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.

Effect of Endometriosis on Cumulus ATP, Number of Mitochondria and Oocyte Maturity in Cumulus Oocyte Complex in Mice.

OBJECTIVE: Endometriosis causes a decrease in oocyte quality. However, this mechanism is not fully understood. The present study aimed to analyze the effect of endometriosis on cumulus cell adenosine triphosphate ATP level, the number of mitochondria, and the oocyte maturity level. METHODS: A true experimental study with a post-test only control group design on experimental animals. Thirty-two mice were divided into control and endometriosis groups. Cumulus oocyte complex (COC) was obtained from all groups. Adenosine triphosphate level on cumulus cells was examined using the Elisa technique, the number of mitochondria was evaluated with a confocal laser scanning microscope and the oocyte maturity level was evaluated with an inverted microscope. RESULTS: The ATP level of cumulus cells and the number of mitochondria in the endometriosis group increased significantly (p < 0.05; p < 0.05) while the oocyte maturity level was significantly lower (p < 0.05). There was a significant relationship between ATP level of cumulus cells and the number of mitochondrial oocyte (p < 0.01). There was no significant relationship between cumulus cell ATP level and the number of mitochondrial oocytes with oocyte maturity level (p > 0.01; p > 0.01). The ROC curve showed that the number of mitochondrial oocytes (AUC = 0.672) tended to be more accurate than cumulus cell ATP level (AUC = 0.656) in determining the oocyte maturity level. CONCLUSION: In endometriosis model mice, the ATP level of cumulus cells and the number of mitochondrial oocytes increased while the oocyte maturity level decreased. There was a correlation between the increase in ATP level of cumulus cells and an increase in the number of mitochondrial oocytes.

Effect of Endometriosis on Cumulus ATP, Number of Mitochondria and Oocyte Maturity in Cumulus Oocyte Complex in Mice / Efeito da endometriose no cumulus ATP, número de mitocôndrias e maturidade oocitária no complexo oocitário cumulus em camundongos

Abstract Objective Endometriosis causes a decrease in oocyte quality. However, this mechanism is not fully understood. The present study aimed to analyze the effect of endometriosis on cumulus cell adenosine triphosphate ATP level, the number of mitochondria, and the oocyte maturity level. Methods A true experimental study with a post-test only control group design on experimental animals. Thirty-two mice were divided into control and endometriosis groups. Cumulus oocyte complex (COC) was obtained from all groups. Adenosine triphosphate level on cumulus cells was examined using the Elisa technique, the number of mitochondria was evaluated with a confocal laser scanning microscope and the oocyte maturity level was evaluated with an inverted microscope. Results The ATP level of cumulus cells and the number of mitochondria in the endometriosis group increased significantly (p < 0.05; p < 0.05) while the oocyte maturity level was significantly lower (p < 0.05). There was a significant relationship between ATP level of cumulus cells and the number of mitochondrial oocyte (p < 0.01). There was no significant relationship between cumulus cell ATP level and the number of mitochondrial oocytes with oocyte maturity level (p > 0.01; p > 0.01). The ROC curve showed that the number of mitochondrial oocytes (AUC = 0.672) tended to be more accurate than cumulus cell ATP level (AUC = 0.656) in determining the oocyte maturity level. Conclusion In endometriosis model mice, the ATP level of cumulus cells and the number of mitochondrial oocytes increased while the oocyte maturity level decreased. There was a correlation between the increase in ATP level of cumulus cells and an increase in the number of mitochondrial oocytes.

Clinical Diagnosis and Early Medical Management for Endometriosis: Consensus from Asian Expert Group.

