Intravaginal use of natural micronised progesterone to prevent pre-term birth: A randomised trial in India

Abstract

In a prospective, randomised trial, 100 pregnant women with >/= one prior spontaneous pre-term birth were randomised into two groups. Group 1 women received 100 mg natural micronised progesterone intravaginally once daily from 20-24 weeks' gestation until 36 weeks. Group 2 women did not receive progesterone. Both groups were regularly supervised until delivery. Pre-term birth (<37 and <34 weeks) and other maternal, neonatal outcomes were primary and secondary outcomes, respectively. Chi-square test and Fisher exact test were used to compare categorical variables. Independent sample t-test and one-way ANOVA were used to compare continuous variables and multiple comparisons, respectively. Pre-term births <37 weeks were significantly lower in Group 1 (12% vs 38%, p = 0.002), but pre-term births <34 weeks were similar. The mean birth weight of neonates born to women in Group 1 was significantly higher (2800 vs 2,500 g, p = 0.023). We concluded intravaginal administration of 100 mg of natural micronised progesterone significantly reduced the incidence of pre-term birth <37 weeks in women with > or = one prior pre-term birth. Future research is warranted to assess the long-term safety and efficacy of progesterone.

Vaginal micronized natural progesterone treatment and reduced risk of recurrent preterm birth

“…Dose of progesterone may be one of the important factors associated with preventing recurrent PTB. In previous studies, 100 mg progesterone was used in women with previous PTB history [11,13,19] and 200 mg progesterone was used in women with short cervical length [15]. But, in our study, there were no standardized criteria for the dose of progesterone and this is another main limitation of this retrospective study.…”

“…Preterm birth before 34 weeks of gestation was significantly lower in progesterone group (2.8%) compared to placebo group (18.6%). In another randomized placebo-controlled trial of Majhi et al [19], 100 mg of vaginal progesterone were used in women with previous PTB history from 20−24 to 36 weeks of gestation, and result showed that PTB rate was significantly lower in progesterone group than placebo group (12% vs. 38%; RR, 0.32; 95% CI, 0.14−0.72). In 2011, Cetingoz et al [13], reported a randomized placebo controlled trial of 100 mg vaginal progesterone in high risk women starting from 24 to 34 weeks of gestation.…”

“…In 2004, two randomized controlled trials suggested that the prophylactic administration of progesterone in pregnant women at high risk for PTB, including those with prior history of PTB, is associated with a reduction of 60% to 78% in PTB rate [11,12]. After on, several randomized controlled trials reported that the use of progesterone reduced the risk of recurrent PTB [13][14][15][16][17][18][19]. In 2008, the American College of Obstetricians and Gynecologist published a committee opinion recommending the use of progesterone supplementation to prevent recurrent PTB in women with a singleton pregnancy and a prior spontaneous PTB due to spontaneous preterm labor or premature rupture of membranes [20].…”

Twin and Preterm Labor: Prediction and Treatment

“…The positive effect of vaginal progesterone on reducing the rate of preterm birth in singleton pregnancies with short cervix, as well as singleton patients with history of previous preterm birth, has been confirmed by a large number of randomized studies [48][49][50][51][52][53][54]55•]. However, in twins the situation was found to be different; two large, randomized, controlled studies-the PREDICT study [56••] and the STOPPIT study [57••]-showed no reduction of the preterm birth rate with natural vaginal progesterone administration in twin pregnant patients with short cervices [58].…”

Progesterone treatment for the prevention of preterm birth

“…IM 17OHPC 250 mg weekly PTB <37 wk: 32% vs. 60% (P<0.05) da Fonseca et al [17] Vaginal P tablet 100 mg daily PTB <37 wk: 13.8% vs. 28.5% (P=0.03) PTB <34 wk: 2.8% vs. 18.6% (P=0.002) Majhi et al [18] Vaginal P tablet 100 mg daily PTB <37 wk: 12% vs. 38% (P=0.0027) Cetingoz et al [19] Vaginal P tablet 100 mg daily PTB <37 wk: 40% vs. 57.2% (P=0.036) PTB <34 wk: 8.8% vs. 24.3% (P=0.010) O'Brien et al [20] Vaginal P gel 90 mg daily PTB <32 wk:10.0% vs. 11.3% (P>0.05) PTB <37 wk: 41.7% vs. 40.7% (P>0.05) Rai et al [22] Oral P tablet 200 mg daily PTB <37 wk: 39.2% vs. 59.5% (P=0.002) PTB <28-32 wk: 2.7% vs. 20.3% (P=0.001) Glover et al [23] Oral P tablet 400 mg daily PTB <37 wk: 26.3% vs. 57.1% (P=0.15) …”