Proportion of Hypogonadism in Transfusion-Dependent Thalassemia Patients and Its Contributing Factors.

BACKGROUND: Beta thalassemia is a lifelong disease involving malformed red blood cells (RBC). One of the disease's complications is hypogonadism, in which adults tend to exhibit regression in sexual characteristics, experience sexual dysfunction, and therefore have a lower quality of life. Around 3-10% of the Indonesian population carries the beta-thalassemia gene. This study aimed to see the proportions of hypogonadism in transfusion-dependent thalassemia patients and its contributing factors. METHODS: This is a cross-sectional study involving 60 male patients admitted to three Indonesian general hospitals from July 2022 to July 2023. All patients were diagnosed with beta-thalassemia via chromatography hemoglobin analysis. We performed a single-time physical examination and laboratory examinations to determine FSH, LH, and free testosterone levels. The correlation between Hb and sexual hormone levels was analyzed using Spearman's rank correlation coefficient. ROC curve analysis was conducted afterward. All statistical analysis was done in SPSS version 29. RESULTS: 31 out of 60 thalassemia patients had hypogonadism. Pre-transfusion Hb count was found to be linearly correlated with FSH (r = 0.388, p = 0.049), LH (r = 0.338, p = 0.008), and free testosterone (r = 0.255, p = 0.049). ROC analysis indicated that pre-transfusion Hb was viable as a predictor for hypogonadism (AUC = 0.655, 65.5% sensitivity, 67.7% specificity). CONCLUSION: We confirmed the role of pre-transfusion Hb count as a potential predictor for hypogonadism due to the tissue hypoxia mechanism and transfusion-related iron overload in TDT patients. Decreased Hb is linearly correlated with FSH, LH, and testosterone levels. Decreased Hb also downregulates these factors.

The Asian Society of Endometriosis and Adenomyosis guidelines for managing adenomyosis.

This is the first guidelines for adenomyosis from the Asian Society of Endometriosis and Adenomyosis.

IVF outcome with a high level of AMH: a focus on PCOS versus non-PCOS.

BACKGROUND: The purpose of this research was to investigate whether high AMH levels in PCOS patients resulted in different IVF outcomes compared to those in non-PCOS patients. METHODS: A retrospective cohort study was conducted involving 238 women undergoing IVF who had AMH levels > 4 ng/ml. Participants were divided into two groups: PCOS and non-PCOS. RESULTS: The median AMH level was significantly higher in the PCOS group (7.59 ± 4.61 ng/ml vs. 5.91 ± 2.22 ng/ml, p < 0.001). The PCOS group required less gonadotropin but yielded more oocytes after stimulation. Significantly more participants from the PCOS group (41.5% [n = 39]) developed a hyperresponse to ovarian stimulation compared to the non-PCOS group (26.4% [n = 38]) (OR = 1.978, 95% CI 1.138-3.488; p = 0.015). CONCLUSION: There were significant differences in terms of total doses of gonadotropin and the number of oocytes retrieved in the PCOS and non-PCOS groups. Women with PCOS and high AMH levels have a higher risk of hyperresponse after ovarian stimulation than women without PCOS.

Effectiveness of dienogest in improving quality of life in Asian women with endometriosis (ENVISIOeN): interim results from a prospective cohort study under real-life clinical practice.

