Search

Abstract Background Preterm birth (PTB) remains a significant problem in obstetric care. Progesterone supplements are believed to reduce the rate of preterm labor, but formulation, type of administration, and dosage varies in different studies. This study was performed to compare oral Dydrogesterone with intramuscular 17α-hydroxyprogesterone caproate (17α-OHPC) administration in prevention of PTB. Methods In this randomized clinical trial, we studied 150 women with singleton pregnancy in 28Th-34Th Gestational week, who had received tocolytic treatment for preterm labor. Participants were divided to receive 30 mg oral Dydrogesterone daily, 250 mg intramuscular 17α-OHPC weekly, or no intervention (control group). All treatments were continued until 37Th Week or delivery, whichever occurred earlier. Obstetric outcomes, including latency period, gestational age at delivery, birth weight, neonatal intensive care unit (NICU) admission, and neonatal mortality were recorded. All patients were monitored biweekly until delivery. Results Baseline gestational age was not significantly different between groups. Latency period was significantly longer in the progesterone group compared with Dydrogesterone and control groups (41.06 ± 17.29 vs. 29.44 ± 15.6 and 22.20 ± 4.51 days, respectively; P

Abstract Background Progestin-primed ovarian stimulation (PPOS) has been used in infertility cases in recent years, and several reports have stated that it has oocyte collection results similar to those of gonadotropin-releasing hormone antagonist (GnRH-ant) protocol. For emergency fertility preservation, random-start ovarian stimulation is usually recommended. Therefore we compared the clinical outcomes of random-start PPOS with those of conventional random-start GnRH-ant protocols in fertility-preserving cases. Methods We retrospectively examined 86 cycles of oocyte collection, of which 56 were random-start GnRH-ant and 30 were random-start PPOS for fertility preservation at our hospital between January 2016 and April 2021. The primary outcome was the number of mature oocytes per cycle. The secondary outcome was the number of vitrified blastocysts per cycle for embryo freezing cases. Results No significant differences were noted in the number of days of stimulation, total dose of gonadotropin preparation, and the number of mature oocytes and vitrified blastocysts. The number of hospital visits for monitoring was significantly lower in the PPOS group. The start of menstruation before oocyte collection was significantly less in the PPOS group. Conclusions Random-start PPOS and GnRH-ant were similar in oocyte collection results. PPOS can reduce the number of hospital visits, thus reducing patient stress. PPOS at the start of the luteal phase can prevent the start of menstruation during ovarian stimulation.

IntroductionThe number of frozen embryo transfers increased substantially in recent years. To increase the chances of implantation, endometrial receptivity and embryo competency must be synchronized. Maturation of the endometrium is facilitated by sequential administration of estrogens, followed by administration of progesterone prior to embryo transfer. The use of progesterone is crucial for pregnancy outcomes. This study compares the reproductive outcomes and tolerability of five different regimens of hormonal luteal phase support in artificial frozen embryo transfer cycles, with the objective of determining the best progesterone luteal phase support in this context.DesignThis is a single-center retrospective cohort study of all women undergoing frozen embryo transfers between 2013 and 2019. After sufficient endometrial thickness was achieved by estradiol, luteal phase support was initiated. The following five different progesterone applications were compared: 1) oral dydrogesterone (30 mg/day), 2) vaginal micronized progesterone gel (90 mg/day), 3) dydrogesterone (20 mg/day) plus micronized progesterone gel (90 mg/day) (dydrogesterone + micronized progesterone gel), 4) micronized progesterone capsules (600 mg/day), and (5) subcutaneous injection of progesterone 25 mg/day (subcutan-P4). The vaginal micronized progesterone gel application served as the reference group. Ultrasound was performed after 12-15 days of oral estrogen (≥4 mg/day) administration. If the endometrial thickness was ≥7 mm, luteal phase support was started, up to six days before frozen embryo transfer, depending on the development of the frozen embryo. The primary outcome was the clinical pregnancy rate. Secondary outcomes included live birth rate, ongoing pregnancy, and miscarriage and biochemical pregnancy rate.ResultsIn total, 391 cycles were included in the study (median age of study participants 35 years; IQR 32-38 years, range 26–46 years). The proportions of blastocysts and single transferred embryos were lower in the micronized progesterone gel group. Differences among the five groups in other baseline characteristics were not significant. Multiple logistic regression analysis, adjusting for pre-defined covariates, showed that the clinical pregnancy rates were higher in the oral dydrogesterone only group (OR = 2.87, 95% CI 1.38–6.00, p=0.005) and in the dydrogesterone + micronized progesterone gel group (OR = 5.19, 95% CI 1.76–15.36, p = 0.003) compared to micronized progesterone gel alone. The live birth rate was higher in the oral dydrogesterone-only group (OR = 2.58; 95% CI 1.11–6.00; p=0.028) and showed no difference in the smaller dydrogesterone + micronized progesterone gel group (OR = 2.49; 95% CI 0.74–8.38; p=0.14) compared with the reference group.ConclusionThe application of dydrogesterone in addition to micronized progesterone gel was associated with higher clinical pregnancy rate and live birth rate and then the use of micronized progesterone gel alone. DYD should be evaluated as a promising LPS option in FET Cycles.

Abstract Purpose Vaginal progesterone (VP) alone has been used as luteal support (LS) in HRT‐FET cycles without measuring serum progesterone concentrations (SPC) because it can achieve adequate intrauterine progesterone levels. However, several reports showed that the co‐administration of progestin produced better outcomes than VP alone. We tried to address this discrepancy, focusing on SPC. Methods VP was given to 180 women undergoing HRT‐FET. We measured SPC when pregnancy was diagnosed on day 14 of LS. We compared assisted reproductive technology outcomes between VP alone versus VP + dydrogesterone (D). Results When using VP alone, average SPC in the miscarriage cases (9.6 ng/mL) were significantly lower compared with the ongoing pregnancy (OP) cases (14.7 ng/mL). The cut‐off value for progesterone, 10.7 ng/mL, was a good predictor for the subsequent course of the pregnancy. Of 76 women receiving D ± VP from the start of LS and achieving a pregnancy, the numbers of OP were 44 (84.6%) in SPC ≥ 10.7 ng/mL and 20 (83.3%) in SPC ≤ 10.7 ng/mL with no significant difference. Conclusion VP alone resulted in lower SPC in some pregnant women in HRT‐FET cycles and exhibited a lower OP rate. The co‐administration of D improved an OP rate of low progesterone cases to the level comparable with non‐low progesterone cases.

