Prevention is the most effective treatment for PTB. Currently, the widely used method for prevention of PTB is adjuvant progesterone therapy. The use of progesterone has also been recommended by the American Congress of obstetricians and gynecologists (ACOG) to prevent PTB in pregnant women with risk factors such as preterm labor .
There has been a growing advancement in the understanding of progesterone signaling pathways lately, which has shed light into novel targets for progestin-based therapies to prevent PTB. It has been suggested that new selective progestin agents can boost anti-inflammatory activities that prevent preterm labor .
Herein, we studied the therapeutic effect of 17α-OHPC and Dydrogesterone in comparison with no intervention at all for the prevention of PTB and delaying the delivery. We observed no significant differences in outcomes between the Dydrogesterone and control groups.
We found that 17α-OHPC induced a markedly longer latency period and subsequently led to more favorable obstetric and neonatal outcomes, compared to both the Dydrogesterone and the control groups. Moreover, we observed no serious side effects in the participants and only few cases of nausea and bruises at the injection site occurred, which were trivial and resolved spontaneously without any specific treatment.
Shahgheibi and colleagues compared weekly intramuscular injections of 17α-OHPC (250 mg) with placebo in 100 high-risk pregnant women in 24Th-34Th Weeks of gestation. Consistent with our findings, they reported a significant effect for 17α-OHPC injection on prevention of PTB . This consistency is important because their study had similar methodology and sample size and this can somehow confirm the reliability of our results. Similar results have also been reported by Ibrahim et al. In a randomized trial comparing weekly intramuscular injections of 17α-OHPC with placebo in prevention of PTB among 50 women with a prior history of PTB .
A recent open-label clinical trial by Pustotina compared the efficacy of 17-OH progesterone, Dydrogesterone, and vaginal or oral micronized progesterone with cerclage to prevent PTB in women with a short cervix. They studied 95 women with singleton pregnancy at 15-24 weeks and short cervix, of whom 60 had symptoms of preterm labor. They divided the patients to receive 30 mg daily oral Dydrogesterone, 250 mg weekly 17OHP, 400 mg daily oral progesterone, or 400 mg daily vaginal progesterone capsules .
In contrast with our findings, Pustotina found that vaginal progesterone prevents about 94% of the PTBs in pregnant women with a short cervix, while Dydrogesterone, 17-OH progesterone, and oral micronized progesterone were associated with PTB in 91.7% of cases. She also found that vaginal progesterone is associated with lower risk of low birth weight . The inconsistency between our results and that of the mentioned study probably stems from the fundamental difference in our sample population and methods used. Our sample size was relatively larger and our participants were all in 28Th-34Th Gestational weeks and had evident preterm labor.
Fonseca et al. Also showed the efficacy of vaginal progesterone at a dose of 200 mg daily in the prevention of PTB in women with a short cervix. Nevertheless, they did not find any significant reduction in neonatal morbidity with this intervention . This finding is in line with the results of the prior mentioned study by pustotina, which indicated that vaginal progesterone has a dose-dependent effect on pregnancy outcomes .
Born and colleagues randomized 70 pregnant women with preterm labor to receive either 400 mg daily vaginal progesterone suppository or no treatment. They found that vaginal progesterone not only significantly increases the latency period, but also decreases the neonatal complications such as low birth weight and respiratory distress syndrome. However, it was not found to be effective in reducing the rate of NICU admissions and sepsis . These results are not directly comparable with our findings because of the different route of administration and type of progesterone, but somehow support the main theoretical basis of our findings, i.e. The beneficial effects of progesterone in preventing PTB and neonatal complications.
We did not compare Dydrogesterone and 17α-OHPC with vaginal or oral micronized progesterone. However, a previous study compared daily vaginal micronized progesterone (200 mg) and weekly intramuscular 17α-OHPC (250 mg) with no progesterone, in 60 women at 20-24 weeks gestation and reported equal efficacy for both intramuscular and vaginal progesterone in the prevention of preterm labor .
Norman et al. in a large-scale study compared 200 mg daily vaginal progesterone and placebo in prevention of PTB and adverse neonatal outcomes. In contrast with the results of the above mentioned studies, they reported that vaginal progesterone was not associated with reduced risk of PTB or neonatal complications .
A randomized, double blinded, placebo controlled trial by Areeruk and Phupong investigated the efficacy of oral Dydrogesterone (20 mg daily) in the management of preterm labor in 48 pregnant women at 24Th-34Th Gestational weeks. They found no significant difference between Dydrogesterone and placebo groups in terms of recurrent uterine contractions, latency period, gestational age at delivery, mode of delivery, birth weight, Apgar score, neonatal morbidity, and mortality . These results were completely compatible with our results regarding the comparison of outcomes between Dydrogesterone group and the controls, even though we used higher doses of Dydrogesterone compared with that in Areeruk’s study.
To the best of our knowledge, few studies with comparable sample size have investigated the efficacy of both 17α-OHPC and Dydrogesterone in a controlled trial design to prevent PTB in high-risk pregnancies. However, there are several limitations to our study. First, our study was not blinded and this could put the findings at risk of possible bias. Second, although we tried to minimize the baseline differences between the study groups, we could not completely match the maternal age of participants. This might have had a confounding effect on our findings. Lastly, including vaginal progesterone along with our two interventions might have led to a better understanding of the effect of different routes of administration on the preventive role of progesterone in the PTB.17α-OHPC injection can strongly prolong the latency period and improve neonatal outcomes and therefore, is superior to oral Dydrogesterone in the prevention of PTB.
In conclusion, although 17α-OHPC may be a more invasive option in the prevention of PTB, its benefits outweigh its drawbacks and it can be recommended for women with preterm labor and risk of PTB. Further studies are required to improve diagnostic and therapeutic strategies for prevention of PTB, especially in women with high-risk pregnancies.