Impact of dydrogesterone use in cycles with low progesterone levels on the day of frozen embryo transfer.

PURPOSE: This study aims to evaluate whether the clinical outcomes of cycles with frozen embryo transfer (FET) in hormonal replacement treatment supplemented with dydrogesterone (DYD) following detection of low circulating levels of progesterone (P4) were comparable to the results of cycles with otherwise normal serum P4 values. METHODS: Extended analyses of a retrospective cohort that included FET cycles performed between July 2019 and March 2022 after a cycle of artificial endometrial preparation using valerate-estradiol and micronized vaginal P4 (400 mg twice daily). Whenever the serum P4 value was considered low on the morning of the planned transfer, 10 mg of DYD three times a day was added as a supplement. Only single-embryo transfers of a blastocyst were considered. The primary endpoint was live birth rate. RESULTS: Five-hundred thirty-five FET cycles were analyzed, of which 136 (25.4%) underwent treatment with DYD. There were 337 pregnancies (63%), 207 live births (38.6%), and 130 miscarriages (38.5%). The P4 values could be modeled by a gamma distribution, with a mean of 14.5 ng/ml and a standard deviation of 1.95 ng/ml. The variables female age on the day of FET, ethnicity, and weight were associated with a variation in the serum P4 values. There were no differences in the results between cycles with or without the indication for DYD supplementation. CONCLUSIONS: Live birth rate did not vary significantly in females with low and normal serum P4 levels on the day of FET when DYD was used as rescue therapy.

Hospital-based interventional two-arm parallel comparative study on dydrogesterone vs combined oral contraceptive pills for functional ovarian cysts.

Background: Functional ovarian cysts are common among women of reproductive age, often necessitating medical intervention. This hospital-based interventional study compares the efficacy and safety of combined oral contraceptive pills (COC) and dydrogesterone in managing functional ovarian cysts. Methods: This randomized controlled trial will be conducted over two years at the Department of Obstetrics & Gynecology, AVBRH, Datta Meghe Institute of Medical Sciences. The study population consists of reproductive-age women seeking care at the outpatient unit of Obstetrics and Gynecology at AVBRH hospital. The sample size of 46 participants per group has been calculated based on a 95% confidence interval and the estimated prevalence of functional ovarian cysts. Group A will receive low-dose COC for three menstrual cycles. At the same time, Group B will be administered dydrogesterone (10 mg twice daily) for ten days during the luteal phase, repeated across three cycles. Expected outcomes: The primary outcomes include evaluating the recession of cysts within three months, monitoring alterations in menstrual patterns (frequency, regularity, duration, and volume), assessing the necessary treatment duration, and observing potential side effects (e.g., nausea, vomiting, weight gain, and acne) and complications (e.g., thromboembolism, delayed menstrual cycles post-treatment, and interactions with other drugs). Data analysis will encompass descriptive statistics, comparative tests, and regression models to assess the primary outcomes. The significance level for hypothesis testing will be 0.05 with a two-tailed approach. Registration: CTRI/2023/04/051811.

Research progress of dydrogesterone in the treatment of endometriosis.

Endometriosis is a common gynecological disease among women of reproductive age. It is a chronic estrogen and progestin related inflammatory disease. At present, the main treatments for endometriosis are drug therapy and surgery. In drug therapy, progesterone is listed as the first-line recommendation in multinational guidelines. Dydrogesterone, as an oral reversal progesterone, can slow down the metabolism of progesterone, inhibit angiogenesis and extracellular matrix degradation to inhibit the proliferation of the ectopic endometrium, induce the atrophy of the ectopic endometrium through the pro-apoptotic pathway, and treat endometriosis through multiple mechanisms of regulating inflammatory factors to reduce inflammation. Clinically, dydrogesterone treatment of endometriosis can relieve patients' symptoms, promote fertility, be used in combination, and is safe. This article will review the mechanism and clinical application of dydrogesterone in the treatment of endometriosis.

Oral dydrogesterone for prevention of miscarriage in threatened miscarriage: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine the effectiveness of oral dydrogesterone in preventing miscarriage in threatened miscarriage. METHODS: A randomized, controlled trial study was conducted among pregnant Thai women at the gestational age of six to less than 20 weeks who visited King Chulalongkorn Memorial Hospital, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand with threatened miscarriage from August 2021 to August 2022. These pregnant women were randomized to receive oral dydrogesterone 20 mg per day or placebo twice a day until one week after vaginal bleeding stopped or otherwise for a maximum of six weeks. RESULTS: A total of 100 pregnancies were recruited. Fifty of them were assigned to receive oral dydrogesterone and 50 were assigned to receive placebo. The rate of continuing pregnancy beyond 20 weeks of gestational age was 90.0% (45 out of 50 women) in the dydrogesterone group and 86.0% (43 out of 50 women) in the placebo group (p = 0.538). The incidence of adverse events did not differ significantly between the groups. CONCLUSION: Oral dydrogesterone 20 mg/day could not prevent miscarriages in women with threatened miscarriage.