What should be the optimal route of luteal support in programmed frozen embryo transfer (FET) cycles? This was a randomized, parallel, phase IV pilot trial with three groups of women undergoing FET along with hormone replacement therapy for endometrial preparation at a tertiary private IVF centre (NCT03948022). Women with at least one autologous cryopreserved blastocyst were included. After preparing the endometrium with oestradiol, 151 women were randomly assigned to one of the following three progesterone arms before embryo transfer: oral (10 mg) dydrogesterone (DYD), total daily dose 40 mg (n = 52); 8% (90 mg) progesterone vaginal gel (VAG), total daily dose 180 mg (n = 55); or intramuscular progesterone (IMP) 50 mg/ml in oil, total daily dose 100 mg (n = 44). One or two vitrified-warmed blastocysts were transferred after 5 days' progesterone support. Baseline demographic features and embryological data were comparable among the groups. Ongoing pregnancy rates (40.4%, 38.2% and 45.5% in the DYD, VAG and IMP arms; P = 0.76) and live birth rates (40.4%, 38.2% and 43.2% in the DYD, VAG and IMP arms, P = 0.61) were statistically similar. Biochemical pregnancy rates and clinical miscarriage rates were also statistically similar among the groups. Significantly more patients with at least one side effect and moderate-to-severe side effects were documented in the IMP arm than the other groups (P < 0.001). Treatment with 40 mg/day oral DYD, 180 mg/day progesterone VAG gel or 100 mg/day IMP revealed similar reproductive outcomes in programmed FET cycles. Side effects were significantly more frequent in the IMP arm. [ABSTRACT FROM AUTHOR]

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

Objective: To observe the clinical efficacy of Honghua Xiaoyao tablets combined with Dydrogesterone in the treatment of menstrual irregularities, and to analyze its effect on hormone level and hemorheology. Methods: 68 patients with Menstrual Irregularities who were treated in The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine from April 2019 to February 2021 were selected, and they were randomly divided into control group (n=34)and observation group (n=34)according to random number table method. Patients in the control group were treated with Dydrogesterone tablets, while patients in the observation group were treated with Honghua Xiaoyao tablets combined with Dydrogesterone tablets. The clinical total effective rate, hormone level,hemorheology, related scale score and adverse reactions of the two groups were observed. Results: Compared with 61.76% (21/34)of the control group, the clinical total effective rate of the observation group was 88.24% (30/34)further increased (P<0.05). Compared with the control group at 2 cycles after treatment, the observation group had lower scores on Pictorialblood loss assessment chart (PBAC), higher scores on Chinese quality of life scale (ChQOL), lower levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), whole blood high and low shear viscosity (HBV and LBV), fibrinogen (FIB), and higher levels of progesterone (P)and estradiol (E2)(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion: Honghua Xiaoyao tablets combined with Dydrogesterone can effectively improve the clinical symptoms of patients with Menstrual Irregularities, and improve the quality of life of patients, which may be related to the improvement of hormone levels and hemorheology. [ABSTRACT FROM AUTHOR]

Do differences exist in euploidy rates in preimplantation genetic testing for aneuploidy (PGT-A) cycles with oral dydrogesterone primed ovarian stimulation protocol or the flexible gonadotropin-releasing hormone (GnRH) antagonist protocol? A retrospective cohort study. Patients received the oral dydrogesterone or the GnRH antagonist in the first PGT-A cycle between November 2017 and May 2019. Propensity matching was used to identify a propensity-matched antagonist group based on age, BMI and AMH with a 1:1 ratio. The primary outcome was the rate of euploid embryos. A total of 780 cycles were included, consisting of 390 cycles receiving dydrogesterone and 390 cycles receiving GnRH antagonist protocol. No significant difference was found in patient baseline and cycle characteristics in the two groups. No statistical difference was found in the number of oocytes retrieved, metaphase II oocytes, embryos biopsied and embryo testing between the two groups. As no biopsy blastocysts formed in some cycles, only 262 cycles in the study group and 263 cycles in the antagonist group received next-generation sequencing testing, respectively. Similar to our overall data, the euploid rate per embryo biopsied was not significantly different. No significant differences were found between the two groups after stratifying by age and controlling for PGT-A testing modality. Ovulation inhibition by exogenous progestins in ovarian stimulation cycles should, therefore, be considered a valid modality in freeze-all PGT-A cycles, in view of its demonstrated effectiveness and known safety enhancement. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the efficacies of Femoston and Dydrogesterone therapy in patients with incomplete abortions., Methods: Patients with incomplete abortions were included if they preferred medication over surgical intervention. The participants were categorized into three groups: the Femoston group received Femoston, the Dydrogesterone group was administered Dydrogesterone, and the control group was followed up without treatment. Basic clinical information, complete abortion success rate, and menstrual recovery rate were collected to evaluate the efficacy of Femoston and Dydrogesterone in patients with incomplete abortions., Results: We analyzed 332 patients with incomplete abortions. The success rate of complete abortion was significantly higher in the Femoston group than in the control group (relative risk (RR)=1.708, 95% CI 1.304-2.237, p  = .001) and the Dydrogesterone group (RR = 1.200, 95% CI 1.015-1.418, p  = .023). The effectiveness of Dydrogesterone was also significantly higher than that in the control group (RR = 1.439, 95% CI 1.068-1.938, p  = .015). After 60 days, the rate of menstrual recovery in the Femoston group was significantly higher than that in the control group (RR =1.322, 95% CI 1.103-1.609, p  = .001), while the rate in the Dydrogesterone group was significantly lower than that in the Femoston group (RR =1.200, 95% CI 1.035-1.391, p  = .009)., Conclusions: Femoston and Dydrogesterone were effective in treating incomplete abortions, with Femoston being more effective. Patients receiving Femoston had shorter menstrual recovery times than those receiving dydrogesterone. Therefore, Femoston and Dydrogesterone are potential treatment options for incomplete abortion, with Femoston being the more effective.

