Sue Yazaki Sun

Polymorphisms in VEGF, progesterone receptor and IL-1 receptor genes in women with recurrent spontaneous abortion

Hormonal, inflammatory and vascular alterations during pregnancy are thought to be involved in pregnancy loss. The role of progesterone, the actions of which involve cytokines and vascular endothelial growth factor (VEGF), has been thoroughly studied. Genetic factors are involved in modulation of these molecules, and several genes have been associated with recurrent spontaneous abortion (RSA), as well other obstetric conditions. Here we investigate the relationship between RSA and gene polymorphisms of the progesterone receptor (PROGINS), interleukin-1 receptor 1 (PstI) and vascular endothelial growth factor (VEGF) (-634, 936). This case-controlled study comprised a total of 89 women with idiopathic RSA and a control group of 191 women with at least two successful pregnancies and no miscarriages. Genomic DNA was extracted from whole blood, and polymorphism genotyping was conducted by digesting PCR products with specific restriction endonucleases. No correlations were found in any of the investigated polymorphisms, even among dominant, co-dominant and additive inheritance models and alleles. Our results support the hypothesis that these specific gene polymorphisms are not the major determinant of pregnancy success. Although we did not find any correlations, the investigation of these and other polymorphisms remains a challenge in the evaluation of RSA.

Changing presentation of complete hydatidiform mole at the New England Trophoblastic Disease Center over the past three decades: Does early diagnosis alter risk for gestational trophoblastic neoplasia?

OBJECTIVE To compare the clinical presentation and incidence of postmolar gestational trophoblastic neoplasia (GTN) among recent (1994-2013) and historical (1988-1993) cases of complete hydatidiform mole (CHM). METHODS This study included two non-concurrent cohorts (1988-1993 versus 1994-2013) of patients from the New England Trophoblastic Disease Center (NETDC). Clinical and pathologic reports of patients diagnosed with CHM between 1994 and 2013 were reviewed. Gestational age at evacuation, features of clinical presentation, human chorionic gonadotropin (hCG) levels, and the rate of progression to GTN were compared. RESULTS In the current cohort (1994 to 2013) the median gestational age at diagnosis continued to decline compared to our prior cohort (1988-1993) (9weeks versus 12weeks). Patients from the current cohort were significantly more likely to be diagnosed prior to the 11th week of gestation (56 versus 41%, p=0.04). Patients in the current cohort were also significantly less likely to present with vaginal bleeding (46 versus 84%, p<0.001). Earlier diagnosis of complete mole did not result in a decrease in the rate of postmolar GTN. The frequencies of postmolar GTN in the current (1994-2013) and prior (1988-1993) cohorts were 19 and 23%, respectively. In the current cohort, even diagnosis prior to ten weeks gestation did not decrease the risk of developing GTN. CONCLUSIONS This study indicates that complete mole continues to be diagnosed progressively earlier resulting in a further decrease in some classical presenting symptoms. However, despite earlier detection, the risk of development of postmolar GTN has not been affected.

Clinical Presentation of Complete Hydatidiform Mole and Partial Hydatidiform Mole at a Regional Trophoblastic Disease Center in the United States Over the Past 2 Decades.

Objective The aim of this study was to compare the clinical presentation and incidence of postmolar gestational trophoblastic neoplasia (GTN) among cases of complete mole (CM) and partial mole (PM) from 1994 to 2013. Methods This study included all cases of patients with CM and PM from our trophoblastic disease center between 1994 and 2013. Their clinical and pathologic reports were reviewed. Gestational age at evacuation, features of clinical presentation, human chorionic gonadotropin levels, and the rate of progression to GTN were compared. Results The median gestational age at evacuation was 9 weeks for CM and 12 weeks for PM (P < 0.001). Patients with PM had lower pre-evacuation serum human chorionic gonadotropin levels (P < 0.001), and they were also less likely to present with vaginal bleeding (P < 0.001), biochemical hyperthyroidism (P < 0.001), anemia (P < 0.001), uterine size greater than dates (P < 0.001), and hyperemesis (P = 0.002). Consequently, patients with PM were less likely to have been clinically diagnosed as moles compared with CM prior to uterine evacuation (P < 0.001). The development of GTN occurred in 17.7% (33/186) and 4.1% (7/169) of patients with CM and PM, respectively (P < 0.001). Conclusions This study indicates that, at our center over the past 20 years, both CM and PM were usually evacuated in the first trimester of pregnancy. Because CM more commonly presents with the signs and symptoms of molar disease than PM, CM is more commonly diagnosed prior to evacuation.

