Evaluation of the parameters in predicting single-dose methotrexate therapy success for ectopic pregnancy.

AIM: Methotrexate has demonstrated efficacy in treating ectopic pregnancies. This study explores factors influencing treatment success, focusing on laboratory and ultrasonographic findings, particularly the day 4 to day 1 ß-hCG level ratio. METHODS: Retrospective cohort study was conducted within patients diagnosed with tubal ectopic pregnancy. Patients' characteristics, ultrasound findings, laboratory data, and ß-hCG levels (days 1, 4, 7), and operation findings were reviewed. Women's characteristics were investigated who were treated with single dose of MTX (50 mg/m2). Patients who were performed surgery after MTX treatment were identified as MTX treatment failure. RESULTS: Among 439 women, 259 underwent surgery due to acute symptoms. Of those treated with MTX, 143 experienced treatment success, while 37 underwent surgery after MTX (MTX failure). Comparative analysis revealed significant differences in ß-hCG levels on admission (1128 and 4125 mIU/mL) and the day 4 to day 1 ß-hCG ratio (0.91 and 1.25). The overall MTX success rate was 79%, reaching 93% and 89% for ß-hCG levels <1000 mIU/mL and <2000 mIU/mL, respectively. Success dropped to 50% with levels exceeding 5000 mIU/mL. ROC analysis identified a crucial 2255 mIU/mL cut-off for ß-hCG (sensitivity 70.3% and specificity 68.5%) and a day 4 to day 1 ß-hCG ratio of 95.5% (sensitivity 84.7%, specificity 72.5%, positive predictive value 75.4%) for predicting MTX success. CONCLUSION: Establishing a ß-hCG cutoff can reduce hospital stay. The day 4 to day 1 ß-hCG ratio holds promise as a widely applicable predictor for MTX success or for determining MTX administration on day 4.

Persistently elevated serum concentrations of human chorionic gonadotropin (hCG).

OBJECTIVES: We describe a woman with constantly elevated hCG levels in serum. Since assay interference, pregnancy or cancer did not explain the elevated levels, we measured the concentrations of hCG, its ß subunit (hCGß) and its core fragment (hCGßcf) in serum and urine using specific assays, to understand the nature of the elevated hCG levels. METHODS: We used 3 assays for total hCG (these assays also recognize hCGß and to various degrees hCGßcf), 3 for intact hCG heterodimer, 3 for free hCGß and one for hCGßcf. RESULTS: With an hCG assay detecting total hCG the serum concentrations were in the range of 150-260 IU/L for the whole study period of almost 5 years, except for a peak of 1,200 IU/L, coinciding with a spontaneous abortion. Quantitation of different forms of hCG with specific immunoassays showed that the immunoreactivity in serum consisted of hCGß. Urine contained hCGß and hCGßcf. CONCLUSIONS: The laboratory findings are in keeping with familial hCG syndrome. However, so far the condition remains to be determined in any family members. Elevated hCG levels without any explanation are problematic as they cause suspicion of cancer or ectopic pregnancy and may lead to harmful therapy. Specific assays, as used here, will aid in diagnosis of such cases.

CT measurement of breast glandular tissue and its association with testicular cancer.

OBJECTIVES: To evaluate the associations between breast glandular tissues diameters as determined by CT and b-hCG levels, histological types, tumour spread and prognosis in patients with testicular germ cell tumour. METHODS: Ninety-four patients with pre-treatment CT scan and markers (b-hCG, AFP, LDH) were retrospectively collected. A radiologist measured diameters in all CT examinations and correlation between diameters and log (b-hCG) was assessed (Pearson's coefficient). The ability of measured diameters to predict lymphatic and distant haematogenous metastatic spread was evaluated (ROC curves). The associations between measured diameter cut-off values of 20 and 25 mm and International Germ Cell Cancer Collaborative Group (IGCCCG) classification, lymphatic and distant haematogenous metastatic spread and histological subtypes were evaluated (chi squared test). RESULTS: Breast glandular diameters correlated to log(b-hCG) (r = 0.579) and predicted distant haematogenous metastatic spread (AUC = 0.78). Worse prognosis (intermediate or poor IGCCCG) was shown for 20 mm (27.3 vs. 4.2 %, p = 0.005) and 25 mm (33.3 vs. 6.1 %, p = 0.014). A diameter of 25 mm was associated with non-seminoma (91.7 vs. 48.8 %, p = 0.005). CONCLUSION: Breast glandular tissue diameters correlated with log(b-hCG) and predicted distant haematogenous metastases. Twenty and 25 mm were associated with worse prognosis and 25 mm was able to distinguish between seminoma and non-seminoma. KEY POINTS: • CT breast glandular tissue diameter correlates with log(b-HCG) • Gynaecomastia in CT is associated with worse prognosis • Gynaecomastia in CT is associated with non-seminoma histological subtype.

