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Introduction: This large multicenter study aimed to evaluate clinical outcomes using three follitropin alfa preparations within a progestin-primed ovarian stimulation (PPOS) protocol, while identifying contributing factors to cycle success. Methods: A retrospective, anonymized cohort analysis was conducted on donor-recipient cycles from 12 clinics during 2019 to 2021. 7389 oocyte donors underwent ovarian stimulation (OS) with three follitropin alfa preparations (Ovaleap® [n=3231], Bemfola® [n=3542], Gonal-F® [n=616]) were included. Stimulation began on cycle days 2 or 3 with daily administration of 150-225 IU follitropin alfa. 10 mg medroxyprogesterone acetate (MPA) was administered daily until GnRH agonist trigger using a single dose of 0.2mg GnRH agonist for final follicular maturation. Statistical analysis included ANOVA, Chi-squared, and logistic regression. Results: Whilst there were some differences in patient and stimulation characteristics, including donor age and number of retrieved oocytes, clinical variables did not significantly differ among the three study groups. Linear regression revealed donor age [0.986 (0.974-0.999)] and number of mature oocytes [1.027 (1.007-1.047)] significantly impacted ongoing pregnancy rates, while the type of follitropin alfa [1.048 (0.956-1.149)] used did not. No significant differences were observed in the cumulative live birth rate (CLBR) among oocytes obtained from stimulation with Bemfola (64.9%), Gonal-F (64.1%) and Ovaleap (66.1%), p= 0.385. Discussion: This study demonstrated comparable clinical outcomes and CLBR between biosimilars and the reference product of follitropin alfa within PPOS protocols, hence they are interchangeable in a real-world patient setting. [ABSTRACT FROM AUTHOR]

Simple Summary: Medroxyprogesterone acetate is a synthetic progesterone commonly used as a contraceptive in the United States, used by up to 25% of women aged 18–49 who have had intercourse. Progesterone is reported to be associated with the increased growth of meningiomas, a type of central nervous system tumor that can affect the meninges of the brain or spine, and recently an article utilizing a population of French women noted a significant association between medroxyprogesterone use and cerebral meningioma risk, particularly for patients using it for two years. The current study supported the findings of the prior published research, finding an increased chance of cerebral meningioma for those with use of medroxyprogesterone acetate; this association became stronger with longer duration of use. There were no associations observed for spinal meningiomas. Background/Objectives: Medroxyprogesterone acetate (MPA) is a synthetic progesterone that is most commonly used as a contraceptive. MPA acts by binding to the progesterone receptor of the hypothalamus, and this receptor has been found to be important in the pathophysiology of meningiomas. Recent research has reported an increased association between the use of MPA and intracranial meningioma, though the literature is mostly limited by low numbers of meningioma cases and low exposure to MPA. The objective of the current study is to build upon the previously published literature utilizing a large database from the United States. Methods: Utilizing a large commercial insurance database, the current matched case–control study identified meningioma cases using ICD-10 codes from hospital data and MPA exposure, as established from pharmaceutical claims data. Controls were matched 10:1 to cases based on age, year of enrollment, and duration of enrollment. A conditional logistic regression estimated odds ratios (ORs) for the association between MPA exposure and the odds of developing a meningioma. Results: Among 117,503 meningioma cases and 1,072,907 matched controls, oral MPA exposure was not associated with odds of meningioma; however, injection MPA exposure was associated with a 53% increased odds of being a case (OR 1.53, 95% CI 1.40–1.67). This association was specific to cerebral meningiomas (OR 1.68, 95% CI 1.50–1.87), an association that became stronger with a longer duration of use of injection MPA. Conclusions: The current results are consistent with the prior literature, which reports an association between injection exposures to MPA and a stronger association with increasing use of MPA. Women should be cautioned about the prolonged use of MPA, and future research should examine whether the extended use of MPA is associated with the meningioma grade. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the safety and effectiveness of high‐dose oral medroxyprogesterone acetate (MPA) therapy as a fertility‐sparing treatment for patients diagnosed with atypical endometrial hyperplasia (AEH) and endometrioid carcinoma G1 without myometrial invasion (G1EC). Particular attention was given to the extended administration and readministration of MPA for patients with persistent disease following initial treatment and those with recurrence. Methods: We conducted a retrospective analysis of data from 79 patients who underwent daily oral MPA treatment between 2005 and 2024 at Nagoya University Hospital. Patient characteristics, treatment outcomes, factors contributing to recurrence, and post‐MPA therapy pregnancies were examined. Results: MPA therapy achieved a remarkable complete response (CR) rate of 91.1%. The median time to achieve CR was 26.0 and 40.0 weeks for AEH and G1EC patients, respectively. Importantly, 27 patients (39.7%) attained CR after more than 6 months of treatment, including 8 patients (11.8%) who achieved CR after more than a year of treatment. The recurrence rates were 52.9% for AEH and 64.7% for G1EC. Twenty eight patients resumed MPA treatment, and 23 achieved second CR. Notably, recurrence was not associated with clinical factors such as age, body mass index, or post‐CR pregnancy. Among patients who attempted pregnancy after achieving CR, 22 live births were successfully achieved. Conclusions: High‐dose oral MPA therapy demonstrated both safety and efficacy for preserving fertility in patients with AEH and G1EC, resulting in a high CR rate. MPA extension and readministration proved to be beneficial strategies for managing patients with recurrence and persistent disease following initial treatment. [ABSTRACT FROM AUTHOR]

