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Background: The pathophysiological role of HCG is currently speculative and seems to be paradoxes as certain studies advice it has anti-cancer properties while few others found it to be pro-cancer agent. In this study we have evaluated the status of beta hCG receptors in patients with breast carcinoma and its association with various clinic-pathological factors., Methods: A cross-sectional study was conducted on total of 57 patients who were enrolled in the study, all tests including metastatic work up were done. Patients underwent modified radical mastectomy on the affected side after being declared fit by the anaesthetist. Immunohistochemical analysis was done using ER antibody, PR88, CB11 and for beta hCG was done using ab-53087., Results: The average age at diagnosis was 55.77 years. There was a significant correlation between age at diagnosis and age at first child birth. On correlating size of the tumour with Beta hCG receptor status, Patients with tumour size 2 to 5 cms have shown maximum positivity for beta hCG receptors. On correlating stage of the disease with Beta HCG receptor status, it was found that, carcinoma tissues showed more receptor positivity as the stage increased. In histological staining grade, Nottingham's scoring system was used which showed majority of patients belonged to grade 2., Discussion: Comparison of other tumour characteristics such as histopathological type, grade, tumour size and nodal status were similar among the studies done in Western and Indian regions. The similarities of the current as well as the above mentioned Indian studies with Western countries could be attributed to increasing awareness and better screening protocols for breast carcinoma., (© 2019 Old City Publishing, Inc.)

Objective: Preterm birth (PTB) is a significant public health problem. We aimed to explore whether alpha fetal protein (AFP) or β-human gonadotropin (β-HCG) levels during pregnancy were associated with PTB in Chinese population., Study Design: The clinical data collected Nanjing Medical University Affiliated Suzhou Hospital and Wuxi Maternity and Child Health Care Hospital between January 2006 and December 2011 were analyzed retrospectively. A total of 64,999 pregnant women were registered. In addition, 13,828 pregnant women were collected serum from the second trimester. The maternal serum AFP and β-HCG were measured by enzyme immunoassay., Results: In our study, the rate of PTB is 6.23%. With each unit increase of maternal AFP concentration, the adjusted odds of PTB was increased by 69.3% (odds ratio = 1.693, 95% confidence interval: 1.434-1.999, p  = 0.00). We set AFP concentrations as high, medium, and low levels. When comparing with low concentration of AFP, high concentration of AFP (≥1.179 M) was positively associated with PTB with adjustment for potential confounders ( p  < 0.05). Nevertheless, no statistically significant associations were observed between maternal β-HCG and PTB., Conclusion: In this study, maternal AFP concentration was associated with increased risk of PTB., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background Pregnancy introduces major physiological changes that also alter biochemical analytes. Maternal and perinatal health can be optimized by early intervention and therefore, pregnancy-specific reference intervals (RIs) for the local population are warranted. While the second and third trimester-specific changes are well described, the first trimester is less well characterized. We therefore wanted to facilitate early detection of abnormalities by generating first trimester reference values for 29 common analytes. Methods In a prospective early pregnancy (PEP) cohort (2016-2017), 203 pregnant women were recruited from 4 to 8 weeks' gestation. Consecutive blood samples were drawn every 2 weeks until an ongoing second trimester pregnancy (n = 164) or a miscarriage (n = 39) occurred. After exclusion of women with complicated pregnancies or deliveries (n = 42), 122 women were included. The serum samples collected at <6, 6-8, 8-10, 10-12 and >12 weeks' gestation were analyzed for 29 common analytes. Subsequently the RIs were calculated according to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommendations (2.5-97.5th percentiles) and compared with the conventional RIs for non-pregnant women. Results Human chorionic gonadotropin (hCG), progesterone (P4), estradiol (E2), pregnancy-associated plasma protein A (PAPP-A), cancer antigen 125 (CA125), thyroid stimulating hormone (TSH), creatinine (CREA) and albumin (ALB) showed an early pregnancy-dependent change compared with conventional limits. For ALB the change was seen at 5.5 weeks' gestation. Conclusions We report gestational age-specific RIs available from the early part of the first trimester applicable to everyday clinical care of pregnant women. Well-known alterations of RIs seen in later trimesters are also observed in the first.

Objective: To evaluate the clinical characteristics and diagnostic strategies of early hydatidiform mole. Methods: A retrospective cohort study was conducted of 526 women with hydatidiform mole who underwent suction curettage and were confirmed by histopathology in Dalian Maternal and ChildHealth Care Hospital from Feb. 2013 to Feb. 2018, including 484 women with gestational age less than or equal to 12 weeks (the early group) and 42 women with gestational age greater than 12 weeks (the late group). The clinical characteristics between the two groups were compared, and the pathological diagnosis and pre-evacuation ultrasound examination of the early group were further discussed. Results: Compared with the late group, the clinical characteristics of the early group tended to be atypical, and the incidence of vaginal bleeding, excessive uterine size, theca lutein cysts (>6 cm) and pregnancy complications decreased significantly (all P< 0.05). The serum level of β-hCG in the early group was significantly lower than that in the late group ( Z=- 2.382, P= 0.017). While there was no significant difference in the pre-evacuation ultrasound detection rate between the two groups (53.5% vs 66.7%; χ(2)=2.697, P= 0.101). Five hundred and fifteen patients completed the follow-up, and 38 patients with post-mole neoplasia were all cured. There was no significant difference in the malignant transformation rate of hydatidiform mole between the two groups (7.0% vs 11.9%; χ(2)=0.745, P= 0.388). In the early group, 302 cases of complete hydatidiform mole (CHM), 179 cases of partial hydatidiform mole (PHM) and 3 cases of unclassified hydatidiform mole (UHM) were histologically diagnosed, according to pathological morphology combined with p57(KIP2) immunohistochemical staining. Compared with pathological diagnosis, the overall pre-evacuation ultrasound detection rate in the early hydatidiform mole was 53.5% (259/484), which was significantly better for complete (78.1%, 236/302) versus partial (11.7%, 21/179) hydatidiform moles (χ(2)=199.224, P< 0.01). There was significantly weak negative correlation between the overall ultrasound detection rate and gestational age of hydatidiform mole ( r =-0.211, P< 0.01). The gestational age of early PHM was significantly longer than that of CHM (68.0 vs 58.5 days; Z= -8.048, P< 0.01). Conclusions: The clinical presentations of early hydatidiform mole are not typical. Although ultrasound examination identifies only about half of hydatidiform moles, ultrasonography is still an important auxiliary examination method. Morphological examination combined with p57(K)IP2 immunohistochemical staining could effectively diagnose early hydatidiform mole, so as to reduce the missed diagnosis of hydatidiform mole.

Purpose: The objective of this study is to identify the pregnancy outcomes based on day-16 β-hCG level assessed with modern assays, in fresh single embryo transfers., Methods: A retrospective cohort study at a single academic center between 2013 and 2017. A total of 1076 pregnancies were included., Results: Pregnancies were divided into 10% groupings of 107-108 patients each. The 10 groups did not differ for baseline characteristics. There was no difference on outcomes based on cleavage or blastocyst transfer. At a serum β-hCG level of 103 ± 13 (range 74-135), 50% had a biochemical loss. Biochemical pregnancy losses remained 21% at serum β-hCG range (136-197). It was only once serum β-hCG level reached 199-252 that the probability of a biochemical pregnancy loss was 12%. Interestingly, if a clinical pregnancy is present even at low day-16 serum β-hCG levels, the likelihood of live birth is approximately 50%. This maximizes to 75% when the serum β-hCG level was at least 253 IU/L. The relationship between serum day-16 β-hCG levels and clinical pregnancy or live birth is quite strong with correlation coefficients above 0.8 which accounted for more than 75% of the variability in outcomes in both cases. Receiver operator curves determined that the cut-off for a clinical pregnancy was 190 and for live birth, it was 213 IU/L., Conclusion: An increase in the serum β-hCG levels at which to expect a reassuring outcome is required based on modern assays, as compared with the old cut-off levels.