Serum hCG-ß levels of postovulatory day 12 and 14 with the sequential application of hCG-ß fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle.

PURPOSE: To investigate hCG-ß level on postovulatory day (POD) 12 and its fold increase as predictors for pregnancy outcome after in vitro fertilization (IVF) cycles. METHODS: A retrospective cohort study was performed in total 1408 fresh and 598 frozen cycles between November 2008 and October 2011, which resulted in biochemical pregnancy, early pregnancy loss, or live birth of singleton pregnancy. The serum hCG-ß levels of POD 12 and 14 were compared among biochemical pregnancy, early pregnancy loss, and live birth groups. The cutoff values of POD 12 and 14 hCG-ß levels and the degree of hCG-ß increase from POD 12 to 14 were determined for each pregnancy outcome. RESULTS: POD 12 and 14 hCG-ß levels stratified based on pregnancy outcomes were significantly different among the biochemical pregnancy, early pregnancy loss, and live birth in both fresh and frozen cycles. Serum hCG-ß levels of POD 12 and 14 and the fold increase of hCG-ß levels from POD 12 to 14 significantly predict pregnancy outcomes after fresh and frozen cycles. Among these, the cutoff value of POD 14 hCG-ß had the highest sensitivity and positive predictive value (PPV). In fresh cycles, the cutoff values of POD 12 and 14 serum hCG-ß levels for clinical pregnancies were 30.2 mIU/mL (sensitivity 81.3 %, specificity 79.6 %, and PPV 92.3 %) and 70.5 mIU/mL (sensitivity 88.4 %, specificity 85.2 %, and PPV 94.7 %). In pregnancies with POD 12 serum hCG-ß levels ≥30.2 mIU/mL, the cutoff level of increase of hCG-ß for clinical pregnancy was 2.56 (sensitivity 73.6 %, specificity 72.4 %, and PPV 97.8 %). Sequential application of cutoff values such as POD 12 hCG-ß and fold increase of hCG-ß improved predictability of pregnancy outcome as compared with that of POD 12 hCG-ß alone. The cutoff values of POD 12 and 14 serum hCG-ß levels for live birth were 40.5 mIU/mL (sensitivity 75.2 %, specificity 72.6 %, PPV 78.9 %) and 104.5 mIU/mL (sensitivity 80.3 %, specificity 74.1 %, PPV 80.8 %). In the frozen cycles, the cutoff values of POD 12 and 14 serum hCG-ß level for clinical pregnancy were 31.5 IU/L (sensitivity 80.4 %, specificity 71.1 % and PPV 90 %) and 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %). In pregnancies with POD 12 serum hCG-ß level ≥31.5 mIU/mL, the cutoff value for fold increase of hCG-ß was 2.38 for clinical pregnancy (sensitivity 81.6 %, specificity 71.4 % and PPV 87.9 %). The cutoff values of POD 12 and 14 for live birth were 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %) and 101.6 mIU/mL (sensitivity 79.6 %, specificity 71.1 %, PPV 78.4 %). Sequential application of cutoff values for POD 12 hCG-ß level and fold increase of hCG-ß significantly increased PPV for live birth but not clinical pregnancy in frozen cycles. CONCLUSIONS: Early prediction of pregnancy outcome by using POD 12 and 14 cutoff levels and sequential application of cutoff value of fold increase could provide appropriate reference to health care providers to initiate earlier management of high-risk pregnancies and precise follow-up of abnormal pregnancies.