Diagnosis of Heterotopic Pregnancy Using Ultrasound and Magnetic Resonance Imaging in the First Trimester of Pregnancy: A Case Report

Heterotopic pregnancy is a condition characterized by implantation of one or more viable embryos into the uterine cavity while another one is implanted ectopically, particularly into the uterine tube. Its occurrence has increased drastically over the last few years due to assisted reproduction procedures. In general, the diagnosis is made during the first trimester by using endovaginal two-dimensional ultrasound (2DUS), through observing a complex para- or retrouterine mass in association with a viable uterine pregnancy. However, under some conditions such as atypical ultrasonographic presentations, 2DUS does not clarify the situation whereas magnetic resonance imaging (MRI) of the pelvis is able to do so. We present the case of a pregnant woman in her fifth pregnancy, with a clinical condition of lower abdominal pain and pallor. Endovaginal 2DUS showed a complex voluminous mass in the left pelvic region in association with a viable intrauterine pregnancy. 2DUS in power Doppler mode showed “ring” vascularization, compatible with an ectopic gestational sac. MRI was of great importance in that it suggested that the mass had hematic content, which together with the clinical features, indicated that laparotomy should be performed. This surgical choice was essential for the woman to achieve a clinical improvement and for good continuation of the intrauterine pregnancy.

Gestação em portadora de arterite de Takayasu

We describe here the pregnancy follow-up and outcome in a patient with Takayasus arteritis, with a detailed account of the complications during gestation and delivery and the impact of the disease on the newborns health.

Complete molar pregnancy in adolescents from North and South America: Clinical presentation and risk of gestational trophoblastic neoplasia

OBJECTIVES To compare complete hydatidiform mole (CHM) clinical presentation and risk factors associated with GTN development between North American and South American adolescents. METHODS This non-concurrent cohort study was undertaken including adolescents with CHM referred to centers in North America (New England Trophoblastic Disease Center, Harvard University, USA), and South America (Botucatu Trophoblastic Disease Center-São Paulo State University, Brazil; Trophoblastic Unit of Central University of Venezuela and Maternidad Concepcion Palacios of Caracas, Venezuela) between 1990 and 2012. Data were obtained from medical records and pathology reports. Study participants were allocated into 2 groups: North America (NA) and South America (SA). RESULTS In NA and SA, 13.1% and 30.9% of patients with hydatidiform mole were adolescents, respectively. Of these, 77.6% in NA and 86.1% in SA had pathologic diagnosis of CHM (p=0.121). Vaginal bleeding (SA=69% vs NA=51%; p=0.020), anemia (SA=48% vs NA=18%; p<0.001), and elevated serum hCG (SA=232,860mIU/mL vs NA=136,412mIU/mL; p=0.039) were more frequent in SA than in NA. Median gestational age at diagnosis (SA=12weeks, NA=11weeks; p=0.030) differed whereas GTN development rate (SA=20%, NA=27%; p=0.282) showed no significant difference between groups. Compared to NA, medical complications and clinical factors associated with post-molar GTN were more frequent among SA adolescents. CONCLUSIONS Medical complications and clinical factors associated with GTN development were more frequent in SA than in NA adolescents with CHM, suggesting that, in South America, awareness about the importance of diagnosing molar pregnancy early and considering CHM in the differential diagnosis in adolescents suspected to be pregnant should be raised.

The effect of adolescence and advanced maternal age on the incidence of complete and partial molar pregnancy

OBJECTIVE To compare the age-specific incidence of complete (CM) and partial molar (PM) pregnancy in a large tertiary care center in the United States. METHODS Incidence rates of CM and PM per 10,000 live births were calculated using databases from Brigham and Womens Hospital, between 2000 and 2013. Age-specific rates were calculated for women younger than 20 years old (adolescents), 20-39 years old (average age), and 40 years and older (advanced maternal age). Pearson χ(2) test was used to evaluate potential differences among groups. Rate ratios (RR) and 95% confidence intervals (CI) were used to compare risk of molar pregnancy among average age women with that of adolescents and women of advanced age. Holm-Bonferonni adjustment was used to correct for multiple comparisons. RESULTS Between 2000 and 2013, there were 255 molar pregnancies (140 CM and 115 PM) and 105,942 live births, corresponding to a molar pregnancy rate of 24 per 10,000 live births (95% CI 21-27). Rates of CM and PM were 13 (95% CI 11-16) and 11 (95% CI 9-14) per 10,000 live births respectively. The incidence of CM differed significantly among maternal age groups (p<0.001). Compared to average age women, adolescents were 7.0 times as likely to develop CM (95% CI 3.6-8.9, p<0.001), and women with advanced maternal age were nearly twice as likely (1.9, 95% CI 1.8-4.7, p=0.002). The rate of PM did not vary significantly among age groups (p=0.26). CONCLUSIONS Adolescence and advanced maternal age were associated with increased risk of complete mole, but not partial mole.

