PREGNANCY OUTCOME IN SHORT CERVIX: PROGESTERONE VS CERVICAL ENCERCLAGE

* Nikita Gandotra 1 and Vandana Nimbargi 2 . 1. Resident, Department of Obstetrics and Gynaecology, BharatiVidyapeeth Deemed University Medical College, Pune, Maharashtra, India. 2. Professor, Department of Obstetrics and Gynaecology, BharatiVidyapeeth Deemed University Medical College, Pune, Maharashtra, India. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History

Progesterone is considered a key hormone for pregnancy maintenance, and a decline of progesterone action is implicated in the onset of parturition. If such a decline occurs in the midtrimester, cervical shortening may occur, and this would predispose to preterm delivery. [7][8][9][10][11][12][13][14] Various randomized clinical trials and data meta-analysis showed that vaginal progesterone decreases the rate of preterm delivery and neonatal morbidity/mortality in women with a sonographic short cervix [15][16][17] .
Cervical encerclage has also been widely used as a surgical method to prevent recurrent mid-trimester pregnancy loss in women at risk. Elective cerclage placement may benefit some women with proven cervical insufficiency. Although highly contentious, more recent data suggest that cervical encerclage may reduce the risk of preterm delivery in that subgroup of asymptomatic singleton pregnancies with both shortening on TVS and a history of spontaneous preterm birth 18 .
The Present study aimed at comparing the effects of micronized natural progesterone and cervical encerclage in pregnancy with short cervix. Routine ANC profile 7.

Ultrasonography
The cases were followed thereafter in antenatal clinic till delivery and outcome was noted. The primary outcome measures were preterm birth <32 weeks of gestation and composite perinatal morbidity and mortality (defined as the occurrence of any of the following events: respiratory distress syndrome, grade III/IV intraventricular haemorrhage, necrotizing enterocolitis, neonatal sepsis, bronchopulmonary dysplasia, or perinatal death).
Secondary outcome measures included preterm birth at <37, 34-37, and <28 weeks of gestation, respiratory distress syndrome, necrotizing enterocolitis, grade III/IV intraventricular hemorrhage, neonatal sepsis, bronchopulmonary dysplasia, perinatal mortality, a composite neonatal morbidity outcome (defined as the occurrence of any of the above mentioned neonatal morbidities), birth weight <1500 g and <2500 g, and admission to the neonatal intensive care unit (NICU).
Data Analysis:-Data was analyzed using SPSS 21.0 (SPSS Inc., Chicago, IL, USA) using appropriate statistical tests.

Results:-
The mean maternal age was 22.44 years in progesterone group and 22.64 years in cerclage group (p-0.514). Maximum number of women, 28% of progesterone group and 44% of cerclage group, were noted between 18-20 weeks gestation while 20% of progesterone and 44% of cerclage were between 20-22 weeks (p-). Maximum number of women (44%) of progesterone group had cervical length of 1.5-2 cm whereas 44% of cerclage group had cervical length of 2.1-2.5cm ( Table 1).The outcome of pregnancy with natural micronised progesterone reflected 36% births between 28-32 weeks of gestation, 28% after completion of 37 weeks and only 16% before 28 weeks of gestation whereas outcome with cerclage 36% between 28-32 weeks, 44% after completion of 37 weeks and 8% before 28 weeks (p-0.56; Table 2). The difference in secondary outcome measures (PPROM, LSCS rate) in both the group were also statistically non-significant (p-1.0; Table 3). Our study also compared neonatal outcome (mean birth weight, APGAR, duration of NICU admission, respiratory distress, development of IVH, NEC and neonatal sepsis) in cerclage and progesterone group.No statistically significantdifference was observed between the groups regarding neonatal parameters (p>0.05; Table 4).