Objective: Src homology phosphotyrosin phosphatase 2 (SHP2) has been implicated in the progression of several cancer types. However, its function in endometrial cancer (EC) remains unclear. Here, we report that the ten-eleven translocation 3 (TET3)-mediated DNA demethylation modification is responsible for the oncogenic role of SHP2 in EC and explore the detailed mechanism. Methods: The transcriptomic differences between EC tissues and control tissues were analyzed using bioinformatics tools, followed by protein-protein interaction network establishment. EC cells were treated with shRNA targeting SHP2 alone or in combination with isoprocurcumenol, an epidermal growth factor receptor (EGFR) signaling activator. The cell biological behavior was examined using cell counting kit-8, colony formation, flow cytometry, scratch assay, and transwell assays, and the median inhibition concentration values to medroxyprogesterone acetate/gefitinib were calculated. The binding of TET3 to the SHP2 promoter was verified. EC cells with TET3 knockdown and combined with SHP2 overexpression were selected to construct tumor xenografts in mice. Results: TET3 and SHP2 were overexpressed in EC cells. TET3 bound to the SHP2 promoter, thereby increasing the DNA hydroxymethylation modification and activating SHP2 to induce the EGFR/extracellular signal-regulated kinase (ERK) pathway. Knockdown of TET3 or SHP2 inhibited EC cell malignant aggressiveness and impaired the EGFR/ERK pathway. Silencing of TET3 inhibited the tumorigenic capacity of EC cells, and ectopic expression of SHP2 or isoprocurcumenol reversed the inhibitory effect of TET3 knockdown on the biological activity of EC cells. Conclusion: TET3 promoted the DNA demethylation modification in the SHP2 promoter and activated SHP2, thus activating the EGFR/ERK pathway and leading to EC progression. [ABSTRACT FROM AUTHOR]

