Clinician Perceptions of the Available Progesterone in Clinical Practice:
According to World Health Organization (WHO), every year about 15 million babies are born prematurely around the world and that is more than one in ten of all babies born globally. Almost 1 million children die each year due to complications of preterm birth (2013). Across 184 countries, the rate of preterm birth ranges from 5 to 18% of babies born. In India, out of 27 million babies born every year (2010 data), 3.5 million babies born are premature. Newborn deaths (those in the first month of life) account for 40% of all deaths among children fewer than 5 years of age. Preterm birth is the world's number one cause of newborn deaths, and the second leading cause of all child deaths under the age of 5 years, after pneumonia.'
Preterm labor occurs when regular contractions result in the opening of your cervix after week 20 and before week 37 of pregnancy. Preterm labor can result in premature birth. The earlier the premature birth, the greater the health risks for the baby.
Use of antiprogesterone drugs for medicated termination of pregnancy has proved that progesterone withdrawal can cause pregnancy discontinuation. This strengthened the hypothesis that progesterone has a central role in the maintenance of early pregnancy and progesterone deficiency or insufficiency can be the cause of some miscarriages. A study from China with 726 participants presented that threatened miscarriage revealed a greater risk of abortion when the serum progesterone level was less than 90.62 nmol/L.
Furthermore, pathways leading to occurrence of preterm delivery seem to be having a common factor which is influenced by progesterone inadequacy. Such hypotheses resulted in numerous clinical trials of progesterone supplementation in women at high risk of miscarriage and preterm-delivery. Especially women with bleeding in the first pregnancy, history of recurrent pregnancy losses, and cervix are identified to be at risk and several trials has shown some benefit of progesterone therapy in these situations.
In 1953, the first randomized trial of progesterone was conducted in women with recurrent miscarriage subsequently 11 such trials were conducted till date is referred. In 1987, the first trial of use of progesterone women with threatened miscarriage was published followed by seven similar trials.
These trials failed to give any solid foundation to evidence-based recommendations with regard to the efficacy of progesterone therapy or type of formulations preferred route owing to weak methodology and size. Thus the two most influencing guidelines, such as the American College of Obstetricians and Gynecologists (ACOG) and the National Institute for Care and Excellence (NICE), could not mention the progesterone therapy with conviction with COG concluding the use of progestin in threatened miscarriage as controversial, 5 while the NICE expecting a larger multiset randomized cohort to rely on such a therapy. Additionally, progesterone formulations used were heterogeneous therefore choosing a particular progesterone formula and a requisite dose is completely based on the perception of the clinicians offering these treatment. Recently two trials, PROMISE (progesterone in recur miscarriage) and PRISM (progesterone in spontaneous mis-carriage), have been conducted.
Progesterone therapy is a commonly used treatment for threatened miscarriage, threatened preterm labor, and prevention of both miscarriages and preterm labor. This is based on the fact that progesterone is essential for the notation and continuation of pregnancy. There is an increasing evidence of the utility of such an approach in both these conditions though some robust data are still awaited to support this approach.
The doubts about the efficacy of progesterone treatment are probably due to many other confounding factors responsible for both mis-carriages and preterm deliveries even though many of the pathogenic mechanisms seem to be routed through progesterone deficiency of inefficiency. Despite every clinician's recommendations, progesterone therapy for such obstetric situations in the perceived belief of progesterone deficiency could be possibly ameliorated. This article will address these clinician perceptions based actually on a meager evidence with no head-to-head comparison among the formulations but with an intention to achieve successful pregnancy outcomes in the form of live births. The dilemma further is made complex due to the various formulations of progesterone that are available for use in clinical practice.
Girija Wagh, MD, FICOG, FICS - Department of Obstetrics and Gynecology, Bharati Vidyapeeth, University Medical College, Pune, Maharashtra, India