Administration Of Medroxyprogesterone Acetate Research Articles

Comprehensive meta-analysis of the effects of oral medroxyprogesterone acetate plus conjugated equine oestrogens on the lipid profile in women: Insights from randomized controlled trials.

Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone replacement therapy (HRT) in order to control menopause symptoms and correct hormone imbalances; however, HRT can impact serum lipids' concentrations. At present, data on the effect of the administration of medroxyprogesterone acetate plus conjugated equine oestrogens (MPACEE) on the lipid profile in females are uncertain, as the investigations conducted so far have produced conflicting results. Thus, we aimed to clarify the impact of MPACEE prescription on the serum lipids' values in women by means of a systematic review and meta-analysis of randomized controlled trials (RCTs). We employed a random-effects model based on the DerSimonian and Laird method to determine the combined estimates of the intervention's impact on the lipid profile. The computation of the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) relied on the mean and standard deviation values from both the MPACEE and control group, respectively. A total of 53 RCTs were included in the meta-analysis with 68 RCT arms on total cholesterol (TC), 70 RCT arms on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and 69 RCT arms on high-density lipoprotein cholesterol (HDL-C). Administration of MPACEE resulted in a significant reduction of TC (WMD = -11.93 mg/dL; 95% CI: -13.42, -10.44; p < .001) and LDL-C (WMD = -16.61 mg/dL; 95% CI: -17.97, -15.26; p < .001) levels, and a notable increase in HDL-C (WMD = 3.40 mg/dL; 95% CI: 2.93, 3.86; p < .001) and TG (WMD = 10.28 mg/dL; 95% CI: 7.92, 12.64; p < .001) concentrations. Subgroup analysis revealed that changes in the lipid profile were influenced by several factors: body mass index (for TC, HDL-C, TG), MPACEE dosages (for TC, LDL-C, HDL-C, TG), age (for TC, LDL-C, HDL-C, TG), durations of the intervention (for TC, LDL-C, HDL-C, TG), continuous/sequential administration of MPACEE (continuous for TC; sequential for LDL-C, TG) administration of MPACEE and serum lipids' concentrations before enrolment in the RCT (for TC, LDL-C, HDL-C, TG). MPACEE administration can influence serum lipids' concentrations in females by raising HDL-C and TG levels and reducing LDL-C and TC values. Therefore, postmenopausal women who suffer from hypercholesterolaemia might benefit from this type of HRT.

Microbiological and hematological aspects of canine pyometra and associated risk factors

Canine Pyometra, also known as cystic endometrial hyperplasia complex, is a common reproductive issue in bitches. This study aimed to identify associated risk factors, hematological variation, bacteria involved, and the most potent anti-bacterial against bacterial isolates of canine pyometra. Forty-five bitches of different habitats, breeds, and ages infected with pyometra were included in the study. The samples were cultured to isolate bacteria associated with the pyometra and antibiotic sensitivity was done for each bacterial isolates to get antibiogram. The study findings showed that potential risk factors such as age group, medroxyprogesterone acetate administration, and changes in the white blood cells parameters were significantly associated (P < 0.05) with the type of pyometra. Closed cervix pyometra in dogs showed significantly higher prevalence of clinical signs including depression, vomiting, abdominal enlargement, and fever compared to the open cervix pyometra. Low levels of red blood cells, pack cell volume, and hemoglobin indicated that the pyometra-infected dogs were more likely to have normocytic, normochromic, and non-regenerative anemia. Pyometra was attributed to an increase in AST (Aspertate aminotransferase), ALT (Alanine transaminase), ALP (Alkaline phosphatase), BUN (Blood Urea Nitrogen), and Creatinine while a decrease in serum albumin. Of the all bacterial isolates, E. coli (35.55%) was the most common pathogen isolated from canine pyometra, followed by Pseudomonas spp. (26.66%). E coli and Pseudomonas spp. were susceptible to Imipenem, Amikacin, and Gentamicin while highly resistant to Ampicillin and Erythromycin. Imipenem, Amikacin, and Gentamicin were the most sensitive antibiotics, while Ampicillin and Erythromycin were the most resistant antibiotics for the bacterial strain isolated from canine pyometra. Multidrug resistant was observed in 26 of the isolated bacteria, indicating acquired resistance due to improper and uncontrolled use. Hence early diagnosis and close monitoring of antimicrobial susceptibility before therapeutic intervention is indispensable in preventing the global threat of antimicrobial resistance.

