The efficacy of levonorgestrelintrauterine system, drospirenone & ethinylestradiol tablets (II) and dydrogesterone in preventing the recurrence of endometrial polyps.

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.

Ultra-low-dose continuous combined estradiol and dydrogesterone in postmenopausal women: A pooled safety and tolerability analysis.

Objective: To assess the safety and tolerability of ultra-low dose estradiol and dydrogesterone (E0.5 mg/D2.5 mg) among postmenopausal women. Methods: This pooled analysis of data from three clinical studies assessed the effects of continuous combined ultra-low-dose estradiol and dydrogesterone among postmenopausal women. Participants received E0.5 mg/D2.5 mg or placebo for 13 weeks (double-blind, randomized, European study), E0.5 mg/D2.5 mg or placebo for 12 weeks (double-blind, randomized, Chinese study), or E0.5 mg/D2.5 mg for 52 weeks (open-label, European study). Safety outcomes included treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment discontinuation due to a TEAE, and adverse events of special interest (AESIs). Results: Overall, 1027 women were included in the pooled analysis (E0.5 mg/D2.5 mg, n = 736; placebo, n = 291). Mean treatment exposure was 288.9 days in the E0.5 mg/D2.5 mg group and 86.6 days in the placebo group. The proportion of women experiencing ≥1 TEAE was similar in the E0.5 mg/D2.5 mg and placebo groups (50.1% vs 49.5%, respectively). TESAEs occurred in 12 (1.6%) women receiving E0.5 mg/D2.5 mg and 9 (3.1%) women receiving placebo. Discontinuation of study treatment was infrequent in both groups (E0.5 mg/D2.5 mg: 1.5%; placebo: 2.4%). The occurrence of breast pain was more common in the E0.5 mg/D2.5 mg group than in the placebo group (2.0% vs 0.3%) as was uterine hemorrhage (6.5% vs 2.4%). The incidence of acne, hypertrichoses and weight increased was similar between groups. Conclusions: Across three studies, ultra-low-dose estradiol plus dydrogesterone was well tolerated among postmenopausal women, with no increase in TEAEs or TESAEs compared with placebo.

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

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

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

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

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

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

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

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

Comparison between oral dydrogesterone versus micronized vaginal progesterone gel in clinical outcome within the first HRT-FET cycle: a retrospective analysis.

OBJECTIVE: The purpose of this study is to compare the clinical efficacy of oral dydrogesterone and micronized vaginal progesterone (MVP) gel during the first HRT-FET cycle. METHODS: A retrospective cohort study based on a total of 344 women undergoing their first HRT-FET cycles without Gonadotropin-Releasing Hormone agonist (GnRH-a) pretreatment was conducted. All the cycles were allocated to two groups in the reproductive medical center at the University of Hong Kong-Shenzhen Hospital. One group (n = 193) received oral dydrogesterone 30 mg/d before embryo transfer, while the other group (n = 151) received MVP gel 180 mg/d. RESULTS: The demographics and baseline characteristics of two groups were comparable. We found no statistically significant difference in live birth rate (24.35% vs. 31.13%, P = 0.16), clinical pregnancy rate (34.72% vs. 36.42%, P = 0.74), embryo implantation rate (25.09% vs. 28.36%, P = 0.43), positive pregnancy rate (42.49% vs 38.41%, P = 0.45), miscarriage rate (9.33% vs 3.97%, P = 0.05), or ectopic pregnancy rate (0.52% vs. 0.66%, P = 0.86) between the oral dydrogesterone group and MVP gel group. In the multivariate logistic regression analysis for covariates, medication used for luteal support was not associated with live birth rate (OR = 0.73, 95% CI: 0.32-1.57, P = 0.45). And the different luteal support medication did not have a significant positive association with the live birth rate in the cycles with day 2 embryo transferred (OR = 1.39, 95% CI:0.66-2.39, P = 0.39) and blastocyst transferred (OR = 1.31 95% CI:0.64-2.69, P = 0.46). CONCLUSION: 30 mg/d oral dydrogesterone and 180 mg/d MVP gel revealed similar reproductive outcomes in HRT-FET cycles in the study.

