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Objective: To analyze the efficacy of levonorgestrelintrauterine system, Drospirenone & ethinylestradiol tablets (II), and dydrogesterone in preventing the recurrence of endometrial polyps after hysteroscopic endometrial polypectomy., Methods: One hundred seventy patients who underwent hysteroscopic endometrial polypectomy in the Gynecology Department of Tianmen First People's Hospital in Hubei Province from January 2022 to June 2023 were randomly divided into the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, dydrogesterone group, and a control group. The recurrence rates, endometrial thickness, and menstrual volume changes at 6 and 12 months post-operation were compared among these four groups., Results: The recurrence rates in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group were lower than the control group, with statistical significance (P < 0.01), with the levonorgestrelintrauterine system group having the lowest recurrence rate. The endometrial thickness at 6 and 12 months post-operation in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group was thinner than that of the control group and thinner than pre-operation, with statistical significance (P < 0.01). The menstrual volume at 3 months post-operation in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group was significantly less than the control group, and less than the pre-operation volume., Conclusion: Dydrogesterone, drospirenone & ethinylestradiol tablets (II), and levonorgestrelintrauterine system all play a role in preventing the recurrence of endometrial polyps, but levonorgestrelintrauterine system is significantly better than dydrogesterone and Drospirenone & ethinylestradiol tablets (II) in terms of postoperative recurrence rate, endometrial thickness, menstrual changes, and compliance, and is worth promoting in clinical application., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Study Objective: The absence of corpus lutea in artificial cycle (AC) frozen embryo transfers (FET) may increase the chances of pregnancy loss. In this retrospective cohort study, the efficacy of AC endometrial preparation was compared natural cycle (NC) endometrial preparation in terms of ongoing pregnancy., Methods: One thousand six hundred and eighteen consecutive vitrified-warmed blastocyst FET performed between December 2021 and November 2022 were included, with 1023 compared after exclusions according to the endometrial preparation method; 293 NC-FET, 143 modified NC-FET, 204 unprogrammed AC-FET, and 383 oral contraceptive pill (OCP) programmed AC-FET. Intensive method-specific luteal phase support (LPS) was administered in NC- (human chorionic gonadotropin and micronized vaginal progesterone), mNC- (micronized vaginal progesterone), and in AC-FET (micronized vaginal progesterone, intramuscular progesterone, and oral dydrogesterone)., Results: Clinician choice of endometrial preparation method resulted in the NC- or AC-FET groups having distinct differences, with female age, antral follicle count and body mass index as well as the percentage of DOR or PCOS diagnosed patients significantly different. The unadjusted ongoing pregnancy and total pregnancy loss rates for NC-, mNC-, AC-, and ocp-AC-FET were 61.8 %, 55.2 %, 57.4 %, and 58.5 %, and 19.2 %, 24.0 %, 23.5 % and 23.8 %, respectively. In multivariate logistic regressions to predict the dependent outcomes of ongoing pregnancy and total pregnancy loss, none of the FET methods were selected as independent predictors., Conclusion: Patients undergoing NC- and AC-FET with method-specific progesterone LPS had comparable ongoing pregnancy rates as well as total pregnancy loss rates, with NC-FET ranked first in the regression analysis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest associated with the publication of the study., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

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.

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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Conflicts to interest: none to declare., (© 2024. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved.)

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., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Shaikh M and Acharya N.)

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., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

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.

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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.

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., (© 2023. The Author(s).)

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.

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 &lt; .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., (© 2022. The Author(s).)

Competing Interests: The author has no conflict of interests to declare.

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., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Xuehong Chen et al.)

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 statement What 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.

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., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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 28 Th -34 Th  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 37 Th  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., (© 2022. The Author(s).)

Objective: To assess and compare the feasibility of progestin-primed ovarian stimulation (PPOS) protocol with mild stimulation protocol for advanced age women with diminished ovarian reserve (DOR) undergoing their first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle., Methods: Patients aged ≥35 years and DOR undergoing their first IVF/ICSI cycle were enrolled in this retrospective cohort study: 139 and 600 patients underwent the PPOS and mild stimulation protocols, respectively. The primary outcomes were cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLBR). The secondary outcomes were the number of oocytes retrieved and top-quality embryos., Results: There was nearly no significant difference of baseline characteristics between the two groups. Although a greater amount of total gonadotropin (1906.61 ± 631.04 IU vs. 997.72 ± 705.73 IU, P <0.001) and longer duration of stimulation (9 (10-7) vs. 6 (8-4), P <0.001) were observed in the PPOS group, the number of retrieved oocytes (3 (6-2) vs. 2 (4-1), P <0.001) and top-quality embryos (1 (2-0) vs. 1 (2-0), P =0.038) was greater in the PPOS group than the mild stimulation group. Meanwhile, the incidence of premature luteinizing hormone (LH) surge rate was significantly lower in the PPOS group (0.7% vs.8.3%, P =0.001) than the mild stimulation group. However, there was no significant difference in conservative CCPR, conservative CLBR, optimistic CCPR, and optimistic CLBR between the two groups (all P >0.05). A multivariate logistic regression model showed significant positive effects of the number of retrieved oocytes and number of top-quality embryos on conservative CCPR (OR=1.236, 95%CI: 1.048-1.456, P =0.012, OR=2.313, 95%CI: 1.676-3.194, P <0.001) and conservative CLBR (OR=1.250, 95%CI: 1.036-1.508, P =0.020, OR=2.634, 95%CI: 1.799-3.857, P <0.001) respectively, while significant negative effects of age were identified for conservative CCPR (OR=0.805, 95%CI: 0.739-0.877, P <0.001) and conservative CLBR (OR=0.797, 95%CI: 0.723-0.879, P <0.001)., Conclusion: The PPOS protocol is an effective alternative to the mild stimulation protocol for advanced age patients with DOR, as it provides comparable reproductive outcomes and better control of premature LH surge. Further, more oocytes and top-quality embryos were obtained in the PPOS group, which had a positive association with conservative CCPR and CLBR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tu, You, Jing, Lin and Zhang.)

