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.

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.

Role of Dydrogesterone for Luteal Phase Support in Assisted Reproduction.

Clinical outcomes of in vitro fertilization (IVF) have significantly improved over the years with the advent of the frozen-thawed embryo transfer (FET) technique. Ovarian hyperstimulation during IVF cycles causes luteal phase deficiency, a condition of insufficient progesterone. Intramuscular or vaginal progesterone and dydrogesterone are commonly used for luteal phase support in FET. Oral dydrogesterone has a higher bioavailability than progesterone and has high specificity for progesterone receptors. Though micronized vaginal progesterone has been the preferred option, recent data suggest that oral dydrogesterone might be an alternative therapeutic option for luteal phase support to improve clinical outcomes of IVF cycles. Dydrogesterone has a good safety profile and is well tolerated. Its efficacy has been evaluated in several clinical studies and demonstrated to be non-inferior to micronized vaginal progesterone in large-scale clinical trials. Oral dydrogesterone may potentially become a preferred drug for luteal phase support in millions of women undergoing IVF.

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.

Sanji Peiyuan decoction combined with dydrogesterone in the treatment of massive subchorionic hematoma: A case report.

RATIONALE: Subchorionic Hematoma, often referred to as Bruce hematoma, can lead to serious obstetric complications such as intrauterine growth restriction and fetal death, as well as early and late pregnancy miscarriage, placental abruption, and premature rupture of membranes, posing great harm to both mother and fetus. PATIENT CONCERNS: At present, Western medical treatments have not shown satisfactory results, necessitating the discovery of more effective clinical treatment methods. DIAGNOSES: Threatened miscarriage, Subchorionic hematoma, Iron deficiency anemia (mild). INTERVENTIONS: Sanji Peiyuan decoction combined with dydrogesterone. OUTCOMES: Following 17 days of treatment with Sanji Peiyuan decoction and oral dydrogesterone tablets, the hematoma was no longer detectable by ultrasound. The patient experienced no symptoms such as abdominal pain, bloating, or vaginal bleeding. She successfully gave birth around her due date, with both the mother and child in good health. LESSONS: The combination of Sanji Peiyuan decoction and oral dydrogesterone tablets shows promising clinical efficacy in treating Massive Subchorionic Hematomas. This method merits further clinical research.

Evaluation of allylestrenol for clinical pregnancies in patients treated with assisted reproductive techniques: a retrospective, propensity score matched, observational study.

BACKGROUND: Allylestrenol is an oral progestogen being increasingly used for luteal phase support in assisted reproductive techniques. However, evidence of the clinical efficacy of allylestrenol in luteal phase support is lacking. Dydrogesterone is a representative drug used for luteal phase support, the efficacy of which has been clinically confirmed. As such, we aimed to compare the effects of allylestrenol with the standard dydrogesterone on clinical pregnancy rates and pregnancy outcomes. METHODS: This retrospective study included 3375 assisted reproductive technique cycles using either allylestrenol or dydrogesterone between January 2015 and March 2020. Patients using either allylestrenol or dydrogesterone were matched in a 1:1 ratio using propensity scores. The primary outcomes were clinical pregnancy rate and pregnancy outcomes. RESULTS: No significant difference was found in the clinical pregnancy rate (53.5% vs. 53.2%, P = 0.928) and pregnancy outcomes (all P > 0.05) between allylestrenol and dydrogesterone. Compared with dydrogesterone, the use of allylestrenol significantly reduced the rate of biochemical pregnancies (6.4% vs. 11.8%, P < 0.001) and multiple gestation rate (16.8% vs. 26.3%, P = 0.001). Moreover, endometrial thickness, morphology, and blood flow were significantly improved by allylestrenol treatment (all P < 0.05). CONCLUSIONS: Allylestrenol exhibited similar effects on clinical pregnancy rates and pregnancy outcomes as dydrogesterone. Moreover, allylestrenol can significantly reduce the biochemical pregnancy rate and improve the endometrial receptivity.