BACKGROUND: Dienogest has been shown to substantially improve endometriosis-associated symptoms such as debilitating chronic pelvic pain, and in turn, health-related quality of life (HRQoL). To date, there is no data on patient-reported outcomes reflecting the real-world practice in Asia where endometriosis is a relevant health, social and economic burden. This non-interventional, multi-center, prospective study aims to investigate the influence of dienogest on HRQoL. METHODS: Asian women received dienogest (2 mg/daily) and were followed for 24 months. The effectiveness of dienogest to improve HRQoL and endometriosis-associated pelvic pain (EAPP) was assessed by patient-reported outcomes. HRQoL, especially the "pain" domain as primary endpoint, was evaluated with the Endometriosis Health Profile-30 (EHP-30) questionnaire. The numeric rating scale served to determine changes in the severity of EAPP. Within the presented interim analysis (data cut-off: 2017-11-27), the mean changes in EHP-30 and EAPP scores from baseline to 6 months upon availability of the data were evaluated. Treatment-emergent adverse events (TEAEs) and bleeding profiles were documented. RESULTS: Dienogest therapy decreased EHP-30 scores in all assessed domains (score 0-100, lower scores indicate better HRQoL). Primarily, the "pain" domain was improved in 78.4% of patients. EAPP was reduced (score 0-10, lower scores reflect less pain), highlighted by a mean reduction of the pain score by - 4.5 points. Patients with a higher EAPP score at baseline had an increased response to dienogest (- 6.2 points mean change) compared to patients with low baseline EAPP severity (- 1.4 points mean change). Both surgically and clinically diagnosed patients described comparable pain reduction, as well as women with or without prior treatment. Drug-related TEAEs were documented for 31.5% of patients, with amenorrhoea (5.9%) and metrorrhagia (5.1%) being the most common events. The bleeding pattern was changed upon dienogest, characterized by decreased normal bleeding (84.2 to 28.8%) and increased amenorrhea (3.2 to 42.9%) at 6 months. CONCLUSION: The data indicate an amelioration of HRQoL and EAPP upon dienogest therapy. No new safety signals were observed. Therefore, its use as first-line therapy for long-term management of debilitating and chronic endometriosis-associated pain represents an interesting option that remains to be further investigated. TRIAL REGISTRATION: Name of registry: Clinical Trials Clinicaltrials.gov registration number: NCT02425462 Registration date: 2015-04-24. Registration timing: prospective.

Anti-mullerian hormone as a diagnostic and prognostic tool for PCOS patients.

PURPOSE: To determine whether the measurement of serum AMH can be used to diagnose PCOS and as a tool to predict the prognosis of PCOS. METHODS: This is a case-control study. Women of reproductive age (18-35 years) were recruited consecutively at a tertiary academic hospital during the period of March 2009-October 2011 and were divided into case (PCOS patients defined by the Rotterdam criteria) and control groups (non-PCOS patients). Menstrual history, clinical manifestations of hyperandrogenism, ovarian ultrasound assessments, and the levels of AMH, LH, FSH, and estradiol were collected. RESULTS: Seventy-one cases and 71 controls were recruited. AMH serum levels were significantly higher in PCOS patients than in controls. The Area Under the Curve (AUC) of the serum AMH assay in PCOS patients reached a value of 0.870. With a cut-off value of 4.45 ng/ml, the serum AMH level had a sensitivity of 76.1 % and a specificity of 74.6 %. The most common phenotypes of PCOS in this study were anovulation and polycystic ovary (63.4 %). However, the mean level of AMH was highest in the phenotypes of anovulation, polycystic ovaries and hyperandrogenism (11.1 ng/ml). CONCLUSIONS: In Indonesian women, AMH can be used as an alternative diagnostic criteria for PCOS patients with a cut-off value of 4.45 ng/ml. AMH value rise when hyperandrogenism is present therefore serum AMH levels also reflect the phenotype of PCOS. However, these findings must be confirmed with larger clinical studies.

