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OBJECTIVES: Indonesia is the fifth country with the highest number of preterm births worldwide. More than a third of neonatal deaths in Indonesia were attributed to preterm birth. Residential areas affected the occurrence of preterm birth due to differing socioeconomic and environmental conditions. Many studies have investigated the determinants of prematurity in Indonesia, however, most of them were performed in rural areas. This study is the first meta-analysis describing the determinants of preterm birth in urban Indonesia, which aimed to become the foundation upon implementing the most suitable preventative measure and policy to reduce the rate of preterm birth. METHODS: We collected all published papers investigating the determinants of preterm birth in urban Indonesia from PubMed MEDLINE and EMBASE, using keywords developed from the following key concepts: "preterm birth", "determinants", "risk factors", "Indonesia" and the risk factors, such as "high-risk pregnancy", "anemia", "pre-eclampsia", and "infections". Exclusion criteria were multicenter studies that did not perform a specific analysis on the Indonesian population or did not separate urban and rural populations in their analysis, and articles not available in English or Indonesian. The Newcastle Ottawa Scale was used to assess the risk of bias. This systematic review was registered in PROSPERO. RESULTS: Sixteen articles were included in the analysis and classified into five categories: genetic factors, nutrition, smoking, pregnancy characteristics or complications, and disease-related characteristics. CONCLUSIONS: Our meta-analysis revealed adolescent pregnancy, smoking, eclampsia, bacterial vaginosis, LC-PUFA, placental vitamin D, and several minerals as the significant determinants of preterm birth in urban Indonesia.
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Eclampsia , Nacimiento Prematuro , Adolescente , Embarazo , Recién Nacido , Humanos , Femenino , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Indonesia/epidemiología , Placenta , Recien Nacido PrematuroRESUMEN
OBJECTIVES: The purpose of this study was to define the underlying biological mechanisms of polycystic ovarian syndrome (PCOS) utilizing the protein-protein interaction networks (PPINs) that were constructed based on the putative disease-causing genes for PCOS. DESIGN: No animals were used in this research because this is an in silico study that mainly uses software and online analysis tools. Participants/Materials, Settings: Gene datasets related to PCOS were obtained from Genecards. METHODS: The PPINs of PCOS were created using the String Database after genes related to PCOS were obtained from Genecards. After that, we performed an analysis of the hub-gene clusters extracted from the PPIN using the ShinyGO algorithm. In the final step of this research project, functional enrichment analysis was used to investigate the primary biological activities and signaling pathways that were associated with the hub clusters. RESULTS: The Genecards database provided the source for the identification of a total of 1,072 potential genes related to PCOS. The PPIN that was generated by using the genes that we collected above contained a total of 82 genes and three different types of cluster interaction interactions. In addition, after conducting research on the PPIN with the shinyGO plug-in, 19 of the most important gene clusters were discovered. The primary biological functions that were enriched in the key clusters that were developed were ovarian steroidogenesis, the breast cancer pathway, regulation of lipid and glucose metabolism by the AMPK pathway, and ovarian steroidogenesis. The integrated analysis that was performed in the current study demonstrated that these hub clusters and their connected genes are closely associated with the pathogenesis of PCOS. LIMITATIONS: Several of the significant genes that were identified in this study, such as ACVR1, SMAD5, BMP6, SMAD3, SMAD4, and anti-mullerian hormone. It is necessary to do additional research using large samples, several centers, and multiple ethnicities in order to verify these findings. CONCLUSIONS: The integrated analysis that was performed in the current study demonstrated that these hub clusters and their connected genes are closely associated with the pathogenesis of PCOS. This information may possibly bring unique insights for the treatment of PCOS as well as the investigation of its underlying pathogenic mechanism.