Research Question: To investigate the association between anti-Müllerian hormone (AMH) concentration and maternal age with single euploid cryopreserved embryo transfer., Design: Retrospective cohort study from 2014 to 2018 at an academic medical centre, including 389 cycles of IVF with 24-chromosome Day 5/6 preimplantation genetic testing for aneuploidies (PGT-A). Multivariate logistic regression was used to study AMH and age in relation to IVF outcomes (positive beta human chorionic gonadotrophin [bHCG], ongoing pregnancy and pregnancy loss rates) for patients with at least one euploid embryo for transfer, controlling for patient and cycle confounders., Results: In this cohort the overall unadjusted positive bHCG rate was 69.2% and ongoing pregnancy rate was 52.7% per transfer, while the pregnancy loss rate was 23.4% per cycle with positive bHCG. Multivariate analysis found that compared with the reference group of AMH 1 to <5 ng/ml, AMH <1 and 5+ did not have any significant difference in positive bHCG (odds ratio, OR 0.65 [0.30-1.44] and 1.27 [0.61-2.65] for AMH <1 and AMH 5+, respectively) or ongoing pregnancy (OR 0.80 [0.43-1.50] and 1.41 [0.68-2.90]). However, AMH <1 had statistically significant lower euploid miscarriage rates compared with the reference group with OR 0.32 (0.12-0.85, P = 0.022); AMH 5+ did not have any statistical difference in miscarriage rate. Neither age at retrieval nor age at transfer were significantly associated with transfer outcomes., Conclusions: AMH concentration was not associated with positive bHCG or ongoing pregnancy for euploid embryo transfers after adjustment for potential confounders. Maternal age was not associated with euploid transfer outcomes. Further study is warranted in larger cohorts., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: Stage IS testicular cancer is defined by the persistence of elevated serum tumor markers, including α-fetoprotein and/or β-human chorionic gonadotropin, after orchiectomy without radiological evidence of metastatic disease. Current treatment recommendations include cisplatin based chemotherapy up front but the recommendations are based on limited single center series., Materials and Methods: We retrospectively analyzed clinical and pathological characteristics, and long-term outcomes in 110 patients uniformly treated with primary chemotherapy between 1994 and 2016. The primary objective was to evaluate long-term disease-free survival. We also explored factors associated with the need for additional treatment., Results: The elevated prechemotherapy tumor markers were α-fetoprotein in 48% of cases, β-human chorionic gonadotropin in 14%, and α-fetoprotein and β-human chorionic gonadotropin in 38%. Median α-fetoprotein and β-human chorionic gonadotropin values were 71 ng/ml and 80 mIU/ml, respectively. The IGCCCG (International Germ Cell Cancer Collaborative Group) prognostic classification was good in 94% of cases. Mixed nonseminomatous germ cell tumor was found in 78% of cases. Of the patients 103 achieved a complete response to chemotherapy. In 6 patients radiological signs of progressive disease developed during chemotherapy, while 8 experienced relapse after an initial complete response. At a median followup of 108 months 108 patients were alive and disease-free. Five and 10-year disease-free survival rates were 87% and 85 % , respectively. The predominance of embryonal carcinoma in the primary tumor was the only factor associated with the probability of needing additional therapy., Conclusions: Stage IS testicular cancer is more commonly associated with elevated α-fetoprotein, an IGCCCG good prognosis and mixed nonseminomatous germ cell tumor. Treatment with cisplatin based chemotherapy leads to cure in most cases. However, a proportion of patients require the integration of additional therapies, including more frequently when embryonal carcinoma is not predominant.

Objective: To evaluate the relationship between first and second trimester maternal serum-free β-hCG and the risk of spontaneous preterm delivery (PTD). Study design: This was a case-control study of women evaluated and delivered at our institution from 2011 to 2015. Spontaneous PTD was defined as delivery before 37 weeks due to spontaneous preterm labor or premature rupture of membranes. Patient with multifetal gestation and those with medically indicated term or PTD were excluded. Results: Of 877 women meeting the inclusion criteria, 173 delivered preterm and 704 delivered at term, and 8.1% had high free β-hCG in one or both trimesters. High maternal first and/or second trimester free β-hCG (≥95th percentile) was associated with lower rates of PTD. Thirty-two women with high free β-hCG in both first and second trimesters delivered at term. Gestational age at delivery and birth weights were lower in women who did not have high free β-hCG in any trimester. Low free β-hCG (≤5th percentile) in either trimester was not associated with an increased or decreased likelihood of PTD. Logistic regression demonstrated an independent association of high free β-hCG (≥95th percentile) with a reduced likelihood of PTD. Stratified analysis revealed a stronger impact of this association in women with no prior history of PTD. Conclusions: High free β-hCG, in the absence of risk factors for medically indicated PTD, is associated with a reduced likelihood of spontaneous PTD and may represent a marker indicating lower risk.

Objective: To evaluate the performance of first trimester biochemical markers, pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (fβ-hCG), and nuchal translucency (NT) in detection of severe congenital heart defects (CHDs). Methods: During the study period from 1 January 2008 to 31 December 2011, biochemical markers and NT were measured in 31,144 women as part of voluntary first trimester screening program for Down's syndrome in Northern Finland. Data for 71 severe CHD cases and 762 controls were obtained from the hospital records and from the National Medical Birth Register, which records the birth of all liveborn and stillborn infants, and from the National Register of Congenital Malformations that receives information about all the CHD cases diagnosed in Finland. Results: Both PAPP-A and fβ-hCG multiple of median (MoM) values were decreased in all severe CHDs: 0.71 and 0.69 in ventricular septal defects (VSDs), 0.58 and 0.88 in tetralogy of Fallot cases (TOFs), 0.82 and 0.89 in hypoplastic left heart syndromes (HLHSs), and 0.88 and 0.96 in multiple defects, respectively. NT was increased in all study groups except of VSD group. ROC AUC was 0.72 for VSD when combining prior risk with PAPP-A and fβ-hCG. Adding NT did not improve the detection rate. With normal NT but decreased (<0.5 MoM) PAPP-A and fβ-hCG odds ratios for VSD and HLHS were 19.5 and 25.6, respectively. Conclusions: Maternal serum biochemistry improves the detection of CHDs compared to NT measurement only. In cases with normal NT measurement but low concentrations of both PAPP-A and fβ-hCG, an alert for possible CHD, especially VSD, could be given with thorough examination of fetal heart in later ultrasound scans.