Research progress of dydrogesterone in the treatment of endometriosis.

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

Progestin primed ovarian stimulation using dydrogesterone from day 7 of the cycle onwards in oocyte donation cycles: a longitudinal study.

RESEARCH QUESTION: Does a progestin-primed ovarian stimulation (PPOS) protocol with dydrogesterone from cycle day 7 yield similar outcomes compared with a gonadotrophin-releasing hormone (GnRH) antagonist protocol in the same oocyte donors? DESIGN: This retrospective longitudinal study included 128 cycles from 64 oocyte donors. All oocyte donors had the same type of gonadotrophin and daily dose in both stimulation cycles. The primary outcome was the number of cumulus-oocyte complexes (COC) retrieved. RESULTS: The number of COC retrieved (mean ± SD 19.7 ± 10.8 versus 19.2 ± 8.3; P = 0.5) and the number of metaphase II oocytes (15.5 ± 8.4 versus 16.2 ± 7.0; P = 0.19) were similar for the PPOS and GnRH antagonist protocols, respectively. The duration of stimulation (10.5 ± 1.5 days versus 10.8 ± 1.5 days; P = 0.14) and consumption of gonadotrophins (2271.9 ± 429.7 IU versus 2321.5 ± 403.4 IU; P = 0.2) were also comparable, without any cases of premature ovulation. Nevertheless, there was a significant difference in the total cost of medication per cycle: €898.3 ± 169.9 for the PPOS protocol versus €1196.4 ± 207.5 (P < 0.001) for the GnRH antagonist protocol. CONCLUSION: The number of oocytes retrieved and number of metaphase II oocytes were comparable in both stimulation protocols, with the advantage of significant cost reduction in favour of the PPOS protocol compared with the GnRH antagonist protocol. No cases of premature ovulation were observed, even when progestin was started later in the stimulation.

The combination of dydrogesterone and micronized vaginal progesterone can render serum progesterone level measurements on the day of embryo transfer and rescue attempts unnecessary in an HRT FET cycle.

PURPOSE: To evaluate the role of serum progesterone (P4) on the day of embryo transfer (ET) when dydrogesterone (DYD) and micronized vaginal progesterone (MVP) are combined as luteal phase support (LPS) in a hormone replacement therapy (HRT) frozen ET (FET) cycles. METHODS: Retrospective study, including single euploid HRT FET cycles with DYD and MVP as LPS and P4 measurement on ET day. Initially, patients with P4 levels < 10 ng/ml increased MVP to 400 mg/day; this "rescue" was abandoned later. RESULTS: 560 cycles of 507 couples were included. In 275 women, serum P4 level was < 10 ng/ml on the ET day. Among those with low P4 levels, MVP dose remained unchanged in 65 women (11.6%) and was increased in 210 women (37.5%). Women with P4 levels ≥ 10 ng/ml continued LPS without modification. Overall pregnancy rates in these groups were 61.5% (40/65), 54.8% (115/210), and 48.4% (138/285), respectively (p = n.s.). Association of serum P4 levels with ongoing pregnancy rates was analyzed in women without any additional MVP regardless of serum P4 levels (n = 350); multivariable analysis (adjusted for age, BMI, embryo quality (EQ)) did not show a significant association of serum P4 levels with OPR (OR 0.96, 95% CI 0.90-1.02; p = 0.185). Using inverse probability treatment weights, regression analysis in the weighted sample showed no significant association between P4 treatment groups and OP. Compared to fair EQ, the transfer of good EQ increased (OR 1.61, 95% CI 1.22-2.15; p = 0.001) and the transfer of a poor EQ decreased the odds of OP (OR 0.73, 95% CI 0.55-0.97; p = 0.029). CONCLUSION: In HRT FET cycle, using LPS with 300 mg/day MVP and 30 mg/day DYD, it appears that serum P4 measurement and increase of MVP in patients with P4 < 10 ng/ml are not necessary.

