Vaginal versus Intramuscular Progesterone in the Prevention of Recurrent Preterm Labour

INTRODUCTION

Preterm labour (PTL) is the major reason of perinatal and neonatal mortality and morbidity, which is closely related to developmental and neurological disorders later in life. ¹

The occurrence of this issue is growing and is estimated to be 15% of pregnancy in the developed world. Preventing it is also regarded a major challenge for obstetricians. ²

Survival of the preterm infant is directly related to gestational age at delivery; Survival increases from less than 50% before 24 weeks to more than 95% by 33 weeks' gestation and a corresponding inverse association exists among the risk of serious disability in survivors and the pregnancy age at birth.³

Premature birth complications, such as premature retinopathy, necrotizing enterocolitis, intraventricular hemorrhage, respiratory diseases and sepsis, are not limited to the neonatal period; they may also represent sequelae, like abnormal neurophysiological development in early childhood and school under-achievement. ⁴

Early diagnosis of pregnant women who are at high risk of preterm labor can be the most successful. ⁵

Thereby, bed rest, cervical cerclage, bacterial vaginosis treatment, and prophylactic use of progesterone could be one of the managements in this high-risk population. ⁶

There is still considerable uncertainty about the best form of progesterone, path of administration, dose and timing of initiation of therapy in risky women to avoid PTL. ⁷

The purpose of this research has been to compare the efficacy of vaginal and intramuscular progesterone in preventing Preterm labour and on serum progesterone level in patients with history of recurrent spontaneous preterm labour.

PATIENTS AND METHODS

This comparative clinical trial study was carried out from April 2020 to November 2020 at Al-Hussein Hospital, Al-Azhar University. One hundred (100) of pregnant women have been selected and divided into 3 groups (vaginal progesterone group (A), intramuscular progesterone group (B) and control group (C)) with a history of prior spontaneous premature labor.

The study included women selected for this study who were sought to be at high risk for preterm labor have all the following criteria. singleton pregnancy, gestational Age of 20 to 24 weeks and patient with ast history of one or more spontaneous preterm labor.

While patients with multi-fetal pregnancy, history of ante partum PROM, cervical Incompetence or current cervical cerclage, known fetal anomaly, hypertension requiring medications, progesterone or Heparin treatment in current pregnancy or history of thrombo-embolic disorders, known allergy to progesterone, known liver disease and established preterm labor were excluded from the study.

All women were subjected to:

A. At the first antenatal visit; Full History taking, complete general and abdominal examination and Routine laboratory investigations (full labs). Estimation of gestational age; Estimation based on the last menstruation cycle and ultrasonography up to 12 weeks or two congruent scans among 12 and 24 weeks. Routine trans-abdominal ultrasound to assess the gestational age and to exclude fetal anomalies. Trans-vaginal ultrasound every four weeks to assess cervical length and funneling, Prophylactic medical treatment; All pregnant women in the study received prophylactic medical treatment for bacterial vaginosis and Chlamydial infection in the form of Azithromycin tablets 500 mg. orally once daily for 3 days and Metronidazole tablets 250 mg. three times per day for 7 days. Medications were given just before starting progesterone therapy. Treatment was started at 20-24 weeks gestation; The first 35 patients (Group A) will be given micronized progesterone tablets vaginally 200mg twice daily and the second 35 patients (Group B) will be given 100mg of intramuscular progesterone every third day While the third group (Group C) included 30 women who did not receive any PTL prevention progesterone and settled in the control group. Treatment will be continued until completed 36 weeks gestation or until occurrence of PROM or delivery. All women were advised about the benefit of the drug used and a written approval of the study was taken from each woman. A schedule of next visits was given to each woman. The fetal middle cerebral artery, umbilical artery and uterine artery will be examined by Doppler prior and one week following progesterone administration, progesterone will be continued until 36 weeks of pregnancy or childbirth.⁸ Serum progesterone monitoring will be done before progesterone administration and in the late second/early third trimester.

B. At the follow up visits: For 28 to 36 weeks of pregnancy, all pregnant women in the left lateral position underwent uterine contraction tracking with an external tocodynamomerer every other week for 60 min with an external monitor.

We determine the duration of contractions. Before the 30th week of pregnancy, four or more contractions per hour were deemed positive and after the 30th week, six or more contractions per hour were deemed positive. All pregnant women were questioned whether they had encountered any symptoms of preterm labor, such as heaviness, cramping, abdominal colic, or a sudden flow of fluid.

Statistical analysis:

The findings are represented as mean ± standard deviation or number (percent). If significant findings were reported, a one-way ANOVA with LSD test was used to compare numerical data in three studied groups. A Chi square test was used to compare categorical results. For data processing, the SPSS computer software (version 19 windows) was used. Significant was defined as a P value of less than or equal to 0.05, and highly significant as a P value of less than 0.01.

Outcome data were available for 100 women, 35 women in the vaginal progesterone group (Group A), 35 women in the intramuscular progesterone group (Group B) & 30 women in the control group (Group C).

RESULTS

There are no statistically significant differences among all groups with respect to age, parity and number of previous preterm labors (Table 1).

There are no statistically significant differences among all groups with respect to Mode of delivery (Table 2).

There were statistically significant differences among the progesterone groups & the control group with respect to NICU admission with higher percentage of NICU admission among the control group (63.3%) compared to the progesterone groups (25.2%)

Also, there were statistically significant differences among the vaginal progesterone group & the intramuscular progesterone group as regards NICU admission with higher percentage of NICU admission among the intramuscular progesterone group (40%) compared to the vaginal progesterone group (11.4%) (Table 3).

There were statistically significant differences among both progesterone groups pre and post progesterone administration as regards mean values of MCA RI with higher MCA RI before progesterone administration (0.86) than after (0.79) (Table 4).

There were no statistically significant differences among both progesterone groups before and after progesterone administration as regards mean values of UA RI (Table 5).

Table 1: Demographic features of different studied groups.( Data is represented as mean ± SD; NS= p> 0.05= not significant)

Table 2: Mode of delivery in different studied groups.( Data is represented as number (%).; NS= p> 0.05= not significant)

Table 3: The admission of the Neonatal Intensive Care Unit (NICU) in different studied groups..( Data is represented as number (%).; P< 0.01= highly significant).

Table 4: Comparison among average values of MCA RI calculated pre and post progesterone administration in different studied groups .( Data is represented as mean ± SD; NS= p> 0.05= not significant; **p< 0.01= highly significant; aa p< 0.01 relative to control group)

Table 5: Comparison among average values of UA RI calculated pre and post progesterone administration in different studied groups .( Data is represented as mean ± SD; NS= p> 0.05= not significant).