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.

Combined clinical and ultrasound criteria could accurately predict the Y chromosome in primary amenorrhea patient.

This study aimed to assess the combined clinical and ultrasound criteria as a diagnostic tool for screening the Y chromosome related to primary amenorrhea. This cross-sectional study involving 59 subjects was taken from medical records at the Reproductive Immunoendocrinology Polyclinic of Cipto Mangunkusumo General Hospital, Jakarta, Indonesia. The medical records of subjects were then cross-checked with karyotyping analysis results. Sensitivity, specificity, and predictive values were analyzed to assess the criteria. Two subjects were presented with a Y chromosome, and one without a Y chromosome was misclassified into another group. After analysis, we found that combined clinical and ultrasound criteria could predict the Y chromosome related to primary amenorrhea with 95.9% accuracy, with sensitivity and specificity of 80% and 97.96%, respectively. Combined clinical and ultrasound criteria (introduced as Kanadi Sumapraja Criteria) could be used as a diagnostic tool for screening a Y chromosome related to primary amenorrhea.

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.

Social factors influence on anxiety, depression level and psychological trauma of obstetrics and gynecology residents during COVID-19 pandemic.

Background and aim: The novel coronavirus disease 2019 (COVID-19) has enforced obstetrics and gynecology (ObGyn) residency training process to undergo wide changes including lessons modifications, yet their mental health were not evaluated. Hence, this study aimed to evaluate the influence of social factors on anxiety, depression level, and psychological trauma of ObGyn residents during the COVID-19 pandemic as well as the impact of COVID-19 to residency training program. Methods: A cross-sectional study was conducted in three institutions in Indonesia: the University of Indonesia, the University of Lambung Mangkurat, and the University of Syiah Kuala. A total of 169 ObGyn residents agreed to participate and were enrolled in this study. Results: Total 169 residents were eligible with a mean age of 26-42 years. 76.9% of the residents were exposed to COVID-19 patients during clinical rotation. Approximately half of them (52.6%) thought COVID-19 has brought negative effects. Long-distance learning was considered of good quality by 40.2% of participants. The majority experienced enough resting periods, nearly half of them (45.5%) were concerned about the impact of being a less competent specialist. Conclusion: Overall, no significant statistical relationship were revealed between social factors and depression, anxiety and psychological trauma in ObGyn residents during COVID-19 pandemic.

Characteristics of menstrual disorders and reproductive hormones in women with epilepsy at an Indonesian national referral hospital.

Objective: Menstrual disorders are more common in women with epilepsy than in those without epilepsy. This study aimed to examine the characteristics of reproductive function in women with epilepsy at an Indonesian national referral hospital. Methods: A case-control study was conducted from March 2020 to March 2021. Women with and without epilepsy aged ≥18 years were enrolled. All women were premenopausal before epilepsy diagnosis. Data on demographic characteristics, menstrual profiles, epileptic syndrome, seizure type, seizure frequency, etiology, localization, and anticonvulsant medication were collected. Hormone levels (follicle stimulating hormone, luteinizing hormone, prolactin, and estradiol) were measured. Results: A total of 72 women with and 50 without epilepsy (controls) were included. Dysmenorrhea was more common in women with epilepsy than in those without (59.7 vs. 20%, p < 0.001; odds ratio: 5.931 [95% confidence interval: 2.566-13.709]). Marriage rates were higher in women without epilepsy (82 vs. 45.8%, p < 0.001). No difference was found in hormone levels between the groups. The frequency of seizures was associated with prolactin and estradiol levels (p < 0.001). Polytherapy with clobazam was associated with menstrual cycle regularity. In women with epilepsy with menstrual disorders, valproic acid was associated with higher estradiol levels (p = 0.001) and lamotrigine with lower follicle stimulating hormone levels (p = 0.008). Significance: Women with epilepsy experienced more dysmenorrhea. A higher frequency of seizures associated with lower prolactin and estradiol levels. Polytherapy with clobazam was associated with irregular menstrual cycles, while valproic acid and lamotrigine was associated with estradiol and follicle stimulating hormone levels.

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.

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.

Effect of conditioned medium of umbilical cord-derived mesenchymal stem cells as a culture medium for human granulosa cells: An experimental study.

BACKGROUND: The umbilical cord-derived mesenchymal stem cells conditioned medium (UC-MSCs-CM) produces secretomes with anti-apoptotic properties, and has the potential to prevent apoptosis of granulosa cells (GC) during controlled ovarian hyperstimulation. OBJECTIVE: To observe the effect of UC-MSCs-CM on the interaction between pro- and anti-apoptotic proteins and the influence of growth differentiation factor 9 (GDF9) production in GC. MATERIALS AND METHODS: UC-MSCs-CM was collected from umbilical cord stem cell culture on passage 4. GC from 23 women who underwent in vitro fertilization were cultured and exposed to UC-MSCs-CM for 24 hr. Then RNA of the GC was extracted and the mRNA expression of BCL-2 associated X (BAX), survivin and GDF9 were analysed using quantitative real-time PCR. The spent culture media of the GC were collected for measurement of insulin growth factor 1 using ELISA. RESULTS: The expression of BAX was significantly different after UC-MSCs-CM exposure (4.09E-7 vs. 3.74E-7, p = 0.02). No significant changes occurred in survivin, BAX/survivin ratio, and GDF9 expression after UC-MSCs-CM exposure (p > 0.05). The IGF-1 level of the CM was significantly higher after the CM was used as a culture medium for GC (2.28 vs. 3.07 ± 1.72, p ≤ 0.001). A significant positive correlation was found between survivin and GDF9 (r = 0.966, p ≤ 0.001). CONCLUSION: IGF-1 produced by UC-MSCs-CM can work in paracrine fashion through the IGF receptor, which can inhibit BAX and maintain GDF9 production. Moreover, under the influence of UC-MSCs-CM, GC are also capable of producing IGF-1, which can impact GC through autocrine processes.

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.

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.

Body fat percentage is a better marker than body mass index for determining inflammation status in polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrinopathic disorder most commonly experienced by women of reproductive age, and it is characterized by a low-grade chronic inflammatory condition. Excessive fat deposit has been long considered as an etiological factor in the pathogenesis of this inflammatory condition. Currently, body mass index (BMI) or percentage of body fat is used as a marker to assess the body fat composition of a person. OBJECTIVE: To determine whether BMI or body fat percentage (BFP) can be used as a better marker for measuring inflammation related to body fat accumulation in polycystic ovary syndrome patients. MATERIALS AND METHODS: This study took place at the Center for Reproductive Medicine, Yasmin Clinic, Cipto Mangunkusumo Hospital from January to December 2015. In this cross-sectional study, 32 reproductive age women with PCOS according to the Rotterdam criteria (2003) participated. Women with hyperandrogenism caused by non-classic congenital adrenal hyperplasia, pregnant and lactating women, etc., were excluded. Some variables such as BMI, clinical hyperandrogenism sign, BFP, and inflammatory markers were assessed and statistically analyzed. RESULTS: From a total of 32 subjects of the study, BFP had a significant positive correlation with procalcitonin levels (r=0.35; p=0.048), while BMI did not (r=0.27; p=0.131). CONCLUSION: BFP can be used as a better marker for measuring inflammation related to body fat accumulation in PCOS subjects.

Anti-mullerian hormone as a diagnostic and prognostic tool for PCOS patients.

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.

Chronological age vs biological age: an age-related normogram for antral follicle count, FSH and anti-Mullerian hormone.

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.