A Comparison of Prevention and Treatment of Recurrent Pregnancy Loss with Vaginal Progesterone or Oral Dydrogesterone (original) (raw)
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Oral versus Vaginal Micronized Progesterone for the treatment of threatened miscarriage
Pakistan Journal of Medical Sciences, 2021
Objectives: This study was planned with an aim to find out the effectiveness of oral versus vaginal micronized progesterone for the treatment of threatened miscarriage. Methods: This randomized controlled trial was conducted at The Department of Obstetrics and Gynaecology, Nishtar Hospital Multan, from August 2019 to January 2020. A total of 136 pregnant women, aged 18 to 45 years having vaginal bleeding were included and divided into two groups (68 women in each group). Participants in the Group-A were given oral micronized progesterone as 200mg twice a day while Group-B participants were given vaginal progesterone suppository 400mg once a day. All women were followed up until 20th week of their pregnancy. Outcome was labeled as prevention of miscarriage if woman had no bleeding per vagina and pregnancy went beyond 20th weeks of gestation. Results: In a total of 136 women enrolled, mean age was noted to be 30.85+3.34 years. Overall, mean gestational age was noted to be 9.3+2.7 week...
Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence
American Journal of Obstetrics and Gynecology
Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone supplementation may reduce the risk of miscarriage in women with recurrent or threatened miscarriage. Cochrane Reviews summarized the evidence and found that the trials were small with substantial methodologic weaknesses. Since then, the effects of first-trimester use of vaginal micronized progesterone have been evaluated in 2 large, high-quality, multicenter placebo-controlled trials, one targeting women with unexplained recurrent miscarriages (the PROMISE [PROgesterone in recurrent MIScarriagE] trial) and the other targeting women with early pregnancy bleeding (the PRISM [PRogesterone In Spontaneous Miscarriage] trial). The PROMISE trial studied 836 women from 45 hospitals in the United Kingdom and the Netherlands and found a 3% greater live birth rate with progesterone but with substantial statistical uncertainty. The PRISM trial studied 4153 women from 48 hospitals in the United Kingdom and found a 3% greater live birth rate with progesterone, but with a P value of .08. A key finding, first observed in the PROMISE trial, and then replicated in the PRISM trial, was that treatment with vaginal micronized progesterone 400 mg twice daily was associated with increasing live birth rates according to the number of previous miscarriages. Prespecified PRISM trial subgroup analysis in women with the dual risk factors of previous miscarriage(s) and current pregnancy bleeding fulfilled all 11 conditions for credible subgroup analysis. For the subgroup of women with a history of 1 or more miscarriage(s) and current pregnancy bleeding, the live birth rate was 75% (689/914) with progesterone vs 70% (619/886) with placebo (rate difference 5%; risk ratio, 1.09, 95% confidence interval, 1.03e1.15; P¼.003). The benefit was greater for the subgroup of women with 3 or more previous miscarriages and current pregnancy bleeding; live birth rate was 72% (98/137) with progesterone vs 57% (85/148) with placebo (rate difference 15%; risk ratio, 1.28, 95% confidence interval, 1.08e1.51; P¼.004). No short-term safety concerns were identified from the PROMISE and PRISM trials. Therefore, women with a history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone 400 mg twice daily. Women and their care providers should use the findings for shared decision-making.
Journal of Clinical Medicine
Background: Recurrent pregnancy loss (RPL) is defined as the loss of two or more pregnancies. Several treatment options are available, including progesterone, which is one of the few treatments that improve live birth rates in RPL patients. Objective: To compare the live birth rates, medical and obstetric characteristics, and RPL evaluation results of women with and without progesterone treatment. These women attended the RPL clinic at Soroka University Medical Center. Methods: A retrospective cohort study based on 866 patients was conducted. The patients were divided into two groups and examined: the dydrogesterone treatment group consisting of 509 women and a group of 357 patients who did not receive the treatment. All the patients had a subsequent (index) pregnancy. Results: The two groups were not statistically different in terms of their demographic and clinical characteristics or evaluation results. In a univariate analysis, no statistically significant differences were found ...
