Transvaginal sonographic imaging of early second-trimester fetal anatomy assisted by uterine fundal pressure.

OBJECTIVE: To assess the advantage of applying uterine fundal pressure to assist transvaginal sonographic imaging of early second-trimester fetal anatomy. METHODS: One hundred consecutive patients with singleton fetuses underwent routine transvaginal sonographic assessment of fetal anatomy between 13 and 17 weeks' gestation. If the entire fetal anatomy including cardiac outflow tracts was not depicted, uterine fundal pressure was applied with the operator's nonscanning hand in a bimanual fashion, to facilitate transvaginal imaging. Transabdominal sonography was performed when visualization of the entire fetal anatomy was not obtainable with transvaginal or uterine fundal pressure-assisted transvaginal sonography. Observed fetal structures with and without fundal pressure were compared. Factors assessed that may have modified the value of fundal pressure included patient weight, gestational age, fetal presentation, previous abdominal surgery, and the presence of uterine fibroids. Statistical analysis included McNemar test, chi 2, Fisher exact test, and t test, with P < .05 considered significant. RESULTS: Visualization of lower limbs, head (including intracranial structures), upper limbs, kidneys, spine, gender, feet, hands (digits), face, four-chamber view, and cardiac outflow tracts was significantly enhanced by uterine fundal pressure-assisted versus nonassisted transvaginal sonography. Uterine fundal pressure improved transvaginal sonographic imaging in 91% of subjects, and in 51% of all subjects, a complete examination was thus obtained. In 20% of all subjects, transabdominal sonography was required to complete the examination. Complete fetal anatomic scanning was unobtainable despite uterine fundal pressure supplemented by transabdominal sonography in 29% of cases. Completion of the transvaginal sonographic fetal anatomic survey with uterine fundal pressure was related to gestational age (P < .02) and maternal weight (P < .05) yet not related to fetal presentation (P = .13), previous abdominal surgery (P = .06), or uterine fibroids (P = .26). CONCLUSION: Uterine fundal pressure applied during early second-trimester transvaginal sonographic evaluation of fetal anatomy significantly improves visualization of fetal structures otherwise located beyond the effective range of the transvaginal transducer.

Ultrasonography of fetal heart failure in early gestation.

Cardiac dysfunction was observed with transvaginal ultrasound in 12 fetuses at 13-17 weeks' gestation. Impaired contractility of the heart and significant reduction of the left ventricular fractional shortening were noted in these fetuses. Three of the fetuses also had supraventricular tachycardia. Many of the fetuses had cardiomegaly, oligohydramnios, a thick placenta, or associated cardiac and structural anomalies.

Abnormal biochemical serum screening versus 2nd-trimester ultrasound-detected minor anomalies as predictors of aneuploidy in low-risk patients.

OBJECTIVE: To compare the yield of multiple-marker biochemical screening with that of minor fetal anomalies observed on ultrasound for detection of aneuploidy in low-risk patients. METHODS: The results of 1,073 amniocenteses performed because of abnormal biochemical screening tests were compared against 197 amniocenteses performed for minor anomalies as detected on level II ultrasound at 15-22 weeks of gestation. RESULTS: False-positive results were observed in about 7% of serum screening patients and in 1.7% of the ultrasound cases. Chromosomally abnormal fetuses were detected in 2% of the amniocenteses performed because of abnormal serum screening and in 2.5% of the cases with ultrasound-defined minor anomalies. CONCLUSIONS: Both methods identify patients at risk for abnormal karyotypes. Although the evaluation of serum biochemical markers yielded more false-positive results, it is more suitable than ultrasound for mass population screening.

Second-trimester minor ultrasound anomalies: impact on the risk of aneuploidy associated with advanced maternal age.