Serum ß-hCG levels post-treatment of ectopic pregnancy with a single dose of intramuscular methotrexate.

BACKGROUND: The cytotoxic management of ectopic pregnancy using a single dose of intramuscular methotrexate injection has been well established as effective for a select number of women with unruptured tubal ectopic pregnancy where there are minimal symptoms. AIM: The purpose of this study was to create centile curves of serum ß-hCG levels following successful treatment with a single dose of 50 mg/m(2) of intramuscular methotrexate to treat ectopic pregnancy. MATERIAL AND METHODS: Data were retrieved from women treated at the Royal Women's Hospital for ectopic pregnancy between 2006 and 2012. Only women with minimal symptoms, initial serum ß-hCG ≤5000 IU/L and ectopic mass size of ≤35 mm on ultrasound were included. Two hundred and fifty-three cases of ectopic pregnancy were analysed. RESULTS: Initial ß-hCG of women in the study ranged from 18 to 3995 IU/L with a median of 497 (25th to 75th centiles; 222-1160) IU/L. The median levels of ß-hCG levels at day 4, 7 and 14 postmethotrexate injection were 73.8, 47.2 and 10.4% of the initial ß-hCG level, respectively. The 90th centiles of ß-hCG levels at day 4, 7 and 14 were 124.7, 93.8 and 40.0% of initial ß-hCG level, respectively. CONCLUSIONS: Whilst no comparison with those unsuccessfully treated was made, pending further validation studies, the use of these curves may reduce the reliance on specialist units and streamline care for many women with ectopic pregnancy, such as those whose ß-hCG regress in line with centile values without crossing a certain threshold.

Beta-human Chorionic Gonadotropin-secreting Lung Adenocarcinoma.

Overexpression of beta-human chorionic gonadotropin (ß-hCG) is frequently associated with germ cell tumours, especially choriocarcinoma. Ectopic secretion of ß-hCG by non-small cell lung cancer is exceptional. We present an exceedingly rare case of pulmonary adenocarcinoma that secretes ß-hCG. Our patient is a 62-year-old postmenopausal woman, a nonsmoker, who presented with a six-month history of progressive dyspnoea, associated with decreased appetite and significant weight loss. Her serum ß-hCG was very high (11211.9 mIU/ml), which prompted investigations to exclude germ cell tumour. Radiological imaging revealed a 10-cm right lung mass with adrenal metastasis. No other focal lesions were detected. Microscopy of the lung biopsy specimen showed replacement of normal lung tissue by sheets of malignant cells, forming vague glands in some areas. Immunohistochemically, the malignant cells showed focal immunopositivity for thyroid transcription factor 1 (TTF-1), napsin A, cytokeratin 7 (CK7) and ß-hCG. A diagnosis of ß-hCG-secreting pulmonary poorly differentiated adenocarcinoma was rendered. Serum ß-hCG level decreased significantly to 168.6 mIU/ml after the first cycle of chemotherapy. In conclusion, ß-hCG expression in lung cancer should be recognised to facilitate prompt diagnosis and initiation of appropriate intervention.

Uterine malignant leiomyosarcoma associated with high levels of serum beta-human chorionic gonadotropin: A case report.

We present the case of a 54-year-old woman diagnosed with uterine leiomyosarcoma that produced beta-human chorionic gonadotropin (ß-hCG), evident by both serum and immunohistologic examination. Based on this and similar cases from the available literature, ß-hCG-producing sarcomas tend to have poorer prognosis, indicating that ß-hCG could potentially be used as a marker of disease status and response to the therapy; however, this association is inconsistent and should be further investigated.

Interstitial ectopic pregnancy rupture at 17 weeks of gestation: A case report and literature review.

