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PubMed2005

Preoperative serum hCGbeta as a prognostic marker in primary fallopian tube carcinoma.

OBJECTIVES: It was the aim of this study to evaluate the prognostic value of the pretreatment serum concentrations of the beta-subunit of human chorionic gonadotropin (hCGbeta), CA 125 and tumour-associated trypsin inhibitor (TATI) in primary fallopian tube carcinoma (PFTC). METHODS: The pretreatment serum concentrations of hCGbeta, CA 125 and TATI were analyzed in serum samples from 60 women with a mean age of 61 years, treated for PFTC between 1985 and 2000. Of the 91 patients treated during this period, 31 were excluded because no serum sample was available. The patients were followed-up for recurrence and survival until February 14, 2003. The prognostic value of the serum markers were compared with those of stage, grade and histological type. RESULTS: The median survival time was 27 months and the overall 5-year survival rate 33%. Stage and size of the residual tumour (<1 vs. > or =1 cm) predicted both overall and disease-free survival (p < 0.050). Histology (serous vs. others) (p = 0.023) also influenced overall survival. Overall 5-year survival was 38% when serum hCGbeta was below 3.5 pmol/l, while it was 18% when the level was higher (p = 0.052). The corresponding disease-free 5-year survival was 38 and 20%, respectively (p = 0.014). Patients with CA 125 values above 1,017 kU/l had an overall 5-year survival of 39% as compared with 14% for those with lower values (p = 0.009), while the disease-free survival was 37 and 23%, respectively (p = 0.096). Serum TATI was not a prognostic marker. Serum concentrations of hCGbeta and CA 125 correlated significantly with stage (p = 0.049 and p = 0.050, respectively). In multivariate Cox proportional hazards regression analysis, only hCGbeta, stage and histology emerged as independent prognostic factors. CONCLUSIONS: Clearly elevated serum concentrations of hCGbeta and CA 125 predict survival in fallopian tube carcinoma, but in multivariate analyses, only hCGbeta is a prognostic factor independent of stage and histology.

Adult↗

PubMed2006

If nuchal translucency screening is combined with first-trimester serum screening the need for fetal karyotyping decreases.

BACKGROUND: This case-control study was performed to evaluate whether adding first-trimester maternal serum testing to nuchal translucency measurement would improve the antenatal detection of Down's syndrome and decrease the number of women offered fetal karyotyping. METHODS: In the Swedish Nuchal Translucency Trial (the NUPP trial), 39,572 pregnant women were randomized to a routine scan at 12-14 gestational weeks including nuchal translucency screening for Down's syndrome, or a routine scan at 16-18 gestational weeks. From the early scan group 47 pregnancies with Down's syndrome were identified and for each case three controls were chosen. Of the 189 women asked to participate, 31 cases and 108 controls with a singleton pregnancy and frozen serum from 8-14 gestational weeks available for analysis accepted participation. Maternal sera were analyzed for free beta human chorionic gonadotrophin and pregnancy-associated plasma protein A. The risk for Down's syndrome was calculated using combinations of maternal age, crown-rump length, nuchal translucency, and biochemistry. A risk > or =1/250 was considered increased and an indication for fetal karyotyping. RESULTS: Risk calculated on the basis of maternal age alone would have identified 21 of the 31 Down's syndrome cases by karyotyping 61 of the 139 fetuses. Maternal age and nuchal translucency would have identified 29 cases by karyotyping 51 fetuses. Maternal age, nuchal translucency, and biochemistry would also have identified 29 cases by karyotyping 37 fetuses. CONCLUSIONS: By adding first trimester biochemistry to nuchal translucency measurement the detection rate of fetuses with Down's syndrome seems to remain unchanged whereas the antenatal risk group to be offered fetal karyotyping decreases.

Adult↗

PubMedDate not supplied

Immunofluorescent localization of placental lactogen, chorionic gonadotrophin and its alpha and beta subunits in organ cultures of human placenta.