Background : Progestin-primed ovarian stimulation (PPOS) stimulates ovaries to block the premature surge of luteinizing hormone (LH) by using micronized progesterone or a progestin during the follicular phase instead of the conventional gonadotropin-releasing hormone (GnRH) analogues or GnRH antagonists downregulating LH to obtain multi-follicle engagement. Current work aims to assess the influence of progestogen treatment on ovarian stimulation and the ability to control LH surge, its efficacy and suitability in retrieving oocytes, without affecting the embryo quality and its benefit among infertile women long-term outcomes on children compared to standard stimulation protocols. Materials and Methods: The literature review used the randomized control trials published in the Pubmed database from January 2015 to April 2021. To generate the citation list, the following keywords were used: 'progestin-primed ovarian stimulation', 'PPOS', 'micronized progesterone', 'medroxyprogesterone', and/or 'dydrogesterone'. The selected articles analyzed the cohort, intervention, and scheme of the progestin-primed ovarian stimulation protocol in controlled ovarian stimulation (COS) for in-vitro fertilization (IVF)/intra cytoplasmic sperm injection (ICSI) used in Assisted Reproductive Technologies (ART). Results: Overall we concluded that PPOS for IVF/ICSI in ART results in a higher number of obtained embryos, lower incidence of OHSS, equal duration of stimulation, number of retrieved oocytes, and number of MII oocytes. It is also suggested that long-term safety in children shows no significant difference between the study and control groups. Conclusions: Despite the outcomes of progestin stimulation cycles among all cohorts, we concluded that poor ovarian responders, patients with PCOS, women of advanced age and oocyte donors benefit the most from using PPOS.

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.

The etiopathology of recurrent miscarriage is a combination of various factors, including chromosomal defects, genetic or structural abnormalities, endocrine abnormalities, infections, immune dysfunction, thrombophilia disorders, antiphospholipid syndrome, and unexplained causes. It has long been known that progesterone is needed to maintain pregnancy and its physiological development. Insufficient progesterone secretion and its low level in the blood serum in early pregnancy is associated with the threat of miscarriage and loss of pregnancy at a later stage – up to 16 weeks of gestation. The effectiveness of the vaginal micronized progesterone (VMP) at a dose of 400 mg twice a day in the first trimester of pregnancy was evaluated in two recent large high-quality multicenter placebo-controlled studies, one of which included pregnant women with recurrent miscarriages of unexplained origin (PROMISE Trial), and the other study included women with early pregnancy loss (PRISM Trial). A key finding, pioneered in the PROMISE study and later confirmed in the PRISM study, was that VMP treatment associated with an increase in live births in line with the number of previous miscarriages. It has been shown that there is no evidence regarding safety concerns with natural micronized progesterone. Treatment with an VMP should be recommended for women with bleeding in early pregnancy and a history of one or more miscarriages. The recommended treatment regimen is 400 mg 2 times a day (800 mg/day) intravaginal, starting from the moment bleeding is detected up to 16 weeks of pregnancy. In the future, there remains uncertainty effectiveness and safety of alternative progestogens (dydrogesterone) for the treatment of women at high risk of threatened abortion and recurrent miscarriage. It is important that dydrogesterone is a synthetic progestin, its structure is significantly different from natural progesterone, and therefore it is necessary to unequivocally prove the short- and long-term safety of this drug before considering its use in clinical practice.

ObjectiveThe need of luteal support after FET is no longer to be proven. Different routes of progesterone administration are available with interindividual differences in metabolization and serum progesterone levels, the latter being highly correlated with pregnancy and delivery rates. The administration of 2 different routes of progestogen significantly improves success rates in FET. The aim of the current study was to investigate the added value to combine intramuscular administration of progesterone to dydrogesterone in fresh embryo transfer.MethodsThis is a retrospective study from prospectively collected data. Patient, aged between 18 and 43 years old, had received a fresh blastocyst transfer between January 2021 and June 2021. In the first group, all patients received only oral dydrogesterone 10mg, three times a day, beginning the evening of oocyte retrieval. In the second group, patients received, in addition to dydrogesterone, a weekly intramuscular injection of progesterone started the day of embryo transfer. Primary endpoint was ongoing pregnancy rate.Results171 fresh single blastocyst transfers have been performed during this period. 82 patients were included in “dydrogesterone only” and 89 patients in “dydrogesterone + IM”. Our two groups were comparable except for body mass index. After adjustment on BMI, our two groups were comparable regarding implantation rate, early pregnancy rate (46.1 versus 54.9, OR 1.44 [0.78; 2.67], p=0.25) miscarriage rate, ongoing pregnancy rate (30.3 versus 43.9, OR 1.85 [0.97; 3.53] p= 0.06).ConclusionUsing systematically long acting intramuscular progesterone injection in addition to oral dydrogesterone as luteal phase support seems to have no significant impact on IVF outcomes when a single fresh blastocyst transfer is performed.

No data support the suggestion that first-trimester dydrogesterone use increases the risk of fetal abnormalities; however, two low-quality retrospective studies (one retracted by the journal) have suggested such a link. A scoping review and meta-analysis were carried out to address this discrepancy. The literature was reviewed but it was not possible to identify any evidence of a plausible mechanism for potential causality between dydrogesterone and fetal abnormalities. To investigate whether any evidence existed, a preliminary meta-analysis was undertaken of clinical studies published since 2005 on first-trimester dydrogesterone use with assessment of fetal abnormalities. A fixed effects model was used to determine pooled odds ratios with 95% confidence intervals (95% CI). From 83 articles identified, six randomized controlled trials were included. Pooled risk ratios (RR) for maternal dydrogesterone use and fetal abnormalities gave a RR approaching 1 (RR 0.96; 95% CI 0.57, 1.62), confirming previous conclusions of no causal association between fetal abnormalities and first-trimester dydrogesterone use. Physicians, scientists and journal reviewers should exercise due diligence to prevent promulgation of retracted data. We are confident in using dydrogesterone, if indicated, in the treatment of threatened or recurrent miscarriage, and believe that its favourable safety profile should extend to its appropriate use in assisted reproductive technologies. [ABSTRACT FROM AUTHOR]

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. 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. [ABSTRACT FROM AUTHOR]