Evaluation of The Effect of Metformin and Progesterone on The Endometrium in Cases of Peri Menopausal Bleeding

Background: Numerous epidemiologic and experimental studies have suggested that unopposed estrogen may be a major factor in the development of benign, premalignant, and malignant endometrial lesions. Objective: To assess the unique effects of progesterone and metformin on simple endometrial hyperplasia and disorganized proliferative endometrium, and to ascertain if metformin is clinically helpful in this situation. Patients and Methods: The study was conducted between April 2023 and September 2023 at the obstetrics and gynecology department of Damanhur Medical National Institute. The study was a double blinded randomized study. 100 patients were involved in this study who were divided into 2 groups: The 1st one (50 cases) was treated with metformin (Glucophage) 500 mg in the first week then raise the dose to reach 1000 mg in the 4th week, for three months long. The 2nd group (50 cases) was administered medroxy progesterone acetate (Provera) 4mg once per day for 3 months long. Next 3 months all cases in both groups were gone for 2nd time endometrial biopsy for assessment of response of treatment and will have ultrasound examination every three months also. Result: Uterine hemorrhage after treatment and endometrial thickness after treatment did not statistically differ between the two study groups. Additionally, there was no statistically significant difference in patient satisfaction or hysterectomy between the two study groups. There was no discernible difference in the two groups' treatment lengths. While there was a high statistical rise in the incidence of nausea, vomiting, and diarrhea in group 2 compared to group 1, there was a strong statistical increase in the incidence of sore breasts, weakness, and metallic taste in group 1 compared to group 2. Conclusion: Progesterone and metformin may both be useful in treating benign endometrial proliferative lesions. To prevent its problems, endometrial proliferative lesions should be identified and treated properly.

The Gonadal Maturity and Gene Expressions of Female Giant Freshwater Prawn (Macrobrachium rosenbergii) after Dietary Administration of Medroxyprogesterone Acetate

Abstract One of the problems in giant prawn cultivation is female giant prawns laying eggs during rearing. They will incubate their eggs for three weeks so that the energy from the expected feed for growth is used for egg development and other reproductive activities. Giving MPA hormone to giant prawns either by injection or oral could inhibit gonadal maturation and increase growth rate. The maturation process of the prawn ovary consists of the activation of some complex cellular mechanisms involving genes that regulate the stages of oocyte development. This study aimed to evaluate the response of gonadal maturity and the expression of the MrvWD-Kazal gene in giant prawns fed with a diet containing MPA hormone. The design used in this study was a completely randomized design with four treatments and five replications. The treatments were feeding a diet added with MPA with a concentration of 0 mg.kg-1 feed as control (K), 50 mg.kg-1 feed (P1), 100 mg.kg-1 feed (P2), and 150 mg.kg-1 feed (P3). MPA hormone at a concentration of 50-150 mg/kg feed could inhibit the gonadal maturation of female prawns. In 100 mg/kg of feed concentration showed the lowest gene expression level, indicating an inhibition of gonadal maturation molecularly. The administration of MPA hormone through the feed is a recommended method of aquaculture because it is more applicable and effective than by injection, even though it has a non-uniform impact on each individual. Highlight Research Administration of MPA hormone through the feed to female giant freshwater prawns can inhibit the level of gonad maturity. Expression of von Willebrand factor D (vWD) – Kazal gene were analyzed in different levels of prawn maturity Gonadosomatic index and gonadal histology confirmed that different levels of administration of MPA hormone through the feed could affect the gonad development. The administration of MPA hormone through the feed is a recommended method for aquaculture because it is more applicable and effective to inhibit early maturation of prawns.

Evaluations of memory, anxiety, and the growth factor IGF-1R after post-surgical menopause treatment with a highly selective progestin

Progestogens are a key component of menopausal hormone therapies. While some progestogens can be detrimental to cognition, there is preclinical evidence that progestogens with a strong progesterone-receptor affinity benefit some molecular mechanisms believed to underlie cognitive function. Thus, a progestin that maximizes progesterone-receptor affinity and minimizes affinities to other receptors may be cognitively beneficial. We evaluated segesterone-acetate (SGA), a 19-norprogesterone derivative with a strong progesterone-receptor affinity and no androgenic or estrogenic-receptor activity, hypothesizing that it would enhance cognition. Middle-aged rats underwent Sham or Ovariectomy (Ovx) surgery followed by administration of medroxyprogesterone-acetate (MPA; used as a positive control as we have previously shown MPA-induced cognitive deficits), SGA (low or high dose), or vehicle (one Sham and one Ovx group). Spatial working and reference memory, delayed retention, and anxiety-like behavior were assessed, as were memory- and hormone- related protein assays within the frontal cortex, dorsal hippocampus, and entorhinal cortex. Low-dose SGA impaired spatial working memory, while high-dose SGA had a more extensive detrimental impact, negatively affecting spatial reference memory and delayed retention. Replicating previous findings, MPA impaired spatial reference memory and delayed retention. SGA, but not MPA, alleviated Ovx-induced anxiety-like behaviors. On two working memory measures, IGF-1R expression correlated with better working memory only in rats without hormone manipulation; any hormone manipulation or combination of hormone manipulations used herein altered this relationship. These findings suggest that SGA impairs spatial cognition after surgical menopause, and that surgical menopause with or without progestin administration disrupts relationships between a growth factor critical to neuroplasticity.

