Targeted therapies in ovarian cancer: where we stand and where we are heading

Ovarian cancer is a highly lethal gynecological cancer globally. The standard treatment for this disease is cytoreductive surgery followed by platinum-based chemotherapy. However, most patients develop platinum resistance after multiple relapses and have an inadequate response to second-line chemotherapy. Additionally, molecular heterogeneity poses a challenge to effective treatment.Current Concepts: Advancements in understanding the molecular mechanisms of cancer progression provide insight into novel targeted therapies, which have emerged as groundbreaking and promising cancer treatment strategies. Poly(ADP-ribose) polymerase inhibitors and anti-vascular endothelial growth factor monoclonal antibodies are currently the two approved and most effective targeted drugs for ovarian cancer.Discussion and Conclusion: This review article discusses related clinical trials assessing the efficacy and safety of promising targets in ovarian cancer as well as challenges associated with targeted therapy, including drug resistance, heterogeneity, and toxicity. Additionally, possible solutions to optimize treatment effects are proposed. Targeting these molecular abnormalities will bring us closer to the goal of personalized therapy and improve the prognosis for patients with ovarian cancer.

Lymph Node Ratio Is a Strong Prognostic Factor in Patients with Early-Stage Cervical Cancer Undergoing Minimally Invasive Radical Hysterectomy

Purpose@#To determine whether the prognostic impact of lymph node ratio (LNR), defined as the ratio between the number of positive lymph nodes and removed lymph nodes, differs between open and minimally invasive surgical approaches for radical hysterectomy (RH) in node-positive, early-stage cervical cancer. @*Materials and Methods@#We retrospectively identified 2009 International Federation of Gynecology and Obstetrics stage IB1-IIA2 patients who underwent primary type C RH between 2010 and 2018. Among them, only those with pathologically proven lymph node metastases who received adjuvant radiation therapy were included. The prognostic significance of LNR was investigated according to open surgery and minimally invasive surgery (MIS). @*Results@#In total, 55 patients were included. The median LNR (%) was 9.524 (range, 2.083–62.500). Based on receiver operating characteristic curve analysis, the cut-off value for LNR (%) was determined as 8.831. Overall, patients with high LNR (≥8.831%;n=29) showed worse disease-free survival (DFS) than those with low LNR (<8.831%, n=26) (p=0.027), whereas no difference in overall survival was observed. Multivariate analyses adjusting for clinicopathologic factors revealed that DFS was adversely affected by both MIS [adjusted hazard ratio (HR), 8.132; p=0.038] and high LNR (adjusted HR, 10.837; p=0.045). In a subgroup of open surgery cases, LNR was not associated with disease recurrence. However, in a subgroup of MIS cases, high LNR was identified as an independent poor prognostic factor for DFS (adjusted HR, 14.578; p=0.034). @*Conclusion@#In patients with node-positive, early-stage cervical cancer, high LNR was associated with a significantly higher disease recurrence rate. This relationship was further consolidated among patients who received MIS RH.

Delayed diagnosis of gestational diabetes mellitus and perinatal outcomes in women with large for gestational age fetuses during the third trimester

Objective@#We evaluated the incidence of newly diagnosed gestational diabetes mellitus (GDM) during the 3rd trimester in women with suspected large for gestational age (LGA) fetuses on ultrasound and assessed their perinatal outcomes. @*Methods@#A retrospective cohort study was performed. Singleton pregnant women with suspected LGA on the 3rd trimester ultrasound and whose results of GDM screening at midpregnancy had been normal were enrolled. All participants were retested with 100-g oral glucose tolerance test (OGTT) within 2 days after diagnosis of LGA. We compared perinatal outcomes between the newly diagnosed with GDM group and the non-GDM group. @*Results@#Among 169 pregnant women, 13% (23/169) were newly diagnosed with GDM. The women in the GDM group had a higher HbA1c level at diagnosis (5.8 vs. 5.3, P<0.01) and earlier gestational age at delivery (38.0 vs 38.9 weeks of gestation, P=0.003) than those in the non-GDM group. The rate of cesarean delivery (CD) was significantly higher in the GDM group than that in the non-GDM group (73.9%, vs. 49.3%, P=0.028) with similar proportions for the indications of CD except CD on maternal request (CDMR). The CDMR rate was higher in the GDM group than nonGDM group (41.2% vs. 23.6%) but it did not reach statistical significance. There were no significant differences in the obstetrical and neonatal complications between the two groups. @*Conclusion@#Among pregnant women with suspected LGA, 13% were newly diagnosed with GDM in late pregnancy. Nonetheless, there were no differences in the perinatal outcomes between women with newly diagnosed GDM and those without GDM. However, concerns over shoulder dystocia appear to increase CD rates in the GDM group.

