Trends in vacuum and forceps delivery in teaching hospitals and academic health systems in West Java, Indonesia: A retrospective study.

Objectives: Recently, there has been a decline in the use of vacuums and forceps. This is due to complications that occur in the mother and baby as well as the operator's ability to operate the instruments. Concerning Professional Education Standards for Obstetrics and Gynecology Specialists, the minimum skill that must be achieved by vacuum extraction and forceps is a minimum of five cases. This is difficult to achieve with the number of obstetrics and gynecology residents in West Java. Methods: A retrospective study was conducted using medical records based on the International Classification of Disease 10th Revision from 1 to 28 February 2023 at teaching hospitals and Academic Health System in West Java, namely Hasan Sadikin Hospital, Al-Ihsan Hospital Bandung, and Cikalong Wetan Hospital West Bandung, in the period 1 January 2018 to 31 December 2022. The main outcome was vacuum and forceps extraction with consecutive sampling. The relationship between maternal characteristics such as maternal age, parity, gestational age, and indication for delivery with vaginal operative delivery was descriptive statistics analyzed using IBM SPSS Statistics 26. Results: Trends indicate that the percentage of vaginal operative deliveries tends to be low, below 5%. Vacuum deliveries decreased from 0.75% in 2018 to 0.68% in 2022, while forceps deliveries decreased from 2.77% to 0.98% over the same period. Conclusion: This study concludes that there was an insufficiency of vacuum extraction and forceps delivery cases at the teaching hospital and Academic Health System in West Java to achieve a minimum case of vacuum and forceps. Further research studying how educational interventions improve operative delivery skills might be considered.

The administration of long in-vitro fertilization protocol in adenomyosis: case series.

Background: Adenomyosis is a gynaecological condition characterized by the infiltration of endometrial glands and stroma resulting in ectopic intramyometrial, leading to the generalized enlargement of the uterus. Various cyclical regimens are employed globally to assist infertile women with adenomyosis during in-vitro fertilization (IVF) treatment because there is no consensus regarding the best protocol for managing adenomyosis. Case: The authors reported two cases the administration of long IVF protocol in Adenomyosis with pregnancy outcome. In both cases examined were found that the levels of anti-Mullerian hormone (AMH) were below the 25th percentile. Nevertheless, in both of these cases, the number of oocytes successfully retrieved was more than 5, which may have been influenced by the use of GnRH agonists in previous cycles of long protocol. Both of them were diagnosed with intrauterine pregnancy after transfer embryo. Conclusion: Although there is currently no consensus on the most suitable protocol for adenomyosis cases, the application of a long protocol in both of the aforementioned cases has yielded positive IVF outcomes.

Comparison of salpingectomy and tubal occlusion for hydrosalpinx in in-vitro fertilization outcome.

The occurrence of hydrosalpinx can reduce the success rate of assisted reproductive technology. The laparoscopic salpingectomy and tubal occlusion have been shown to improve in-vitro fertilization (IVF) outcomes in this disease. The primary goal of this review was to assess and compare the IVF outcome following salpingectomy or tubal occlusion in the published literature. The authors included studies with at least one of the following outcomes: days of controlled ovarian hyperstimulation, retrieved oocyte number, fertilization rates, clinical pregnancy rate, miscarriage rate, or ectopic pregnancy rate. In conclusion, proximal tubal occlusion outperforms salpingectomy in terms of fertilization rate while offering no evident advantages in terms of days of controlled ovarian hyperstimulation, retrieved oocytes number, IVF results, or problems in treating hydrosalpinx patients prior to IVF. These data may help clinicians choose the best therapy for patients with hydrosalpinx prior to IVF.

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.

Intelligence, motoric and psychological outcomes in children from different ART treatments: a systematic review and meta-analysis.