A randomized crossover study to evaluate local tolerability following subcutaneous administration of a new depot medroxyprogesterone acetate contraceptive formulation

ObjectivesThis study aimed to evaluate and compare local tolerability of investigational drug TV-46046 and reference drug Depo-subQ Provera 104, both containing medroxyprogesterone acetate (MPA) as an active ingredient. Study designWe conducted a randomized, crossover, single-center study. Twenty-seven healthy women aged 25 to 47 years at low risk of pregnancy received a subcutaneous injection of each of the four study drugs (120 mg/0.3 mL of TV-46046, 60 mg/0.3 mL of diluted TV-46046, 0.3 mL of TV-46046 placebo, and 104 mg/0.65 mL of Depo-subQ 104) in different quadrants of the abdomen. We assessed local tolerability by occurrence of injection site reactions (ISRs), as well as injection site pain and overall safety for at least 9 months postinjections. ResultsOf a total of 108 study injections, three injections were partial due to needle blockage. We observed a total of 30 ISRs following 105 full-dose injections, including hypopigmentation (n = 24), bruising (n = 4), and atrophy/dimple (n = 2). Eleven cases of hypopigmentation occurred following 25 full-dose injections of undiluted TV-46046 (44.0%), six following 27 full-dose injections of diluted TV-46046 (22.2%), and seven following 26 full-dose injections of Depo-subQ 104 (26.9%). Hypopigmentations occurred on average 8 months postinjection. Injection pain was minimal and dissipated quickly after all four injections. ConclusionsSubcutaneous administration of MPA in a suspension formulation is associated with the delayed onset of hypopigmentation at the site of injection. Although not statistically significant, the rate of ISRs was over 60% higher for undiluted TV-46046 compared to Depo-subQ 104. This difference bears careful monitoring in future studies of TV-46046. ImplicationsFrom a safety standpoint, investigational drug TV-46046 is appropriate for further clinical testing as a 6-month contraceptive injectable. The previously underreported hypopigmentation associated with subcutaneous administration of MPA warrants further investigation and acceptability assessment among users of existing Depo-subQ 104 as well as careful monitoring of local tolerability of TV-46046 in future clinical trials. Trial registrationRegistered at clinicaltrials.gov no: NCT02817464

The comparison of two different protocols ultra-long versus medroxyprogesterone acetate in women with ovarian endometriosis: a prospective randomized controlled trial

BackgroundThis study aimed to investigate the medroxyprogesterone acetate (MPA) + HMG protocol vs ultra-long gonadotrophin releasing hormone (GnRH) agonist protocol in patients with advanced ovarian endometriosis who received in vitro fertilization (IVF).MethodsThree hundred patients with advanced ovary endometriosis who underwent IVF were included, and embryological and clinical outcomes were assessed between March 2017 and September 2017. Patients were divided into MPA + HMG group and 1-month ultra-long GnRHa protocol group.ResultsLower hMG dose and shorter medication time were found in the MPA + HMG group than in the GnRHa group (P < 0.05). Follicle to-Oocyte Index was significantly different between MPA + HMG group and GnRHa group (P < 0.001). No differences were found in the ovary response and numbers of mature oocytes, fertilized oocytes and viable embryos. The clinical pregnancy and live birth outcomes were similar between MPA + HMG group and GnRHa group, and these outcomes were independent of fresh or frozen embryo transfer in the GnRHa protocol group. There were no significant differences in the time to embryo transfer, medical cost and adverse effects.ConclusionThe number of oocytes retrieved and pregnancy outcomes after MPA + HMG protocol are similar to those after ultra-long GnRHa protocol in women with ovarian endometriosis. MPA + HMG protocol may be an alternative to ultra-long GnRHa protocol for IVF in ovary endometriosis patients.Trial registration The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-INR-17010924)Plain English summaryIn conclusion, the administration of MPA in COH showed similar number of oocytes retrieved, no premature LH surge, and similar pregnancy and live birth outcomes in patients with advanced ovarian endometriosis undergoing IVF/ICSI as compared to the one-month long protocol. The use of MPA in COH appears to be promising although many questions remain to be elucidated, including the dose and time of progestin priming as well as its possible influence on the oocyte development potential and microenvironment. Given their good tolerability, few metabolic influence, and low cost, progestogens provide a novel alternative to the conventional protocol for patients with endometriosis.