Abstract Purpose To assess the efficacy and safety of dydrogesterone in Japanese women with ovarian endometrioma in a real‐world setting. Methods The post‐marketing study involved 15 sites in Japan. Dydrogesterone 10 mg twice daily orally was administered for 21 days (day 5‐25 of each menstrual cycle) for 4 cycles. The primary outcome measure was the change in ovarian endometrioma volume from baseline. Secondary outcome measures included total dysmenorrhea score (0 = absent to 3 = severe), severity of dysmenorrhea pain [0‐10cm visual analog scale (VAS)], serum carbohydrate antigen 125 (CA‐125) levels, and safety. Results The study group comprised women with an endometrioma aged 20 to 49 (47.4% cases aged ≥40 years). Endometrioma volume was reduced in 50% (26/52), unchanged in 25% (13/52), and increased in 25% (13/52) of women from baseline to the end of cycle 5; three‐quarters of patients thus had either reduced or unchanged ovarian endometrioma volume. Dydrogesterone significantly reduced total dysmenorrhea scores and severity of dysmenorrhea pain VAS during treatment compared with baseline. CA‐125 levels were not significantly changed during the study. The incidence of adverse events and adverse drug reactions in 59 subjects was 13.6% and 11.9%. Conclusions Dydrogesterone prevented an increase in endometrioma size in many women, and it also significantly improved total dysmenorrhea scores and severity of dysmenorrhea pain, and was well tolerated. The ClinicalTrials.gov identifier of the study was NCT02921763.

Dysmenorrhoea and intermenstrual pelvic pain are the most common symptoms of clinical manifestations of adenomyosis, which significantly impair the quality of women’s life. Adequate and long-term pain correction and alternative therapeutic approaches became extremely important for patients with adenomyosis during the COVID-19 pandemic. Research objective: to examine the clinical efficacy of nitric oxide donor (L-arginine) in the complex treatment of pelvic pain syndrome associated with adenomyosis. Materials and methods. The study included 63 women diagnosed with adenomyosis. Patients were divided into 2 groups by simple randomization: I (D) group (n = 31) received dydrogesterone 30 mg from 5 to 25 days of the menstrual cycle, II (D+T) group (n = 32) in addition to dydrogesterone received a nitric oxide donor L-arginine (Тivortin) according to the scheme. Pelvic pain was assessed before treatment with a Visual Analogue Scale and a McGill Pain Questionnaire, and an assessment of the overall pain impact on women's well-being was based on the SF-36 Health Status Survey. The effectiveness of pelvic pain therapy was assessed after the first and third months of treatment, as well as three months after the end of therapy with the above methods. Results. Researchers achieved a therapeutic effect in the treatment of chronic pelvic pain in both study groups, but in group II (D + T) after 3 months of treatment there was a significant reduction in pelvic pain, while patients of the standard therapy group have prolonged progestogen intake. There was a further improvement in the clinical condition in group I (D) after 6 months of follow-up, as well as no recurrence of pain in group II (D + T). Conclusions. The results of study demonstrate a significant effect of Tivortin as part of complex therapy on the rate of achievement and duration of therapeutic effect in the treatment of pelvic pain associated with adenomyosis.

The aim of this study is to develop a universal, rapid and affordable method for the identification of dydrogesterone, troxerutin, and ademetionine in drugs by multisensor digital colorimetry using a unique two-dimensional code. The developed approach can be applied to rapid detection of counterfeit drugs at the preliminary stage of the analysis (before using more expensive specialized equipment).Materials and methods. To implement the proposed approach, the substances of dydrogesterone (“Abbott Biologicals B.V.”, Netherlands), troxerutin (JSC “Interfarma”, Prague, Czech Republic) and ademetionine (LLC “Farmamed”, Moscow, Russia), troxerutin capsules 300 mg (LLC “Pranafarm”, Samara, Russia), lyophilisate for an intravenous solution and the intramuscular administration “Heptral”® (ademetionine) 400 mg (“Abbott Laboratories”, GMBH, Germany), tablets “Duphaston”® (dydrogesterone) 10 mg (“Abbott Healthcare Products B.V.”, Netherlands), were used. A multisensor colorimetry method has been implemented using the following set of 8 sensors (C1-C8): an intact solution – a 96% (v/v) aqueous ethanol solution – C1; 1 mM alcoholic solution of anthraquinone green (CAS#4403-90-1) – C2; a 0.2% aqueous solution of 3-methylbenzothiazolinone hydrazone (CAS#1128-67-2) – C3; a 0.2% methyl orange aqueous solution (CAS#547-58-0) – C4; a 1 mM alcoholic solution of sulforhodamine B (CAS#3520-42-1) – C5; a 1 mM alcoholic solution of 1-hydroxypyrene (CAS#5315-79-7) – C6; 1 mM alcoholic solution of allura red AC (CAS#25956-17-6) – C7; a 1 mM aqueous solution of iron (III) chloride – C8. Transparent flat-bottomed polypropylene plates with 96 cells, with a cell volume of 350 µl (Thermo Fischer Scientific, USA, cat. No. 430341) were used as a base for the chip. For obtaining raster images, an Epson Perfection 1670 office flatbed scanner (CCD-matrix) with a removable cover was used. The obtained digital images of the cells were processed using the ImageJ software (Wayne Rasband, National Institutes of Health, USA; http://imagej.nih.gov/ij) with a 24-bit RGB color model (8 bits per channel).Results. The adequacy of the developed approach was confirmed by the analysis of the above-listed drugs. It has been shown that the results obtained have no statistically significant differences from the values determined by the spectrophotometric method.Conclusion. The possibility of using multisensor digital colorimetry for pharmaceutical analysis has been shown. The developed methods for the identification of the active substances can serve as a good supplement to the more expensive traditional methods.

In the age of broad medical options, women’s health has received sufficient attention. The different periods of a woman’s life are characterised by specific physiological changes, based on the age-related characteristics of the reproductive system. The onset of menopause can have a negative impact on health in varying degrees. Clinicians have a clear understanding of the effects of estrogen deficiency and the therapeutic options for managing it with menopausal hormone therapy (MHT) and alternative methods of treatment. However, to date, methods for optimising and individualising the correction of menopausal disorders continue to improve. The individualization of MHT is aimed at increasing the efficacy of menopausal management and minimizing possible adverse events. Individualization is based on the selection of a hormone drug taking into account age, menopausal status, somatic health of the woman and her main complaints against the background of estrogen deficiency. The next stage of transformation of MHT concerned the composition of the drugs and the doses of their components. The evolution of the estrogenic component began with the use of conjugated estrogens, whose metabolism is not fully clarified, and stopped at the production of bioidentical estrogens (17p-estradiol and estradiol valerate), which in their structure are as close as possible to ovarian estradiol. The type, dose and combination of estrogens and progestogens determine the severity and specificity of the effect of the hormone. This article will present a clinical case study of the low- and ultra-low-dose combination of 17p-estradiol and dydrogesterone (E/DG).

