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Mark I Evans

Publications and source records attributed to Mark I Evans.

17 recordsLinked to original sources
PubMed2003

Intact fetal cells in maternal plasma: are they really there?

Rare fetal cells can be recovered from maternal blood, which suggests that non-invasive prenatal diagnosis is possible. However, recovery and analysis of fetal cells from blood is complex, and sensitivity is low because of the rarity of these cells in the maternal circulation. An alternative strategy, which suggested that intact fetal cells can be found in maternal plasma by use of simple enrichment methods, has been reported. We aimed to replicate this technique. However, five independent laboratories were unable to identify any intact male cells from the plasma of 38 women known to be carrying male fetuses. Although apoptotic intact fetal cells could contribute to the detection of fetal DNA in maternal plasma, we believe that recovery of these cells is difficult and not clinically practical.

Aneuploidy↗
PubMed2003

Selective reduction.

Multifetal pregnancy reduction continues to be controversial. Attitudes about MFPR have not, in our experience, followed a simple "pro-choice/pro-life" dichotomy. As far back as the mid to late 1980s, opinions about the subject were varied. Even then, when much less was known about the subject, opinions did not always parallel the usual pro-choice/theological boundaries. We believe that the real debate over the next 5 to 10 years will not be whether or not MFPR should be performed with triplets or more. The fact is that MFPR does improve those outcomes. A serious debate will emerge over whether or not it is appropriate to offer MFPR routinely for twins, even natural ones, for whom the outcome is commonly considered "good enough." Our data suggest that reduction of twins to a singleton improves the outcome of the remaining fetus. No consensus on appropriateness of routine 2-1 reductions is ever likely to emerge. The ethical issues surrounding MFPR will always be controversial. Over the years, much has been written on the subject. Opinions will always vary from outraged condemnation to complete acceptance. No short paragraph could do justice to the subject other than to state that most proponents do not believe this is a frivolous procedure but do believe in the principle of proportionality ie, therapy to achieve the most good for the least harm). Over the past 15 years, MFPR has become a well-established and integral part of infertility therapy and attempts to deal with the sequelae of aggressive infertility management. In the mid 1980s, the risks and benefits of the procedure could only be guessed. We now have clear and precise data on the risks and benefits of the procedure and an understanding that the risks increase substantially with the starting and finishing number of fetuses in multifetal pregnancies. The collaborative loss rate numbers (ie, 4.5% for triplets, 8% for quadruplets. 11% for quintuplets, and 15% for sextuplets or more) seem reasonable to present to patients for the procedure performed by an experienced operator. Our experiences and anecdotal experiences from other groups suggest that less experienced operators have worse outcomes. Pregnancy loss is not the only poor outcome. The other main issue with which to be concerned is very early premature delivery, where there is an increasing rate of poor outcomes correlated with the starting number. The finishing numbers are also critical, with twins having the best outcomes for cases starting with three or more. Triplets and singletons do not do as well. We hope that MFPR will become obsolete as better control of ovulation agents and assisted reproductive technologies make multifetal pregnancies uncommon.

Female↗
PubMed2003

Standardization of methods reduces variability: explanation for historical discrepancies in biochemical screening.

Over the past decade, many studies have argued the relative merits of different chromosome abnormality biochemical screening protocols in different labs. Results and interpretations have varied markedly (e.g., double vs. triple screening). In this study we sought to compare coefficients of variation (CV) among 12 laboratories in one system, using identical and different methodologies for the three parameters. Ten identical specimens were processed as part of the 1999 College of American Pathologists (CAP) (FP-A, FP-B) proficiency tests. Results were compared among 12 laboratories using the Abbott ELISA for alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG), and two methods for estriol [Diagnostic Services Laboratory (DSL) and an "in house" assay]. The range on the 10 specimens of means for AFP varied from 12.56 to 117.87; hCG 14.05-68.08; and estriol 0.61-2.73. CV for AFP specimens averaged 10%, hCG 8%, and estriol 35% (F = 22.4). However, when only DSL was used for estriol, the CV was reduced to 8.7%. Standardization of AFP and hCG across 12 labs has reduced CV to <10%, which is similar to accepted between run results. Wide variation of uE3 among different methods may explain the widely divergent results in the literature. With national standardization of all parameters, the widely divergent results seen in the literature should narrow, and regional medians will no longer be necessary.