Cervical and Vaginal Microbiomes in Early Miscarriages and Ongoing Pregnancy with and without Dydrogesterone Usage.

Emerging evidence suggests that the reproductive tract microbiota is a key modulator of local inflammatory and immune pathways throughout pregnancy and may subsequently impact pregnancy outcomes. In this study, our objective was to analyze the cervical and vaginal microbiomes during early pregnancy among three groups: women with healthy ongoing pregnancies, women undergoing dydrogesterone treatment, and those who experienced miscarriages. The experiment involved 51 women at 8-11 weeks of gestation. The microbiome was examined using 16S rRNA sequencing on the Ion Torrent PGM platform. Across all groups, Lactobacillus iners was predominant, suggesting that the vaginal community type CST III is common among the majority of participants. Notably, our data highlighted the significant roles of Gardnerella vaginalis and Mycoplasma girerdii in the pathogenesis of early miscarriage. Conversely, L. iners and Bifidobacterium longum have a protective effect in early pregnancy. Moreover, dydrogesterone intake appeared to influence notable differences between the cervical and vaginal microbiomes. Overall, our study enhanced our understanding of the cervical and vaginal microbiome composition in the eastern European population during early pregnancy.

Effects of two different types of luteal support on pregnancy outcomes following antagonist fresh embryo transfer: a retrospective study.

BACKGROUND: Only a small number of studies have reported the use of progesterone vaginal gel in combination with dydrogesterone as part of the antagonist protocol for fresh embryo transfer. Therefore, this study aimed to compare the effects of two types of luteal support on pregnancy outcomes following the antagonist protocol for fresh embryo transfer. METHODS: We performed a retrospective analysis of clinical data from infertile patients who underwent fresh embryo transfer via the antagonist protocol (2785 cycles) between February and July 2019 and between February and July 2021 at the Peking University Third Hospital Reproductive Medicine Centre. According to the luteal support received, the cycle groups were divided into the progesterone vaginal gel group (single medication or VP group; 1170 cycles) and the progesterone vaginal gel plus dydrogesterone group (combination medication or DYD + VP group; 1615 cycles). After propensity score matching, the clinical pregnancy, ongoing pregnancy, early miscarriage, and ectopic pregnancy rates were compared between the two groups. RESULTS: In total, 1057 pairs of cycles were successfully matched via propensity scores. The clinical and ongoing pregnancy rates in the combination medication group were significantly higher than those in the single medication group (P < 0.05), whereas no significant differences were noted in the early miscarriage and ectopic pregnancy rates between the two groups (both P > 0.05). CONCLUSIONS: Combined luteal support after the antagonist protocol is preferred for patients undergoing fresh cycle embryo transfer.

Adjuvant Treatment with Oral Dydrogesterone in the Prevention of Preterm Labor: A Randomized, Double-Blinded, Placebo-Controlled Trial.

We conducted a double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy of oral dydrogesterone (DG) on maternal and neonatal consequences in the treatment of preterm labor. We included 100 nulliparous mothers (24-34 weeks) with normal pregnancy who had preterm labor pain. Participants who received magnesium sulfate were randomly assigned to the investigation group (DG 30 mg/day) or placebo group. Maternal and neonatal outcomes were compared between the two groups. Recurrent uterine contraction (UC) rates (92% vs. 88%, P = 0.862) and the incidence of preterm delivery (66% vs. 58%, P = 0.834) were not different in the DG and placebo groups. No significant differences were observed in terms of gestational age at delivery (33.5 ± 3.5 vs. 34.2 ± 3.2, P = 0.281), latency period (5.53 ± 2.29 days vs. 5.59 ± 2.57 days, P = 0.622), cervical dilation (1.82 ± 0.26 cm vs. 1.84 ± 0.29 cm, P = 0.281), and effacement (53 ± 4.47% vs. 57.21 ± 6.27%, P = 0.622) between the placebo and DG groups. The percentage of neonates with a 1-min Apgar score < 7 was higher in the placebo group compared with that of the DG group (12% vs. 0%, P = 0.0001). However, both groups were similar in the frequency of a 5-min Apgar score < 7. No differences in the term of adverse effects of medications were recorded. Our results showed that DG adjuvant to magnesium sulfate could not be effective in improving the incidence of preterm labor, rate of recurrent UC, latency period, pregnancy outcomes, and maternal and neonatal outcomes when compared with the placebo group.