A Randomized Trial of Progesterone in Women with Recurrent Miscarriages
The New England journal of medicine, 2015
Background Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain. Methods We conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice-daily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation. Results A total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally wit...
Innovative publication, 2016
Background Progestogens have been considered as a viable therapeutic option for the treatment of miscarriage for more than half a century. Aim: The aim of the present review is to provide a comprehensive view of the literature regarding the clinical efficacy and safety effects of progestogens for preventing recurrent miscarriages and managing threatened miscarriage during early pregnancy. Methods: A literature search was performed using electronic databases like Pubmed/ Medline to identify from 1953 to 2015. The search yielded around 27 original studies and review articles. Results: Dydrogesterone (oral) and various micronized progesterone (MCP) given orally, vaginally and intramuscularly are the most commonly used progestogens for the treatment of recurrent and threatened miscarriages. Pharmacokinetic profile of dydrogesterone exhibits better bioavailability, receptor affinity, quick onset of action and a better half-life imparting long and stable effect. Dydrogesterone exhibits 47% and 29% statistically significant reduction in odds ratio of threatened and recurrent miscarriage when compared to standard of care. While, literature supports use of MCP (vaginal), recent findings suggest no statistically significant difference in live birth rate when compared to placebo (65.8% vs. 63.3%). MCP (vaginal) is associated with vaginal discharge and irritation whereas dydrogesterone (oral) avoids vaginal discharge and no birth defects have been associated with its use. Conclusion: Treatment with dydrogesterone and other progestogens in general suggest dydrogesterone has number of advantages over other progestogens in terms of pharmacokinetic parameter clinical efficacy and safety profile. However, further studies are warranted to establish and promote the role of these progestogens in management of threatened and recurrent miscarriage. Key Messages: Bioavailability Oral bioavailability of dydrogesterone is approximately 5.6 times better than oral MCP. 32,37,82 Dydrogesterone is selective for progesterone receptor with 1.5 times better affinity than oral MCP. 32 Dydrogesterone exhibits quick onset of action reaching peak absorption levels within 30 minutes with a half-life of 5-7 hours imparting long and stable effect. 37 Efficacy and safety Based on PROMISE study data vaginal MCP therapy did not significantly improve live birth rate in women with unexplained recurrent miscarriage compared to placebo. 57 Dydrogesterone leads to a 47% statistically significant reduction in the odds of a threatened miscarriage. 38 Dydrogesterone leads to 29% statistically significant reduction in the odds of a recurrent miscarriage. 39 Clinical experience with dydrogesterone does not provide evidence of a causal link between maternal dydrogesterone use during pregnancy and birth defects. 41 Use of medroxyprogesterone and hydroxyprogesterone in the management of miscarriages has not been supported in literature. They are indicated as contraceptive and for preventing preterm labor; respectively. 61,62,73 Recommendations Dydrogesterone has been approved for pregnancy indication including threatened miscarriage, habitual miscarriage, and infertility. 81 Dydrogesterone has been recommended for the treatment of threatened and recurrent miscarriage by FOGSI and EPC guideline. 79,80 Oral MCP is not indicated for threatened and/or recurrent miscarriages. 81
Fertility and sterility, 2014
To study the impact of administration of dydrogesterone in early pregnancy on pregnancy outcome and its correlation with Th1 and Th2 cytokine levels. Double-blind, randomized, placebo-controlled study. A medical college and its associated hospital. Women with either: [1] a history of idiopathic recurrent pregnancy loss (RPL), in either a dydrogesterone group or a placebo group, or [2] no history of miscarriage. Dydrogesterone 20 mg/day from confirmation of pregnancy to 20 weeks of gestation. Occurrence of another pregnancy loss and concentrations of T-helper (Th)1 (interferon-γ and tumor necrosis factor-α) and Th2 (interleukin (IL)-4 and IL-10) cytokines in serum at recruitment (4-8 weeks of gestation) and at abortion or 20 weeks of gestation, using commercially available ELISA kits. Occurrence of another abortion after 3 consecutive abortions was significantly higher (29 of 173; 16.76%) in women with RPL compared with healthy pregnant controls (6 of 174; 3.45%). Risk of occurrence ...
