Medroxyprogesterone Acetate Group Research Articles

Effect of medroxyprogesterone acetate dose in progestin-primed ovarian stimulation on pregnancy outcomes in poor ovarian response patients with different body mass index levels.

For the poor ovarian response (POR) population, the relationship between medroxyprogesterone acetate (MPA) dose in progestin-primed ovarian stimulation (PPOS) and clinical outcome is still unclear. This study aims to explore the effect of MPA dose in PPOS on clinical outcomes in POSEIDON group 3 and 4 patients with different body mass index (BMI) levels, hoping to provide clinical doctors with better options for controlled ovarian hyperstimulation (COH) programs. This is a retrospective analysis of 253 oocyte retrieval cycles of POSEIDON group 3 and 4 patients who underwent PPOS protocol in IVF/ICSI treatment at the Reproductive Medical Center of Renmin Hospital of Wuhan University from March 2019 to April 2022. The effects of different MPA doses (8 mg/d or 10 mg/d) on pregnancy outcomes were compared in normal BMI (18.5-24 kg/m2) and high BMI (≥24 kg/m2) patients, and multivariate logistic regression analysis was performed to analyze the factors affecting pregnancy outcomes. For normal BMI patients, the 8-mg/d MPA group had a higher embryo implantation rate (33.78% vs. 18.97%, P = 0.012). For high BMI patients, the 10-mg/d MPA group had a higher HCG positive rate (55.00% vs. 25.00%, P = 0.028), clinical pregnancy rate (50.00% vs. 20.00%, P = 0.025), and cumulative pregnancy rate (37.74% vs. 13.79%, P = 0.023) compared with the 8-mg/d MPA group. There was no significant difference in cumulative live birth rate between the 8-mg/d and 10-mg/d MPA groups in patients with normal or high BMI. The results of multivariate logistic regression showed a significant correlation between MPA dose and cumulative pregnancy in the high BMI population (OR = 0.199, 95% CI: 0.046~0.861, P = 0.031). For POR patients with high BMI, 10 mg/d of MPA in the PPOS protocol had a higher cumulative pregnancy rate than 8 mg/d of MPA, but it had no significant effect on the cumulative live birth rate.

Oral medroxyprogesterone acetate for the use of ovulation suppression in in vitro fertilization: a cohort trial

To broadly assess the efficacy of medroxyprogesterone acetate (MPA) for ovulatory suppression during in vitro stimulation (IVF) when compared to gonadotropin releasing hormone (GnRH) antagonist cycles DESIGN: Cohort Trial SETTING: A single academic-affiliated private fertility practice SUBJECTS: Patients of all diagnoses aged 18-44 years undergoing autologous IVF for fertility treatment between 2020-2023 EXPOSURE: Comparison of MPA vs. antagonist IVF stimulation cycles MAIN OUTCOME MEASURES: Rates of premature ovulation, oocyte and embryo yield, embryo quality, pregnancy rates, and logistical benefits RESULTS: Prospective data was collected on 418 patients who underwent MPA-protocol ovarian stimulation (MPA group) which was compared to 419 historical control GnRH antagonist cycles (control group). Age was similar between groups (35.6 +/- 4.6 vs. 35.7 +/- 4.8 years; p = 0.75). There were no cases of premature ovulation in the MPA group compared to a total of five cases in the control group (0% vs. 1.2%; RR 0.09, 95% CI 0.01-1.66). No differences were seen between number of oocytes retrieved (14.3 +/- 10.2 vs. 14.3 +/- 9.7; p = 0.83), blastocysts (4.9 +/- 4.6 vs. 5.0 +/- 4.6; p = 0.89), or euploid blastocysts (2.4 +/- 2.6 vs. 2.2 +/- 2.4; p = 0.18) in the MPA vs. control group respectively. Clinical pregnancy rate was similar between groups (70.4% vs. 64.2%; RR 0.92, 95% CI 0.72 - 1.18). There was no difference in length of IVF stimulation or dose of stimulation medications. Patients in the MPA group saved an average of $491 +/- $119 on medications, had an average of one less monitoring visit (4.4 +/- 0.9 vs. 5.6 +/- 1.1; p < 0.01), and 5.0 +/- 1.2 less injections per cycle. When adjusting for age and ovarian reserve, protocol group (MPA vs. control) did not influence having an embryo available for transfer (76.6% vs. 73.4%; adjusted RR 1.05, 95% CI 0.94 - 1.14). For ovulatory suppression during IVF cycles, MPA was effective at preventing ovulation while demonstrating similar cycle and reproductive outcomes, with the additional benefits of patient cost savings, increased convenience with decreased number of visits, and fewer injections.

The comparison between fixed versus degressive doses of medroxyprogesterone acetate combined with letrozole in patients of progestin-primed ovarian stimulation protocol: a propensity score-matched study.

