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Detection of fetal DNA in trans-cervical swabs from first trimester pregnancies by gene amplification: a new route to prenatal diagnosis?

OBJECTIVE: To determine whether fetal sex can be predicted from fetal DNA retrieved transcervically from the lower part of the uterine cavity in the first trimester of pregnancy. DESIGN: Prospective observational study. SETTING: St James's University Hospital, Leeds. SUBJECTS: 33 women undergoing legal termination of pregnancy at 9 to 13 weeks gestational age. INTERVENTIONS: Before termination of pregnancy samples for DNA analysis were obtained with cotton wool swabs from the vagina, cervix and transcervically in 26 women. In the other seven women samples were obtained using a transcervical cell retrieval (TraCeR) procedure involving flushing the lower uterine cavity with 5 ml saline. MAIN OUTCOME MEASURES: Detection of Y-chromosome specific DNA sequences by the polymerase chain reaction (PCR) in cotton wool swabs taken from the lower uterus in the first trimester of pregnancy to predict fetal sex in comparison with standard cytogenetic analysis. Histological and immunohistochemical analysis of samples obtained by flushing of the lower uterine cavity (TraCeR) to confirm the presence of trophoblast. RESULTS: Fetal sex was predicted accurately in 25 of the 26 pregnancies investigated. Immunohistochemical analysis identified syncytial trophoblast fragments in all seven pregnancies investigated by TraCeR. CONCLUSION: Trophoblast may be retrieved from the lower uterus in the first trimester by swabs or TraCeR. When purification of these syncytial fragments can be achieved using immuno-magnetic technology, this test will enable prenatal diagnosis of single gene defects in the fetus by the polymerase chain reaction.

Cervix Uteri↗

Ethical decision making in first trimester pregnancy screening.

Many couples enter pregnancy without an intricate understanding of the potential maternal and fetal/newborn complications. While it is reasonable for expectant couples to consider only the positive outcomes, it is the role of the healthcare professional to educate the parents on the options for fetal screening and testing. Once couples have this information, it is their opportunity to consider the options according to their beliefs and values. In reviewing the principles of ethics, healthcare professionals will gain a better understanding of their role in the couple's decision making. Recommendations are made for maintaining and improving optimal patient care in first trimester pregnancy screening.

Adult↗

Suppression of mixed lymphocyte reaction by cells of human first trimester pregnancy endometrium.

In order to identify an immunological role for decidual tissue in pregnancy we have prepared single cell suspensions from the tissues of normal pregnant women and examined the effects of these cells on one-way mixed-lymphocyte reactions (MLR). The separated cells were heterogeneous, containing classical decidual cells, glandular epithelial cells, granular endometrial cells, macrophages and small lymphoid cells. [3H]Thymidine incorporation at day 6 of the MLR was suppressed by addition of the cells at the initiation of the cultures and the degree of suppression was inversely correlated to the gestational age of the decidual tissue, apparently through inhibition of the antigen recognition phase of the MLR. These findings support the view that the cells of the human first trimester pregnancy endometrium may play an important role in protecting the feto-placental unit from rejection, at least in the early phase of pregnancy.

Antigens, Surface↗

Evaluation of first trimester pregnancy in cases of threatened abortion by means of doppler sonography.

OBJECTIVE: Threatened abortion is one of the major problems in Obstetrics and applies to (1/3) of all pregnancies. The aim of this study was to establish normal ranges for Doppler indices of the flow velocity waveforms in uterine arteries (S/D, RI, PI) and ss-hCG serum concentrations in a control group in the first trimester of pregnancy. The obtained values were compared with those obtained in pregnancies threatened by abortion (6 - 11 weeks). METHODS: Investigated groups: 55 controls and 47 with symptoms of threatened abortion, 27 of them aborted. Ultrasound examinations were carried out by means of an endovaginal probe. Serum ss-hCG was determined by immunoenzymatic method. The standards for measured values were established based on means from measurements obtained in the control group in the corresponding week of pregnancy. RESULTS: We observed negative correlation between gestational age and RI and negative tendencies for S/D and PI indices in the control group. Positive correlation (p < 0.05) was found between ss-hCG serum concentration and gestational age (up to 9(th) week) and significant differences in ss-hCG concentrations between both examined groups. There were also statistical differences for S/D, RI and PI indices in both analyzed groups for each week of pregnancy. CONCLUSION: We conclude that measurement of the quality parameters of the flow velocity waveforms in uterine arteries and calculation of beta-hCG concentration in serum are useful methods in diagnosis of threatened abortion in the first trimester of pregnancy.