This study aimed to evaluate the efficacy and safety of ultra-low-dose estradiol plus dydrogesterone for vasomotor symptoms in postmenopausal women in China (trial registration CTR20160689). A total of 332 patients were randomized to continuous combined estradiol 0.5 mg + dydrogesterone 2.5 mg or placebo for 12 weeks. The primary efficacy endpoint was change in the number of hot flushes per day from baseline to end of treatment. Secondary efficacy endpoints included change in the number of moderate-to-severe hot flushes per day, menopausal symptoms from baseline and quality of life. Between baseline and end of treatment, change in the mean number of hot flushes per day was −5.9 (95% confidence interval [CI] − 6.6, −5.2) with estradiol + dydrogesterone and −4.5 (95% CI −5.1, −3.8) with placebo, with a mean difference of −1.4 hot flushes per day (95% CI −2.2, −0.7; p < 0.001). Significant differences in favor of estradiol + dydrogesterone were also observed in several secondary efficacy endpoints. The study treatment was well tolerated. Continuous combined estradiol 0.5 mg + dydrogesterone 2.5 mg reduced hot flushes in postmenopausal women in China. This ultra-low-dose regimen provides an additional option for women experiencing the vasomotor symptoms of menopause. These data are consistent with previous results in other populations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The present I in vitro i investigation therefore was designed to test for potential interference of DYD/DHD with routinely and widely spread used P4 assays over a range of concentrations of DYD/DHD and P4. Keywords: -dihydrodydrogesterone; cross-reaction; Duphaston; dydrogesterone; interference; progesterone immunoassay EN -dihydrodydrogesterone cross-reaction Duphaston dydrogesterone interference progesterone immunoassay 1039 1045 7 05/26/22 20220601 NES 220601 Introduction Progesterone (P4) is an endogenous steroid hormone which is mainly secreted by the corpus luteum, a temporary endocrine structure in the ovary, and by the placenta during pregnancy. Graph: Figure 2: Graphical presentation of the recovery of progesterone (P4) in the samples with H(igh), M(edium), and L(ow) P4 concentration after addition of DYD/DHD at H(igh) and M(edium) concentration in the seven tested assay. For each sample to which DYD and DHD were added, the percent recovery was calculated against the corresponding P4 plasma sample to which no DYD and DHD was added. [Extracted from the article]

To provide an evidence-based safety and tolerability overview of dydrogesterone under various progesterone-deficient conditions as a commemoration of its role in managing women's reproductive health over the past 60 years. To identify relevant publications, we used a semi-systematic approach, which included performing a structured search through the PubMed and Cochrane central databases as well as an unstructured search for publications published in English from 2010 onward with human clinical data. A total of 32 relevant clinical studies were identified. Results were reported in the context of overall adverse events (AEs) and segregated according to various progesterone-deficient conditions. AEs concerning breasts (breast cancer risk), the endometrium (endometrial cancer risk), venous thromboembolism risk, and cardiovascular risk were found to be minimal when dydrogesterone was used as part of a menopausal hormone therapy regimen lasting ≤260 weeks. Vagina-related AEs, such as bleeding, discharge, irritation, and difficult coitus, occurred less frequently with dydrogesterone when used as luteal phase support in the context of assisted reproductive techniques (ARTs). However, other common AEs, such as headache, dizziness, abdominal pain, flatulence, and nausea, occurred more frequently with dydrogesterone. No maternal complications or congenital anomalies could be linked to dydrogesterone usage during ARTs or during early pregnancy to prevent recurrent miscarriages. Studies on dydrogesterone in endometriosis and premenstrual syndrome remain scarce. Post-approval, dydrogesterone has displayed a favorable safety and tolerability profile during its 60-year use, which is reassuring, considering its important role in managing women's reproductive health. [ABSTRACT FROM AUTHOR]

Introduction: Despite the positive evidence on the effect of progesterone on protection of pregnancy in patients with threatened abortion, the results of studies regarding its drug type have been controversial. This study was performed with aim to compare the effect of vaginal progesterone and dydrogesterone on pregnancy outcome in cases with threatened abortion. Methods: In this single-blind randomized clinical trial, 160 pregnant women with threatened abortion who referred to Qazvin Kowsar Hospital in 2018 were randomly assigned to receive dydrogesterone (Duphaston) 10 mg twice daily or vaginal progesterone (Cyclogest) 400 mg daily. Finally, pregnancy outcomes were compared between the two groups. Data were analyzed by SPSS software (version 18) and Chi-square, independent t-test and Mann-Whitney tests. P0.05). In addition, incidence of preeclampsia, gestational diabetes mellitus, placenta previa and intrauterine fetal death as well as neonatal weight were not significantly different between the two groups (P >0.05). Finally, maternal and neonatal complications showed no significant difference between the two groups (P = 0.675). Conclusion: Pregnancy outcomes after administration of dydrogesterone are not different with vaginal progesterone in the treatment of threatened abortion.

Aim. To investigate the modern condition of the problem of infertility and obstetric complications in endometriosis and the main management aspects of women with endometriosis in pregnancy planning. Materials and methods. The article presents a systematic literature review on the results of search for studies in electronic databases MEDLINE, PubMed, EMBASE, Cochrane Library and eLibrary. Results. Endometriosis is one of the most common causes of infertility. A cascade of adverse reactions caused by endometriosis prevents a successful pregnancy. Currently, there is an evidence that patients with endometriosis have a high risk of several obstetric complications, such as spontaneous miscarriage, premature birth, preeclampsia, low birth weight and gestational diabetes. Progestogens belong to the first line of therapy of endometriosis, and dydrogesterone is a drug that meets all the necessary requirements. The use of dydrogesterone in the treatment of endometriosis helps to reduce the negative symptoms of endometriosis, improve the quality of life and increase fertility. Dydrogesterone is the only progestogen that has two effective regimens for endometriosis, which allows prescribing therapy for women who are planning pregnancy and for those who have already realized their reproductive plans. Dydrogesterone is the only progestogen that has been suggested to increase the chances of pregnancy in women with endometriosis. Dydrogesterone has been shown to be effective in supporting the luteal phase in ART programs, treating threatening and recurrent miscarriages. Conclusion. Endometriosis is associated with infertility and a high risk of obstetric complications. Dydrogesterone has a number of advantages compared to other progestogens.