OBJECTIVE: To determine the impact of the presence or absence of minor ultrasound anomalies for the risk of aneuploidy in patients already at high risk because of advanced maternal age. METHODS: Eleven hundred forty-four women having amniocentesis for advanced maternal age were divided into those with minor ultrasound anomalies (n = 62) and those without (n = 1082). Two hundred fifty-nine women younger than 35 years but with minor anomalies on ultrasound were also included. RESULTS: Fetal aneuploidy was found in six of 62 (9.7%) women of advanced maternal age with minor ultrasound anomalies, in five of 1082 (0.5%) women older than 35 years with normal ultrasound results, and in five of 259 (1.9%) women younger than 35 years with minor ultrasound anomalies. CONCLUSION: Minor ultrasound anomalies increase considerably the risk of aneuploidy in women older than 35 years, and their absence lowers that risk slightly. Minor ultrasound anomalies in the fetuses of women younger than 35 raises their risk to that of a 39-year-old women in her second trimester. Ultrasound can be used to modify genetic risks at counseling and may help patients in their decision to have invasive testing.

Increased amniotic fluid alpha-fetoprotein in patients with fetal nuchal edema.

The alpha-fetoprotein concentration in the amniotic fluid of 51 fetuses with isolated nuchal edema and normal karyotypes was compared to that of the next 51 patients of comparable gestational age with normal ultrasounds and karyotypes. The mean alpha-fetoprotein in amniotic fluid was 1.26 +/- 0.45 in the nuchal edema group and 1.01 +/- 0.3 in controls (t = 3.287, p = 0.002). Acetylcholinesterase evaluation was indicated by abnormally elevated alpha-fetoprotein in 4% of amniotic fluid samples from the study group and none of the controls. We concluded that alpha-fetoprotein is higher in amniotic fluid from pregnancies with isolated fetal nuchal edema and normal karyotype. Possible leakage of protein from enlarged cervical lymphatics associated with fetal nuchal edema may explain these findings.

Aneuploidy among prenatally detected neural tube defects.

We have reported previously a 10% aneuploidy detection rate among 39 cases of fetal neural tube defects (NTD). Subsequently we amassed an additional experience of over 17,000 prenatal diagnosis cases over a 5-year period. During this period 106 cases of NTDs were identified; 44 with anencephaly, 62 with open spina bifida. The average maternal age of this population with NTDs was 29 years (15-40); 6 patients declined amniocentesis. Six of 100 cytogenetic studies were aneuploid; one anencephalic fetus had inherited a maternal marker chromosome, and 5 NTD cases had trisomy 18. The average maternal age of the aneuploid cases was 31 (19-40); 3 were 35 years or older. Four of 5 trisomy 18 cases had multiple congenital anomalies (MCA). The overall aneuploidy detection rate in our cohort was 5-6%, while aneuploidy occurred in 2% of the isolated NTD cases, and 24% of the MCA cases. Combining the earlier experience, 4/39 aneuploidy (2 trisomy 18, 4p+, del 13q) yields an aneuploidy detection frequency of 10/145 (7%), of which most (7/10) had trisomy 18. These data support fetal karyotyping for accurate diagnosis, prognosis, and recurrence-risk counseling.

Induction of labor.

Several mechanical and biochemical methods have been used to induce labor throughout modern obstetrics. We review and compare mechanical and medical methods of labor induction, along with several new uterotonic agents such as mifepristone (RU 486) and misoprostol, which can be conveniently administered orally and managed in the outpatient clinic.

Early prenatal diagnosis of axillary cystic hygroma.

Fetal axillary cystic hygroma has been reported rarely and only as a sonographic finding late in gestation. A retrospective study of 19,200 early second trimester screening ultrasonograms for anomalies revealed five cases of axillary cystic hygroma. All of the axillary hygromas were small, transient, nonloculated cysts. Three cysts were associated with chromosomal abnormalities: trisomy 21 in two cases and a single case of trisomy 18 in which structural abnormalities also were detected. Early fetal axillary cystic hygroma appears to be different from postnatal axillary cysts on the basis of differences in prevalence, structure, and appearance. It also may be a normal variant in the development of the fetal lymphatic system.

Role of ultrasonography in pregnancies with marker chromosome aneuploidy.