Delayed diagnosis of gestational diabetes mellitus and perinatal outcomes in women with large for gestational age fetuses during the third trimester

Objective@#We evaluated the incidence of newly diagnosed gestational diabetes mellitus (GDM) during the 3rd trimester in women with suspected large for gestational age (LGA) fetuses on ultrasound and assessed their perinatal outcomes. @*Methods@#A retrospective cohort study was performed. Singleton pregnant women with suspected LGA on the 3rd trimester ultrasound and whose results of GDM screening at midpregnancy had been normal were enrolled. All participants were retested with 100-g oral glucose tolerance test (OGTT) within 2 days after diagnosis of LGA. We compared perinatal outcomes between the newly diagnosed with GDM group and the non-GDM group. @*Results@#Among 169 pregnant women, 13% (23/169) were newly diagnosed with GDM. The women in the GDM group had a higher HbA1c level at diagnosis (5.8 vs. 5.3, P<0.01) and earlier gestational age at delivery (38.0 vs 38.9 weeks of gestation, P=0.003) than those in the non-GDM group. The rate of cesarean delivery (CD) was significantly higher in the GDM group than that in the non-GDM group (73.9%, vs. 49.3%, P=0.028) with similar proportions for the indications of CD except CD on maternal request (CDMR). The CDMR rate was higher in the GDM group than nonGDM group (41.2% vs. 23.6%) but it did not reach statistical significance. There were no significant differences in the obstetrical and neonatal complications between the two groups. @*Conclusion@#Among pregnant women with suspected LGA, 13% were newly diagnosed with GDM in late pregnancy. Nonetheless, there were no differences in the perinatal outcomes between women with newly diagnosed GDM and those without GDM. However, concerns over shoulder dystocia appear to increase CD rates in the GDM group.

Asian Society of Gynecologic Oncology International Workshop 2018 / 부인종양

The Asian Society of Gynecologic Oncology International Workshop 2018 on gynecologic oncology was held in the Ajou University Hospital, Suwon, Korea on the 24th to 25th August 2018. The workshop was an opportunity for Asian doctors to discuss the latest findings of gynecologic cancer, including cervical, ovarian, and endometrial cancers, as well as the future of fertility-sparing treatments, minimally invasive/radical/debulking surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Clinical guidelines and position statement of Asian countries were presented by experts. Asian clinical trials for gynecologic cancers were reviewed and experts emphasized the point that original Asian study is beneficial for Asian patients. In Junior session, young gynecologic oncologists presented their latest research on gynecologic cancers.

Six months response rate of combined oral medroxyprogesterone/levonorgestrel-intrauterine system for early-stage endometrial cancer in young women: a Korean Gynecologic-Oncology Group Study / 부인종양

OBJECTIVE: To evaluate the efficacy of combined oral medroxyprogesterone acetate (MPA)/levonorgestrel-intrauterine system (LNG-IUS) treatment and to compare the diagnostic accuracy of endometrial aspiration biopsy with dilatation & curettage (D&C) in young women with early-stage endometrial cancer (EC) who wished to preserve their fertility. METHODS: A prospective phase II multicenter study was conducted from January 2012 to January 2017. Patients with grade 1 endometrioid adenocarcinoma confined to the endometrium were treated with combined oral MPA (500 mg/day)/LNG-IUS. At 3 and 6 months of treatment, the histologic change of the endometrial tissue was assessed. The regression rate at 6 months treatment and the consistency of the histologic results between the aspiration biopsy and the D&C were evaluated. RESULTS: Forty-four patients were enrolled. Nine voluntarily withdrew and 35 patients completed the protocol treatment. The complete regression (CR) rate at 6 months was 37.1% (13/35). Partial response was shown in 25.7% of cases (9/35). There were no cases of progressive disease and no treatment-related complications. A comparison of the pathologic results from aspiration biopsy and D&C was carried out for 33 cases. Fifteen cases were diagnosed as “EC” by D&C. Among these, only 8 were diagnosed with EC from aspiration biopsy, yielding a diagnostic concordance of 53.3% (ĸ=0.55). CONCLUSION: Combined oral MPA/LNG-IUS treatment for EC showed 37.1% of CR rate at 6 months. Considering the short treatment periods, CR rate may be much higher if the treatment continued to 9 or 12 months. So, this treatment is still a viable treatment option for young women of early-stage EC. Endometrial aspiration biopsy with the LNG-IUS in place is less accurate than D&C for follow-up evaluation of patients undergoing this treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01594879