Objective: To show the relation between fetal gender and preterm birth (PTB) in low values of first trimester aneuploidy test markers., Material and Method: A total of 29,528 patients included the study of them 7382 was PTB and all patients grouped according to fetal gender. Demographic data and perinatal complications were determined. According low PAPP-A MoM (<0.4) and low free BhCG MoM (<0.5) values PTB subgroup relative risks were calculated for each fetal gender., Results: The PTB rate and birth weight was significantly higher in male gender. At low PAPP-A MoM values Late PTB in male infant (aRR 95% CI 2.028) and late miscarriage (LM) category with low free BhCG MoM values in female infant (aRR 95% CI 0.907) was determined statistically significant., Conclusions: Male gender has an effect on PTB rate. İn low values of first trimester aneuploidy test markers late PTB risk is increasing in male gender and also LM risk is decreasing in female gender. Further studies are required in order to determine the relation between PTB and fetal gender and first trimester aneuploidy screening test., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Study Question: What is the association of female and male partner marijuana smoking with infertility treatment outcomes with ART?, Summary Answer: Women who were marijuana smokers at enrollment had a significantly higher adjusted probability of pregnancy loss during infertility treatment with ART whereas, unexpectedly, there was a suggestion of more favorable treatment outcomes in couples where the man was a marijuana smoker at enrollment., What Is Known Already: Data on the relation of female and male partner marijuana use with outcomes of infertility treatment is scarce despite increased use and legalization worldwide., Study Design, Size, Duration: We followed 421 women who underwent 730 ART cycles while participating in a prospective cohort (the Environment and Reproductive Health Study) at a fertility center between 2004 and 2017. Among them, 200 women (368 cycles) were part of a couple in which their male partner also enrolled in the study., Participants/materials, Setting, Methods: Participants self-reported marijuana smoking at baseline. Clinical endpoints were abstracted from electronic medical records. We used generalized linear mixed models with empirical standard errors to evaluate the association of baseline marijuana smoking with ART outcomes adjusting for participants' age, race, BMI, tobacco smoking, coffee and alcohol consumption, and cocaine use. We estimated the adjusted probability of implantation, clinical pregnancy, and live birth per ART cycle, as well as the probability of pregnancy loss among those with a positive B-hCG., Main Results and the Role of Chance: The 44% of the women and 61% of the men had ever smoked marijuana; 3% and 12% were marijuana smokers at enrollment, respectively. Among 317 women (395 cycles) with a positive B-hCG, those who were marijuana smokers at enrollment (N = 9, cycles = 16) had more than double the adjusted probability of pregnancy loss than those who were past marijuana smokers or had never smoked marijuana (N = 308, 379 cycles) (54% vs 26%; P = 0.0003). This estimate was based on sparse data. However, couples in which the male partner was a marijuana smoker at enrollment (N = 23, 41 cycles) had a significantly higher adjusted probability of live birth than couples in which the male partner was a past marijuana smoker or had never smoked marijuana (N= 177, 327 cycles) (48% vs 29%; P = 0.04), independently of the women's marijuana smoking status. Treatment outcomes of past marijuana smokers, male and female, did not differ significantly from those who had never smoked marijuana., Limitations, Reasons for Caution: Marijuana smoking was self-reported with possible exposure misclassification. Chance findings cannot be excluded due to the small number of exposed cases. The results may not be generalizable to couples from the general population., Wider Implications of the Findings: Even though marijuana smoking has not been found in past studies to impact the ability to become pregnant among pregnancy planners in the general population, it may increase the risk of pregnancy loss among couples undergoing infertility treatment. Marijuana smoking by females and males may have opposing effects on outcomes of infertility treatment with ART., Study Funding/competing Interest(s): The project was financed by grants R01ES009718, P30ES000002, and K99ES026648 from the National Institute of Environmental Health Sciences (NIEHS). None of the authors has any conflicts of interest to declare., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background -The first trimester combined test (FTCT) is an effective screening tool to estimate the risk of fetal aneuploidy. It is obtained by the combination of maternal age, ultrasound fetal nuchal translucency (NT) measurement, and the maternal serum markers free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein A (PAPP-A). However, conflicting data have been reported about the association of FTCT, β-hCG, or PAPP-A with the subsequent diagnosis of gestational diabetes mellitus (GDM). Research design and methods -2410 consecutive singleton pregnant women were retrospectively enrolled in Calabria, Southern Italy. All participants underwent examinations for FTCT at 11-13 weeks (plus 6 days) of gestation, and screening for GDM at 16-18 and/or 24-28 weeks of gestation, in accordance with current Italian guidelines and the International Association Diabetes Pregnancy Study Groups (IADPSG) glycemic cut-offs. Data were examined by univariate and logistic regression analyses. Results -1814 (75.3%) pregnant women were normal glucose tolerant, while 596 (24.7%) were diagnosed with GDM. Spearman univariate analysis demonstrated a correlation between FTCT values and subsequent GDM diagnosis ( ρ = 0.048, p = 0.018). The logistic regression analysis showed that women with a FTCT <1:10000 had a major GDM risk ( p = 0.016), similar to women with a PAPP-A <1 multiple of the expected normal median (MoM, p = 0.014). Conversely, women with β-hCG ≥2.0 MoM had a reduced risk of GDM ( p = 0.014). Conclusions -Our findings indicate that GDM susceptibility increases with fetal aneuploidy risk, and that FTCT and its related maternal serum parameters can be used as early predictors of GDM.

Background: When a new measurement method is introduced into a clinical laboratory, a comparison study is often needed to ensure that the measurement by the existing method is reproducible by the new method with clinical acceptability. The comparison study of ARCHITECT i2000SR analyzer and i-CHROMATM reader analyzer in measuring plasma human chorionic gonadotropin beta subunit (β-HCG) has not been reported., Methods: Blood samples for β-HCG were collected from pregnant women seen at the outpatient clinic, and they were divided into two groups, those below 20 mU/mL or above, due to its wide concentration range in pregnant women. A comparison study was performed according to EP09-A3 guidelines of the National Clinical and Laboratory Standards Institute (NCCLS). β-HCG's levels measured from the analyzers being compared were inspected on Bland-Altman plot and outliers were identified by Extreme Studentized Deviate (ESD). Correlation analysis was performed using Passing-Bablok model., Results: Passing-Bablok regression analysis showed that slope B 95% CIs (confidence intervals) of the two groups fall outside of 1, indicating there was a proportional difference between the two methods. Both groups had a ratio of less than 95% percent of the values in the ± 1.96 RSD (residual standard deviation) interval, indicating that there might be inconsistencies between the two methods with respect to random differences. According to Bland-Altman analysis, 95% Limit of Agreement (LOA) between the two methods exceeded the clinically acceptable limits. The deviation between these two detecting platforms was beyond clinically acceptable ranges when samples fell within the concentrations of 15,000 - 30,000 and 1.2 - 20 mU/mL., Conclusions: Measurements of β-HCG by ARCHITECT i2000SR and i-CHROMATM Reader are consistent and reproducible only at a certain concentration range. Further research is needed to reduce the biases between these two analyzers.

Ectopic pregnancy occurs when a fertilized ovum attaches outside the uterus. As a complication in approximately 1‑2% of all pregnancies, ectopic pregnancies may cause catastrophic hemorrhage as a result of invading maternal blood vessels. Therefore, early diagnosis and timely treatment are crucial for women with ectopic pregnancy. In this study, we aimed to identify and determine the efficacy of serum biomarkers for the prompt diagnosis of ectopic pregnancy. For this purpose, the serum concentrations of progesterone, β human chorionic gonadotropin (β‑hCG) and cancer antigen‑125 (CA125) were detected by solid‑phase, competitive binding chemiluminescent enzyme immunoassays. Flow cytometry was used to analyze the percentage of CD3+ T cells in women with ectopic pregnancy. Pathological analysis of tubal and villus tissues was performed by hematoxylin and eosin (H&E) staining. After receiving an injection of methotrexate (MTX), patients were examined by transvaginal ultrasound to detect the size of the echogenic mass. The results revealed that the serum levels of progesterone, β‑HCG and CA125 were significantly decreased in women with ectopic pregnancy, whereas the percentage of CD3+ T cells was increased in women with ectopic pregnancy. Histopathological examination revealed blood clots with small tissue fragments of a tubal‑type epithelium and incomplete pile structures. Five days after the MTX injection, an echogenic mass was found with a size of 1.7x1.2x1.6 cm that contained a gestational sac‑like structure and a yolk sac. On the whole, the findings of this study indicate the at the joint detection of progesterone, β‑HCG, CA125 serum levels and the CD3+ T cell percentage could be applied as a reliable indicator for the early diagnosis of ectopic pregnancy. MTX administration was determined to be an efficacious approach for the treatment of ectopic pregnancy.

ᅟ: Detection and quantitative measurements of diffused tumor markers in blood samples of patients with cancer is a facile and convenient method to determine prognosis and the appropriateness of the treatment. This study was done to evaluate the level of CA125, CEA, AFP, Beta HCG, and CA19-9 tumor markers and their relation to the stage and grade of the disease in patients with gastric adenocarcinoma., Materials and Methods: In a descriptive cross-sectional study, of 81 patients referred to the oncology department of Tohid Hospital, Sanandaj, Iran, in 1 year, with recently detected gastric adenocarcinoma, serum level of CEA, CA19-9, CA125, AFP, and Beta HCG tumor markers was measured by ELISA method before chemotherapy and surgery. Patients were divided into four groups based on stage of disease (I, II, III, IV), and in terms of tumor differentiation, degrees were classified in to three groups: low, high, and intermediate. To determine the correlation of tumor markers level with the stage and grade of the disease, the Kruskal-Wallis and Mann-Whitney U tests were used., Results: By progression, the stages of the disease, the serum level of CA19-9, CA125, and AFP tumor markers demonstrated a significant increase. But this difference between level of HCG and CEA was not significant with the staging. There was no significant difference between the serum level of tumor markers and the grading of disease in the patients., Conclusion: Preoperative CA19-9, CA125, and AFP tumor markers measurements could be beneficial in detecting the progressed stages of the disease.

