Evaluation of pretreatment and early treatment changes in serum ß-hCG with methotrexate.

BACKGROUND: Serum beta-human chorionic gonadotropin (ß-hCG) is an important biomarker for the detection of ectopic pregnancies (EPs). The ß-hCG levels between days 1 and 4 after methotrexate (MTX) treatment as an indicator of the success of the MTX in EP have been the focus of research. OBJECTIVES: To determine whether the change in the ß-hCG levels at day 1 and 4 and pretreatment at 48-hour increments can predict early treatment failure of single-dose MTX in EP. MATERIAL AND METHODS: This was a retrospective study of 1120 EPs treated with a single dose of MTX. Treatment failure was defined as an obligation to proceed to surgery or the need for additional doses of MTX. RESULTS: A total 722 out of 1120 EPs had an increase in ß-hCG on day 4 after MTX treatment. The logistic regression analysis indicated that 3 dependents were significantly associated with treatment failure: 1) a pretreatment 48-hour increase in ß-hCG (odds ratio (OR): 1.249, 95% confidence interval (95% CI): 1.008-2.049, p < 0.001); 2) a change in ß-hCG between day 1 and 4 (OR: 1.384, 95% CI: 1.097-2.198, p < 0.001); and 3) a history of EP (OR: 1.208, 95% CI: 1.041- 2.011, p < 0.001). The optimal cutoff point for the prediction of treatment failure was an increase of more than 19% in the 48 h before the treatment, and an increase of more than 36% between day 1 and day 4 in ß-hCG concentrations. Patients with an increase in ß-hCG levels of less than 36% on day 4 experienced MTX treatment failure in 4.2% (n = 25), compared to 74.5% (n = 88) of the patients with an increase above 36%. CONCLUSIONS: A serum ß-hCG increase of more than 36% on day 4 after the administration of MTX alongside a more than 19% increase in ß-hCG concentration 48 h before the MTX treatment may predict the early failure of medical treatment for an EP.

Embarazo ectópico roto con fracción beta de la hormona gonadotropina coriónica humana negativa: reporte de caso / Ruptured ectopic pregnancy with negative human chorionic gonadotropin hormone beta fraction: case report

Resumen El embarazo ectópico roto es una emergencia quirúrgica cuyo diagnóstico, gracias a la interrelación de la cuantificación de la fracción beta de la hormona gonadotropina coriónica humana (HCG-β) y los hallazgos ultrasonográficos, se ha hecho más preciso. Sin embargo, el diagnóstico se vuelve difícil cuando clínicamente se encuentran datos sugestivos de embarazo ectópico con una HCG-β negativa. Presentamos el caso de una mujer de 25 años acude a valoración por referir 12,2 semanas de retraso menstrual, asociado a sangrado transvaginal y signos de irritación peritoneal, que cuenta con HCG-β negativa (< 5 mUI/ml). Se realizó un rastreo ultrasonográfico encontrando abundante líquido libre en cavidad, sin evidencia de embarazo intrauterino. Ante la alta sospecha de embarazo ectópico se realizó laparotomía exploradora, encontrando hallazgos sugestivos de embarazo ectópico roto, y se realizó salpingectomía. Finalmente, en el estudio posoperatorio se confirmó por histopatología un embarazo ectópico roto. Existen muy pocos reportes en la literatura internacional de pacientes con características clínicas de embarazo ectópico roto, con HCG-β negativa. Es importante la difusión de este tipo de casos con la finalidad de mejorar los abordajes diagnósticos y no restar importancia ante la sospecha clínica, a pesar de presentar una HCG-β negativa.

