Efficacy and Safety of Natural Micronized Progesterone Sustained Release Formulations in High-Risk Pregnancies

28 Nov, 22

Introduction

Management of high-risk pregnancy is a major challenge faced by the clinicians globally. Unexplained Bad Obstetric History (BOH) or Preterm Birth (PTB) have been associated with significant fetal morbidity and mortality. Progesterone supplementation has been beneficial in preventing PTB. However, there is scarcity of data on optimal timing, mode of administration, optimal dose especially with sustained release formulations. Once-daily oral natural micronized progesterone offers high patient compliance and greater bioavailability of upto 33% with the current formulations using hydroxypolymethyl cellulose polymer or Matrix technology. The anti-inflammatory, immunomodulatory and uterine quiescence effects of natural progesterone make it an ideal choice in maintenance of pregnancy while avoiding complications of PTB.

Aim

The clinical efficacy and safety of natural micronized progesterone sustained release (NMP SR) formulation as primary or secondary prophylactic strategy was assessed in high-risk women presenting with risk factors for PTB or BOH.

Method

Study Design

Retrospective case-cohort analyses.

Treatment Strategy

The analyses included oral NMP SR prescriptions for BOH utilising the Drug utilisation surveillance (DUS) sheet across 40 centres in India
Demographics and medical history of the cohort was recorded
The cohort underwent hormonal assessment wherein the levels of beta-hCG and antiphospholipid antibodies (APLA) were measured
Risk assessment for delivery or pregnancy outcome was documented based on transvaginal ultrasound at every follow-up visit
The numerical and categorical (nominal and continuous) data was recorded using the descriptive statistics.

Results

The analyses included consecutive prescription records of 185 patients with high-risk pregnancy
Baseline characteristics were as follows:
- Mean age of 28.4 years
- Body weight 60.5 kg
- Mean abortion rate of 1.5 and 2 for BOH cases with first or second trimester loss.
Oral NMP SR was supplemented for PTB prophylaxis in BOH cases with first or second trimester loss cases, cervical factor, still birth, spotting and placenta previa.
Among the BOH cases, 50 women had a preceding history of >2 pregnancy losses; with 56% (n=28) assessed as unexplained recurrent pregnancy loss (RPL) after ruling out of APLA syndrome and 44% (n=22) were high risk cases of spontaneous pregnancy loss
Oral NMP 300 mg was preferred in women with unexplained RPL, cervical factor and threatened miscarriage for mean duration of 18+5, 19 and 10+1 weeks respectively.
No adverse health outcomes were reported and pregnancy was continued till 34th week.
Treatment-emergent adverse events (TEAEs) were mild and treated symptomatically with none requiring hospitalization or referral.
The incidence of TEAEs are shown in Figure 1.

Figure 1. Incidence of TEAEs

Conclusion

Long-term supplementation with oral natural micronized progesterone sustained release (NMP SR) formulations is effective and safe in high-risk pregnancies with risk factors for bad obstetric history or preterm birth.
The preferred dose of NMP SR was 300 mg, initiated between 16 to 26 weeks and continued upto 34 weeks
Long-term supplementation with NMP SR was well tolerated with no adverse health outcomes.

J Clin Diagnostic Res. 2018; 12(10): QC04-QC-06.