HIV acquisition risk with norethisterone (NET) enanthate (NET-EN) is reportedly less than for depo-medroxyprogesterone acetate intramuscular (DMPA-IM). We investigated the effects of these progestin-only injectable contraceptives on serum testosterone and sex hormone binding globulin (SHBG) levels, since these may play a role in sexual behavior and HIV acquisition. The open-label WHICH clinical trial, conducted at two sites in South Africa from 2018–2019, randomized HIV-negative women aged 18–40 years to 150 mg DMPA-IM 12-weekly (n = 262) or 200 mg NET-EN 8-weekly (n = 259). We measured testosterone by UHPLC-MS/MS and SHBG by immunoassay in matched pairs of serum samples collected at baseline (D0) and at peak serum progestin levels at 25 weeks post initiation (25W) (n = 214–218 pairs). Both contraceptives substantially decreased, from D0 to 25W, the total testosterone [DMPA-IM D0 0.560, 25W 0.423 nmol/L, -24.3% (p < 0.0001); NET-EN D0 0.551, 25W 0.253 nmol/L, -54.1%, (p < 0.0001)], SHBG [DMPA-IM D0 45.0, 25W 32.7 nmol/L, -29.8% (p < 0.0001); NET-EN D0 50.2, 25W 17.6 nmol/L, -65.1% (p < 0.0001)], and calculated free testosterone levels [DMPA-IM D0 6.87, 25W 5.38 pmol/L, -17.2% (p = 0.0371); NET-EN D0 6.00, 25W 3.70, -40.0% (p < 0.0001)]. After adjusting for change from D0, the total testosterone, SHBG and calculated free testosterone levels were significantly higher for DMPA-IM than NET-EN (64.9%, p < 0.0001; 101.2%, p < 0.0001; and 38.0%, p = 0.0120, respectively). The substantial and differential decrease in testosterone and SHBG levels does not explain our previous finding of no detected decrease in risky sexual behavior or sexual function for DMPA-IM or NET-EN users from D0 to 25W. Medroxyprogesterone (MPA) and NET are androgenic and are both present in molar excess over testosterone and SHBG concentrations at 25W. Any within or between contraceptive group androgenic effects on behavior in the brain are likely dominated by the androgenic activities of MPA and NET and not by the decreased endogenous testosterone levels. The clinical trial was registered with the Pan African Clinical Trials Registry (PACTR 202009758229976). [ABSTRACT FROM AUTHOR]

Key Clinical Message: A 19‐year‐old woman had stage IA endometrial carcinoma treated with medroxyprogesterone acetate and experienced a recurrence. This patient's experience illustrates the importance of a thorough history and endometrial assessment in younger patients. [ABSTRACT FROM AUTHOR]

Abstract Background Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age and the most common cause of infertility due to anovulation. PCOS in adolescents is concerning. Nigella sativa is effective in improving gonadotropins and sex hormones. The current study was designed to investigate the effect of Nigella sativa supplementation on PCOS symptoms and their severity in adolescents. Methods The current randomized clinical trial was conducted on 114 adolescents with PCOS who were referred to gynecologist offices and clinics in Gonabad, Iran from March 2022 to March 2023. Participants were randomly allocated to the intervention (Nigella sativa 1000 mg/day) and control (10 mg/day medroxyprogesterone from the 14th day of the cycle for 10 nights) groups. The study duration was 16 weeks. Ovarian volume (measured by ultrasound), anthropometric and blood pressure; serum testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone (LH), hirsutism severity (Ferriman–Gallwey score) levels were evaluated before and after the study. Results Data from 103 participants (control group = 53, intervention group = 50) were analyzed. The mean age of participants was 17.0 (Interquartile range [IQR]:2.0). The mean difference in hirsutism score changes (p

