Subunit Of Human Chorionic Gonadotropin Research Articles

Recurrent Ipsilateral Ectopic Pregnancy After Partial Salpingectomy

Ectopic pregnancies are those that occur in any place other than the uterine cavity. During the last 20 years, the incidence of ectopic pregnancies has increased fourfold and now accounts for up to 2% of all pregnancies in the United States [1]. Ectopic pregnancy is an important issue during early pregnancy because of the associated maternal morbidity and even mortality [2]. Here, we present two patients with unusual ipsilateral tubal remnant ectopic pregnancies: one occurring in the proximal remnant of the fallopian tube and the other in the distal remnant of the fallopian tube. Both patients had undergone previous partial salpingectomies with laparoscopy. In Case 1, a 38-year-old multigravid woman with a history of previous ectopic pregnancy had undergone laparoscopic right partial salpingectomy 2 years prior to this admission. She had suffered from low abdominal pain for 2 days and had a positive pregnancy test result at the emergency department (ED) of Taipei Medical University–Wan Fang Medical Center. The concentration of serum β subunit of human chorionic gonadotropin (β-hCG) at the ED was 8,869 mIU/mL. The findings of a pretreatment ultrasound examination performed at the ED were consistent with an empty uterus with a moderate amount of cul-de-sac fluid. An ectopic pregnancy with internal bleeding was suggested. The patient underwent therapeutic laparoscopic surgery with diagnostic dilatation and curettage (D&C). The findings of the laparoscopic surgery revealed hemoperitoneum and a bulging mass about 2 cm in diameter at the proximal end of the previous partial salpingectomy remnant area (Figure 1). All the intra-abdominal bloody contents were evacuated during surgery, and the portion of the tube was removed and sent for pathologic examination. Corpus luteum was noted in the patient’s left ovary. Histopathologic examination of the laparoscopic specimen showed a fallopian tube with trophoblast, which was consistent with the findings of a tubal pregnancy. Examination of the D&C specimen showed the existence of decidual tissues. Our patient was, therefore, diagnosed with an ipsilateral ectopic pregnancy in the proximal tubal remnant portion of the previous partial salpingectomy. In Case 2, a 29-year-old multigravid woman with a history of previous ectopic pregnancy had undergone laparoscopic right partial salpingectomy 3 years prior to this admission. At presentation, she was suffering from severe low abdominal pain and had a positive pregnancy test result at the obstetrics and gynecology clinic of Taipei Medical University–Wan Fang Medical Center. The serum level of β-hCG on admission was 14,638 mIU/mL. The findings of a pretreatment transvaginal ultrasound examination performed at our

Determination of median levels of the free β subunit of human chorionic gonadotropin in women from mainland China using a new time-resolved fluoroimmunoassay

The free beta subunit of human chorionic gonadotropin (free beta-hCG) is an important serum marker for biochemical screening. Its weekly median value varies with ethnicity. Most of the fluorometers for lanthanide chelates are designed for the detection of signals from europium (Eu(3+)) chelates only. We developed a two-site, one-step assay using two monoclonal antibodies (MAbs) against free beta subunit and beta subunit with Eu(3+) chelates as labels. Using the present assay, we evaluated 24,634 normal serum samples in Chinese pregnant women during 8-20 weeks of gestation. The detection limit using this assay was <0.05 ng/mL. The within-run and between-run imprecision was <6.0% and 7.0% using control material. Free beta-hCG concentrations measured using the current assay in 999 maternal serum samples correlated well with those obtained by samarium (Sm(3+))-labeled DELFIA free hCGbeta assay (r=0.987). The medians for 8-20 weeks for maternal serum free beta-hCG were higher in the women from mainland China compared to reports from other countries. The present assay is suitable for use in biochemical screening of women in mainland China. Our study on the median concentrations of free beta-hCG will help establish reference values that are specific for ethnic populations from the Chinese mainland. These will be useful for studying the importance of ethnic factors in biochemical screening.

