Use of progesterone supplement therapy for prevention of preterm birth: review of literatures

Abstract

Preterm birth (PTB) is one of the most common complications during pregnancy and it primarily accounts for neonatal mortality and numerous morbidities including long-term sequelae including cerebral palsy and developmental disability. The most effective treatment of PTB is prediction and prevention of its risks. Risk factors of PTB include history of PTB, short cervical length (CL), multiple pregnancies, ethnicity, smoking, uterine anomaly and history of curettage or cervical conization. Among these risk factors, history of PTB, and short CL are the most important predictive factors. Progesterone supplement therapy is one of the few proven effective methods to prevent PTB in women with history of spontaneous PTB and in women with short CL. There are 2 types of progesterone therapy currently used for prevention of PTB: weekly intramuscular injection of 17-alpha hydroxyprogesterone caproate and daily administration of natural micronized progesterone vaginal gel, vaginal suppository, or oral capsule. However, the efficacy of progesterone therapy to prevent PTB may vary depending on the administration route, form, dose of progesterone and indications for the treatment. This review aims to summarize the efficacy and safety of progesterone supplement therapy on prevention of PTB according to different indication, type, route, and dose of progesterone, based on the results of recent randomized trials and meta-analysis.

Vaginal compared with intramuscular progestogen for preventing preterm birth in high‐risk pregnant women (VICTORIA study): a multicentre, open‐label randomised trial and meta‐analysis

“…Currently, progestogen supplement therapy is recommended for women with a history of spontaneous PTB or with short CL by many guidelines, including those of the National Institute for Health and Care Excellence and the American College of Obstetricians and Gynecologists 32–35 . There is no clear consensus on the optimal indication, route of administration or dose among these guidelines, however, because the selection criteria of the study populations and methods of progestogen therapy vary substantially among the available studies 14 …”

“…Progestogen supplement therapy is one of the few proven effective methods for preventing PTB in women with a history of spontaneous PTB or with short CL 9–13 . Progestogens are available in natural micronised or synthetic formulations for intramuscular, vaginal (tablet or gel) or oral administration 14 . Previous studies have reported that the injection of 17α‐hydroxyprogesterone caproate (17‐OHPC) can reduce recurrent PTB in women with a previous history of PTB 15–17 .…”

“…Vaginal micronised natural progesterone therapy has also been found to be effective in preventing PTB in women with a history of PTB or with short CL in many trials, 18–22 but not in all 23 . The efficacy of progestogen to prevent PTB may vary depending on indication, type, administration route and dose of drug 14 . Data regarding which progestogen therapy is better for preventing PTB are insufficient, however 24 .…”

Oral Micronized or Parenteral Progesterone versus Health Education in the Prevention of Preterm Birth: A Single Blinded Randomized Controlled Trial

“…Currently, no evidence exists on which progesterone supplementation can maximize the preventative effects while minimizing the side effects. Therefore, further researches are still required to define the optimal type, dose and duration of progesterone depending on various indications of treatment [13].…”

Vaginal Progesterone Has No Diabetogenic Potential in Twin Pregnancies: A Retrospective Case-Control Study on 1686 Pregnancies

“…In the last decade, the utility of progesterone administration has been extensively studied, in particular for its effect on prolonging pregnancy and thereby ensuring better neonatal outcome. This led to a substantial increase in the use of synthetic and natural progestogens in singleton and twin pregnancies [ 16 , 17 , 18 ].…”