Progesterone is a key hormone to support pregnancy and pregnancy onset. Problem of low fertility, infertility is becoming increasingly important, which in turn further exacerbates miscarriage. The aim of this systematic review is to elucidate new information based on current scientific evidence, evidence-based medicine and world clinical protocols, summarize actual knowledge of the importance of sequential use of one type of gestagen for pre-conceptual preparation, treatment, and prevention of the risk of pregnancy termination in different clinical settings. Analysed data indicate that it is n

Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their lifetime, and 15% to 20% of pregnancies ending in a miscarriage. Progesterone has an important role in maintaining a pregnancy, and supplementation with different progestogens in early pregnancy has been attempted to rescue a pregnancy in women with early pregnancy bleeding (threatened miscarriage), and to prevent miscarriages in asymptomatic women who have a history of three or more previous miscarriages (recurrent miscarriage). To estimate the relative effectiveness and safety profiles for the different progestogen treatments for threatened and recurrent miscarriage, and provide rankings of the available treatments according to their effectiveness, safety, and side-effect profile. We searched the following databases up to 15 December 2020: Cochrane Central Register of Controlled Trials, Ovid MEDLINE(R), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies. We included all randomised controlled trials assessing the effectiveness or safety of progestogen treatment for the prevention of miscarriage. Cluster-randomised trials were eligible for inclusion. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved. We excluded quasi- and non-randomised trials. At least two review authors independently assessed the trials for inclusion and risk of bias, extracted data and checked them for accuracy. We performed pairwise meta-analyses and indirect comparisons, where possible, to determine the relative effects of all available treatments, but due to the limited number of included studies only direct or indirect comparisons were possible. We estimated the relative effects for the primary outcome of live birth and the secondary outcomes including miscarriage (< 24 weeks of gestation), preterm birth (< 37 weeks of gestation), stillbirth, ectopic pregnancy, congenital abnormalities, and adverse drug events. Relative effects for all outcomes are reported separately by the type of miscarriage (threatened and recurrent miscarriage). We used the GRADE approach to assess the certainty of evidence. Our meta-analysis included seven randomised trials involving 5,682 women, and all provided data for meta-analysis. All trials were conducted in hospital settings. Across seven trials (14 treatment arms), the following treatments were used: three arms (21%) used vaginal micronized progesterone; three arms (21%) used dydrogesterone; one arm (7%) used oral micronized progesterone; one arm (7%) used 17-α-hydroxyprogesterone, and six arms (43%) used placebo. Women with threatened miscarriage Based on the relative effects from the pairwise meta-analysis, vaginal micronized progesterone (two trials, 4090 women, risk ratio (RR) 1.03, 95% confidence interval (CI) 1.00 to 1.07, high-certainty evidence), and dydrogesterone (one trial, 406 women, RR 0.98, 95% CI 0.89 to 1.07, moderate-certainty evidence) probably make little or no difference to the live birth rate when compared with placebo for women with threatened miscarriage. No data are available to assess the effectiveness of 17-α-hydroxyprogesterone or oral micronized progesterone for the outcome of live birth in women with threatened miscarriage. The pre-specified subgroup analysis by number of previous miscarriages is only possible for vaginal micronized progesterone in women with threatened miscarriage. In women with no previous miscarriages and early pregnancy bleeding, there is probably little or no improvement in the live birth rate (RR 0.99, 95% CI 0.95 to 1.04, high-certainty evidence) when treated with vaginal micronized progesterone compared to placebo. However, for women with one or more previous miscarriages and early pregnancy bleeding, vaginal micronized progesterone increases the live birth rate compared to

The etiopathology of recurrent miscarriage is a combination of various factors, including chromosomal defects, genetic or structural abnormalities, endocrine abnormalities, infections, immune dysfunction, thrombophilia disorders, antiphospholipid syndrome, and unexplained causes. It has long been known that progesterone is needed to maintain pregnancy and its physiological development. Insufficient progesterone secretion and its low level in the blood serum in early pregnancy is associated with the threat of miscarriage and loss of pregnancy at a later stage – up to 16 weeks of gestation. The

Bookshelf. A service of the National Library of Medicine, National Institutes of Health. Coomarasamy A, Harb HM, Devall AJ, et al. Progesterone to prevent miscarriage in women with early pregnancy bleeding: the PRISM RCT. Southampton (UK): NIHR Journals Library; 2020 Jun. (Health Technology Assessment, No. 24.33.) Progesterone to prevent miscarriage in women with early pregnancy bleeding: the PRISM RCT. Show details Health Technology Assessment, No. 24.33. Coomarasamy A, Harb HM, Devall AJ, et al. Southampton (UK): NIHR Journals Library ; 2020 Jun. Contents Search term &lt; Prev Next &gt; Chapter 1 Introduction Existing knowledge Progesterone in pregnancy Progesterone is an endogenous hormone that is essential to achieve and maintain a healthy pregnancy. Progesterone prepares the lining of the uterus (endometrium) to allow the implantation of the early embryo and stimulates glands in the endometrium to secrete nutrients for the embryo. During the first 8 weeks of pregnancy, progesterone is produced by the corpus luteum; however, between 8 and 12 weeks, the placenta takes over the progesterone-producing role and maintains the pregnancy thereafter. The physiological importance of progesterone has prompted researchers, physicians and patients to consider progesterone supplementation during early pregnancy to prevent miscarriages. Progesterone supplementation in early pregnancy has been attempted in two contexts: the first is to prevent miscarriages in asymptomatic women with a past history of recurrent miscarriages and the second is to rescue a pregnancy in women who have started to bleed in early pregnancy. 1 Our Progesterone in Recurrent Miscarriage (PROMISE) study, published in the New England Journal of Medicine , addressed the first context. 2 In 2012, the National Institute for Health and Care Excellence (NICE) Clinical Guideline 154 3 called for a large randomised placebo-controlled clinical trial to test whether or not progesterone therapy in the first trimest

Duphaston among others, is a progestin medication which is used for a variety of indications, including threatened or recurrent miscarriage during pregnancy Dydrogesterone, sold under the brand name Duphaston among others, is a progestin medication which is used for a variety of indications, including threatened or recurrent miscarriage during pregnancy, dysfunctional bleeding, infertility due to luteal insufficiency, dysmenorrhea, endometriosis, secondary amenorrhea, irregular cycles, premenstrual syndrome, and as a component of menopausal hormone th Dydrogesterone, sold under the brand name Duphaston among others, is a progestin medication which is used for a variety of indications, including threatened or recurrent miscarriage during pregnancy, dysfunctional bleeding, infertility due to luteal insufficiency, dysmenorrhea, endometriosis, secondary amenorrhea, irregular cycles, premenstrual syndrome, and as a component of menopausal hormone therapy. It is taken by mouth. Side effects of dydrogesterone include menstrual irregularities, headache, nausea, breast tenderness, and others. Dydrogesterone is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. The medication is an atypical progestogen and does not inhibit ovulation. It has weak antimineralocorticoid activity and no other important hormonal activity. Dydrogesterone was developed in the 1950s and introduced for medical use in 1961. It is available widely throughout Europe, no longer available in the United Kingdom, since 2008 and is also marketed in Australia and elsewhere in the world. The medication was previously available in the United States, but it has been discontinued in that country.