Interstitial pregnancy is a rare type of ectopic pregnancy that commonly results in uterine rupture and life-threatening haemorrhage. Interstitial ectopic pregnancies are associated with a 2-5% mortality rate and a high risk of uterine rupture before 12 weeks of gestation when compared to tubal pregnancy. Due to the thickness and distensibility of the interstitial segment of the Fallopian tube, ectopic pregnancy in this location attains a considerable size before complications arise. Unfortunately, this clinical entity may prove to be a diagnostic challenge, leading to delays in treatment and significant morbidity and mortality in women of reproductive age. Herein, we report a case of a ruptured interstitial ectopic pregnancy occurring at 17 weeks of gestation that was successfully managed with surgical intervention, after proving to be a diagnostic challenge.

Misdiagnosis of intramural ectopic pregnancy and invasive gestational trophoblastic disease on ultrasound: A challenging case at Tu Du Hospital in Vietnam in COVID-19 pandemic peak and mini-review of literature.

Differentiation between intramural ectopic pregnancy and molar ectopic pregnancy is very difficult because of their exceptional rarity. Herein, we present a misdiagnosed case of intramural pregnancy and invasive trophoblastic disease on ultrasound. A 45-year-old female patient was admitted to our tertiary referral hospital due to abdominal pain and unusual ultrasonography findings. Initially, a diagnosis of intramural ectopic pregnancy was identified based on transvaginal color Doppler ultrasonography, 3-dimensional ultrasound, and serial serum beta-human chorionic gonadotropin, thus the patient underwent laparotomy with hysterectomy. However, the histopathological endpoint showed an invasive trophoblastic disease. Clinically, this pathology should be included in the differential diagnosis of intramural ectopic pregnancy since an imaging scan remains quite unclear.

Association of maternal exposure to bisphenol A with her ß-hCG level and neonatal anthropometric measures.

Bisphenol A (BPA) is one of the organic compounds that might interfere with estrogenic receptors, which would make difficulties in pregnancy hormones and fetal growth. Human chorionic gonadotropin (ß-hCG) is one of the important pregnancy hormones that might be affected by environmental pollutants. The aim of this study is to investigate the probable impacts of maternal exposure to BPA on anthropometric measures of newborns. This cross-sectional study was conducted in 2019-2020 in Isfahan, Iran. During the first trimester of pregnancy, we measured the urinary BPA concentration and serum ß-hCG level of 120 pregnant women, who were randomly selected from participants of a birth cohort. BPA concentration was measured using gas chromatography-mass spectrometry (GC-MS). Serum blood sample was derived and used for ß-hCG analysis. Anthropometric measurement of neonates was conducted at the time of birth. BPA and ß-hCG level were grouped by quartiles, and their associations with birth weight, height, and head circumference were tested using multiple linear regression model. The adjustment was done for urine creatinine, gender, and gestational age, as well as maternal age, body mass index, and education level. Data of 119 pairs of mothers and infants were available for the present study. The mean (SD) age of mothers was 29.19 (5.75) years; 56.3% of newborns were boys. Geometric mean of urinary BPA and ß-hCG concentrations were 0.36 ng/g crea. (creatinine) and 17736 mIU/ml, respectively. Across the BPA tertiles, the differences in mean values were not significant for none of the anthropometric measurements and gestational age (GA). Furthermore, no significant association existed between unadjusted and adjusted tertiles of BPA and ß-hCG with abovementioned birth outcomes. It seems that the non-significant association found in this study is because of low levels of urinary BPA levels than in other studies; the adverse effects on infants might be related to high concentration of BPA passed from placenta. Future longitudinal studies with large sample size are necessary to document the adverse health effects of maternal exposure to endocrine disruptor chemicals including BPA.

Amenorrhea and elevated ßhuman chorionic gonadotropin of unknown origin: An unexpected location of choriocarcinoma.

Choriocarcinoma is a rare malignancy originating from trophoblastic cells that is known to arise from the placenta. In this report, we describe the case of a 28-year-old female who consulted for amenorrhea and elevated ßhCG mimicking a pregnancy of an unknown location, which ultimately turned out to be primary choriocarcinoma of the lung.

Nonseminomatous Germ-Cell Tumor Presenting as Bilateral Adrenal Masses.