Background: In the progestin-primed ovarian stimulation protocol, the oral administration of medroxyprogesterone acetate has been observed to effectively inhibit the LH surge during ovarian stimulation in patients experiencing infertility. Nevertheless, the use of utilizing medroxyprogesterone acetate during ovarian stimulation can result in more pronounced pituitary suppression, potentially necessitating increased doses of gonadotropins and extended treatment durations. Therefore, it is necessary to determine the optimal dose of medroxyprogesterone acetate, aiming to use relatively lower concentrations of medroxyprogesterone acetate to effectively and safely suppress early LH surges. Method: This retrospective cohort study included 710 patients who underwent cycles of in vitro fertilization or intracytoplasmic sperm injection and were subjected the progestin-primed ovarian stimulation protocol utilizing letrozole between from 1st January 2021 to 31st December 2021. The study population was divided into low, medium, and high concentration groups based on the daily dosage of medroxyprogesterone acetate. The primary focus of this investigation was on the cumulative live birth rate. Secondary outcomes encompassed the occurrence of a premature surge in luteinizing hormone, the quantity of retrieved oocytes, viable embryos, and high-quality embryos, as well as clinical pregnancy rate, abortion rate, ectopic pregnancy rate, and multiple pregnancy rate. Results: In this study, significant differences were observed among three groups in various parameters including body mass index, baseline levels of Anti- Müllerian hormone and luteinizing hormone, antral follicle count, total dose of gonadotropin, and duration of gonadotropin administration (p<0.05). The number of oocytes and viable embryos were significantly higher in medium group and higher than those in the low dose group. Following adjustments for confounding factors related to medroxyprogesterone acetate for various outcome measures, we conducted multiple regression analysis to investigate the independent effects of daily medroxyprogesterone acetate dosage within the combined progestin-primed ovarian stimulation and letrozole protocol. Following multivariable regression analysis, no disparities were found in embryo characteristics (number of oocytes retrieved, number of available embryos, number of high-quality embryos) or pregnancy outcomes (clinical pregnancy rate, cumulative live birth rate) among the three groups. Conclusion: Progestin-primed ovarian stimulation with letrozole using different dose of medroxyprogesterone acetate per day was comparable in terms of the number of oocytes retrieved, the number of high-quality embryos, clinical pregnancy rate and cumulative live birth rate after frozen embryo transfer. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age and the most common cause of infertility due to anovulation. PCOS in adolescents is concerning. Nigella sativa is effective in improving gonadotropins and sex hormones. The current study was designed to investigate the effect of Nigella sativa supplementation on PCOS symptoms and their severity in adolescents. Methods: The current randomized clinical trial was conducted on 114 adolescents with PCOS who were referred to gynecologist offices and clinics in Gonabad, Iran from March 2022 to March 2023. Participants were randomly allocated to the intervention (Nigella sativa 1000 mg/day) and control (10 mg/day medroxyprogesterone from the 14th day of the cycle for 10 nights) groups. The study duration was 16 weeks. Ovarian volume (measured by ultrasound), anthropometric and blood pressure; serum testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone (LH), hirsutism severity (Ferriman–Gallwey score) levels were evaluated before and after the study. Results: Data from 103 participants (control group = 53, intervention group = 50) were analyzed. The mean age of participants was 17.0 (Interquartile range [IQR]:2.0). The mean difference in hirsutism score changes (p < 0.001), right (p = 0.002), and left (p = 0.010) ovarian volume, serum LH (p < 0.001) and testosterone (p = 0.001) were significantly higher in the intervention group compared to the control group. The frequency of oligomenorrhea, menometrorrhagia, and amenorrhea, were significantly reduced after the study in the intervention group compared to the control group (ps < 0.001). Conclusions: Short-term Nigella sativa supplementation may be effective in reducing ovarian volume and improving hormonal balance, and menstrual irregularities in adolescents with PCOS. Further research and long-term studies are warranted to validate the potential therapeutic effects of Nigella sativa in adolescents with PCOS. IRCT registration number: IRCT20221017056209N1 Registration date: 2022-11-22. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effects of medroxyprogesterone acetate (MPA) treatment in comparison to those of gonadotropin releasing hormone (GnRH) antagonists for the prevention of premature luteinizing hormone surges during controlled ovarian hyperstimulation (OS) and the impact of these effects on developing embryos and pregnancy outcomes. Data from 757 cycles of GnRH antagonist treatment and 756 cycles of MPA treatment were evaluated at the Akdeniz University Faculty of Medicine Assisted Reproductive Treatment Center between October 2018 and April 2022. Patient records were obtained from the electronic database of the centre and analysed. In our centre, GnRH antagonist protocols were used between 2018 and 2020, and MPA protocols were used between 2020 and 2022. We chose our study population by year. Our study is a comparative retrospective study. All methods in this study were performed in accordance with the relevant guidelines and regulations. Patients using MPA were significantly older (33.9 ± 5.6 vs. 32.6 ± 5.6, p < 0.001) and had a lower number of antral follicles (AFC) (10.7 ± 8.6 vs. 11.9 ± 10.8, p = 0.007) than those using GnRH antagonists. Both MPA (2.9%) and GnRH antagonists (2.2%) had similar effectiveness in preventing premature ovulation (p = 0.415). There was no significant difference between the two groups in terms of the number of total developed embryos (1.3 ± 1.3 vs. 1.2 ± 1.2, p = 0.765). There was no significant difference in the clinical pregnancy rates with the first ET (%35.4 vs. %30.1, p = 0.074), per total number of transfers (35.3% vs. 30.1%, p = 0.077). MPA was found to be effective at preventing premature ovulation during OS treatment, and the incidence of developing embryo and pregnancy outcomes in patients using MPA were similar to those in patients using GnRH antagonists. Therefore, the use of MPA instead of GnRH antagonists during OS may be a viable alternative for patients not scheduled for fresh ET. [ABSTRACT FROM AUTHOR]