BACKGROUND: Subtle abnormalities in children's intelligence, motor skills, and psychology from various assisted reproductive treatments (ARTs) might be underdiagnosed. Understanding the prognosis of intelligence, motor skills, and psychology in children from ART would provide parents with reasonable expectations and enable them to plan relevant support to achieve the optimum potential in ART children. METHODS: We searched PubMed, EMBASE, Ovid, Google Scholar, and Scopus databases until April 13, 2021, to identify relevant studies. Thirty-four studies met the inclusion and exclusion criteria. The meta-analysis employed a standardized mean difference model. The outcome of this study is to compare intelligence quotient (IQ), motoric ability, and behavioral problems between all ARTs, in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) to naturally conceived (NC) children. Subdomains of intelligence based on the Cattell, Horn, and Carroll Model (CHC Model) of cognitive architecture, including fluid reasoning, short-term and working memory, processing speed, visual-spatial ability, long-term memory retrieval, and crystalized intelligence (knowledge), were evaluated and summarized in details. Motor skill was stratified into two domains: gross motoric and fine motoric. Behavioral problem was categorized as externalizing and internalizing behavior. RESULTS: Meta-analysis showed that verbal intelligence score in IVF toddlers is significantly lower than NC toddlers (p = 0.02); conversely, ICSI toddlers scored significantly higher verbal intelligence score compared to NC toddlers (p = 0.005). Toddlers born after ART had significantly lower non-verbal intelligence score (p = 0.047). IVF toddlers scored significantly lower fine motor score (p = 0.01) compared to naturally conceived toddlers. Based on parent's CBCL, NC toddlers had higher total (p = 0.01) and externalizing behavior (p = 0.001) scores  compared to ART toddlers. Evaluation of full scale IQ and all domains of intelligence in preschool and primary school children revealed that no significant differences exist between ART and NC children. Based on preschool and primary school parents' CBCL, IVF children had significantly lower externalizing behavior score compared to NC children (p = 0.04). Meta-analyses of studies on young adolescents revealed that ART young adolescents scored higher academically than their NC counterparts, including on mathematics (p < 0.00001) and reading or language (p < 0.00001). CONCLUSIONS: Despite differences in certain aspects, this finding suggests that ART is unlikely to cause negative impacts on children's neurodevelopment.

Female Genital Tuberculosis: Clinical Presentation, Current Diagnosis, and Treatment.

Female genital tuberculosis is a disease caused by Mycobacterium tuberculosis infection in the female reproductive tract. The disease burden among women leads to infertility is significant, especially in developing countries. The bacteria can spread from the lung into the reproductive organ through lymphatic or hematogenous. Many patients present with atypical symptoms, which mimic other gynecological conditions. Several investigations are needed to establish the diagnosis. Almost all cases of genital TB affect the fallopian tube and cause infertility in patients and endometrial involvement. Current treatment still relies on antituberculosis therapy with a combination of tubal surgery. The present review describes the epidemiological data, clinical presentation, diagnosis, and currently available treatment to cure the disease and for in vitro fertilization.

The effect of oocyte denudation time and intracytoplasmic sperm injection time on embryo quality at assisted reproductive technology clinic - A cross-sectional study.

Background: This study aims to determine whether there is an effect of oocyte denudation time and ICSI time on embryo quality at assisted reproductive Technology clinic. Methods: An observational analytic retrospective study was conduct using cross-sectional study. The subject were oocytes from in-vitro fertilization procedures using the ICSI method at the assisted reproductive technology clinic in a private hospital in Bandung for the period 2017 - 2019. Three variables were oocyte denudation time, ICSI time and embryo quality collected from samples that met the research criteria. Data will be grouped based on denudation time (T1) and Intracytoplasmic Sperm Injection time (T2). Result: From the 5 groups of denudation time; 3-4 hours, 4-5 hours, 5-6 hours, 6-7 hours and more than 7 hours group, the denudation time of 3-4 hours group showed the highest number (66.7%) for excellent embryo quality results, while denudation time of more than 7 hours showed the lowest number (29.2%) for excellent embryo quality results with p < 0.001. From these figures, it shows that the ICSI time of 3-4 hours is superior to the ICSI time of 2-3 hours because the outcome of excellent embryo quality is higher while the outcome of poor embryo quality is lower, although the difference is not significant (p = 0.140). Conclusion: This study shows there was a significant difference in the effect of oocyte denudation time on embryo quality at assisted reproductive technology clinic. There was no significant difference in the effect of intracytoplasmic sperm injection (ICSI) time on embryo quality at assisted reproductive technology clinic.