Role of Dydrogesterone for Luteal Phase Support in Assisted Reproduction.

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

Non-inferiority of progestin-primed ovarian stimulation versus GnRH antagonist protocol: A propensity score-weighted analysis.

PURPOSE: To evaluate the effectiveness of the progestin-primed ovarian stimulation (PPOS) protocol versus the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol in ovarian stimulation. METHODS: In this retrospective cohort study, we included 804 patients who were treated between January 1st, 2022, and July 1st, 2023. Outcomes of ovarian stimulation were compared between the PPOS (n = 206) and GnRH-ant (n = 598). The primary outcome was the number of good cleavage embryos. RESULTS: Baseline characteristics were comparable in both groups. In both unadjusted and adjusted analysis, the mean number of good cleavage embryos in PPOS (6.33) was non-inferior to GnRH-ant (6.44; unadjusted ratio of two means 1.02, 95%CI 0.92, 1.13). The trigger-day estradiol level in patients with PPOS was higher than in patients with GnRH-ant (4,420 vs 3,830 pg/ml, respectively) despite similar total follicle stimulating hormone dose and fewer days of ovarian stimulation. The number of oocytes, MII oocytes, cleavage and blastocyst embryos were comparable between the two protocols. After the first transfer of embryos, the clinical pregnancy rate and implantation rate were higher in the PPOS group, while the pregnancy rate and ongoing pregnancy were not significantly different. None of the PPOS patients had an unexpected LH surge, and serum LH levels decreased slightly during ovarian stimulation. CONCLUSIONS: The PPOS protocol with dydrogesterone provided similar embryo outcomes to the GnRH-ant protocol, with notable distinctions in clinical pregnancy and implantation rate. The serum LH concentration during ovarian stimulation using PPOS was well-controlled.

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

Abstract 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.

Oral dydrogesterone versus micronized vaginal progesterone for luteal phase support: a double-blind crossover study investigating pharmacokinetics and impact on the endometrium.