Abstract Broken ectopic pregnancy is a surgical emergency that due to the relation between the serum quantification of the of the beta subunit of human chorionic gonadotropin (β-HCG) and the ultrasonographic findings, there have been improvements to reach a precise diagnosis. However, there are very few reported cases in the literature where a broken ectopic pregnancy is described with negative serum results in β-HCG. We present a case report of a 25-year-old patient came to the evaluation for referring 12.2 weeks of menstrual delay, associated with transvaginal bleeding and data of peritoneal irritation, she had a negative β-HCG fraction (< 5 mIU/ml). A scan was performed ultrasound finding abundant free fluid in the cavity, without evidence of intrauterine pregnancy. Given the high suspicion of ectopic pregnancy, an exploratory laparotomy was performed, finding findings suggestive of a ruptured ectopic pregnancy, a salpingectomy was performed. Finally, in the postoperative study, a ruptured ectopic pregnancy was confirmed by histopathology. There are very few reported internationally were found a patient with clinical characteristics of broken ectopic pregnancy, with a β-HCG negative. It is important the scientific diffusion of this type of cases with the purpose of improving the diagnostic approaches and not underestimating importance to the clinical suspicion, despite presenting negative β-HCG results.

Value of C-11 methionine PET/CT in patients with intracranial germinoma.

PURPOSE: The purpose of this study was to investigate the value of C-11 methionine (MET) positron emission tomography (PET)/computed tomography (CT) in patients with intracranial germinoma (IG). MATERIAL AND METHODS: We conducted a retrospective analysis of 21 consecutive patients with pathologically confirmed IGs and eight patients with intracranial non-germinomas (INGs) located in a similar region. Clinical characteristics, imaging findings, and tumor markers such as α-fetoprotein (AFP) and ß-human chorionic gonadotropin (HCG) were used as clinical variables. Maximum standardized uptake value (SUVmax), tumor-to-normal tissue (T/N) ratio, and visual scoring of tumor were used as MET PET parameters. RESULTS: All IGs were well visualized on MET PET with a three-grade visual scoring system. In addition, SUVmax of IGs was higher than that of INGs (P = 0.005). Pre-treatment (Pre-Tx) T/N ratio was significantly correlated with pre-Tx serum HCG (P = 0.031). Moreover, MET PET parameters showed significant associations with tumor location, sex, KRAS variant, and symptoms. CONCLUSION: MET PET/CT could be a useful diagnostic tool in patients suspected of having IGs. In addition, the MET avidity of tumor is a potential surrogate biomarker of HCG, which has been used as a diagnostic marker for IGs. Tumor MET parameters also had significant differences according to tumor locations, sex, symptoms, and KRAS mutation. However, MET avidity of tumors had no significant prognostic value.

Impact of preimplantation genetic testing for aneuploidies (PGT-A) on first trimester biochemical markers - PAPP-A (placenta-associated plasma protein) and free ß-hCG (human chorionic gonadotropin).