Profiling the Glycoforms of the Intact α Subunit of Recombinant Human Chorionic Gonadotropin by High-Resolution Capillary Electrophoresis−Mass Spectrometry

With the rapid growth of complex heterogeneous biological molecules, effective techniques that are capable of rapid characterization of biologics are essential to ensure the desired product characteristics. To address this need, we have developed a method for analysis of intact glycoproteins based on high-resolution capillary electrophoretic separation coupled to an LTQ-FT mass spectrometer. We evaluated the performance of this method on the alpha subunit of mouse cell line-derived recombinant human chorionic gonadotrophin (r-alpha hCG), a protein that is glycosylated at two sites and is part of the clinically relevant gonadotrophin family. Analysis of r-alpha hCG, using capillary electrophoresis (CE) with a separation time under 20 min, resulted in the identification of over 60 different glycoforms with up to nine sialic acids. High-resolution CE-Fourier transform mass spectrometry (FT-MS) allowed separation and analysis of not only intact glycoforms with different numbers of sialic acids but also intact glycoforms that differed by the number and extent of neutral monosaccharides. The high mass resolution of the FT-MS enabled a limited mass range to be targeted for the examination of the protein glycoforms, simplifying the analysis without sacrificing accuracy. In addition, the limited mass range resulted in a fast scan speed that enhanced the reproducibility of the relative quantitation of individual glycoforms. The intact glycoprotein analysis was complemented with the analysis of the tryptic glycopeptides and glycans of r-alpha hCG to enable the assignment of glycan structures to individual sites, resulting in a detailed characterization of the protein. Samples of r-alpha hCG obtained from a CHO cell line were also analyzed and briefly shown to be significantly different from the murine cell line product. Taken together, the results suggest that the CE coupled to high-resolution FT-MS can be one of the effective tools for in-process monitoring as well as for final product characterization.

Chorangiocarcinoma: A Case Report and Review of the Literature

Chorangiocarcinoma is the name designated to a chorangioma with trophoblastic proliferation manifesting increased proliferative activity. Only 3 such cases have been published so far. Other studies challenged this entity by demonstrating that proliferation of the trophoblast around chorangioma is a common phenomenon. We present a case of a unique vascular lesion in a term placenta with a malignant trophoblastic component. Microscopic examination of a well-demarcated placental mass revealed a chorangioma with multiple nodules composed of pleomorphic cells displaying focal multinucleation, large areas of necrosis, and high mitotic activity. Immunohistochemical stains of these cells were strongly positive for pancytokeratin and the beta subunit of human chorionic gonadotropin and focally positive for HSD3B1. There was no invasion of the basement membrane, and no free-floating tumor cells in the intervillous space. No evidence of metastasis was found on follow-up of the mother and newborn. It is concluded that the tumor presented herein, displaying a histologically unequivocal malignant trophoblastic component in a benign chorangioma, is a true chorangiocarcinoma, and should be included within the category of gestational neoplasia as a tumor closely related to choriocarcinoma.

Decreased First-trimester Maternal Serum Free-β Subunit Human Chorionic Gonadotropin and Preterm Birth in Twin Gestations

We investigated whether abnormal concentrations of first-trimester free-beta subunit human chorionic gonadotropin (fsshCG) and pregnancy-associated plasma protein A (PAPP-A) are associated with preterm delivery in twin gestations. This was a hospital-based, retrospective study of 70 twin gestations between 11 (1)/ (7) and 13 (6)/ (7) weeks' gestation undergoing first-trimester screening. Free betahCG and PAPP-A multiples of the median were determined by our laboratory standards. Odds ratios (ORs) were estimated that compared the prevalence of very preterm (< 32 weeks), preterm (> or = 32 and < 37 weeks), and term birth (> or = 37 weeks) between the lower and higher percentile groups for each analyte. FsshCG levels < or = 25th percentile were associated with very preterm birth < 32 weeks' gestation (OR 5.10; 95% confidence interval [CI]: 1.19 to 21.95), but not with preterm birth > or = 32 and < 37 weeks' gestation (OR 0.50; 95% CI: 0.16 to 1.61). PAPP-A was not associated with very preterm (OR 2.95; 95% CI: 0.69 to 12.60) or preterm birth (OR 0.71; 95% CI: 0.23 to 2.21). Low first-trimester fsshCG was a strong predictor for very preterm birth in twin gestations. Low first-trimester PAPP-A was associated with a trend in increased risk of very preterm birth.