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.

Purpose: To discuss the effects of dydrogesterone combined with letrozole on the effectiveness, sex hormone levels, and serological indicators in patients with endometriosis. This study is registered with PROSPERO (CRD42020213172)., Methods: We searched relevant randomized controlled trials (RCTs) through PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP Database. The standardized mean differences (SMDs), the mean differences (MDs), or odds ratios (ORs) with their 95% confidence intervals (95% CIs) were computed to be outcome indicators, including total effectiveness, Vascular Endothelial Growth Factor (VEGF) level, Carbohydrate Antigen 125 (CA125) level, Follicle-Stimulating Hormone (FSH) level, Luteinizing Hormone (LH) level, estrogen (E2) level, progesterone (P) level, interleukin-6 (IL-6) level, and tumor necrosis factor-a (TNF-a) level., Results: A total of 19 RCTs involving 1,591 patients were included in this study. Our results showed that letrozole combined with dydrogesterone can significantly reduce the levels of VEGF (SMD -2.23, 95% CI -2.39 to -2.07; p < 0.00001), CA125 (MD -10.53, 95% CI -11.19 to -9.88; p < 0.00001), E2 (SMD -1.64, 95% CI -1.81 to -1.47; p < 0.00001), P (MD -5.11, 95% CI -6.26 to -3.96; p < 0.00001), IL-6 (MD -4.41, 95% CI -5.16 to -3.67; p < 0.00001), and TNF-a (MD -5.67, 95% CI -6.34 to -5.00; p < 0.00001) in patients with endometriosis compared with the control group. In addition, the results indicated that total effectiveness was significantly higher in the experiment group (OR 6.21, 95% CI 4.17 to 9.24; p < 0.00001) compared to the control. However, there was no significant difference between FSH and LH levels in both groups ( p > 0.05)., Conclusion: This combination therapy can effectively decrease the levels of VEGF, CA125, E2, P, IL-6, and TNF-a and increase the total effectiveness when comparing with the control group., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Shumei Sun et al.)

Background: This study aimed to explore the clinical efficacy of dydrogesterone in treating recurrent spontaneous abortion (RSA), analyze the influence of dydrogesterone on cellular immune factors, and provide evidence for clinical medication., Methods: We used the China National Knowledge Infrastructure (CNKI) platform, Wanfang Data resource, PubMed, Web of Science, and Embase database to conduct a literature search to screen clinical studies published between 2005 and 2021 concerning dydrogesterone treatment for RSA. Stata 16.0 was used for meta-analysis and sensitivity analysis, and Begg's funnel chart was used to test publication bias., Results: Only 13 studies, which included a total of 2,454 RSA patients, met the study inclusion criteria. The experimental group was treated with dydrogesterone, and the control group was treated with progesterone, human chorionic gonadotropin (hCG), placebo, or active immunization. Meta-analysis showed that the pregnancy success rate of the experimental group was higher than the control group, and the adverse reaction rate was lower than the control group. In addition, subgroup analysis also revealed that the experimental group had a higher pregnancy success rate than the control group and a lower adverse reaction rate. Levels of progesterone and hCG in the experimental group were dramatically higher than the control group after treatment. The experimental group also had higher levels of interleukin 4 (IL-4) and interleukin 10 (IL-10) than the control group, while levels of interferon-gamma (IFN-γ) were lower., Discussion: Dydrogesterone, a safe and effective synthetic progesterone drug, had a significant clinical effect on RSA and effectively improved hormone levels and related cellular immune factors in RSA patients.

Background: It remains under subject of debate regarding the optimal route of luteal support for hormone replacement therapy- frozen embryo transfer (HRT-FET) cycles. We compared efficacy of vaginal progesterone gel combined with oral dydrogesterone and intramuscular progesterone for HRT-FET lutein support., Methods: This is a retrospective observational study. After matching for propensity score of getting vaginal + oral treatment, a total of 208 FET cycles in the vaginal progesterone combined with oral dydrogesterone and 624 cycles in the intramuscular progesterone group were enrolled. Pregnancy outcomes and neonatal outcomes including chemical pregnancy rate, clinical pregnancy rate, implantation rate, spontaneous abortion rate, live birth rate, gestational weeks, pre-term delivery, birth weight, and congenital anomalies rate were compared., Results: No significant differences were observed in patient characteristics such as age, duration of infertility, type of infertility, or hormone level after matching. Chemical pregnancy rate (68.3 % versus 70.5 %), clinical pregnancy rate (64.9 % versus 64.4 %), implantation rate (52.3 % versus 50.2 %), spontaneous abortion rate (21.5 % versus 18.4 %), and live birth rate (49.0 % versus 51.3 %) were similar in both group without statistically significant difference. No significant differences in neonatal outcomes were observed between the two groups., Conclusion: We observed similar pregnancy outcomes in both vaginal progesterone gel combined with oral dydrogesterone and intramuscular progesterone protocol. Vaginal progesterone gel combined with oral dydrogesterone can be substituted for intramuscular progesterone given that vaginal plus oral use has good safety and is more convenient and may be associated with less side effect caused by intramuscular injection., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Dydrogesterone is an orally active synthetic progestogen, with a molecular structure similar to that of natural progesterone. As dydrogesterone does not inhibit ovulation at standard doses, is devoid of estrogenic or androgenic properties, and does not induce metabolic side effects, it is suitable for use throughout a woman's lifetime, from adolescence to older age, for conditions associated with altered levels of endogenous progesterone. Aside from its well established role as a component of menopausal hormone therapy, dydrogesterone is indicated in younger women for treatment of dysmenorrhea, irregular menstrual cycles, premenstrual syndrome, and threatened or recurrent miscarriage; and is effective as luteal phase support during assisted reproduction techniques. In this narrative review, evidence is examined for use of dydrogesterone across a range of disorders affecting menses and pregnancy. A case study woven into the review illustrates the clinical uses of dydrogesterone during a young woman's journey to become a mother.