Background: Epithelioid trophoblastic tumor (ETT) derived from intermediate trophoblasts is one type of gestational trophoblastic neoplasia (GTN), and it accounts for less than 2% of all gestational trophoblastic diseases (GTD). Extrauterine ETT is extremely rare, and there is currently no consistent strategy for its treatment and management. Therefore, the aim of the study is to analyze and summarize the clinicopathologic features of extrauterine ETT with or without metastasis., Method: The Web of Knowledge, Google Scholar, EMbase, congress of library, and PubMed were searched for extrauterine ETT without primary uterine lesions. All available data were extracted from published case reports or serial case reports, and then, the clinical and pathological characteristics were analyzed., Results: Twenty-two clinical studies consisting of 27 patients diagnosed with extrauterine ETT, according to the given inclusion and exclusion criteria, were included in the study. A total of 27 cases of extrauterine ETT were identified. Of these cases, four (14.81%) were located in the lungs, three (11.11%) in the ovaries, two (7.41%) in the vagina, and eight (29.63%) patients had other primary lesions. The patients originated from different continents, with 59% located in Asia and 26% in North America. Among 23 patients, the antecedent pregnancy prior to the diagnosis was full-term in 12 cases, abortion in 6 cases, hydatidiform mole in 3 cases, and invasive mole in 1 case. From the available antecedent information on pregnancy, the median interval from pregnancy to diagnosis of extrauterine ETT was 4 years. Additionally, the median gravidity and para of the patients was three times and two times, respectively. The median hCG titer was 14,374 mIU/mL in 5 patients, and the mean β-HCG titer was 3,724,805 mIU/mL in 14 patients. For all patients, the disease was confined to extrauterine ETT at diagnosis. From the available information, 20 cases were successfully treated by extraction of local lesions, and 12 cases received chemotherapy. Diagnosis was confirmed by histological tests. The Ki-67 staining ranged from 8.7 to 80%, and tumors were positive for hCG, PLAP, EMA, and p63., Conclusion: In this study, we observed that abnormal levels of serum hCG titers and the local presentation of lesions with varying intervals after antecedent term pregnancy were the most common presenting features of extrauterine ETT. In addition, we found that the extraction of extrauterine lesions was needed for the treatment of extrauterine ETT. Of course, the follow-up was also important.

Persistent trophoblast after ectopic pregnancy has been demonstrated at the surgical site or as peritoneal implants. A 37-year-old woman (G5P2) experienced persistently low levels of beta-human chorionic gonadotropin (hCG) after surgical treatment for an interstitial pregnancy. Evaluation for persistent trophoblast, gestational trophoblastic neoplasm and heterophilic antibodies was negative. After 15 months without resolution, she elected for hysterectomy. We found four smooth, freely floating avascular cysts intraoperatively; pathological evaluation identified the cysts as trophoblastic tissue. Serum beta-hCG resolved postoperatively and remained negative at 1 year. Our case demonstrates the novel finding of trophoblastic tissue existing as free-floating cysts in the peritoneal cavity. With appropriate suspicion, these cysts can be identified on radiologic investigation and removed laparoscopically., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

We investigated various monitoring protocols on the success of methotrexate therapy in patients with tubal ectopic pregnancy. The data from patients who received single-dose methotrexate therapy as their first-line treatment was reviewed. The Beta-human chorionic gonadotropin (BhCG) days 1-4 and days 1-7 follow-up protocols were compared with the BhCG day 4-7 follow-up protocol, in terms of the treatment. Cut-off values were determined for the reduction of BhCG between the days 1-4 and days 1-7. There were no significant differences between the groups in terms of the demographic data, except for BhCG fourth- and seventh-day values. There was a 21% decrease in BhCG between days 1 and 4 and a 32% decrease for BhCG between days 1 and 7 as good predictors for treatment success. These follow-up protocols allow earlier and more cost-effective methods than the protocol based on a 15% reduction in BhCG levels between days 4 and 7. Impact statement What is already known on this subject? A decrease of 15% BhCG levels between days 4 and 7 is a common protocol for predicting the success of a single-dose methotrexate therapy of an ectopic pregnancy. What do the results of this study add? This clinical study offers the cut-off values for the various BhCG follow-up protocols recently found in the literature for single-dose methotrexate therapy for the treatment of ectopic pregnancy. What are the implications of these findings for clinical practice and/or further research? We identified the importance of fourth-day BhCG for measuring the success of single-dose methotrexate therapy. Therefore, after randomised, multicentre, prospective clinical trials, the most common follow-up protocol can be changed to a single-dose methotrexate therapy for ectopic pregnancy.

Objective: We aimed to determine the correlation between serum alpha-fetoprotein (AFP), the free human chorionic gonadotropin beta subunit (free beta-HCG) in pregnant women during the mid-trimester, and fetal hypospadias, and tried to establish a risk prediction model., Methods: A multi-center case-control study was conducted. We divided the fetuses into two groups (69 with fetal hypospadias and 62 without fetal hypospadias). Time-resolved immunofluorescence was used to determine the serum levels of AFP and free beta-HCG. The best cut -value and area under curve (AUC) were determined based on the Receiver operating characteristics (ROC) curve, and the diagnostic value of AFP and free beta-HCG was evaluated., Results: The level of AFP in the study group was 1.14 multiple of Median(MOM), which was higher than in the control group (0.96 MOM); the difference was significant (Z = 2.831, P = .005). Similarly, the free beta-HCG level was 1.30 MOM in the study group, and was also significantly higher than in the control group (0.84 MOM; Z = 3.131, P = .004). We used the AFP and free beta-HCG levels separately to predict fetuses with hypospadias, and the AUCs were 0.644 (95% Confidence interval (CI): 0.5500.737, P = .005) and 0.659 (95% CI: 0.5650.752, P = .002), respectively. According to the ROC curve, the best cut-off values for AFP and free beta-HCG were 0.945 MOM and 1.275 MOM, respectively. When we combined the AFP level with the free beta-HCG level, the AUC was 0.700 (95% CI: 0.610-0.789, P < .001), with a sensitivity of 0.551 and a specificity of 0.855., Conclusion: Combined screening for fetal hypospadias with maternal serum AFP and free beta-HCG levels during the early second trimester has high sensitivity and specificity, which can be used as a new marker., (Copyright © 2019 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Research Question: Several studies have tried to identify early markers of treatment outcome after methotrexate (MTX) treatment for ectopic pregnancy, including pretreatment and day 4 human chorionic gonadotrophin (HCG) concentrations and their corresponding changes, and the increment in HCG during the initial 24 h after treatment. There have, however, been conflicting results. This study aimed to re-evaluate the role of these markers in the earlier identification of treatment success in a large cohort of women., Design: This was a retrospective cohort study including women diagnosed with an ectopic pregnancy and treated with a regimen of a single dose of MTX. A comparison of maternal and gestation characteristics was made between groups in whom treatment was successful or failed., Results: A total of 292 women treated with single-dose intramuscular MTX for ectopic pregnancy were included in this study. In the overall cohort, the treatment success rate with a single dose of MTX was 62.7% (183/292). Only two independent determinants were significantly associated with treatment success: the initial 24-h percentage increase in HCG (adjusted odds ratio [OR] 1.82, 95% confidence interval [CI] 1.26-2.63; P < 0.001) and the percentage change in HCG from day 1 to day 4 (adjusted OR 1.12, 95% CI 1.04-1.21; P < 0.001). The optimal cut-off points for prediction of treatment success were an increment of less than 17% in the 24 h before treatment and a decrease of more than 22% between the day 1 and day 4 HCG concentrations., Conclusions: A small increase in HCG concentration 24 h before treatment with MTX, alongside a decline in HCG concentration from day 1 to day 4, may predict the success of medical treatment for an ectopic pregnancy., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Our aim of the study was to evaluate the efficacy and complication rate of our inpatient medical management protocol for missed miscarriages. Three-hundred and ninety women hospitalised at our tertiary centre because of a missed miscarriage/anembryonic pregnancy in 2012-2013 were included in this retrospective study. The women underwent either a low (until 9 + 0 weeks of gestation) or high gestational age (from 9 + 1 until 15 + 6 weeks of gestation) management protocol. The success rate, curettage in the first 48 hours after the procedure, the complication rate and the factors that might influence these outcomes were evaluated. The overall success rate was 83.3%. The curettage in the first 48 hours after the procedure was performed in 7.4% of the patients and was more often in the high gestational age protocol. Complications that required another outpatient visit or hospitalisation occurred in 9% of the patients. Higher beta-hCG values 14 days after the procedure and the absence of evacuation of products of conception during hospitalisation were associated with a higher complication rate. IMPACT STATEMENT What is already known on this subject? As much as 10-20% of clinically recognised pregnancies end in a spontaneous abortion. A missed miscarriage and a blighted ovum represent a form of spontaneous abortion, which has long been treated with surgical evacuation. However, nowadays, medical management represents a well-established alternative with very high success rates and is considered as an equivalent and safe method that is also very well accepted by patients. What do the results of this study add? According to our results, a medical management of a first trimester missed miscarriage and a blighted ovum is very effective with an overall success rate of 83.3% and a very low percentage of curettage in the first 48 hours after the procedure (7.4%). Our study was also able to identify higher beta-hCG values 14 days after procedure and absence of evacuation of products of conception during hospitalisation as risk factors for complication occurrence. What are the implications of these findings for clinical practice and/or further research? Our study helps to identify patients who are at greater risk for developing complications after the medical management of a first trimester missed miscarriage.