Biomarkers↗
PubMed2002

Screening.

Historically, obstetrician/gynaecologists have utilized screening procedures as a major component of their routine clinical practice. The Papanicolaou (Pap) smear technique for cervical cancer is more than 50 years old and has saved countless lives by identifying who among the supposedly low-risk group of patients is in fact at high risk of cervical cancer. The introduction of alpha-fetoprotein screening for neural tube defects in the 1970s, low alpha-fetoprotein level for Down syndrome in the 80s, multiple markers in the 90s and now, after the millennium combined ultrasound and biochemistry for a more precise risk identification, has radically changed our approach towards optimizing the sensitivity, specificity and positive and negative predictive values of screening. As these techniques improve, old mainstays of attributable risks such as advanced maternal age will probably fade into oblivion as stand-alone criteria. The specifics of screening techniques will vary by disorder, but the general principles are important and can be applied to all new technologies as they come on line. In fact, the real 'take-home message' is that one must use these principles when looking at new technologies to understand their role in emerging practice.

Adult↗
PubMed2002

Fetal therapy.

Over the past 40 years, a small but increasing number of fetal genetic and congenital anomalies has become amenable to in utero treatment. Successful fetal therapies have included open procedures for congenital diaphragmatic hernia, cystadenomatoid malformation of the lung and saccrococygeal teratoma, shunts for uropathies and thoracic fluids, pharmacological therapies for congenital adrenal hyperplasia and neural tube defect prevention, and the stem cell treatment of severe combined immunodeficiency disorder.

Adrenal Hyperplasia, Congenital↗
PubMed2002

Procedural risks versus theology: chorionic villus sampling for Orthodox Jews at less than 8 weeks' gestation.

OBJECTIVE: According to Orthodox Jewish law, abortion is only permitted before 40 days post conception. This evaluation was performed to determine the feasibility and safety of performing chorionic villus sampling (CVS) at 7 to 8 weeks' gestation so that genetic results would be useful for these patients. STUDY DESIGN: We evaluated a sequential series of 82 Orthodox Jewish patients who chose CVS at <63 days' gestation. Outcome measures included procedure success rates, laboratory success rates, pregnancy outcomes, and complications. RESULTS: CVS was successful in all cases. Ninety-one percent were performed transcervically, with 30% requiring 2 or more insertions. Abnormal results were found in 16 (20%). Of 61 cases with normal genetic and ultrasound results, spontaneous losses at less than 28 weeks occurred in 3 (5%). These rates are higher than the 2.3% loss rate and the 1.2% multiple insertion rate seen at our center when sampling is performed at the usual gestational ages of 10 to 12 weeks. One baby had a severe limb reduction defect (1.6%). CONCLUSION: In very experienced hands, CVS can be safely and reliably performed at very early gestational ages. The ability to obtain an early diagnosis may be associated with increased but acceptable complication rates, including a 1% to 2% risk of limb reduction defects. There are patients for whom the usual paradigms do not suffice, and obtaining an early disgnosis provides them the opportunity to trade increased risks for reproductive choice. The ethical issues are complex, but such decisions can be supported by extensive and detailed informed consent.

Abortion, Spontaneous↗
PubMed2002

Correction for insulin-dependent diabetes in maternal serum alpha-fetoprotein testing has outlived its usefulness.