Effectiveness and safety of sublingual misoprostol in medical treatment of the 1st trimester miscarriage: experience of off-label use in Korea

OBJECTIVE: This study was conducted to determine the effectiveness and safety of medical treatment with sublingual misoprostol (MS) in the 1st trimester miscarriage under the approval by Health Insurance Review and Assessment Service (HIRA) for off-label usage by the single medical center in Korea. METHODS: A retrospective cohort study was performed in one institution between April 2013 and June 2016. Ninety-one patients diagnosed with miscarriage before 14 weeks of gestation and wanted to try medical treatment were included. A detailed ultrasound scan was performed to confirm the diagnosis. Patients took 600 microgram (mcg) of MS sublingually at initial dose, and repeated the same dose 4–6 hours apart. Successful medical abortion was defined as spontaneous expulsion of gestational products (including gestational sac, embryo, fetus, and placenta). If gestational products were not expelled, surgical evacuation was performed at least 24 hours later from the initial dose. Information about side effects was obtained by medical records. RESULTS: About two-thirds of patients had a successful outcome. The median interval time from pill to expulsion was 18 hours in the successful medical treatment group. There was no serious systemic side effect or massive vaginal bleeding. Presence or absence of vaginal spotting before diagnosis of miscarriage, uterine leiomyomas, subchorionic hematoma, or distorted shape of gestational sac on ultrasound scan were not statistically different between the two groups. CONCLUSION: Medical treatment with sublingual MS can be a proper option for the 1st trimester miscarriage, especially for the patient who want to avoid surgical procedure. We can reduce the unnecessary sedation or surgical intervention in the patients with the 1st trimester miscarriage.

Erratum: Correction of Acknowledgements

The Acknowledgements was published incorrectly. The authors apologize for any inconvenience that it may have caused.

The clinical significance of D-dimer concentrations in patients with gestational hypertensive disorders according to the severity

OBJECTIVE: Pregnancy is a major risk factor of thromboembolism, and the patients with preeclampsia (PE) are known to have higher risk of thromboembolic complications than normal pregnant women. D-dimer is a well-established laboratory marker for the screening of venous thromboembolism (VTE), but the concentrations of d-dimer tend to increase physiologically in pregnant women throughout the gestational age. We performed this study to evaluate the clinical significance of d-dimer concentrations in patients with gestational hypertensive disorders (GHD) according to the severity. METHODS: Retrospective cohort study was performed in one institution. Singleton pregnant women with GHD were enrolled, and their antepartum concentrations of d-dimer were measured as a part of routine evaluation for patients suspected with PE. Patients with multiple gestations, rheumatic diseases, autoimmune diseases, or suspected VTE were excluded. A categorization of severity about PE was based on the general criteria. RESULTS: In 73.3% of study population, their d-dimer concentrations exceeded the normal range (>0.55 mg/L). A significantly greater proportion of pregnant women had excessive concentrations of d-dimer in the severe GHD than in the non-severe GHD (89.8% vs. 53.7%; P<0.01). Patients with severe GHD had significantly higher median concentrations of d-dimer than those with non-severe GHD (median [range], 2.00 mg/L [0.11 to 7.49] vs. 0.71 mg/L [0.09 to 5.39]; P<0.01) although their earlier gestational ages of sampling. CONCLUSION: Maternal concentrations of d-dimer were significantly elevated in patients with severe features than those without severe features among those with GHD. Some pregnant women with GHD can have markedly elevated concentrations of d-dimer without any evidence of current VTE.