Abortion, Threatened↗

Activation of complement in humans with a first-trimester pregnancy loss.

Serum complement (C') activity in recurrent spontaneous aborters and primiparous controls with successful and unsuccessful pregnancies was quantified so as to define the dynamics of C' activation in early pregnancy loss. C' hemolytic activity was shown to be stable throughout the first trimester of pregnancy and did not differ from preconception levels in all of the successful pregnancies of recurrent aborters and controls and in the majority of pregnancy losses. However, 30% of recurrent aborters and 20% of controls with a pregnancy loss demonstrated activation of C' by the alternate pathway as early as the 7th week with a progressive decline in C' activity until abortion was clinically completed. Circulating levels of C3 dropped from 1.34 to 0.53 mg/dl, and factor B levels declined from 0.34 to 0.14 mg/dl in these hypocomplementemic women. Pregnancy loss is therefore associated with C' activation in a subset of both recurrent and nonrecurrent aborters and this occurs largely before loss of fetal viability.

Abortion, Habitual↗

Fetal blood group determination in first-trimester pregnancy for the management of severe immunization.

The presence or absence of Rho (D) and Kell antigens on fetal red blood cells was determined in the first trimester of pregnancy on erythrocytes obtained by chorionic villi sampling with the use of mixed agglutination and solid phase microimmunofluorescence techniques. Pregnancies in one Kell-sensitized woman and seven severely RH-sensitized women with a poor obstetric history and a partner heterozygous for the offending antigen were examined. A conclusive diagnosis could be made in seven of the eight cases studied.

Blood Grouping and Crossmatching↗

Oral administration of the prostaglandin enisoprost induces uterine activity and softens the cervix during first trimester pregnancy.

48 patients in the first trimester of pregnancy received a single oral dose of placebo or enisoprost (prostaglandin E1 analogue): 10, 25, 50, 100, 200 or 400 micrograms. Uterine activity was recorded for 1 h before and for 4 h after administration of the study drug with a Millar microtransducer. There was a dose-related increase in mean resting and active pressure, but not in frequency of pressure cycles. At the highest dose used, namely 400 micrograms, all 6 subjects bled. Enisoprost dilated the cervix and any further dilatation required was easy to accomplish.

Abortion, Induced↗

Effect of local lignocaine gel application for pain relief during suction termination of first-trimester pregnancy: a randomized controlled trial.

BACKGROUND: This study evaluated the effectiveness of local lignocaine gel application in pain control during first-trimester suction termination of pregnancy (STOP). METHODS: In this prospective randomized placebo-controlled double-blind trial, 131 women undergoing STOP between 7 and 10 weeks of gestation were studied. They were computer-randomized to receive 2% lignocaine gel or placebo (KY Jelly) locally applied to the cervix 1 min before cervical manipulation/dilatation. They all had cervical priming with misoprostol and premedication with diazepam and pethidine. Pain scores on a verbal analogue scale preoperative, at cervical manipulation/dilatation, intraoperative and 1 h post-operative, as well as the patients' satisfaction level towards pain control, were compared. RESULTS: The lignocaine gel group had significantly reduced overall intraoperative pain score compared with placebo group (P = 0.021). No significant difference in pain score between the two groups was demonstrated at other time points. Subgroup analysis revealed that the difference in overall intraoperative pain scores between the two groups was evident in the multiparous (P = 0.015) but not the nulliparous subjects. CONCLUSION: The use of local lignocaine gel application reduces overall intraoperative pain in multiparous women undergoing first-trimester STOP preceded by misoprostol cervical priming and premedication for conscious sedation.

Abortion, Induced↗

Fas and Fas-ligand are expressed in the uteroplacental unit of first-trimester pregnancy.