Background: Primary hypogonadism (low testosterone and high luteinizing hormone, LH) is present in approximately 20% of testicular cancer (TC) survivors after orchidectomy with or without chemotherapy., Objectives: We investigated insulin-like factor 3 (INSL3), a novel marker of Leydig cell function, in TC patients., Materials and Methods: We analyzed: (I) a cross-sectional cohort of TC patients after orchidectomy with or without chemotherapy (1988-1999) at long-term follow-up (median 36 and 35 years of age at follow-up, respectively) and healthy men of similar age; (II) a longitudinal cohort of chemotherapy-treated TC patients (2000-2008), analyzed before and 1 year after chemotherapy (median 29 years of age at chemotherapy). INSL3, testosterone, and LH were compared between groups and over time and related to pre-chemotherapy β-hCG levels., Results: In the cross-sectional cohort, TC patients at median 7 years after orchidectomy and chemotherapy (n = 79) had higher LH (p < 0.001), lower testosterone (p = 0.001), but similar INSL3 as controls (n = 40). After orchidectomy only (n = 25), higher LH (p = 0.02), but no differences in testosterone or INSL3 were observed compared to controls. In the longitudinal cohort, patients with normal pre-chemotherapy β-hCG (≤5 mU/L, n = 35) had increased LH 1 year after chemotherapy compared to pre-chemotherapy (p = 0.001), and no change in testosterone or INSL3. In contrast, patients with high β-hCG pre-chemotherapy (n = 42) had suppressed LH, markedly elevated testosterone, and low INSL3 at start of chemotherapy, with increased LH, decreased testosterone, and increased INSL3 1 year later (all p < 0.001)., Discussion: Changes in LH show that gonadal endocrine function is disturbed before chemotherapy, 1 year later, and at long-term follow-up in chemotherapy-treated TC patients., Conclusion: Pre-chemotherapy, β-hCG-producing tumors affect the gonadal endocrine axis, demonstrated by increased testosterone and decreased LH. INSL3 did not uniformly follow the pattern of testosterone., (© 2019 American Society of Andrology and European Academy of Andrology.)

Introduction: Pregnancies resulting from fertility treatments are at higher risk of placenta-mediated complications. Hence, we aimed to estimate the association between fertility treatment and levels of first-trimester markers of placentation., Methods: We conducted a cohort study in an academic center from 03/2011 to 12/2014. Adult nulliparous women with singleton pregnancies were recruited between 11  +   0 and 13  +   6 weeks of gestation. Data on maternal characteristics, medical history, and pregnancies conceived through fertility treatments (whether ovulation agents, insemination or assisted reproductive technologies) were collected. Maternal serum concentrations of PlGF, sFlt-1, PAPP-A, AFP, and free β-hCG were obtained, and notches and UtA-PI were measured using Doppler ultrasound. Mean Multiple of the Medians (MoM) and frequencies were computed to estimate the mean differences (MD) or risk ratios (RR) comparing fertility treatment to spontaneous pregnancies., Results: 427 (9%) pregnancies out of 4815 were conceived through fertility treatments, using ovulation agents (n = 233, 5%), insemination (n = 174, 4%) and/or assisted reproductive technologies (n = 85, 2%). The latter were associated with significantly lower log 10 PAPP-A MoM (adjusted MD: -0.02, 95%CI: -0.04 to -0.01), lower log 10 PlGF MoM (adjusted MD: -0.04, 95%CI: -0.06 to -0.01) and higher log 10 free β-hCG MoM (adjusted MD: 0.05, 95%CI: 0.01 to 0.09) compared to spontaneous pregnancies. Ovulation agents and insemination were associated with the presence of notches (adjusted RR: 1.24, 95%CI: 1.14 to 1.35; and 1.27, 95%CI: 1.15 to 1.42, respectively) and higher log 10 UtA-PI MoM (adjusted MD: 0.16, 95%CI: 0.08 to 0.24; and 0.17, 95%CI: 0.07 to 0.27, respectively) than spontaneous pregnancies., Conclusion: Fertility treatments are associated with significant variations in markers of placentation., (Copyright © 2019. Published by Elsevier Ltd.)

A 35-year-old Nepalese woman, referred by her general practitioner for per vaginal spotting and abdominal pain for the past 12 days with a background history of 5 weeks of amenorrhoea and a quantifiable beta-human chorionic gonadotrophin of 18 900 IU/L. Subsequent pelvic ultrasound revealed a cystic lesion with peripheral vascularity in the pouch of Douglas indicating possible ectopic pregnancy with no intrauterine gestational sac seen. Subsequent to that, she underwent a diagnostic laparoscopy that revealed 150 mL of blood in the pouch of Douglas with no other obvious evidence of tubal or ovarian ectopic pregnancy seen. There was, however, a resemblance of trophoblastic tissue noted on the wall of the pouch of Douglas that was further investigated to reveal a primary ectopic pregnancy of the pouch of Douglas with no trophoblastic infiltration., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To bring new accuracy to the prognosis of outcomes of euploid fetuses with an extremely high risk in the first-trimester combined screening when compared to the low-risk group., Study Design: The data included pregnancies with a trisomy 21 risk ≥ 1:50 in the combined first-trimester screening but normal fetal chromosomes. The control group had a risk value ≤ 1:300. Miscarriage, termination of pregnancy, stillbirth, premature delivery, and delivery of an unhealthy child were considered adverse outcomes. The impact of each component in the combined first-trimester screening was analyzed separately. Statistical comparisons were made by using the chi-square test, Fisher-Freeman-Halton test, Mann-Whitney test or t-test., Results: The study comprised 483 women (161 cases and 322 controls). The mean follow-up time of children born alive was 61.4 months. An adverse outcome was detected in 11.8% of the cases and in 5.9% of the controls. After adjusting the values of mother´s age, parity, and smoking habit the odds ratio for an adverse outcome was 2.1 (95% CI: 1.0-4.5, p = 0.05) for cases. When evaluating the effect of 1 SD increase in MOM of PAPP-A or 1 SD decrease in MOM of NT or β-hCG to any adverse outcome, 1 SD increase in PAPP-A MOM decreased the risk of adverse outcome by OR 0.48 (95% CI: 0.3 - 0.8, p = 0.05) while the others were not significant., Conclusion: Euploid fetuses with a high risk in the combined first-trimester screening have a twofold risk for adverse outcomes when compared to those with a low risk., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The aim of this study was to assess the effect of plasma volume alteration determined by hematocrit on biochemical parameters of the first trimester screening test., Methods: Enrolled in this study were 1,424 pregnant women in their first trimester who underwent a first trimester screening test. Fetal Nuchal Trancluciency measurement was obtained by ultrasonographic evaluation. Blood samples were taken for complete blood count, serum free β-HCG, and PAPP-A between 11 and 14 weeks of gestation. The effect of plasma volume alteration on the screening test was evaluated. Mean corpuscular volume was used to rule out possible iron deficiency anemia., Results: There were 59 women with combined risk > 1/270. Of these 59 women, there were 21 false positive results (1.5%). Serum Htc significantly predicted the false positive cases (AUC: 0.839, p < 0.001). The optimal cutoff value was obtained at a value of 30.2% with 85% sensitivity and 75% specificity., Conclusions: Our study suggests that the degree of plasma alterations may affect the serum levels of the biochemical components of the first trimester screening test for aneuploidy, thereby leading to false positive test results.