OBJECTIVE: The objective of the study was to study the effect of preimplantation genetic testing for aneuploidies (PGT-A) performed at blastocyst stage on the levels of first trimester biomarkers. METHODS: This is an observational, collaborative, retrospective study. Seven hundred and twenty-eight patients were included in the study. Patients were with singleton pregnancies resulting from either natural conception (NC), or assisted reproductive techniques (ARTs) with PGT-A and frozen embryo transfer (FET) (ART/PGT-A/FET) or after ART without PGT-A and fresh ET (ART/no PGT-A/fresh ET) or FET (ART/no PGT-A/FET), who had first trimester combined screening test between 11 and 14 gestational weeks. They were stratified into four groups: group A (ART/PGT-A/FET) - 143 patients; group B (ART/no PGT-A/FET) - 100 patients; group C (ART/no PGT-A/fresh ET) - 346 patients, and group D (NC) - 139 patients. RESULTS: Statistically significant differences among the examined groups were observed for maternal age, BMI, ethnicity, and parity. The median placenta-associated plasma protein (PAPP-A) was lowest in the group with ART/PGT-A/FET and the highest result was obtained in the group with ART/no PGT-A/FET. Statistically significant difference in the median PAPP-A levels was identified among the examined groups (p = .0186). When a subgroup analysis was performed, a statistically significant difference was observed in the median PAPP-A between ART/PGT-A/FET group versus ART/no PGT-A/FET group (p = .01) and NC versus ART/no PGT-A/FET (p = .01). A similar trend toward statistical significance was noted when comparing NC versus ART/no PGT-A/fresh ET (p = .06). Multivariate analysis elucidated that when age is present in the model, the effect of any method of conception or testing for aneuploidy disappears. The other factors (BMI, ethnicity, and parity) do not influence the levels of PAPP-A. The lowest median free human chorionic gonadotropin (ß-HCG) was recorded in the NC group and the highest result was identified in the group with IVF/PGT-A/FET. No statistically significant difference was observed in the median concentration levels of free ß-hCG among the compared groups (p = .5789) and when subgroup analysis was performed (p>.05). The normality of the distribution of variables was analyzed by the Kolmogorov-Smirnov test and the median PAPP-A and free ßhCG concentration difference by the Wilcoxon rank-sum test with nonparametric ANOVA. CONCLUSIONS: Testing for aneuploidy (PGT-A) and the decision to transfer either fresh or cryopreserved embryos (ET) appear not to affect the levels of first trimester biochemical markers. The findings of the present study should be a baseline for future studies and could be used to improve the antenatal screening counseling for women with ART pregnancies and PGT-A.

A multivariate modeling method for the prediction of low fetal fraction before noninvasive prenatal testing.

OBJECTIVE: To investigate factors associated with fetal fraction and to develop a new predictive method for low fetal fraction before noninvasive prenatal testing. METHODS: The study was a retrospective cohort analysis based on the results of noninvasive prenatal testing, complete blood count, thyroxin test, and Down's syndrome screening during the first or second trimester in 14,043 pregnant women. Random forests algorithm was applied to predict the low fetal fraction status (fetal fraction < 4%) through individual information and laboratory records. The performance of the model was evaluated and compared to predictions using maternal weight. RESULTS: Of 14,043 cases, maternal weight, red blood cell, hemoglobin, and free T3 were significantly negatively correlated with fetal fraction while gestation age, free T4, pregnancy-associated plasma protein-A, alpha-fetoprotein, unconjugated estriol, and ß-human chorionic gonadotropin were significantly positively correlated with fetal fraction. Compared to predictions using maternal weight as an isolated parameter, the model had a higher area under the curve of receiver operating characteristic and overall accuracy. CONCLUSIONS: The comprehensive predictive method based on combined multiple factors was more effective than a single-factor model in low fetal fraction status prediction. This method can provide more pretest quality control for noninvasive prenatal testing.

Identification and semi-relative quantification of intact glycoforms of human chorionic gonadotropin alpha and beta subunits by nano liquid chromatography-Orbitrap mass spectrometry.

The human chorionic gonadotropin (hCG) protein belongs to a family of glycoprotein hormones called gonadotropins. It is a heterodimer made of two non-covalently linked subunits. The α-subunit structure, hCGα, has 2 N-glycosylation sites, while the beta subunit, hCGß, has 2 N- and 4 O-glycosylation sites. This leads to numerous glycoforms. A method based on the analysis of hCG glycoforms at the intact level by nano-reversed phase liquid chromatography coupled to high resolution mass spectrometry (nanoLC-HRMS) with an Orbitrap analyzer was previously developed using a recombinant hCG-based drug, Ovitrelle®, as standard. It allowed the detection of about 30 hCGα glycoforms, but didn't allow the detection of hCGß glycoforms. This method was thus here significantly modified (addition of a pre-concentration step of the sample to increase the sample volume from 70 nl to 1 µl, optimization of the gradient slope and the nature and content of the acidic additive in the mobile phase). It led to an improvement of the separation of hCGα and hCGß glycoforms, which allowed for the first time the detection of 33 hCGß glycoforms at intact level. In addition, a higher number of hCGα glycoforms (42 in total, i.e. a 40% increase) was detected. The figures of merit of this new method were next assessed. The relative standard deviations (RSDs) of the retention time ranged between 0.02 and 0.95% (n = 3), with an average value of 0.36% for the alpha glycoforms and between 0.01 and 1.08% (n = 3) with an average value of 0.23% for the beta glycoforms. The RSDs of the relative peak area measured on the extracted ion chromatogram of each glycoform were below 20% (n = 3), with an average value of 9.8%, thus allowing semi-relative quantification. Therefore, this method has a high potential for rapid quality control aiming for the detection and comparison of glycoforms present in glycoprotein-based pharmaceutical preparations.