Is chemotherapy always necessary for patients with nonmetastatic gestational trophoblastic neoplasia with histopathological diagnosis of choriocarcinoma

OBJECTIVE To evaluate expectant management versus immediate chemotherapy following pathological diagnosis of gestational choriocarcinoma (GCC) in patients with nonmetastatic disease. METHODS Multicenter retrospective cohort that included patients with histological diagnosis of GCC with nonmetastatic disease followed at one of thirteen Brazilian referral centers for gestational trophoblastic disease from January 2000 to December 2016. RESULTS Among 3191 patients with gestational trophoblastic neoplasia, 199 patients with nonmetastatic GCC were identified. Chemotherapy was initiated immediately in 152 (76.4%) patients per FIGO 2000 guideline, while 47 (23.6%) were managed expectantly. Both groups presented with similar characteristics and outcomes. All patients (n=12) who had normal human chorionic gonadotropin (hCG) in the first 2-3weeks of expectant management achieved complete sustained remission with no chemotherapy. Only 44.7% (21 patients) of patients who were expectantly managed needed to receive chemotherapy due to plateauing or rising hCG level in the first 2-3weeks of follow up. The outcome of patients receiving chemotherapy after initial expectant management was similar to those who received chemotherapy immediately after the diagnosis in terms of need for multi-agent chemotherapy or number of cycles of chemotherapy. There was no case of relapse or death in either group. Logistic regression analysis showed that age≥40years and hCG≥92,428IU/L at GCC diagnosis were risk factors for needing chemotherapy after initial expectant management of nonmetastatic GCC. CONCLUSION In order to avoid exposing patients unnecessarily to chemotherapy, close surveillance of women with pathological diagnosis of nonmetastatic GCC seems to be a safe practice, particularly for those who have a normal hCG at the time of diagnosis. If confirmed by other studies, the FIGO guidelines may need to be revised.

Effect of race/ethnicity on risk of complete and partial molar pregnancy after adjustment for age

OBJECTIVE To quantify the effect of race/ethnicity on risk of complete and partial molar pregnancy. METHODS We conducted a cross-sectional study including women who were followed for complete or partial mole and those who had a live singleton birth in a teaching hospital in the northeastern United States between 2000 and 2013. We calculated race/ethnicity-specific risk of complete and partial mole per 10,000 live births, and used logistic regression to estimate crude and age-adjusted relative risks (RR) of complete and partial mole. RESULTS We identified 140 cases of complete mole, 115 cases of partial mole, and 105,942 live births. The risk of complete mole was 13 cases per 10,000 live births (95% confidence interval [CI] 11-16) and that of partial mole was 11 cases per 10,000 live births (95% CI 9-13). After age-adjustment, Asians were more likely to develop complete mole (RR 2.3 95% CI 1.4-3.8, p<0.001) but less likely to develop partial mole (RR 0.2; 95% CI 0.04-0.7, p=0.02) than whites. Blacks were significantly less likely than whites to develop partial mole (RR 0.4; 95% CI 0.2-0.8, p=0.01) but only marginally less likely to develop complete mole (RR 0.6; 95% CI 0.3-1.0, p=0.07). Hispanics were less likely than whites to develop complete mole (RR 0.4; 95% CI 0.2-0.7, p=0.002) and partial mole (RR 0.4; 95% CI 0.2-0.9, p=0.02). CONCLUSION Race/ethnicity is a significant risk factor for both complete and partial molar pregnancy in the northeastern United States.

Gestational Trophoblastic Neoplasia after Ectopic Molar Pregnancy: Clinical, Diagnostic, and Therapeutic Aspects

This report presents the case of a patient with gestational trophoblastic neoplasia after a partial hydatidiform mole formed in the Fallopian tube. Ectopic molar pregnancy is a rare condition, with an estimated incidence of 1 in every 20,000 to 100,000 pregnancies; less than 300 cases of it have been reported in the Western literature. The present report is important because it presents current diagnostic criteria for this rare condition, which has been incorrectly diagnosed in the past, not only morphologically but also immunohistochemically. It also draws the attention of obstetricians to the occurrence of ectopic molar pregnancy, which tends to progress to Fallopian tube rupture more often than in cases of ectopic non-molar pregnancy. Progression to gestational trophoblastic neoplasia ensures that patients with ectopic molar pregnancy must undergo postmolar monitoring, which must be just as thorough as that of patients with intrauterine hydatidiform moles, even if chemotherapy results in high cure rates.