Mechanism of elevated LH/FSH ratio in lean PCOS revisited: a path analysis.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 5-20% of reproductive-age women. However, the treatment of PCOS is mainly based on symptoms and not on its pathophysiology. Neuroendocrine disturbance, as shown by an elevated LH/FSH ratio in PCOS patients, was thought to be the central mechanism of the syndrome, especially in lean PCOS. LH and FSH secretion are influenced by GnRH pulsatility of GnRH neurons in the hypothalamus. Kisspeptin is the main regulator of GnRH secretion, whereas neurokinin B (NKB) and dynorphin regulate kisspeptin secretion in KNDy neurons. This study aims to deepen the understanding of the neuroendocrine disorder in lean PCOS patients and its potential pathophysiology-based therapy. A cross-sectional study was performed at Dr. Cipto Mangunkusumo Kencana Hospital and the IMERI UI HRIFP cluster with 110 lean PCOS patients as subjects. LH, FSH, LH/FSH ratio, kisspeptin, NKB, dynorphin, leptin, adiponectin, AMH, fasting blood glucose, fasting insulin, HOMA-IR, testosterone, and SHBG were measured. Bivariate and path analyses were performed to determine the relationship between variables. There was a negative association between dynorphin and kisspeptin, while NKB levels were not associated with kisspeptin. There was no direct association between kisspeptin and the LH/FSH ratio; interestingly, dynorphin was positively associated with the LH/FSH ratio in both bivariate and pathway analyses. AMH was positively correlated with the LH/FSH ratio in both analyses. Path analysis showed an association between dynorphin and kisspeptin levels in lean PCOS, while NKB was not correlated with kisspeptin. Furthermore, there was a correlation between AMH and the LH/FSH ratio, but kisspeptin levels did not show a direct significant relationship with the LH/FSH ratio. HOMA-IR was negatively associated with adiponectin levels and positively associated with leptin and FAI levels. In conclusion, AMH positively correlates with FAI levels and is directly associated with the LH/FSH ratio, showing its important role in neuroendocrinology in lean PCOS. From the path analysis, AMH was also an intermediary variable between HOMA-IR and FAI with the LH/FSH ratio. Interestingly, this study found a direct positive correlation between dynorphin and the LH/FSH ratio, while no association between kisspeptin and the LH/FSH ratio was found. Further research is needed to investigate AMH and dynorphin as potential therapeutic targets in the management of lean PCOS patients.

The Efficacy and Safety of DLBS3233, A Combined Bioactive Fraction of Cinnamomum burmanii and Lagerstroemia speciosa Plants on The Endocrine-Metabolic Profile of Women with Polycystic Ovary Syndrome: A Randomized Clinical Trial.

BACKGROUND: A bioactive fraction of Cinnamomum burmanii and Lagerstroemia speciosa, DLBS3233, has recently been used for type-2-diabetes treatment due to its favorable effect on insulin sensitivity. The insulin resistance leading to metabolic syndrome is closely linked to hyperandrogenemia in polycystic ovary syndrome (PCOS). This study evaluated the metabolic and reproductive efficacy and safety of DLBS3233 in insulin-resistant PCOS women. MATERIALS AND METHODS: This was a 2-arm, randomized, double-blind, controlled, noninferiority clinical study over a 6-month therapy with DLBS3233 100-mg daily in comparison to metformin-XR 750 mg twice daily, involving 124 PCOS women with insulin resistance. The primary efficacy endpoint was the improvement of Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). Secondary endpoints were improvements in other metabolic and reproductive parameters. Safety endpoints were based on blood pressure, heart rate, electrocardiogram findings, liver and renal function, and adverse events. RESULTS: After 6 months, HOMA-IR improvement in DLBS3233-treated group (-1.03 ± 0.50) and metformin-XR (-1.19 ± 0.50) were comparable, with a between-group difference fell within the pre-set non-inferiority margin (0.16; 95% confidence interval (CI): -1.24, 1.56; P=0.3168). The HOMA-IR in both groups were significantly improved from baseline. On all secondary endpoints, both groups showed comparable effects. Markedly fewer adverse events occurred in the DLBS3233 treated group than in the Metformin-XR-treated group and most were mild clinically and had been resolved by the end of the study. CONCLUSION: Treatment with DLBS3233 100-mg daily in PCOS women demonstrated comparable efficacy to metformin- XR 750-mg twice daily in improving insulin resistance. However, the non-inferiority of DLBS3233 to metformin- XR remains inconclusive. DLBS3233 was more tolerable than metformin-XR (registration number: NCT01733459).

Altered expression of kisspeptin, dynorphin, and related neuropeptides in polycystic ovary syndrome: A cross-sectional study.