Purpose: Previous studies suggested that serum levels of microRNA (miR)-371a-3p (so-called M371 test) have a much higher sensitivity and specificity than the classic markers of testicular germ cell tumors (GCTs) and are applicable toward both seminoma and nonseminoma. We sought to confirm the usefulness of this test as a novel biomarker for GCT., Patients and Methods: In a prospective, multicentric study, serum samples of 616 patients with testicular GCTs and 258 male controls were examined for serum levels of miRNA-371a-3p (miR levels) by quantitative polymerase chain reaction. The GCT population encompassed 359 patients with seminoma and 257 with nonseminoma; 371 had clinical stage I disease, 201 had systemic disease, and 46 had relapses. Paired measurements before and after orchiectomy were performed in 424 patients; 118 with systemic disease had serial measurements during treatment. miR levels were compared with those of β-human chorionic gonadotropin, α-fetoprotein, and lactate dehydrogenase., Results: For the primary diagnosis of GCT, the M371 test showed a sensitivity of 90.1%, a specificity of 94.0%, an area under the curve of 0.966 upon receiver operating characteristic analysis, and a positive predictive value of 97.2%. α-Fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase had sensitivities of less than 50% in seminoma and slightly higher sensitivities in nonseminomas. miR levels were significantly associated with clinical stage, primary tumor size, and response to treatment. Relapses had elevated miR levels that subsequently dropped to normal upon remission. Teratoma did not express miR-371a-3p., Conclusion: The M371 test outperforms the classic markers of GCT with both a sensitivity and a specificity greater than 90%. All histologic subgroups, except teratoma, express this marker. The test could be considered for clinical implementation after further validation.

Research Question: Does the blastocyst development stage on embryo transfer day affect serum β-human chorionic gonadotrophin (β-HCG) concentration 9 and 16 days after embryo transfer in women whose pregnancy progresses beyond 13 weeks?, Design: Retrospective study involving 204 cases where pregnancy progressed beyond 13 weeks of single blastocyst transfer in fresh (n = 66) or frozen embryo transfer (FET) (n = 138) cycles from January 2015 to September 2016., Results: β-HCG concentrations 9 and 16 days after embryo transfer in FET cycles (median 223 IU/l and 4378 IU/l, respectively) were significantly (P < 0.001) higher than in fresh cycles (157 IU/l and 2813 IU/l). Among fresh cycles, faster-growing blastocysts (expanded + hatching + hatched blastocysts) produced significantly (P < 0.001) higher β-HCG concentrations 9 days after embryo transfer (191 IU/l) than slower-growing blastocysts (cavitating + full blastocyst, 106 IU/l); however no significant difference was found between the faster- and slower-growing groups by day 16 (2359 IU/l and 3025 IU/l, respectively). Among FET cycles, there was no difference in β-HCG concentration between blastocysts of different development stages 9 and 16 days after transfer., Conclusions: Faster-growing blastocysts produced significantly higher serum β-HCG concentrations 9 days after transfer than slower-growing blastocysts in fresh cycles, but the difference was not significant by day 16 after transfer. Also, β-HCG concentrations 9 and 16 days after embryo transfer in FET cycles were higher than in fresh embryo transfer cycles. Interpretation of β-HCG results 9 days after blastocyst transfer should consider the blastocyst growth rate and whether fresh or cryopreserved embryo was transferred., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: We aimed to assess the relationship between gynecomastia and tumor markers, histologic subtypes, and prognosis in patients with testicular germ cell tumors., Methods: This study included 73 testicular germ cell cancer patients with pretreatment chest, abdomen and pelvis computed tomography (CT) scans and tumor markers (β-human chorionic gonadotropin [β-hCG], lactate dehydrogenase [LDH], α-fetoprotein [AFP]). The volumetric analysis of the breast glandular tissue, the presence of gynecomastia and metastatic disease were determined using CT scans. Patients were classified according to the International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic classification. The association between gynecomastia, breast glandular tissue volume, tumor markers, metastatic disease, and disease prognosis were evaluated., Results: Thirty-four of the patients (46.6%) had gynecomastia. A breast volume cutoff value of 0.78 cm3 to diagnose gynecomastia led to 85% sensitivity and 95% specificity. Serum β-hCG level correlated with the breast glandular tissue volume weakly (r=0.242, P = 0.039). Gynecomastia was more common in patients with elevated β-hCG levels (P = 0.047), and was not associated with pulmonary, nonpulmonary distant, or nodal metastases (P = 0.378, P = 0.884, P = 0.333, respectively). No significant association was found between the disease prognosis and gynecomastia (P = 0.556)., Conclusion: Gynecomastia was common among testicular germ cell cancer patients with elevated β-hCG. However, it was not associated with metastatic disease and prognosis.

Introduction: To identify the prevalence and types of fetal chromosomal polymorphisms in pregnant women and to examine possible associations with screening test parameters., Materials and Methods: Fetal chromosomal polymorphism rate was investigated in pregnant women who had been implemented for invasive prenatal test in a tertiary reference center in Thrace Region of Turkey. Fetal chromosomal polymorphisms were determined and their effects on screening tests' parameters were investigated. Possible differences in the first and second-trimester screening test parameters between women; with fetal chromosomal polymorphism who had screening test results (Group 1) and those with a normal karyotype (Group 2) were evaluated., Results: Fetal chromosomal polymorphism prevalence was 5.3% (n = 101). The most common polymorphisms were identified on chromosome 9, 1, and 16 [54.5% (n = 55); 8.9% (n = 9), and 6.9% (n = 7), respectively]. The most common polymorphic variant was 9qh+ (n = 23; 22.8%). Among the screening test parameters, significantly lower pregnancy-associated plasma protein-A (PAPP-A) (p = .028) and higher unconjugated estriol (uE3) (p = .019) values were found in Group 1. In patients having fetuses with polymorphic variants on chromosome 9, a significantly lower PAPP-A values were observed compared to women with other fetal polymorphic variants (p = .048) or women having fetuses with normal karyotype (p = .007)., Conclusions: Lower PAPP-A and higher uE3 levels were observed in women having fetuses with chromosomal polymorphisms, which might affect screening test results. Lower PAPP-A levels were apparent in women having fetuses with polymorphism on chromosome 9.

Objective: To evaluate the efficacy and toxicity of VMP regimen applied to the patients with low-risk gestational trophoblastic neoplasia (LR-GTN) treated in Anhui provincial hospital., Materials and Methods: Between 2005 and 2017, 87 patients with low-risk gestational trophoblastic neoplasia received VMP regimen, consisted of vincristine (VCR), methotrexate (MTX) and platinum (cisplatin, carboplatin or nedaplatin), 68 of whom received VMP as their first-line chemotherapy, and 19 methotrexate-failed patients received VMP regimen as their second-line chemotherapy. The staging and scoring system was based on International Federation of Gynecology and Obstetrics (FIGO 2000) criteria. We describe and analyze their baseline characteristics, remission/resistance/recurrence rates, adverse reactions and prognosis., Results: The first-line VMP protocol can achieve an 83.8% remission rate and it tended to develop resistance when the pretreatment β-hCG reaches 7503.5 IU/L, and can achieve complete remission with FAV and EMA-CO as the salvage regimen. Among the 19 methotrexate-failed patients, 2 of whom were yet resistant to VMP regimen, followed by several courses of salvage chemotherapy such as FAV and EMP, and achieved 89.5% remission rate in second-line VMP group. Resistance to this regimen was obviously related with higher pre-treatment HCG whether used as primary or salvage treatment. Severe myelosuppression (grade 3 or 4) was shown in 4 (5.9%) of 68 cases, of which none was grade 4., Conclusion: For patients diagnosed with LR-GTN VMP regimen was a safe and effective treatment with a high rate of remission., (Copyright © 2019. Published by Elsevier B.V.)