OBJECTIVE: Many tumors can metastasize to the adrenal glands, making the diagnosis of adrenal masses challenging. Awareness that rare primary tumors can metastasize to the adrenals and consideration of biopsy for their diagnosis, sometimes at extra-adrenal sites, is essential to prevent unnecessary adrenalectomies and facilitate the right treatment. We report a rare case of bilateral adrenal masses due to metastasis from a nonseminomatous germ-cell tumor of a retroperitoneal lymph node origin. METHODS: The diagnosis of the adrenal masses from the nonseminomatous germ-cell tumor of a retroperitoneal lymph node origin was based on a retroperitoneal lymph node core biopsy. An initial core biopsy of the adrenal gland revealed necrotic tissue and inflammatory cells without evidence of malignancy. Due to nondiagnostic findings, the core biopsy was repeated, which showed degenerating cells with a high mitotic index and immunohistochemical staining positive for vimentin, suggesting the possibility of a high-grade sarcoma. A retroperitoneal lymph node biopsy was performed. The patient was started on chemotherapy. RESULTS: A 34-year-old man presented with acute left upper-abdominal pain of 2 weeks and tenderness on the left upper quadrant of the abdomen, and he was found to have bilateral adrenal masses. Laboratory results showed the following: adrenocorticotropic hormone 41 pg/mL (7-69 pg/mL), metanephrine <0.1 nmol/L (0-0.49 nmol/L), normetanephrine 0.99 nmol/L (0-0.89 nmol/L), and morning cortisol 3.1 µg/dL after a 1-mg dexamethasone-suppression test. His dehydroepiandrosterone sulfate level was 62 µg/dL (120-520 µg/dL), and 17OH progesterone level was 36 ng/dL (<138 ng/dL); androstenedione and serum estradiol levels were normal. Laboratory tests for tumor markers revealed the following: testosterone 21 ng/dL (241-827 ng/dL), prostate-specific antigen 0.57 ng/mL (0-4 ng/mL), alpha-fetoprotein 1.9 IU/mL (0.6-6 IU/ml), and beta-human chorionic gonadotropin 134 mIU/mL (0-1 mIU/mL). CONCLUSION: We report a rare case of rapidly progressing adrenal masses in a young man, found to have metastasized from nonseminomatous germ-cell tumors. Histopathologic confirmation of the metastatic tumor was done, which prevented unnecessary adrenalectomy. The patient received appropriate chemotherapy.

Metastatic choriocarcinoma with hemorrhagic complications and spontaneous ovarian hyperstimulation syndrome: A case report.

Gestational choriocarcinoma is a malignant trophoblastic tumor arising from any gestational event, even with a long latency period, generally in the reproductive female. It is associated with a high level of beta-human chorionic gonadotropin. Its primary site is usually the uterus but not all patients have a detectable lesion in this site. Regression of the primary tumor after it has metastasized is not uncommon, and one-third of cases manifest as complications of metastatic disease. In this report we present an uncommon case of gestational choriocarcinoma with lung, liver and jejunal metastases at the time of diagnosis without evidence of pelvic disease, in 34-year-old woman. The main points of interest of our case were the development of the ovarian hyperstimulation syndrome with massive multicystic ovarian enlargement induced by high level of beta-human chorionic gonadotropin and the bleeding of jejunal and liver metastases, due to the high vascularity of the tumor tissue, a condition known as "Choriocarcinoma Syndrome". We will focus on the radiological findings of metastases, bleeding complications and ovarian hyperstimulation syndrome.

Long-term survival in multiresistant metastatic choriocarcinoma after pembrolizumab treatment: A case report.

•Checkpoint inhibitor therapy affecting PD-L1 as treatment for advanced solid tumors.•Success in trial pembrolizumab therapy in multiresistant metastatic choriocarcinoma.•Long-term remission after pembrolizumab therapy in multiresistant choriocarcinoma.•Only six reported cases, one with comparable follow-up and outcome.

Evaluation of indications for amniocentesis in cases of normal fetal ultrasound results.