Background: Since kisspeptin (KISS1) in the hypothalamus is affected by the inhibitory effect of dynorphin, it raises questions about the controlled balance of these 2 neuropeptides in women with and without polycystic ovary syndrome (PCOS). Objective: This study compares the expression levels of KISS1, dynorphin, neurokinin-B, leptin, and neuropeptide-Y in women with and without PCOS. Materials and Methods: In this cross-sectional study, the peripheral blood samples of 20 women with PCOS and 20 women without PCOS who referred to Yamin Kencana Clinic, Cipto Mangunkusumo hospital, Jakarta, Indonesia were enrolled from August-December 2022. mRNA relative expression of genes related to the central factors associated with PCOS, such as leptin, neuropeptide-Y, KISS1, tachykinin-3, and prodynorphin (PDYN), in PCOS and non-PCOS populations were examined. Gene quantification was carried out by the quantitative polymerase chain reaction method. Results: The KISS1/PDYN ratio was significantly higher in the PCOS group than in the control group (p = 0.02), and the PDYN was lower in the PCOS group than the control group (p < 0.001). Moreover, the positive correlation between KISS1 and the KISS1/PDYN ratio was significantly stronger in the PCOS group than in the control group (R = 0.93; p < 0.001 vs. R = 0.66, p < 0.001). Conclusion: Our results suggest that an increased KISS1/PDYN ratio in PCOS women is related to diminished dynorphin expression. Low expression of the gene encoding dynorphin and a high KISS1/PDYN ratio is highly specific to PCOS.

Ten years of in vitro fertilization in Indonesia: Access to infertility care in a developing country.

OBJECTIVE: This research was conducted to assess access to assisted reproductive technologies (ART) and the current status of the in vitro fertilization (IVF) program that have been implemented in Indonesia over the last 10 years. METHODS: We established a retrospective cohort study and descriptive analysis of the current state of access to infertility care in Indonesia. The data were collected from all IVF centers, clinics, and hospitals in Indonesia from 2011 to 2020, including the number of IVF clinics, total ART cycles, retrieved fresh and frozen embryos, average age of IVF patients, IVF pregnancy rate, and causes of infertility. RESULTS: The number of reported fertility clinics in Indonesia has increased from 14 clinics in 2011 to 41 clinics by 2020. As many as 69 569 ART cycles were conducted over the past 10 years, of which 51 892 cycles used fresh embryos and 17 677 cycles used frozen embryos. The leading cause of consecutive infertility diagnosis was male infertility. Nearly half of the women who underwent IVF procedures (48.9%) were under 35 years old. The pregnancy rate outcome of women who underwent IVF ranged from 24.6% to 37.3%. CONCLUSION: Developments in ART in Indonesia have led to improvements in the ART cycles performed throughout the 10 year period. The identification of key areas that require improvement can provide an opportunity to enhance access to infertility care.

Chronological age vs biological age: an age-related normogram for antral follicle count, FSH and anti-Mullerian hormone.

OBJECTIVE: To evaluate the correlation between chronological and biological age by comparing the normograms of AFC, AMH, and FSH. DESIGN: Retrospective study SETTING: Data were taken from patients who visited the Infertility Clinic at Dr. Cipto Mangunkusumo General Hospital Jakarta, Indonesia, between January 2008 and December 2010. PATIENT(S): Infertile women who visited the Infertility Clinic. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Normogram of AFC (n = 366), AMH (n = 1616) and FSH (n = 415). RESULT(S): The correlations among AFC, AMH, FSH, and age are statistically significant. Normograms of AFC and AMH with 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles showed a decrease in age where FSH increased. A cut-off value of AFC, AMH, and FSH for poor responders was plotted at the 50th percentile of each normogram. Serum AMH and AFC started to decline in women between 34 and 35 years old. We found a relatively lower slope increase of FSH in older patients compared to that of AFC and AMH. FSH was observed to be a later predictor of biological age than AMH and AFC. CONCLUSION(S): AMH predicted biological age earlier than FSH or AFC. Normograms can provide a reference guide for physicians to counsel infertile women. However, future validation with longitudinal data is still needed.

Influence of internet, mobile phone use, and sociodemographic factors on women's knowledge and attitude towards contraception in Indonesia.