Practice guidelines for management of uterine corpus cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement / 부인종양

Clinical practice guidelines for gynecologic cancers have been developed by many organizations. Although these guidelines have much in common in terms of the practice of standard of care for uterine corpus cancer, practice guidelines that reflect the characteristics of patients and healthcare and insurance systems are needed for each country. The Korean Society of Gynecologic Oncology (KSGO) published the first edition of practice guidelines for gynecologic cancer treatment in late 2006; the second edition was released in July 2010 as an evidence-based recommendation. The Guidelines Revision Committee was established in 2015 and decided to produce the third edition of the guidelines as an advanced form based on evidence-based medicine, considering up-to-date clinical trials and abundant qualified Korean data. These guidelines cover screening, surgery, adjuvant treatment, and advanced and recurrent disease with respect to endometrial carcinoma and uterine sarcoma. The committee members and many gynecologic oncologists derived key questions from the discussion, and a number of relevant scientific literatures were reviewed in advance. Recommendations for each specific question were developed by the consensus conference, and they are summarized here, together with other details. The objective of these practice guidelines is to establish standard policies on issues in clinical areas related to the management of uterine corpus cancer based on the findings in published papers to date and the consensus of experts as a KSGO Consensus Statement.

Ruptured Corpus Luteal Cyst: Prediction of Clinical Outcomes with CT

OBJECTIVE: To evaluate the determinant pretreatment CT findings that can predict surgical intervention for patients suffering from corpus luteal cyst rupture with hemoperitoneum. MATERIALS AND METHODS: From January 2009 to December 2014, a total of 106 female patients (mean age, 26.1 years; range, 17–44 years) who visited the emergency room of our institute for acute abdominal pain and were subsequently diagnosed with ruptured corpus luteal cyst with hemoperitoneum were included in the retrospective study. The analysis of CT findings included cyst size, cyst shape, sentinel clot sign, ring of fire sign, hemoperitoneum depth, active bleeding in portal phase and attenuation of hemoperitoneum. The comparison of CT findings between the surgery and conservative management groups was performed with the Mann-Whitney U test or chi-square test. Logistic regression analysis was used to determine significant CT findings in predicting surgical intervention for a ruptured cyst. RESULTS: Comparative analysis revealed that the presence of active bleeding and the hemoperitoneum depth were significantly different between the surgery and conservative management groups and were confirmed as significant CT findings for predicting surgery, with adjusted odds ratio (ORs) of 3.773 and 1.318, respectively (p 5.8 cm and concurrent active bleeding, the OR for surgery increased to 5.786. CONCLUSION: The presence of active bleeding and the hemoperitoneum depth on a pretreatment CT scan can be predictive warning signs of surgery for a patient with a ruptured corpus luteal cyst with hemoperitoneum.

Controversies in the management of endometrial cancer: a survey of the Korean Gynecologic Oncology Group / 부인종양

OBJECTIVE: To identify current practice patterns for unresolved issues in the surgical and adjuvant management of endometrial cancer in Korea. METHODS: We designed and conducted a survey of all 218 active members of the Korean Gynecologic Oncology Group to try to identify how they would manage various case scenarios for endometrial cancer. Data were collected using an Internet survey database. RESULTS: A total of 108 members (49.5%) responded to the survey. Laparoscopy (81.6%) was the most commonly used mode of surgery in early-stage endometrial cancer. Of all the respondents, 19.8% stated that lymphadenectomy could be omitted and 21.7% recommended selective lymphadenectomy based on sentinel biopsy or frozen results for patients with presumed stage IA/grade 1 disease. On the other hand, 71.9% of respondents recommended para-aortic lymphadenectomy for patients with presumed stage IB/grade 1 disease and 86.4% recommended this treatment for presumed stage IB/grade 3 disease. The majority of respondents performed adjuvant therapy for stage IB/grade 2 (91.7%), IB/grade 3 (99.0%), and stage II (89.6%). Whole pelvic radiotherapy and vaginal brachytherapy were the most frequently used options among these patients. All respondents administered adjuvant therapy when node metastasis was found, and concurrent chemoradiotherapy (53.2%) was the most preferred option for stage IIIC1 disease. CONCLUSION: There is broad variation in both the surgical and adjuvant treatment of endometrial cancer among Korean gynecologic oncologists.