OBJECTIVES: The objective of this study was to analyze indications for amniocentesis in cases of patients with normal fetal ultrasound results between 11+0 and 13+6 weeks of gestation. MATERIAL AND METHODS: The results of first-trimester screening tests performed between 2014 and 2018 on 6,863 patients of the Prenatal Testing Outpatient Clinic at the Clinical Department of Obstetrics and Gynecology, Pomeranian Medical University, Szczecin, Poland, were analyzed. The inclusion criteria were a singleton pregnancy and normal results of fetal ultrasound between 11+0- and 13+6-weeks' gestation. Depending on the calculated risk of fetal trisomy 21, the patients were divided into three groups (group A = RS > 1:300, group B = RS 1:300 - 1:999, group C = RS ≤ 1:1000). Subsequently, values such as PAPP-A and fß-hCG protein levels and maternal age were analyzed for each of the groups. RESULTS: The patients, 6,310 (91.94%) met the inclusion criteria. A high risk of fetal trisomy 21 was identified for 514 women (8.15%). Group B had 733 (11.62%) and group C 5,063 (80.23%) patients. In group A, an fß-hCG level of ≥ 2.000 MoM was shown for 50.97% of the women. A PAPP-A level ranging from 0.001 to 0.499 MoM was observed for 38.72% of group A patients. The mean maternal age in groups A, B and C was 36.45, 36.08 and 31.64 years, respectively. CONCLUSIONS: In the first-trimester, patients with normal ultrasound results obtained during prenatal screening tests, the main cause of an increased risk of trisomy 21 was elevated PAPP-A and fß-hCG concentrations. According to this paper's authors, in these cases extension of diagnosis to include other gestational complications, e.g. preeclampsia, should be considered.

Raloxifene augmentation in men and women with a schizophrenia spectrum disorder: A study protocol.

Although acute psychotic symptoms are often reduced by antipsychotic treatment, many patients with schizophrenia are impaired in daily functioning due to the persistence of negative and cognitive symptoms. Raloxifene, a Selective Estrogen Receptor Modulator (SERM) has been shown to be an effective adjunctive treatment in schizophrenia. Yet, there is a paucity in evidence for raloxifene efficacy in men and premenopausal women. We report the design of a study that aims to replicate earlier findings concerning the efficacy of raloxifene augmentation in reducing persisting symptoms and cognitive impairment in postmenopausal women, and to extend these findings to a male and peri/premenopausal population of patients with schizophrenia. The study is a multisite, placebo-controlled, double-blind, randomised clinical trial in approximately 110 adult men and women with schizophrenia. Participants are randomised 1:1 to adjunctive raloxifene 120 mg or placebo daily during 12 weeks. The treatment phase includes measurements at three time points (week 0, 6 and 12), followed by a follow-up period of two years. The primary outcome measure is change in symptom severity, as measured with the Positive and Negative Syndrome Scale (PANSS), and cognition, as measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Secondary outcome measures include social functioning and quality of life. Genetic, hormonal and inflammatory biomarkers are measured to assess potential associations with treatment effects. If it becomes apparent that raloxifene reduces psychotic symptoms and/or improves cognition, social functioning and/or quality of life as compared to placebo, implementation of raloxifene in clinical psychiatric practice can be considered.

Evidence for, and Associated Risks with, the Human Chorionic Gonadotropin Supplemented Diet.

Trend diets can be commonplace amongst those who are trying to lose weight but in most cases there is some shred of evidence to suggest they might be of some benefit. Seldom is there a diet which is such a fad that it is not only completely unfounded but also potential harmful. The human chorionic gonadotropin or "hCG diet" is such a diet, which after half a century still has no evidence to support its efficacy; in fact all scientific publications subsequent to the original article counter these claims. In this short communication, we review the literature and present data on exactly what some of the hCG diet preparations actually contain and highlight that, based on current data, these may do more harm than good. It is worrying that more consideration is not given to the possible danger of administration of hCG preparations to individuals without an evidence-based rational.

Characterizing urinary hCGßcf patterns during pregnancy.