External validation of models to predict the outcome of pregnancies of unknown location: a multicentre cohort study.

OBJECTIVE: To validate externally five approaches to predict ectopic pregnancy (EP) in pregnancies of unknown location (PUL): the M6P and M6NP risk models, the two-step triage strategy (2ST, which incorporates M6P), the M4 risk model, and beta human chorionic gonadotropin ratio cut-offs (BhCG-RC). DESIGN: Secondary analysis of a prospective cohort study. SETTING: Eight UK early pregnancy assessment units. POPULATION: Women presenting with a PUL and BhCG >25 IU/l. METHODS: Women were managed using the 2ST protocol: PUL were classified as low risk of EP if presenting progesterone ≤2 nmol/l; the remaining cases returned 2 days later for triage based on M6P. EP risk ≥5% was used to classify PUL as high risk. Missing values were imputed, and predictions for the five approaches were calculated post hoc. We meta-analysed centre-specific results. MAIN OUTCOME MEASURES: Discrimination, calibration and clinical utility (decision curve analysis) for predicting EP. RESULTS: Of 2899 eligible women, the primary analysis excluded 297 (10%) women who were lost to follow up. The area under the ROC curve for EP was 0.89 (95% CI 0.86-0.91) for M6P, 0.88 (0.86-0.90) for 2ST, 0.86 (0.83-0.88) for M6NP and 0.82 (0.78-0.85) for M4. Sensitivities for EP were 96% (M6P), 94% (2ST), 92% (N6NP), 80% (M4) and 58% (BhCG-RC); false-positive rates were 35%, 33%, 39%, 24% and 13%. M6P and 2ST had the best clinical utility and good overall calibration, with modest variability between centres. CONCLUSIONS: 2ST and M6P performed best for prediction and triage in PUL. TWEETABLE ABSTRACT: The M6 model, as part of a two-step triage strategy, is the best approach to characterise and triage PULs.

Early and late pregnancy loss in women with polycystic ovary syndrome undergoing IVF/ICSI treatment: a retrospective cohort analysis of 21 820 pregnancies.

OBJECTIVE: To examine early and late pregnancy loss in women with and without polycystic ovary syndrome (PCOS) undergoing IVF/ICSI transfers. DESIGN: Retrospective cohort study. SETTING: Reproductive medicine centre at a tertiary hospital. POPULATION: We studied women with a positive ß-human chorionic gonadotropin (ß-hCG) after in vitro fertilisation/intra-cytoplasmic sperm injection (IVF/ICSI) treatment from May 2014 to April 2019. METHODS: Odds ratios (OR) for early (≤13 weeks) and late (>13 weeks) pregnancy loss were calculated among women with and without PCOS for plurality of the pregnancy with adjustment for confounding factors. MAIN OUTCOME MEASURES: Early pregnancy loss (EPL) and late pregnancy loss (LPL). RESULTS: From 21 820 women identified with a positive ß-hCG, 2357 (10.8%) women had PCOS, and 19 463 (89.2%) women did not. EPL occurred in 16.6% (391) of women with PCOS versus 18.3% (3565) in women with non-PCOS (OR 0.89, 95% CI 0.79-0.99, P = 0.04). After adjustment for age and other confounders, the rate of EPL was not statistically significantly associated with PCOS status (adjusted OR [aOR] 0.91, 95% CI 0.80-1.05). Women with PCOS demonstrated a higher rate of LPL (6.4% in PCOS versus 3.6% in non-PCOS, OR 1.81, 95% CI 1.48-2.21, P < 0.001). In multivariable analysis, the potential impact of PCOS was less strong (aOR 1.38, 95% CI 0.96-1.98), with BMI and maternal comorbidities also associated with LPL (aOR 1.08, 95% CI 1.04-1.1 and aOR 2.07, 95% CI 1.43-3.00, respectively). CONCLUSIONS: Polycystic ovary syndrome was not independently associated with EPL. There was an increased risk of LPL but this difference was not statistically significant. TWEETABLE ABSTRACT: Polycystic ovary syndrome women are at increased risk of late pregnancy loss, partly driven by elevated BMI and maternal comorbidities.