Concordant activity of transgene expression cassettes inserted into E1, E3 and E4 cloning sites in the adenovirus genome

Expression cassettes can be inserted at several positions into recombinant adenoviral genomes but the implications of this choice for transgene expression level have not been determined. Knowledge of the relative expression levels of transgenes inserted at different sites in the adenoviral genome is of particular significance for transgene expression monitoring approaches that rely on the concordant expression of a marker transgene inserted elsewhere in the viral genome. Three expression cassettes, each comprising a cytomegalovirus promoter driving one of three marker peptides [serum carcinoembryonic antigen (sCEA), beta subunit of human chorionic gonadotropin (betahCG) or human sodium iodide symporter (hNIS)], were inserted into E1, E3 or E4 cloning sites in a recombinant adenoviral vector backbone. High titer stocks of bicistronic adenoviral vectors coding for combinations of marker peptides were prepared. A panel of human cells of various lineages was infected with the vectors and expression ratios of the transgene-encoded proteins were analysed. Serum levels of the soluble proteins and hepatic uptake of radioactive iodine were also compared in vivo in nude rats after intravenous vector infusion. High concordance of expression between the inserted transgenes was observed in all of the bicistronic vectors irrespective of whether the expression cassettes were placed in the E1, E3 or E4 regions. Concordance was maintained across multiple cell lineages. In vivo, in athymic rats, blood and urine levels of betahCG were highly concordant with serum levels of sCEA at all timepoints after intravenous infusion of the bicistronic vectors encoding both of these soluble markers. Hepatic radioiodine uptake was concordant with serum CEA concentration in mice infused with a bicistronic vector expressing CEA and NIS. The expression level of a given transgene in an adenoviral vector genome can be accurately and quantitatively inferred from the expression of a marker protein encoded by a second transgene inserted elsewhere in the vector genome.

Production of Bovine Nuclear Transfer Embryos Using Fibroblasts Transfected with Single-Chain Human Follicle-Stimulating Hormone Gene

Human follicle-stimulating hormone (hFSH) is a pituitary glycoprotein that regulates follicular development and ovulation. Clinically, hFSH has been used to induce follicular growth in infertile women. The hormone is composed of heterodimers, including a common a subunit among the gonadotropin family and a hormone-specific β subunit. Since assembly of the heterodimer is a rate-limiting step in the production of functional hFSH, transgenic clone cows carrying a single-chain hFSH transgene may efficiently produce functional hormone. Genes encoding the a and β subunits of hFSH were linked using the C-terminal peptide sequence from the β subunit of human chorionic gonadotropin. Bovine fetal fibroblasts were transfected with the gene construct, including the goat β-casein promoter and a single-chain hFSH coding sequence. Transfected fibroblasts were transferred into enucleated oocytes, and individual nuclear transfer (NT) embryos developed to the blastocyst stage were analyzed for the transgene by polymerase chain reaction. Seventy eight blastocysts (30.8%) were developed from 259 reconstructed embryos. Among these blastocysts, the hFSH gene was detected in 70.8% (34/48) of the embryos. Subsequent transfer of hFSH-transgenic clone embryos to 31 recipients results in 11 (35.5%) early pregnancies. However, all fetuses were lost before reaching day 180 of gestation. The results from this study demonstrated that bovine NT embryos carrying single-chain hFSH could be produced, and further extensive studies in which NT embryos are transferred to more recipients may give rise to single chain hFSH-transgenic cows for biomedical applications.