STUDY QUESTION: How do plasma progesterone (P) and dydrogesterone (D) concentrations together with endometrial histology, transcriptomic signatures, and immune cell composition differ when oral dydrogesterone (O-DYD) or micronized vaginal progesterone (MVP) is used for luteal phase support (LPS)? SUMMARY ANSWER: Although after O-DYD intake, even at steady-state, plasma D and 20αdihydrodydrogesterone (DHD) concentrations spiked in comparison to P concentrations, a similar endometrial signature was observed by histological and transcriptomic analysis of the endometrium. WHAT IS KNOWN ALREADY: O-DYD for LPS has been proven to be noninferior compared to MVP in two phase III randomized controlled trials. Additionally, a combined individual participant data and aggregate data meta-analysis indicated that a higher pregnancy rate and live birth rate may be obtained in women receiving O-DYD versus MVP for LPS in fresh IVF/ICSI cycles. Little data are available on the pharmacokinetic (PK) profiles of O-DYD versus MVP and their potential molecular differences at the level of the reproductive organs, particularly at the endometrial level. STUDY DESIGN, SIZE, DURATION: Thirty oocyte donors were planned to undergo two ovarian stimulation (OS) cycles with dual triggering (1.000 IU hCG + 0.2 mg triptorelin), each followed by 1 week of LPS: O-DYD or MVP, in a randomized, cross-over, double-blind, double-dummy fashion. On both the first and eighth days of LPS, serial blood samples upon first dosing were harvested for plasma D, DHD, and P concentration analyses. On Day 8 of LPS, an endometrial biopsy was collected for histologic examination, transcriptomics, and immune cell analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: All oocyte donors were <35 years old, had regular menstrual cycles, no intrauterine contraceptive device, anti-Müllerian hormone within normal range and a BMI ≤29 kg/m2. OS was performed on a GnRH antagonist protocol followed by dual triggering (1.000 IU hCG + 0.2 mg triptorelin) as soon as ≥3 follicles of 20 mm were present. Following oocyte retrieval, subjects initiated LPS consisting of MVP 200 mg or O-DYD 10 mg, both three times daily. D, DHD, and P plasma levels were measured using liquid chromatography-tandem mass spectrometry. Histological assessment was carried out using the Noyes criteria. Endometrial RNA-sequencing was performed for individual biopsies and differential gene expression was analyzed. Endometrial single-cell suspensions were created followed by flow cytometry for immune cell typing. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 21 women completed the entire study protocol. Subjects and stimulation characteristics were found to be similar between groups. Following the first dose of O-DYD, the average observed maximal plasma concentrations (Cmax) for D and DHD were 2.9 and 77 ng/ml, respectively. The Cmax for D and DHD was reached after 1.5 and 1.6 h (=Tmax), respectively. On the eighth day of LPS, the first administration of that day gave rise to a Cmax of 3.6 and 88 ng/ml for D and DHD, respectively. For both, the observed Tmax was 1.5 h. Following the first dose of MVP, the Cmax for P was 16 ng/ml with a Tmax of 4.2 h. On the eighth day of LPS, the first administration of that day showed a Cmax for P of 21 ng/ml with a Tmax of 7.3 h. All 42 biopsies showed endometrium in the secretory phase. The mean cycle day was 23.9 (±1.2) in the O-DYD group versus 24.0 (±1.3) in the MVP group. RNA-sequencing did not reveal significantly differentially expressed genes between samples of both study groups. The average Euclidean distance between samples following O-DYD was significantly lower than following MVP (respectively 12.1 versus 18.8, Mann-Whitney P = 6.98e-14). Immune cell profiling showed a decrease of CD3 T-cell, γδ T-cell, and B-cell frequencies after MVP treatment compared to O-DYD, while the frequency of natural killer (NK) cells was significantly increased. LIMITATIONS, REASONS FOR CAUTION: The main reason for caution is the small sample size, given the basic research nature of the project. The plasma concentrations are best estimates as this was not a formal PK study. Whole tissue bulk RNA-sequencing has been performed not correcting for bias caused by different tissue compositions across biopsies. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study comparing O-DYD/MVP, head-to-head, in a randomized design on a molecular level in IVF/ICSI. Plasma serum concentrations suggest that administration frequency is important, in addition to dose, specifically for O-DYD showing a rapid clearance. The molecular endometrial data are overall comparable and thus support the previously reported noninferior reproductive outcomes for O-DYD as compared to MVP. Further research is needed to explore the smaller intersample distance following O-DYD and the subtle changes detected in endometrial immune cells. STUDY FUNDING/COMPETING INTEREST(S): Not related to this work, C.Bl. has received honoraria for lectures, presentations, manuscript writing, educational events, or scientific advice from Abbott, Ferring, Organon, Cooper Surgical, Gedeon-Richter, IBSA, and Merck. H.T. has received honoraria for lectures, presentations, manuscript writing, educational events, or scientific advice from Abbott, Ferring, Cooper Surgical, Gedeon-Richter, Cook, and Goodlife. S.M. has received honoraria for lectures, presentations, educational events, or scientific advice from Abbott, Cooper Surgical, Gedeon-Richter, IBSA, and Merck and Oxolife. G.G. has received honoraria for lectures, presentations, educational events, or scientific advice from Merck, MSD, Organon, Ferring, Theramex, Gedeon-Richter, Abbott, Biosilu, ReprodWissen, Obseva, PregLem, Guerbet, Cooper, Igyxos, and OxoLife. S.V.-S. is listed as inventor on two patents (WO2019115755A1 and WO2022073973A1), which are not related to this work. TRIAL REGISTRATION NUMBER: EUDRACT 2018-000105-23.

A comparison of the effects of oral dydrogesterone and levonorgestrel-releasing intrauterine device on quality of life and sexual function in patients with abnormal uterine bleeding.