To explore the cycle characteristics and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) using fixed versus degressive doses of medroxyprogesterone acetate (MPA) in conjunction with letrozole (LE) in infertile women by propensity score matching (PSM) analysis. A retrospective cohort study. Tertiary-care academic medical center. A total of 3173 infertile women undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment within the period from January 2017 to December 2020. A total of 1068 and 783 patients who underwent a fixed dose of MPA combined with LE and a degressive dose of MPA combined with LE protocols, respectively, were enrolled in this study. The freeze-all approach and later frozen-thawed embryo transfer (FET) were performed in both groups. Propensity score matching (1:1) was performed. The primary outcomes were the dosage of MPA and the incidence of premature luteinizing hormone (LH) surges. The secondary outcomes were the number of oocytes retrieved, the cumulative live birth rate (CLBR) and the fetal malformation rate. We created a perfect match of 478 patients in each group. The dosage of MPA, the LH serum level on the eighth day of stimulation, progesterone (P) level and LH level on the hCG trigger day were significantly higher in the LE + fixed MPA group than in the LE + degressive MPA group (52.1 ± 13.1 mg vs. 44.9 ± 12.5 mg; 5.0 ± 2.7 IU/L vs. 3.7 ± 1.7 IU/L; 0.9 ± 0.5 ng/ml vs. 0.8 ± 0.5 ng/ml; 3.3 ± 2.4 IU/L vs. 2.8 ± 1.9 IU/L; P < 0.01). The duration of Gn, the number of follicles with diameter more than 16mm on trigger day, the estradiol (E2) level on the hCG trigger day were lower in the LE + fixed MPA group than in the LE + degressive MPA group (9.7 ± 1.7 days vs. 10.3 ± 1.5 days; 5.6 ± 3.0 vs. 6.3 ± 3.0; 1752.5 ± 1120.8 pg/ml vs. 1997.2 ± 1108.5 pg/ml; P < 0.001). No significant difference was found in the incidence of premature LH surge, the number of oocytes retrieved, the number of top-quality embryos, clinical pregnancy rate (CPR), CLBR or fetal malformation rate between the two groups. The combination of a degressive MPA dose with LE proved effective in reducing the total MPA dosage with comparable premature LH surge and pregnancy outcomes in women undergoing the PPOS protocol.

Comparison of the effects and safety of dydrogesterone and medroxyprogesterone acetate on endometrial hyperplasia without atypia: a randomized controlled non-inferior phase Ⅲ clinical study

Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ2=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.

Obstetric outcomes after medroxyprogesterone acetate treatment for early stage endometrial cancer or atypical endometrial hyperplasia: a single hospital-based study.

To investigate perinatal outcomes in pregnancy after high-dose medroxyprogesterone acetate (MPA) therapy for early stage endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) and to determine whether pregnancy after MPA therapy is at a higher risk of placenta accreta. Data of 51 pregnancies in 46 women who received MPA therapy for EC or AEH and delivered after 22weeks of gestation at Keio University Hospital were reviewed. A retrospective matched case-control study was performed to determine the risk of placenta accreta in pregnancy after MPA therapy compared with singleton pregnancies without any history of maternal malignancy treatments. The incidence of placenta accreta was higher in the MPA group than in the control group (15.7 vs. 0%, p = 0.0058). However, no differences in other perinatal outcomes were observed between groups. While gestational weeks at delivery in the MPA group were later than those in the control group (p = 0.0058), no difference in the incidence of preterm delivery was recorded between groups. In the MPA therapy group, the number of patients who underwent ≥ 6 dilation and curettage (D&C) was higher in the placenta accreta group than in the non-placenta accreta group (50.0 vs. 14.0%, p = 0.018). Patients with ≥ 6 D&Cs demonstrated a 6.0-fold increased risk of placenta accreta (p = 0.043, 95% CI 1.05-34.1) than those receiving ≤ 3 D&Cs. Pregnancy after MPA therapy is associated with a high risk of placenta accreta. In cases in which the frequency of D&C is high, placenta accreta should be considered.

The effectiveness of desogestrel for endometrial protection in women with abnormal uterine bleeding-ovulatory dysfunction: a non-inferiority randomized controlled trial