Localization of human placental lactogen (HPL), chorionic gonadotrophin (HCG) and its free alpha and beta subunits in mature and immature placental villi before and during organ culture was examined with an 'indirect' immunofluorescent technique using highly specific antisera. HPL fluorescence was strictly localized to the syncytiotrophoblast and the intensity of this fluorescence increased with gestational age and decreased with the time of culture. Undissociated HCG and HCG beta immunofluorescence was localized to the syncytiotrophoblast. Maximum intensity was observed in immature placentae and was not significantly affected by the duration of culture. However, irregular and patchy HCG and HCG beta immunofluorescence was seen in the cytotrophoblasts under conditions of extensive syncytiotrophoblastic damage. HCG alpha immunofluorescence was localized in the syncytiotrophoblast of immature placentae and was more intense in mature placentae. Beginning the third day of culture, HCG alpha fluorescence increased and was also present in the cytotrophoblast. On the basis of these observations and additional data, the possibility is discussed that cytotrophoblastic cells, better preserved than the syncytiotrophoblast in case of restricted energy and oxygen supply, may actively synthesize free HCG alpha, in addition to syncytiotrophoblastic production of this subunit. By contrast, HPL, undissociated HCG, and HCG beta are mainly or exclusively eleborated in the syncytiotrophoblastic layer.

Animals↗

PubMed1994

The association between alpha-fetoprotein and beta hCG levels prior to and following chorionic villus sampling in cases that spontaneously miscarried.

Maternal serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta hCG) measurements taken prior to chorionic villus sampling (CVS) in 21 patients who subsequently miscarried were compared with measurements in a control group of 113 patients with uneventful pregnancies. Patients with AFP levels of 10 iu/ml or more prior to the CVS had a 4.3 times greater risk of miscarriage (95 per cent confidence interval 1.3-13.6). AFP levels obtained 1 week after the CVS in the 13 patients with late miscarriages were higher than in the control group (P = 0.06). Patients miscarrying had a greater rise in AFP (P = 0.06) and a greater fall in beta hCG levels (P = 0.04) following the CVS procedure, compared with the control subjects. Each 10-unit change in the difference between AFP or beta hCG levels prior to and 1 week following the CVS was associated with a significantly increased risk for late miscarriage. Elevated maternal serum AFP levels early in pregnancy and changes in AFP and beta hCG levels following CVS may predict an increased risk for subsequent miscarriage.

Abortion, Spontaneous↗

PubMed2004

Impact of trisomy 21 on human trophoblast behaviour and hormonal function.

Although trisomy 21 (T21) is the most frequent genetic abnormality and some maternal serum markers for this fetoplacental aneuploidy are of placental origin, little is known of its impact on placental development. We therefore studied the influence of T21 on trophoblast behaviour. Using cultured cells from 46 human T21 pregnancies, we confirmed the defective morphological and functional differentiation of the villous cytotrophoblast in this setting; indeed, villous cytotrophoblast cells aggregate normally but fuse inefficiently to form the syncytiotrophoblast. This is in part related to the abnormal oxidative status of the T21 cytotrophoblast, characterized by a gene dosage-related increase in SOD-1 (copper-zinc superoxide dismutase) expression and activity. This was associated with a significant (P < 0.01) increase in catalase activity but no significant change in glutathione peroxidase activity. On the basis of these in vitro findings and studies of large panels of maternal serum, we propose a pathophysiological explanation for trisomy 21 maternal serum markers of placental origin.

Adult↗

PubMedDate not supplied

Immunohistochemical localization of HLA antigens and placental proteins (alpha hCG, beta hCG CTP, hPL and SP1 in villous and extravillous trophoblast in normal human pregnancy: a distinctive pathway of differentiation of extravillous trophoblast.

Immunohistochemical localization of HLA antigens and placental proteins (alpha hCG, beta hCG CTP, hPL and SP1) in villous and extravillous trophoblast at various stages of normal human gestation were studied, using hysterectomy specimens. In the chorionic villi, the capacity for synthesizing placental proteins seemed to develop in parallel with the morphological change from mononuclear cells to multinucleated syncytiotrophoblast and no villous trophoblast expressed HLA antigens. In contrast, extravillous trophoblast, including the multinucleated trophoblastic cells at the deciduomuscular junction, expressed HLA-A, -B, and -C, and their capacity for synthesizing placental proteins did not seem to correspond with the degree of morphological change: the location of alpha hCG, beta hCG CTP and SP1 was restricted to mononuclear trophoblast in the superficial decidua, while hPL was present extensively in extravillous trophoblast. These findings strongly suggest that extravillous trophoblast possesses many distinctive biological features and differentiates in an independent manner. Mononuclear trophoblast forming the cell columns was also positive for HLA-A, -B, and -C, and no placental protein was demonstrated in these cells; this, together with previous morphological observations, may indicate the germinative nature of these cells.