OBJECTIVE: Elevated concentrations of hCG beta core fragment (hCGßcf) are known to cause false-negative results in qualitative urine pregnancy test devices, but the pattern of urinary hCGßcf during normal pregnancy has not been well characterized. Here, we evaluate the relationship between urine hCG, hCGßcf, and hCG free ß subunit (hCGß) during pregnancy. DESIGN AND METHODS: Banked second trimester urine specimens from 100 pregnant women were screened for high concentrations of hCGßcf using a qualitative point-of-care device known to demonstrate false-negative results in the presence of elevated hCGßcf concentrations. Additional first and third trimester specimens from the same pregnancy were obtained from 10 women who generated negative/faint positive results, 5 women who generated intermediate positive results, and 10 women who generated strong positive results on the point-of-care device. Intact hCG, hCGßcf, hCGß, and specific gravity were quantified in these 75 specimens. RESULTS: Urinary hCGßcf concentrations were greater than intact hCG concentrations at all times. A strong correlation (r(2)=0.70) was observed between urine intact hCG and hCGßcf concentrations. A poor correlation was observed between specific gravity and intact hCG (r(2)=0.32), hCGß (r(2)=0.32), and hCGßcf (r(2)=0.32). The highest hCGßcf concentrations were observed between 10 and 16weeks gestation but individual women demonstrated very different patterns of hCGßcf excretion. CONCLUSIONS: Urine specimens with elevated hCGßcf are frequently encountered during pregnancy but hCGßcf excretion patterns are unpredictable. Manufacturers and clinicians must appreciate that hCGßcf is the major immunoreactive component in urine during pregnancy and must design and interpret qualitative urine hCG test results accordingly.

Estimating the hCGßcf in urine during pregnancy.

OBJECTIVE: Elevated urine concentrations of hCG beta core fragment (hCGßcf) are known to cause false negative qualitative point-of-care hCG test results, but limited information is available regarding urine hCGßcf. In this study, we evaluate the relationship between serum and urine hCG concentrations and the frequency of elevated urine hCGßcf concentrations. DESIGN AND METHODS: Paired serum and urine specimens were obtained from 60 women at various stages of pregnancy and hCG was measured using the Abbott Architect and Roche Cobas e602 assays. Urine specimens with the greatest difference in urine hCG concentrations between these two instruments were tested using a qualitative point-of-care device and hCGßcf was quantified using LC-MS/MS. RESULTS: Urine hCG concentrations were lower than serum and the magnitude of the difference depended on whether the hCG assay detected hCGßcf. Elevated hCGßcf concentrations (>280,000pmol/L) were observed in 12% of specimens from an unselected patient population. There was a significant correlation (r=0.97; p<0.0001) between the difference (Roche hCG-Abbott hCG) and the hCGßcf concentration as measured by LC-MS/MS (Roche-Abbott difference IU/L=(hCGßcf (pmol/L)∗0.131+656)). CONCLUSIONS: A correlation exists between serum and urine hCG concentrations but this correlation is variable. hCGßcf concentrations can be estimated using two automated assay reagent platforms that differ in their recognition of hCGßcf.

Evaluation of a semi-quantitative pregnancy device for susceptibility to interference caused by hCGßcf.

OBJECTIVE: Previous work has documented the ability of the Clearblue Advanced Test with Weeks Estimator, a new over-the-counter (OTC) urine hCG device, to accurately estimate weeks since ovulation in early pregnancy. In this study, the performance of this device in more advanced pregnancy was assessed. METHODS: The Clearblue Advanced Test with Weeks Estimator device was used to test solutions containing purified intact hCG and hCGßcf at concentrations consistent with early, middle and late pregnancy. Urine samples from three normal pregnant patients 9-13 weeks of gestation and from a patient 12 weeks of gestation known to generate false negative results on qualitative urine test devices due to excess hCGßcf were also evaluated. RESULTS: The Clearblue Weeks Estimator device gave expected results using solutions containing purified intact hCG and hCGßcf at concentrations observed throughout pregnancy. The device generated expected results using urine from three of four patients tested between 9 and 13 weeks of gestation. However, when urine from a patient with elevated concentrations of hCGßcf was used, the device correctly indicated pregnancy although the estimate for the date was incorrect. CONCLUSION: This device gave expected "pregnant" results using all samples tested. However, the "Weeks Estimator" should be interpreted with caution when used by patients after seven weeks of pregnancy.