Non-invasive molecular assessment of human embryo development and implantation potential.

In vitro fertilization (IVF) is the most common assisted reproductive technology used to treat infertility. Embryo selection for transfer in IVF cycles relies on the morphological evaluation by embryologists, either by conventional microscopic assessment or more recently by time-lapse imaging systems. Despite the introduction of time-lapse imaging improvements in IVF success rates have failed to materialize, therefore alternative approaches are needed. Recent studies have shown that embryos resulting in successful pregnancy differ in their secretome and metabolism compared to embryos that fail to implant, suggesting that molecular analysis of embryo culture medium could assist in non-invasive single embryo selection. However, this approach has yet to be adopted clinically due to the lack of appropriate highly sensitive screening technologies needed to assess volume-limited samples. Here we report the detection of hCGß, IL-8 and TNFα from conditioned culture media of single human embryos using electrochemical impedance spectroscopy. The impedimetric immunosensors revealed that morphologically non-viable embryos produce higher levels of IL-8 and TNFα, associated with abnormal cell division and cell death, respectively. More importantly, hCGß detection was able to discriminate apparently morphologically identical viable embryos. This work brings an objective dimension to embryo selection, which could overcome the major limitations of morphology-based embryo selection for implantation. Future work should include the validation of these biomarkers in a large patient cohort.

Linker-free antibody conjugation for sensitive hydrogel microparticle-based multiplex immunoassay.

Multiplex immunoassay, or the simultaneous detection of multiple proteins in a single sample, is expected to enable a new level of protein analysis across diverse disciplines, such as medical diagnostics and biomarker discovery. A bead-based assay using graphically encoded hydrogel microparticles synthesized using stop flow lithography has been a promising platform because of its high multiplex capacity and its superior sensitivity and dynamic range compared to the enzyme-linked immunosorbent assay (ELISA). The functionalization of these particles has been dependent on the use of a heterobifunctional linker to conjugate the capture antibodies on the hydrogel. However, the linker chemistry, which is based on linking the primary amine groups of antibodies with acrylate functional groups on the hydrogel monomer, is vulnerable to hydrolysis in aqueous conditions and can potentially damage the antigen binding region of the antibody. In this work, we introduce a new antibody conjugation method that avoids the use of the linker and further enhances the sensitivity of hydrogel microparticle-based immunoassays. Disulfide bonds in antibodies are reduced to liberate free thiols, which can directly bond with the double bonds remaining in the hydrogel after particle synthesis. We characterize the optimal reduction of antibodies for producing the highest detection signal and demonstrate an average two-fold improvement in sensitivity compared to the linker-dependent antibody conjugation method. Lastly, we validate the accuracy and specificity of the multiplex assays with particles conjugated with antibodies using the linker-free method.

Early prediction of the success of methotrexate treatment success by 24-hour pretreatment increment in HCG and day 1-4 change in HCG.

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.