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The presence of cell-free DNA in spent embryo culture media (SECM) has unveiled its possible utilization for embryonic ploidy determination, opening new frontiers for the development of a non-invasive pre-implantation genetic screening technique. While a growing number of studies have shown a high concordance between genetic screening using cell-free DNA (cfDNA) and trophectoderm (TE), the mechanism pertaining to the release of cfDNA in SECM is largely unknown. This review aims to evaluate research evidence on the origin and possible mechanisms for the liberations of embryonic DNA in SECM, including findings on the self-correction abilities of embryos which might contribute to the presence of cfDNA. Several databases including EMBASE, PUBMED, and SCOPUS were used to retrieve original articles, reviews, and opinion papers. The keywords used for the search were related to the origins and release mechanism of cfDNA. cfDNA in SECM originates from embryonic cells and, at some levels, non-embryonic cells such as maternal DNA and exogenous foreign DNA. The apoptotic pathway has been demonstrated to eliminate aneuploid cells in developing mosaic embryos which might culminate to the release of cfDNA in SECM. Nonetheless, there is a recognized need for exploring other pathways such as cross-talk molecules called extracellular vesicles (EVs) made of small, round bi-layer membranes. During in vitro development, embryos physiologically and actively expel EVs containing not only protein and microRNA but also embryonic DNA, hence, potentially releasing cfDNA of embryonic origin into SECM through EVs.
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Ácidos Nucleicos Libres de Células , Diagnóstico Preimplantación , Humanos , Femenino , Embarazo , Medios de Cultivo/metabolismo , Ácidos Nucleicos Libres de Células/genética , Implantación del Embrión , Blastocisto/metabolismo , Aneuploidia , ADN/genética , ADN/metabolismo , Técnicas de Cultivo de Embriones , Diagnóstico Preimplantación/métodosRESUMEN
PURPOSE: This pilot study aimed to evaluate the potential synergistic role of three-dimensional power Doppler angiography ultrasound and the expression of Leukemia Inhibitory Factor (LIF) protein in predicting the endometrial receptivity of fresh In-Vitro Fertilization (IVF) cycles. MATERIALS AND METHODS: This prognostic cohort study involved 29 good prognosis women who underwent fresh IVF cycles with fresh blastocysts transfer. Serial measurements of sub-endometrial parameters including vascularity index (VI), flow index (FI), and vascularization flow index (VFI) were conducted consecutively via power Doppler angiography on the day of oocyte maturation trigger, oocyte retrieval, and blastocyst transfer. Aspiration of endometrial secretion was performed on the day of embryo transfer. RESULTS: The mean index of VI and VFI on the trigger and oocyte retrieval day and also LIF protein concentration at the window of implantation were significantly higher in clinically pregnant women than that of the non-pregnant women (p < 0.05). The area under the curve (AUC) of VI and VFI was shown to have a powerful predictive value to forecast receptive endometrium on either trigger day (0.788 and 0.813, respectively) or oocyte retrieval day (0.813 and 0.818). Likewise, LIF concentration on the day of embryo transfer was adequate to become a predictor for endometrial receptivity (AUC 0.874). A combination of the VI and VFI on the trigger day and LIF concentration at specific cut-off values (VI > 5.381, VFI > 1.483, LIF 703.5 pg/mL) produced an algorithm with high AUC (0.881) and high specificity (94.4%) for an adequate prediction of non-receptive endometrium. CONCLUSION: VI and VFI index assessed on maturation trigger day and the expression of LIF protein concentration at the window of implantation provided sufficient information to predict endometrial receptivity. A large randomized control trial is needed to validate these findings.
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Endometrio , Fertilización In Vitro , Angiografía , Estudios de Cohortes , Endometrio/diagnóstico por imagen , Femenino , Fertilización In Vitro/métodos , Humanos , Factor Inhibidor de Leucemia , Proyectos Piloto , Ultrasonografía Doppler/métodosRESUMEN
BACKGROUND: The accuracy of an artificial intelligence model based on echocardiography video data in the diagnosis of heart failure (HF) called LIFES (Learning Intelligent for Effective Sonography) was investigated. METHODS: A cross-sectional diagnostic test was conducted using consecutive sampling of HF and normal patients' echocardiography data. The gold-standard comparison was HF diagnosis established by expert cardiologists based on clinical data and echocardiography. After pre-processing, the AI model is built based on Long-Short Term Memory (LSTM) using independent variable estimation and video classification techniques. The model will classify the echocardiography video data into normal and heart failure category. Statistical analysis was carried out to calculate the value of accuracy, area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio (LR). RESULTS: A total of 138 patients with HF admitted to Harapan Kita National Heart Center from January 2020 to October 2021 were selected as research subjects. The first scenario yielded decent diagnostic performance for distinguishing between heart failure and normal patients. In this model, the overall diagnostic accuracy of A2C, A4C, PLAX-view were 92,96%, 90,62% and 88,28%, respectively. The automated ML-derived approach had the best overall performance using the 2AC view, with a misclassification rate of only 7,04%. CONCLUSION: The LIFES model was feasible, accurate, and quick in distinguishing between heart failure and normal patients through series of echocardiography images.
