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R Muharam,1– 3 Anom Bowolaksono,1,4 Mila Maidarti,1– 3 Ririn Rahmala Febri,1 Kresna Mutia,1 Pritta Ameilia Iffanolida,1 Muhammad Ikhsan,1– 3 Kanadi Sumapraja,1– 3 Gita Pratama,1– 3 Achmad Kemal Harzif,1– 3 Andon Hestiantoro,1– 3 Budi Wiweko1– 3 1Human Reproduction, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia Jakarta, Jakarta, 10430, Indonesia; 2Division of Reproductive Endocrinology and Infertility Department of Obstetrics and Gynecology, Faculty of Medicine Universitas Indonesia, DKI Jakarta, 10430, Indonesia; 3Yasmin IVF Clinic, Dr. Cipto Mangunkusumo General Hospital, Jakarta, 10430, Indonesia; 4Cellular and Molecular Mechanisms in Biological System (CEMBIOS) Research Group, Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, Depok, 16424, IndonesiaCorrespondence: R Muharam, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology - Faculty of Medicine Universitas Indonesia, Jl. Diponegoro No. 71, Salemba, Jakarta Pusat, DKI Jakarta, 10430, Indonesia, Tel +62 3928720 / +62 816 1188027, Email rmuharam@yahoo.comPurpose: This study aimed to measure the correlation between miR-183 and gene expression that regulates apoptosis and adhesion mechanism that may be linked to the pathogenesis of endometriosis.Patients and Methods: Forty-four subjects, including 22 control subjects, participated in this study. We collected ectopic endometriosis and endometrial samples. For the control, the sample was taken from endometrial tissue through pipelle biopsy. RNA was extracted from all tissues using RNA mini kit, and the expression was assessed using quantitative-real time PCR. Relative mRNA and miRNA expression were presented using the formula of the Livak method. The data were statistically analyzed using GraphPad Prism 8.Results: The expression of Caspase-3, Survivin, Integrin β 1 (ITGB1), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) (adhesion- and apoptosis-related gene) were calculated using the relative expression method. We found significant differences in Caspase-3, Survivin, ITGB1, MMP-9, and TIMP-1 expression between ectopic endometriosis tissues of women with endometriosis compared to healthy endometrium. MMP-9, Survivin, and ITGB1 was significantly increased in the endometriosis group, while Caspase-3, TIMP-1, and miR-183 were significantly reduced in the endometriosis group. No correlation was found between the expression level of miR-183 and Caspase3, Survivin, ITGB1, and Cadherin in both tissue types.Conclusion: Despite the difference in expression levels of miR-183 and associated adhesion- and apoptosis-related genes, there was no significant association between miR-183 with specific adhesion and apoptosis genes in endometriosis tissue.Keywords: endometriosis, miR-183, MMP-9, TIMP1, apoptosis, antiapoptosis

Background: Chromosomal mosaicism, a phenomenon observed in a minority of embryos, showcases its prevalence and inherent unpredictability, leading to variations in embryo mosaic rates across different centers. This research endeavors to assess the prevalence of mosaicism and its characteristics within the scope of our preimplantation genetic testing-A (PGT-A) services in Indonesia. Specifically focusing on our center's experience since 2020, this study aims to elucidate mosaic rates among embryos in our care. Materials and Methods: In a retrospective approach, we collected secondary data sourced from our PGT-A outcomes dating back to 2020. A total of 196 embryos underwent analysis, their characteristics were documented and presented descriptively. Notably, the incidence of specific chromosome abnormalities was outlined. We assess a comparative analysis to investigate the relationship between mosaicism and its corresponding clinical characteristics. Results: In the analysis of 196 embryos, 106 (54.1%) displayed chromosomal anomalies spanning from low-level mosaicism to whole chromosome aneuploidy. Low mosaicism was observed in 25 (12.8%) of the embryos, while high mosaicism was identified in 8 (4.1%) embryos. Notably, low-level mosaicism predominated in chromosome 9 (n=10, 5.1%), whereas abnormality prevalence was highest in chromosome 21 (n=20, 10.2%). Statistical analysis revealed no significant disparity in mean maternal age among embryos with low-level mosaicism, high mosaicism, and normal chromosomes (33.88 vs. 35 vs. 33.26 years old, respectively). However, a statistically significant difference in mean maternal age (35.84 vs. 33.26 years) was observed between embryos with aneuploidy (monosomy or trisomy) and those with normal chromosomes. Furthermore, a significant difference in high mosaicism rates was detected in patients with unexplained infertility (P<0.05). Conclusion: In contrast to the study conducted elsewhere, our center had a higher mosaicism rate. Chromosomes 9, 8, and 6 were the most frequently affected. There was a significant difference in the high mosaicism rate for PGT-Arelated unexplained infertility causes. [ABSTRACT FROM AUTHOR]