Problem: The decidualization process conditions monocytes to the immunosuppressive and tolerogenic dendritic cell (DC)‐10 profile, a DC subset with high IL‐10 production. Since the implantation process implies an embryo‐endometrium‐immune crosstalk, here we focused on the ability of embryonic soluble factors to modify decidual DC conditioning accordingly with its quality. Method of Study: Human endometrial stromal cell line (HESC) decidualized with medroxyprogesterone and dibutyryl‐cAMP (Dec) was stimulated with human embryo‐conditioned media (ECM), classified as normal (ND) or impaired developed (ID) for 48 h (n = 18/group). Monocytes isolated from six healthy women were differentiated to DCs with rhGM‐CSF+rhIL‐4 in the presence/absence of conditioned media (CM) from decidualized cells stimulated with ECM or nontreated. Results: We found that decidualized cells stimulated with ECM sustain a myeloid regulatory cell profile on monocyte‐derived culture with increased frequency of CD1a‐CD14+ and CD83+CD86low cells. ND‐Dec sustained the higher expression of the DC‐10 markers, HLA‐G and IL‐10 whereas ID‐Dec diminished IL‐10 production (ID‐Dec: 135 ± 37.4 vs. Dec: 223.3 ± 49.9 pg/mL, p < 0.05). The treatment with ECM‐Dec sustained a higher IL‐10 production and prevented the increase of CD83/CD86 after LPS challenge regardless of embryo quality. Notably, TNF‐α production increased in ID‐Dec cultures (ID‐Dec: 475.1 ± 134.7 vs. Dec: 347.5 ± 98 pg/mL, p < 0.05). Conclusions: Although remaining in a tolerogenic profile compatible with DC‐10, DCs can differentially respond to decidual secreted factors based on embryo quality, changing their secretome. These results suggest that in the presence of arrested embryo, DCs could differentially shape the immunological microenvironment, contributing to arrested embryo clearance during the menstrual phase. [ABSTRACT FROM AUTHOR]

Objective: We sought to determine the association of hormonal contraception (HC) and cardiometabolic outcomes among women with human immunodeficiency virus (HIV). Methods: We included women with HIV aged 18–45 years in clinical care in the Southeastern United States between 1998 and 2018. Oral and injectable HC use was captured from medication records. Our outcomes included incident cardiovascular/thrombotic disease (CVD) (atherosclerosis, hypertension, cerebrovascular disease, thrombosis, and heart failure) and incident metabolic disorders (diabetes, dyslipidemia, obesity, and non-alcoholic steatohepatitis). We excluded women with prevalent conditions. We used multivariable marginal structural models to examine time-varying current and cumulative HC use and cardiometabolic outcomes in separate analyses, adjusting for age, race, smoking, time-varying comorbidities, CD4 cell count, HIV RNA, and antiretroviral use. Women with HC exposure were compared with women without HC exposure. Results: Among the 710 women included, 201 women (28%) used HC. CVD analyses included 603 women without prevalent CVD and 93 incident events; metabolic analyses included 365 women without prevalent metabolic disease and 150 incident events. Current and cumulative oral HC use was associated with increased odds of CVD, though this was not statistically significant (adjusted odds ratio [aOR] = 2.08, [95% confidence interval (CI): 0.80–5.43] and aOR = 1.24 [95% CI: 0.96–1.60] per year of use, respectively). Oral HC was not associated with risk of incident metabolic disorders. Depot medroxyprogesterone acetate (DMPA) was not associated with risk of incident CVD. Current and cumulative DMPA use was significantly associated with decreased odds of incident metabolic disorders (aOR = 0.48 [95% CI: 0.23, 1.00] and aOR = 0.65 [95% CI: 0.42–1.00] per year of use, respectively). Conclusion: Our results suggest that cardiovascular risk should be considered when selecting contraception for women with HIV. [ABSTRACT FROM AUTHOR]