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Inteligencia Artificial , Insuficiencia Cardíaca , Estudios Transversales , Ecocardiografía/métodos , Insuficiencia Cardíaca/diagnóstico por imagen , Humanos , UltrasonografíaRESUMEN
The COVID-19 pandemic has caused disruption in all aspects of life, and countries around the world have been combating this pandemic using multiple approaches. Success in one country does not guarantee a transferable approach to other countries with different contexts. This review describes the challenges of COVID-19 management in Indonesia as a populous, socially and culturally diverse, and archipelagic country. It aims to provide multidisciplinary perspectives for a safe, evidence-based, and productive new normal as well as a comprehensive and integrated actionable policy for COVID-19 control.
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COVID-19/epidemiología , Política de Salud , Pandemias/economía , COVID-19/prevención & control , COVID-19/transmisión , Humanos , Indonesia , Salud Laboral , Política Organizacional , Salud Pública , Cuarentena/economía , Factores SocioeconómicosRESUMEN
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.
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Hormona Antimülleriana/sangre , Síndrome del Ovario Poliquístico/sangre , Adulto , Área Bajo la Curva , Estudios de Casos y Controles , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Hiperandrogenismo/sangre , Folículo Ovárico/metabolismo , Sensibilidad y EspecificidadRESUMEN
Introduction and importance: International Federation of Gynecology and Obstetrics (FIGO) and WHO report the incidence of postpartum haemorrhage (PPH) reaches 1-10% and contributes to an increase in postpartum maternal mortality with uterine atony as the most common cause. B-Lynch method is a suturing technique to overcome PPH. Although this method has proven useful as an emergency life-saving measure, the post-procedure complications are still able to occur. Presentation of case: The patient was not menstruating for 14 months after giving birth through caesarean section with B-Lynch due to PPH. Before pregnancy, she had regular menstruation cycle and normal menstrual duration. Her general and gynaecological status were normal. Ultrasound showed the impression of uterine hypoplasia and endometrium that were difficult to assess while both ovaries were normal. Diagnostic hysteroscopy showed a severe degree of Asherman's syndrome. The results of FSH, LH and estradiol were normal. Discussion: B-lynch suture is performed as a method to stop PPH in uterine atony. Secondary amenorrhoea occurs as a complication of B-lynch. Compression action of B-lynch can cause progressive myometrium necrosis resulting in synechiae and blockade of uterine blood flow. This will interfere with the development of the uterus. Intrauterine adhesions and amenorrhoea with normal levels of FSH, LH, and estradiol support the diagnosis of Asherman's syndrome. Conclusion: This case shows that the B-Lynch procedure, which is the worldwide recommended method for treating postpartum haemorrhage due to its high success rate, can cause complications of Asherman's syndrome and cause secondary amenorrhoea.
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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.