Purpose: Endometriosis is a common, chronic gynecological disease that affects women's fertility potential. Dydrogesterone is an effective and safe drug that is under-utilized due to limited clinical research. The purpose of this evidence mapping is to identify, describe, and analyze the current available evidence regarding dydrogesterone for the treatment of endometriosis., Materials and Methods: We performed a search in electronic databases: Medline, The Cochrane Library, EMBASE, PubMed, CNKI, Wanfang, VIP, and CBM. We also hand-searched google for relevant studies. Our primary outcomes included changes in pain relief including pelvic pain, dysmenorrhea, and dyspareunia. Secondary outcomes included pregnancy rate, frequency of analgesic use, and other reported outcomes according to specific settings in the studies., Results: Of 377 references screened, 19 studies were included in the data synthesis involving 1709 female participants. Nearly three-quarters were either randomized control trials or clinical control trials. Compared with gestrinone, dydrogesterone relieved dysmenorrhea, increased the pregnancy rate, and reduced the risk of certain adverse events. Compared with GnRH-a, dydrogesterone also lowered the risk of endometriosis recurrence and elevated transaminase levels. Whether there was any difference in efficacy between dydrogesterone and leuprolide acetate, letrozole or traditional Chinese medicine remains unclear due to insufficient data., Conclusions: The amount and quality of evidence evaluating the effects of dydrogesterone for the treatment of endometriosis is generally very low. Limited evidence suggests that dydrogesterone may have some advantages over gestrinone, GnRH agonists, and other therapeutic interventions in treating endometriosis. However, this conclusion should be interpreted with caution.