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 2017
The current study aims to evaluate the effect of peri-conceptional progesterone started early in the luteal phase before confirmation of pregnancy in preventing miscarriage in women with history of unexplained recurrent miscarriage (RM). The current study was a randomized double blind controlled trial (NCT01608347) conducted at Assiut Women's Health Hospital from 2012 through 2015 included patients of unexplained RM. Participants were randomly assigned to receive either 400 mg progesterone pessaries or placebo twice daily, started in the luteal phase and continued after a positive pregnancy test till 28 weeks of gestation. The main study outcome was the miscarriage rate. Seven hundred women were enrolled (n = 350 in each group). The miscarriage rate was significantly lower in progesterone group (12.4% vs. 23.3% in the placebo group, P = 0.001). There was significant improvement in rate of pregnancy continuation beyond 20 weeks as well as the live birth rate in the progesterone g...
Efficacy of Progesterone in the Management of Threatened Miscarriage
Journal of Evidence Based Medicine and Healthcare, 2020
BACKGROUND There is a great probability of foetal demise and abnormal outcomes in the first trimester of a recognized pregnancy. 20% pregnancies have first trimester complications out of which the most common is miscarriage. Threatened miscarriage is a risk factor occurring in about 20-25% of confirmed pregnancies which may progress or resolve. Inadequate progesterone secretion has been implicated in the aetiology of miscarriage. The current study was undertaken to study the efficacy of progesterone in the management of first trimester threatened miscarriage. METHODS A prospective randomized clinical trial was conducted in a rural tertiary health care center from Jan 2018 to March 2019. A total of 100 pregnant women who had a viable pregnancy who were admitted for threatened abortion in the first trimester, fulfilling the inclusion and exclusion criteria, were selected after taking an informed consent. Patients were further divided into 2 groups of 50 patients each. Group A was treated with progesterone and Group B was given supportive treatment without progesterone. They were observed for relief of symptoms, and progression to second trimester or spontaneous miscarriage. RESULTS Parameters like age, gravidity, period of gestation and body mass index at the time of admission did not have a significant difference between the two groups. Symptoms like vaginal bleed and abdominal pain reduced in 54% and 52% of patients who received progesterone respectively; while, vaginal bleed and abdominal pain reduced only in 40% and 38% of patients who received only symptomatic treatment respectively. 54% of patients who received progesterone and 38% of patients who received only symptomatic treatment could continue the pregnancy further. CONCLUSIONS Pregnant women with first trimester threatened miscarriage have a great risk for spontaneous loss of pregnancy. Progesterone may help clinically, but has no statistically significant improvement in the outcome of pregnancy. Further trials are required utilizing other forms and dosages of progesterone and other routes of administration.
The role of dydrogesterone in recurrent (habitual) abortion
The Journal of Steroid Biochemistry and Molecular Biology, 2005
The published evidence regarding the administration of dydrogesterone in the treatment of habitual abortion is summarised in this review. Habitual abortion is defined as the loss of three or more consecutive pregnancies without known maternal or foetal pathology. The immunology of early pregnancy seems to determine the rejection or non-rejection of the allogenic embryo. When peripheral mononuclear cells from recurrent aborters are incubated with progesterone or dydrogesterone in vitro, T-helper (Th)2 cytokines such as interleukin (IL)-4 and IL-6 markedly increase whereas the Th1 cytokine interferon-␥ decreases. Additionally, both progesterone and dydrogesterone are thought to inhibit the activity of natural killer cells at the foeto-maternal interface in humans. Progesterone-induced blocking factor (PIBF) mediates the immunological effects of progesterone and dydrogesterone in pregnancy. It affects various phases of the maternal immune response involving both the cellular and humoral immune system, exerts anti-abortive effects and inhibits the release of arachidonic acid. It also favours the production of socalled asymmetric, pregnancy-protecting antibodies. In rodents, blockade of this factor results in the termination of pregnancy and in women considerably lower levels are found in those with threatened abortion or pre-term labour. In order to draw final conclusions as to the usefulness of dydrogesterone in women with a history of recurrent miscarriage, further controlled, blinded, randomised clinical trials are needed.