OBJECTIVE: Historically, alpha-fetoprotein (AFP) levels in insulin-dependent diabetes (IDDM) have shown an approximately 20% decrement, and a correction factor is used to standardize multiples of the median (MOMs). With new laboratory methods and improved precision, we sought to re-evaluate the correctness of this approach. STUDY DESIGN: Consecutive biochemical screens were conducted among 60,287 nondiabetic patients and 307 patients with IDDM. Analyses were conducted in one laboratory, and comparisons were made with use of standard formula weight adjustments including a 20% correction factor for IDDM. Patients were then stratified according to maternal weight. RESULTS: Nondiabetic patients averaged 1.00 MOM, IDDM patients 0.91 MOM with no adjustments, 0.96 MOM adjusting for weight only, and 1.20 MOM adjusting for weight and diabetes status. To explain the "overcorrection," analysis by maternal weight showed significant overrepresentation of IDDM patients at 175 pounds or above. In fact, the mean weight in pounds for nondiabetic subjects was 151 +/- 35 and for those with IDDM 174 +/- 52 (P <.001). With use of an upper limit weight cutoff of 200 pounds, results are within 4% of normal. CONCLUSIONS: With current methodologies, the 20% correction factor for IDDM erroneously overcorrects. Two hundred pounds is sufficient, the weight correction for diabetic status should be abandoned.

Body Weight↗
PubMed2002

Maternal weight correction for alpha-fetoprotein: mathematical truncations revisited.

The objective of this study was to determine if maternal weight correction as implemented 20 years ago for alpha-fetoprotein (AFP) testing is still appropriate, and what should be the weight cutoff for correction. AFP measurements from 44,951 biochemical screening cases from a single laboratory were divided by maternal weight, and separated into high >/=2.5 multiples of the median (MOM), and low <0.4 MOM. Without weight correction, AFP values are still skewed to lower levels of higher maternal weight (1.1% >/= 2.5 MOM). Using a truncated range to 200 lbs. (for women greater than 200), produces more uniform results than using an upper cutoff of 250 for truncation (2.7% vs 5.0% >/= 2.5 MOM). The same relationship is seen for "lows." Without correction, higher weight lowers AFP, correction to 250 lbs. overcompensates, and 200 lbs. gives the most even distribution, and, therefore, optimizes the distribution of highs.

Body Weight↗
PubMed1993

The choices women make about prenatal diagnosis.

Despite the rapid advancement and increasing utilization of prenatal diagnostic technologies, there has been a paucity of investigation into the psychological, socioeconomic, and demographic features associated with the choices women make about both the uptake of services, and the actions taken after fetal abnormalities are discovered. From 1986 through 1991 we have completed four studies initiating a proposed comprehensive evaluation of these factors. The first two studies concentrated on patient features influencing uptake of prenatal diagnostic procedures in both a priori 'high risk' pregnancies (advanced maternal age) as well as in previously 'low risk' pregnancies which had become 'high risk' by virtue of abnormal maternal alpha-fetoprotein (MSAFP) screening. The second two studies evaluated features influencing abortion decisions after the discovery of either chromosomal anomalies, or non-aneuploid ultrasonographically detected structural abnormalities. Data suggested that (1) older and more highly educated women tended to choose CVS over amniocentesis; (2) perceptions of genetic risk within couples was most influenced by attributes of their partners; (3) anxiety and perception of risk was higher in young women having abnormal screening MSAFP, than in the advanced maternal age group although this difference appeared to be commensurate with actual risks; (4) for fetal aneuploidy, the specific karyotype and, to a lesser extent, coexistent structural anomalies are the major determinants of decisions to abort; (5) for euploid fetal structural abnormalities the prognostic severity and potential for beneficial medical intervention (either antenatally or postnatally) as counselled by the physician were the principal determinants influencing abortion decisions. Further study is needed and important questions still to be addressed are discussed.

Abortion, Eugenic↗
PubMedDate not supplied

Spontaneous abortions in couples declining multifetal pregnancy reduction.