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Hormona Luteinizante , Síndrome del Ovario Poliquístico , Femenino , Humanos , Dinorfinas/metabolismo , Leptina , Kisspeptinas/metabolismo , Estudios Transversales , Adiponectina , Neuroquinina B/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Folículo EstimulanteRESUMEN
Background: As one of Indonesia's major social media platforms, Instagram provides abundant information, including fertility topics. However, fertility information in Bahasa (Indonesian language) had never been mapped before. This study aims to determine the prevalence, authorship, and types of fertility-related information in Bahasa shared on Instagram using hashtag and content analysis. Additional outcomes included a comparison of post content stratified by author type (healthcare providers vs. non-healthcare providers). Materials and methods: Five hashtags comprising fertility terms in Bahasa (Indonesian language) were derived. Content analysis was performed on the top 100 posts for each hashtag to determine the authorship and content type. The contents posted by healthcare providers were analyzed and compared to those published by non-healthcare providers. Results: Our search yielded 3 883 000 posts for the five most popular hashtags. The three most popular hashtags were 'promil', 'program hamil' and 'bayitabung'. Authorship of the top posts for each hashtag was predominantly by for-profit healthcare institutions (27.6%), followed by commercial alternative/herbal medicine (20.2%), patients (20%), physicians (11.8%), allied health professionals (3.2%), professional societies (0.8%), and others (16.4%). Of these posts, 35.4% were advertisements, 28% were related to patient experience, and 18% were educational. Healthcare provider groups were more likely to author educational posts than advertisements, while non-healthcare providers were more likely to post content for commercial purposes (P < 0.001). Conclusion: Fertility-related posts were dominated by for-profit healthcare institutions and alternative/herbal medicines for commercial purposes. The physician group authored more of the educational content. There is plenty of room for optimal utilization of social platforms as educational media.
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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.
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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).
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OBJECTIVE: The presence of embryonic cell-free DNA (cfDNA) in spent embryo culture media (SECM) may offer valuable advantages for non-invasive testing of embryo ploidy or genetic characteristics compared to trophectoderm (TE) biopsy. This study aimed to assess the diagnostic potential of SECM cfDNA as a non-invasive sample for chromosomal copy number testing in blastocysts within the clinical setting of in-vitro fertilization. METHOD: This prospective observational study collected 28 SECM cfDNA samples matched with TE biopsy samples from 21 infertile couples who underwent IVF-PGT-A cycles. SECM samples were obtained from blastocysts that were cultured for approximately 5/6 days in an uninterrupted time-lapse incubator. Both sets of samples were collected during the biopsy procedure. The Variseq Illumina platform was utilized for ploidy measurement. The study evaluated the informativity and interpretability of SECM cfDNA, concordance of general ploidy status, and sex chromosome agreement between the two sample types. RESULTS: SECM cfDNA had a high informativity rate (100â¯%) after double amplification procedure, with a result interpretability of 93â¯%. Two out of the 28 SECM cfDNA samples were uninterpretable and regarded as overall noise samples. The diagnostic potential of SECM cfDNA, when compared to TE biopsy the standard reference, was relatively low at 50â¯%. Maternal DNA contamination remains the major obstacle that hinders the widespread clinical adoption of SECM cfDNA in the routine practice of pre-implantation genetic testing for aneuploidy within IVF settings. CONCLUSION: A significant modification must be implemented in the IVF laboratory to minimize DNA contamination and this necessitates suggesting adjustments to oocyte denudation, embryo culture media preparation, and sample collection procedures.
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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.
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Países en Desarrollo , Fertilización In Vitro , Accesibilidad a los Servicios de Salud , Humanos , Indonesia/epidemiología , Femenino , Estudios Retrospectivos , Fertilización In Vitro/estadística & datos numéricos , Embarazo , Adulto , Masculino , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Índice de Embarazo , Infertilidad/terapia , Infertilidad/epidemiología , Técnicas Reproductivas Asistidas/estadística & datos numéricos , Clínicas de Fertilidad/estadística & datos numéricosRESUMEN
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.