Women with chronic abnormal uterine bleeding-ovulatory dysfunction (AUB-O) are at increased risk of endometrial neoplasia. We conducted a non-inferiority randomized controlled trial to determine the effectiveness of two cyclic-progestin regimens orally administered 10 d/month for 6 months on endometrial protection and menstruation normalization in women with AUB-O. There were 104 premenopausal women with AUB-O randomized to desogestrel (DSG 150 µg/d, n = 50) or medroxyprogesterone acetate (MPA 10 mg/d, n = 54) group. Both groups were comparable in age (44.8 ± 5.7 vs. 42.5 ± 7.1 years), body mass index (24.8 ± 4.7 vs. 24.9 ± 4.7 kg/m2), and AUB characteristics (100% irregular periods). The primary outcome was endometrial response rate (the proportion of patients having complete pseudodecidualization in endometrial biopsies during treatment cycle-1). The secondary outcome was clinical response rate (the proportion of progestin withdrawal bleeding episodes with acceptable bleeding characteristics during treatment cycle-2 to cycle-6). DSG was not inferior to MPA regarding the endometrial protection (endometrial response rate of 78.0% vs. 70.4%, 95% CI of difference − 9.1–24.4%, non-inferiority limit of − 10%), but it was less effective regarding the menstruation normalization (acceptable bleeding rate of 90.0% vs 96.6%, P = 0.016).Clinical trial registration: ClinicalTrials.gov (NCT02103764, date of approval 18 Feb 2014).

Medroxyprogesterone acetate is a useful alternative to a gonadotropin-releasing hormone antagonist in oocyte donation: a randomized, controlled trial

To compare ovarian response and reproductive outcomes in oocyte donors undergoing pituitary suppression with medroxyprogesterone acetate (MPA) versus those undergoing conventional treatment with a gonadotropin-releasing hormone (GnRH) antagonist. A prospective, randomized, controlled trial of cycles was conducted from October 2017 to June 2019 to evaluate ovarian response in terms of the number of oocytes. The reproductive outcomes of the recipients were retrospectively analyzed later. A university-affiliated private invitro fertilization center. We randomly divided 318 donors into 2 groups in a 1:1 ratio. The oocytes obtained were assigned to 364 recipients. One hundred sixty-one donors were treated with a daily dose of 10 mg of MPA administered orally from the beginning of ovarian stimulation (OS), and 156 were treated with a GnRH antagonist (initiated once the leading follicle reached a diameter of 13 mm). Transvaginal ultrasound was performed, and serum estradiol, luteinizing hormone, and progesterone levels were recorded during monitoring. The following additional parameters were analyzed: endocrine profile (in follicular fluid), number of metaphase II oocytes, and pregnancy outcome. The donors included in the study group were stimulated using recombinant follicle-stimulating hormone and MPA at 10 mg/day, simultaneously begun on cycle day 2 or 3. Ovulation was induced using a GnRH agonist when dominant follicles matured. A short protocol with ganirelix at 0.25 mg/day was used for the control group. Oocytes were assigned to the recipients, followed by routine invitro fertilization procedures in which 1 embryo was usually transferred. The primary outcome measure was the numbers of oocytes and metaphase II oocytes retrieved. The secondary outcomes were the incidence of premature luteinizing hormone surge, serum and follicular fluid hormone profiles, and clinical pregnancy outcomes in the recipient group. The number of oocytes retrieved was 21.4 ± 11.7 in the MPA group and 21.2 ± 9.2 in the antagonist group (mean difference 0.14; 95% confidence interval -2.233, 2.517). The total dose of recombinant follicle-stimulating hormone, duration of OS, and endocrine profiles of the serum and follicular fluids were comparable in the 2 groups. No early ovulation was observed in either group. No statistically significant differences with respect to implantation rate (68.1% in the MPA group vs. 62% in the antagonist group), clinical pregnancy rate (64.5% in the MPA group vs. 57.8 in the antagonist group), ongoing pregnancy rate (55.4% in the MPA group vs. 48.5% in the antagonist group), live birth rate (55.1% in the MPA group vs. 48.5% in the antagonist group), or cumulative live birth rate (73.8% in the MPA group vs. 70.7% in the antagonist group) were observed between the groups. The administration of MPA resulted in oocyte retrieval rates, endocrine profiles, viable embryo numbers, and pregnancy outcomes similar to those achieved with the GnRH antagonist. Therefore, MPA can be recommended for OS in oocyte donation because it permits a more patient-friendly approach. NCT03300960.

Medroxyprogesterone acetate used in ovarian stimulation is associated with reduced mature oocyte retrieval and blastocyst development: a matched cohort study of 825 freeze-all IVF cycles.