Dydrogesterone supplementation in addition to routine micronized progesterone administration for luteal support in cycles triggered with lone GnRH agonist results in an acceptable pregnancy rate and avoids the need to freeze embryos.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is reduced when using antagonist cycle with gonadotrophin releasing hormone (GnRH) agonist trigger before ovum pick up. This trigger induces short luteinizing hormone (LH) and follicle stimulating hormone (FSH) peaks, resulting in an inadequate luteal phase and a reduced implantation rate. We assessed whether the luteal phase can be rescued by supplementing with oral dydrogesterone (duphaston) in antagonist cycles after a lone GnRH agonist trigger. METHODS: A retrospective cohort study. The study group (N.=123) included women who underwent IVF. Patients received a GnRH-antagonist with a lone GnRH-agonist trigger due to imminent OHSS. The control group (N.=374) included patients who underwent a standard antagonist protocol with a dual trigger of a GnRH-agonist and human chorionic gonadotrophin (hCG). All the patients were treated with micronized progesterone (utrogestan) for luteal phase support. Study patients were given duphaston in addition. RESULTS: The fertilization rate was comparable between the two groups. The mean number of embryos transferred, the clinical pregnancy rate and the take-home baby rate were comparable between groups (1.5±0.6 vs. 1.5±0.5 and 46.3% vs. 41.2%, and 66.7% vs. 87.7%, respectively). No OHSS event was reported in either group. CONCLUSIONS: This study was the first to evaluate outcomes of duphaston supplementation for luteal support in an antagonist cycle with lone GnRH agonist trigger. The functionality of the luteal phase of those cycles could be restored by adding duphaston. This approach was found to be safe and prevented the need to postpone embryo transfer in case of pending OHSS.

Additional dydrogesterone for the treatment of chronic endometritis treated with antibiotic in premenopausal women with endometrial polyps: a retrospective cohort study.

BACKGROUND: To assess the efficacy of dysdrogesterone in the treatment of chronic endometritis (CE) treated with antibiotic in premenopausal women with endometrial polyps (EPs). METHODS: Routine detection of endometrium was simultaneously conducted to determine whether there was CE by syndecan-1 (CD138), while women underwent hysteroscopic polypectomy in our hospital. Antibiotic was given for the treatment of CE. A total of 235 premenopausal women with CE who underwent hysteroscopic polypectomy were enrolled in the retrospective observational study. In the control group, single antibiotic was given for the treatment of CE form January 2016 to December 2018, and in the treatment group additional dydrogesterone was used from January 2019 to November 2020. Comparison of cure rates of CE with different treatment regimens was performed. RESULTS: The cure rates of CE in dydrogesterone and antibiotic combination group and the single antibiotic group were 85.2% and 74.3%, respectively, with overall cure rate of 80.0% (188/235). The combination group showed better effects regarding the cure rate of CE (P < .05). Multivariate analysis confirmed that the cure rate of CE was not affected by age, body mass index, number of EPs, the status of estrogen receptor and the status of progesterone receptor. Conversely, dydrogesterone and endometrial scratching were beneficial factors for cure rate increase with antibiotic treatment. CONCLUSION: Combination of dydrogesterone and antibiotic was more effective for cure rate of CE than antibiotic alone in premenopausal women after hysteroscopic polypectomy. Endometrial scratching also contributed to the cure rate increase with antibiotic treatment.