Discussion:-
The first randomized clinical trial to examine the effects of vaginal progesterone on the prevention of preterm birth in women with a short cervix was reported by da Fonseca et al. 19 The primary outcome of the trial was the frequency of spontaneous preterm delivery at <34 weeks of gestation. Patients allocated to receive vaginal progesterone had a lower rate of preterm delivery (<34 weeks) than those in the placebo group [19.2% (24/125) vs. 34.4% (43/125)]. In another trial, termed as "PREGNANT" trial 20 , It was estimated that 14 women with a cervical length between 10-20mm would need to be treated with vaginal progesterone to prevent one case of preterm birth before 33 weeks of 1147 gestation. In addition, there was a significant decrease in the rate of preterm delivery <35 and <28 weeks of gestation. Since then, various trials and meta-analysis have shown the efficacy of vaginal progesterone to prevent preterm birth in cases with short cervix [21][22][23][24][25][26][27][28][29] .
Cervical cerclage was introduced in 1955 by V. N. Shirodkar, Professor of Midwifery and Gynecology at the Grand Medical College in Bombay, India. 30 The procedure was developed in response to his observation that "some women abort repeatedly between the fourth and seventh months, and no amount of rest and treatment with hormones seemed to help them in retaining the product of conception."Despite the 50 years that have elapsed since the introduction of cerclage as a procedure, there is conflicting evidence about its efficacy for standard indications (i.e. prophylactic) or for some patients with a sonographic short cervix.Several randomized clinical trials have been conducted to date which have yielded mixed results [31][32][33][34][35][36][37][38] A meta-analysis of randomized clinical trials of patients with a prior history of preterm birth and a short cervical length (<25mm) suggests that cervical cerclage is effective in reducing the rate of preterm birth and perinatal morbidity/mortality. 158 A different meta-analysis has suggested that women with a prior spontaneous preterm birth and singleton gestation may be monitored safely with transvaginal sonographic cervical length measurements 39 .
In present study, we observed that both vaginal progesterone and cerclage in patients with a short cervix was associated with a significant reduction in the risk of preterm birth. The key finding is that both are equally effective for the prevention of preterm birth and adverse perinatal outcomes.
Very few studies has directly compared cervical cerclage and vaginal progesterone for the prevention of preterm birth in women with a sonographic short cervix. Most previous randomized trials allocated to receive vaginal progesterone versus placebo /no treatment, or cerclage versus no cerclage for the prevention of preterm birth.
Keeler et al. 40 compared between patients with short cervix on transvaginal ultrasound between 16 and 24 weeks' gestation treated with McDonald cerclage and those treated with weekly intramuscular injections of 17 alphahydroxyprogesteronecaproate. Spontaneous Pre-term Birth (PTB) prior to 35 weeks' gestation occurred in 16/42 (38.1%) of the cerclage group and in 16/37 (43.2%) of the 17OHP-C group (relative risk, 1.14 95% CI, 0.67, 97 1.93). A post hoc analysis of patients with a prior PTB showed no difference in spontaneous PTB <35 weeks between groups.Conde-Agudelo and co-investigators performed an indirect comparison of vaginal progesterone versus cerclage, using placebo/no cerclage as the common comparator. Four studies evaluating vaginal progesterone versus placebo (158 patients) and five evaluating cerclage versus no cerclage (504 patients) were included. Both interventions were associated with a statistically significant reduction in the risk of preterm birth <32 weeks of gestation and composite perinatal morbidity and mortality compared with placebo/no cerclage. Adjusted indirect meta-analyses did not show statistically significant differences between vaginal progesterone and cerclage in reducing preterm birth or adverse perinatal outcomes 41 .
The strength of this study is that it is first study in this region to compare directly between vaginal progesterone and cervical cerclage. All previous studies compare either vaginal progesterone with placebo or cervical cerclage with placebo or conducted an indirect comparison. Our study compares two methods directly to be more practical and to avoid the hidden bias such as selection bias which affect indirect comparing.

Conclusion:-
The observations made in present study suggests that natural micronized progesterone is as effective as cervical cerclage in prevention of premature labour in a women with singleton pregnancy with short cervix. Use of natural micronized progesterone is more preferable in clinical practice because it is non-invasive technique, easy to administer and the patients do not suffer from surgical and anaesthesia procedure related adverse effects such as pain, headache, vomiting and other complications. It is also not associated with any hospital stay and is very economical. Using vaginal progesterone saves time for patients as well as doctors.