To compare the effectivity of flexible-start medroxyprogesterone acetate (MPA) co-treatment ovarian stimulations (OS) with flexible-start gonadotropin-releasing hormone antagonist (GnRH-ant) co-treatment OS, in blastocyst freeze-all IVF cycles. This matched cohort study was performed at a single IVF center. Study cycles were extracted from freeze-all IVF cycles performed between February 2015 and June 2018 with cycles grouped according to the co-treatment protocol (MPA and GnRH-ant groups) used. MPA cycles were matched 1:1 using antral follicle count, female age, infertility duration, and female body mass index, with GnRH-ant cycles, resulting in 825 matched cycles. MPA or CET co-treatment was started when leading follicles reached 11-12 mm. Duration of OS was significantly longer, and total FSH dose was significantly higher in the MPA group. Numbers of mature oocytes retrieved were similar; however, the mature oocyte retrieval rate (83.8 vs. 97.1%; p < 0.001), number of blastocysts, blastocyst rate (36.4 vs. 41.4%; p < 0.001) and > 2 viable blastocyst rate were all significantly lower in the MPA group. The live birth (LB) per transfer rates (51.6 vs. 55.7%; p = 0.155) were similar; however, the LB rate per treatment was significantly lower (40.9 vs. 45.8%; p = 0.05). A linear regression included the OS co-treatment protocol (GnRH-ant; 1.4 (1.07-1.81); p = 0.013) in the final model to predict having > 2 viable blastocysts. Flexible-start MPA co-treatment OS was as effective in freeze-all IVF cycles as GnRH-ant co-treatment, with similar LB per transfer rates; however, increased cycle cancellation and reduced blastocyst numbers reduced LB per treatment rates significantly.

MPA given orally during the first trimester for threatened miscarriage carries no specific risk for foetal abnormalities albeit the rate is higher than non-threatened pregnancies

This observational study examines the outcomes of pregnancies arising in women referred for infertility, where those who experienced threatened miscarriage were treated with medroxyprogesterone acetate (MPA) tablets. The 14-year study period covers comprehensive real-time data entries into the validated electronic database including details of the infertility management, pregnancy outcomes and any foetal anomalies among the infants, each being tracked and recorded. Of 4057 clinical pregnancies, 1343 received MPA for threatened miscarriage; 934 (69.6 %) of which continued to livebirths. These were compared with the remaining 2714 clinical pregnancies without threatened miscarriage or MPA and which resulted in 2075 (76.5 %) livebirths. There were 134 developmental abnormalities recorded among the 3009 livebirths of which 78 (2.6 %) were categorised appropriate for the Western Australian Developmental Abnormalities Register; WARDA. These comprised 55 in the MPA group, 36 of which were categorised as serious (being 2.7 % of clinical pregnancies and 3.9 % of births). In the group without MPA, there were 79 abnormalities, of which 42 were categorised as serious (being 1.7 % of clinical pregnancies and 2.2 % of births). Specifically, there were no cases of androgenisation noted among the female infants. The abnormality rates were low overall and well within the annual WARDA ranges. We cautiously suggest that oral MPA can be considered for studies throughout pregnancy including the early first trimester to assess a potential role in reducing miscarriage, as well as advanced pregnancies to evaluate a potential role in reducing stillbirths and preterm delivery.

Effectiveness and safety of ormeloxifene and medroxyprogesterone acetate in dysfunctional uterine bleeding - A prospective interventional quasi-randomized interval clinical study

Background: Progestogens and selective estrogen receptor modulators are used in treating dysfunctional uterine bleeding (DUB). There is a lack of consensus regarding the best agent. Aim and Objective: To compare the effectiveness and safety of ormeloxifene and medroxyprogesterone acetate (MPA) in DUB. Materials and Methods: A comparative evaluation of gynecology outpatients with DUB at a tertiary care teaching hospital by a prospective interventional quasi-random design. Patients having DUB were allocated into two groups based on treatment with ormeloxifene (n = 20) and MPA (n = 20). Each patient was followed up for 3 months and evaluated for: (a) Menstrual blood loss assessed using pictorial blood loss assessment chart (PBAC) score and presence of clots, (b) endometrial thickness, (c) hemoglobin (Hb) level, (d) assessment of symptoms, and (e) adverse effects. Mann–Whitney U test and Chi-square test were used to compare both groups. Results: There was a significant reduction in PBAC score and passage of clots compared to baseline in both groups. An increase in Hb was statistically significant in MPA group. Decrease in PBAC score, increase in Hb, and decrease in endometrial thickness after treatment was not significant between groups. In ormeloxifene group, symptoms significantly improved after 1 month and 75% patients had amenorrhea. Conclusion: Ormeloxifene, with less frequent administration and higher tolerability, can be used as an effective alternative to MPA for controlling menstrual blood loss.

Comparison of diagnostic accuracy between endometrial curettage and aspiration biopsy in patients treated with progestin for endometrial hyperplasia: a Korean Gynecologic Oncology Group study.