PROBLEM: Fas and Fas-ligand (FasL) are thought to provide a strategy for reducing graft rejection in immunologically 'privileged' tissues by controlling injurious lymphocyte reactions. As the uteroplacental unit is often defined as an immune-privileged site, we investigated the expression of Fas and FasL in this tissue in the first trimester of pregnancy. METHOD OF STUDY: Western blotting, immunohistochemistry, and double immunofluorescence were used for this examination. RESULTS: Western blotting with purified first-trimester trophoblast cells revealed one specific band for FasL. The presence of FasL on different trophoblast populations could be confirmed by immunohistochemistry and double immunofluorescence. In the villous part of the placenta, FasL is mostly located on cytotrophoblast cells with no access to maternal blood flow, whereas in trophoblast-invaded uterine tissue, interstitial trophoblast cells, which are in close contact with maternal leukocytes, revealed a strong signal for FasL, but no staining for Fas on these cells. However, Fas was found on CD45+ maternal leukocytes. CONCLUSION: Based on our experimental findings, we speculate that the abundant presence of FasL on trophoblast cells within the maternal decidua may play an important role in the maintenance of immune privilege in the pregnant uterus by endowing fetal trophoblast cells with a defense mechanism against activated maternal leukocytes, whereas in the villous part of the placenta, the Fas FasL system seems to be involved in the regulation of placental growth.

Apoptosis↗

Decreased endovascular trophoblast invasion in first trimester pregnancies with high-resistance uterine artery Doppler indices.

BACKGROUND: Defective trophoblastic invasion in early pregnancy is involved in the pathogenesis of pre- eclampsia. This study investigates the relationship between Doppler assessment of uterine artery resistance and endovascular trophoblastic invasion in the first trimester of pregnancy. METHODS: Patients undergoing termination of pregnancy for non-medical reasons were categorized as having a low- or high-resistance uterine artery blood flow pattern by transabdominal Doppler ultrasound. Products of conception were examined histologically with regard to the extent of decidual endovascular trophoblast invasion. RESULTS: There were 14 low-resistance and 17 high-resistance uterine artery blood flow pregnancies identified at 10-14 weeks of gestation. Normal intradecidual endovascular trophoblast invasion was identified with a similar frequency in both groups (P=0.79). However, the proportion of decidual vessels with endovascular trophoblast invasion was significantly higher in the low-resistance pregnancies (49%) compared with the high-resistance ones (34%, P=0.02). CONCLUSIONS: The findings of this study support the use of uterine artery Doppler investigation for the non-invasive assessment of trophoblast invasion in early pregnancy. Further studies are necessary to clarify the biological significance of these observations and their potential clinical applications.

Adult↗

Care of women having termination of first-trimester pregnancy.

The care of women having termination of pregnancy has always presented social, ethical and legal concerns to nurses and other healthcare professionals. Women having first-trimester termination of pregnancy may have the choice between medical and surgical methods. The process and procedure of these two approaches are discussed and the implications for nursing practice identified. There is now research evidence that explores women's experiences of these various methods and gives some insight into what the woman may experience. Nurses must have knowledge of these methods of termination to enable women to make the correct choices. The challenge for nurses then is to provide and evaluate information that is as effective as possible in meeting the needs of the individual woman.

Abortifacient Agents↗

The chorionic bump: a first-trimester pregnancy sonographic finding associated with a guarded prognosis.

OBJECTIVE: We describe a series of patients with a previously unreported sonographic finding, the chorionic "bump," which is an irregular, convex bulge from the choriodecidual surface into the first-trimester gestational sac. The pregnancy outcome is investigated in this series of patients and compared with the general population and infertility first-trimester control groups. METHODS: We prospectively noted a cohort of 15 cases with the chorionic bump on first-trimester sonograms (in a total of 2178 patients) performed over 3 years at our institution (prevalence, 0.7%). We then compared pregnancy outcomes against 2 pregnant control groups (15 general, noninfertility patients and 15 infertility patients) who were maternal age and gestational age matched to our patient group. RESULTS: The difference in outcomes between the patients with bumps and the healthy control subjects was statistically significant (7 live births versus 13 live births; P < .03), but the difference in outcomes between the patients with bumps and infertility control subjects was not statistically significant (7 live births versus 11 live births; P = .1). Bump size was not correlated with pregnancy outcome. In most patients with serial sonograms, the bump showed evolutionary changes typical for hematoma. CONCLUSIONS: The finding of a chorionic bump on the first-trimester sonogram is associated with a guarded prognosis for the early pregnancy (live birth rate <50%); it probably represents a small hematoma that bulges into the gestational sac, and, in our series, most patients had a history of infertility treatments.