Background: 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)., Objectives: 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., Search Methods: 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., Selection Criteria: 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., Data Collection and Analysis: 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., Main Results: 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 placebo (RR 1.08, 95% CI 1.02 to 1.15, high-certainty evidence). Women with recurrent miscarriage Based on the results from one trial (826 women) vaginal micronized progesterone (RR 1.04, 95% CI 0.95 to 1.15, high-certainty evidence) probably makes little or no difference to the live birth rate when compared with placebo for women with recurrent miscarriage. The evidence for dydrogesterone compared with placebo for women with recurrent miscarriage is of very low-certainty evidence, therefore the effects remain unclear. 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 recurrent miscarriage. Additional outcomes All progestogen treatments have a wide range of effects on the other pre-specified outcomes (miscarriage (< 24 weeks of gestation), preterm birth (< 37 weeks of gestation), stillbirth, ectopic pregnancy) in comparison to placebo for both threatened and recurrent miscarriage. Moderate- and low-certainty evidence with a wide range of effects suggests that there is probably no difference in congenital abnormalities and adverse drug events with vaginal micronized progesterone for threatened (congenital abnormalities RR 1.00, 95% CI 0.68 to 1.46, moderate-certainty evidence; adverse drug events RR 1.07 95% CI 0.81 to 1.39, moderate-certainty evidence) or recurrent miscarriage (congenital abnormalities 0.75, 95% CI 0.31 to 1.85, low-certainty evidence; adverse drug events RR 1.46, 95% CI 0.93 to 2.29, moderate-certainty evidence) compared with placebo. There are limited data and very low-certainty evidence on congenital abnormalities and adverse drug events for the other progestogens., Authors' Conclusions: The overall available evidence suggests that progestogens probably make little or no difference to live birth rate for women with threatened or recurrent miscarriage. However, vaginal micronized progesterone may increase the live birth rate for women with a history of one or more previous miscarriages and early pregnancy bleeding, with likely no difference in adverse events. There is still uncertainty over the effectiveness and safety of alternative progestogen treatments for threatened and recurrent miscarriage., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Dienogest (DNG) is an oral progestin effective for the treatment of symptomatic endometriosis, such as reduction of endometrial lesion and control of pain intensity. Progestin-primed ovarian stimulation (PPOS) is a new controlled ovarian hyperstimulation (COH) regimen, and several reports have shown that dydrogesterone (DYG) is an appropriate progestin for PPOS. The purpose of this study was to evaluate the efficacy of DNG in patients undergoing PPOS during COH in comparison with DYG. This was a prospective, cohort, parallel-group, non-inferiority trial of 150 women with endometriosis undergoing assisted reproductive technology between February 2018 and May 2020 at the single fertility center. The assignment to each protocol was based on the optimal treatment for each patient. Patients taking DNG 2 mg continuously were assigned in the DNG group(n = 73). The other patients were allocated in DYG group(n = 77). All viable embryos were cryopreserved for subsequent transfer. The main outcome measures were the mature oocyte and fertilization rates. During this study, no premature LH surge was detected. A smaller number of oocytes were retrieved in the DNG group than in the DYG group (6.18 ± 3.60 vs. 9.85 ± 5.77); however, the rate of mature oocytes was significantly higher in the DNG group than in the DYG group (89.1 % vs. 78.9 %). The fertilization rate was comparable between two groups. Therefore, patients taking DNG for PPOS can continue endometriosis treatment and obtain good-quality embryos during COH. Further prospective randomized-controlled trial should be performed to confirm of this novel strategy of DNG., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Study Question: Will use of oral progestogen in women with threatened miscarriage in the first trimester reduce the miscarriage rate when compared with placebo?, Summary Answer: Use of oral progestogen in women with threatened miscarriage in the first trimester did not reduce miscarriage before 20 weeks when compared with placebo., What Is Known Already: Miscarriage is a common complication of pregnancy and occurs in 15-20% of clinically recognized pregnancies. Use of vaginal progestogens is not effective in reducing miscarriage but there is still no good evidence to support use of oral progestogen for the treatment of threatened miscarriage., Study Design, Size, Duration: This was a randomized double-blind controlled trial. A total of 406 women presenting with threatened miscarriage in the first trimester were recruited from 30 March 2016 to May 2018., Participants/materials, Setting, Methods: Women attending Early Pregnancy Assessment Clinics because of vaginal bleeding during the first trimester were recruited and randomly assigned to use dydrogesterone 40 mg orally, followed by 10 mg orally three times a day or placebo until 12 completed weeks of gestation or 1 week after the bleeding stopped, whichever was later. The primary outcome was the miscarriage rate before 20 weeks of gestation., Main Results and the Role of Chance: The two groups of women had comparable age, BMI, number of previous miscarriages, gestation and ultrasound findings at presentation. The miscarriage rate before 20 weeks of gestation was similar in both groups, being 12.8% (26/203) in the progestogen group and 14.3% (29/203) in the placebo group (relative risk 0.897, 95% CI 0.548-1.467; P = 0.772). The live birth rate was 81.3% in the progestogen group versus 83.3% in the placebo group (P = 0.697). No significant differences were found between the two groups in terms of obstetric outcomes and side effects., Limitations, Reasons for Caution: The primary outcome was the miscarriage rate, rather than the live birth rate. Women were recruited from Early Pregnancy Assessment Clinics and those with heavy vaginal bleeding might be admitted into wards directly instead of attending Early Pregnancy Assessment Clinic. The severity of vaginal bleeding was subjectively graded by women themselves. The sample size was not adequate to demonstrate a smaller difference in the miscarriage rate between the progestogen and placebo groups. We did not exclude women with multiple pregnancy, which increased the risk of miscarriage although there was only one set of twin pregnancy in the placebo group., Wider Implications of the Findings: Use of oral progestogen is not recommended in women with threatened miscarriage in the first trimester., Study Funding/competing Interest(s): This study was funded by the Health and Medical Research Fund, HKSAR (reference number 12132341). All authors declared no conflict of interest., Trial Registration Number: ClinicalTrials.gov with an identifier NCT02128685., Trial Registration Date: 1 May 2014., Date of First Patient's Enrolment: 30 March 2016., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Object: To evaluate the efficacy of dydrogesterone for the treatment of premenopausal patients with endometrial polyps (EPs)., Methods: A single-center, open-label, prospective, single-arm clinical treatment trial was conducted in patients of reproductive age with EP(s). Patients were prescribed dydrogesterone from day 15 to day 24 of the menstrual cycle over a period of 3 months. At the 3-month follow-up, the efficacy of dydrogesterone was evaluated based on changes in self-report symptoms and ultrasonographic characteristics. The predictive factors of efficacy as well as the predictive value of the significant factors were also assessed., Results: A total of 60 patients were included. Improvements in both symptoms and ultrasound findings occurred in 31 patients, achieving an efficacy rate of 51.67%. Of 41 patients with clinical presentations, 39 (95.1%) reported improvements in symptoms. In terms of ultrasound findings, 33 (55%) of patients demonstrated improvements. Significant decreases were observed in the mean endometrial thickness (1.17 ± 0.33 cm vs 0.90 ± 0.35 cm, p  < .001) and polyp size (1.10 ± 0.34 cm vs 0.74 ± 0.65 cm, p  = .001) after the application of dydrogesterone. Age ( p  = .006), polyp size ( p  = .006), and blood flow within polyps ( p  = .035) were significant predictors of dydrogesterone efficacy. These factors, when combined, demonstrated a good predictive value ([area under the curve (AUC)=0.81])., Conclusion: Dydrogesterone is effective in the management of EPs in premenopausal patients. Age, polyp size and blood flow should be taken into consideration when prescribing dydrogesterone for this population of women.

Background: Preterm birth is a major challenge in obstetric and perinatal care. It is the leading cause of neonatal death. The primary aim of this study was to evaluate the efficacy of oral dydrogesterone on latency period in managing preterm labor. The secondary aims were to evaluate the gestational age at delivery, percentage of preterm delivery before 34 weeks and 37 weeks, time to recurrent uterine contraction, pregnancy outcomes, neonatal outcomes, compliance and side effects., Methods: This was a randomized, double blinded, placebo-controlled trial. Forty-eight pregnant women with preterm labor, singleton pregnancy, and gestational age of 24-34 weeks were enrolled into the study. The study group received 10 mg of oral dydrogesterone three times per day and the control group received placebo. All pregnant women received standard treatment with tocolytic and antenatal corticosteroids., Results: The median latency periods were not significantly different between the dydrogesterone group (27.5 days) and placebo group (34 days, p = 0.45). Additionally, there were no differences in the gestational age at delivery, percentage of preterm delivery before 34 weeks and 37 weeks, pregnancy outcomes, neonatal outcomes, compliance and side effects. However, the time to the recurrence of uterine contractions in participants that had recurrent preterm labor was longer in the dydrogesterone group than in the placebo group (30.6 ± 12.3 vs 13.7 ± 5.0 days, p = 0.01)., Conclusions: Adjunctive treatment with 30 mg of oral dydrogesterone could not prolong latency period in preterm labor when compared to placebo., Trial Registration: ClinicalTrials.gov (Clinical trials registration: NCT03935152 , registered on May 2,2019).

