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Biomedical subjects

M I Evans

Publications and source records attributed to M I Evans.

At least 19 recordsLinked to original sources
PubMed2003

Anxiety among women who have undergone fertility therapy and who are considering multifetal pregnancy reduction: trends and implications.

OBJECTIVE: Our primary objective was to evaluate the assumption that women carrying multiple fetuses and who have decided upon multifetal pregnancy reduction (MFPR) have a constant high level of anxiety. METHODS: A total of 66 multigestation women considering MFPR were asked to consider how anxious they were when they first started fertility therapy. Using that level of anxiety as a reference point, and using their self-assessments as a vehicle for probing the meaning they attached to their emotional state through time, they then assessed their anxiety level at different points in their pregnancy. RESULTS: Self-reported anxiety across time displayed considerable variation: there was a large drop in anxiety with pregnancy diagnosis. The women's anxiety rose to very high levels with the diagnosis of carrying multiples. Anxiety moderated again on average with consultation, rose sharply during the course of the procedure, and finally dropped to lower levels on average after the procedure was over. CONCLUSIONS: We conclude that women with multigestation experience considerable fluctuations in their level of anxiety from the time that they first start fertility therapy until they learn that they are carrying multiple embryos. Their expectations for the future of becoming pregnant seem at last fulfilled (becoming pregnant), become complicated (with multiples), appear salvageable (with consultation), but with a morally complicated resolution (MFPR) that seems at last to have put the pregnancy back on a normal track (post-MFPR). Those working with MFPR patients before, during and after the operation must understand the nature and variability of the anxiety that their patients are confronting, and how they are attempting to construct a safe passage through the moral dilemma associated with the multiple-gestation situation.

Adult↗
PubMed2002

Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data. National Institute of Child Health and Development Fetal Cell Isolation Study.

OBJECTIVES: The National Institute of Child Health and Human Development Fetal Cell Isolation Study (NIFTY) is a prospective, multicenter clinical project to develop non-invasive methods of prenatal diagnosis. The initial objective was to assess the utility of fetal cells in the peripheral blood of pregnant women to diagnose or screen for fetal chromosome abnormalities. METHODS: Results of fluorescence in situ hybridization (FISH) analysis on interphase nuclei of fetal cells recovered from maternal blood were compared to metaphase karyotypes of fetal cells obtained by amniocentesis or chorionic villus sampling (CVS). After the first 5 years of the study we performed a planned analysis of the data. We report here the data from 2744 fully processed pre-procedural blood samples; 1292 samples were from women carrying singleton male fetuses. RESULTS: Target cell recovery and fetal cell detection were better using magnetic-based separation systems (MACS) than with flow-sorting (FACS). Blinded FISH assessment of samples from women carrying singleton male fetuses found at least one cell with an X and Y signal in 41.4% of cases (95% CI: 37.4%, 45.5%). The false-positive rate of gender detection was 11.1% (95% CI: 6.1,16.1%). This was higher than expected due to the use of indirectly labeled FISH probes in one center. The detection rate of finding at least one aneuploid cell in cases of fetal aneuploidy was 74.4% (95% CI: 76.0%, 99.0%), with a false-positive rate estimated to be between 0.6% and 4.1%. CONCLUSIONS: The sensitivity of aneuploidy detection using fetal cell analysis from maternal blood is comparable to single marker prenatal serum screening, but technological advances are needed before fetal cell analysis has clinical application as part of a multiple marker method for non-invasive prenatal screening. The limitations of the present study, i.e. multiple processing protocols, are being addressed in the ongoing study.

Adult↗
PubMed2001

Prenatal diagnosis of a de novo ring chromosome 11.

Ring chromosomes are uncommon findings in prenatal diagnosis. Growth retardation is the most significant manifestation, in particular among patients with rings of larger chromosomes. A 30-year-old gravida 1, para 0 white woman was referred for genetic counseling because of maternal anxiety. Cytogenetic analysis of amniotic fluid cells at 16 weeks gestation revealed an abnormal mosaic female chromosome complement; 46,XX,r(11)(p15q25)[14]/45,XX,-11[7]. The ring 11 showed no detectable loss of chromosomal material at 450 band level. Both parents had a normal karyotype. Fluorescence in situ hybridization demonstrated intact subtelomeric regions in the ring chromosome. A targeted ultrasound evaluation at the time of consultation suggested no significant abnormalities. The parents were counseled and subsequently decided to terminate the pregnancy. The autopsy revealed an immature female fetus with abnormal craniofacial features including brachycephaly, low-set ears and hypertelorism, bicornuate uterus, and calcifications in the renal tubules. The abnormal phenotypes could be a consequence of the ring instability, submicroscopic deletion, and/or alteration of genetic material at the site of fusion.