This work provides consensus guidance regarding clinical diagnosis and early medical management of endometriosis within Asia. Clinicians with expertise in endometriosis critically evaluated available evidence on clinical diagnosis and early medical management and their applicability to current clinical practices. Clinical diagnosis should focus on symptom recognition, which can be presumed to be endometriosis without laparoscopic confirmation. Transvaginal sonography can be appropriate for diagnosing pelvic endometriosis in select patients. For early empiric treatment, management of women with clinical presentation suggestive of endometriosis should be individualized and consider presentation and therapeutic need. Medical treatment is recommended to reduce endometriosis-associated pelvic pain for patients with no immediate pregnancy desires. Hormonal treatment can be considered for pelvic pain with a clinical endometriosis diagnosis; progestins are a first-line management option for early medical treatment, with oral progestin-based therapies generally a better option compared with combined oral contraceptives because of their safety profile. Dienogest can be used long-term if needed and a larger evidence base supports dienogest use compared with gonadotropin-releasing hormone agonists (GnRHa) as first-line medical therapy. GnRHa may be considered for first-line therapy in some specific situations or as short-term therapy before dienogest and non-steroidal anti-inflammatory drugs as add-on therapy for endometriosis-associated pelvic pain.

The effect of hyperbaric oxygen therapy in the inflammatory response in a mouse model of endometriosis: An experimental study.

Background: Endometriosis pathogenesis is related to the inflammation shown by the secretion of pro-inflammatory mediators. This hypoxia condition can stimulate this condition. Objective: To investigate the effect of hyperbaric oxygen therapy (HBOT) on the inflammation reaction of endometriosis-induced mice. Materials and Methods: The animals were designated into 3 groups: I) the pre-test group, II) the post-test group receiving the HBOT, and III) the post-test group without HBOT. All groups were subjected to induction of endometriosis by xenotransplantation for 15 days. HBOT was given 30 min 3 times a day for 10 days. The evaluation of the HBOT effect was conducted by examining the endometrial tissue. The inflammation level was evaluated using the Klopfleisch semiquantitative scoring system (index remmele scale), whilst the expression of nuclear factor kappa (NF κ B) beta was measured by immunohistochemical staining. Results: The results showed that group I demonstrated the highest level of inflammation degree (9.41 ± 1.99) compared to the post-test groups (group II: 1.60 ± 0.53; group III: 2.42 ± 0.53). The HBOT-groups was found to have the lowest inflammation level compared to the non-HBOT group (p = 0.020). The results demonstrated that HBOT lowered the peritoneal inflammation degree caused by the endometrial lesion in mice. NF κ B expression on the post-test groups was significantly decreased, compared to the pre-test group (p ≤ 0.001), with a strong correlation between the NF κ B expression and the peritoneal inflammation level (p ≤ 0.001, r = 0.670). Conclusion: HBOT significantly reduced the inflammation level on the endometrial lesion in mice, involving the NF κ B pathway.

Effects of bone marrow mesenchymal stem cell transplantation on tumor necrosis factor-alpha receptor 1 expression, granulosa cell apoptosis, and folliculogenesis repair in endometriosis mouse models.

BACKGROUND AND AIM: Endometriosis affects the ovaries and causes a decrease in the oocyte quality during endometrial receptivity. During the development of ovarian follicles, paracrine communication occurs between granulosa cells and oocytes. This study was conducted to determine the effects of bone marrow mesenchymal stem cell transplantation on tumor necrosis factor-alpha (TNF-α) receptor 1 (TNFR1) expression, granulosa cell apoptosis, and folliculogenesis in endometriosis mouse models. MATERIALS AND METHODS: This study involved 42 female mice, which were divided into three groups: Healthy mice (T0), endometriosis mice without transplantation (T1), and endometriosis mice with bone marrow mesenchymal stem cell transplantation (T2). The mice were injected intraperitoneally with endometrial fragments (200 µL) to become endometriosis models. On day 15, the endometriosis models received mesenchymal stem cells. Sample collection was performed on day 29. Granulosa cell apoptosis and TNFR1 expression were examined using immunohistochemical staining, and folliculogenesis was assessed using hematoxylin and eosin staining of ovary samples. The data obtained from both examinations were statistically analyzed using Statistical Package for the Social Sciences. RESULTS: The results showed that TNFR1 expression is significantly decreased in T2 (p<0.004). The apoptosis of granulosa cells was lower in T2 (p<0.000). The primary, secondary, and graafian follicle counts in T2 were significantly increased. CONCLUSION: Bone marrow mesenchymal stem cell transplantation in endometriosis mouse models can reduce TNFR1 expression and granulosa cell apoptosis and improve folliculogenesis.