Introduction: Turner syndrome (TS) is associated with hypergonadotropic hypogonadism due to gonadal dysgenesis, which results in premature ovarian failure and subsequent infertility. Therefore, counseling and evaluation for fertility preservation are required as early as possible for women with TS., Case Presentation: A 23-year-old unmarried woman with mosaic TS (45, X [4/30] 46, XX [26/30]) presented to the pediatric department of our hospital for fertility counseling; she was accompanied by her mother. She was referred to the reproduction center of our hospital for ovarian reserve assessment and counseling regarding fertility preservation. We decided to retrieve oocytes using DuoStim as the controlled ovarian stimulation protocol. During the first and second oocyte retrievals, a total of 17 (9 and 8, respectively) mature metaphase II oocytes were cryopreserved., Conclusion: DuoStim may be a useful option for fertility preservation for women with TS and reduced ovarian reserve. This new strategy may obtain the required number of oocytes in the shortest time and preserve the future fertility of women with TS.

Objectives: Various combinations of estrogens and progestogens are available for menopausal hormone therapy that differ in their efficacy and safety profile. We evaluated the efficacy and long-term safety of low-dose estradiol (0.5 mg) / dydrogesterone (2.5 mg) in subgroups of postmenopausal women with vasomotor symptoms., Analysis: Efficacy analysis was performed on data from 2 previously published studies for subgroups defined by age, duration of menopause, and body mass index at baseline. The primary efficacy variable was the number of moderate to severe hot flushes from baseline to week 13. Long-term safety was evaluated in relation to age and duration of menopause. Safety variables included adverse events to week 52 and change from baseline to endpoint in laboratory and vital sign values., Results: The treatment difference seen in the overall population in favour of low-dose estradiol/dydrogesterone was also observed in the subgroups of patients aged 45 to < 55 years (p < 0.01) and ≥55 years (p < 0.05), with menopause duration of >12 months to <60 months (p < 0.05) and ≥ 60 months (p < 0.005), and with a BMI at baseline of <25 kg/m 2 (p < 0.05) and 25 to <30 kg/m 2 (p < 0.01). Low-dose estradilol/dydrogesterone was well tolerated across the different subgroups. The incidence of breast-related adverse events was very low. No breast malignancy was reported. Only one adverse endometrial outcome of simple hyperplasia was observed., Conclusion: The results of our analyses confirmed the consistent treatment effect on vasomotor symptoms and the favourable safety profile of 0.5 mg 17β estradiol and 2.5 mg dydrogesterone in different patient subgroups., (Copyright © 2020. Published by Elsevier B.V.)

Our goal was determine the effects of dydrogesterone supplementation to reduce the incidence of preeclampsia (PE) in early pregnancy (from 6 to 20 weeks of gestation). A total of 406 pregnant women were involved into the study. The Study group enrolled 169 women, supplemented with dydrogesterone at a dose of 30 mg/d 6-20 weeks of gestation compared with the control group (237 subjects) - without dydrogesterone supplementation. The women were randomized by age, race, obstetrics complications, and their somatic history. The use of dydrogesterone in early pregnancy - before 20 weeks of gestation (at a dose of 30 mg/d) with high-risk factors of PE contributed to a statistically significant reduction in the frequency of this complication (13.1% and 71.4%, p  < .001). It was seen, that women who took dydrogesterone developed significantly less such disorders like hypertension (3.2% and 71.2%, p  < .001), proteinuria (0.0% and 66.18%, p  < .001), fetal growth retardation syndrome (2.2% and 21.58%, p  < .001), destroy of uteri-placenta velocity (3.2% and 21.58%, p  < .001), preterm labor (8.6% and 53.95%, p  < .001). Dydrogesterone supplementation in the first and second period of pregnancy (from 6 to 20 weeks of gestation) significantly reduced the incidence of PE in women with higher risk pregnancy.

The study was to compare the efficacy, safety, and tolerability of low dose versus ultra-low dose hormone therapy (HT) in the management of perimenopause symptoms and quality of life. Retrospective analysis of perimenopause patients prescribed for 25 weeks HT in the outpatient clinic of menopause. A total of 132 perimenopause women were included in two treatment regimens: one with low dose HT (LD-HT) and one with ultra-low dose HT (ULD-HT). Changes in serum levels of follicle-stimulating hormone, estradiol as well as transvaginal ultrasound (TVUS), the 36-item Short Form Health Survey (SF-36), the Kupperman Index (KI), and adverse effects were assessed at baseline, 4, 13, and 25 weeks. By the end of 25 weeks of treatment, each score of SF-36 domains for both LD-HT and ULD-HT groups were increased, the KI decreased, and the endometrial thickness increased in both groups and there was no statistical difference between two groups. Both groups have negligible differences in incidence of adverse effects. Low dose and ultra-low dose HT both can serve in improving symptoms of perimenopause, thereby offering a better quality of life with decreased incidence of side effects. Ultra-low dose treatment may have a better advantage on safety and tolerance.