OBJECTIVE: Rapid population growth has been a problem in Indonesia for several decades. One of the reasons for this phenomenon is limited knowledge of reproductive health and proper contraception. METHODS: . The use of mobile phones and the internet has made it easier to access health information. This study aimed to determine the influence of the internet, mobile phone use, and sociodemographic factors on Indonesian women's knowledge of and attitudes toward contraception. METHODS: The present study used secondary data from the 2017 Indonesian Health and Demographics Survey. Altogether, 49,627 women participated in this study. Descriptive statistics were performed, and bivariate analysis using the chisquared test was performed to measure the association between variables. RESULTS: Knowledge about the ovulation cycle and contraception was positively associated with mobile phone ownership, frequent internet use, higher wealth index, reading printed media, listening to the radio, watching the television, higher educational level, and older age. The use and intention of contraception were positively associated with lower wealth index, watching television at least once a week, primary-secondary educational level, rural residence, and older age. Thus, acquisition of knowledge does not necessarily translate into implementation of contraceptive. METHODS: , since there might be certain digital and social barriers. CONCLUSION: Access to the internet and mobile phones as well as certain sociodemographic factors have contributed to an increase in women's knowledge about contraception, but not necessarily in their knowledge regarding the use of contraception.

Down-Regulation of miR-93 Negatively Correlates with Overexpression of VEGFA and MMP3 in Endometriosis: A Cross-Sectional Study.

BACKGROUND: Endometriosis is identified as presence of the endometrium outside the uterine cavity. Retrograde menstruation contributes to the endometrial tissue implantation and the establishment of endometriotic lesions at ectopic sites. It has been suggested that the endometriotic lesions are rich in angiogenic growth factors, while they have an essential role in survival and invasion of these cells. We investigated regulation of microRNA-93 (miR-93) and its involvement with vascular endothelial growth factor A (VEGFA) and matrix metalloproteinase (MMP) 3 expression in women with endometriosis. MATERIALS AND METHODS: This was a cross-sectional study at Central Surgical Installation, Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia, between October 2020 and November 2021. Eutopic and ectopic endometrial tissues were collected from 30 subjects with laparoscopically-confirmed endometriotic women. Normal endometrial cells of non-endometriosis women served as controls. Total RNA was isolated from all samples and a quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to analyze the expression of miR-93, VEGFA and MMP. RESULTS: There was no significant difference in the expression levels of VEGFA (2.14 ± 0.50, P=0.719) and MMP3 (2.99 ± 0.42, P=0.583) between endometriotic lesions of endometriosis women and the healthy endometrium. Expression of miR-93 was significantly lower in the eutopic endometrium (16.7 fold) and ectopic endometriotic lesion (20 fold) compared to the normal endometrium (P<0.001). Furthermore, we also observed a significant correlation between miR-93, VEGFA expression in eutopic endometrium obtained from women with endometriosis (r=-0.544, P=0.029). Expression of the miR-93 was also negatively correlated with MMP3 expression in both eutopic (r=-0.412, P=0.01) and ectopic (r=-0.539, P=0.03) endometrial cells of women with endometriosis. CONCLUSION: VEGFA and MMP3 expression levels trended to be increased in both eutopic and ectopic endometrial tissues of endometriosis women, while down-regulation of miR-93 might be involved in the alteration of VEGFA and MMP3 in endometriosis.

Twelve Hours Post-Injection Serum Human Chorionic Gonadotropin and Body Mass Index Predicts In Vitro Fertilization Oocyte Maturation Rate: A Cross-Sectional Study.

BACKGROUND: In vitro fertilization (IVF) remains a main treatment for infertility cases. Post-injection human chorionic gonadotropin (hCG) level is an essential factor in determining oocyte maturation rate in IVF. This study aimed to determine the relationship between 12 hours post-injection serum hCG level and oocyte maturation rate among IVF participants. MATERIALS AND METHODS: A cross-sectional study on IVF participants was done at a tertiary hospital in Indonesia from January 2020 to December 2021. Subjects were injected with 250 µg of recombinant-hCG (r-hCG) subcutaneously. Twelve hours post-injection serum hCG levels and oocyte maturation rate data were retrieved and analyzed accordingly. RESULTS: Twenty-eight subjects were recruited into the study. Higher 12 hours post-injection serum hCG was related to oocyte maturation rate (P=0.046). The cut-off point of 12 hours post-injection serum hCG to predict better oocyte maturation rate was 90.15 mIU/mL (sensitivity 68.2%, specificity 83.3%). Oocyte maturation rate may be predicted using body mass index (BMI) and 12 hours post-injection serum hCG. CONCLUSION: Higher 12 hours post-injection serum hCG was associated with a higher oocyte maturation rate in IVF subjects.