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.

Effects of Dydrogesterone Tablets Combined with Zishen Yutai Pills on Threatened Abortion in Early Pregnancy and Pregnancy Outcomes.

Objective: To explore the effect of dydrogesterone tablets combined with Zishen Yutai pills on threatened abortion in early pregnancy and pregnancy outcomes. Methods: This study retrospectively analyzed the clinical data of 100 patients with threatened abortion in early pregnancy who came to the Linhai Second People's Hospital/Taizhou Municipal Hospital from January 13, 2021, to January 13, 2022. According to different treatment methods, 48 patients treated with progesterone injection were assigned to the control group (CG), while 52 cases with the combined therapy of dydrogesterone tablets and Zishen Yutai pills were assigned to the observation group (OG). The two groups were compared in terms of the following parameters: treatment efficacy, whole blood high shear viscosity, hematocrit (HCT), plasma fibrinogen (FIB) level, spiral artery pulsatility index (PI), uterine spiral artery blood flow resistance index (RI), lumbar and abdominal pain relief time, hemostasis time, estrogen levels, pregnancy outcomes, neonatal adverse outcomes, and incidence of adverse reactions. Results: Compared with CG, the therapeutic effect in OG was observed to be evidently better, and its pain relief time and hemostasis time in the waist and abdomen were markedly shorter. After treatment, the whole blood high shear viscosity, FIB, RI, PI, and estrogen levels of both groups improved statistically compared with those before treatment, with more significant improvements in OG compared with CG. OG was also superior to CG with markedly lower incidence of preterm birth, miscarriage, neonatal adverse outcomes, and adverse reactions and a drastically higher full-term pregnancy rate. Conclusion: Zishen Yutai pill combined with dydrogesterone tablets is of remarkable therapeutic effect in treatment of early threatened abortion, which can significantly improve clinical symptoms and pregnancy outcomes of patients, with a high safety profile, which is worthy of clinical application.

Dydrogesterone and 20α-dihydrodydrogesterone plasma levels on day of embryo transfer and clinical outcome in an anovulatory programmed frozen-thawed embryo transfer cycle: a prospective cohort study.