Adult↗
PubMed2001

First-trimester embryo size discordance: a predictor of premature birth following multifetal pregnancy reduction.

OBJECTIVE: We have previously reported a correlation between the starting number of embryos for multifetal pregnancy reduction (MFPR) and discordance in size during the first trimester. Here we evaluated the correlation between the degree of discordance and length of gestation in the remaining fetuses. DESIGN: Observational clinical series. SETTING: Academic medical center with a single physician who performs a large number of MFPRs. PATIENT(S): Analysis of 252 consecutive MFPRs from a 2.5-year period (1996-1998). INTERVENTION(S): MFPR for patients with multifetal pregnancies. MAIN OUTCOME MEASURE(S): We evaluated the correlation between the degree of discordance in embryo size, as measured by the greatest difference in crown-rump length (CRL) (delta max), and the length of gestation. RESULT(S): Embryo size discordance was related to length of gestation of the remaining fetuses after MFPR. Of 72 patients with a delta max >5 mm, the rate of severe premature birth (delivery at <28 weeks' gestation) was 9.7%, compared with 1.7% for patients with a delta max <5 mm (P<.01). Of patients with severe premature birth, 70% had delta max >5 mm, compared with less than 30% in patients who delivered after 28 weeks (P<.05). CONCLUSION(S): Variations in embryo growth patterns in multifetal pregnancies may be observed even in the first trimester, which may be predictive of late pregnancy outcomes. With a delta max > or =5 mm, there is a significant increase in the risk of severe premature birth (delivery at <28 weeks).

Crown-Rump Length↗
PubMed2001

Principles of screening.

Over the past several decades, the principles by which screening tests are performed have slowly been developed and refined. The key distinction for the clinician to understand is the difference between diagnostic tests, which give a definitive answer, and screening tests, which identify who among the low-risk population is at high risk.

Genetic Testing↗
PubMed2001

Screening for neural tube defects.

Neural tube defects are separated into two main categories: (1) abnormalities of the skull and brain (anencephaly, acrania, and encephalocele) and (2) malformations of the spine (meningomyelocele or spina bifida). The cause of neural tube defects is not always clear, and include chromosomal abnormalities, single gene mutations, maternal disease, or maternal exposure to teratogens. Mostly the disorder emerges as a multifactorial trait. Routine screening for neural tube defects was introduced in the United Kingdom in the mid-1970s and the United States in the mid-1980s. The use of screening has resulted in a marked decline in the frequency of neural tube defects diagnosed at birth.

Female↗
PubMed2001

Second-trimester biochemical screening.

The past years have seen considerable progress in the area of biochemical screening. Increasing data have now clearly shown the advantages of multiple markers, particularly beta-hCG over AFP alone. There continues to be considerable controversy over the best mathematic algorithm and which markers are best (e.g., beta-HCG, uE3, and so forth). There seems to be a plateau of detection frequencies at about 65% to 70% with current methodologies. Further work needs to be done, however, including some new approaches, if there is to be substantial improvement of screening sensitivity. The combination of biochemical with biophysical parameters as discussed elsewhere in this issue represents the next level of sophistication in the attempt to identify the highest proportion of abnormalities with the fewest false-positives.

Algorithms↗
PubMed2001

Future directions.

With the continued explosion of genetic technology, the number of disorders amenable to screening is expanding geometrically. Historically, most genetic screening has been in the newborn period. Much more can be done for the fetus if genetic screening and diagnosis are accomplished early in the pregnancy rather than after birth. The principal requirements to make neonatal screening disorders possible in the first trimester center around those tests that can be one on a molecular basis, and the development of fetal cell isolation from the maternal circulation. Over the course of the next decade, it is likely that many of the tests currently performed in the newborn period will be accomplished in the early or mid-gestational period.

Forecasting↗
PubMed2001

Estrogen modulates the expression of L-arginine:glycine amidinotransferase in chick liver.