R Muharam,1 Titi Amalia,1 Gita Pratama,1 Achmad Kemal Harzif,1 Feranindhya Agiananda,2 Mila Maidarti,1 Mazaya Azyati,1 Kanadi Sumapraja,1 Hariyono Winarto,1 Budi Wiweko,1 Andon Hestiantoro,1 Eva Suarthana,3 Togas Tulandi3 1Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 2Department of Psychiatry, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 3Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, CanadaCorrespondence: R MuharamDepartment of Obstetrics and Gynecology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jl. Pangeran Diponegoro No.71, Kenari, Kec. Senen, Kota Jakarta Pusat, Daerah Khusus Ibukota, Jakarta, 10430, Indonesia, Tel +62 812 85143491, Fax +1 205 975-6110, Email rmuharam@yahoo.comBackground: 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 (β = 9.3 (95% CI: 7.15– 11.45; p < 0.001 and β = 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.Keywords: endometriosis, pain, depression, psychiatric disorder, quality of life

Aims and background: Currently, there is no consensus on the standardization of clinical phenotype data for endometriosis patients. The WERF-Endometriosis Phenome and Biobanking Harmonization Project initiated the development of standardization methods for collecting research samples of surgical phenotypes and clinical/biological data related to endometriosis research worldwide. Therefore, translation of the WERF-EPHect Clinical Questionnaire (Standard) (WERF EPQ-S) into Bahasa Indonesia and the validation of this questionnaire is required. To create a standard for taking clinical phenotype data for endometriosis patients by translating and validating WERF EPQ-S content. Materials and Methods: This research was conducted using the transcultural adaptation method. This validation test WERF EPQ-S questionnaire was carried out through a process of forward-backward translation, harmonization by experts, cognitive debriefing to questionnaire targets, and proofreading and finalization by experts. Results: Translation and validation of the Indonesian version of the WERF EPQ-S questionnaire had 10 stages. There are cultural differences from the country of origin of the questionnaire, including medicines available, medical terms that are common in the country of origin but unfamiliar in Indonesia, and the presentation of racial tribes that do not describe variants of Indonesian ethnic tribes. The duration of finishing the questionnaire population was 79.3 minutes, and out of 116 questions, there were 21 that required to be guided. Conclusion: The WERF EPQ-S Indonesian version was obtained with contents according to users' needs. Such a transcultural adaptation method is needed for this tool for the population. The WERF EPQ-S version in the Indonesian language is a valid questionnaire and is ready to be applied to endometriosis patients in Indonesia. Clinical significance: The translation and validation of the WERF-EPHect Clinical Questionnaire into Bahasa Indonesia represent a crucial step toward establishing a standardized and culturally relevant tool for collecting clinical phenotype data from endometriosis patients in Indonesia. [ABSTRACT FROM AUTHOR]