STUDY QUESTION: What are the plasma concentrations of dydrogesterone (DYD) and its metabolite, 20α-dihydrodydrogesterone (DHD), measured on day of embryo transfer (ET) in programmed anovulatory frozen embryo transfer (FET) cycles using 10 mg per os ter-in-die (tid) oral DYD, and what is the association of DYD and DHD levels with ongoing pregnancy rate? SUMMARY ANSWER: DYD and DHD plasma levels reach steady state by Day 3 of intake, are strongly correlated and vary considerably between and within individual subjects, women in the lowest quarter of DYD or DHD levels on day of FET have a reduced chance of an ongoing pregnancy. WHAT IS KNOWN ALREADY: DYD is an oral, systemic alternative to vaginal progesterone for luteal phase support. The DYD and DHD level necessary to sustain implantation, when no endogenous progesterone is present, remains unknown. While DYD is widely used in fresh IVF cycles, circulating concentrations of DYD and DHD and inter- and intraindividual variation of plasma levels versus successful treatment have never been explored as measurement of DYD and DHD is currently only feasible by high-sensitivity chromatographic techniques such as liquid chromatography/tandem mass spectroscopy (LC-MS/MS). STUDY DESIGN, SIZE, DURATION: Prospective, clinical cohort study (May 2018-November 2020) (NCT03507673); university IVF-center; women (n = 217) undergoing a programmed FET cycle with 2 mg oral estradiol (tid) and, for luteal support, 10 mg oral DYD (tid); main inclusion criteria: absence of ovulatory follicle and low serum progesterone on Days 12-15 of estradiol intake; serum and plasma samples were taken on day of FET and stored at -80°C for later analysis by LC-MS/MS; in 56 patients, two or more FET cycles in the same protocol were performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women undergoing FET on Day 2 or Day 3 (D2, D3, cleavage) or Day 5 (D5, blastocyst) of embryonic development had blood sampling on the 3rd, 4th or 6th day of 10 mg (tid) DYD oral intake, respectively. The patient population was stratified by DYD and DHD plasma levels by percentiles (≤25th versus >25th) separately by day of ET. Ongoing pregnancy rates (a viable pregnancy at >10th gestational week) were compared between ≤25th percentile versus >25th percentile for DYD and DHD levels (adjusted for day of ET). Known predictors of outcome were screened for their effects in addition to DYD, while DYD was considered as log-concentration or dichotomized at the lower quartile. Repeated cycles were analyzed assuming some correlation between them for a given individual, namely by generalized estimating equations for prediction and generalized mixed models for an estimate of the variance component. MAIN RESULTS AND THE ROLE OF CHANCE: After exclusion of patients with 'escape ovulation' (n = 14, 6%), detected by the presence of progesterone in serum on day of ET, and patients with no results from LC-MS/MS analysis (n = 5), n = 41 observations for cleavage stage ETs and n = 157 for blastocyst transfers were analyzed. Median (quartiles) of plasma levels of DYD and DHD were 1.36 ng/ml (0.738 to 2.17 ng/ml) and 34.0 ng/ml (19.85 to 51.65 ng/ml) on Day 2 or 3 and 1.04 ng/ml (0.707 to 1.62 ng/ml) and 30.0 ng/ml (20.8 to 43.3 ng/ml) on Day 5, respectively, suggesting that steady-state is reached already on Day 3 of intake. DHD plasma levels very weakly associated with body weight and BMI (R2 < 0.05), DYD levels with body weight, but not BMI. Levels of DYD and DHD were strongly correlated (correlation coefficients 0.936 for D2/3 and 0.892 for D5, respectively). The 25th percentile of DYD and DHD levels were 0.71 ng/ml and 20.675 ng/ml on day of ET. The ongoing pregnancy rate was significantly reduced in patients in the lower quarter of DYD or DHD levels: ≤25th percentile DYD or DHD 3/49 (6%) and 4/49 (8%) versus >25th percentile DYD or DHD 42/149 (28%) and 41/149 (27%) (unadjusted difference -22% (CI: -31% to -10%) and -19% (CI: -29% to -7%), adjusted difference -22%, 95% CI: -32 to -12, P < 0.0001). LIMITATIONS, REASONS FOR CAUTION: Some inter- and intraindividual variations in DYD levels could be attributed to differences in time between last 10 mg DYD intake and blood sampling, as well as concomitant food intake, neither of which were registered in this study. Ninety percent of subjects were European-Caucasian and DYD/DHD blood concentrations should be replicated in other and larger populations. WIDER IMPLICATIONS OF THE FINDINGS: Daily 10 mg DYD (tid) in an artificial FET cycle is potentially a suboptimal dose for a proportion of the population. Measurement of DYD or DHD levels could be used interchangeably for future studies. The pharmacokinetics of oral DYD and associated reproductive pharmacodynamics need further study. STUDY FUNDING/COMPETING INTEREST(S): The trial was financed by university funds, except for the cost for plasma and serum sample handling, storage and shipment, as well as the liquid chromatography-mass spectrometry (LC-MS/MS) analysis of DYD, DHD and progesterone, which was financially supported by Abbott Products Operations AG (Allschwil, Switzerland). Abbott Products Operations AG had no influence on the study protocol, study conduct, data analysis or data interpretation. K.N. has received honoraria and/or non-financial support (e.g. travel cost compensation) from Ferring, Gedeon-Richter, Merck and MSD. A.M. has no competing interests. R.V. has no competing interests. M.D. has received honoraria and/or non-financial support from Ferring and Merck. A.S.-M. has no competing interests. T.K.E. has received honoraria and/or non-financial support from Roche, Novartis, Pfizer, Aristo Pharma, Merck. G.G. has received honoraria and/or non-financial support (e.g. travel cost compensation) from Abbott, Ferring, Gedeon Richter, Guerbet, Merck, Organon, MSD, ObsEva, PregLem, ReprodWissen GmbH, Vifor and Cooper. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03507673.

