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

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

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.

Impacts of COVID-19 Pandemic on Three IVF Clinics of Jakarta, Indonesia: A Retrospective Qualitative and Quantitative Study.

BACKGROUND: Corona virus disease-19 (COVID-19) pandemic also led to a reduction or even the suspension of elective health services. These decisions affected in vitro fertilization (IVF) programs worldwide. Therefore, it is essential to map the readiness of IVF clinics in providing safety in this situation and in the future. MATERIALS AND METHODS: This is a retrospective qualitative and quantitative research done in 2021 that involved three IVF clinics of Jakarta, Indonesia. Those three clinics were government-owned, private-owned, and educational and training center. The qualitative data of each clinic's readiness towards COVID-19 was obtained from interviews with the clinics staff. The quantitative data were collected from the clinics patients' number and demographic data from 2019-2021 as well as from COVID-19 databases. Both data sets were analysed descriptively and only for the quantitative analysis Stata version 16 was used. RESULTS: There were changes in the domiciles and number of patients attending the three clinics. The ratio of patients from Jakarta increased while patients from outside Java Island decreased. There was a drop in annual patient numbers in 2020. However, from June 2020 to December 2021, the number of monthly IVF cycles increased significantly by 3.5 cycles per month (P=0.001). There was no association between IVF patients' attendance numbers and COVID-19 cases (P=0.785). One of the clinics had a negative pressure operating theatre, which made them more confident in treating patients with COVID-19 positive and made them even had higher IVF cycles started than the pre-pandemic period. CONCLUSION: Those three clinics are prepared in facing COVID-19, as they complied with government regulations. As the COVID-19 pandemic progressed, the number of patients gradually returned to normal.

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

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

Comparison of sperm parameters and DNA fragmentation index between infertile men with infection and vaccines of COVID-19.

Several preventive measures, including vaccination, have been implemented owing to the severe global effect of coronavirus disease 2019 (COVID-19), but there is still limited evidence in the effect of this disease and vaccination against it on male fertility. Therefore, this study is to compare sperm parameters of infertile patients with or without COVID-19 infection and the effect of COVID-19 vaccine types on them. Semen samples of infertile patients were collected consecutively at Universitas Indonesia - Cipto Mangunkusumo Hospital (Jakarta, Indonesia). COVID-19 was diagnosed by rapid antigen or polymerase chain reaction (PCR) tests. Vaccination was performed with three types of vaccine, namely inactivated viral vaccine, messenger RNA (mRNA) vaccine, and viral vector vaccine. Spermatozoa were then analyzed on the World Health Organization recommendations, and DNA fragmentation was assayed with the sperm chromatin dispersion kit. The results showed that the COVID-19 group experienced a significant decrease in sperm concentration and progressive motility (both P < 0.05), but there was no significant change in morphology or sperm DNA fragmentation index (DFI; both P > 0.05). The viral vector vaccine caused a decrease in morphology as well as an increase in DFI compared with the control (both P < 0.05), meanwhile results for those who were vaccinated with the inactivated and mRNA types were not significant compared with the control (both P > 0.05). We conclude that COVID-19 has negative effects on sperm parametes and sperm DNA fragmentation, and we found that the viral vector vaccines affect sperm parameter values and DNA fragmentation negatively. Further studies with a larger population and longer follow-up are needed to confirm the results.

Menstrual cycle changes and mental health states of women hospitalized due to COVID-19.

PURPOSE: Many studies have evaluated the impact of the COVID-19 pandemic on women's mental health and menstrual changes. However, most of these studies only included nonhospitalized COVID-19 patients, while information on hospitalized women is very limited. Thus, this study aimed to examine the mental health status and menstrual changes in hospitalized female COVID-19 patients. METHODS: A survey was administered to female COVID-19 patients in the isolation ward of a national referral hospital in Indonesia between January and August 2021, and the women were followed up 3 months after discharge. The survey evaluated menstrual patterns and mental health using the Self Reporting Questionnaire-29 (SRQ-29). RESULTS: The study enrolled 158 female patients. There was an increase in patients who had a cycle length of > 32 or < 24 days, and significant increases in menstrual irregularity and heavy menstrual bleeding were noted. Overall, 37.3% of the patients reported a change in menstrual pattern after infection with COVID-19. Based on SRQ-29 scores, 32.3% of the women had neurotic symptoms, 12.7% had psychotic symptoms, and 38.0% had symptoms of posttraumatic stress disorder. Patients with symptoms of mental health disorders were twice as likely to report a menstrual change (OR 2.17, 95% CI 1.12-4.22; p = 0.021). CONCLUSION: Menstrual changes and increased symptoms of mental health disorders occur in hospitalized female COVID-19 patients. The length of isolation was the key factor affecting overall menstrual changes and mental health in hospitalized female COVID-19 patients.