Outcome findings of COVID-19 vaccine among 31 977 pregnant women in Indonesia.

OBJECTIVE: We provide an overview of the safety of messenger RNA and inactivated coronavirus disease 2019 (COVID-19) vaccine and monitoring of pregnant women after COVID-19 vaccination. The vaccine safety outcome profile is beneficial for further recommendations of COVID-19 vaccination in pregnancy. METHODS: This research was conducted as descriptive research. Sampling was performed using an online questionnaire to be filled out voluntarily and distributed to all pregnant women in Indonesia who received the COVID-19 vaccination. Data collection was performed and descriptive statistics were obtained. RESULTS: Among 31 977 pregnant women, 24 212 (75.7%) received the first dose, 7619 (23.8%) received the second dose, and 146 (4.5%) received the third dose of the COVID-19 vaccine. Sinovac vaccine is the most administered vaccine to pregnant women (27 122 [84%]). Most pregnant women (78.7%) who were vaccinated had no adverse effects after immunization, while the most reported adverse effects were mild symptoms. CONCLUSION: The current study contributed evidence that COVID-19 vaccination during pregnancy has minimal adverse effects. These findings may help pregnant women and healthcare providers to make informed decisions regarding vaccination.

Vitamin B3 (niacin), B6, C, and iron intake are associated with the free androgen index, especially in normoandrogenic polycystic ovary syndrome

Objective: Nutritional intake is one of the most common environmental risk factors for polycystic ovary syndrome (PCOS) because it is associated with obesity and insulin resistance. The aim of this study was to determine the relationship between micronutrient intake and androgen levels associated with PCOS. Material and Methods: This cross-sectional study was performed in patients with PCOS divided into two groups, normoandrogenic (NA) and hyperandrogenic (HA), and healthy controls. Dietary intake assessment was performed using a modified 38-item semi-quantitative food frequency questionnaire. Bivariate, correlation, and multivariate analyses were performed to determine the association between study variables. Results: There were 79 patients with PCOS, of whom 50 were NA and 29 were HA. There were 66 subjects in the healthy control group. The baseline characteristics in all groups were similar, except for body mass index and hormonal profile which were elevated in the HA group compared to the other groups. There was a significant negative correlation between the free androgen index (FAI) and intake of vitamin B1, vitamin B2, niacin, vitamin B6, calcium, and iron in the NA group, while this association was absent in the HA group. Multivariate linear regression analysis showed that the intake of vitamin B6, vitamin C, niacin, and iron had a significant effect on the FAI. Conclusion: There is an effect of micronutrient intake on androgen levels in women with PCOS. The association was more significant in NA PCOS than in the HA PCOS groups. These findings suggest an association between micronutrients, androgens and PCOS at a systemic level.

Mesh-Tissue Integration of Platelet-Rich Plasma-Decellularized Amnion Scaffold-Polypropylene Mesh Sandwiches Implanted in the Vesicovaginal Spaces of Hypoestrogenic Rabbit Models: Protocol for a Randomized Controlled Trial.