The impact of COVID-19 on A fertility center in Indonesia: A brief report.

The coronavirus disease 2019 (COVID-19) affected the delivery of care in the fertility center. The higher transmissibility feature of omricon variant increase the transmission possibility between patients, healthcare professionals, and staff. Herein, we report the impact of the COVID-19 pandemic to the fertility center in Indonesia during the third wave period of the pandemic. Seven in vitro fertilization (IVF) cases were cancelled because the patients were tested positive for COVID-19 during their IVF program. Six of the total seventeen medical staff in our center were also tested positive for COVID-19 and stayed at home for self isolation. The cancellation of the IVF program was due to the lack of data regarding safety of IVF procedure in COVID-19 patients, shortage of medical staff, and the lack of negative pressure room in our fertility center. Our priority is to protect the remaining healthy patients in our center as well as the medical staff. The COVID-19 disadvantage both patients, care provider in reproductive healthcare. Regular screening of COVID-19 in fertility setting is highly recommended.

Female urogenital chlamydia: Epidemiology, chlamydia on pregnancy, current diagnosis, and treatment.

Female urogenital chlamydia is a disease caused by Chlamydia trachomatis infection in the female urogenital tract. It is a common bacterial sexually transmitted disease. The bacteria is transmitted through sexual contact with an infected partner or from mother to newborn during vaginal delivery. The prevalence varies among studies and the number is possibly higher due to the lack of massive screening. Many patients were asymptomatic and still be able to transmit the disease. The undiagnosed and untreated disease could cause pelvic inflammatory disease, which leads to infertility, ectopic pregnancy, and chronic pelvic pain. The prevalence among pregnant women is similar to non-pregnant women, therefore chlamydia screening in pregnant women is highly recommended. The nucleic acid amplification test is the most reliable method for the diagnosis due to high sensitivity. The current treatment is given by prescribing antibiotics.

Developmental outcomes in children from cryopreserved embryos compared to their siblings from fresh embryo transfers: a case series.

OBJECTIVE: This study aimed to evaluate the developmental outcomes in children from cryopreserved embryos, with minimum influences of interparental variation that would cause potential bias. Hence we examined siblings, in which the older sibs were from fresh embryo transfers, while the younger sibs were from cryopreserved embryos. METHODS: Three pairs of siblings were evaluated. All routine prenatal and neonatal evaluation were performed, while personal-social, language, fine and gross motor evaluation were all evaluated by the Denver Developmental Screening Test (DDST)-II. Wechsler Preschool and Primary Scale of Intelligence (WPPSI) test was used to measure the Intelligent Quotient (IQ) in 5 of 6 children. RESULTS: Standard prenatal measurements of all children suggested uneventful pregnancies, followed by uneventful deliveries. DDST-II results showed that the aspects of personal-social, language, fine and gross motor in every child are as expected according to their ages. Results from WPPSI tests suggest that 5 of 6 evaluated children acquired average to high-average intelligences. CONCLUSIONS: The results suggest that the developmental outcomes in children from cryopreserved embryos have no significant differences with the outcomes in children from fresh embryo transfers.

Potential of Mesenchymal Stem Cells and Their Secretomes in Decreasing Inflammation Markers in Polycystic Ovary Syndrome Treatment: A Systematic Review.