Cell Differentiation↗

PubMed2000

HCG concentration and receptor gene expression in placental tissue from trisomy 18 and 21.

Trisomy 21 is associated with high maternal serum concentrations of intact human chorionic gonadotrophin alpha(HCG) and free beta-HCG whereas these concentrations are markedly decreased in trisomy 18. In this study, we investigated the effect of trisomy 21 and 18 on endogenous HCG concentrations and luteinizing hormone (LH)/HCG receptor expression in placental villous tissue in eight trisomy 21, six trisomy 18 and 42 chromosomally normal samples, collected at 12-16 weeks gestation. The tissue concentrations of intact HCG, free alpha-HCG and free beta-HCG subunits were measured using solid-phase two-site immunoradiometric assay. LH/HCG receptor expression was evaluated with immunohistochemistry and in-situ hybridization. Villous tissue in trisomy 21 contained higher beta-HCG concentrations than the controls (P < 0.05). In trisomy 18 cases, the beta-HCG concentration was lower than in the control group (P < 0.01). Both immunocytochemistry and in-situ hybridization demonstrated a more intense staining of the trophoblast in cases of trisomy 21 and 18, compared with controls with the strongest signal in cases of trisomy 18 (P < 0.01). We concluded that in trisomy 21 the high tissue HCG concentration and expression of LH/HCG receptor in the trophoblast may reflect the relative immaturity of the trophoblastic tissue whereas in trisomy 18, the very low concentration of endogenous HCG, associated with an over-expression of LH/HCG receptor in the trophoblast, is probably secondary to the poor differentiation of the cytotrophoblast.

Chorionic Gonadotropin, beta Subunit, Human↗

PubMed2005

First trimester increased nuchal translucency associated with fetal achondroplasia.

A 30-year-old woman, gravida 2, para 1, was referred for nuchal translucency, free beta-human chorionic gonadotropin (beta-hCG), and pregnancy-associated plasma protein A (PAPP-A) screening at 12 weeks gestation. The nuchal translucency was increased to 3.8 mm, resulting in a post-test result of 1:15 risk for Down syndrome by a combination of maternal age plus nuchal translucency, and 1:5 by a combination of maternal age plus nuchal translucency plus free beta-hCG plus PAPP-A. The patient underwent uncomplicated chorionic villus sampling that demonstrated a normal 46,XY fetus. The patient was then followed-up weekly by ultrasound. At 18 weeks gestation, generalized features of rhizomelic micromelia together with macrocrania and narrow thorax were seen. All fetal long bones were less than 2 standard deviations from the mean value. At that time, DNA analysis was performed on stored villi and a G380R mutation in the locus gene encoding for the fibroblast growth factor receptor 3 on chromosome 4p16.3 was found, leading to a prenatal diagnosis of achondroplasia. The couple opted for termination of pregnancy after counseling. Postmortem X-ray was done and confirmed the ultrasound diagnosis of achondroplasia. This is the second known case of increased nuchal translucency in the first trimester associated with prenatal confirmed diagnosis of fetal osteochondrodysplasia.

Abortion, Induced↗

PubMedDate not supplied

Enzymatic isolation of human trophoblast and culture on various substrates: comparison of first trimester with term trophoblast.

A simple method is described for the isolation of trophoblast cells from both first trimester and term placenta. Trophoblast preparations were characterized by light microscopy, scanning and transmission election miscroscopy and immunohistochemistry to distinguish these cells from mesenchyme and endothelium. Trophoblast cells were cultured on various substrates and a comparison made of their ability to attach, proliferate and function. A collagen gel substrate produced by repolymerization of an acid soluble collagen fraction from chorionic villi allowed rapid attachment of trophoblast cells and maintainance of their original morphology. Term trophoblast cells were shown to become fully functional in short term (three day) cultures by virtue of their increased immunocytochemical staining for the presence of beta hCG, hPL and SPI. beta hCG increased significantly by day three thus demonstrating functional activation. Trophoblast cells from first trimester placenta formed proliferating colonies of hormone producing cells while those from term placenta reaggregated into clusters and closely resembled syncytiotrophoblast both morphologically and functionally. This short term culture system for term trophoblast will allow further studies into the biology of trophoblast polypeptide hormone synthesis and secretion.