Knowledge, attitudes, and behaviors of practitioners supporting cancer patients in fertility preservation in DKI Jakarta: A cross-sectional study.

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.

Ovarian cortex freezing as a method of fertility preservation in endometriosis: A case report.

BACKGROUND: Endometriosis affects women in many ways from infertility until reducing ovarian reserve. In women who do not want to immediately conceive, ovarium cortex cryopreservation may be an option for preserving fertility. CASE PRESENTATION: Two patients with chief complaints dysmenorrhea and abdominal enlargement, then checked Anti-Mullerian Hormone (AMH) level and Ca-125 level. Patient underwent transrectal ultrasonography, with the result of endometriosis cyst (sized 12 × 9x3 cm and 7 × 10 × 11 cm for first patient, while second patient had 18 × 10 × 14 cm). Then patients underwent cystectomy and ovarian cryopreservation. Histopathology results revealed endometriosis cyst, with different results of follicle density on the healthy cortex. Patient have an AMH level of 1.82 ng/mL before surgery and may decline after surgery. From the AMH normogram, the patient is below the 25th percentile and almost below the 10th percentile, and her biological age is 34. Normal histopathology result of the ovarian cortex suggested that 1.8 to 166 follicles per mm3 cortical tissue. DISCUSSION: We can see from the histopathology examination the density of the follicle was less than normal in this patient. Patients that suffer from endometriosis may have a low ovarian reserve even before surgery. A thorough consultation, followed by ovarian reserve evaluation, disease progression and recurrence of disease are needed to be monitored closely. CONCLUSION: From all the methods of fertility preservation, we concluded that this patient is most suitable for ovarian cortex freezing.

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

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

Impact of IVF on the Timing and Symptoms of Menopause.

BACKGROUND: Age-related loss of female fertility is characterized by a decline in both the quantity and quality of ovarian follicles. Symptoms of ovarian stimulation, which is part of the process of in vitro fertilization (IVF), vary among women. This study was conducted to analyze the differences in menopausal timing and symptoms in women who had undergone IVF compared to those who had natural pregnancies. METHODOLOGY: In this cross-sectional study, menopausal women were categorized into two groups: those who had undergone IVF (n = 50) and those who had not (n = 50). Clinical data were obtained from the participants' medical records, and patient interviews were conducted using the menopause rating scale (MRS) questionnaires. RESULTS: The IVF had no significant impact on psychological or somatic symptoms in either group (p>0.05). However, it affected urogenital symptoms (p<0.05). Additionally, there was a significant difference in the age of onset of menopause between the groups (p<0.05). CONCLUSION: There is a significant correlation between IVF treatment, urogenital symptoms in menopause, and the age of onset of menopause.

Communication and Respect for Patient Value as Significant Factors in Patient-Centered Infertility Care: A Survey of Patients' Experiences in Two Infertility Centers.

CONTEXT: The patient-centered infertility care (PCIC) approach emphasizes the patient's role in choosing the most appropriate clinical approach in infertility care. The concept can improve the patient satisfaction with care performed as well as the efficacy of the treatment. In addition, this concept can also lead to improve collaboration between patient and care provider, ultimately supporting a more cost-effective health-care scheme. AIMS: This study was developed in order to determine patients' experience in their PCIC. SETTINGS AND DESIGN: This is a descriptive study. We conducted the study in two fertility care clinics, Clinic A and Clinic B. SUBJECTS AND METHODS: The Patient-Centeredness Questionnaire-Infertility (PCQ-I) was used, consisting of 7 essential themes. The questionnaire was completed by consenting patients in two infertility clinics. STATISTICAL ANALYSIS USED: The questionnaire was analyzed using the Statistical Package for the Social Sciences 21 version statistical software. RESULTS: Eighty-eight Clinic A patients who completed the questionnaire responded that the best element of their treatment received was communication (correlation with global score [CGS]: 0.747), whereas the least acceptable aspect was the low accessibility (CGS: 0.211). A total of 20 Clinic B patients responded that the best element of their treatment received was respect for the patient's value (CGS: 0.866), whereas the least acceptable aspect was also the low level of accessibility (CGS: 0.193). CONCLUSIONS: The PCQ-I can be used to evaluate patients' experience during treatment and may help the health-care provider to improve their performance.