Endometrial Cancer Management in Young Women.

Simple SummaryEndometrial cancer is a gynecological neoplasm characterized by a constant increase in incidence in highly developed countries. Due to the tendency towards late motherhood in these regions of the world, it is starting to affect more and more young women as well, often those who have not realized their maternity plans. At the same time, we note a very intensive development of research related to endometrial cancer, both in terms of diagnostics and new therapies. Therefore, nowadays, is there a sparing treatment option for young women?Endometrial cancer (EC) rarely develops in young women. Most cases are associated with known risk factors: BMI > 30, history of Polycystic Ovary Syndrome (PCOs), and race differentiation. The molecular EC classification based on The Cancer Genome Atlas Research Network divides these heterogeneous cancers into four types: Polymerase Epsilon Mutation (POLE), Microsatellite Instability (MSI), Copy Number Low (CNL), and Copy Number High (CNH). This division was introduced to allow for early assessment of neoplastic changes and clinical management, including targeted therapies. The basic technique for imaging endometrium changes is transvaginal sonography. Hysteroscopy is the standard for obtaining endometrial material for histological evaluation. The MRI result permits assessment of the extent of EC cancer infiltration. In young women who want to preserve fertility, apart from surgery, conservative management is often implemented after strict selection based on clinical and pathological data. This pharmacological treatment involves the administration of progestogens MPA (medroxyprogesterone acetate) and MA (megestrol acetate). The use of metformin may increase the effectiveness of such treatment. An alternative option is to apply progestogens locally—via the levonorgestrel-releasing intrauterine device. In addition to pharmacological treatment, hysteroscopic resection may be used—part of the uterine muscle adjacent to the pathologically changed endometrium may also undergo resection. An alternative is the administration of estrogen receptor modulators (e.g., SERMs) or aromatase inhibitors, or GnRH agonists.

Progestogen supplementation during superovulation leads to higher embryo viability and TGFB1 gene expression in sheep

This study aimed to compare the effect of the administration of either medroxyprogesterone acetate (MPA) or progesterone (P4) in superovulation (SOV) treatments applied during the first follicular wave on follicular development, embryo yield, and the expression of genes related to pluripotency maintenance, differentiation of the trophectoderm, cell growth and differentiation, apoptosis and energy metabolism in sheep embryos. The estrous cycle of 36 multiparous ewes was synchronized with a short protocol, and the animals were randomly allocated to three groups. At the beginning of SOV, 12 ewes per treatment received an intravaginal sponge impregnated with 60 mg of MPA (TMPA), or an intravaginal device containing 0.33 g of P4 (TP4), or received no progestogen treatment (CON). The device was kept until the fifth dose of FSH. Ewes were mated with five fertile rams. Gene expression was performed by RT-qPCR using grade I and II blastocysts. The numbers of corpora lutea, total structures and viable embryos recovered per ewe were similar (P > 0.05) among groups. However, the viability rate was higher in TP4 (71.9 ± 16.3%) compared to CON (24.4 ± 16.8%; P = 0.01) and similar to TMPA (49.9 ± 16.3%; P = 0.2). Similarly, when compared with CON, treatment with P4 or MPA positively regulated the TGFB1 transcript involved in cell proliferation and differentiation (P = 0.01 and P = 0.03, respectively). In conclusion, supplementation with P4 during the first follicular wave of the estrous cycle improves embryo viability and alters the expression of the TGFB1 gene.