ObjectiveTo compare the diagnostic accuracy of dilatation and curettage (D&C) versus endometrial aspiration biopsy in follow-up evaluation of patients treated with progestin for endometrial hyperplasia (EH)MethodsA prospective multicenter study was conducted from 2015 to 2018. Patients with EH were treated with progestin, one of the following three treatment regimens: oral medroxyprogesterone acetate (MPA) 10 mg/day for 14 days per cycle, continuous MPA 10 mg/day or the levonorgestrel-releasing intrauterine system (LNG-IUS). At 3 or 6 months of treatment, endometrial tissues were obtained via 2 methods in each patient: aspiration biopsy, followed by D&C. The primary outcome was the consistency of the histologic results between the 2 methods. The secondary outcome was the regression rate at 6 months of treatment.ResultsThe study population comprised 65 patients (55 with non-atypical hyperplasia, 10 with atypical hyperplasia). During the follow-up, a comparison of the pathologic results from aspiration biopsy and D&C was carried out for the 65 cases. Thirty-eight cases were diagnosed as EH by D&C. Among these, only 24 were diagnosed with EH from aspiration biopsy, for a diagnostic concordance of 63.2% (ĸ=0.59). Forty-four patients were followed up at 6 months, and the regression rate was 31.8% (14/44). Responses were obtained for 41.7% (5/12) of the cyclic MPA group, 58.3% (7/12) of the continuous MPA group and 10% (2/20) of the LNG-IUS group.ConclusionAs a follow-up evaluation of patients treated with progestin for EH, aspiration biopsy is less accurate than D&C and might not be a reliable method.Trial RegistrationClinicalTrials.gov Identifier: NCT02412072

LEVONORGESTREL INTRAUTERINE DEVICE VERSUS MEDROXYPROGESTERONE ACETATE IN TREATMENT OF SYMPTOMATIC UTERINE FIBROIDS

Background: Medroxyprogesterone acetate (MPA) and levonorgestrel intrauterine device (LNG-IUD) are two drugs used to treat abnormal uterine bleeding in women with myoma. We organized this study to compare the effectiveness of these two treatments.&#x0D; Methods: This was a retrospective one-year-long cohort study of 95 women with uterine leimyoma. Fifty three women who had received LNG-IUD formed the LNG-IUD group while 42 women who received regular intramuscular injections of 150 mg MPA at every 3 months for one-year period made up the MPA group. Both groups were compared in aspect of demographic, clinical and biochemical characteristics.&#x0D; Results: At the end of one year, the LNG-IUD group had significantly smaller fibroid size, lower visual analogus scale score for pelvic pain, for dysmenorrhea and dyspareunia than the MPA group. There were a significant reduction in the number of patients with menorrhagia and a significant increase in serum hemoglobine levels both in LNG-IUD and MPA groups at the end of the one-year long study period.&#x0D; Conclusions: LNG-IUD appears as a good choice for the reduction in fibroid size and associated pelvic pain.

While women await surgery for type I endometrial cancer, depot medroxyprogesterone acetate reduces tumor glandular cellularity

Multiple population-level studies have demonstrated an adverse effect of long wait times to surgery on survival for women with endometrial cancer. Other retrospective and nonrandomized prospective studies have shown that preoperative administration of depot medroxyprogesterone acetate decreases tumor glandular cellularity, which may be a surrogate marker for clinically meaningful tumor response. We sought to determine whether preoperative injection with depot medroxyprogesterone acetate decreases tumor glandular cellularity when compared to placebo injection in women awaiting hysterectomy for endometrial intraepithelial neoplasia or type I endometrial cancer, and to determine whether depot medroxyprogesterone acetate injection affects quality of life while waiting for surgery. This was a double-blind, randomized controlled trial of 400-mg depot medroxyprogesterone acetate injection or 0.9% saline injection at the preoperative visit. Patients with recent use of progesterone analogs were excluded. A sample size of 76 patients (38 per arm) was calculated to detect a 20% difference in decreased glandular cellularity between arms. Pathologic characteristics including the primary outcome, tumor glandular cellularity, from patients' diagnostic biopsies were reviewed by 2 dedicated gynecologic pathologists and compared to posttreatment hysterectomy specimens. On the night prior to surgery, patients completed the Functional Assessment of Cancer Therapy-Endometrial Survey (Version 4) to report quality of life while waiting for surgery. In comparing characteristics between the intervention and control groups, t tests were used for continuous variables, and χ2 or Fisher exact tests were used where appropriate for categorical data. From March 2015 through March 2016, 148 women were screened and 76 patients were enrolled. In all, 38 patients were randomized to and received depot medroxyprogesterone acetate injection and 38 were randomized to and received placebo injection. Demographics were similar between groups. Patients who received depot medroxyprogesterone acetate injection experienced a larger decrease in tumor glandular cellularity (mean change -64 [-31.8%] vs -14 [-5.5%] cells per quarter high-powered field in depot medroxyprogesterone acetate vs placebo groups, P= .002). This effect was most pronounced in women waiting ≥3 weeks for surgery. Several additional histologic and immunohistochemical markers of tumor differentiation and decreased cell proliferation were more pronounced in the depot medroxyprogesterone acetate group than in the placebo group. There were no significant differences in quality of life between groups on the Functional Assessment of Cancer Therapy-Endometrial Survey. Only 5.3% of patients who were approached declined to participate due to concerns regarding an intramuscular injection. Administration of depot medroxyprogesterone acetate prior to surgery for type I endometrial cancers caused greater tumor effect than placebo injection. Injection of depot medroxyprogesterone acetate was acceptable to and well tolerated by patients. Depot medroxyprogesterone acetate may represent a meaningful bridge to surgery in women who can expect long wait times.

