratory morbidity, and neonatal mortality. Other complications of treatment, such as vaginal discomfort or discharge from progesterone pills, or bleeding, infection, or membrane rupture from cerclage, were also documented. IBM SPSS Statistics version 26.0 was used for entering and analyzing the data. Normality of continuous variables was tested by using suitable graphical and statistical methods. Continuous variables were expressed as mean ± standard deviation (SD), and non-normally distributed variables were expressed as median and interquartile range (IQR). For categorical variables, frequencies and percentages were used. The baseline characteristics of the two groups (vaginal progesterone and cervical cerclage) were compared. The independent-samples t-test was used for comparison of normally distributed continuous variables, while the Mann–Whitney U test was used for non-normally distributed variables. Categorical variables were compared using the Pearson chi-square test and Fisher's exact test. Comparisons of the primary outcome of preterm birth prior to 37 weeks and secondary categorical outcomes were made between the two groups using risk estimates with 95% confidence intervals as appropriate. Multivariable binary logistic regression analysis was used for the primary outcome to account for the possible baseline differences between treatment groups. Clinical relevance or any association with the outcome on univariable analysis was considered for inclusion in the multivariable model. Odds ratios and 95% confidence intervals (CIs) were presented. A two-tailed p-value < 0.05 was regarded as statistically significant.

A total of 188 women were included, with 94 receiving vaginal progesterone and 94 undergoing cervical cerclage. Demographic and obstetric data were similar in both groups. Demographic and obstetric data was similar in both groups. The mean age of the mothers was 29.8 ± 4.6 years and 30.2 ± 4.8 years in the progesterone and cerclage groups, respectively. No significant differences in BMI, gravidity, parity, gestational age at enrolment, previous spontaneous preterm births, or cervical length were seen between the groups (Table 1).

The differences in treatment-related characteristics were also generally comparable. The majority of women in both groups started preventive treatment at < 22 weeks gestation; treatment adherence was good in both groups. There was no significant difference in previous cesarean delivery, previous miscarriage, maternal comorbidities, or overall treatment-related complications between groups. Complications occurred slightly more often after cerclage, but this difference was not statistically significant (Table 2).

Compared to women who underwent a cerclage, the women who received progesterone had 29 (30.9%) who had a preterm birth before 37 weeks, but there was no statistically significant difference (p=0.508). Likewise, no significant differences were observed for preterm birth prior to 35, 32, or 28 weeks, gestational age at delivery, PPROM, antenatal hospitalization, or mode of delivery. There were no significant differences in the rates of maternal infectious complications (Table 3).

Neonatal outcomes were also similar between the two treatment groups. Mean birth weight was 2768 ± 548 g in the progesterone group and 2845 ± 526 g in the cerclage group (p=0.327). There were no significant differences in low birth weight, Apgar scores, admission to the NICU, RDS, neonatal sepsis, or mortality (Table 4).

If outcomes were broken down by cervical length, women with a length <15 mm experienced preterm birth at a higher frequency than women with a length of 15–25 mm (p=0.121). Women with a length <15 mm who received progesterone had a higher frequency of preterm birth than those who received cerclage, but this was not statistically significant (p=0.121). The rates were nearly the same in women with a cervical length of 15–25 mm (p=0.925) (Table 5).

A univariable logistic regression showed that a shorter cervical length of less than 15 mm (p=0.038) and the commencement of preventive treatment after 22 weeks (p=0.049). Treatment modality, maternal age, BMI, previous miscarriage, maternal comorbidity, number of previous preterm births, and treatment adherence were not significantly associated with the primary outcome (Table 6).

Cervical length <15 mm was independently associated with preterm birth before 37 weeks in the multivariable logistic regression model (p=0.047). By contrast, treatment modality (cervical cerclage vs vaginal progesterone) was not an independent predictor after controlling for the other relevant maternal and obstetric factors (p=0.448) (Table 7).

Table 1. Baseline demographic and obstetric characteristics of study participants (n=188)