Background: Polycystic ovary syndrome (PCOS) is a chronic disorder and is one of the most common endocrine disorders in women of a reproductive age. The prevalence of PCOS is growing globally; 52% of women in Southeast Asia alone suffer from this disorder. This disorder is caused by chronic hyperandrogenism, which hinders folliculogenesis. There is also a close relationship between hyperandrogenism and hyperinsulinemia/insulin resistance (IR), and it is estimated that 40-80% of PCOS patients suffer from insulin resistance (IR). Mesenchymal stem cells (MSCs) and their secretomes have been shown to alleviate PCOS symptoms by decreasing IR and androgen secretion by reducing inflammation. This study aimed to systematically review the literature to study the reported potential of MSCs and their secretomes in decreasing inflammation markers in PCOS treatment. Methods: A systematic literature search was performed on EMBASE, PubMed (MEDLINE), and the Cochrane Library with the terms insulin-resistant PCOS, mesenchymal stem cells, and secretome or conditioned medium as the search keywords. A total of 317 articles were reviewed. Four articles were identified as relevant for this systematic review. Results: The results of this study supported the use of mesenchymal stem cells and their secretions in decreasing inflammatory markers in the treatment of polycystic ovary syndrome. Conclusions: This review provided evidence that treatment with mesenchymal stem cells and their secretomes has the potential to treat PCOS due to its ability to downregulate androgen levels and increase insulin sensitivity, which thereby lowers the level of proinflammatory factors.

Management and perinatal outcomes of hypertensive disorders of pregnancy in a low-resource setting in Indonesia.

OBJECTIVES: To provide up-to-date data concerning hypertensive disorders of pregnancy on maternal and neonatal profiles in Indonesia. METHODS: Retrospective clinical audit on all pregnancy-associated hypertensive women between 1 January 2020 and 31 March 2020 at Cianjur General District Hospital. RESULTS: Preeclampsia accounts for 66.8% (235/352) of hypertensive disorders of pregnancy, gestational hypertension 29% (102/352) and chronic hypertension 4.3% (15/352). Compared to other pregnant women, those with preeclampsia, on average, had higher systolic and diastolic blood pressures and poorer kidney (ureum and creatinine) and liver function (aspartate transaminase enzyme and alanine transaminase enzyme) profiles (p < 0.001, < 0.001, < 0.001, 0.003, 0.033 and 0.002, respectively), and required more intensive care admission. Neonates from women with severe forms of preeclampsia (eclampsia and HELLP syndrome (haemolysis, elevated liver enzymes, low platelets)) had, on average, lower birthweight (p = 0.015 and 0.048, respectively) and birth length (p = 0.021, 0.017). Neonates from eclamptic mothers had poorer APGAR (appearance, pulse, grimace, activity and respiration) scores (p = 0.006 and 0.005, respectively). CONCLUSION: Hypertensive disorders of pregnancy exerts adverse maternal and neonatal outcomes, particularly among eclampsia and HELLP-syndrome neonates. Various challenges remain for optimal management.

Administration of Cinnamon and Lagersroemia speciosa Extract on Lipid Profile of Polycystic Ovarian Syndrome Women with High Body Mass Index.

BACKGROUND: Hyperinsulinemia, a common feature in PCOS, have been found to contribute to metabolic disturbance, such as dyslipidaemia and diabetes mellitus type 2. Oral anti-diabetic medications have been prescribed to alleviate this effect. We sought to fnd whether DLBS3233, an insulin sensitizer, could alleviate dyslipidaemia in women with PCOS with high BMI. AIM: This study aimed to investigate the effect of DLBS3233, an herbal combination of C burmanii and L spesiosa extract, on lipid profle, insulin resistance, and free testosterone of women with PCOS with high BMI. STUDY SETTING AND DESIGN: This was a controlled trial conducted in Dr. Cipto Mangunkusumo Hospital, Jakarta, and Dr Hasan Sadikin Hospital, Bandung, Indonesia. MATERIALS AND METHODS: A controlled trial was conducted on 62 volunteers diagnosed with PCOS according to Rotterdam criteria and exhibited insulin resistance as signifed by HOMA-IR > 2.0; baseline lipid profile (LDL, HDL, Triglyceride and Total cholesterol) and free testosterone concentration were obtained. Participants were given 100 mg of DLBS3233 in the morning, and volunteers were followed up monthly, with laboratory tests conducted at the third and sixth months. Data were analysed through intention-to-treat analysis, separating high BMI (≥25 kg/m2) subjects. STATISTICAL ANALYSIS: Repeated-measures model. RESULTS: DLBS3233 improved lipid profle and insulin sensitivity by reducing triglycerides, HOMA-IR, and free testosterone in subjects with high BMI. Limitations and Implications: The current study does not compare the effect of DLBS3233 with a control group. A larger study with a proper control group would have to be conducted to have more conclusive results. CONCLUSION: This study showed that DLBS3233 holds promise as a novel therapy to improve lipid profle for women with PCOS.