BACKGROUND: Mesh-augmented surgery with polypropylene meshes (PPMs) is often used in urogynecology and pelvic reconstructive surgery. However, the various complications that arise from its integration process have resulted in a decrease in the number of mesh-augmented surgeries performed worldwide. An approach to improving mesh-tissue integration is coating PPMs with anti-inflammatory and wound-healing molecules, such as platelet-rich plasma (PRP), which is a component of biotechnologies that are capable of accelerating wound healing. Estrogen is also known to have a beneficial effect on wound remodeling; therefore, a hypoestrogenic status may have negative implications for wound healing. The mechanism of how PRP plays a role in wound remodeling, especially among individuals in a hypoestrogenic state, has not been fully described until now. OBJECTIVE: Our aim is to investigate the impact of applying PRP to PPMs in hypoestrogenic rabbit models. METHODS: Our study will be a randomized controlled trial involving hypoestrogenic rabbit models. Samples were categorized into either the PRP group or the PPM group (1:1 ratio), with a minimum sample size of 16 in each arm, via simple random sampling. All samples were put into a hypoestrogenic state via bilateral oophorectomy. After confirming a decrease in estradiol level, the meshes were implanted in the vesicovaginal space. The samples were euthanized on the 14th, 28th, or 90th day of the surgery. The mesh-tissue integration process will be analyzed based on inflammatory parameters (inflammatory infiltrate, interleukin-17, and interleukin-1B expression); angiogenesis (CD31 expression); and collagen deposition, which will be assessed by using Masson trichrome staining. RESULTS: Our study is in the protocol development stage. A preliminary study regarding its feasibility, including the feasibility of the preparation of hypoestrogenic rabbit models, mesh implantation in the rabbits' vesicovaginal spaces, the PRP and amnion scaffold, started in February 2022. The results of our study are expected to be available by the end of 2022. CONCLUSIONS: Our randomized controlled trial is designed to provide high-quality evidence on the effect of applying a PRP-decellularized amnion scaffold to PPMs in the vesicovaginal spaces of hypoestrogenic rabbit models. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/37942.

Impact of Long-Term Dienogest Therapy on Quality of Life in Asian Women with Endometriosis: the Prospective Non-Interventional Study ENVISIOeN.

Several clinical trials in women with endometriosis demonstrated that dienogest reduces endometrial lesions and improves health-related quality of life (HRQoL). To assess HRQoL in dienogest-treated patients in real-world setting, we conducted a prospective, non-interventional study in 6 Asian countries. Women aged ≥18 years with clinical or surgical diagnosis of endometriosis, presence of endometriosis-associated pelvic pain (EAPP) and initiating dienogest therapy were enrolled. The primary objective was to evaluate HRQoL using the Endometriosis Health Profile-30 (EHP-30) questionnaire. The secondary objectives included analysis of EAPP, satisfaction with dienogest, endometriosis symptoms and bleeding patterns. 887 patients started dienogest therapy. Scores for all EHP-30 scales improved with the largest mean changes at month 6 and 24 in scale pain (-28.9 ± 27.5 and - 34 ± 28.4) and control and powerlessness (-23.7 ± 28.2 and - 28.5 ± 26.2). Mean EAPP score change was -4.6 ± 3.0 for both month 6 and 24 assessments. EAPP decrease was similar in surgically and only clinically diagnosed patients. From baseline to month 24, rates of normal bleeding decreased (from 85.8% to 17.5%) while rates of amenorrhea increased (from 3.5% to 70.8%). Majority of patients and physicians were satisfied with dienogest. Over 80% of patients reported symptoms improvement. 39.9% of patients had drug-related treatment-emergent adverse events, including vaginal hemorrhage (10.4%), metrorrhagia (7.3%) and amenorrhea (6.4%). In conclusion, dienogest improves HRQoL and EAPP in the real-world setting in women with either clinical or surgical diagnosis of endometriosis. Dienogest might be a promising first-line treatment option for the long-term management of debilitating endometriosis-associated symptoms.NCT02425462, 24 April 2015.

Chronic Pelvic Pain in Women with Endometriosis is Associated with Psychiatric Disorder and Quality of Life Deterioration.

BACKGROUND: Endometriosis is a condition associated with pelvic pain, infertility, and possibly with decreased quality of life as well as psychiatric disorder. The purpose of our study was to evaluate the association between pain characteristic, psychiatric disorder, and quality of life in women with endometriosis. METHODS: A cross-sectional study was done involving 160 women with medical diagnosis of endometriosis. Pain intensity was evaluated using Visual Analog Scale (VAS), Quality of Life with Endometriosis Health Profile (EHP-30), and psychologic condition with Mini International Neuropsychiatric Interview International Classification of Diseases (Mini-ICD). RESULTS: VAS and psychiatric disorder were associated with higher EHP-30 score (ß = 9.3 (95% CI: 7.15-11.45; p < 0.001 and ß = 28.51 (95% CI: 20.06-36.05; p < 0.001), respectively) and hence, lower quality of life. The strongest correlation between VAS and EHP-30 was in pain (r=0.586; p<0.001) and 'control and powerlessness' (r = 0.583; p < 0.001). VAS was also higher in subjects with depression (49.5 (25.4-77.8) vs 34.4 (6.1-74.6); p < 0.001). CONCLUSION: We conclude that severe endometriosis-related pain and the presence of psychiatric disorder were associated with lower quality of life. Comprehensive management of endometriosis is crucial to improve patients' quality of life.