Traditional Dry Cupping Therapy Versus Medroxyprogesterone Acetate in the Treatment of Idiopathic Menorrhagia: A Randomized Controlled Trial

Background: Dry cupping has been used as a treatment for abnormal uterine bleeding in Iranian traditional medicine. Objectives: The present study aimed at evaluating the usefulness of dry cupping on excessive menstrual blood loss in menorrhagia with a well- validated menstrual pictogram compared to medroxyprogesterone acetate. Methods: A total of 162 women with menorrhagia were enrolled in this prospective, randomized, controlled trial in Iran from 2015 to 2016. Written informed consent was obtained, then, patients were randomly allocated into dry cupping (three sessions of interrupted and kinetic dry cupping during menstrual bleeding) or medroxyprogesterone acetate (10 mg/day throughout the luteal period) groups using a random number sequence. The number of bleeding days and objective estimation of menstrual blood loss using a pictorial blood loss assessment chart (PBAC) were recorded before the intervention and at specific intervals (one and 3-months post-intervention). Results: At one and 3-months, PBAC scores were significantly lower in women treated with cupping compared with women treated with medroxyprogesterone acetate. These reductions in PBAC score were 214.9 mL with 95% CI (120.5 to 309.2) greater than medroxyprogesterone acetate at one month and 237.3 with 95% CI (143.0 to 331.7) at 3- month follow- up period. Reduction in the number of bleeding days in the cupping group for almost one day was better than the control groups at one and 3-months follow- up (Mean difference:-1.03, 95% CI (-1.78 to -0.26), P = 0.007). Conclusions: Dry cupping is an effective treatment in reducing the intensity of bleeding during the menstrual period compared to medroxyprogesterone acetate.

New application of dydrogesterone as a part of a progestin-primed ovarian stimulation protocol for IVF: a randomized controlled trial including 516 first IVF/ICSI cycles.

Can dydrogesterone (DYG) be used as an alternative progestin in a progesterone primed ovarian stimulation (PPOS) protocol? DYG can be used as an appropriate alternative progestin in a PPOS protocol. PPOS is a new ovarian stimulation regimen based on a freeze-all strategy that uses progestin as an alternative to a GnRH analog for suppressing a premature LH surge during the follicular phase. Medroxyprogesterone acetate (MPA) has been successfully used as an adjuvant to gonadotrophin in the PPOS protocol. However, the use of MPA may lead to stronger pituitary suppression and thus may require a higher dosage of hMG and a longer duration of ovarian stimulation than that of conventional ovarian stimulation protocol. A prospective RCT including 516 patients was performed between November 2015 and November 2016. Computerized randomization was conducted to assign participants at a 1:1 ratio into two treatment groups: an hMG + DYG group (260 patients) or an hMG + MPA group (256 patients) followed by IVF or ICSI with the freeze-all strategy. One cycle per patient was included. The primary outcome of the trial was the number of oocytes retrieved. The sample size was chosen to detect a difference of two oocytes with a power of 90%. Patients under 36 years of age with normal ovarian reserve who were undergoing their first IVF/ICSI procedure due to tubal factor infertility were randomized into two groups based on the oral progestin protocol used: hMG co-treatment with DYG (hMG + DYG) or hMG co-treatment with MPA (hMG + MPA). The different progestin was simultaneously administered at the beginning of menstrual cycle 3 (MC3). Oocyte maturation was co-triggered by administration of a GnRH agonist and hCG. All viable embryos from both protocols were cryopreserved for later transfer. Only the first frozen embryo transfer (FET) cycle was included in our study. The embryological and clinical outcomes were measured. Basic characteristics, such as age, BMI and infertility duration, in both groups were comparable. There was no significant difference in the number (mean ± SD) of oocytes retrieved [10.8 ± 6.3 for the hMG + DYG group versus 11.1 ± 5.8 for the hMG + MPA group, P = 0.33] or the oocyte retrieval rate [74.3 ± 19.6% for the hMG + DYG group versus 75.0 ± 19.5% for the hMG + MPA group, P = 0.69] between the groups. The viable embryo rate per oocyte retrieved did not differ between the two groups [odds ratio (OR): 1.08, 95% CI: 0.97-1.21, P = 0.16]: 37.4% (1052/2815) for the hMG + DYG group versus 35.6% (1009/2837) for the hMG + MPA group. During the whole process of ovarian stimulation, the mean LH level in the hMG + DYG group was always higher than that in the hMG + MPA group (P < 0.001); however, no patient from either group experienced a premature LH surge. In addition, no patients experienced moderate or severe ovarian hyperstimulation syndrome during the ovarian stimulation. No significant difference was found in the clinical pregnancy rate of the first FET cycle between the two groups (OR: 0.82, 95% CI: 0.56-1.21, P = 0.33): 57.6% for the hMG + DYG group (125/217) versus 62.3% for the hMG + MPA group (132/212). The patients and physician were not blinded to the study. Further, a large proportion of patients were still pregnant at the end of the clinical trial, therefore live birth rates were not observed in the follow-up period. The dose-effectiveness of DYG administration was not addressed in the trial design. DYG, which exhibits no or only weak inhibition of ovulation in normal dosage, can serve as an hMG adjuvant during ovarian stimulation. This finding suggests the possibility of a new application of DYG: as an appropriate alternative progestin for a PPOS protocol in IVF. This work was supported by The National Nature Science Foundation of China (Grant no. 81503603), Shanghai Three-year Plan on Promoting TCM Development (Grant no. ZY3-LCPT-2-2006) and the Natural Science Foundation of Shanghai (Grant nos. 15401932700 and 15ZR1424900). None of the authors declare any conflict of interest. Chictr.org.cn: ChiCTR-IPR-15007251. Chictr.org.cn: 22 October 2015. 1 November 2015.