Background: Prenatal diagnosis of fetal trisomy 21 and other chromosomal abnormalities is based on invasive tests, such as amniocentesis and chorionic villus sampling, which are carried out in women identified through screening as being at high risk for these abnormalities. The most widely used method of screening is the first-trimester combined test which utilizes maternal age, and measurements of fetal nuchal translucency thickness (NT) and maternal serum pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (hCG)., Objectives: To assess the influence of SLE on the levels of NT, PAPP-A, and β-hCG and whether any alterations in such levels may increase the rate of false positives and the subsequent number of invasive tests., Method: This was a prospective first-trimester screening study for trisomies 21, 18, and 13 by a combination of maternal age, fetal nuchal translucency thickness, and serum PAPP-A and β-hCG at King's College Hospital, London, between March 2006 and February 2011. The study population included 47 cases with maternal SLE and 45,493 without SLE. The results of biomarkers in the SLE and non-SLE groups were compared., Results: In the SLE group, compared to the non-SLE group, there were no significant differences in median maternal age, fetal NT, or serum PAPP-A MoM, but serum free β-hCG MoM was increased (1.402, IQR 0.872-2.290 vs 0.994, IQR 0.676-1.508)., Conclusion: In first trimester screening for trisomies, the measured value of free ß-hCG should be adjusted for maternal SLE to avoid false positive results and overuse of invasive tests.

Most patients with testicular germ cell tumor present with a painless scrotal mass. We report a 19-year-old patient who presented with neurological complains. Rapid clinical progression to coma was noted during the staging work up. A diagnosis of testicular mixed germ cell tumor with multiorgan metastasis (lymph node, lung, liver and brain) was made. Patients with brain metastasis should receive chemotherapy alone or combined with surgery or radiotherapy. Because the clinical symptoms deteriorated quickly, surgery was used upfront followed by chemotherapy and radiotherapy for the brain tumor. After the first stage of treatment, the clinical symptoms, tumor markers and imaging findings were improved. The residual brain tumor was eliminated by chemotherapy, and only sparse degenerated tumor cells were noted in the brain tissue. Longer follow up is required to assess the impact of our treatment strategy., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Purpose: To evaluate the hysteroscopic management on cervical pregnancy., Materials and Methods: A case series report and literature review on patients with early first trimester cervical pregnancy (CP) treated by hysteroscopy. The symptoms upon admission, β-hCG levels, hysteroscopy technique, blood loss and operation outcomes were presented., Results: Four patients with early CP between 5 and 7 weeks were successfully managed with operative hysteroscopy. Three out of four patients had at least one risk factor for cervical ectopic pregnancy. Two patients were diagnosed on routine examinations and the other two presented with vaginal spotting and pelvic pain. Mechanical hysteroscopy was used in three patients while one case was managed by a 10mm resectoscope. Three women discharged home on the same day and one patient 24h after the operation. Literature review revealed 16 publications of cervical pregnancy managed with operative hysteroscopy. 14 articles demonstrated single case reports and two papers were CP case series. Hysteroscopic surgery was successfully reported in 12 cases as a sole treatment, in seven cases after failure of methotrexate treatment and in eight cases as a combined treatment with uterine artery embolization., Conclusions: Our case series demonstrated that operative hysteroscopy can be used as a sole treatment in early, less than 8-week CPs with safety. Literature review demonstrated that most of the early first trimester CP cases were treated by hysteroscopy and the rest after failure of methotrexate treatment or in combination with uterine artery embolization., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Mid-trimester beta-human chorionic gonadotropin (BHCG) levels are considerably higher in pregnancies resulting from frozen embryo transfer (FET) compared with fresh (FRET), leading to a higher false positive rate in aneuploidy screening tests. We aimed to investigate the dynamics of BHCG increment and its predictive value for cycle outcome. A retrospective analysis of FRET and FET cycles. BHCG values on days 14 and 16 post embryo transfer were compared and stratified according to the number of sacs demonstrated on US scan at six weeks gestation, and pregnancy outcome (biochemical pregnancy, ectopic pregnancy, spontaneous abortion, and a singleton or twin birth). A prediction model for live birth was built. A total of 430 treatment cycles were analyzed. The average BHCG levels were significantly higher in FET compared with FRET group in nonviable pregnancies on day 14, 450 vs. 183 IU/L, p < .05 and day 16, 348 vs. 735 IU/L, p < .05, respectively. The increment of BHCG was significantly steeper in the FET compared with FRET group in biochemical pregnancies (F = 6.485, p = .012*). Optimal cutoff level for live birth prediction in the FRET group was 211 IU/L (sensitivity 84%, specificity 76.2%) for day 14 and 440 IU/L (sensitivity 86.0% and specificity 72.5%) for day 16. The increment in BHCG differed significantly between the FRET and FET cycles in nonviable pregnancies. Nevertheless, the difference in BHCG levels observed in the second trimester in pregnancies conceived after FRET and FET cycle may begin as early as the fourth week of pregnancy.

Purpose: The aim of this study was to evaluate the relationship between serum beta-human chorionic gonadotropin (β-hCG) and preeclampsia (PE) and the effects of βhCG on maternal and perinatal outcomes., Methods: This case-control study included 125 pregnant women who were admitted to the labor ward of the Maternity Teaching Hospital, Erbil City, Kurdistan, Iraq between January and December 2016. Participants included 50 women with severe PE, 25 with mild PE, and 50 who were normotensive. Serum β-hCG concentrations during labor were compared between groups and maternal and perinatal outcomes were recorded., Results: There were no significant differences in maternal age or parity distribution between the three groups. Gestational age was less than 37 weeks in 34% of the women with severe PE and in 12% of women in the mild PE and normotensive groups (p = 0.012). Mean β-hCG concentration was 37,520.56 mIU/mL in women with severe PE, 16,487 mIU/mL in those with mild PE, and 11,699.82 mIU/mL in those who were normotensive (p < 0.001). There were no significant differences in perinatal outcomes between groups; however, those with β-hCG concentrations ≥ 40,000 mIU/mL had worse neonatal outcomes (lower Apgar scores, higher rate of NICU admission, and lower survival rate) and unfavorable maternal outcomes (seizures, abruption, post-partum hemorrhage, and deep vein thrombosis)., Conclusions: There was a significant difference in β-hCG concentrations between women with PE and normotensive women. There were no significant differences in perinatal or maternal outcomes between groups, except in patients with β-hCG ≥ 40,000 mIU/mL.

Objective: To report clinical experience with methotrexate (MTX) treatment for suspected but not definite ectopic pregnancy (EP)., Methods: This was a retrospective cohort study. All patients treated with MTX for presumed EP between 2000 and 2016 were included. Demographic, clinical, sonographic, and outcome data were collected and analyzed., Results: A total of 820 patients were treated with MTX, 692 (84.4%) of which were lacking definitive features of EP; 155 (22.4%) failed to follow up until complete resolution and were excluded. Retrospective sonographic categorization was applied to 537 patients; of those patients, 393 (73.2%) were categorized as probable EPs, 136 (25.3%) pregnancies of unknown location (PULs), and 8 (1.5%) probable intrauterine pregnancies (IUPs). Sixteen were eventually diagnosed with IUP: 6 from the probable EPs, 9 from the PULs, and 1 from the probable IUP group. Patients with final diagnosis of IUP had higher values of β-human chorionic gonadotropin as well as lower prevalence of adnexal mass (38% versus 74%; P = .003), higher prevalence of intracavitary fluid (44% versus 9%; P = .0004) and thicker endometrium (17.1 ± 11.8 versus 9.7 ± 5.6; P = .04). None of the sonographic parameters were able to distinguish patients with IUP. One patient of the 16 with IUP was diagnosed with a viable pregnancy, and 7 additional patients had a possible viable pregnancy. None of them elected to continue the pregnancy., Conclusions: Most patients with suspected EP who are eligible for medical treatment lack definitive sonographic features of EP. Treatment with MTX in such cases should be delayed, as clinically reasonable, to improve the diagnosis and prevent inadvertent administration of MTX to patients with a viable IUP., (© 2018 by the American Institute of Ultrasound in Medicine.)