COVID-19 vaccination, especially vaccines that mimic the structure of the COVID-19 virus (mRNA vaccines), may be wrongly assumed to be disrupting factors affecting in vitro fertilization (IVF) outcome. This study aims to evaluate any significant impact of COVID-19 vaccination in women undergoing IVF to improve vaccine compliance and promote COVID-19 eradication. This was a systematic review study. We searched studies published between 2020 and 2022 using databases such as PubMed, Cochrane, PMC, and CINAHL. Selected studies were carefully analyzed to review the impact of the COVID-19 vaccine on IVF outcomes. Seven retrospective and prospective cohort studies, which involved 3232 female patients undergoing IVF, who also received full doses of COVID-19 vaccinations (mRNA), were included. All studies in the present review showed that despite presenting anti-SARS-CoV-2 antibodies after vaccination, there were no significant differences in IVF outcomes, implantation rates, and pregnancy rates. Contrary to the theory that presumed cross-reactivity between anti- SARS-CoV-2 antibodies and the human syncytin-1 protein could affect syncytiotrophoblast formation and embryo implantation. The present review concluded that COVID-19 vaccination does not result in any detrimental effects on IVF outcomes and is safe for women undergoing IVF treatment. The results of our study are important to tackle misinformation regarding COVID-19 vaccination and infertility that may cause vaccine hesitancy in women of reproductive age. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a chronic disorder and is one of the most common endocrine disorders in women of a reproductive age. The prevalence of PCOS is growing globally; 52% of women in Southeast Asia alone suffer from this disorder. This disorder is caused by chronic hyperandrogenism, which hinders folliculogenesis. There is also a close relationship between hyperandrogenism and hyperinsulinemia/insulin resistance (IR), and it is estimated that 40–80% of PCOS patients suffer from insulin resistance (IR). Mesenchymal stem cells (MSCs) and their secretomes have been shown to alleviate PCOS symptoms by decreasing IR and androgen secretion by reducing inflammation. This study aimed to systematically review the literature to study the reported potential of MSCs and their secretomes in decreasing inflammation markers in PCOS treatment. Methods: A systematic literature search was performed on EMBASE, PubMed (MEDLINE), and the Cochrane Library with the terms insulin-resistant PCOS, mesenchymal stem cells, and secretome or conditioned medium as the search keywords. A total of 317 articles were reviewed. Four articles were identified as relevant for this systematic review. Results: The results of this study supported the use of mesenchymal stem cells and their secretions in decreasing inflammatory markers in the treatment of polycystic ovary syndrome. Conclusions: This review provided evidence that treatment with mesenchymal stem cells and their secretomes has the potential to treat PCOS due to its ability to downregulate androgen levels and increase insulin sensitivity, which thereby lowers the level of proinflammatory factors. [ABSTRACT FROM AUTHOR]

Background: Hyperprolactin is one of the endocrine disorders that causes male infertility (11%). The mechanism is not widely known; it is thought to occur through disruption of LH receptor activity on germ cells. Objective: The aim of study to compare the level of prolactin secretion with receptor expression in non-azoospermic infertile men (NOA). Methods: During the period from July 2019 to July 2021, 40 samples of testicular tissue and serum were obtained from infertile NOA men, aged 25-50 years who were recruited from Ciptomangunkusumo Hospital (RSCM) Jakarta, Faculty of Medicine, Universitas Indonesia and Bunda Hospital Jakarta. Subjects were divided into 4 groups based on prolactin levels (20 ng/ml, 20-50 ng/ml, 50-100 ng/ml and 100ng/ml). This group was tested for significance between groups and continued with a correlation test with the level of LH receptor expression. Results: ANOVA test showed a significant decrease in LH receptor expression between prolactin levels < 20 ng/mL with levels of 50-100 ng/ml and prolactin levels > 100 ng/ml (P < 0.05). Furthermore, the results of the correlation test showed a significant decrease between prolactin levels and LH receptor expression (P < 0.05). Conclusion: The higher the level of prolactin secretion in this sample, there is a decrease in LH receptor expression, so that testosterone production decreases and the spermatogenesis process will be disrupted. [ABSTRACT FROM AUTHOR]

Objective: Ovarian tissue vitrification is widely utilized for fertility preservation in prepubertal and adolescent female patients with cancer. The current literature includes reports of successful pregnancy and live birth following autografting. However, the effects of the vitrification process on cumulus-mural granulosa cells (C-mGCs)-somatic cells in ovarian tissue crucial for oocyte maturation and early embryonic development-remain unclear. This study was conducted to explore the impact of vitrification on the cellular function of C-mGCs by quantifying the expression of growth differentiation factor 9 (GDF-9), bone morphogenetic protein 15 (BMP-15), follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), connexin 37, survivin, and caspase 3., Methods: Mature and immature C-mGCs were obtained from 38 women with polycystic ovary syndrome who participated in an in vitro fertilization program. The C-mGCs were then divided into two groups: fresh and vitrified. The expression levels of target genes were assessed using real-time quantitative polymerase chain reaction., Results: After vitrification, GDF-9 expression was significantly decreased among both mature and immature C-mGCs, with 0.2- and 0.1-fold changes, respectively (p<0.01). Similarly, FSHR expression in the mature and immature groups was reduced by 0.1- and 0.02-fold, respectively, following vitrification (p<0.01). The expression levels of the other genes, including BMP-15, LHR, connexin 37, survivin, and caspase 3, remained similar across the examined groups (p>0.05)., Conclusion: Vitrification may compromise oocyte maturation through reduced GDF-9 and FSHR expression in C-mGCs after warming.