Cell Separation↗

PubMed1989

High frequency of in situ hybridization on thin plastic sections of human placenta with a cDNA probe for beta hCG.

We describe two different techniques with plastic embedding in in situ hybridization histochemistry (ISHH). Their applicability was demonstrated by use of human placenta of the tenth gestational week and a tritium-labeled cDNA probe for the beta-subunit of hCG. In the first method, ISHH was performed on whole pieces of tissue (en bloc ISHH) pretreated with a weak acid solution, embedded in methacrylate, and sectioned at 3 microns for autoradiography. In the second technique, en bloc ISHH was carried out on tissue pre-treated with the weak acid and thereafter with detergent to further facilitate probe penetration. An acrylic resin was used for embedding, and section thickness was reduced to 1 microns. With both techniques, beta hCG cDNA/mRNA hybrids were localized exclusively to the syncytiotrophoblast (ST), in agreement with a previous study using sections of frozen placentas for hybridization to the same probe. However, owing to the higher resolution of the plastic sections the reliability of this localization was greatly increased. The number of autoradiographic grains over the acrylic resin 1-microns sections was found to be considerably higher than that over the methacrylate 3-microns sections. This study showed that treatment of tissue with detergent before en bloc ISHH, with subsequent embedding in acrylic resin and sectioning at 1 microns, gives high resolution in combination with a high signal-to-noise ratio after autoradiography. As the acrylic resin permits cutting of ultrathin sections, the results suggest that the technique may become useful for ISHH studies at the subcellular level.

Autoradiography↗

PubMed1999

Characterization of human placental explants: morphological, biochemical and physiological studies using first and third trimester placenta.

The primary objective of this study was to characterize an in-vitro model of the human placenta using morphological, biochemical and physiological parameters. Placental villi were obtained from normal first trimester and term pregnancies. The villi were incubated with Dulbecco's modified Eagle's medium: Ham's F12 nutrient mixture in a shaking water bath at 37 degrees C for up to 310 min. The viability was determined by the production of beta human chorionic gonadotrophin (HCG) and lactic dehydrogenase (LDH) and the incorporation of [3H]thymidine, [3H]L-leucine and L-[U14C]arginine, while ultrastructure was assessed by transmission electron microscopy. In the first and third trimester group, the release into the medium of the intracellular enzyme LDH remained unaltered throughout the experiment. By contrast, beta-HCG concentrations increased linearly and concentrations were higher in the first trimester than term villi (354.5 +/- 37.8 versus 107 +/- 8.1 IU/g villi protein; P < 0.001). Electron microscopy confirmed preservation of tissue viability for up to 4 h of incubation. The incorporation of thymidine (12.2 +/- 2.9 versus 5.2 +/- 0.5 nmol/g villi protein; P < 0.05), leucine (9.4 +/- 2.1 versus 1.9 +/- 0.4 nmol/g villi protein; P < 0.02) and arginine (17 +/- 4.4 versus 4.2 +/- 0.5 nmol/g villi protein; P < 0.05) were markedly higher in early than in term placenta. Furthermore, placental uptake of L-leucine by the first (9.4 +/- 2.1 versus 17 + 4.4 mol/g villi protein; P < 0.001) and third trimester placental villi (1.9 +/- 0.4 versus 4.2 + 0.5 mol/g villi protein; P < 0.001) was less than that of L-arginine. This study describes a simple technique using placental explants to determine relative rates of uptake of substrate amino acids throughout gestation.

Amino Acids↗

PubMed2005

A link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor (LHCGR) in Down's syndrome pregnancies.

Human chorionic gonadotrophin (hCG) is released from placental trophoblasts and is involved in establishing pregnancy by maintaining progesterone secretion from the corpus luteum. Serum hCG is detected in the maternal circulation within the first 2-3 wks of gestation and peaks at the end of the first trimester before declining. In Down's syndrome (DS) pregnancies, serum hCG remains significantly high compared to gestation age-matched uncompromised pregnancies. It has been proposed that increased serum hCG levels could be due to transcriptional hyper-activation of the CGB (hCG beta) gene, or an increased half life of glycosylated hCG hormone, or both. Another possibility is that serum hCG levels remain high due to reduced availability of the hormone's cognate receptor, LHCGR, leading to lack of hormone utilization. We have tested this hypothesis by quantifying the expression of the hCG beta (CGB) RNA, LHCGR RNA and LHCGR proteins in chorionic villous samples. We demonstrate that chorionic expression of hCG beta (CGB) mRNA directly correlates with high serum hCG levels. The steady-state synthesis of LHCGR mRNA (exons 1-5) in DS pregnancies was significantly higher than that of controls, but the expression of full-length LHCGR mRNA (exons 1-11) in DS was comparable to that of uncompromised pregnancies. However, the synthesis of high molecular weight mature LHCGR proteins was significantly reduced in DS compared to uncompromised pregnancies, suggesting a lack of utilization of circulating hCG in DS pregnancies.