Clinical application of immunomagnetic reduction for quantitative analysis of beta-subunit of human chorionic gonadotropin in blastocyst culture media to differentiate embryo quality.

BACKGROUND: The most important factor for a successful pregnancy after in vitro fertilization is embryo quality. The aim of this study was to explore the possibility that using the immunomagnetic reduction (IMR) assay to quantitatively measure ß-subunit of human chorionic gonadotropin (ß-hCG) in blastocyst culture media to differentiate embryo quality. METHODS: This was a prospective case-control study including 28 samples of blastocyst culture media. We used single-step blastocyst culture and IMR assay to analyze ß-hCG concentrations in culture media. We also explored the relationship between IMR signals of ß-hCG and morphological grading of blastocysts. RESULTS: ß-hCG concentration-dependent IMR signals were highly correlated with blastocyst morphological quality (Spearman correlation coefficient: 0.731). Receiver-operating characteristic curve analysis showed a cut-off IMR value to differentiate embryo quality of 0.873%, with an area under the curve of 0.947, sensitivity of 0.882 and specificity of 0.818. Furthermore, subanalysis also revealed a positive correlation between ß-hCG concentration-dependent IMR signals and trophectoderm grading, with a Spearman correlation coefficient of 0.576. CONCLUSIONS: An IMR assay can quantitatively measure ß-hCG in blastocyst culture media, and may be a potential clinical tool to assist in the assessment of good blastocyst quality before embryo transfer.

Use of beta subunit of human chorionic gonadotropin assay as a diagnostic tool for prelabor rupture of membranes.

PURPOSE: The study aimed at assessment of the accuracy of the ß-hCG test in vaginal washing fluid for diagnosis of prelabor rupture of membranes (PROM). PATIENTS AND METHODS: Two groups of pregnant women from 17 to 38 weeks of gestation were recruited. The first group (PROM group) included 50 pregnant women with unequivocal PROM. The other group included 50 pregnant women with intact membranes. A sterile speculum examination was performed. If less than 5 cc was collected or no fluid found, 10 cc sterile saline was sprinkled on the vaginal wall and 5 cc were recollected in a sterile syringe. Two drops of collected fluid were used for qualitative testing of ß-hCG. The remaining fluid was used for quantitative assessment of ß-hCG. RESULTS: The quantitative ß-hCG test results were significantly higher in PROM group (median and range: 138.5 (23-475) versus 13 (1-55); the difference in medians and 95% CI: 105 (91-166); p value: <.001). The qualitative ß-hCG test was positive in 42/50 (84%) of the PROM group, while it was negative in 50/50 (100%) of the intact membranes group. Areas under receiver operating characteristics (AUC) for both the quantitative and qualitative ß-hCG tests were high (0.97, 95% CI: 0.91-0.99, p value: <.001 and .92, 95% CI: 0.84-0.96, p value: <.001, respectively). The suggested cut-off of ß-hCG for the quantitative test was 32 mIU/ml. The sensitivity of quantitative and qualitative tests are: 94, 95% CI: 83.5-98.7% and 84, 95% CI: 70.9-92.8%, respectively. The specificity of quantitative and qualitative tests are: 94, 95% CI: 83.5-98.7% and 100, 95% CI: 92.9-100%, respectively. CONCLUSION: ß-hCG test (either quantitative or qualitative) in vaginal washing fluid can be used in the diagnosis of PROM in both preterm and term cases.

Cytokeratin 7, inhibin, and p63 in testicular germ cell tumor: superior markers of choriocarcinoma compared to ß-human chorionic gonadotropin.