Efficacy of methotrexate therapy in patients with tubal pregnancy and a serum human chorionic gonadotropin level above 10,000 IU/L / 대한생식의학회지

OBJECTIVE: To estimate the failure rate of medical treatment and to identify variables associated with treatment failure in patients with tubal pregnancy and an initial serum level of human chorionic gonadotropin (HCG) over 10,000 IU/L. METHODS: The inclusion criteria were tubal pregnancy diagnosed using ultrasonography, primary treatment of intramuscular methotrexate injection at one of the four institutions between January 2003 and December 2011, a serum HCG level within two days before treatment>10,000 IU/L, and follow-up data to determine treatment success or failure. Exclusion criteria were other primary treatments besides intramuscular methotrexate injection. The clinicopathologic data of 36 patients were collected and analyzed. RESULTS: Medical treatment failed and surgery was performed in 19 (53%) patients. In univariable analysis, age, parity, and size of the gestational sac were associated with treatment failure, but none of the variables were associated with treatment failure in multivariable analysis. The failure rate in the subgroup with age or =1.1 cm was significantly higher than those of the other subgroups (82% vs. 41% [mean of the other subgroups], respectively). CONCLUSION: Patients with a serum HCG level>10,000 IU/L who received medical treatment had a high failure rate. Among them, patients aged or =1.1 cm had an extremely high failure rate.

Successful laparoscopic surgery for 14-month-old infant with ovarian torsion

The prevalence of ovarian torsion is 4.9 among 100,000 females between ages 1 to 20 years. The diagnosis of ovarian torsion in children, especially in infants, is very difficult. Since they cannot explain related symptoms accurately, and reproductive organs lie high in the abdomen, physical examination shows unclear findings. For these reasons, we use imaging studies, such as ultrasonography and magnetic resonance imaging, to diagnose ovarian torsion. However, it is of limited value to diagnose by using these modalities alone. Therefore, clinical suspicion is important for diagnosis. Though pediatric laparoscopic surgery was introduced 20 years ago, it has been widely performed since the mid 1990s with the development of 3-mm instruments. In addition, usually the pediatric operation is done in the pediatric surgery office, even though it is a gynecologic procedure. In addition, laparotomy is still more frequently conducted in current clinical practice, although the frequency of laparoscopic surgery has increased. However, it is thought that expert gynecologic surgeons can perform pediatric laparoscopic operations if they pay attention to some precautions. We report herein the case of a 14-month-old infant who underwent emergency laparoscopic untwisting of ovarian torsion successfully without complications by a gynecologic surgeon, with a brief review of the literature.

Metastatic malignant melanoma with peritoneal seeding in a young woman: A case report

Malignant melanomas of the uterus, either primary or metastatic, are extremely rare. They can be mistaken as other tumors, such as uterine sarcomas during diagnosis. We describe here the first case of a metastatic melanoma of the uterus with peritoneal seeding in a young woman. It was first diagnosed as a uterine sarcoma from a frozen-section biopsy.

Improvements to the FIGO staging for ovarian cancer: reconsideration of lymphatic spread and intraoperative tumor rupture / 부인종양

OBJECTIVE: To evaluate the improvement in prognosis prediction with reassignment of International Federation of Gynecology and Obstetrics (FIGO) stages for ovarian carcinoma. METHODS: This was a retrospective study of patients with epithelial ovarian, fallopian tube, and primary peritoneal cancers. Sub-staging criteria used in stage reassignment were defined as follows: surgical spillage (IC1), capsule rupture before surgery or tumor on the surface (IC2), and positive cytology results (IC3); microscopic (IIB1) and macroscopic (IIB2) pelvic spread; microscopic extrapelvic spread (IIIA1) and retroperitoneal lymph node (LN) metastasis without extrapelvic spread (IIIA2); and supraclavicular LN metastasis (IVA) and other distant metastasis (IVB). Survival outcomes associated with the current and reassigned stages were compared. RESULTS: Overall, 870 patients were eligible for analysis. The median follow-up period was 45 months (range, 0 to 263 months). The 5-year overall survival rates (5YSRs) according to the current staging were 93.5% (IA), 82.5% (IC), 75.0% (IIB), 74.5% (IIC), 57.5% (IIIA), 54.0% (IIIB), 38.5% (IIIC), and 33.0% (IV). The 5YSRs of patients with IC1, IC2, and IC3 after sub-staging were 92.0%, 85.0%, and 71.0%, respectively (p=0.004). Patients who were reassigned to stage IIIA2 had a better 5YSR than those with extrapelvic tumors >2 cm (66.3% vs. 35.8%; p=0.005). Additionally, patients with newly assigned stage IVA disease had a significantly better 5YSR than those with stage IVB disease (52.0% vs. 28.0%; p=0.015). CONCLUSION: The modified FIGO staging for ovarian carcinoma appears superior to the current staging for discriminating survival outcomes of patients with surgical spillage, retroperitoneal LN metastasis without extrapelvic peritoneal involvement, or distant metastasis to supraclavicular LNs.