P–687 Impact of medroxyprogesterone acetate (MPA) as pituitary suppression on oocyte quality and clinical outcomes in egg donation recipients

Abstract Study question To compare the impact on oocyte quality and reproductive outcomes in patients who received oocytes from donors stimulated with MPA versus GnRH antagonist protocol. Summary answer Compared to GnRH antagonist, MPA does not exert a major effect on oocyte quality and yields similar reproductive outcomes in egg donation recipients. What is known already Conventional ovarian stimulation (OS) protocols have classically used GnRH analogues, both agonists and antagonists, to avoid premature follicular luteinization. The oral administration of MPA or micronized progesterone during the follicular phase of OS has emerged as an attractive alternative to conventional protocols in the prevention of early luteinization. Compared to progesterone, MPA is characterized by a moderate-strong progestanic action, lower androgenic properties and does not interfere with the measurement of endogenous progesterone. In our group, administration of MPA during the follicular phase of OS has been included in the routine clinical practice of our donor program since late 2019. Study design, size, duration Multicentre, retrospective, observational, cohort study carried out in eleven private university-affiliated IVF centers. The present study included a total of 14,282 fresh ovum donation cycles performed from October 2017 to March 2020. Oocyte donors were recruited and stimulated under either MPA (n = 4,665) or GnRHa (n = 9,617) to suppress the pituitary during the follicular phase of OS, and GnRH agonist was administered to trigger final oocyte maturation in all the participants. Participants/materials, setting, methods Recipients were divided according to the protocol used for premature luteinization prevention during the follicular phase of the ovum donation matched-cycle: Group 1, recipients who received oocytes from donors treated with 10 mg/day of MPA (ProgeveraÒ); Group 2, recipients who received oocytes from GnRH antagonist (FyremadelÒ) down-regulated donor cycles. All the procedures were approved by an Institutional Review Board (1910-VLC–091-JG) and complied with Spanish law on assisted reproductive technologies (14/2006). Main results and the role of chance Regarding donoŕs baseline characteristics, age and antral follicle count were significantly different between groups, but not clinical differences. The length of ovarian stimulation was similar in both groups (10.7 days [95% Confidence Interval (CI) 10.5–10–8] vs 10.5 days [95% CI 10.0–11.00]). Despite slightly higher mean total dose of FSH administered in Group 1 compared to Group 2 (1.841 IU [95% CI 1.813–1.868] vs 1.739 IU [95% CI 1.723–1.754]), there were no differences in the total dose of hMG administered between both groups (967 IU [95% CI 901–1.034] vs 971 IU [95% CI 944–998]). With regard to IVF data, both the number of retrieved oocytes (22.9 [95% CI 22.4–23.4] vs 24.1 [95% CI 23.8–24.3]), and mature oocytes (18.7 [95% CI 18.3–19.1] vs 19.3 [95% CI 19.1–19.6]), were slightly lower in Group 1 compared to Group 2, whereas fertilization rate was significantly higher in Group 1 compared to Group 2 (82.1% [95% CI 81.7–82.6] vs 80.8% [95% CI 80.6–81.2]),. Regarding the clinical outcomes, no differences were observed in either implantation rate (58.7% [95% CI 56.7–60.7] vs 59.3% [95% CI 57.3–61.3]) or clinical pregnancy rate (59.5% vs 59.8%, P = 0.04) between both groups. Limitations, reasons for caution As a consequence of being a retrospective study, only association, and not causation, can be inferred from the results. A further limitation is that donors are healthy young women and do not perfectly match other populations, as infertile patients who may be older, low or high responders to OS. Wider implications of the findings: MPA emerges as an effective oral alternative to GnRH analogues for preventing premature luteinizing hormone surges in donors undergoing OS in ovum donation program. Compared with GnRH antagonists, MPA has advantages of being an oral administration route and providing easy access, yielding similar clinical results. Trial registration number 1910-VLC–091-JG

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.

Depot medroxyprogesterone acetate administration increases cervical CCR5+CD4+ T cells and induces immunosuppressive milieu at the cervicovaginal mucosa

Depot medroxyprogesterone acetate (Depo-Provera) is the most commonly used injectable hormone contraceptive in Sub-Saharan Africa where HIV incidence is high. We determined the impact of Depo-Provera on cervical immune cells and mediators in healthy women. In this longitudinal study, vaginal, endocervical, and rectal swabs were collected at baseline (visit 1), 1 month (visit 2), and 3 months (visit 3) after Depo-Provera injection. Cervical cells were collected by cytobrush and immune markers on cervical CD4 T cells were analyzed by multicolor flow cytometry at three different visits. The levels of immune mediators in cytobrush supernatants as well as vaginal, cervical, and rectal secretions from swabs were analyzed by multiplex assays and ELISA. Compared with baseline levels, we found a significant increase in the frequency of cervical CCR5CD4 T cells and a significant decrease in the frequency of cervical central memory CD4 T cells. Depo-Provera treatment had little effect on expression of immune mediators in rectal mucosa but significantly suppressed numerous immune mediators at cervicovaginal mucosa. Levels of MCP-1, G-CSF, IL-6, IL-10, GM-CSF, and IP-10 were significantly decreased in both vaginal and cervical secretions after Depo-Provera injection. In cervical samples collected by cytobrush, we found reduced levels of 22 of 25 immune mediators after Depo-Provera injection. Changes in immune mediators differed between vaginal and cervical mucosa, demonstrating compartment-specific responses. Depo-Provera altered immune profiles of cervical CD4 T cells and suppressed host immune response at cervicovaginal mucosa, suggesting its likely effect on transmission of sexually transmitted infections including HIV.