Lotus II, a randomized, open-label, multicenter, international study compared the efficacy and safety of oral dydrogesterone versus micronized vaginal progesterone (MVP) gel for luteal support in IVF. A prespecified subgroup analysis was performed on 239 Chinese mainland subjects from the overall study population ( n  = 1034), who were randomized to oral dydrogesterone 30 mg or 8% MVP gel 90 mg daily from the day of oocyte retrieval until 12 weeks of gestation. The aim was to demonstrate non-inferiority of oral dydrogesterone to MVP gel, assessed by the presence of a fetal heartbeat at 12 weeks of gestation. In the Chinese mainland subpopulation, there was a numerical difference of 9.4% in favor of oral dydrogesterone, with ongoing pregnancy rates at 12 weeks of gestation of 61.4% and 51.9% in the oral dydrogesterone and MVP gel groups, respectively (adjusted difference, 9.4%; 95% CI: -3.4 to 22.1); in the overall population, these were 38.7% and 35%, respectively (adjusted difference, 3.7%; 95% CI: -2.3 to 9.7). In both the Chinese mainland subpopulation and the overall population, dydrogesterone had similar efficacy and safety to MVP gel. With convenient oral administration, dydrogesterone has potential to transform luteal support treatment.

Objective: To evaluate the therapeutic effect of auricular acupuncture combined with dydrogesterone for threatened abortion in early pregnancy complicated with subchorionic hematoma., Methods: A total of 80 patients were randomized into an observation group and a control group, 40 cases in each one. In the control group, dydrogesterone was taken orally twice a day, 10 mg a time until 12-week into pregnancy. In the observation group，auricular acupuncture was applied at penqiang (TF 5 ), pizhixia (AT 4 ), shen (CO 10 ), xin(CO 15 ), gan (CO 12 ), jiaogan (AH 6a ) and neifenmi (CO 18 ) on the basis of the control group, the auricular points on both sides were used alternatively. The auricular points were replaced every 3 days with 1 day break, totally 3 weeks (20 days) were required. Before treatment and after 10, 20 days of treatment, the percentage of helper T lymphocyte (Th) and inhibitory T lymphocyte (Ts), ratio of Th and Ts and serum level of CA125 were compared in the two groups. The areas of subchorionic hematoma and gestational sac were evaluated by B ultrasound. The therapeutic effect in the two groups were compared., Results: The effective rate in the observation group was 80.0% (32/40), which was superior to 65.0% (26/40) in the control group ( P <0.05). After 10, 20 days of treatment, the percentage of Th and ratio of Th and Ts were lower than before treatment, the percentage of Ts were increased in the two groups ( P <0.01). After 20 days of treatment, the percentage of Th and ratio of Th and Ts in the observation group were lower than the control group ( P <0.01), the percentage of Ts was higher than the control group ( P <0.01). After 10, 20 days of treatment, the serum levels of CA125 were reduced compared before treatment in the two groups ( P <0.01), and the serum levels of CA125 in the observation group were lower than the control group ( P <0.01). After 10, 20 days of treatment, the ratio of subchorionic hematoma area and gestational sac area in the observation group was lower than the control group ( P <0.01)., Conclusion: Auricular acupuncture combined with dextroprogesterone can improve the effective rate of patients with threatened abortion in early pregnancy complicated with subchorionic hematoma, regulate immune factors, promote the hematoma absorption, and has a better synergistic effect with dextroprogesterone.

A prospective observational study was conducted on 186 patients with clomifene citrate (CC)-resistant polycytic ovary syndrome (PCOS) who were allocated into two treatment arms for three months; letrozole alone (n = 92) and letrozole with luteal support using vaginal dydrogestrone (n = 94). Patients received luteal support experienced significantly higher clinical pregnancy rate than those who received letrozole alone (48.9% vs. 23.9%, respectively). Luteal support in letrozole treated CC-resistant PCOS significantly improves pregnancy rate and should be implemented in ovulation induction regimens.

The aim of the study is to compare the bone sparing effect of half-dose with standard-dose conjugated equine estrogen (CEE) combined with progestin. A total of 123 participants were administrated with 0.625 mg of CEE and 100 mg of micronized progesterone (MP) in group A, 0.3 mg of CEE and 100 mg of MP in group B, 0.625 mg of CEE and 10 mg of dydrogesterone (DDG) in group C for one year. Percent changes from baseline in BMD at lumbar spine and fracture rate were primary outcomes. Secondary endpoints included changes of BMD at femoral neck, total hip and arm, bone markers (alkaline phosphatase, calcium and phosphorus), serum alanine aminotransferase (ALT) and endometrial thickness. No fractures occurred during the treatment. Standard dose of CEE leads to significant changes in lumbar spine and arm. The 3.78% growth of BMD at femoral neck in group C marked a statistically difference. There was no statistically remarkable bone loss at hip in all three groups. Bone turnover markers and ALT significantly decreased from basic values. Endometrium thickened more with traditional dose of CEE. Both the half and standard dose CEE are effective in BMD preservation among early menopausal women with subtle side effects. Low-dose estrogen is less efficacious than traditional one.