Coexistent gastric primary choriocarcinoma and adenocarcinoma

Choriocarcinomas are commonly gestational and intrauterine or gonadal in origin. Nongestational and extragonadal disease, especially in the stomach is extremely rare with a poorer prognosis and early metastasis. We herein describe a case of primary gastric choriocarcinoma with liver metastasis in a 69-year-old male. The patient presented with abdominal pain and irregular bowel habits of one month duration. Both endoscopic and radiographic imaging revealed an ulcerated and necrotic circumferential tumor in the pyloric antrum of the stomach. The histopathologic findings of the resected tumor were that of an extensively necrotic and hemorrhagic neoplasm with combined choriocarcinomatous and adenocarcinomatous element. A strongly positive immunohistochemical staining for beta- subunit of human chorionic gonadotropin (beta-HCG) in the choriocarcinomatous component and a proper correlation with elevated serum beta-HCG levels confirmed the diagnosis.

The diagnostic significance of hCG and hPL via immunohistochemistry of placental tissues in pregnancies diagnosed with IUGR and IUD

SummaryPlacentas of patients diagnosed with intrauterine growth restriction (IUGR) and intrauterine death (IUD) were examined by immunohistochemistry for alpha–beta subunits of human chorionic gonadotropin (hCG) and human placental lactogen (hPL) antibodies, and compared with placentas from women with healthy pregnancies. In total, 114 subjects were evaluated. The patient group comprised 27 cases of IUGR and 57 of IUD, and the control group consisted of 30 women with normal pregnancies. Placental specimens were examined for primary antibodies using immunohistochemical techniques. Placentas from 22 cases of IUGR were stained positively for α-hCG. All 27 specimens obtained from this group were stained positively for β-hCG and hPL. Among the cases of IUD, 44 placentas were stained positively for α-hCG, and all 57 specimens were stained positively for β-hCG and hPL.

Beta human chorionic gonadotropin (β-hCG) expression in pituitary adenomas: relationship to endocrine function and tumour recurrence

The beta subunit of human chorionic gonadotropin (beta-hCG) is a marker of malignancies. Recent studies have also reported its expression in pituitary adenomas, although its significance is unclear. In this retrospective study, the authors quantitatively investigated the immunohistochemical expression of beta-hCG in 123 patients undergoing surgery for pituitary adenomas and explored its relationship to the rest of the endocrine function, tumour recurrence and Ki-67 nuclear labelling. Based on the endocrine profile and immunohistochemistry, the pituitary adenomas were grouped into non-functioning (NFPA; N = 78) and functioning pituitary adenomas (N = 45). The latter included, 20 growth hormone (GH), 12 prolactin (PRL), 8 adreno-corticotrophin hormone (ACTH) and 5 mixed GH-PRL-producing adenomas. Ninety-three (76%) tumours were classified as primary and 30 (24%) tumours classified as recurrent adenomas. Immunohistochemically, 107 (87%) of pituitary adenomas expressed beta-hCG, which was more common in NFPA (91%) than functioning pituitary adenomas (80%). beta-hCG expression was not different between primary (86%) and recurrent pituitary adenomas (90%) and it was also not related to raised Ki-67 labelling. But, Ki-67 labelling was raised in recurrent pituitary adenomas (33%), compared to primary pituitary adenomas (11%). Although, beta-hCG is expressed in the majority of pituitary adenomas, more especially in NFPA, it is un-related to the risk of tumour recurrence or cellular proliferation as measured by Ki-67 nuclear labelling. The high incidence of beta-hCG expression in pituitary adenomas may provide a target for specific beta-hCG-directed tumour therapies in the future.