Relationship Between Estradiol and Hemostasis Determined Through Thromboelastography Profile in Controlled Ovarian Stimulation Cycles.

PURPOSE: We aimed to analyze the relationship between estradiol level and thromboelastography profile. PATIENTS AND METHODS: This prospective study with comparative analysis was performed on nineteen samples undergoing an IVF procedure in two fertility clinics in Bandung city. Blood samples taken on the second and twelfth days of the IVF cycle. RESULTS: There were significant differences in the value of estradiol, fibrin formation time (α), and coagulation index (CI) (p<0.05). Correlation tests showed no relationship and no significant correlation between an increased level of estradiol and coagulation index (CI) (r s=0.054; p=0.827) and between an increased level of estradiol and fibrinolysis time (LY30) (r s=-0.151; p=0.536). A moderate significant relationship was observed between age and coagulation index (CI) (r s=-0.430; p=0.033) and between age and maximum amplitude (MA) (r s=-0.494; p=0.032). CONCLUSION: Supraphysiological estradiol levels in controlled ovarian stimulation cycles affect the coagulation index and change mainly the fibrin formation time.

Frozen vs. fresh cycles IVF outcomes: retrospective study from an Indonesian IVF centre.

OBJECTIVE: To compare the live birth rates (LBR) and neonatal outcomes of frozen cycle in vitro fertilization (IVF) with fresh cycle IVF in the Indonesian population. RESULTS: This was retrospective study using secondary data of IVF patients at a private fertility centre. Study recruitment was between 3/8/2018 and 31/12/2019. Total sampling included all patients undergoing oocyte retrieval and embryo transfer within recruitment period. Patients undergoing fresh IVF cycles and frozen IVF cycles were compared. 351 patients were recruited: 68.1% (239/351) underwent fresh cycles and 31.9% (112/351) frozen cycles. AMH was significantly higher in frozen cycle group (p = 0.04). Ovulatory disorder was significantly higher in frozen cycle group (p = 0.001). Among patients aged ≤ 30, fresh cycle group had significantly higher LBR (p = 0.02). Among those with ovulatory disorder, LBR was significantly higher with frozen cycle. No significant LBR difference was noted with other infertility causes. When stratified according to pregnancy order, frozen cycle patients had significantly higher birth lengths (p = 0.03) but not length of gestation nor neonatal birthweights. There was no significant difference in the proportion of biochemical pregnancy resulting in LBR (p = 0.08). To conclude, frozen cycle provided higher LBR among patients with ovulatory disorder but fresh cycle was beneficial among patients aged ≤ 30.

Current views on the potentials of convalescent plasma therapy (CPT) as Coronavirus disease 2019 (COVID-19) treatment: A systematic review and meta-analysis based on recent studies and previous respiratory pandemics.