Abstract 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: NCT 03935152 , registered on May 2,2019).

Pregnancy is not nearly as successful as laypersons might assume, challenged as it is by several complications such as threatened abortion, spontaneous miscarriage, preeclampsia, and preterm delivery, among others. The maternal immune system has been shown to contribute to the etiopathogenesis of some of these pregnancy complications. Pro-inflammatory and anti-inflammatory cytokines have been studied for their effects on pregnancy because of their powerful and versatile effects on cells and tissues. This review addresses the relationship between pro-inflammatory cytokines and recurrent miscarriage, which is an important complication of pregnancy. References for this review were identified by using PRISMA-IPD (Preferred Reporting Items for a Systematic Review and Meta-analysis of Individual Participant Data) Guidelines by conducting searches for published articles from January 1, 1990 until March 1, 2020 in the following databases: PubMed, Google Scholar, and MEDLINE via OVID by the use of the search terms “recurrent spontaneous miscarriage,” “cytokines,” “progesterone,” “progestogen,” “dydrogesterone,” and “immunomodulation.” This review also presents the proposed mechanisms of action of pro-inflammatory cytokines in pregnancy loss, and then goes on to discuss the modulation of cytokine profiles to a state that is favorable to the success of pregnancy. In addition to its indispensable endocrinologic role of progesterone in pregnancy, it also has some intriguing immunomodulatory capabilities. We then summarize studies that show that progesterone and dydrogesterone, an orally-administered progestogen, suppress the production of pro-inflammatory cytokines and enhance the production of anti-inflammatory cytokines before mentioning clinical studies on progestogen supplementation. These studies support the contention that progestogens should be explored for the immunotherapeutic management of pregnancy complications.

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

Objective: To study Effect of dydrogesterone combined with oral progesterone capsule on serum statin A and sex hormones in patients with threatened abortion with luteal insufficiency. Methods: 125 patients with threatened abortion with luteal insufficiency treated in our hospital from September 2018 to September 2020 were divided into experimental group (n=63) and control group (n=62) by random number table method. The control group was treated with progesterone capsule, and the experimental group was treated with dydrogesterone on the basis of the control group. Clinical efficacy, statin A, estradiol (E2), progesterone (P), human chorionic gonadotropin (HCG), improvement of clinical symptoms, pregnancy outcome and the incidence of adverse reactions were compared between the two groups. Results: After treatment, the total effective rate between the two groups was significantly different (P<0.05). Before treatment, there were no significant differences in serum statin A, E2, P and HCG between the experimental group and the control group. After treatment, the serum levels of statin A, E2, P and HCG in experimental group and control group were increased with the passage of time, and the difference was significant(P<0.05). The hemostasis time, improvement time of abdominal pain and improvement time of low back pain in experimental group were significantly lower than those in control group, the differences were significant (P<0.05); The success rate of fetal preservation, neonatal body weight and Apgar score of neonates in experimental group were significantly higher than those in control group (P<0.05). The total incidence of ADR in the two groups was 7.94% and 9.68% (P>0.05). Conclusion: In patients with threatened abortion with luteal insufficiency, the application of dydrogesterone combined with oral progesterone capsule has significant effect, which may be related to the effective improvement of serum statin A and sex hormone levels without increasing adverse reactions. [ABSTRACT FROM AUTHOR]

This matched cohort study was retrospectively performed, with cycles extracted from freeze-all-IVF treatments performed between March and November 2019, to compare the efficacy of flexible-start dydrogesterone (DYG) co-treatment ovarian stimulations (OS) with flexible-start medroxyprogesterone acetate (MPA) co-treatment OS. DYG cycles were matched 1:1 with MPA cycles using female age and antral follicle count, resulting in 236 matched cycles. OS durations and total FSH doses were similar in DYG and MPA OS cycles. The numbers of mature oocytes retrieved were similar; however, the mature oocyte retrieval rate was significantly lower (66.7 vs. 78.2%; p =.001) and the cycle cancellation rates were higher (29.2 vs. 21.2%; p =.056) in DYG co-treatments. A linear regression selected OS co-treatment protocol (0.53 DYG (0.356–0.776), p =.001) into the final model to predict a ≥ 80% mature oocyte retrieval rate. The per transfer (47.2 vs. 49.7; p =.721) and per treatment ongoing pregnancy rates (32.2 vs. 38.1%, p =.210) were similar in the two co-treatment groups. Flexible-start DYG co-treatment OS was as effective in blastocyst freeze-all-IVF cycles as MPA co-treatment, with similar ongoing pregnancy rates; however, mature oocyte retrieval was significantly decreased and cycle cancellation increased in DYG cycles. What is already known on this subject? Progestin (i.e. artificial progesterone) co-treatment has long been known to be a feasible alternative to conventional GnRH-analogue co-treatment in OS for IVF, because of the long-standing evidence that progestin formulations have in oral contraceptive therapies. The recent evolution of effective freeze-all-IVF (in which high mid-cycle progesterone levels is not of concern because of the postponement of embryo transfer) has now made it possible to investigate progestin co-treatment OS in IVF. What do the results of this study add? Ongoing pregnancy rates from blastocyst frozen embryo transfers in flexible-start dydrogesterone (DYG) co-treatment ovarian stimulation (OS) cycles were similar to rates in flexible-start medroxyprogesterone acetate (MPA) co-treatment OS cycles. The mature oocyte retrieval rate was significantly lower and the cycle cancellation rate higher in DYG than in MPA cycles. What are the implications of these findings for clinical practice and/or further research? The evidence suggests that MPA co-treatment should be preferred in OS for IVF. Further investigation is required to refine progestin co-treatment protocols, because of their potential to reduce the number of viable blastocysts. [ABSTRACT FROM AUTHOR]