Controlled ovulation of the dominant follicle using progestin in minimal stimulation in poor responders

BackgroundThe use of progestin (P) during ovarian stimulation is effective in blocking the luteinizing hormone (LH) surge in women with normal ovarian reserve, however, its effects have not been determined in poor responders. This study aimed to explore the follicular dynamics in P-primed minimal stimulation in poor responders.MethodsA total of 204 infertile women with diminished ovarian reserve were allocated into the medroxyprogesterone acetate (MPA) group or the natural-cycle control group in an alternating order. MPA (10 mg) was administered daily beginning from the early follicular phase and a low dose of hMG was added in the late follicular phase if the serum FSH level was lower than 8.0mIU/ml. When a dominant follicle reached maturity, triptorelin 100 μg and hCG 1000 IU were used for trigger, and oocytes were retrieved 34-36 h later.All viable embryos were cryopreserved for subsequent frozen embryo transfer. Natural cycle IVF was used as controls.ResultsCompared with the natural cycle group, the MPA group exhibited a larger pre-ovulatory follicle (18.7 ± 1.8 mm vs 17.2 ± 2.2 mm), a longer follicular phase (13.6 ± 3.6 days vs 12.3 ± 3.2 days), and higher peak oestradiol values (403.88 ± 167.16 vs 265.26 ± 122.16 pg/ml), while maintaining lower LH values (P < 0.05). The incidences of spontaneous LH surge and premature ovulation decreased significantly (1.0% vs 50%; 2% vs. 10.8%, respectively; P < 0.05). A greater number of oocytes and viable embryos were harvested from the MPA group than from the natural cycle group (P < 0.05). Moreover,the clinical pregnancy rate was slightly higher in the MPA group than in the natural cycle controls, but the difference was not significant (11.8% vs 5.9%, P > 0.05).ConclusionThis study supported the hypothesis that P-primed minimal stimulation achieved ovulation control of the dominant follicle and did not adversely affect the quality of oocytes in poor responders. Therefore, P-priming is a promising approach to overcome premature ovulation in minimal stimulation for poor responders.Trial registrationChiCTR-OCH-14004176. Registered on January 8, 2014.

Partial ablation of endometrial glands in dogs after exposure to progestin during the neonatal period.

Bitches with uteri devoid of endometrial glands should be sterile, and consequently could contribute to the population control of dogs. Considering that an inadequate exposure of the female reproductive system to steroids can lead to the formation of the uterine gland knock-out (UGKO) phenotype in some species, the aim of this study was to evaluate the effect of serial applications of medroxyprogesterone acetate (MPA) from birth until the age of six months on the development of endometrial glands in bitches. For this purpose, 16 female mongrel dogs from different litters were distributed into either an MPA group (n = 8), animals treated with 10 mg kg sc (Promone-E®, Pfizer, Brasil) at 3-week intervals, from day one after birth until the age of six months, or a control group (n = 8), composed of animals that only received a 0.9% NaCl solution in place of MPA. At six months of age, ovariohysterectomy was performed and uterine horn samples were collected for histological and immunohistochemical examinations. The bitches from the MPA-treated group presented a 35% decrease in the number of endometrial glands, a larger diameter of the endometrial glands, a greater epithelial height, as well as a greater thickness of the uterine wall, endometrium, and myometrium. However, no significant differences were observed between the two groups in the expression of ER-α, ER-β, and PR on the surface epithelium and endometrial stroma. Therefore, the serial application of MPA from birth until the age of 6 months do not completely ablate the development of the endometrial glands in bitches, but impair it by 35%.