IN-SILICO dynamic analysis of Sulawesi propolis as anti-endometriosis drug: Interaction study with TNF alpha receptor, NF-kB, estrogen receptor, progesterone receptor and prostaglandin receptor.

INTRODUCTION: Endometriosis is a disease that impacts around 10% of all women in reproductive age, with pelvic pain and infertility as its main clinical features. Current medical treatment targeting lowering estrogen activity has not shown sufficient result due its side effects and reproductive function suppression. Propolis has been widely studied, showing anti inflammation and pro-apoptosis property, that could potentially be used in the treatment of endometriosis. This study investigates the interaction between Sulawesi Propolis' active components and receptors and protein related to endometriosis pathogenesis. METHODS: Active components of Sulawesi Propolis were initially identified with their targeted protein receptors. Lipinski rules were used to screen potential components. The ligands and proteins were tested using Autodock program to predict the most active compound and possible binding sites between propolis and some target proteins associated with inflammatory and apoptotic activity in endometriosis models. Receptor modelling is then performed using Swiss-Model. RESULTS: These active components of Sulawesi Propolis showed a strong binding potential towards TNF- α, NF-kb, Estrogen-α, Estrogen-ß, progesterone B, PGE2 EP2 and EP3 subtype respectively: Sanggenon C, Sanggenon H, Epicryptoacetalide, Chrysin-7-O-ß-D-glucopyranodside, Irilone, Polydatin and Epicryptoacetalide. Compared to its negative ligand, Sulawesi Propolis displayed a stronger binding capacity to TNF-α, Estrogen-α, and Progesterone B receptors. CONCLUSION: Sulawesi Propolis has the ability to interact with receptors related to reproductive function, apoptotic reactions and inflammatory processes, a significant factor associated with the pathogenesis of endometriosis.

Effect of conditioned medium of umbilical cord-derived mesenchymal stem cells as a culture medium for human granulosa cells: An experimental study.

BACKGROUND: The umbilical cord-derived mesenchymal stem cells conditioned medium (UC-MSCs-CM) produces secretomes with anti-apoptotic properties, and has the potential to prevent apoptosis of granulosa cells (GC) during controlled ovarian hyperstimulation. OBJECTIVE: To observe the effect of UC-MSCs-CM on the interaction between pro- and anti-apoptotic proteins and the influence of growth differentiation factor 9 (GDF9) production in GC. MATERIALS AND METHODS: UC-MSCs-CM was collected from umbilical cord stem cell culture on passage 4. GC from 23 women who underwent in vitro fertilization were cultured and exposed to UC-MSCs-CM for 24 hr. Then RNA of the GC was extracted and the mRNA expression of BCL-2 associated X (BAX), survivin and GDF9 were analysed using quantitative real-time PCR. The spent culture media of the GC were collected for measurement of insulin growth factor 1 using ELISA. RESULTS: The expression of BAX was significantly different after UC-MSCs-CM exposure (4.09E-7 vs. 3.74E-7, p = 0.02). No significant changes occurred in survivin, BAX/survivin ratio, and GDF9 expression after UC-MSCs-CM exposure (p > 0.05). The IGF-1 level of the CM was significantly higher after the CM was used as a culture medium for GC (2.28 vs. 3.07 ± 1.72, p ≤ 0.001). A significant positive correlation was found between survivin and GDF9 (r = 0.966, p ≤ 0.001). CONCLUSION: IGF-1 produced by UC-MSCs-CM can work in paracrine fashion through the IGF receptor, which can inhibit BAX and maintain GDF9 production. Moreover, under the influence of UC-MSCs-CM, GC are also capable of producing IGF-1, which can impact GC through autocrine processes.