Free β-Subunit of Human Chorionic Gonadotropin in Serum Is a Diagnostically Sensitive Marker of Seminomatous Testicular Cancer

We studied whether measurement of the free beta subunit of human chorionic gonadotropin (hCGbeta) in serum offers additional diagnostic information compared to determination of intact hCG alone in testicular cancer. We determined hCG and hCGbeta with ultrasensitive assays in 94 serum samples obtained preoperatively, 22 samples obtained during relapse, and 3687 samples obtained during routine follow-up of 351 patients with testicular tumors. In preoperative samples, isolated increases of hCGbeta were seen in 40% of the samples from seminoma patients (n = 42) and in 8% of those from patients with nonseminomatous testicular cancer (NSGCT) (n = 51). Both markers were increased in 12% of the seminoma and 71% of the NSGCT patients and were within reference intervals in 43% of the seminoma and 20% of the NSGCT patients. Specific determination of hCGbeta increased the frequency of marker-positive seminomas from 17% to 57% and of marker-positive relapses from 32% to 59% (n = 22). Theoretically, about 40% of marker-positive seminomas and relapses would have been missed with an assay measuring hCG and hCGbeta together. Preoperative hCG and hCGbeta concentrations correlated with stage, tumor histology, and disease-related mortality. Additionally, hCGbeta correlated with tumor size. hCGbeta is a diagnostically sensitive marker for testicular cancer. In patients with seminomatous testicular cancer, hCGbeta is superior to hCG, and in some NSGCT patients it provides additional information.

Recurrent Ectopic Pregnancy After Ipsilateral Segmental Salpingectomy

We report an unusual case of recurrent ectopic pregnancy in the distal remnant after partial salpingectomy. A 23-year-old woman underwent laparoscopic right partial salpingectomy because of right tubal pregnancy. She returned to our hospital 2 years later with a positive pregnancy test and lower abdominal pain. Transvaginal ultrasonography revealed no intrauterine gestational sac but a right adnexal mass measuring 2.4 x 2.3 cm. The serum beta-hCG (beta subunit of human chorionic gonadotropin) level was 2,918.06 mIU/mL. Videolaparoscopy was performed, and an ectopic pregnancy in the distal remnant of the right fallopian tube was identified. Right salpingectomy was effective and the pathologic report confirmed the diagnosis. The patient's postoperative recovery was uneventful. If conservative methods are not suitable for a patient with tubal pregnancy, total salpingectomy is the preferred option over partial salpingectomy. A remnant poses a risk for recurrent ectopic pregnancy owing to potential transperitoneal migration of either embryos or sperms.

Combination of serum hCGβ and p53 tissue expression defines distinct subgroups of serous ovarian carcinoma

Serous ovarian carcinoma comprises a clinically heterogenous group of tumors, and molecular markers stratifying patients into clinically meaningful subgroups are needed. Numerous markers have been evaluated, but none of them has yet been routinely incorporated into clinical practice. Previously we have found that elevated serum levels of the free beta subunit of human chorionic gonadotropin (hCG beta) and aberrant p53 expression confer poor prognosis in ovarian carcinoma. The aim of our study was to evaluate their combined effect in predicting the outcome of patients with serous ovarian carcinoma. The study material consisted of 173 consecutive patients treated for primary serous ovarian carcinoma in 1 institution between 1990 and 2000. The preoperative serum level of hCG beta was analyzed by a ultrasensitive and specific immunofluorometric assay, and p53 tumor tissue expression by immunohistochemistry using a novel classification. Elevated serum hCG beta (>or=2.0 pmol/L) was detected in 57 (33%) of 173 patients, and aberrant p53 expression in 103 (62%) of 167 interpretable cancers. Elevated hCG beta and aberrant p53 expression were strongly associated with poor prognosis (p < 0.0001 for both). Their additive prognostic effect was marked. Five-year survival was 14% (0-29%) when both markers were aberrant, 44% (29-60%) when either one was aberrant and 82% (70-94%) when both were normal. Preoperative serum hCG beta and tumor tissue p53 expression are feasible markers that divide serous ovarian carcinomas into clinically relevant subgroups.