Comparison of a novel flexible progestin primed ovarian stimulation protocol and the flexible gonadotropin-releasing hormone antagonist protocol for assisted reproductive technology

To determine whether a flexible progestin primed ovarian stimulation (fPPOS) protocol is effective for preventing premature ovulation. Retrospective cohort study. Private assisted reproduction center. Eighty-seven oocyte donors and 191 recipients of fresh oocytes. Each donor was stimulated with a flexible gonadotropin-releasing hormone (GnRH) antagonist protocol in one cycle and with the new fPPOS protocol in the other, within a period of 6months. FSH was started on cycle day 2-3, and 0.25mg/day GnRH antagonist or 10mg/day medroxyprogesterone acetate (MPA) was started on stimulation day 7 or when the leading follicle reached 14mm, whichever came first. Duration of stimulation, gonadotropin consumption, duration of GnRH antagonist or MPA administration, number of metaphase II oocytes, and pregnancy rates in fresh oocyte recipients. Duration of stimulation was 11 (10-11) days in both groups. Total gonadotropin consumption was similar. Pituitary suppression was started on day 7 and lasted for 5days in each group. There were no premature ovulations in any group. The fPPOS yielded a significantly higher number of cumulus oocyte complexes than GnRH antagonist cycles (33 [21-39] vs. 26 [18-36], respectively). Likewise, the fPPOS generated significantly more metaphase II oocytes than GnRH antagonist cycles (24 [17-34] vs. 21 [15-28], respectively). Recipients of fresh oocytes from fPPOS and GnRH antagonist cycles had similar cleavage, blastulation, implantation, and live birth/ongoing pregnancy rates (50% vs. 48.6%). FPPOS with MPA seems to be an effective choice for preventing premature ovulation in women undergoing ovarian stimulation without compromising oocyte quality.

Exogenous progestogen does not affect first-wave follicle populations and oocyte quality during ovarian stimulation with FSH in sheep

The effect of short-term administration of medroxyprogesterone acetate (MPA) or natural progesterone (P4) during ovarian stimulation with FSH on oocyte recovery was investigated in Santa Inês ewes. Ewes were treated with an intravaginal sponge containing MPA for 6 d; GnRH was applied 36 h after sponge removal and FSH was given in 3 injections (40, 24, and 16 mg, respectively) every 12 h after (D0, approximate ovulation time). At the first FSH dose, the ewes received either a new MPA sponge (n = 10) or a controlled device for internal release impregnated with P4 (n = 10) or did not receive any device (n = 10). Ovarian dynamics were assessed every 12 h by transrectal ultrasonography from D-3 to D2. Oocytes were recovered by laparoscopic ovum pick-up (LOPU) on D2 and graded by morphologic quality. The number of small, medium, and large follicles at D0 and D2 (ultrasound examinations), number of both follicles aspirated and oocytes recovered at LOPU, recovery rate, and oocyte grade did not differ (P > 0.05) among treatments. Thus, the short-term use of MPA or P4 during ovarian stimulation did not affect the first-wave follicle population or morphologic quality of oocytes. We would suggest that, in this protocol, the use of exogenous progestin is unnecessary.

Coexistence of endometrial mesonephric-like adenocarcinoma and endometrioid carcinoma suggests a M\xfcllerian duct lineage: a case report