Background: Progestin-primed ovarian stimulation (PPOS) has been used in infertility cases in recent years, and several reports have stated that it has oocyte collection results similar to those of gonadotropin-releasing hormone antagonist (GnRH-ant) protocol. For emergency fertility preservation, random-start ovarian stimulation is usually recommended. Therefore we compared the clinical outcomes of random-start PPOS with those of conventional random-start GnRH-ant protocols in fertility-preserving cases. Methods: We retrospectively examined 86 cycles of oocyte collection, of which 56 were random-start GnRH-ant and 30 were random-start PPOS for fertility preservation at our hospital between January 2016 and April 2021. The primary outcome was the number of mature oocytes per cycle. The secondary outcome was the number of vitrified blastocysts per cycle for embryo freezing cases. Results: No significant differences were noted in the number of days of stimulation, total dose of gonadotropin preparation, and the number of mature oocytes and vitrified blastocysts. The number of hospital visits for monitoring was significantly lower in the PPOS group. The start of menstruation before oocyte collection was significantly less in the PPOS group. Conclusions: Random-start PPOS and GnRH-ant were similar in oocyte collection results. PPOS can reduce the number of hospital visits, thus reducing patient stress. PPOS at the start of the luteal phase can prevent the start of menstruation during ovarian stimulation. [ABSTRACT FROM AUTHOR]

On September 11–12, 2020, in Kyiv hosted the International Women's Health Summit “From Menarche to Menopause” with the participation of leading foreign and domestic experts in the field of obstetrics and gynecology. The event was devoted to such topical topics as miscarriage, infertility, menstrual irregularities, menopausal hormone therapy (MHT). The current concern in clinical practice is not overuse of MHT, but it underutilization, and the fact that only a small number of women with impaired quality of life through menopausal symptoms receive treatment, despite that they perfectly fit the patient's profile for such therapy. All types of MHT are characterized by following effects: a positive effect on the cardiovascular system if MHT was start before 60 ages or in the first 10 years after menopause onset; the mortality rate from all causes is not increased in patients on MHT. The “ideal” MHT should relieve vasomotor symptoms, influence urogenital symptoms, prevent fractures and bone loss, protect the cardiovascular system and endometrium, and should not increase the risks of breast cancer, deep vein thrombosis and pulmonary embolism. Estradiol + dydrogesterone (Femoston®) scheme fits perfectly into these criteria. Femoston® is an oral MHT preparation that is effective in relieving symptoms of estrogen deficiency with a proven safety profile on the cardiovascular system and breast. This drug helps to reduce the manifestations of symptoms of estrogen deficiency, increase bone mineral density, and has a positive effect on metabolic processes. Numerous studies have shown that combination of estradiol + dydrogesterone is not only highly effective against menopausal symptoms, but also extremely important features, in particular, a proven safety profile for breast cancer.

An issue of habitual miscarriage poses a high social importance especially during COVID-19 pandemic. Meanwhile, healthcare workers faced a mass media campaign against using micronized progesterone upon habitual miscarriage, which, as viewed by publication authors, displays signs of prejudiced data manipulation and may disorient practitioners. Authors of published letter provide objective information on accumulated data regarding gestagens efficacy and safety. They invoke healthcare professionals to make decisions deserving independent primary source trust presented by original scientific papers published in peer-reviewed journals, clinical recommendations proposed by professional medical communities as well as treatment standards and protocols.

Hyperproliferative diseases of the endometrium play an important role in the structure of gynecological pathology, which are a spectrum of irregular morphological changes. Particularly difficult is evaluation of the phenotypic characteristics of the endometrium hyperplastic processes (EHP) in premenopausal women in the presence of an unstable menstrual cycle. Diagnosis and EHP prognosis remains a difficult task given that it can occur as focal or diffuse lesions with various structural and cytological differences. Objective of the study: to evaluate the immunohistochemical features (phenotypic variants) of benign endometrial hyperplasia in premenopausal women. Material and methods. 33 premenopausal women with abnormal uterine bleeding and verified benign endometrial hyperplasia were examined. Expression of the α-receptors for estrogens type 1 (ER1), progesterone receptors and Ki-67 nuclear protein in the endometrium stroma and glands was analyzed. Micromorphometry was performed and the D-score was calculated. Results. Prevalence of comorbid lesions in patients was the combination of endometrial hyperplasia and fibroids (51.4%), cases of abnormal uterine bleedings against submucosal fibroids (13.5%), endometrial polyps (8.1%), combinations of EHP and peritoneal endometriosis (10.8%), adenomyosis and myoma (8.1%), or other combinations of endometrial and myometrial proliferative pathology. D-score for surgery averaged 1.78 ± 0.11 indicating a low risk of malignancy. There were changes after treatment in the quantitative presentation of the studied proteins in stroma and endometrial glands. Thus, before treatment in the glands was determined up to 100% of cells containing ER1 in large quantities, while after treatment their number decreased by an average of 20%. Similar dynamics was observed with progesterone receptors activity. Conclusions. The main prognostic significant phenotypes of endometrial proliferative pathology have been identified. After removing of pathologically chanced endometrium and subsequent treatment with dydrogesterone during 6 months there is prognostically positive decreasing in the ER1 density as well as the Ki-67 protein expression

The article is devoted to the extremely pressing issue of the treatment of endometriosis, which is the object of a thorough study by scientists around the world. There is no drug that is 100% effective against endometrioid heterotopias and has no pronounced side effects either in our country, or abroad. In addition, the quality of evidence base generated on the basis of randomized clinical trials on the effectiveness of drug therapy for endometriosis is not sufficient in terms of research methodology.The Russian clinical guidelines for the management of endometriosis postulate that operational intervention is the main stage in the treatment of this disease. The treatment of endometriosis is aimed to remove the endometriotic lesion, reduce pain intensity, treat infertility, prevent progression or recurrences of the disease.There is currently no universal drug therapy for endometriosis, and the drug therapy used to treat it is nonspecific and primarily aims to reduce the severity of existing symptoms. The drug therapy for endometriosis is chosen on case-by-case basis, depending on the extent of the disease, clinical symptoms and the patient’s needs. In addition to the above, the choice of hormone therapy for endometriosis should take into account the efficacy of a drug, its individual tolerance, the cost of treatment, the doctor’s experience in using this drug, the patient’s compliance with the doctor’s recommendations.The article presents possible algorithms for choosing strategies in the treatment of endometriosis using surgical and pharmaceutical methods. The authors discussed the principles and mechanisms of action of hormonal drugs intended for the treatment of endometriosis. The review and analysis of modern clinical data on the problem of treatment of endometriosis is presented.