OBJECTIVE: The purpose of this study is to compare the effects of cyclic oral dydrogesterone treatment and levonorgestrel-releasing intrauterine device (LNG_IUD) on quality of life (QoL) and sexual function in patients diagnosed with abnormal uterine bleeding (AUB). STUDY DESIGN: The study was conducted at the University of Health Sciences Turkey Health Istanbul Kanuni Sultan Süleyman Training and Research Hospital, on 171 sexually active patients, aged 18-45, who were under a minimum of 6 months of treatment for AUB. 85 patients were treated with oral cyclic dydrogesterone, and 86 patients received LNG-IUD. Following a minimum of 6 months of treatment, these patients were recruited to the study and were asked to complete a 36-Item Short Form Survey (SF-36) and the Female Sexual Function Index (FSFI). RESULTS: When the FSFI scores of the patients were compared, it was observed that the total FSFI score was significantly higher in the cyclic dydrogesterone group (p < 0.05). Likewise, it was observed that sexual desire, arousal, and lubrication domains were significantly higher in the cyclic dydrogesterone group (p < 0.05). No significant differences were found between the treatment groups in 7 out of the 8 dimensions of SF-36. The energy/vitality dimension was found to be significantly higher in the cyclic dydrogesterone group. CONCLUSION: Total FSFI score, as well as sexual desire, arousal, and lubrication scores, were significantly higher in the cyclic dydrogesterone group compared to the LNG-IUD group indicating that cyclic dydrogesterone has a more positive impact on sexual function when compared to LNG-IUD.

The Role of Dydrogesterone in the Management of Luteal Phase Defect: A Comprehensive Review.

The luteal phase of the menstrual cycle is a pivotal period characterized by hormonal intricacies that lay the foundation for successful embryo implantation and early pregnancy development. Luteal phase defect (LPD), marked by abnormalities in luteal function, presents challenges that can impede reproductive outcomes. This comprehensive review article explores the role of dydrogesterone in LPD management, elucidating its mechanisms of action, evidence of efficacy, safety profile, and potential in combination therapies. Dydrogesterone, a synthetic progestogen, closely mirrors natural progesterone's actions, effectively supplementing the luteal phase and enhancing endometrial receptivity. Clinical studies demonstrate improved pregnancy rates, extended luteal phase support, and enhanced reproductive outcomes with dydrogesterone supplementation. Its favorable safety profile, minimal side effects, and reduced risk of unwanted hormonal effects contribute to its appeal. Furthermore, dydrogesterone's inclusion in international guidelines solidifies its importance in LPD management. Combination therapies, leveraging synergistic effects, offer a comprehensive approach. As gaps in knowledge persist, future research directions and personalized treatment strategies pave the way for a future where dydrogesterone stands as a beacon of hope in conquering the challenges of LPD and achieving successful reproductive outcomes.

Association of serum progesterone levels on the transfer day with pregnancy outcomes in hormone replacement frozen-thawed cycles with oral dydrogesterone for strengthened luteal phase support.

OBJECTIVE: To investigate the relationship between serum progesterone (P) levels on the day of blastocyst transfer and pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles using hormone replacement therapy (HRT) with oral dydrogesterone for strengthened luteal phase support (LPS). MATERIALS AND METHODS: This was a retrospective study including 1176 FET cycles. All patients received 40 mg of intramuscular (IM) P daily for endometrium transformation plus oral dydrogesterone 10 mg BID from transfer day for strengthened LPS. Pregnancy outcomes were compared between serum P levels on the transfer day ≥10 ng/ml and <10 ng/ml. Furthermore, cycles were divided into 10 groups by deciles of P and ongoing pregnancy rate (OPR) was calculated in each group. Analyses using deciles of serum P were completed to see if these could create further prognostic power. RESULTS: No differences were observed in clinical pregnancy rates (CPRs), OPRs and live birth rates (LBRs) between serum P levels ≥10 ng/ml and <10 ng/ml. Patients with serum P levels <5.65 ng/ml (10th percentile) had a significantly lower OPR (48.31% vs. 58.98%, p = 0.03) and LBR (43.22% vs. 57.75%, p = 0.003) than the rest of the patients. Multivariate logistic regression analysis showed serum P levels on the transfer day were not associated with pregnancy outcomes. CONCLUSION: Measuring serum P levels on the day of HRT-FET is of clinical importance. Lower serum P levels impact the success of HRT-FET cycles, suggesting that there may be a threshold below which it is difficult to improve pregnancy outcomes via oral dydrogesterone to strengthen LPS.