Practice guidelines for the early detection of cervical cancer in Korea: Korean Society of Gynecologic Oncology and the Korean Society for Cytopathology 2012 edition / 부인종양

The consensus guideline development committee of Korean Society of Gynecologic Oncology was reconvened in March 2012. The committee consisted of 36 experts representing 12 university hospitals and professional organizations. The objective of this committee was to develop standardized guidelines for cervical cancer screening tests for Korean women and to distribute these guidelines to every clinician, eventually improving the quality of medical care. Since the establishment of the consensus guideline development committee, evidence-based guidelines have either been developed de novo considering specific Korean situations or by adaptation of preexisting consensus guidelines from other countries. Recommendations for cervical cancer screening tests, management of atypical squamous and glandular cells, and management of low-grade and high-grade squamous intraepithelial lesions were developed. Additionally, recommendations for human papillomavirus DNA testing and recommendations for adolescent and pregnant women with abnormal cervical screening test results were also included.

Asian society of gynecologic oncology workshop 2010 / 부인종양

This workshop was held on July 31-August 1, 2010 and was organized to promote the academic environment and to enhance the communication among Asian countries prior to the 2nd biennial meeting of Australian Society of Gynaecologic Oncologists (ASGO), which will be held on November 3-5, 2011. We summarized the whole contents presented at the workshop. Regarding cervical cancer screening in Asia, particularly in low resource settings, and an update on human papillomavirus (HPV) vaccination was described for prevention and radical surgery overview, fertility sparing and less radical surgery, nerve sparing radical surgery and primary chemoradiotherapy in locally advanced cervical cancer, were discussed for management. As to surgical techniques, nerve sparing radical hysterectomy, optimal staging in early ovarian cancer, laparoscopic radical hysterectomy, one-port surgery and robotic surgery were introduced. After three topics of endometrial cancer, laparoscopic surgery versus open surgery, role of lymphadenectomy and fertility sparing treatment, there was a special additional time for clinical trials in Asia. Finally, chemotherapy including neo-adjuvant chemotherapy, optimal surgical management, and the basis of targeted therapy in ovarian cancer were presented.

Multiple benign metastasizing leiomyomas in the pelvic and para-aortic lymph nodes: A case report / 대한산부인과학회지

Benign metastasizing leiomyoma (BML) is a rare entity, defined as a muscle tumor in association with one or more smooth muscle tumor of the uterus and without evidence of any extra uterine primary site. The lung is the most common site of involvement,(2) and the etiology of BML remains unknown. We experienced a case of BML arising in pelvic and para-aortic lymph nodes and report with a brief review of literature.

Decrease in acceptance of genetic amniocentesis after alteration of social conditions toward pregnancy termination / 대한산부인과학회지

OBJECTIVE: To investigate the effect of alteration of social conditions towards pregnancy termination on the acceptance of genetic amniocentesis. METHODS: Retrospective review of medical records was conducted for women ( 35 years in the 2010 group (5/30, 17%) were less likely to accept genetic amniocentesis than 2009 group (15/30, 50%; P=0.01). Similar results were observed in those who were indicated for genetic amniocentesis. (9/35, 26% vs 19/34, 56%; P=0.02). Acceptance rate of genetic amniocentesis was increased for those who were referred from private clinic, but without statistical significance (15/21, 71% vs 13/14, 93%; P=0.20). CONCLUSION: After strict regulation of pregnancy termination, acceptance rate of genetic amniocentesis was significantly decreased among women who had increased risk for chromosomal abnormalities or neural tube defect at our center. Whereas, there were no significant change in acceptance rate for those who were referred for amniocentesis from private clinic.