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.

Correlation of anti-Müllerian hormone levels with metabolic syndrome events in polycystic ovary syndrome: A cross-sectional study.

BACKGROUND: Various endocrine disorders have been reported in women of reproductive age, 10% of which is affected by polycystic ovary syndrome (PCOS). OBJECTIVE: This study aimed to evaluate the correlation of anti-Müllerian hormone (AMH) levels with the metabolic syndrome in patients with PCOS. MATERIALS AND METHODS: This cross-sectional study employed a consecutive sampling method using medical records from January 2013 to December 2017 at Dr. Cipto Mangunkusumo General Hospital polyclinic and Yasmin in vitro fertilization Clinic (Kencana), Jakarta, Indonesia. The primary outcome of the study was the AMH levels as independent variable correlated with metabolic syndrome. The secondary outcome was also the AMH levels correlated with each PCOS phenotype. The tertiary outcome was each PCOS phenotype as independent variable correlated with metabolic syndrome. RESULTS: Women with phenotype 1 of PCOS had a median AMH level of 13.92 (range: 3.88-34.06) ng/ml. 21% patients had metabolic syndrome, with a median AMH level 7.65 (3.77-20.20) ng/ml, higher than the women without metabolic syndrome (p = 0.38). The most frequent phenotype in women with PCOS was phenotype 4, oligo- or anovulation and polycystic ovary morphology (OA/PCOM) in 41.3%. The most frequent phenotype in women with metabolic syndrome was phenotype 1, OA + PCOM + hyperandrogenism in 56.5%. CONCLUSION: All PCOS phenotypes exhibited significant correlations with the AMH level. Phenotype 1 (OA + PCOM + hyperandrogenism) was associated with the highest AMH level and was significantly associated with metabolic syndrome.

Overview of risk factor and bacterial pattern in patient with surgical site infection after caesarean section in Ciptomangunkusumo Hospital from 2016 to 2018.

Background: Caesarean section is one of the most commonly performed surgeries both in the hospital. The incidence of infections in cesarean section varies greatly around the world at 3-15%. SSI on is a multifactorial process that starts from the perioperative preparation, the patient, the type of surgery, the type of germ and other factors. Aims: To determine the characteristics of patients, bacterial patterns, and risk factors for the incidence of SSI in Cipto Mangunkusumo National General Hospital in 2016-2018. Method: This study was an observational study using a retrospective cohort method. The subject of this study were patients undergoing cesarean section in Cipto Mangunkusumo National General Hospital in 2016-2018 recruited using consecutive sampling method. Based on the data obtained, bivariate and multivariate analysis were conducted to determine the factors affecting post-caesarean SSI. Results: A total of 2052 subjects were included in the study. There were 85 cases of surgical site infection (SSI) out of 2052 operations (4.14 %). A total of 85 SSI cases and 1967 control groups were included in the risk factor analysis. The most common bacteria found in surgical site infection culture were Staphylococcus aureus (16,5%), Klebsiella pneumoniae (12,9%), Escherichia coli (9,4%), Enterococcus faecalis (9,4%), and others (21,2%). Variables associated with SSI in this study is fetal distress (p=0,002; AOR = 2,265 CI 95 % 1,350-3,801) and BMI ≥30 kg/m2 (p=0,028; AOR 1,824 CI 95% 1,066-3,121). Conclusion: Factors influencing the incidence of SSI post cesarean section was fetal distress (p=0,002; AOR = 2,265 CI 95 % 1,350-3,801) and BMI ≥30 kg/m2 (p=0,028; AOR 1,824 CI 95% 1,066-3,121).