Convalescent plasma therapy (CPT) has been investigated as a treatment for COVID-19. This review evaluates CPT in COVID-19 and other viral respiratory diseases, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and influenza. PubMed and Google scholar databases were used to collect eligible publications until 8 December 2020. Meta-analysis used Mantel-Haenszel risk ratio (RR) with 95% confidence interval (CI) and pooled analysis for individual patient data with inverse variance weighted average. The study is registered at PROSPERO with the number of CRD4200270579. Forty-four studies with 36,716 participants were included in the pooled analysis and 20 studies in the meta-analysis. Meta-analysis showed reduction of mortality (RR 0.57, 95% CI [0.43, 0.76], z = 3.86 [p < 0.001], I2  = 44% [p = 0.03]) and higher number of discharged patients (RR 2.53, 95% CI [1.72, 3.72], z = 4.70 [p < 0.001], I2  = 3% [p = 0.39]) in patients receiving CPT compared to standard care alone. A possible mechanism of action is prompt reduction in viral titre. Serious transfusion-related adverse events were reported to be less than 1% of cases, suggesting the overall safety of CPT; nevertheless, the number of patients participating in the studies was still limited. It is also important to notice that in all the studies, the majority of patients were also given other medications, such as antivirals, antibiotics and corticosteroid; furthermore, randomized controlled studies involving more patients and in combination with other treatment modalities are urgently needed.

Correlation of Anti-Mullerian Hormone Level and Antral Follicle Count with Oocyte Number in A Fixed-Dose Controlled Ovarian Hyperstimulation of Patients of In Vitro Fertilization Program.

BACKGROUND: This study was conducted to determine the correlation of anti-Mullerian hormone (AMH) level and antral follicle count (AFC) with oocyte count in women who had received controlled ovarian hyperstimulation in an in vitro fertilization (IVF) program. MATERIALS AND METHODS: We retrospectively gathered the data of 42 patients who underwent IVF during 2005-2017 at Aster Clinic in Dr. Hasan Sadikin Hospital and Bandung Fertility Center Limijati Hospital, Indonesia. Details of the subjects such as identity, characteristics, history of illness, history of previous therapy, levels of ovarian reserve markers examined (AFC and AMH), follicle-stimulating hormone (FSH) dose given, and number of oocytes produced were recorded. RESULTS: A significant positive correlation between AMH (P≤0.001, r=0.530), AFC (P≤0.001, r=0.687), and AMHAFC combination (P≤0.001, r=0.652), and the number of oocytes was found at the FSH dose of 225 IU. CONCLUSION: AFC and AMH are able to reliably predict ovarian response to FSH.

Correlation of Serum Anti-Mullerian Hormone (AMH) Level on Ovarian Volume in Women with Endometrioma.

BACKGROUND: The correlation between endometrioma and serum Anti-mullerian hormone (AMH) level is a benchmark in determining the prognosis and management of endometrioma. Endometrioma causes a decrease in ovarian reserve due to tissue damage that affects the formation of serum AMH. Serum AMH levels in daily practice are useful as a tool to determine ovarian reserve, markers for diagnosis and prognosis in infertility and reproductive abnormalities. The purpose of this study was to determine the relationship of serum AMH level in women with endometrioma and their correlation to ovarian volume. METHODS: This research was an analytical observational study with a cross-sectional design in women of reproductive age who were diagnosed with endometrioma within the period of August 2019-March 2020 at Hasan Sadikin Hospital, Bandung. Forty-four women who met the inclusion and exclusion criteria were then divided into endometrioma (n=22) and control (n=22) groups. In both groups, transvaginal ultrasound examination was performed to measure the volume of the ovary, then a laboratory examination of serum AMH level was carried out. RESULTS: Serum AMH levels in the endometrioma group were significantly lower than those in the control group (P<0.001). Serum AMH level did not differ significantly based on laterality of the observation group (P=1.000). There was a negative correlation between serum AMH level and the volume of ovarian endometrioma, although not statistically significant (r=-0.332; P=0.066). CONCLUSION: There was a correlation between serum AMH level and endometrioma. Serum AMH levels were significantly lower in the endometrioma group but were not influenced by their laterality. We found a negative correlation between serum AMH level and ovarian volume containing endometrioma, but not statistically significant.

Risk of neurodevelopmental disorders in children born from different ART treatments: a systematic review and meta-analysis.