Identification of estrogen-responsive genes is important to understand the molecular mechanisms of estrogen action. Suppression subtractive hybridization was employed to screen estrogen-responsive genes in chick liver. A single injection of estrogen into 6-week-old chick induced up-regulation of several known genes encoded for yolk proteins, such as Vitellogenin I and II and very low density lipoprotein II (apo-VLDL II). One novel sequence displayed a dramatic change (3-fold increase) in response to estrogen treatment. This cDNA fragment was extended and the resultant sequence was analyzed. Translated amino acid sequence was 90, 88, 83 and 87% identical to the L-arginine:glycine amidinotransferase of pig, rat, frog and human, respectively. The sequence has a conservative catalytic site of L-arginine: glycine amidinotransferase. The expression pattern of this gene in organs is consistent with previous reports of L-arginine:glycine amidinotransferase in chick. Thus, this clone represented the chicken L-arginine:glycine amidinotransferase. It appeared that estrogen-induced alteration of arginine:glycine amidinotransferase was not dependent on protein synthesis, because concurrent administration of cycloheximide did not affect the estrogen-mediated expression pattern. This is the first study demonstrating that L-arginine:glycine amidinotransferase is a target of the estrogen receptor.

Amidinotransferases↗
PubMed2001

Improvement in outcomes of multifetal pregnancy reduction with increased experience.

OBJECTIVE: This study was undertaken to evaluate a decade of data on multifetal pregnancy reductions at centers with extensive experiences. STUDY DESIGN: A total of 3513 completed cases from 11 centers in 5 countries were analyzed according to year (before 1990, 1991-1994, and 1995-1998), starting and finishing numbers of embryos or fetuses, and outcomes. RESULTS: With increasing experience there has been a considerable improvement in outcomes, with decreases in rates of both pregnancy loss and prematurity. Overall loss rates in the last few years were correlated strongly with starting and finishing numbers (starting number > or =6, 15.4%; starting number 5, 11.4%; starting number 4, 7.3%; starting number 3, 4.5%; starting number 2, 6.2%: finishing number 3, 18.4%; finishing number 2, 6.0%; finishing number 1, 6.7%). Birth weight discordance between surviving twins was increased with greater starting number. The proportion of cases with starting number > or =5 diminished from 23.4% to 15.9% to 12.2%. The proportion of patients >40 years old increased in the last 6 years to 9.3%. Gestational age at delivery did not vary with increasing maternal age but was inversely correlated with starting number. CONCLUSION: Multifetal pregnancy reduction outcomes at our centers for both losses and early prematurity have improved considerably with experience. Reductions from triplets to twins and now from quadruplets to twins carry outcomes as good as those of unreduced twin gestations. Patient demographic characteristics continues to change as more older women use assisted reproductive technologies. In terms of losses, prematurity, and growth, higher starting numbers carry worse outcomes.

Abortion, Spontaneous↗
PubMed2000

Determinants of parental decisions after the prenatal diagnosis of down syndrome: bringing in context.

This article develops the concept of decision context to refer to the combinations of factors that are important in understanding and predicting termination decisions after a prenatal diagnosis of trisomy 21. Four factors are examined: maternal age, gestational age, prior voluntary abortion, and existing children. The cases were studied at the Wayne State University's Reproductive Genetics Clinic. Qualitative comparative analysis, a technique specifically designed for examining the impact of combinations of factors, is used to isolate influential decision contexts. Odds and odds ratios are used to pinpoint outcome differences among different decision contexts. Four alternative decision contexts are especially conducive to choosing to terminate a pregnancy. Two of these involve women of any age and are formed from combinations of gestational age and existing children (existing children and low gestational age, and no children combined with late gestational age). Older women who have not had an abortion and who discover the trisomy 21 anomaly early are likely to choose termination. Younger women who have had an abortion are also likely to choose termination. Our data suggest there are added layers of complexity to patients' decisions that derive from combinations of conditions. An additional, strong implication is that qualitative comparative analysis may be particularly useful in understanding such complexity.

Abortion, Induced↗
PubMed2000

Fiscal impact of a potential legislative ban on second trimester elective terminations for prenatally diagnosed abnormalities.