Ectopic Pregnancy and Ultrasound: A Review

Abstract First trimester bleeding occurs in up to 30% of all diagnosed pregnancies. Important causes of first trimester bleeding include spontaneous abortion, missed or threatened abortion, ectopic pregnancy, and gestational trophoblastic disease. One of the greatest dilemmas for clinicians is to accurately diagnose the cause of pain or bleeding, and specifically to determine if an ectopic pregnancy exists due to its grave consequences. Ectopic pregnancy occurs in almost two percent of all reported pregnancies in the United States and is the leading cause of pregnancy-related death in first trimester. When an early pregnant patient is identified who has bleeding or pain, it is crucial step to determine where the pregnancy is located. Ultrasound as a first line diagnostic tool offers an excellent opportunity for pregnancy localization. The use of the beta subunit of human chorionic gonadotropin (beta-hCG) quantification is a valuable adjunct to help determine the course and possible outcome of an early pregnancy. The goal should be to preserve the health and future reproductive capabilities of our patients.

Refining the Optimal Chemotherapy Regimen in Good Prognosis Germ Cell Cancer: Interpretation of the Current Body of Knowledge

Refining the Optimal Chemotherapy Regimen in Good Prognosis Germ Cell Cancer: Interpretation of the Current Body of Knowledge

Intracerebral hemorrhage as initial presentation of gestational choriocarcinoma: a case report and literature review

Choriocarcinoma is the most malignant tumor of gestational trophoblastic neoplasia. It grows rapidly and metastasizes to the lung, liver, and, less frequently, to the brain. One rare case of metastatic cerebral choriocarcinoma with initial presentation of intracerebral hemorrhage is reported. A 40-year-old woman initially presented sudden onset of headache. Intracerebral hemorrhage resulting from ruptured pseudoaneurysm was suspected. Emergent surgery with excision of the pseudoaneurysms was performed. Metastatic choriocarcinoma was accidentally found with positive immunohistochemical staining of cytokeratin and beta subunit of human chorionic gonadotropin (beta-HCG). Choriocarcinoma with brain metastases was diagnosed. She then received chemotherapy with regimen of etoposide, methotrexate, actinomycin-D, cyclophosphamide, and vincristine (EMACO). Elevated serum beta-HCG (30.3 mIU/mL) and new pulmonary lesions were noted by computed tomography 4 months after completion of EMACO. Salvage chemotherapy with etoposide, methotrexate, actinomycin-D, etoposide, and cisplatin (EMAEP) regimen was given. Seven months later after completion of EMAEP, two new pulmonary lesions were detected by positron emission tomography (PET) scan. So she received video-assisted thoracoscopic surgery with tumor excision. Pathologic report confirmed the diagnosis of lung metastases. The patient recovered well. She is free of disease for 12 months. The diagnosis of metastatic cerebral choriocarcinoma was only made by histopathology after craniotomy. Metastatic choriocarcinoma should be always in the differential diagnosis for women at childbearing age presenting with unexplained stroke-like symptoms. In addition, PET scan may be valuable in detecting occult metastatic lesions of choriocarcinoma.

Metastatic Germ-Cell Cancer

A 60-year-old man presented with progressive swelling of the right side of the scrotum. He reported no history of trauma to this area and no sexually transmitted infections. The alpha-fetoprotein level was elevated at 3100 μg per liter (normal value, <8), and the serum level of the beta subunit of human chorionic gonadotropin was less than 1 IU per liter. Multidetector computed tomography with multiplanar reformation (Panel A) showed a large testicular tumor with lymphangitic spread along the testicular vessels to the associated draining lymph nodes below the renal hilus. Right-sided hydronephrosis is present because of compression of the ureter . . .