Table 2. Maternal and treatment characteristics

Table 3. Primary and secondary obstetric outcomes

Table 4. Neonatal outcomes

Table 5. Comparison of primary outcome according to cervical length

Table 6. Univariable logistic regression analysis for preterm birth <37 weeks

Table 7. Multivariable logistic regression analysis for preterm birth <37 weeks

In women who had a singleton pregnancy, previous SPTB, and a short cervix, the present study revealed that vaginal progesterone and cervical cerclage had similar outcomes overall. The proportion of women who were born prematurely (before 37 weeks) was 30.9% in the vaginal progesterone group and 26.6% in the cerclage group, which was not statistically different. In singleton pregnancies with a sonographically short cervix, there was no overall advantage of cerclage for major neonatal outcomes according to Huang et al. (2021), who compared cerclage with conservative management. Their conclusions lend credence to the notion that treatment choice should be individualized to the level of cervical shortening and the obstetric risk of the individual patient and should not be decided solely on the basis that cerclage is always best.[16] The comparable efficacy we have found was similar to that found by Gulresen et al. (2021), who assessed women who had an extremely short cervix (≤10 mm). Their population was not spontaneously preterm before cerclage, but pregnancy latency increased, and the hazard of preterm delivery decreased, especially for those women who were already taking progesterone.[17] This differs in some ways from our results, where cerclage resulted in a numerical decrease in preterm birth but no significant difference in gestational length. This difference may be partly due to the fact that the study by Boelig et al. included a population at higher risk due to the significantly shorter cervical lengths, in which the potential benefit of cerclage may become more evident with extreme cervical shortening. The association of cervical length with outcome was especially interesting, as we found this to be more significant than the treatment modality. Women with a cervical length <15 mm had a higher prevalence of preterm birth compared with women with a cervical length of 15–25 mm, and cervical length <15 mm remained an independent predictor after multivariable adjustment. This finding is in agreement with Gulersen et al. (2025), who conducted an individual-patient-data meta-analysis of randomized trials that showed no statistically significant difference between cerclage and standard care for the reduction of preterm births among women with a short cervix at 24 weeks of gestation, and that the treatment effect did not differ significantly among the subgroups according to cervical length.[18] The results highlight the value of cervical shortening as a determinant of underlying risk and the possible variability in the relative benefit of cerclage depending on gestational age and cervical phenotype. The present study also confirmed the similar gestational age at delivery in both groups, 36.1 weeks in the progesterone group and 36.5 weeks in the cerclage group. This was similar to a 2022 retrospective cohort study that compared vaginal progesterone in women with threatened preterm labor and a short cervix (identified at 24 weeks or later). In that study, progesterone was correlated with a decrease in delivery before 37 weeks and an increase in time from diagnosis to delivery when compared to no progesterone. In this study, the comparator is no treatment, but the results confirm that vaginal progesterone is effective as a non-surgical method of prolonging pregnancy in certain high-risk women.[18] The lack of significant difference between progesterone and cerclage in our study was also consistent with the results of the SuPPoRT multicentre randomized controlled trial published in 2024. The rates of preterm birth before 37 weeks were 30.7% for cerclage and 24.2% for vaginal progesterone in 381 women with a cervical length <25 mm, but this difference was not statistically significant. Also, no difference was found for preterm delivery before 34 or 30 weeks, respectively, and adverse perinatals.[19] These results are similar to our results, in which the rate of preterm birth was numerically lower with cerclage, but not statistically superior to the progesterone group. Equivalence between these two approaches was corroborated by our neonatal findings. There was no significant difference between groups in terms of birth weight, Apgar scores, admission to NICU, respiratory distress syndrome, neonatal sepsis, or neonatal mortality. This was similar to the results from the SuPPoRT trial, which showed no difference in adverse perinatal outcomes with cerclage, pessary, or vaginal progesterone.[20] Likewise, a 2024 meta-analysis conducted on women who were pregnant with a singleton pregnancy and a short cervix and included 2,741 women found that vaginal progesterone significantly lowered preterm birth <34 and <32 weeks, admission to the Neonatal Intensive Care Unit, respiratory distress syndrome, intraventricular hemorrhage, neonatal death, and very low birth weight compared to placebo and no treatment. While this analysis did not make direct comparisons between progesterone and cerclage, it represents additional evidence that progesterone can be used to gain clinically relevant neonatal benefit without undergoing a surgical procedure.[8] There is recent evidence that progesterone could still be effective if the short cervix is detected relatively late in pregnancy. Dominsky et al. (2026) assessed the effect of vaginal progesterone use in women with a short cervix diagnosed after 24 weeks and found a significant reduction in risk of preterm birth with the use of progesterone as opposed to not using it. These findings are clinically relevant for our results as they confirm the potential of progesterone as a practical and less invasive intervention, especially where surgical intervention may be less available, or patients would rather not have a procedure. However, there are some differences between the two cohorts in terms of the gestational age at diagnosis and the study design, which limits the ease of comparison.[21] There were several limitations to this study. The prospective comparative cohort study design was not randomized, and the treatment selection was based on clinical decision-making, which may have resulted in selection and confounding bias. The study was performed at a single hospital, and the sample size was fairly small, so the results may not be generalizable to other populations and health care settings. Multivariable logistic regression was used to control for the following potential confounding factors, but the possibility of unmeasured confounding was not excluded. Clinically, adherence to treatment was assessed, but it may have been subject to reporting bias. Moreover, pregnancy and early neonatal outcomes were mainly studied, and long-term neurodevelopmental outcomes of the infants were not evaluated. Larger multicenter, randomized trials with longer follow-up are thus needed to validate these results.

Vaginal progesterone and cervical cerclage showed similar effectiveness in preventing recurrent preterm birth in women with a singleton pregnancy and a short cervix as well as in women with a history of spontaneous preterm birth. Preterm birth and NICU admission were not significantly different, although there were numerically fewer cases after cerclage. Cervical length of <15 mm was also independently associated with preterm birth, which suggests that the degree of cervical shortening is a more important predictor of the incidence of preterm birth than the treatment. Therefore, vaginal progesterone may be a sensible non-surgical choice of treatment in the correctly chosen women, and cerclage may still be useful in women with significant cervical shortening and a high-risk obstetric history. Cervical length, past obstetric history, gestational age, predispositions to complications, and patient preference should all be taken into account when making individual treatment decisions.

Ward, V.C., et al., Overview of the global and US burden of preterm birth. Clinics in Perinatology, 2024. 51(2): p. 301-311.

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