The pharmacological and physiological profiles of progestogens used for luteal phase support during assisted reproductive technology are likely to be important in guiding clinical choice towards the most appropriate treatment option. Various micronized progesterone formulations with differing pharmacological profiles have been investigated for several purposes. Dydrogesterone, a stereoisomer of progesterone, is available in an oral form with high oral bioavailability; it has been used to treat a variety of conditions related to progesterone deficiency since the 1960s and has recently been approved for luteal phase support as part of an assisted reproductive technology treatment. The primary objective of this review is to critically analyse the clinical implications of the pharmacological and physiological properties of dydrogesterone for its uses in luteal phase support and in early pregnancy., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

There has not been conclusive evidence in literature on the efficacy of progestogen in the treatment of threatened miscarriage, although some studies showed benefits. In our centre, threatened miscarriage is treated with either micronised progesterone (MP) or dydrogesterone (DYD)., Objective: The aim of this study is to compare clinical outcomes of miscarriage, extent of vaginal bleeding at follow-up and side effects between treatment groups., Study Design: This study was a prospective parallel-group, open-label, randomized controlled trial. 141 women presenting with threatened miscarriage were randomised to either MP or DYD of which 118 were included in the analysis. Baseline maternal demographics and serum progesterone levels were collected at presentation. Post-treatment bleeding pattern and self-reported side effects were recorded at the follow-up visit (on day 4-10 of treatment). The occurrence of spontaneous miscarriage was ascertained at week 16 of gestation., Results: The population with miscarriage and resolution of bleeding were not statistically different between MP and DYD groups. A significantly higher percentage of women treated with MP reported drowsiness (p = 0.003). After stratification into low and high serum progesterone levels, a significantly higher miscarriage rate was found in the low progesterone group, regardless of treatment type., Conclusion: In conclusion, extent of bleeding at day 4-10 and subsequent miscarriage rates were comparable between MP and DYD groups. However, fewer patients treated with DYD reported drowsiness and giddiness. The finding of significantly higher miscarriage rates in women with low progesterone levels despite treatment is an important factor to consider in counselling and prognosticating pregnancy outcomes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To identify, appraise, and summarize the evidence from randomized controlled trials (RCTs) comparing oral dydrogesterone to vaginal progesterone capsules for luteal-phase support (LPS) in women offered fresh or frozen embryo transfers following in vitro fertilization., Methods: Two independent authors screened the literature for papers based on titles and abstracts, then selected the studies, extracted data, and assessed the risk of bias. Dydrogesterone and progesterone were compared based on risk ratios (RR) and the precision of the estimates was assessed through the 95% confidence interval (CI)., Results: An electronic search performed on June 7, 2017 retrieved 376 records, nine of which were papers deemed eligible and included in this systematic review and quantitative analysis. Good quality evidence indicates that oral dydrogesterone provided at least similar results than vaginal progesterone capsules on live birth/ongoing pregnancy (RR=1.08, 95%CI=0.92-1.26, I2=29%, 8 RCTs, 3,386 women) and clinical pregnancy rates (RR 1.10, 95% CI 0.95 to 1.27; I2=43%; 9 RCTs; 4,061 women). Additionally, moderate quality evidence suggests there is no relevant difference on miscarriage rates (RR=0.92, 95%CI=0.68-1.26, I2=6%, 8 RCTs, 988 clinical pregnancies; the quality of the evidence was downgraded because of imprecision)., Conclusions: Good quality evidence from RCTs suggest that oral dydrogesterone provides at least similar reproductive outcomes than vaginal progesterone capsules when used for LPS in women undergoing embryo transfers. Dydrogesterone is a reasonable option and the choice of either of the medications should be based on cost and side effects.

Background: Current medical treatments for endometriosis are very limited. Progestin and selective progesterone receptor modulators (SPRM) are developed but their efficacy, safety, mechanism and recurrence in endometriosis are not fully studied., Methods: In order to compare therapeutic, side effects and therapeutic actions of Esmya, Duphaston and Dienogest in endometriosis. Experimental endometriosis was induced by either intraperitoneal or subcutaneous mouse endometrium transplantation. Lesion size, weight and histology at the end of intervention were compared. Expression of related markers in the endometriotic lesions were examined. Body, uterus and ovary weights, endometrial glands and thickness (ETI), and follicle count were measured. For recurrent study, lesion growth before and after intervention was monitored., Results: After Esmya, Duphaston, Dienogest treatment, lesion size and weight were significantly decreased. Proliferation Pcna expression was significantly decreased in all groups, but proliferation cells were significantly decreased only in Duphaston group. Apoptosis Mapk1 expression and TUNEL-positive cells were significantly increased in Duphaston group. Adhesion Mmp2 and Itgavβ3 expression were significantly increased in Esmya group. Plau, Hif1α and Vegfa expression, peritoneal fluid PGE2 levels, and ERα and ERβ expression were not affected; while PR expression was significantly lower in all groups. Endometrial gland count in uterus was significantly increased in Dienogest group, ETI was significantly decreased in Duphaston group, and AFC were significantly increased in Esmya group. Upon treatment cessation, lesion growth rebound quickly in Dienogest and Duphaston groups, but slowly in Esmya group., Conclusion: Esmya, Duphaston and Dienogest are effective anti-endometriosis drugs targeting proliferation, apoptosis and adhesion. Esmya, Duphaston and Dienogest are all well tolerable, although endometrial glandular hyperplasia was found in Dienogest, endometrial atrophy in Duphaston, follicle accumulation in Esmya.

Background: While progesterone affects sleep, different types of it might affect sleep differently., Methods: One hundred Thai women, who complained of insomnia, visited the Menopause Clinic at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand from February 2014 to March 2015, and were divided randomly into two groups. Both groups received daily hormonal treatment that included estradiol valerate (progynova) at 1 mg. The first group also received dydrogesterone (duphaston ® ) at 10 mg and the second group micronized progesterone (utrogestran ® ) at 100 mg. The clinical symptoms and Pittsburgh Sleep Quality Index (PSQI) were recorded for three consecutive months after treatment. This study was registered with clinicaltrial.gov (code number NCT02086032)., Results: Sleep quality improved in both groups (10.52 ± 4.27 to 4.91 ± 3.15 in the dydrogesterone group and 10.16 ± 3.60 to 6.27 ± 3.04 in the micronized progesterone group, p value 0.08). Women in the micronized progesterone group had fewer overall side effects than those in the dydrogesterone group., Conclusion: Sleep quality of peri-postmenopausal women with insomnia improved dramatically after the first month of hormonal treatment. However, more participating patients are necessary to ascertain the differences in sleep quality from dydrogesterone and micronized progesterone treatment.