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.

Dysregulation of Kisspeptin and Leptin, as Anorexigenic Agents, Plays Role in the Development of Obesity in Postmenopausal Women.

During the menopausal period, women have a higher tendency to develop obesity and any other metabolic syndromes. Dysregulation of leptin and kisspeptin signaling as anorexigenic agents is believed to be the connection between metabolic disorders and altered reproductive function. Therefore, this study aimed at investigating the association between leptin, soluble leptin receptor (sOBR), free leptin index, kisspeptin concentrations, and body mass index (BMI) in postmenopausal women. A cross-sectional study was carried out among 171 postmenopausal women aged 40-75 years from 2017 to 2018. Subjects were assigned into 2 groups according to their BMIs: obese group (84 subjects) and nonobese group (87 subjects). In addition to anthropometric measurement, blood sample was collected from each subject for leptin, sOBR, free leptin index (FLI), and kisspeptin evaluation. Bivariate and correlation analysis discovered that leptin and FLI were positively correlated with BMI, while sOBR and kisspeptin were negatively correlated with BMI. Among those variables, multivariate analysis found that leptin, sOBR, and kisspeptin were independently associated with obesity. Therefore, it can be concluded that higher serum leptin concentration and FLI, as well as lower serum sOBR and kisspeptin concentrations, are significantly associated with obesity in postmenopausal women.

Trans-arterial embolization of acquired uterine arteriovenous malformation after Cesarean section: A case series.

BACKGROUND: Acquired uterine arteriovenous malformation (AVM) is a rare condition due to traumatic episodes in cesarean section. The patient can suffer from life-threatening hemorrhage or recurrent vaginal bleeding. Establishing this diagnosis is difficult, often misdiagnosed due to lack of information and number of cases. Trans-Arterial Embolization (TAE) procedure is rarely performed in our center. All of the cases were found with history of massive bleeding and diagnosed lately after recurrent bleeding history. Even though promising, one of our cases failed to be managed with TAE. It is important to diagnose early symptoms of AVM in order to prevent the life threatening event. CASE PRESENTATION: In these case series, four cases of AVMs after cesarean procedures will be reviewed. One could be diagnosed in less than a month but the other three took several months. The symptom of vaginal bleeding might occur a few weeks after the procedure is done, and most patients need transfusion and hospitalization. Three out of four patients were initially sent to the hospital in order to recover from shock condition, and one patient was sent for a diagnostic procedure. AVMs diagnostic was established with ultrasound with or without angiography. Three of our cases were succeeded by performing TAE procedure without further severe vaginal bleeding. One case failed to be treated with embolization and had to proceed with hysterectomy. CONCLUSION: AVM should be considered early-on in patient with abnormal uterine bleeding and history of cesarean section. Embolization is still the first-choice treatment of AVMs, otherwise definitive treatment is hysterectomy in a patient without fertility need, or impossible to perform TAE.

Correlation between luteinizing hormone receptor gene expression in human granulosa cells with oocyte quality in poor responder patients undergoing in vitro fertilization: A cross-sectional study.

Background: This study was performed to evaluate the role of luteinizing hormone (LH) and granulosa cell LH receptor (LH-R) in poor responder patients who underwent controlled ovarian stimulation. Expression levels of LH-R mRNA in granulosa cells was investigated and compared with oocyte morphology, oocyte maturity and fertilization rate.  Methods: Granulosa cells were obtained from 30 patients who underwent in vitro fertilization (IVF) at Dr. Cipto Mangunkusumo Hospital, Jakarta. The patients were divided into two groups: group I (n=10) poor responders; and group II (n=20) non-poor responders. After the extraction of total RNA from granulosa cells, semi-quantitative RT-PCR was performed and the amount of LH-R mRNA was quantified. The relative values were calculated as the ratio of LH-R mRNA and actin beta mRNA. Statistical analysis was performed using Mann-Whitney test and Spearman correlation.  Results: The relative value of LH-R mRNA was higher in group I compared with group II (27.37[0.00-28939.37] vs 0.00[0.00-7196.12]). Oocyte maturity (r=0.267) and morphology (r=0.267) in group I consistently showed a positive correlation with LH-R mRNA; in group II a negative correlation with LH-R mRNA was shown for oocyte maturity (r= -0.552) and morphology (r= -0.164). Group I had a positive correlation between LH-R expression with fertilization rate (r=0.430), and group II showed a negative correlation (r=-0.340).  Conclusions: The expression of LH-R mRNA has a positive correlation with oocyte quality in poor responder patients and a negative correlation in non-poor responders. Our study suggests an optimal expression of LH- R mRNA in granulosa cells during controlled ovarian stimulation to obtain good quality oocytes.