Comparison of Dydrogesterone and GnRH-a Effects After Laparoscopic Surgery in Patients with Stage III and IV Endometriosis.

Objective: To compare the spontaneous pregnancy rates between dydrogesterone and Gonadotropin-releasing hormone agonist (GnRH-a) treatments in patients with endometriosis stage III and IV after laparoscopy. Methods: The clinical data of patients with endometriosis stage III and IV administered laparoscopic surgery in our hospital from January 2018 to March 2020 were retrospectively analyzed. Totally 151 cases were divided into two groups according to postoperative medication, including the study (70 cases) and control (81 cases) groups treated with dydrogesterone and GnRH-a, respectively. The spontaneous pregnancy and subsequent pregnancy outcomes were assessed within 12 months. Results: Totally 49 patients had spontaneous pregnancy. Among them, there were 31 cases in the dydrogesterone group (spontaneous pregnancy rate of 44.3%, 31/70), including 25 live birth cases (35.7%, 25/70), 4 miscarriage cases, and 2 ectopic pregnancy cases. The time to conception was 1-10 months (median value of 5 months). Totally 18 cases in the GnRH-a group had spontaneous pregnancy (22.2%, 18/81), including 16 live birth cases (19.8%, 16/81). 81) and 2 miscarriage cases; the time to conception was 3-11 months (median value of 6 months). There were significant differences in spontaneous pregnancy rate and cumulative spontaneous pregnancy rate between the two groups (P = 0.005 and 0.003, respectively). Conclusion: Dydrogesterone after laparoscopic surgery in patients with endometriosis stage III and IV improved the natural pregnancy rate.

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

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

A comparative study between Dydrogesterone alone and combined with Non-Steroidal Anti-Inflammatory Drugs in the treatment of Mild Endometriosis.

Objective: To evaluate the clinical efficacy of dydrogesterone combined with non-steroidal anti-inflammatory drugs(NSAIDs) in the treatment of patients with mild endometriosis. Methods: This was a clinical comparative study. Eighty patients with mild endometriosis were recruited at Affiliated Hospital of Hebei University, randomly divided experimental group (n=40) and control group (n=40) from March 2022 to March 2023. Both groups started treatment with dydrogesterone on the 5th day of menstruation. Patients in the control group were treated with dydrogesterone monotherapy, while those in the experimental group were treated with mefenamic acid the basis of the therapy of the control group. The clinical efficacy, differences in the levels of humoral immune indexes, the levels of inflammatory factor and the incidence of adverse drug reactions of the two groups was compared and analyzed. Results: The efficacy of the experimental group was significantly higher than the control group, with a statistically significant difference(P=0.02). The levels of C3 and C4 in the experimental group after treatment were significantly lower than those in the control group, with a statistically significant difference(P=0.00). After treatment, TNF-a, CRP, IL-6 and other indexes in the experimental group were significantly lower than those in the control group, with statistically significant differences(P=0.00). The incidence of adverse reactions after treatment had no statistically significant difference(P=0.45). Conclusion: Dydrogesterone combined with non-steroidal anti-inflammatory drugs is a safe and effective treatment for patients with endometriosis. It can improve various obvious curative effects, such as marked relief of pain symptoms, reduction of complement and inflammatory factor levels without a significant increase in adverse reactions.