[Comparison of oral dydrogesterone with micronized vaginal progesterone in fresh embryo transfert in IVF/ICSI]. / Comparaison de la dydrogestérone avec une progestérone micronisée vaginale dans le transfert d'embryon frais en FIV/ICSI.

INTRODUCTION: Luteal insufficiency corresponds to a progesterone deficiency affecting women who receive treatment for in vitro fertilization (IVF). Different routes of progesterone administration exist and have varying degrees of acceptability to patients. The aim of this study was to compare two luteal phase support (LPS) treatments: oral dydrogesterone versus micronized vaginal progesterone on the clinical pregnancy occurrence after fresh embryo transfer. MATERIAL AND METHODS: This study was a monocentric historical and observational cohort study carried out in the reproductive medicine department at the University Hospital, Femme Mère Enfant in Lyon. All the data were collected retrospectively. Women between 18 and 43 years old, who completed an IVF cycle with or without ICSI, followed by fresh embryo transfer on the second or third day after oocyte retrieval (D2 or D3) or at the blastocyst stage (D5 or D6) between July 2019 and July 2020 were included. The 290 patients included between July 2019 and January 2020 received 600mg per day of PMV. The 290 patients in the OD group included between January and July 2020 received 30mg OD per day. RESULTS: In the univariate analysis, the clinical pregnancy occurrence per transfer was comparable between the MVP and OD groups (P>0.05) (OR [95% CI]): 0.904 [0.630 ; 1.296]. In the multivariate analysis, OD also appeared to be associated with a similar pregnancy occurrence compared to MVP, with a non-significant difference (OR [95% CI]): 0.940 [0.640; 1.380]. The use of OD compared to MVP did not significantly influence the clinical pregnancy occurrence in any age group. There was no significant difference between the two groups in the clinical pregnancy occurrence, whether the patients belonged to the reference population of the center or not (P>0.05) (OR [95% CI]): 2.367 [0.568; 3.568]. CONCLUSION: This important French retrospective study confirms the safety and efficacy of OD.

Gongning granules plus low dose hormone in pubertal functional uterine hemorrhage: Analysis of hemodynamics and clinical efficacy.

To evaluate the clinical effect of Gongning granules combined with low-dose hormone therapy in pubertal dysfunctional uterine bleeding (PDUB) and its effect on uterine hemodynamics. A total of 164 PDUB patients who were treated in the gynecological outpatient department of our hospital from December 2018 to June 2020 were randomized into study group and control group, with 82 cases each. The control group received estrogen progesterone, and the study group received Gongning granules plus. The clinical efficacy and uterine arterial hemodynamics were compared. The clinical efficacy of the study group was superior to the control group (91.46% vs. 76.83%, P<0.05). The study group yielded shorter bleeding control time and complete hemostasis time than the control group (P<0.05). The amount of menstrual bleeding and duration of menstruation in both groups decreased significantly with time and the study group was significantly lower than the control group (all P<0.05). The endometrial thickness in the study group was significantly thinner than the control group, and the maximum follicle diameter was significantly longer than that in the control group (all P<0.05). After treatment, the platelet count, hemoglobin level of peripheral blood, uterine arterial blood flow and mean flow velocity in the study group were significantly higher than those in the control group (all P<0.05). In addition, there was no significant difference in adverse drug reaction (ADR) between the two groups (P>0.05). In PDUB patients, Gongning granules plus low-dose hormone can significantly relieve bleeding symptoms, improve hemodynamic status and has good safety.