This study was designed to determine the fiscal impact of a theoretical legislative ban on elective terminations for prenatally diagnosed abnormalities at Hutzel Hospital/Wayne State University. A fiscal comparison was completed for patients who had second trimester elective terminations for prenatally diagnosed abnormalities versus not allowing the procedure. An eight-year database of genetics cases and hospital and physician cost estimates for performing elective terminations for prenatally diagnosed abnormalities, and published reports of the average lifetime costs per selected birth defects, were used to calculate the net cost. The estimated lifetime cost for an average cohort year of a legislative ban on elective terminations for prenatally diagnosed abnormalities was found to be at least $8.5 million for patients treated at Hutzel Hospital. Extrapolated, a similar ban on second trimester elective terminations would have a net cost of $74 million in Michigan and $2 billion annually in the United States.

Abortion, Induced↗
PubMed2000

Routine prenatal diagnosis of aneuploidy by FISH studies in high-risk pregnancies.

This study is a prospective clinical trial with fluorescent in situ hybridization (FISH) as a "routine" test for prenatal detection of the most common aneuploidies in high-risk pregnancies. Since April 1996, FISH studies with multicolor, commercially available, specific probes for chromosomes 13, 18, 21, X, and Y have been routinely performed in our cytogenetic laboratory on uncultured chorionic villous samplings (CVS), amniotic fluid samples, or fetal blood obtained by cordocentesis from patients with major or minor fetal anomalies detected by ultrasonography. Among the 4,193 prenatal samples analyzed between April 1996 and June 1998, routine FISH studies were ordered by the referring physicians on 301 (7.2%) cases. Aneuploidies were detected in 32 (10.6%) samples. Fourteen trisomy-21, 10 trisomy-18, 3 trisomy-13, 4 monosomies of X, and 1 case of triploidy were diagnosed by FISH. All 1,505 hybridizations were informative, and all 301 results were available and reported to the referring physicians in 24-48 hr. All relevant FISH results were confirmed by subsequent cytogenetic analysis. In 10 (3.8%) cases with normal FISH results, the final cytogenetic analysis revealed abnormal chromosomal rearrangements that could not be detected by the routine FISH studies. We conclude that rapid FISH analysis of interphase, uncultured fetal cells is an accurate and very sensitive method for routine prenatal diagnosis of the most common aneuploidies in high-risk pregnancies.

Aneuploidy↗
PubMed2000

Ultrasound screening for fetal chromosome anomalies.

Ultrasound evidence for aneuploidy may be found in almost every organ of the fetus and can be used to modify the risk of aneuploidy. The diagnosis of these minor anomalies on second-trimester ultrasonography will increase the risk of an abnormal karyotype whereas the absence of these findings may reduce this danger. The most specific and most ominous isolated markers for fetal aneuploidy are nuchal findings (edema or cysts), indicating the need to obtain a fetal karyotype in all cases irrespective of maternal age or results of biochemical serum screening. Hyperechoic fetal bowel is apparently also a strong indicator of fetal aneuploidy. Other isolated sonographic markers may increase the risk of an abnormal karyotype three- to ninefold. Most sonographic markers for aneuploidy specify an increased risk for Down syndrome, but choroid plexus cysts are apparently more specific for trisomy 18. Along with other screening methods, ultrasound screening for fetal aneuploidy should be used routinely to identify additional pregnancies at need for evaluation of fetal karyotype.

Aneuploidy↗
PubMed2000

Expression and regulation of vascular endothelial growth factor in a first trimester trophoblast cell line.

Embryo implantation and development are critically dependent upon the spatial and temporal regulation of angiogenesis and localized vascular permeability. A key mediator of these effects is the endothelial cell mitogen vascular endothelial growth factor (VEGF). VEGF has been shown to promote endometrial vascular permeability, fetal vasculogenesis and placental, fetal and maternal angiogenesis. However, the mechanism through which this regulation occurs in the placenta is poorly understood. This study was conducted to determine if the pro-angiogenic cytokines, TNF-alpha and TGF-beta1, affect VEGF expression in human first trimester trophoblasts. Culture of a first trimester trophoblast cell line (HTR-8/SVneo), in the presence of either TNF-alpha or TGF-beta1, resulted in the expression of significant levels of VEGF in culture. The trophoblast cell line also showed a time-dependent and a dose-dependent increase in VEGF mRNA levels when cultured in the presence of either TNF-alpha or TGF-beta1. These results suggest that both TNF-alpha and TGF-beta1 may regulate the production of VEGF in early gestational trophoblasts and may therefore serve to modulate placental vascular permeability and angiogenesis that are necessary for embryo implantation and placentation.

Adult↗