Endometrial hyperplasia (EH), an abnormal proliferation of the endometrial cells, is considered as one of the most common causes of abnormal uterine bleeding. Previous studies have reported that melatonin plays a fundamental role in disease treatment. This study aimed the comparison of the effects of progesterone, as the most common therapeutic approach, and melatonin with progesterone alone in improvement of non-atypical endometrial hyperplasia (NEH) and changes in pro-inflammatory cytokine levels. Study population consisted of 40 patients with NEH. Patients were divided into two groups, including 20 subjects treated with melatonin and progesterone and 20 individuals treated with progesterone alone. The blood and endometrial sampling was performed from participants before and after a three-month treatment. The histological examination was microscopically done. The serum levels of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) were measured using ELISA. There was no significant difference in the diabetes status and mean age between patients treated with progesterone and melatonin and those treated with progesterone alone. The improvement rate in the EH was significantly higher in individuals treated with progesterone and melatonin than those treated with progesterone alone (p < 0.05). Additionally, the patients treated with progesterone and melatonin showed significant increases inIFN-γ and TNF-αlevels compared to the control group (p < 0.001-P < 0.05). Melatonin supplementation has a beneficial effect in the treatment of EH due perhaps to enhance the level of IFN-γ and TNF-α. [ABSTRACT FROM AUTHOR]

Introduction: Contraceptive switching from a more effective to a less effective method is a concern, especially in developing countries with high unmet needs for family planning. Indeed, the lack of understanding regarding the reasons behind contraceptive switching behavior in the study area poses a significant challenge in effectively addressing this issue. Objective: This study aimed to assess the magnitude and factors associated with long-acting contraceptive switching in Mizan-Aman town, southwest Ethiopia. Methods: A community-based cross-sectional study was conducted, involving 345 women randomly selected from the population of married women in their reproductive age group. Data collection was conducted through interviewer-administered questionnaires. Bivariate and multivariable logistic regression analyses were employed to ascertain factors linked with contraceptive method switching status. Statistical significance was determined at a P -value of less than.05. Results: Out of the 345 participants interviewed, the prevalence of switching from long-acting to short-acting contraceptives was 28.4%, 95% CI (13.6%, 33.2%). Upon adjusting for confounding variables, factors significantly associated with contraceptive switching included women aged 31–35 [adjusted odds ratio (AOR) = 0.58; 95% CI (0.36, 0.74)] and aged 41–49 [AOR = 0.54; 95% CI (0.48, 0.82)], those with formal education [AOR = 0.79; 95% CI (0.52, 0.87)], those desiring future pregnancy [AOR = 2.12; 95% CI (1.98, 3.38)], experiencing complications from previous method use [AOR = 3.67; 95% CI (2.57, 7.40)], and encountering stockouts of their preferred contraceptive choice [AOR = 2.01; 95% CI (1.39, 3.24)]. Conclusion and recommendation: The study area exhibited a notable prevalence of switching from long-acting contraceptives. Complications arising from prior method use and the unavailability of preferred contraceptive options emerged as significant factors influencing this switching behavior. Thus, it underscores the importance of providing counseling and ongoing support to women, ensuring access to safer and more effective modern contraceptive methods. [ABSTRACT FROM AUTHOR]