Evaluating the cost utility of estradiol plus dydrogesterone for the treatment of menopausal women in China.

AIM: Evaluate the cost utility of menopausal hormone therapy for women in China. MATERIALS AND METHODS: A bespoke Markov cost utility model was developed to evaluate a cohort of symptomatic perimenopausal women (>45 years) with intact uterus in China in accordance with China's Pharmacoeconomic guideline. Short (5-year) and long (10-year) treatment durations were evaluated over a lifetime model time horizon with 12-month cycle duration. Societal and healthcare payer perspectives were evaluated in the context of a primary care provider/prescriber, outpatient setting with inpatient care for patients with chronic conditions. Disease risk and mortality parameters were derived from focused literature searches, and China Diagnosis-related Group cost data was included. Comprehensive scenario, univariate and probabilistic sensitivity analysis were undertaken along with independent validation. This is the first model to include MHT-related disease risks. RESULTS: According to base case results, the total cost for MHT was 22,516$ (150,106¥) and total quality adjusted life years 12.32 versus total cost of no MHT 30,824$ (205,495¥) and total quality adjusted life years 11.16 resulting in a dominant incremental cost effectiveness ratio of -7,184$ (-47,898¥) per QALY. Results hold true over a range of univariate deterministic sensitivity and scenario analyses. Probabilistic analysis showed a 91% probability of being cost effective at a willingness to pay threshold of three times Gross Domestic Product per capita in China. CONCLUSION: Contingent on the structure and assumptions of the model, combination of estradiol plus dydrogesterone MHT is potentially cost saving in symptomatic women over the age of 45 years in China.

Menopausal hormone therapy is publicly funded in many countries to alleviate symptoms of menopause; however, uptake has been comparatively slow in China. This has implications for the estimated 168 million menopausal-aged women. This analysis is the first to evaluate the cost effectiveness of menopausal hormone therapy in China using best practice principles and incorporating longer term disease risks. Menopausal hormone therapy is potentially cost saving in the context of China.

Real-world utilization pattern of dydrogesterone in 7287 Indian women with obstetric and gynecological conditions: data from multicentric, retrospective study.

Objective: Despite the literature on dydrogesterone, studies on dydrogesterone utilization patterns are largely lacking in Indian patients. Methods: This was a multi-center, retrospective, observational, cross-sectional, and descriptive study across 817 centers in India. Data of patients who received dydrogesterone in past and provided consent for future use of their medical record for research purpose was were retrieved and analyzed. Results: Data of 7287 subjects (aged 29.55±4.84 years) was analyzed. Threatened abortion was the most common indication for which the subjects received dydrogesterone (46.9%) followed by recurrent pregnancy loss. Polycystic ovary syndrome (PCOS), thyroid disorders and anemia were the most common comorbid conditions and prior pregnancy loss, advanced maternal age and obesity were the most common risk factors seen in subjects who received dydrogesterone. Total 27.5% of subjects received a loading dose of dydrogesterone, and majority (64%) received 40 mg as loading dose. 10 mg dose was used as maintenance or regular dose in 81.4% of the subjects. Twice daily (BID) was the most common dosing frequency (66.6%). The most common concomitant medications being taken by the subjects on dydrogesterone included folic acid (45.1%), iron supplements (30.3%) and calcium and vitamin D3 supplements (25.5%). Another progesterone preparation (oral, injection, vaginal, tubal) other than dydrogesterone was used concurrently in 7.8% of subjects. Conclusion: The study helped to identify the patient population that is benefitted by dydrogesterone and the preferred indications, risk factors, comorbid conditions and concomitant medication used in this patient population at real-life scenario.

The Addition of Dydrogesterone after Frozen Embryo Transfer in Hormonal Substituted Cycles with Low Progesterone Levels / Uso adicional de didrogesterona após transferência de blastocisto em ciclos substituídos com valores baixos de progesterona