Choriocarcinoma can be difficult to differentiate from other subtypes of testicular germ cell tumor and can occur unexpectedly in a distant, late metastasis. The aim of this investigation was to identify a marker superior to ß-human chorionic gonadotropin (ß-hCG) for choriocarcinoma. Sixty-two primary and metastatic testicular germ cell tumors (27 choriocarcinomas, 19 yolk sac tumors, 29 embryonal carcinomas, 28 seminomas, 22 teratomas, 3 epithelioid trophoblastic tumors [ETTs]) were analyzed for immunohistochemical expression of cytokeratin 7 (CK7), inhibin, p63, and ß-hCG. All choriocarcinomas and ETTs were strongly positive for CK7, whereas seminomas were negative and 52% of embryonal carcinomas had weak reactivity. Eighty-four percent of yolk sac tumors and 59% of teratomas were CK7 positive. Eighty-nine percent of choriocarcinomas and 100% of ETTs were positive for inhibin, with reactivity highlighting syncytiotrophoblasts, whereas seminomas, embryonal carcinomas, yolk sac tumors, and teratomas were negative. Eighty-five percent of choriocarcinomas expressed p63, with staining mostly in mononucleated trophoblasts, whereas seminomas, embryonal carcinomas, and yolk sac tumors were negative. Teratomas expressed p63 in 32% of cases. ß-hCG was reactive in 96% of choriocarcinomas, 33% of ETTs, 46% of seminomas, 54% of embryonal carcinomas, 47% of yolk sac tumors, and 32% of teratomas. ß-hCG staining within other subtypes was more likely if choriocarcinoma was present elsewhere in the tumor (P = .0002). CK7 is a highly sensitive marker for choriocarcinoma and differentiates choriocarcinoma from seminoma and embryonal carcinoma. Inhibin and p63 are sensitive and specific for choriocarcinoma versus seminoma, embryonal carcinoma, and yolk sac tumor. To identify choriocarcinoma, CK7, inhibin, and p63 are superior to ß-hCG.

Hepatic toxicity following actinomycin D chemotherapy in treatment of familial gestational trophoblastic neoplasia: A case report.

RATIONALE: Familial hydatidiform mole is extremely rare while familial gestational trophoblastic neoplasia (GTN) has never been reported. Inspired by 2 biological sisters with postmolar GTN and liver toxicity, we reviewed susceptible maternal-effect genes and explored the role of possible drug transporter genes in the development of GTN. PATIENT CONCERNS: We reported one Chinese family where the two sisters developed postmolar GTN while experiencing fast remission and significant hepatic toxicity from actinomycin D chemotherapy. DIAGNOSES: The index pregnancy was diagnosed with curettage. The following GTN was confirmed when there was a rise in beta-hCG for three consecutive weekly measurements over at least a period of 2 weeks. Computed tomography was used to identify lung metastasis. The elder sister was diagnosed with gestational trophoblastic neoplasia (III: 2) while the younger sister was diagnosed as III: 3 according to WHO scoring system. INTERVENTIONS: Patients were treated with actinomycin D of 10 µg/kg intravenously for 5 days every 2 weeks. When hepatic toxicity was indicated, polyene phosphatidyl choline and magnesium isoglycyrrhizinate were prescribed. OUTCOMES: Both patients responded extremely well to the 5-day actinomycin D regimen. Beta-hCG remained less than 2 mIU/ml after 5 cycles while computed tomography scan showed downsized pulmonary nodules. Both experienced significant rise in ALT and AST levels that could be ameliorated with corresponding medication. Monthly followed-up showed negative beta-hCG levels and normal liver enzyme levels. LESSONS: We speculated that the known or unknown NLRP7 and KHDC3L mutations might be correlated with drug disposition in liver while liver drug transporters such as P-glycoprotein family that are also expressed in trophoblasts might be correlated to GTN susceptibility. Future genomic profiles of large samples alike using next generation sequencing are needed to confirm our hypothesis and discover yet unknown genes.

The first trimester aneuploidy biochemical markers in IVF/ICSI patients have no additional benefit compared to spontaneous conceptions in the prediction of pregnancy complications.