BackgroundEndometrial mesonephric-like adenocarcinomas exhibit classical histologic features of mesonephric carcinoma; however, it remains unclear whether these tumors represent mesonephric (Wolffian) carcinoma or endometrioid (Müllerian) carcinomas that closely mimic mesonephric carcinoma.Case presentationA 32-year-old Japanese primigravida presented with atypical vaginal bleeding. An endometrial biopsy suggested low-grade endometrioid carcinoma, and she was administered medroxyprogesterone acetate. Her tumor recurred 6 years later, and she underwent hysterectomy, salpingo-oophorectomy, and omentectomy, at which point she was diagnosed with mesonephric-like adenocarcinoma of the uterine endometrium. Retrospective pathological review of the initial biopsy confirmed coexisting low-grade endometrioid carcinoma and mesonephric-like adenocarcinoma of the uterine endometrium. On immunohistochemistry, the endometrioid carcinoma component was diffuse positive for estrogen and progesterone receptors but negative for thyroid transcription factor 1. However, the mesonephric-like adenocarcinoma component exhibited a mixture of estrogen receptor- and thyroid transcription factor 1-positive cells within the same glands.ConclusionsWe encountered a patient with coexisting endometrial mesonephric-like adenocarcinoma and low-grade endometrioid carcinoma, which was treated using medroxyprogesterone acetate therapy, resulting in recurrence of mesonephric-like adenocarcinoma alone. These clinicopathological findings support the prevailing notions that mesonephric-like adenocarcinoma is a Müllerian adenocarcinoma exhibiting mesonephric differentiation.

Cervical and systemic concentrations of long acting hormonal contraceptive (LARC) progestins depend on delivery method: Implications for the study of HIV transmission

Progestin-only long-acting reversible contraceptives (LARCs) are increasingly popular among women seeking contraception; however, recent epidemiological studies suggest that systemically administered medroxyprogesterone acetate (MPA) may increase HIV acquisition. In order to determine the exact mechanisms underlying increases in transmission specific to MPA use and to test safer, alternative contraceptive progestin types and delivery methods, in vitro modeling studies must be performed. To achieve this, it is imperative that accurate hormone concentrations be utilized when modeling progestin-mediated outcomes, as the down-stream effects are dose-dependent. The local concentrations of progestins to which the lower female genital tract tissues are exposed after initiation of LARCs are unknown, but they likely differ from peripheral concentrations, dependent upon the progestin type and delivery method. Here, we measured in vivo endocervical and plasma concentrations of (1) systemically-delivered depo MPA (DMPA), (2) levonorgestrel (LNG) delivered via intrauterine system (IUS) and (3) etonogestrel (ETG) delivered via vaginal ring in women who recently initiated contraception treatment. Levels of ETG and LNG in cervical secretions were 100–200 fold higher than plasma levels. In contrast, measurable MPA levels were approximately 10-fold higher in plasma compared to cervical secretions. These results will inform the design of accurate in vitro studies on the influence of progestins on epithelial cells, tissue explants, and peripheral blood cells, to be able to better predict in vivo outcomes. Subsequent observations will aid in determining how MPA might influence HIV acquisition and may facilitate identification of optimal progestin-containing LARC alternatives for women at high risk for HIV infection.

Different progestin-primed ovarian stimulation protocols in infertile women undergoing in vitro fertilization/intracytoplasmic sperm injection: an analysis of 1188 cycles.

To evaluate the efficacy in suppressing the premature LH surge, embryo quality and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) protocols using medroxyprogesterone acetate versus utrogestan in women of all ages undergoing in vitro fertilization or intracytoplasmic sperm injection. 1188 patients were enrolled in the retrospective study, of which 1002 patients were treated with medroxyprogesterone acetate (M group) and recombinant follicle-stimulating hormone (r-FSH)simultaneously from day 3 of the cycle until trigger day, while 186 patients were treated with utrogestan (U group) and r-FSH instead. Viable embryos were cryopreserved for later transfer in both groups. Differences in baseline characteristics, ovarian stimulation characteristics, endocrinological characteristics, embryo development and clinical outcome between two groups were assessed. Statistical analyses were performed stratified by age and number of oocytes retrieved. No significant differences were observed in the baseline characteristics, ovarian stimulation characteristics and clinical outcome of patients between groups. However, blastulation rate in the U group was significantly higher than that in the M group (49.4% vs. 32.9%, P < 0.001). During ovarian stimulation, LH levels remained steady in both groups. Higher percentage of premature LH surge was found in the U group (2.4% vs. 10.2%, P < 0.001), especially for patients aged more than 35years or who had three oocytes or less retrieved. Both the administration of medroxyprogesterone acetate and utrogestan in PPOS were sufficient to prevent an untimely LH rise, while for patients with poor ovarian response or aged above 35years, MPA may result in a more satisfactory LH level. PPOS protocol using medroxyprogesterone acetate or utrogestan was comparable in terms of oocytes and pregnancy outcome, whereas the administration of utrogestan may result in an improved blastulation than medroxyprogesterone acetate, which needs further exploration.