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Objective: To provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction (JP) and to explore its mechanism of anti-cancer cachexia. Methods: A mouse model of colon cancer (CT26)-induced cancer cachexia (CC) was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate (MPA). Thirty-six mice were equally divided into 6 groups: normal control, CC, MPA (100 mg•kg−1•d−1), MPA + low-dose (20 mg•kg−1•d−1) JP (L-JP), MPA + medium-dose (30 mg•kg−1•d−1) JP (M-JP), and MPA + high-dose (40 mg•kg−1•d−1) JP (H-JP) groups. After successful modeling, the mice were administered by gavage for 11 d. The body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after implantation. The liver, heart, spleen, lung, kidney, tumor and gastrocnemius muscle of mice were collected and weighed. The pathological changes of the tumor was observed, and the cross-sectional area of the gastrocnemius muscle was calculated. The protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western blot. In addition, an in vitro C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle atrophy. In vitro experiments were divided into control, model, and JP serum groups. After 2-d administration, microscopic photographs were taken and myotube diameters were calculated. Western blot was performed to measure the protein expressions of STAT3 and E3 ubiquitinase. Results: JP combined with MPA restored tumor-induced weight loss (P<0.05, vs. CC) and muscle fiber size (P<0.01, vs. CC). Mechanistically, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induced muscle atrophy in vivo (P<0.05, vs. CC). In addition, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation (P<0.05 or P<0.01 vs. model group) in C2C12 myotubes treated with dexamethasone in vitro. Conclusions: Administration of JP combined with MPA restores tumor-induced cachexia conditions. In addition, the profound effect of JP combined with MPA on tumor-induced cachexia may be due to its inhibition of muscle proteolysis (E3 ubiquitinase system). [ABSTRACT FROM AUTHOR]

Background: Contraceptive use has complex effects on sexual behaviour and mood, including those related to reduced concerns about unintended pregnancy, direct hormonal effects and effects on endogenous sex hormones. We set out to obtain robust evidence on the relative effects of three contraceptive methods on sex behaviours, which is important for guiding contraceptive choice and future contraceptive developments. Methods: This is a secondary analysis of data from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial in which 7,829 HIV-uninfected women from 12 sites in Eswatini, Kenya, South Africa and Zambia seeking contraception were randomly assigned to intramuscular depot-medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (Cu-IUD) or the levonorgestrel (LNG) implant. Data collected for 12 to 18 months using 3-monthly behavioural questionnaires that relied on recall from the preceding 3 months, were used to estimate relative risk of post-baseline sex behaviours, as well as sexual desire and menstrual bleeding between randomized groups using modified Poisson regression. Results: We observed small but generally consistent effects wherein DMPA-IM users reported lower prevalence of specified high risk sexual behaviours than implant users than Cu-IUD users (the '>' and '<' symbols indicate statistically significant differences): multiple sex partners 3.6% < 4.8% < 6.2% respectively; new sex partner 3.0% < 4.0% <5.3%; coital acts 16.45, 16.65, 17.12 (DMPA-IM < Cu-IUD); unprotected sex 65% < 68%, 70%; unprotected sex past 7 days 33% <36%, 37%; sex during vaginal bleeding 7.1%, 7.1% < 8.9%; no sex acts 4.1%, 3.8%, 3.4% (DMPA-IM > Cu-IUD); partner has sex with others 10% < 11%, 11%. The one exception was having any sex partner 96.5%, 96.9% < 97.4% (DMPA-IM < Cu-IUD). Decrease in sexual desire was reported by 1.6% > 1.1% >0.5%; amenorrhoea by 49% > 41% >12% and regular menstrual pattern by 26% <35% < 87% respectively. Conclusions: These findings suggest that women assigned to DMPA-IM may have a modest decrease in libido and sexual activity relative to the implant, and the implant relative to the Cu-IUD. We found more menstrual disturbance with DMPA-IM than with the implant (and as expected, both more than the Cu-IUD). These findings are important for informing the contraceptive choices of women and policymakers and highlight the need for robust comparison of the effects of other contraceptive methods as well. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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 (18.524 kg/m²) and high BMI (≥24 kg/m²) patients, and multivariate logistic regression analysis was performed to analyze the factors affecting pregnancy outcomes. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

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.