OBJECTIVES: The aim of this study was to determine if the levels of biochemical aneuploidy markers in in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) pregnancies differ from those in spontaneous pregnancies and to verify if biochemical markers could predict pregnancy outcome in IVF/ICSI gestations. METHODS: This was a prospective observational study performed in a group of 551 patients who underwent a combined first trimester prenatal screening (ultrasound scan and serum markers). All patients were divided into two groups according to the mode of conception: IVF/ICSI pregnancies (study group) and spontaneous conceptions (control group). The concentrations of first trimester biochemical markers were presented as multiples of median (MoM) and were compared between the study and control groups. Analysed pregnancy complications included: preterm delivery (PTD), small for gestational age (SGA), gestational hypertension (GH), preeclampsia (PE) and gestational diabetes (GDM). RESULTS: The analysis was performed on 183 IVF/ICSI and 368 spontaneously conceived gestations, with complete data regarding obstetric outcome. There were no significant differences in the concentrations of biochemical markers between the analysed groups. Pregnancy-associated plasma protein-A (PAPP-A) levels were lower in hypertensive than in normotensive patients, although the difference was not significant. Twenty-three patients had GDM (12.5%), 16 had GH or PE (8.7%), SGA was diagnosed in 18 (9.8%) and 25 delivered preterm (13.6%). CONCLUSIONS: The trend for lower PAPP-A MoM was visible in all affected patients, although the results did not reach statistical significance. The first trimester biochemical markers in assisted reproduction technique (ART) pregnancies do not seem to have additional effect on predicting the risk of pregnancy complications.

On-chip signal amplification of magnetic bead-based immunoassay by aviating magnetic bead chains.

In this work, a Lab-on-a-Chip (LOC) platform is used to electromagnetically actuate magnetic bead chains for an enhanced immunoassay. Custom-made electromagnets generate a magnetic field to form, rotate, lift and lower the magnetic bead chains (MBCs). The cost-effective, disposable LOC platform was made with a polymer substrate and an on-chip electrochemical sensor patterned via the screen-printing process. The movement of the MBCs is controlled to improve the electrochemical signal up to 230% when detecting beta-type human chorionic gonadotropin (ß-hCG). Thus, the proposed on-chip MBC-based immunoassay is applicable for rapid, qualitative electrochemical point-of-care (POC) analysis.

Gestación ectópica molar abscesificada sobre cicatriz de cesárea anterior, a propósito de un caso / Caesarean scar ectopic pregnancy, a case report

El embarazo molar es una forma anormal de gestación poco frecuente en nuestro medio. Su diagnóstico se suele producir como consecuencia de manifestaciones clínicas, que se confirman posteriormente, utilizando la determinación de beta-gonadotropina coriónica humana (B-HCG) en sangre y la ecografía transvaginal. El tratamiento se basa en la evacuación del tejido trofoblástico anómalo mediante legrado uterino aspirativo bajo control ecográfico. El seguimiento de este tipo de gestaciones posterior al tratamiento es muy importante, debido al riesgo de malignización y diseminación a otros órganos, que requiere en ocasiones tratamiento quimioterápico. La implantación trofoblástica en tejidos cicatriciales uterinos es un fenómeno poco usual y escasamente descrito en la literatura, y que dificulta el diagnóstico, tratamiento y seguimiento de este tipo de dolenciaS

Molar pregnancy is a very rare form of gestation. Current practices in its diagnosis are based on clinical manifestations, which are later confirmed by using a beta-human chorionic gonadotropin (B-HCG) blood test and transvaginal ultrasonography. The treatment is based on the removal of the trophoblastic abnormal tissue by uterine suction legrado under ultrasonographic control. Monitoring this type of gestation after treatment is of crucial importance due to the risk of malignisation and spread to other organs, requiring chemotherapy treatment in some cases. Trophoblastic implantation in uterine scar tissues is a rare and scarcely reported phenomenon that hinders the diagnosis, treatment, and follow-up of this type of pathology