Differential effects of depot medroxyprogesterone acetate administration on vaginal microbiome in Hispanic White and Black women

ABSTRACT The use of depot medroxyprogesterone acetate (DMPA), a 3-monthly injectable hormonal contraceptive, is associated with an increased risk of HIV acquisition possibly through alteration of the vaginal microbiome. In this longitudinal interventional study, we investigated the impact of DMPA administration on the vaginal microbiome in Hispanic White and Black women at the baseline (visit 1), 1 month (visit 2), and 3 months (visit 3) following DMPA treatment by using 16S rRNA gene sequencing. No significant changes in the vaginal microbiome were observed after DMPA treatment when Hispanic White and Black women were analysed as a combined group. However, DMPA treatment enriched total vaginosis-associated bacteria (VNAB) and Prevotella at visit 2, and simplified the correlational network in the vaginal microbiome in Black women, while increasing the network size in Hispanic White women. The microbiome in Black women became more diversified and contained more VNAB than Hispanic White women after DMPA treatment. While the Firmicutes to Bacteroidetes (F/B) ratio and Lactobacillus to Prevotella (L/P) ratio were comparable between Black and Hispanic White women at visit 1, both ratios were lower in Black women than in Hispanic White women at visit 2. In conclusion, DMPA treatment altered the community network and enriched VNAB in Black women but not in Hispanic White women. The Lactobacillus deficiency and enrichment of VNAB may contribute to the increased risk of HIV acquisition in Black women. Future studies on the impact of racial differences on the risk of HIV acquisition will offer insights into developing effective strategies for HIV prevention. Abbreviations: DMPA: depot medroxyprogesterone acetate; PCR: polymerase chain reaction; OTU: operational taxonomic unit; STI: sexually transmitted infections; VNAB: vaginosis-associated bacteria

P1-143 - Outcome of progestin therapy in patients with endometrial cancer recurrence

Objective: The aim of this study was to elucidate the efficacy of progestin therapy in patients with endometrial cancer recurrence. Methods: Patients who received 200 mg/day of oral medroxyprogesterone acetate (MPA) therapy for endometrial cancer recurrence at our hospital between 2005 and 2016 were retrospectively recruited. Patients who had no target lesion and discontinued MPA within one month were excluded from the analysis. The association of clinicopathological factor with response rate to MPA and progression free survival (PFS) was examined. Results: Seven patients were examined. The median duration of MPA administration was 12.4 months. The complete response was observed in no patient, partial response in 2 patients, stable disease in 3 patients, and progressive disease in 2 patients. The response rate was 28.6% and the median PFS was 9.2 months (range: 1-26.7 months). The adverse events including thrombosis were absent. In two patients with partial response, the histological type was endometrioid carcinoma and the relapse site was lung. However, in two patients with progression disease, the histological types were serous and endometrioid carcinoma, both cases of estrogen receptor-negative, and the relapse sites were peritoneal dissemination and bone. Conclusion: This study suggested that while the effect of progestin therapy was limited on patients with endometrial cancer recurrence, there were some cases where progestin therapy could control the disease progression without side effects for a long time.

Simultaneous TLC-densitometric determination of tamoxifen citrate and medroxyprogesterone acetate and UV-degradation kinetic study of medroxyprogesterone acetate.

Coadministration of tamoxifen citrate (TMC) and medroxyprogesterone acetate (MPA) is preferred to increase the response rate and the percentage recovery in patients with endometrial carcinoma. Administration of TMC and MPA and their combination affects estrogen and progestin receptor concentrations in advanced endometrium carcinoma by affecting 17β-hydroxyl steroid dehydrogenase activity and serum hormone concentrations. A sensitive, accurate and robust thin-layer chromatography method has been established for simultaneous analysis of TMC and MPA. Method development was carried out on silica gel F254 using butanol-acetic acid-water (6:0.5:0.5, v/v/v) as mobile phase. Densitometric scanning was carried out at 241 nm for simultaneous detection of TMC and MPA. Retardation factor (Rf ) values for TMC and MPA were 0.21 and 0.85, respectively. The method was validated according to ICH guidelines. Regression plots revealed linear relationships in the concentration range of 50-500 and 25-250 ng/band for TMC and MPA, successively. Accuracy was ≥99.60 and 98.72% for TMC and MPA, respectively. Forced degradation studies using UV photodegradation was applied on MPA after exposure to UV light for different times and applying a kinetic study for calculating the degradation rate constant (k) and half-life time (t1/2 ).