Introduction: Assisted reproductive techniques (ARTs) result in a deficient luteal phase, requiring the administration of intramuscular, intravaginal or oral exogenous progesterone. Dydrogesterone, an oral retroprogesterone with good bioavailability, has been used in assisted reproductive cycles with outcomes that are comparable to those of vaginal or intramuscular progesterone. However, there are limited reviews on its use for luteal phase support in ARTs, in terms of pregnancy outcomes and associated fetal anomalies. This study aimed to review the live birth rates and associated fetal anomalies of women who were given dydrogesterone for luteal phase support in assisted reproductive cycles at a tertiary hospital in Singapore., Methods: This retrospective descriptive study included 1,050 women who underwent in vitro fertilisation/intracytoplasmic sperm injection at the Centre for Assisted Reproduction of Singapore General Hospital between 2000 and 2011. The women were given dydrogesterone for luteal phase support. The main outcome measures were rates of pregnancy, live birth, miscarriage and fetal anomalies., Results: The pregnancy and live birth rates were 34.7% and 27.7%, respectively. Among those who achieved pregnancy, 17.0% miscarried, 0.8% had ectopic pregnancies and 0.3% had molar pregnancies. Fetal anomalies were detected in 1.9% of pregnancies, all of which were terminated by choice., Conclusion: Since the outcomes of dydrogesterone are comparable to those of intramuscular and vaginal progesterone, it is a reasonable option to provide luteal phase support for women who are uncomfortable with injections or vaginal insertions. Randomised controlled studies are needed to determine the optimal dosage of dydrogesterone for luteal phase support in ARTs., (Copyright: © Singapore Medical Association)

Study Question: Is oral dydrogesterone 30 mg daily (10 mg three times daily [TID]) non-inferior to micronized vaginal progesterone (MVP) 600 mg daily (200 mg TID) for luteal support in in vitro fertilization (IVF), assessed by the presence of fetal heartbeats determined by transvaginal ultrasound at 12 weeks of gestation?, Summary Answer: Non-inferiority of oral dydrogesterone versus MVP was demonstrated at 12 weeks of gestation, with a difference in pregnancy rate and an associated confidence interval (CI) that were both within the non-inferiority margin., What Is Known Already: MVP is routinely used in most clinics for luteal support in IVF, but it is associated with side effects, such as vaginal irritation and discharge, as well as poor patient acceptance. Dydrogesterone may be an alternative treatment due to its patient-friendly oral administration., Study Design, Size, Duration: Lotus I was an international Phase III randomized controlled trial, performed across 38 sites, from August 2013 to March 2016. Subjects were premenopausal women (>18 to <42 years of age; body mass index (BMI) ≥18 to ≤30 kg/m2) with a documented history of infertility who were planning to undergo IVF. A centralized electronic system was used for randomization, and the study investigators, sponsor's study team, and subjects remained blinded throughout the study., Participants/materials, Setting, Methods: In total, 1031 subjects were randomized to receive either oral dydrogesterone (n = 520) or MVP (n = 511). Luteal support was started on the day of oocyte retrieval and continued until 12 weeks of gestation (Week 10), if a positive pregnancy test was obtained at 2 weeks after embryo transfer., Main Results and the Role of Chance: In the full analysis set (FAS), 497 and 477 subjects in the oral dydrogesterone and MVP groups, respectively, had an embryo transfer. Non-inferiority of oral dydrogesterone was demonstrated, with pregnancy rates at 12 weeks of gestation of 37.6% and 33.1% in the oral dydrogesterone and MVP treatment groups, respectively (difference 4.7%; 95% CI: -1.2-10.6%). Live birth rates of 34.6% (172 mothers with 213 newborns) and 29.8% (142 mothers with 158 newborns) were obtained in the dydrogesterone and MVP groups, respectively (difference 4.9%; 95% CI: -0.8-10.7%). Oral dydrogesterone was well tolerated and had a similar safety profile to MVP., Limitations, Reasons for Caution: The analysis of the results was powered to consider the clinical pregnancy rate, but the live birth rate may be of greater clinical interest. Conclusions relating to the differences between treatments in live birth rate, observed in this study, should therefore be made with caution., Wider Implications of the Findings: Oral dydrogesterone may replace MVP as the standard of care for luteal phase support in IVF, owing to the oral route being more patient-friendly than intravaginal administration, as well as it being a well tolerated and efficacious treatment., Study Funding/competing Interest(s): Sponsored and supported by Abbott Established Pharmaceuticals Division. H.T.'s institution has received grants from Merck, MSD, Goodlife, Cook, Roche, Besins, Ferring and Mithra (now Allergan) and H.T. has received consultancy fees from Finox, Ferring, Abbott, ObsEva and Ovascience. G.S. has nothing to disclose. E.K. is an employee of Abbott GmbH. G.G. has received investigator fees from Abbott during the conduct of the study; outside of this submitted work, G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, Glycotope, as well as personal fees from VitroLife, NMC Healthcare LLC, ReprodWissen LLC and ZIVA LLC., Trial Registration Number: NCT01850030 (clinicaltrials.gov)., Trial Registration Date: 19 April 2013., Date of First Patient's Enrollment: 23 August 2013., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.)