Animals↗

PubMed2006

Tumour necrosis factor-alpha impairs chorionic gonadotrophin beta-subunit expression and cell fusion of human villous cytotrophoblast.

Growth factors expressed at the fetal-maternal interface modulate hormone expression of placental trophoblasts. The aim of this study was to investigate the effects of different cytokines on hCG subunit mRNA expression in differentiating villous cytotrophoblasts. Quantitative real-time PCR revealed a 1.8- and 6.9-fold increase of hCG-alpha and hCG-beta mRNA levels, respectively, between 36 and 60 h of term trophoblast syncytialization. Compared with controls, neither interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, IL-13 and IL-15 nor tumour necrosis factor (TNF)-alpha significantly altered hCG-alpha mRNA expression. Similarly, the ILs did not affect hCG-beta transcript levels. In contrast, TNF-alpha suppressed hCG-beta mRNA 3.8- and 1.8-fold at 36 and 60 h of term trophoblast differentiation. Accordingly, hCG secretion was impaired by TNF-alpha but not by the different ILs. Moreover, TNF-alpha reduced luciferase expression of reporter plasmids harbouring the proximal hCG-beta5 promoter to 35 and 77%, respectively, in primary term trophoblasts and trophoblastic SHGPL-5 cells. In addition, counting of nuclei in syncytialized, desmoplakin-negative areas revealed a 1.9-fold reduction of term trophoblast fusion in the presence of TNF-alpha. Similarly, floating explant cultures prepared from first trimester-denuded villi recovered the syncytium 2.8-fold less efficiently during 72 h of cytokine treatment. Concomitantly, TNF-alpha impaired induction of endogenous and secreted hCG-beta protein levels in these cultures. The data suggest that TNF-alpha decreases hCG-beta mRNA and protein expression by reducing gene transcription and trophoblast cell fusion. Suppression of these processes by TNF-alpha could partly explain the adverse effects of the cytokine on placental function and pregnancy outcome.

Cell Differentiation↗

PubMed1999

The predictive value of endometrial stripe thickness in patients with suspected ectopic pregnancy who have an empty uterus at ultrasonography.

UNLABELLED: Prior research suggests that, in patients with empty uteri at ultrasonography, endometrial stripe thickness may be predictive of ectopic pregnancy or the likelihood of obtaining chorionic villi after a dilatation and evacuation procedure (D+E). However, it is unclear whether the predictive value of endometrial stripe thickness is confined to patients with low beta-human chorionic gonadotropin (beta-hCG) values. OBJECTIVE: To determine whether endometrial stripe thickness is predictive of the risk of ectopic pregnancy or the likelihood of obtaining chorionic villi after D+E in patients with beta-hCG values >1,000 mIU/mL or < or =1,000 mIU/mL. METHODS: In an urban academic ED, the authors conducted a retrospective chart review of consecutive ED patients from August 1991 to August 1997 with abdominal pain or vaginal bleeding, a positive beta-hCG value, and an empty uterus by transvaginal ultrasound examination. Patients were divided into four groups-group 1: endometrium thin, beta-hCG value < or =1,000 mIU/mL; group 2: endometrium thick, beta-hCG value < or =1,000 mIU/mL; group 3: endometrium thin, beta-hCG value >1,000 mIU/ mL; and group 4: endometrium thick, beta-hCG value >1,000 mIU/mL. The secondary analysis was limited to patients who had a D+E performed within 48 hours of the ED visit. The risks of ectopic pregnancy and the likelihoods of obtaining chorionic villi after D+E were compared using chi-square or Fishers' exact test where appropriate, with a p-value of 0.05 being significant. RESULTS: 224 patients were enrolled in the initial analysis. Intergroup differences in the frequency of ectopic pregnancy were of borderline significance (p = 0.08). However, when the comparison was limited to the groups with beta-hCG values < or =1,000 mIU/mL, the predictive value of endometrial stripe thickness reached statistical significance (group 1: 27/99 [27%], group 2: 2/28 [7%], p = 0.05). 79 patients had a D+E performed. Intergroup differences in the rate of obtaining chorionic villi were significant (p = 0.002). Group 1 had the lowest frequency of having chorionic villi identified (4/26 [15%]) and was the only group in which villi were obtained in fewer than 50% of cases. CONCLUSION: Endometrial stripe thickness may be predictive of the risk of ectopic pregnancy and the likelihood of obtaining chorionic villi at D+E. However, its predictive value appears to be confined to patients with beta-hCG values < or =1,000 mIU/mL.