Habitual miscarriage is a fairly common complication of early pregnancy. In the opinion of most authors, the term habitual miscarriage is used to describe a loss of two or more pregnancies during the first 22 weeks of pregnancy. Issues of terminology and management continue to be relevant and debatable in medical professional communities and need further discussion. In addition to the medical sides of the issue, habitual miscarriage has a significant psychological impact on women and their partners. Regardless of the gestational age, the loss of pregnancy for most couples is similar in importance to the loss of a newborn and is associated with the loss of hope and plans that future parents connected with a baby who has not yet been born. After repeated losses, bereavement and emotional upheaval are further exacerbated irrespective of the term of abortion. Repeated pregnancy loss is a significant negative event in the life of a couple both from a medical and psychological point of view, that’s why the provision of adequate medical care is one of the objectives of a specialist managing pregnancy. This also involves the choice of effective disease management. Previously it was shown that luteal phase deficiency might be the cause of this phenomenon, and that hormonal deficiency had to be replenished. Many modern publications confirm that progesterone and its derivatives have an important immunomodulatory role in the habitual miscarriage. The article describes the role of progesterone in maintaining pregnancy and the results of studies devoted to the role of dydrogesterone. It also presents data of international studies on the treatment of women with habitual miscarriage.

Jialyu Huang,* Qin Xie,* Jiaying Lin, Xuefeng Lu, Jing Zhu, Hongyuan Gao, Renfei Cai, Yanping Kuang Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Renfei Cai; Yanping KuangDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People’s Republic of ChinaTel +86-21-2327 1699 Ext 5539Fax +86-21-6313 6856Email cairenfei070@sina.com; kuangyp9hospital@126.comPurpose: Dydrogesterone (DYG) is an alternative progestin in progestin-primed ovarian stimulation (PPOS) protocol with weaker pituitary suppression than medroxyprogesterone acetate (MPA) in normal ovulatory women. However, the endocrinological characteristics, oocyte retrieval and pregnancy outcomes of DYG application in polycystic ovarian syndrome (PCOS) patients undergoing in vitro fertilization (IVF) remain unclear.Patients and methods: This retrospective cohort study included 420 PCOS patients who underwent controlled ovarian stimulation with human menopausal gonadotropin (hMG) and DYG (n=105) or MPA (n=315) from January 2014 to December 2017. Baseline characteristics of the two groups were balanced with propensity score matching using the nearest-neighbor random matching algorithm in a ratio of 1:3. The primary outcome measure was the number of oocytes retrieved. Other main outcome measures included the number of viable embryos, incidence of premature luteinizing hormone (LH) surge and live birth rate per frozen-thawed embryo transfer (FET) cycle.Results: A similar number of oocytes was retrieved in the two protocols (16.1±6.5 vs 15.1±10.0, P=0.342). Patients in both groups achieved consistent LH suppression with no premature LH surge detected. In the DYG + hMG group, the mean LH levels were significantly higher than the MPA + hMG group on cycle day 9–11 and trigger day (all P

Background: The quality of the luteal phase is the most important issue affecting pregnancy outcomes in assisted reproductive technology (ART). Luteal-phase support with the administration of gonadotropin-releasing hormone (GnRH) agonist or progesterone improves the likelihood of pregnancy in ART. Due to disagreements regarding the best pharmaceutical form of progesterone for success of in vitro fertilization (IVF) in ART methods, the present study aimed to compare the clinical efficacy of oral dydrogesterone with vaginal progesterone on the outcome of pregnancy in IVF. Materials and Methods: This unblinded randomized clinical trial was conducted at the Shahid Beheshti Hospital, Obstetrics and Gynecology Centre in Isfahan, Iran, between june 2021 and September 2021. In total, 126 couples were included in the study. All patients underwent controlled ovarian stimulation and IVF. Patients were randomly divided into two groups (n = 63 per group). After embryo transfer, group I was treated with Cyclogest 400 mg twice daily, and group II was treated with oral Duphaston 10 mg twice daily. Results: No significant differences were observed between the two groups in terms of the mean endometrial thickness (P = 0.613), the mean number of transferred embryos (P = 0.100), and the number of implanted embryos (P = 0.338). Additionally, no statistically significant differences in the pregnancy rate were detected between the two groups (P = 0.875). Conclusions: The evidence from this study indicates that Duphaston is as effective as Cyclogest for luteal-phase support.

Background: The objective was to compare the use of micronized vaginal progesterone 800 mg daily and oral dydrogesterone 40 mg daily in the endometrial preparation for frozen-thawed embryo transfer (FET). Methods: Prospective randomized study with women undergoing FET along with hormone replacement therapy for endometrial preparation, between September 2019 and February 2021. A total of 73 patients were randomly selected and orally received 40 mg/day dydrogesterone (DYD group, n = 36) or 800 mg/day micronized vaginal progesterone (MVP group, n = 37) after endometrial preparation with transdermal estradiol. The main outcome was a viable ongoing pregnancy with 12 weeks of gestation. Biochemical pregnancy, clinical pregnancy and live birth rates were the secondary outcome. Results: The reproductive outcomes in FET cycles were similar, with pregnancy and Live birth rates in the didrogesterone and MVP treatment groups being respectively: Biochemistry (38.9%/37.8%; p = 0.189 [95% confidence interval (CI) = –23.4–21.2]), Clinical (33.3%/35.1%; p = 0.192 [95% CI = –20.0–23.6]); 12 Weeks Pregnancy (33.3%/32.4%; p = 0.196 [95% CI = –22.4–20.6]); Live birth (33.3%/32.4%; p = 0.196 [95% CI = –22.4–20.6]). Conclusions: 40 mg/day dydrogesterone and 800 mg/day MVP revealed similar reproductive results in FET cycles. The use of oral dydrogesterone is a reasonable option, may be more accepted by patients in terms of ease of use and lower cost. Clinical Trial Registration: U1111-1247-1845.