Abstract Objective To determine whether a rescue strategy using dydrogesterone (DYD) could improve the outcomes of frozen embryo transfer cycles (FET) with low progesterone (P4) levels on the day of a blastocyst transfer. Methods Retrospective cohort study including FET cycles performed between July 2019 and October 2020 following an artificial endometrial preparation cycle using estradiol valerate and micronized vaginal P4 (400 mg twice daily). Whenever the serum P4 value was below 10 ng/mL on the morning of the planned transfer, DYD 10 mg three times a day was added as supplementation. The primary endpoint was ongoing pregnancy beyond 10 weeks. The sample was subdivided into two groups according to serum P4 on the day of FET: low (< 10 ng/mL, with DYD supplementation) or normal (above 10 ng/mL). We performed linear or logistic generalized estimating equations (GEE), as appropriate. Results We analyzed 304 FET cycles from 241 couples, 11.8% (n = 36) of which had serum P4 below 10 ng/mL on the FET day. Baseline clinical data of patients was comparable between the study groups. Overall, 191 cycles (62.8%) had a biochemical pregnancy, of which 131 (44,1%) were ongoing pregnancies, with a 29,8% miscarriage rate. We found no statistically significant differences in the hCG positive (63 vs 64%) or ongoing pregnancy rates (50 vs 43,3%) between those FETs with low or normal serum P4 values, even after multivariable logistic regression modelling. Conclusion Our results indicate that DYD 10 mg three times a day administered in women who perform FET with P4 serum levels < 10 ng/mL, allows this group to have pregnancy rates beyond 12 weeks at least as good as those with serum levels above 10 ng/mL.

Resumo Objetivo Determinar se uma estratégia de resgate usando didrogesterona (DYD) pode melhorar os resultados dos ciclos de transferência de embriões congelados (TEC) com baixos níveis de progesterona (P4) no dia de uma transferência de blastocisto. Métodos Estudo de coorte retrospectivo que incluiu ciclos TEC realizados entre julho de 2019 e outubro de 2020 após um ciclo de preparação endometrial artificial usando valerato de estradiol e P4 vaginal micronizado (400 mg duas vezes ao dia). Sempre que o valor de P4 sérico estava abaixo de 10 ng/mL na manhã da transferência planejada, adicionou-se 10 mg de DYD tri-diário como suplementação. O desfecho primário foi gravidez evolutiva após 10 semanas. A amostra foi subdividida em dois grupos de acordo com o P4 sérico no dia da TEC: baixo (< 10 ng/mL, com suplementação de DYD) ou normal (acima de 10 ng/mL). Realizamos equações de estimativa generalizada linear ou logística (GEE), conforme apropriado. Resultados Analisaram-se 304 ciclos de FET de 241 casais, dos quais 11,8% (n = 36) tinham valores de P4 sérico abaixo de 10 ng/mL no dia da TEC. Os dados clínicos e demográficos dos pacientes eram comparáveis entre os grupos. Globalmente, 191 ciclos (62,8%) tiveram uma gravidez bioquímica, dos quais 131 (44,1%) foram gestações em curso, com uma taxa de aborto espontâneo de 29,8%. Não encontramos diferenças estatisticamente significativas na taxa de gravidez bioquímica (63 vs. 64%) ou nas taxas de gravidez evolutiva (50 vs. 43,3%) entre TEC com valores séricos de P4 baixos ou normais, mesmo após modelação com regressão logística multivariável. Conclusão Nossos resultados indicam que a suplementação com DYD 10 mg três vezes ao dia em mulheres com níveis séricos de P4 abaixo de 10 ng/mL em ciclos de TEC substituídos parecem conseguir resultados pelo menos tão bons como nos ciclos com valores superiores para taxas de gravidez em curso além de 12 semanas.

Ameaça de aborto: conduta baseada em evidências / Threatened miscarriage: conduct based on evidences

A ameaça de aborto é definida como sangramento vaginal, geralmente indolor, que ocorre na primeira metade da gravidez com concepto vivo sem dilatação cervical. Muitas intervenções são utilizadas para a ameaça de aborto espontâneo. Quando uma causa específica é identificada, o tratamento direcionado pode reduzir taxas de abortamento. No entanto, na maioria dos casos, a fisiopatologia permanece desconhecida. Intervenções inespecíficas como repouso no leito e ausência de relações sexuais, apesar de comumente aconselhadas pelos médicos, não têm comprovação de benefício. A didrogesterona, um derivado progestínico, parece reduzir o risco de abortamento. Esta revisão mostra a qualidade das evidências científicas e o grau de recomendação das várias condutas para o tratamento da ameaça de aborto, concluindo que ainda é necessário realizar outros ensaios clínicos maiores, placebo-controlados e randomizados sobre o tratamento da ameaça de aborto para definir a eficácia da maioria das intervenções

Threatened miscarriage is defined as a vaginal bleeding, usually painless, which occurs in the first half of viable pregnancy without cervical dilatation. Many interventions are used for threatened and recurrent miscarriage. When a specific cause is identified, directed treatment may reduce miscarriage rates. However, in the majority of cases, the pathophysiology remains unknown. Unspecific interventions, as bed rest and avoidance of sexual intercourse, though commonly advised, are of no proven benefit. Dydrogesterone, a progesterone derivative, may further reduce miscarriage rates. This review shows the scientific evidence and classification quality of several interventions for the treatment of threatened miscarriage. Larger, randomized and controlled trials on the treatment of threatened miscarriage are needed to support the majority of the interventions