Academic Medical Centers↗

PubMed2002

The first trimester 'combined test' for the detection of Down syndrome pregnancies in 4939 unselected pregnancies.

The high detection rate (DR) for Down syndrome (DS) pregnancies which can be achieved by measuring fetal nuchal translucency (NT) early in pregnancy can be improved by combining it with placental hormones [pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotrophin (fbeta-hCG)] and maternal age ('combined test'). In this study we wanted to assess the DR using the 'combined test' in an unselected population of self-referred pregnant women at a false-positive rate (FPR) of about 5%. NT, PAPP-A, fbeta-hCG and maternal age were measured in all women with singleton pregnancies who booked for delivery in our hospital from 1 December 1997 to 31 April 2000 and who were between 10 and 13 completed weeks of gestation [crown-rump length (CRL) 35-70 mm]. The specific DS risk was calculated using the computer program Alpha Version 5aa (Logical Medical Systems, London, UK). A total of 4939 women were tested. Out of 14 DS pregnancies that occurred during this period of time, 12 were detected with the test. A total of 246 women had a false-positive test result in a non-DS pregnancy (FPR 5.0%). This makes the 'combined test' by far the best test for the detection of DS pregnancies in a low-risk population. The constant increase in maternal age at the time of delivery can also lead to an improved DR if a simple age-dependant protocol for DS detection is used, but only at the price of a much higher number of amniocenteses and subsequent abortions. The DR for DS can be increased much more markedly using the 'combined test' with a FPR that still remains at the level as it was in the early 1970s.

Abortion, Spontaneous↗

PubMed1999

The utility of a dilatation and evacuation procedure in patients with symptoms suggestive of ectopic pregnancy and indeterminate transvaginal ultrasonography.

OBJECTIVES: To ascertain the overall frequency of obtaining chorionic villi (CV) in patients with indeterminate transvaginal ultrasound (US) examinations who have had a dilatation and evacuation (D+E) procedure performed, to determine whether the frequency of obtaining CV is dependent on whether the endometrial cavity is empty at US, and to determine the likelihood of ectopic pregnancy in patients without CV after D+E and with or without an empty endometrial cavity at US. METHODS: A retrospective review was made of consecutive ED patients presenting to an urban teaching hospital from August 1991 through August 1997 with abdominal pain or vaginal bleeding and a positive beta-human chorionic gonatropin (beta-hCG) test. Patients who had a transvaginal US that was read as indeterminate (no extrauterine findings of ectopic pregnancy, and no intrauterine fetal pole or yolk sac) and who had a D+E performed within 48 hours of the ED visit were eligible. US exams were subdivided into two groups, those with empty endometrial cavities and those with endometrial cavities that contained fluid, echogenic material, or sac-like structures. The presence or absence of CV was based on the official pathology report. Patients were excluded if pathology results were not available. RESULTS: A total of 255 patients met eligibility criteria. Of these, pathology results were not available for five patients. Of the remaining patients, 177 of 250 (70.8%: 95% CI = 64.7% to 76.3%) had CV identified in the pathology specimen. The difference in the frequencies of obtaining CV in those with empty endometrial cavities (35/78; 44.9%: 95% CI = 34% to 56%) vs. those without empty endometrial cavities (142/172; 82.6%: 95% CI = 76% to 88%) was significant (p<0.001). Ectopic pregnancy was diagnosed in 17 of 42 (40.0%) with empty uteri at US and no CV at pathology vs 5 of 26 (19.2%) in whom the uterus was not empty and no CV were obtained (p = 0.07). CONCLUSION: In symptomatic patients with indeterminate transvaginal ultrasound exams, CV will be identified after D+E in approximately 70% of cases. Although CV were found with increased frequency when the endometrial cavity was not empty, still almost half of the patients with empty uteri had villi identified. Finally, although the frequency of ectopic pregnancy was higher in the patients with empty uteri and no CV at D+E, vs. those without an empty uterus and no CV, this difference did not reach statistical significance.