Research Question: What is the diagnostic value of maternal kisspeptin in patients with asymptomatic first-trimester pregnancies, and what is the prognostic significance of kisspeptin versus beta-HCG in early pregnancies., Design: Case-control study in academic medical centres. Patients with no confounding co-morbidities who conceived by IVF and intracytoplasmic sperm injection were analysed. Maternal serum samples were assessed at the time of pregnancy testing. Women who achieved a positive pregnancy test were asked to take serum samples 4 days later. According to the follow-up results, patients who experienced biochemical pregnancy loss (n = 24) and early miscarriage (n = 21), and women who achieved a viable pregnancy (n = 28), were included in this study. Serum samples were collected to detect kisspeptin and beta-HCG, respectively., Results: Single serum determinations of kisspeptin and beta-HCG were correlated with the different pregnancy outcomes. Women who experienced biochemical pregnancy loss showed lower kisspeptin levels than those in groups B and C. No significant difference, however, was observed at the time of pregnancy testing in women who had experienced early miscarriage and those who had achieved viable pregnancy. Sequential measurements of serum kisspeptin are not as effective as beta-HCG in determining pregnancy outcome. Increased kisspeptin level was associated with reduced miscarriage risk., Conclusion: Single serum measurement of kisspeptin is significantly altered in pregnant and non-pregnant women. However, it failed to discriminate between miscarriage and ongoing pregnancies in first-trimester pregnancy. Neither single nor sequential kisspeptin have higher diagnostic performance for miscarriage than beta-HCG in early stage., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Primary malignant mediastinal germ cell tumors (PMMGCTs) including seminomas and nonseminomatous germ cell tumors (NSGCTs) are rare, and sometimes the diagnosis is very difficult., Purpose: The purpose of this study is to compare the clinical characteristics, biomarkers, and imaging findings of seminomas and NSGCTs and to determine whether these features could help distinguish these two types of PMMGCT., Material and Methods: A retrospective study of 24 male patients with histopathologically proven PMMGCT was performed. We collected the information of computed tomography (CT) (the scan area ranged from the apex of lung to the costophrenic angles) and magnetic resonance imaging blood test and histology characteristics of these patients., Results: Twelve of 24 cases were confirmed to be seminomas, whereas the other 12 cases were NSGCTs. Alfa-fetoprotein (AFP) was found to be elevated in all patients with NSGCT, whereas none of the patients with seminomas had elevated AFP level. Beta-human chorionic gonadotropin (β-HCG) level was elevated in all the patients with seminomas (seven/seven), whereas in NSGCT only two of seven patients had elevated β-HCG. Lactate dehydrogenase level was increased in five of the nine patients with seminomas, as well as in the eight patients with NSGCT. CT imaging revealed that 12 masses from the seminoma group were homogeneous, soft tissue opacity and showed minimal contrast enhancement. On the contrary, all 12 NSGCT cases showed cystic and solid masses; on contrast-enhanced CT, heterogeneous enhancement was found on the capsule of the tumor, septum, and solid masses., Conclusion: Seminomas and NSGCT showed different profiles of tumor biomarkers and radiographic features. Evidence from serum test, histopathological analysis, and imaging should be combined to ensure the accurate diagnosis of these two types of PMMGCT., Competing Interests: None

Early diagnosis of an extrauterine pregnancy is important for safe and effective management. However, a pregnancy's location often cannot be easily determined with abnormal implantations or prior to 5-6 weeks' gestation. Multiple testing strategies exist to diagnose an abnormal pregnancy when location is unknown, but caution needs to be used to avoid a false diagnosis. Medical treatment is optimal when an abnormal pregnancy is diagnosed early. Because most of these pregnancies are intrauterine, additional testing to localize the pregnancy will allow the correct choice of therapy and avoids unnecessary exposure to a toxic therapy. This testing strategy should be reserved for patients with significant concern for ectopic pregnancy, based on either risk factors or clinical findings. Overuse of this approach can lead to interruption of normal pregnancies., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To determine the effect of embryonic factors on serum beta human chorionic gonadotropin (β-hCG) levels in pregnancy and live birth resulting after a single fresh cleavage embryo and blastocyst transfer., Study Design: This was a retrospective cohort study conducted at a tertiary care hospital. All fresh single embryo transfers (sETs) between September 2011 and December 2016 were included. The correlation analysis was performed to determine the association of embryo morphological parameters on mean serum β-hCG levels on day 12 after the transfer of a fresh single cleavage embryo and a fresh single blastocyst embryo., Results: Out of a total of 455 fresh sETs, 60 positive β-hCG results after the transfer of a single fresh cleavage-stage embryo and 82 after the transfer of a single fresh blastocyst. The mean β-hCG level resulting from a single fresh blastocyst ET was 371.7 ± 52.7 IU/L, which was similar to the mean β-hCG level resulting from a cleavage ET (314.5 ± 36.9 IU/L) (p = .70). Interestingly, serum β-hCG levels resulting from a single fresh blastocyst ET showed a correlation with day 5 blastocoele expansion, trophectoderm cell number and blastocyst quality score in ongoing pregnancy (r = .33, p = .02; r = .29, p = .04; and r = .31, p = .03, respectively). Moreover, day 5 blastocoele expansion and blastocyst quality score showed a correlation with the serum β-hCG levels resulting from a single fresh blastocyst ET in live birth (r = .36, p = .02; r = .31, p = .04, respectively)., Conclusion: Our study suggests that serum β-hCG levels resulting from a single fresh blastocyst ET showed a correlation with day 5 blastocoele expansion and blastocyst quality score in both ongoing pregnancy and live birth., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Approximately one-fourth of pregnant women will experience bleeding in the first trimester. The differential diagnosis includes threatened abortion, early pregnancy loss, and ectopic pregnancy. Pain and heavy bleeding are associated with an increased risk of early pregnancy loss. Treatment of threatened abortion is expectant management. Bed rest does not improve outcomes, and there is insufficient evidence supporting the use of progestins. Trends in quantitative ß subunit of human chorionic gonadotropin (ß-hCG) levels provide useful information when distinguishing normal from abnormal early pregnancy. The discriminatory level (1,500 to 3,000 mIU per mL) is the ß-hCG level above which an intrauterine pregnancy should be visible on transvaginal ultrasonography. Failure to detect an intrauterine pregnancy, combined with ß-hCG levels higher than the discriminatory level, should raise concern for early pregnancy loss or ectopic pregnancy. Ultrasound findings diagnostic of early pregnancy loss include a mean gestational sac diameter of 25 mm or greater with no embryo and no fetal cardiac activity when the crown-rump length is 7 mm or more. Treatment options for early pregnancy loss include expectant management, medical management with mifepristone and misoprostol, or uterine aspiration. The incidence of ectopic pregnancy is 1% to 2% in the United States and accounts for 6% of all maternal deaths. Established criteria should be used to determine treatment options for ectopic pregnancy, including expectant management, medical management with methotrexate, or surgical intervention.

Objective: This study aimed to determine the diagnostic value of magnetic resonance imaging (MRI), hysteroscopy, and laparoscopy to avoid unnecessary treatment when patients present with clinical manifestations that are close to those of gestational trophoblastic neoplasia (GTN)., Methods: Three patients who were falsely diagnosed with presumed GTN and received needless chemotherapy in our hospital from July 2011 to March 2012 were studied. We also reviewed data of patients with similar clinical features who were diagnosed as having residual pregnancy in recent years. Clinical manifestations were evaluated., Results: All three patients had persistently high serum β-human chorionic gonadotrophin levels and a mass with abundant blood supply in the uterus after termination of pregnancy. The patients were diagnosed with GTN and underwent chemotherapy. They responded poorly to chemotherapy and underwent surgery. The pathological diagnosis in all patients was residual pregnancy. In recent years, no patients were misdiagnosed because pelvic MRI, hysteroscopy, or laparoscopy was used when residual pregnancy could not be excluded., Conclusion: Gynecologists should diagnose carefully when patients present with clinical manifestations that are close to those of GTN to avoid unnecessary treatment. MRI, hysteroscopy, and laparoscopy could be important examinations for excluding residual pregnancy.