Adult↗

Echogenic adnexal masses associated with first-trimester pregnancy: sonographic appearance and clinical significance.

In a retrospective survey of a large obstetrical ultrasound experience, 10 echogenic adnexal masses in nine patients with a coexistent intrauterine pregnancy were detected and analyzed. Definitive follow-up data available for seven of the nine patients disclosed three ovarian teratomas, two hemorrhagic corpus luteum cysts, one endometrioma, one inflammatory mass, and one colonic pseudomass. In one additional patient, an echogenic ectopic pregnancy with an intrauterine pseudogestational sac simulated the above entities. Conservative management with follow-up sonography is generally indicated for echogenic masses coexistent with first-trimester intrauterine pregnancies.

Adnexa Uteri↗

[Severe hydrops fetalis in a first trimester pregnancy with Ulrich-Turner syndrome].

We report about a case of abundant hydropic evolution of a fetus in the first trimester of gestation. Already in the 8th week of gestation we diagnosed the first references of failure with transvaginal ultrasound. In the following three weeks we observed the progression of the hydrops. The genetic research of fetal tissue after induced abortion show the karyotype 45 X0.

Adult↗

Apoptotic nuclei within the uterine decidua of first trimester pregnancy arise from CD45 positive leukocytes.

PROBLEM: The Fas/Fas-ligand (FasL) system is discussed to be one of the main components responsible for the formation and maintenance of an immune privilege. As we were able to detect FasL on fetal trophoblast cells infiltrating the maternal uterine tissue and Fas on decidual leukocytes (Hammer et al., Am J Reprod Immunol, 1999; 41: 41-51), we investigated whether apoptosis occurs in the maternal decidua during the first trimester of pregnancy. METHOD OF STUDY: A TUNEL-assay was performed in combination with immunofluorescence to detect and characterize cells undergoing apoptosis. RESULTS: Apoptotic nuclei mainly arising from CD45+ leukocytes could be detected in the trophoblast-invaded decidua basalis as well as in the non-invaded decidua parietalis. However, while in the decidua parietalis the apoptotic leukocytes are scattered within the whole functional stroma, in the decidua basalis they are concentrated in the area around the so-called "necrotic foci" and especially in the primary feto-maternal contact zone. where trophoblast cells from the cell columns begin to invade the maternal tissue. CONCLUSION: Because of the irregular distribution of apoptotic CD45+ leukocytes in the decidua basalis we think that some of the maternal leukocytes are activated and killed by fetal trophoblast cells which express FasL.

Apoptosis↗

First trimester pregnancy loss associated with varicella zoster virus infection: histological definition of a case.

Pathological demonstration of varicella infection in first trimester aborted tissue is reported. A 24-year-old primigravida manifested chickenpox infection about 38 days after her last menstrual period or at 24 days age of the embryo. The conceptus survived another 4 to 5 weeks. The macerated embryo and placental tissue revealed nuclear changes consistent with varicella infection. Immunohistochemical stains and electron microscopy were confirmatory.

Adult↗

Uterine and fetal umbilical artery flow velocity waveforms in normal first trimester pregnancies.

In 85 normal singleton pregnancies between 8 and 13 weeks gestation, Doppler flow velocity waveform recordings were attempted from the left and right uterine artery and fetal umbilical artery. Acceptable waveforms were obtained from the uterine arteries in 83 and from the fetal umbilical artery in 61 of the 85 pregnancies. There was virtually no difference between the left and right uterine artery on average. The marked decrease in pulsatility (PI) and resistance (RI) indices from both uterine arteries reflects the ongoing process of secondary trophoblast invasion into the muscular part of the spiral arteries. Absent end-diastolic velocities were observed in 59 of 61 fetal umbilical artery flow velocity waveform recordings. PI values from the fetal umbilical artery suggest unaltered umbilical placental vascular resistance during the first trimester of pregnancy.

Blood Flow Velocity↗