Gasto energético e medidas antropométricas de novas usuárias do contraceptivo injetável trimestral de acetato de medroxiprogesterona de depósito

Objetivo:Avaliar o gasto energético e as medidas antropométricas de mulheres durante o primeiro ano de uso do método contraceptivo de acetato de medroxiprogesterona de depósito.Métodos:Estudo prospectivo com grupo de comparação. Foram incluídas mulheres saudáveis, não obesas, nunca usuárias de acetato de medroxiprogesterona de depósito e sem antecedentes que pudessem contribuir para a variação do peso corporal; foram distribuídas em dois grupos, 28 usuárias de acetato de medroxiprogesterona e 24 usuárias de dispositivo intrauterino de cobre, pareadas por idade (±1 ano) e índice de massa corporal (kg/m2). As variáveis estudadas foram sociodemográficas (idade, etnia, tabagismo, etilismo, atividade física, classe econômica e escolaridade), peso (kg), índice de massa corporal, gasto energético basal e total, medidas de circunferência de cintura e quadril (cm) e relação cintura-quadril.Resultados:A idade das mulheres variou de 20-39 anos. As médias de idade/índice de massa corporal foram 29,6 (DP=±5,2) anos/23,9 (±3,6 kg/m2), no grupo de acetato de medroxiprogesterona de depósito, e de 28,6 (DP=±5,2) anos/ 24,5 (±2,7 kg/m2), no grupo de dispositivo intrauterino de cobre. Após análise de variância para medidas repetidas, as usuárias de acetato de medroxiprogesterona de depósito apresentaram ganho de 2,2 kg no peso corporal e de -0,2 kg no grupo do dispositivo intrauterino de cobre, sem diferença estatisticamente significativa entre eles. Não houve discrepância nas demais variáveis estudadas.Conclusão:Mulheres saudáveis e jovens não apresentaram mudança no peso, nas medidas e nos gastos energéticos durante o primeiro ano de uso do contraceptivo acetato de medroxiprogesterona. A orientação em relação aos hábitos saudáveis de vida e o monitoramento de medidas são importantes para o controle do peso corporal em usuárias de métodos contraceptivos.

Cyclic versus continuous medroxyprogesterone acetate for treatment of endometrial hyperplasia without atypia: a 2-year observational study.

To assess the efficacy, safety and acceptability of cyclic medroxyprogesterone acetate (MPA) compared to continuous MPA for treatment of endometrial hyperplasia (EH) without atypia. A prospective observational study conducted on premenopausal women with EH without atypia (n = 80) who were randomly assigned into two groups; 40 patients received cyclic 15 mg MPA and 40 patients received continuous 15 mg MPA. Follow-up endometrial sampling was done after 6 months. Primary outcome measure was regression of hyperplasia. Secondary outcome measures include side effects and patient acceptability. There was no significant difference between the two groups regarding regression of endometrial hyperplasia (90 % in the cyclic MPA group in comparison to 82.5 % in the continuous MPA group with p value >0.05). There was a significant higher women suffering from nausea, acne and menstrual changes in the continuous MPA group (p value <0.05). Cyclic MPA regimen was more acceptable to the patients in comparison to continuous MPA intake. Cyclic MPA regimen seems a safer and more acceptable therapy in comparison to continuous MPA regimen in patients with endometrial hyperplasia without atypia. Larger studies are warranted to confirm these results.

Development of a subcutaneous endometriosis rat model.

To present a rat model of subcutaneous endometriosis for the study of pathophysiology and the effects of drugs. Fifty three-month-old female Wistar rats (Rattus norvergicus) were distributed into one control group and four treatment groups: estradiol (2.5; 5; 10 mg/kg s.c.), medroxyprogesterone acetate (0.5; 2; 5 mg/kg s.c.), triptorelin pamoate (0.18; 0.56 mg/kg s.c.) and acetylsalicylic acid (3 mg/kg per os). The animals were autoimplanted subcutaneously with 4x4-mm uterine fragments to induce endometriosis. The endometriomas were measured on days 1, 7, 14 and 21. The relative dry and wet weights of the endometrioma were used to evaluate response to the drug. Endometrial-like tissue was confirmed by histology. The greatest weight gain was observed on day 14 (relative wet weight: 29.1 ± 6.7 mg%, relative dry weight: 5.3 ± 0.9 mg %). Treatments were administered between day 5 and day 14. The relative wet weight of the hemiuterus in the 10 mg/kg estradiol group differed significantly from control and the other two estradiol groups (p=0.0001). In the medroxyprogesterone acetate group the weight decreased significantly but this decrease was not dose-dependent. Weight reduction was also significant in the triptorelin pamoate and the acetylsalicylic acid groups. The model of subcutaneous endometriosis is reproducible, low-cost and easy to perform, and suitable for the study of pathophysiology and the effects of drugs.