Objectives: Endometriosis is a common gynecological disease with a significant economic burden. Growing evidence has suggested the role of aberrant gene expression and epigenetic mechanisms in the pathogenesis of endometriosis. This study aims to identify potential key genes, epigenetic features, and regulatory networks in endometriosis using an integrated bioinformatic approach., Methods: Six microarray and RNA-sequencing datasets (GSE23339, GSE7305, GSE25628, GSE51981, GSE120103, GSE87809) were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) of each dataset were analyzed using the GEO2R tool, and their mRNA, miRNA, and lncRNA components were identified subsequently. The common DEGs between datasets were combined, and the Gene ontology (GO) and pathway enrichment were analyzed using the ShinyGo. The protein-protein interaction (PPI) network of DEGs, miRNA, and lncRNA was constructed using STRING and Cytoscape, and then the top 15 hub genes in the PPI network were identified using CytoHubba., Results: A total of 551 common DEGs were identified from four or more studies, including 292 upregulated and 259 downregulated genes. Besides alterations in protein-coding genes (mRNA), 16 miRNA (5 upregulated and 11 downregulated) were identified from all studies, along with 12 lncRNA (10 upregulated and 2 downregulated) that were common in at least three studies. Enriched DEGs were mainly associated with extracellular matrix (ECM) interaction, P53 signaling pathway, and focal adhesion, which are suggested to play vital roles in the pathogenesis of endometriosis. Through PPI network construction of common DEGs, 178 nodes and 683 edges were obtained, from which 15 hub genes were identified, including CDK1, CCNB1, KIF11, CCNA2, BUB1B, DLGAP5, BUB1, TOP2A, ASPM, CEP55, CENPF, TPX2, CCNB2, KIFC, NCAPG., Conclusions: Our in-depth bioinformatics analysis reveals the critical molecular basis underlying endometriosis. The role of identified hub genes, miRNA, and lncRNA may also have an opportunity to be explored as potential biomarkers for endometriosis diagnosis and prognosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Endometriosis is a disease characterized by dysmenorrhea, chronic pelvic pain, and infertility. The pathogenesis of endometriosis and its relationship to infertility are still not fully understood. In vitro fertilization (IVF) is considered an effective treatment for patients with endometriosis-associated infertility. This study compared the pregnancy rates of endometriosis patients who underwent IVF with those of patients with tubal obstruction., Methods: This was a retrospective cross-sectional study of 225 patients with endometriosis and tubal factor infertility who underwent IVF at Yasmin Clinic, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia, between January 2013 and August 2021. Demographic data, anti-Mullerian hormone (AMH) levels, the initial and total dose of recombinant follicle stimulating hormone (rFSH), the total dose of recombinant luteinizing hormone (rLH), stimulation duration, oocyte maturation rates, fertilization rates, embryo cleavage rates, and pregnancy rates (biochemical, clinical and ongoing) were obtained., Results: AMH level, number of oocytes retrieved, and embryo cleavage rates were significantly lower in the endometriosis group. Initial and total doses of rFSH and total dose of rLH were higher, and the duration of stimulation was longer in the endometriosis group compared to the tubal factor group. In the endometriosis group, the biochemical (47.3% vs. 52.7%, p=0.375), clinical (43.1% vs. 56.9%, p=0.215), and ongoing (45.5% vs. 54.5%, p=0.511) pregnancy rates were lower than those in the tubal factor group. However, there were no statistically significant differences between the two groups. There was no significant difference in pregnancy rates between the short antagonist and ultra-long protocols (three months of downregulation). From multivariate analysis, only rLH supplementation was found to be significantly related to pregnancy outcomes in patients with endometriosis., Conclusion: AMH levels, number of oocytes retrieved, and embryo cleavage rates were lower in patients with endometriosis. However, pregnancy rates were not significantly different from patients with tubal factors. Supplementation with rLH may improve pregnancy rates in patients with endometriosis who have undergone IVF programs., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Research Ethics Committee of the Faculty of Medicine, University of Indonesia issued approval KET-721/UN.F1/ETIK/PPM.00.02/2019. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nurindah et al.)

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., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2024 Hestiantoro et al.)