Antigen presenting cell (APC)-targeted hCGβ vaccine for cancer therapy

3013 Background: CDX-1307 is a novel vaccine approach designed to target antigens directly into the endocytic compartments of dendritic cells (DCs) and other professional APCs. The β subunit of human chorionic gonadotropin (hCGβ) is selectively over-expressed by a number of epithelial tumors and has been reported to correlate with stage of disease and prognosis. We have coupled this tumor-associated antigen to a human monoclonal antibody (B11) that targets mannose receptors on human dendritic cells and macrophages, and have demonstrated the efficacy of this approach in preclinical models using hCGβ-expressing tumors and cell lines. Methods: In this phase I, dose-escalating study, sequential cohorts of 6 patients with relapsed epithelial tumors receive 4 biweekly intradermal injections of CDX-1307 at either 0.3, 1.0 or 2.5 mg, or 2.5 mg concurrent with GM-CSF. Objectives: safety and tolerability; DLT, humoral and cellular immune response, and clinical activity. Results: Enrollment in the first three cohorts (n=18) is complete with no DLTs. Common potential treatment-related toxicities were injection site reaction (n=5) and fatigue/malaise (n=4), and were generally mild to moderate in severity. One transient Grade 3 generalized allergic reaction in the 1.0 mg cohort was suspected possibly related to either a nut allergy or CDX-1307. One mixed response was seen, with variable effects on circulating hCGβ. CDX-1307 localized to dermal macrophages and DCs in post-treatment biopsies. Conclusions: Administration of CDX-1307 is well tolerated and results in antigen localization in APCs of the skin. Immune Response and tumor impact are under evaluation. Further development includes systemic delivery that may provide antigen targeting to a broad APC population, and combination with immunostimulants to generate optimal immune responses. No significant financial relationships to disclose.

Clinical first-trimester routine screening for Down syndrome in singleton pregnancies in northern Finland

The purpose of this study was to compare the efficacy of both separate and combined maternal serum testing and fetal nuchal translucency measurement in the first trimester screening for Down syndrome in northern Finland. The following screening tests were evaluated: measurement of nuchal translucency (NT) alone; serum screening (pregnancy-associated plasma protein A [PAPP-A] and free beta subunit of human chorionic gonadotropin [beta-hCG]) alone; and combined screening (NT plus PAPP-A and free beta-hCG). The participants comprised 7534 pregnant women during the 10+0-12+6 weeks of pregnancy. All 7534 women participated in serum screening, and 4765 women participated in combined screening. In the serum screening-alone group, there were 30 cases of trisomy 21, of which 23 (76%) were detected. In the combined-screening group, there were 24 cases of trisomy 21 and 21 (87.5%) were detected. In the combined-screening group NT alone detected 15 cases of Down syndrome (62%). Combined screening is the method of choice for Down syndrome screening.

Comparative Study of Three Amniotic Fluid Markers in Premature Rupture of Membranes: Prolactin, Beta Subunit of Human Chorionic Gonadotropin, and Alpha-Fetoprotein

Objective: To evaluate whether prolactin, α-fetoprotein (AFP) or B-human chorionic gonadotropin (BHCG) is the most effective marker in vaginal fluid for diagnosing prelabor rupture of membranes (PROM). These proteins are present in amniotic and vaginal fluid and have been reported to be potent markers of PROM, but have not been used clinically nor compared to each other. Study Design: A total of 100 pregnant women between 28 and 37 weeks of gestation were recruited for the study. Patients were divided into 2 groups. The first group consisted of 50 pregnant women diagnosed with ruptured membranes. The second group consisted of 50 normal pregnant women seen during routine antenatal clinic visit (control) group. All women underwent speculum examination aiming to sample prolactin, BHCG and AFP in the vaginal fluid. Ultrasonographic examination for gestational age and amniotic fluid index measurement was performed. The electrochemoluminescence (ECLIA) method was used for quantitative measurement of the three proteins (the total duration of the assay was 18 min). Results: Vaginal fluid concentrations of the three markers were significantly higher in the PROM group than in the control group (p < 0.001). Receiver operator curve analysis indicated that AFP had 94% specificity, sensitivity, positive and negative predictive values, and efficiency. The other two markers have lower specificity, sensitivity, positive and negative predictive values, and efficiency: 70, 76, 71.7, 74.5 and 73% for prolactin and 72, 84, 75, 81.8 and 78% for BHCG, respectively. Conclusion: This work demonstrates that of the three markers investigated AFP has the highest diagnostic performance. Using the ECLIA method it can be an ideal marker for diagnosing PROM particularly in equivocal cases. The technique could be introduced into laboratory tests to meet clinical needs.