Abortion, Therapeutic↗

PubMed2003

Applications of monoclonal anti-human inhibin alpha subunit in endometrial curettings.

AIMS: Using archival material, we studied the immunoreactivity and utility of monoclonal anti-human inhibin alpha subunit in the identification of chorionic villi (CV) and trophoblastic subpopulations in endometrial curettings (EC) from patients who had intra-uterine, ectopic, molar and, particularly, probable intra-uterine pregnancies. We also compared its expression with those of betaHCG, HPL and CAM 5.2. METHODS: The four groups of EC investigated included: Group 1, 15 patients with intra-uterine pregnancies (IUP); Group 2, 15 patients with tubal pregnancies (TP); Group 3, 15 patients with hydatidiform moles (HM); and Group 4, 20 patients with purported history of intra-uterine pregnancies (PIUP). Positive and negative control cases were from Groups 1 and 3 and Group 2, respectively. The test cases were from Group 4. Immunohistochemistry was performed on each case testing for expression of inhibin alpha, betaHCG, HPL and CAM 5.2. RESULTS: Trophoblastic populations, which included syncytiotrophoblast (ST), cytotrophoblast (CT) and intermediate trophoblast (IT), were absent in all 15 negative control cases (Group 2). The 30 positive control cases (Groups 1 and 3) revealed the following: (a) ST, CT and IT were identified in all cases and were positive for CAM 5.2, (b) inhibin alpha, betaHCG and HPL (except one case) were reactive for all cases with ST, but not CT, and (c) IT positivity for betaHCG, HPL and inhibin alpha was 67, 80-93 and 100%, respectively. From the 20 test cases (Group 4), the findings were: (a) CT was absent in all cases, (b) scattered ST cells, which were identified only in 10 cases, were positive for all antibodies, (c) scattered IT cells were present in 17 cases and showed 100% CAM 5.2 positivity, and (d) IT positivity for betaHCG, inhibin alpha and HPL was 58.8% (10/17), 76.5% (13/17) and 82.4% (14/17), respectively. Background staining was observed in 22 of 65 cases (33.8%) stained with betaHCG and HPL; half of these cases came from Group 3. Inhibin alpha and CAM 5.2 staining did not show this problem. CONCLUSIONS: We suggest that inhibin alpha is a useful antibody in diagnosing IUP and HM and in documenting intra-uterine gestations in cases with PIUP because it is a sensitive marker in immunolabelling IT and ST. Combined application of inhibin alpha and CAM 5.2 might be more useful than betaHCG and HPL because the latter showed background staining in one third of the cases.

Adolescent↗

PubMed2005

First-trimester screening for trisomy 21 in twin pregnancy: does the addition of biochemistry make an improvement?

OBJECTIVE: To evaluate the effectiveness of the addition of first-trimester biochemistry to fetal nuchal translucency (NT) measurement in the Combined Test when screening for trisomy 21 in twin pregnancies. METHODS: Maternal serum free beta-hCG and PAPP-A were determined at 8 to 12 weeks and fetal NT was measured at 11 to 14 weeks. The individual risks were estimated for each of the fetuses using both NT screening alone and the Combined Test. An invasive diagnostic procedure was offered when the risk was 1:250 or over in either one of the fetuses. In the first period, only the results of NT screening were clinically applied. After previous analysis, the Combined Test was introduced into clinical practice. RESULTS: In the two-and-a-half-year study period, a complete follow-up was obtained in 100 twin pregnancies. Three fetuses (two pregnancies) with trisomy 21 were detected by both methods. The false-positive rate achieved by NT screening (14.3% of pregnancies and 8.6% of fetuses) was substantially reduced when first-trimester biochemistry was added in the Combined Test (5.1% of pregnancies and 3.6% of fetuses). CONCLUSION: The Combined Test appears to maintain the detection rate achieved by NT screening for trisomy 21 in twin pregnancies, but false-positive rates and invasive diagnostic procedures are reduced.

Adult↗