Future of Health Services: The Role of Physicians in the Disruptive Era.

This article aimed to address the role of physicians in future health in the disruptive era. Physicians in this disruptive era must increase their capability and knowledge to compensate for this development. Advances in technology increase the impact on health care and the significance of disruption. Disruptive innovation encompasses several fields, such as physics, digital, and biology. Big data as one of the most important parts in clinical aspects encompass high-throughput cellular and protein-binding assays toward chemoinformatic-driven databases. Health status can be modified by changing epigenetic factor, such as lifestyle and environment. As a result, they affect human genetics and provide the insight of pathophysiology of disease, clinical treatment, and early preventive action. Disruptive innovations in health-care align with the development of artificial intelligence, machine learning, robotics, Internet of things, digitalization, and genomics. New paradigm shifting in physician-patient relationships is relevant to consumer health informatics.

In vitro Activation of Mouse Oocytes through Intracellular Ca2+ Regulation.

BACKGROUND: Ca2+ signaling pathway is suggested to play an essential role in mediating oocyte maturation. AIMS: The aim of this study was to evaluate intracellular Ca2+ of resistant immature oocytes that failed to resume meiosis following subsequent in vitro culture reach metaphase II after calcium ionophore A23187 activation. SETTINGS AND DESIGN: This in vitro analytical experimental study was conducted at Animal Science Laboratory of Indonesian Medical Education and Research Institute (IMERI), Human Reproductive Infertility and Family Planning of IMERI, and Electrophysiology Imaging of Terpadu Laboratory, Faculty of Medicine, University of Indonesia. METHODS: A total of 308 oocytes classed as resistant immature following in vitro culture were randomly allocated to control (n = 113) and treatment groups (n = 195). The oocyte activation group was exposed to A23187 solution for 15 min and then washed extensively. Maturation was evaluated by observing the first polar body extrusion 20‒24 h after A23187 exposure. Ca2+ imaging was conducted using a confocal laser scanning microscope to identify the dynamic of Ca2+ response. STATISTICAL ANALYSIS: SPSS 20, Chi-square, and Mann-Whitney U-test were used in this study. RESULTS: Activation of resistant immature oocytes with A23187 significantly increased the number of oocyte maturation compared with the control group (P < 0.001). Furthermore, fluorescent intensity measurements exhibited a significant increase in the germinal vesicle stage when activated (P = 0.005), as well as the metaphase I stage, even though differences were not significant (P = 0.146). CONCLUSION: Artificial activation of resistant immature oocyte using chemical A23187/calcimycin was adequate to initiate meiosis progress.

Suppressing HOXA-10 Gene Expression by MicroRNA 135b During the Window of Implantation in Infertile Women.

BACKGROUND: Implantation failure has long been identified as a common problem underlying low success rate of IVF. Currently, endometrial receptivity has gained expert attention as it is demonstrated to contribute to successful embryo implantation. MicroRNAs (miRNAs) is known to affect endometrial receptivity through post-transcriptional gene expression regulation. This study aimed to evaluate the expression of miRNA 135b and HOXA-10 during the implantation window in endometrial tissue of infertile women. METHODS: A total of 14 patients diagnosed with infertility in the gynaecology clinic of Cipto Mangunkusumo and Daya Medika hospitals Jakart, Indonesia were selected as the observed group, and 9 fertile patients were enrolled in the control group. Total RNA was isolated from endometrial tissues collected at the secretory phase of the menstrual cycle. The miRNA 135b and HOXA-10 mRNA expression were measured using quantitative real-time PCR (qPCR). The correlation between these variables was then determined using Pearson's correlation coefficient. RESULTS: The expression of miRNA 135b in the infertile group was significantly higher by 1.81-fold compared to the control group (p<0.01), whereas, expression of HOXA-10 mRNA was significantly lower in the infertile group compared to the controls (p=0.047). Significant negative correlation was observed between the expression of miRNA 135b and HOXA-10 mRNA in infertile women (p=0.021; r=-0.607). CONCLUSION: Taken together, this study provides that alteration of miRNA expression is involved in regulating the implantation process partly via modulation of the expression of gene required for implantation.

Analysis of factors associated with ovarian reserve in a group of poor responders to in vitro fertilization: A cross-sectional study.

BACKGROUND: Poor ovarian reserve and a high rate of pregnancy failure associated with low quality and quantity of oocytes are observed in poor responders to in vitro fertilization. OBJECTIVE: To assess the effect of age, body mass index (BMI), endometriosis, and history of ovarian surgery on ovarian reserve in a group of poor responders. MATERIALS AND METHODS: In this cross-sectional study 749 women who referred to Yasmin Clinic of Dr. Cipto Mangunkusumo National General Hospital from January 2013 to June 2017 were enrolled. Two definitions of poor responders and Poseidon criteria and consecutive sampling techniques were used. Participants were divided into good and poor responder groups based on the ovarian reserve test; participant with oocyte ≤ 3 was classified as a poor responder. Based on this, 188 participants with nine (4-47) oocytes were included in the poor responder group. While, good responder comprised of two (0-3) oocytes. RESULTS: Age and anti-Mullerian hormone level (AMH) were significantly associated with ovarian reserve in the poor-responder group (p < 0.001). However, in multivariate analyses, age was the only significant predictor of ovarian response in the poor-responder group (p = 0.004). While endometriosis was the significant predictor of Poseidon groups 1 and 4, surgical history was the significant predictor of Poseidon groups 2 and 3. Meanwhile, an increase in BMI decreased the risk of classification under Poseidon group 3. CONCLUSION: Age, AMH, BMI, endometriosis, and history of ovarian surgery affected the risk of classification of the Poseidon group.

Impact of Serum Human Chorionic Gonadotropin and Luteinizing Hormone Receptor Expression to Oocyte Maturation Rate: A Study of Controlled Ovarian Stimulation.

BACKGROUND: Few studies have assessed the impact of serum human chorionic gonadotropin (hCG) levels before oocyte retrieval and luteinizing hormone receptor (LHR) mRNA expression. AIMS: The objective was to assess the correlations between serum hCG levels at 12-h posttrigger granulosa cell LHR mRNA expression during the in vitro fertilization (IVF) cycle with oocyte maturation rate and to determine the cutoff level of serum hCG at 12-h posttrigger. SETTINGS AND DESIGN: A cross-sectional was conducted for this study at the IVF center of Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia. MATERIALS AND METHODS: Recombinant follicle-stimulating hormone was used on day 2 of the menstrual cycle with multiple doses of a gonadotropin-releasing hormone antagonist. Recombinant hCG was used to trigger ovulation. At 12-h posttrigger, hCG serum levels were measured using an enzyme-linked immunosorbent assay. STATISTICAL ANALYSIS: Pearson's correlation coefficient was used to evaluate the correlation between oocyte maturation rates, serum hCG levels, and LHR mRNA levels. Cutoff values were determined using a receiver operating characteristic (ROC) curve. RESULTS: Serum hCG levels were positively correlated (r = 0.467;P < 0.01), and LHR mRNA expression was weakly correlated (r = 0.073; P = 0.701) with oocyte maturation. The cutoff of serum hCG for a high maturation rate was 77 mIU/mL, with an area under the ROC curve of 0.765 (95% confidence interval: 0.598-0.939) andP < 0.001. CONCLUSION: Oocyte maturation is correlated with serum hCG levels with 77 mIU/mL as the cutoff point for oocyte retrieval.