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., (© 2024 International Federation of Gynecology and Obstetrics.)

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.

Background: Endometriosis is believed to be associated with dysfunction of the lymphocyte population and cytotoxicity of natural killer (NK) cells, induced by the production of interleukin-2 (IL-2)., Objective: This study aimed to investigate T lymphocytes and NK cell activity in the peripheral blood mononuclear cells (PBMCs) of women with endometriosis., Materials and Methods: PBMCs were obtained from the peripheral venous blood samples of 14 women with and without endometriosis (n = 7 for each group). Then, the PBMCs were co-cultured for 4 days and were treated with recombinant IL-2 for cytotoxic activity toward target cells (Daudi and K562 cells). The cytotoxicity activity was determined using the 51 chromium release assay before and after stimulation. Flow cytometry measurement was used to examine the expression of T lymphocytes and NK cells before and after being treated with IL-2., Results: The concentration of CD3+CD28+ (co-stimulatory) was significantly lower in the endometriosis group (65.62 ± 5.38) compared to in its counterpart (50.24 ± 4.22) (p = 0.04) before stimulation. However, no significant differences were observed in any other T lymphocytes and NK cells. It was also found that there was a significant increase of CD3-CD28+ after treatment with IL-2 only in the healthy control but not in women with endometriosis., Conclusion: Increased expression of CD160 and decreased CD28 play a role in inhibiting NK cell activation and T cell response in women with endometriosis., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2022 Muharam et al.)

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 B 1 , vitamin B 2 , niacin, vitamin B 6 , 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 B 6 , 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.

Background: Acupuncture is a nonpharmacological treatment which has been known to improve ovulatory function in polycystic ovary syndrome (PCOS) women. Acupuncture modulates the somatic and autonomic nervous systems, which regulate endocrine and metabolic functions to impact ovulatory functions., Objective: To investigate the effectiveness of electroacupuncture (EA) and pharmacological combination therapy on improving insulin resistance in women with PCOS., Materials and Methods: This double-blind, randomized clinical trial was performed on 44 participants from March to September 2018 at Cipto Mangunkusumo National hospital, Jakarta, Indonesia. Participants were randomly allocated to treatment (true EA + medication) and control group (sham EA + medication) in a 1:1 ratio using a web-based computer random-number generator. Randomization was carried out by an independent project manager. Both groups received 12 sessions of acupuncture therapy and metformin as pharmacological therapy., Results: This study showed a significant decrease in the Homeostatic Model Assessment for Insulin Resistance index in the true EA + medication group before and after therapy (p = 0.014)., Conclusion: The combination of EA and pharmacological therapy effectively improves insulin sensitivity in women with PCOS., Competing Interests: The authors declare to have not no conflict of interest., (Copyright © 2022 Muharam et al.)

Background: More than 135,000 people aged under 45 yr are diagnosed with cancer annually in Indonesia. Good detection and management of cancer increase the quality of life., Objective: To determine the knowledge, attitudes, and behaviors of practitioners supporting cancer patients in fertility preservation., Materials and Methods: This cross-sectional study was conducted in 18 type D government hospitals and Dr. Cipto Mangunkusumo Hospital, in Jakarta, Indonesia, between January 2018 and August 2019. This study involved practitioners providing care to cancer patients. Data were described descriptively., Results: Most of the general practitioners, specialists, and subspecialists who participated in this study were aged 26-30 yr (65.4%), 31-35 yr (70.4%), and 31-40 yr (53.0%), respectively. The fertility treatment most known by general practitioners was in vitro fertilization with embryo cryopreservation (12.1%); for specialists it was sperm cryopreservation (24.5%). Meanwhile, subspecialists knew most about in vitro fertilization with embryo cryopreservation and sperm cryopreservation using a GnRH agonist (such as leuprolide injection) pre-cancer treatment (13%). A positive attitude towards fertility preservation as an important priority for cancer patients was shown in 72.0% of general practitioners, 73.3% of specialists, and 100% of subspecialists. General practitioners mostly referred patients to fertility specialists (44.4%). Many specialists (54.9%) and subspecialists (67%) discussed the possible impact of the patient's condition and / or treatment on fertility., Conclusion: The knowledge of and practices related to fertility preservation differed among general practitioners, specialists, and subspecialists. However, positive attitudes among them were similar., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2022 Kemal Harzif et al.)