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Envejecimiento/sangre , Hormona Antimülleriana/sangre , Hormona Folículo Estimulante/sangre , Infertilidad Femenina/sangre , Adulto , Femenino , Humanos , Infertilidad Femenina/patología , Persona de Mediana Edad , Folículo Ovárico/citología , Folículo Ovárico/metabolismo , Adulto JovenRESUMEN
While morphokinetic evaluation of embryos has become the most commonly used technique in IVF to select embryos for transfer, studies have demonstrated that mitochondrial DNA (mtDNA) copy number is correlated with embryo viability and transfer outcomes. Correspondingly, this cohort study aims to evaluate the association between the mtDNA copy number in cumulus granulosa cells (CGCs) with embryo morphokinetic parameters and chromosomal status. Real-time PCR was employed to measure the mtDNA copy number of the 129 CGCs in samples obtained from 30 patients undergoing the IVF-IMSI program at Morula IVF Jakarta between July and October 2020. Bivariate and multiple analyses were utilized to determine its relationship with embryo morphokinetics, blastocyst yield, and chromosomal status. According to the analysis, there was a significant correlation between the mtDNA copy number and the blastocyst status after adjusting for the maternal age and sperm morphology (coefficient 0.832, p value = 0.032, RR value 2.299). Moreover, a significant link was observed between mtDNA copy number in CGC and early embryo developmental phase M1 (t2-t8), using the equation of M1 is 5.702-0.271 mtDNA copy number of CGCs + 0.017 maternal age + 0.013 sperm motility -0.115 sperm morphology (p value = 0.032). However, no correlation was found between the mtDNA copy number in CGCs with the other morphokinetic parameters (M2: tC-tEB, M3: t2-tEB, DC, RC, MN with p > 0.05), or the chromosomal status of the embryos (euploid: 139.44 ± 133.12, aneuploid: 142.40 ± 111.30, p = 0.806). In conclusion, our study suggests that mtDNA copy number in CGCs can serve as a useful biomarker for blastocyst status and early embryo developmental phase but not for chromosomal status.
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ADN Mitocondrial , Fertilización In Vitro , Femenino , Humanos , Masculino , Recién Nacido , ADN Mitocondrial/genética , Estudios de Cohortes , Variaciones en el Número de Copia de ADN , Células del Cúmulo , Motilidad Espermática , Semen , Blastocisto , CromosomasRESUMEN
Embryo selection for in vitro fertilization (IVF) is an effort to increase the success rate of embryo implantation. Factors influencing the success of embryo implantation include embryo quality, endometrial receptivity, embryo characteristics, and maternal interactions. Some molecules have been found to influence these factors, but their regulatory mechanisms are unclear. MicroRNAs (miRNAs) are reported to play an essential role in the embryo implantation process. miRNAs are small non-coding RNAs consisting of only 20 nucleotides that play an essential role in the stability of gene expression regulation. Previous studies have reported that miRNAs have many roles and are released by cells into the extracellular environment for intracellular communication. In addition, miRNAs can provide information related to physiological and pathological conditions. These findings encourage research development in determining the quality of embryos in IVF to increase the implantation success rate. Moreover, miRNAs can provide an overview of embryo-maternal communication and potentially be noninvasive biological markers of embryo quality, which could increase assessment accuracy while reducing mechanical damage to the embryo itself. This review article summarizes the involvement of extracellular miRNAs and the potential applications of miRNAs in IVF.
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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.
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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.
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Background: Adolescence is a development period marked by the onset of a new set of health needs. The present study sought to quantify the prevalence of foregone care (not seeking medical care when needed) and identify which adolescents are at greater risk of having unmet healthcare needs. Methods: A multi-stage random sampling strategy was used to recruit school participants (grade 10-12) in two provinces in Indonesia. Respondent driven sampling was used to recruit out-of-school adolescents in the community. All participants completed a self-reported questionnaire which measured healthcare seeking behaviours, psychosocial wellbeing, use of healthcare services, and perceived barriers to accessing healthcare. Multivariable regression analysis was performed to examine factors associated with foregone care. Findings: A total of 2161 adolescents participated in the present study and nearly one in four adolescents reported foregone care in the past year. Experiences of poly-victimisation and seeking care for mental health needs increased the risk of foregone care. In-school adolescents who reported psychological distress [adjusted risk ratio (aRR) = 1.88, 95%CI = 1.48-2.38] or had high body mass index (aRR = 1.25, 95%CI = 1.00-1.57) were at greater risk of foregone care. The leading reason for foregone care was lack of knowledge of available services. In-school adolescents predominantly reported non-access barriers to care (e.g., perception of the health concern or anxiety about accessing care) whereas most out-of-school adolescents reported access barriers (e.g., did not know where to get care or could not pay). Interpretation: Foregone care is common among Indonesian adolescents, especially in adolescents with mental and physical health risks. Differences between in-school and out-of-school adolescents suggest that interventions to promote appropriate healthcare use will need tailoring. Further research is needed to determine causal relationships around barriers in access to healthcare. Funding: Australia-Indonesia Centre.