Comparison of oral Dydrogesterone and 17-α hydroxyprogesterone caprate in the prevention of preterm birth.

BACKGROUND: Preterm birth (PTB) remains a significant problem in obstetric care. Progesterone supplements are believed to reduce the rate of preterm labor, but formulation, type of administration, and dosage varies in different studies. This study was performed to compare oral Dydrogesterone with intramuscular 17α-hydroxyprogesterone caproate (17α-OHPC) administration in prevention of PTB. METHODS: In this randomized clinical trial, we studied 150 women with singleton pregnancy in 28Th-34Th Gestational week, who had received tocolytic treatment for preterm labor. Participants were divided to receive 30 mg oral Dydrogesterone daily, 250 mg intramuscular 17α-OHPC weekly, or no intervention (control group). All treatments were continued until 37Th Week or delivery, whichever occurred earlier. Obstetric outcomes, including latency period, gestational age at delivery, birth weight, neonatal intensive care unit (NICU) admission, and neonatal mortality were recorded. All patients were monitored biweekly until delivery. RESULTS: Baseline gestational age was not significantly different between groups. Latency period was significantly longer in the progesterone group compared with Dydrogesterone and control groups (41.06 ± 17.29 vs. 29.44 ± 15.6 and 22.20 ± 4.51 days, respectively; P < 0.001). The progesterone group showed significantly better results compared with the other two groups, in terms of gestational age at delivery, birth weight, and Apgar score (P < 0.001). None of the participants showed severe complications, stillbirth, or gestational diabetes. CONCLUSION: Progesterone caproate can strongly prolong the latency period and improve neonatal outcomes and therefore, is superior to oral Dydrogesterone in the prevention of PTB.

The effect of dydrogesterone on sexual function in endometriosis.

Endometriosis is an oestrogen-dependent chronic disease, which is commonly regarded as a disease of reproductive-aged women. We aimed to evaluate the sexual function with Female Sexual Function Index (FSFI) in women with endometriosis who received dydrogesterone for 6 months. A total of 79 women with endometriomas were recruited in the study group and received 10 mg dydrogesterone tablets orally for 6 months. FSFI and visual analog scale (VAS) scores for each patient before and after treatment were recorded. When before treatment VAS scores and after treatment VAS scores (5.7 ± 1.27, 3.97 ± 1.01, respectively) were compared, a significant decrease was observed (p = .001). A significant increase in mean orgasm scores (3.23 ± 0.6 vs. 3.57 ± 0.65, p = .01) and means satisfaction scores (3.85 ± 0.48 vs. 4.10 ± 0.38, p < .001) were observed. In addition, means desire scores were also significantly higher following treatment (p = .01). In conclusion, this study showed that FSFI scores were increased after 6 months of dydrogesterone treatment in patients with endometriosis. Desire, satisfaction, orgasm and pain scores improved significantly, and sexual dysfunction decreased after treatment.Impact statementWhat is already known on this subject? Endometriosis is a chronic inflammatory disease associated with severe dysmenorrhoea, pelvic pain, dyspareunia, painful gastrointestinal symptoms and sub-fertility are among the symptoms. These symptoms can be responsible for a significant decrease in the quality of life scores of the patients. Dydrogesterone is a synthetic progesterone derivative, which suppresses oestrogen levels and ovulation. Dydrogesterone's effect on pain relief in endometriosis patients has already been shown, but it's role on the sexual dysfunction observed in women with endometriosis has not yet been questioned.What do the results of this study add? To the best of our knowledge this is the first study showing the effects of dydrogesterone on sexual function in patients with endometriosis.What are the implications of these findings for clinical practice and/or further research? Dydrogesterone can safely be used in medical treatment of endometriosis not only for pain relief but also patients with additional complaints such as sexual dysfunction can benefit from this treatment. Future studies with larger cohorts and long-term follow-ups are needed to validate our results.