Anti-Mullerian hormone levels in female cancer patients of reproductive age in Indonesia: A cross-sectional study.

Background: Efforts in reproductive preservation for cancer patients have become one of the important aspects of cancer management. In fact, decline in reproductive function is known to occur after exposure to anti-cancer treatments. Measuring anti-Müllerian hormone (AMH) levels is known to be the best parameter in predicting ovarian reserves, which indicates reproductive function. In total, 68% of cancer survivors of reproductive age who underwent anti-cancer treatments suffer from infertility. Meanwhile, ovarian reserves also decrease with increasing age. There is ongoing debate on whether the ovarian reserves of cancer patients could be reduced long before exposure to anti-cancer therapy. Therefore, it is important to know whether ovarian reserves in cancer patients decrease before or after anti-cancer therapy. This can help predict the reproductive function in such cases and the effectiveness of ovarian preservation efforts. Methods: A cross-sectional study was conducted, comparing the AMH levels of 44 female cancer patients of reproductive age before cancer therapy, to 44 non-cancer patients of reproductive age (age matched) . The AMH was determined from blood.The biological ages from both groups were adjusted using the Indonesian Kalkulator of Oocytes. Results: The median age in both groups was 28 years old. The AMH levels in the blood of the cancer group were found to be significantly lower in contrast to those in the non-cancer group (1.11 [0.08-4.65] ng/ml vs. 3.99 [1.19- 8.7]; p- value <0.001). Therefore, the biological age in the cancer group was 10 years older than that of the non-cancer group, indicating that ovarian aging occurs earlier in cancer patients. Conclusions: AMH levels of cancer patients of reproductive age were already reduced before cancer therapy, given an older biological age, in contrast to that of the non-cancer patients. Proper counseling and implementation of fertility-preserving methods is highly recommended in this group of patients.

Changes in culture expanded human amniotic epithelial cells: implications for potential therapeutic applications.

Human amniotic epithelial cells (hAEC) isolated from term placenta have stem cell-like properties, differentiate into tissue specific cells and reduce lung and liver inflammation and fibrosis following transplantation into disease models established in mice. These features together with their low immunogenicity and immunosuppressive properties make hAEC an attractive source of cells for potential therapeutic applications. However, generation of large cell numbers required for therapies through serial expansion in xenobiotic-free media may be a limiting factor. We investigated if hAEC could be expanded in xenobiotic-free media and if expansion altered their differentiation capacity, immunophenotype, immunosuppressive properties and production of immunomodulatory factors. Serial expansion in xenobiotic-free media was limited with cumulative cell numbers and population doubling times significantly lower than controls maintained in fetal calf serum. The epithelial morphology of primary hAEC changed into mesenchymal-stromal like cells by passage 4-5 (P4-P5) with down regulation of epithelial markers CK7, CD49f, EpCAM and E-cadherin and elevation of mesenchymal-stromal markers CD44, CD105, CD146 and vimentin. The P5 hAEC expanded in xenobiotic-free medium differentiated into osteocyte and alveolar epithelium-like cells, but not chondrocyte, hepatocyte, α- and ß-pancreatic-like cells. Expression of HLA Class IA, Class II and co-stimulatory molecules CD80, CD86 and CD40 remained unaltered. The P5 hAEC suppressed mitogen stimulated T cell proliferation, but were less suppressive compared with primary hAEC at higher splenocyte ratios. Primary and P5 hAEC did not secrete the immunosuppressive factors IL-10 and HGF, whereas TGF-ß1 and HLA-G were reduced and IL-6 elevated in P5 hAEC. These findings suggest that primary and expanded hAEC may be suitable for different cellular therapeutic applications.