Health system and quality of care factors contributing to maternal deaths in East Java, Indonesia.

Despite most Indonesian women now receiving antenatal care on the nationally recommended four occasions and being delivered by skilled birth attendants, the nation's maternal mortality ratio (MMR) is estimated as 177 per 100,000 live births. Recent research in a rural district of Indonesia has indicated that poor service quality due to organizational and personnel factors is now a major determinant of this high MMR. The present research is an in-depth analysis of possible health service organizational and quality of care related causes of death among 30 women admitted to a peak referral hospital in a major Indonesian city. Despite their condition being complex or deteriorating, most of these women arrived at the hospital in a state where it was feasible to prevent death with good quality care. Poor application of protocols, poor information flow from frontline hospitals to the peak referral hospital, delays in emergency care, and delays in management of deteriorating patients were the main contributing factors to these deaths. Pyramidal referrals also contributed, as many women were initially referred to hospitals where their condition could not be effectively managed. While generic quality improvement measures, particularly training and monitoring for rigorous application of clinical protocols (including forward planning for deteriorating patients) will help improve the situation, the districts and hospitals need to develop capacity to assess their local situation. Unless local organisational factors, staff knowledge and skill, blood and blood product availability, and local reasons for delays in providing care are identified, it may not be possible to effectively reduce the adverse pregnancy outcomes.

Curcumin improves growth factors expression of bovine cumulus-oocyte complexes cultured in peritoneal fluid of women with endometriosis.

BACKGROUND: Peritoneal fluid (PF) from infertile women with endometriosis contains inflammatory mediators that may interfere with folliculogenesis. OBJECTIVE: The aim was to evaluate the effects of curcumin on growth factors expression by evaluating Growth Differentiation Factor-9 (GDF-9), Kit Ligand (KitL), and Tumor Necrosis Factor α (TNF α ) expressions in bovine cumulus-oocyte complexes (COC)s cultured with PF from infertile women with endometriosis. MATERIALS AND METHODS: In this experimental study, 21 infertile women (aged between 20 and 40 years) who refered to Dr Sutomo Hospital from January to July 2015 were enrolled. COCs were aspirated from antral follicles of bovine ovaries. PF was collected from infertile women with endometriosis undergoing laparoscopy for infertility evaluation. Curcumin, a strong anti-inflammatory turmeric, was added in Tissue Culture Medium 199 (TCM199) and PF for culture medium. Bovine COCs were cultured into three groups of the medium: 1. TCM199, 2. TCM199 + PF, and 3. TCM199 + PF + curcumin. GDF-9, KitL, and TNF α expressions were examined using immunohistochemistry technique. RESULTS: GDF-9 expression of bovine COCs cultured in PF with curcumin addition (2.67 ± 0.98) was found to increase compared to those cultured without curcumin (0.50 ± 0.67) (p ≤ 0.001). It was similar to KitL expression of bovine COCs cultured with curcumin (2.67 ± 1.23), which increased compared to those without curcumin (0.33 ± 0.49) (p ≤ 0.001). A significant difference in TNF α expression was noted between groups with or without curcumin (p ≤ 0.001). CONCLUSION: In the culture of PF from infertile women with endometriosis, curcumin addition improves the growth factors expression of bovine COCs. The increase of GDF-9 and KitL expressions will improve folliculogenesis.

Growth differentiation factor 9 concentration in the follicular fluid of infertile women with endometriosis.

This study evaluated the level of growth differentiation factor 9 (GDF-9) in the follicular fluid of infertile women with endometriosis. The presence of GDF-9 in follicular fluid of preovulatory follicle was confirmed by Western blotting method in the band of 53 kDa, and GDF-9 concentration in women with severe endometriosis was lower than in those without.