Multifetal pregnancy reduction (MFPR) has clearly improved the outcomes of multifetal gestations. Several recent reports have also suggested improved outcomes in nonreduced cases, but there have been methodologic concerns about the denominators, i.e. have all cases been included and is there a 'hidden mortality' of unknown lost cases. Here we assessed the outcome of patients telephoning to discuss MFPR, but who chose not to have the procedure. Over a 3-year period, 446 patients had MFPR by one operator. Nineteen patients chose not to have the procedure. There were 11 preterm births, 1 term delivery, and 5 spontaneous losses (7 of 17) prior to 24 weeks, a loss rate of 35%. Two patients delivering triplets had a loss of 1 fetus/neonate. These data suggest that the loss rates of nonreduced pregnancies may be higher than generally thought, making the improvements with MFPR even bigger than generally realized.

Abortion, Spontaneous↗
PubMedDate not supplied

Multifetal pregnancies: evolution of methods of initiation and impact of REI certification for patients seeking reduction.

OBJECTIVE: Multifetal pregnancy as a result of ovulation induction (OI) and assisted reproductive technologies (ART) correlate with Board certification in reproductive endocrinology and infertility (REI). DESIGN: Retrospective chart analysis of 304 patients referred to Wayne State University (WSU) and Thomas Jefferson University (TJU) for multifetal pregnancy reduction (MFPR) from March 1986 to January 1995 compared to 275 patients referred from January 1 to December 31, 2000 at MCP Hahnemann University. MATERIAL AND METHODS: Chart review for fetal number, pregnancy generation (OI or ART) and physician REI Board certification from the American Board of Specialties Obstetrics and Gynecology. Information was available on 296 of 304 patients studied in the 1986-1995 WSU cohort and 275 patients studied from the MCP Hahnemann 2000 cohort. RESULTS: Analysis of 296 multifetal pregnancies at WSU and TJU for REI Board status showed non-REI Board-certified (NREI) physicians generated 174 pregnancies with quadruplets or more compared to 122 quadruplets or more by REI Board-certified physicians. Board certification did not impact quadruplet or more rates for OI or ART (p < 0.368). Of 275 patients with triplets or more at MCP Hahnemann, 156 (56.7%) were from ARTs versus 41.2% from 1986-1995 (chi(2) = 13.1, p < 0.001). Quintuplets or more decreased from 18.5 to 9.7% (chi(2) = 8.3, p = 0.004), and for REIs from 22.1 to 9.6% (chi(2) = 4.7, p < 0.01), while 14.4% of cases coming from non-REIs had quintuplets versus 9.6% from REIs (p = NS). CONCLUSIONS: Cases of MFPR from ARTs have risen, while percentage of cases with quintuplets have fallen in half. We found no difference in quintuplets between REIs and non-REIs overall, but REI quintuplets fell significantly, and NREI has not.

Adult↗
PubMedDate not supplied

Demographic factors for utilization of invasive genetic testing after multifetal pregnancy reduction.

OBJECTIVE: Pregnant infertility patients are commonly old enough to be offered prenatal diagnosis. However, they may be reluctant to undergo an additional invasive procedure. We, therefore, sought to determine what demographic factors, including race and ethnic group, influenced patients' decisions to undergo genetic testing in addition to multifetal pregnancy reduction (MFPR). METHODS: We retrospectively reviewed MFPR patients from July 1997 to June 1999 at our institution. Invasive genetic testing was routinely discussed. Maternal age, race, ethnicity, religion, egg source for in vitro fertilization (IVF) patients, and the remaining fetuses following MFPR were analyzed for invasive genetic testing determinants and were compared to our experiences with genetic referents to us for singleton pregnancies. 132 consecutive patients, of whom 49 were >/=35 years, including 15 having IVF with donor eggs, were included. RESULTS: Maternal age was the single most significant determinant of testing. In donor egg cases, donor age was significant. Ethnic background, previous children, and the remaining number of fetuses after MFPR were also significant determinants. CONCLUSION: MFPR patients share similar demographics to the advanced maternal age population. Despite the very stressful situations, our data suggest that maternal age, and therefore genetic risk, is the most important determinant of choosing whether or not to have testing. However, patients' decisions are, to varying degrees, modified by religious and ethnic considerations.

Adult↗