BACKGROUND: Various techniques in assisted reproductive technology (ART) have been developed as solutions for specific infertility problems. It is important to gain consensual conclusions on the actual risks of neurodevelopmental disorders among children who are born from ART. This study aimed to quantify the relative risks of cerebral palsy, intellectual disability, autism spectrum disorder (ASD), and behavioral problems in children from different ART methods by using systematic review and meta-analysis. Healthcare providers could use the results of this study to suggest the suitable ART technique and plan optimum postnatal care. METHODS: Pubmed, Google Scholar, and Scopus databases were used to search for studies up to January 2020. Of the 181 screened full manuscripts, 17 studies (9.39%) fulfilled the selection criteria. Based on the Newcastle-Ottawa scale ratings, 7 studies were excluded, resulting in 10 studies that were eventually included in the meta-analyses. Mantel-Haenszel risk ratio model was used in the meta-analysis, and the results are described using forest plot with 95% confidence interval. Heterogeneity was assessed using the I2 value. RESULTS: Pooled evaluation of 10 studies showed that the risk of cerebral palsy in children from assisted reproductive technology (ART) is higher than children from natural conceptions (risk ratio [RR] 1.82, [1.41, 2.34]; P = 0.00001). Risk of intellectual disability (RR 1.46, [1.03, 2.08]; P = 0.03) and ASD (RR 1.49 [1.05, 2.11]; P = 0.03) are higher in intracytoplasmic sperm injection (ICSI) children compared to conventional in vitro fertilization (IVF) children. The differences in the risk of neurodevelopmental disorders in children born after frozen and fresh embryo transfers are not significant. Analysis on potential cofounder effects, including multiple birth, preterm birth, and low birth body weight highlight possibilities of significant correlation to the risks of neurodevelopmental disorders. CONCLUSIONS: Pooled estimates suggest that children born after ART are at higher risk of acquiring cerebral palsy. ICSI treatment causes higher risk of intellectual disability and ASD. These findings suggest the importance of the availability of intensive care unit at the time of delivery and long-term developmental evaluation particularly in children from ICSI.

Efficacy of Oral Vitamin A in Reducing ß-hCG Levels in Low-Risk Gestational Trophoblastic Neoplasia Patients.

OBJECTIVE: Low-risk gestational trophoblastic neoplasia (GTN) is generally treated with single agent chemotherapy and methotrexate (MTX) as a first-line therapy. Vitamin A helps to increase trophoblast cell regression, as well as to decrease ß-hCG levels. Vitamin A also increases the effectiveness of MTX by inducing more malignant cell death than MTX alone. Therefore, the aim of the current study was to analyze the changes in ß-hCG levels in low-risk GTN patients following vitamin A administration. METHODS: This study was a randomized clinical trial, which examined initial serum vitamin A and ß-hCG levels in GTN patients before and after three cycles of MTX therapy. Patients were given vitamin A supplementation of 6,000 IU (1.8 mg RAEs) per day, and the changes in serum ß-hCG were observed after three cycles. Patients were grouped by ß-hCG levels (decreased or stagnant). RESULTS: A total of 32 low-risks GTN patients were divided into the intervention group (16 patients who received vitamin A supplementation) and the control group (16 patients who did not receive vitamin A supplementation). In the intervention group, the average initial ß-hCG level was 170,949.3 ± 354,452.1 mIU/mL, and the average ß-hCG post-cycle level was 1,611.9 ± 3,652.5 mIU/mL. In the control group, the average initial ß-hCG level was 178,834.1 ± 2913844.6 mIU/mL, and the average ß-hCG post-cycle level was 25,388.5 ± 58,437.7 mIU/mL. CONCLUSION: In patients with low-risk GTN who underwent MTX chemotherapy, the levels of ß-hCG and the incidence of chemo resistance in the intervention group were lower than those in the control group. Older age may also influence the incidence of chemo resistance in GTN patients. Oral administration of 6,000 IU vitamin A could help to reduce ß-hCG levels in low-risk GTN patients who receive MTX chemotherapy.
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