The objective of this report was to evaluate the effect of ultrasonographic (US) findings on pregnancy management in patients with marker chromosome (MC) aneuploidy ascertained through prenatal diagnosis. From 1989 through June 1993, 15,522 prenatal diagnostic procedures were performed for accepted indications. Charts of patients with MC on amniocentesis or chorionic villus sampling (CVS) karyotype were evaluated with respect to US anomalies, pregnancy complications, and outcome. Nineteen cases of MC were identified. The prevalence of MC in our study was 0.12% (1:816 procedures). No significant difference between CVS and amniocentesis was found: 5/19 (26%) were CVS specimens, which is comparable to our CVS (3,259/15,522) case distribution. Three cases with incomplete records were excluded from the analysis. Four inherited MC cases were identified: 1 case had anencephaly. Of the 12 de novo MC cases 4 (33%) had abnormal US findings, and an additional 4 were found to have cytogenetic evidence for partial trisomy. Seven of these 8 abnormal de novo MC cases were terminated. MC aneuploidy is more common in pregnancies sampled for usual genetic indications than previously reported in pediatric series. High-resolution US may identify a major malformation not etiologically related to a MC inherited from a normal phenotypic parent. The association of the novo MC with US anomalies confers a poor prognosis, suggesting the expression of genetic imbalance from the accessory chromatin (partial trisomy). However, when US appears normal on initial and follow-up examinations, the chances for a normal-phenotypic newborn are high.

Inability of human sperm to change their orientation in response to external chemical stimuli.

OBJECTIVE: To investigate whether human sperm can respond to external chemical stimuli by orienting themselves toward chemoattractants or withdrawing from hostile environments. DESIGN: Controlled laboratory assays. SETTING: Normal human sperm and two other flagellated micro-organisms were exposed to various potential chemoattractant or chemorepellent substances. INTERVENTION: Human sperm, Euglena viridis, and Escherichia coli were exposed to various substances from the female reproductive system or to various toxic agents by placing them within tiny wells in a sealed minichamber. They were followed by microscopic observation and by intermittent photography. MAIN OUTCOME MEASURE: Images of photographed micro-organisms were analyzed for signs of attraction to or withdrawal from the test substances. RESULTS: Human sperm neither changed their orientation toward nor accumulated next to the well that contained cervical mucus, uterine cavity and follicular fluid, cumulus cells, or intact nonfertilized human eggs. Contrary to other micro-organisms that turned away from sources of hydrochloric acid, sodium hydroxide, ethanol, or glutaraldehyde, human sperm did not withdraw from these solutions. They swam along the ascending chemical gradient, facing ahead while becoming immobilized by these agents. CONCLUSION: It may be implied from the observation that they did not turn away from a hostile environment when expected to do so or turn toward chemoattractants that human sperm do not respond to external chemical stimuli and, most probably, chemotaxis between human sperm and ova in nature does not exist.

Fluorescent in situ hybridization and second-trimester sonographic anomalies: uses and limitations.

The critical need for rapid and reliable karyotype analysis can be no greater than in the setting of sonographic fetal anomalies. Fluorescent in situ hybridization (FISH) directly applied to interphase chromosomes can decrease the time required to identify the common aneuploidies. Our retrospective study reviewed 50 consecutive patients with sonographic fetal anomalies who underwent FISH. Within this high risk group, nonmosaic chromosomal aneuploidies were present in 16% of the fetuses (8 of 50), and 2 additional fetuses had cytogenetic abnormalities: 1 case, 46,XY,-12,+der(12)t(12;13)(p13; q14.1), and 1 case a 10% mosaic for trisomy 21. Of the 10 cytogenetically abnormal fetuses, FISH was able to identify correctly all 8 of the nonmosaic aneuploidies within 2 days of receipt of the specimen in the laboratory. Clinical decisions can be made on the basis of concordant FISH and ultrasound abnormalities, shortening the decision-making process for most of the aneuploid cases. However, our experience demonstrates some of the limitations of current FISH protocols and the continued necessity for formal karyotype analysis.

Risk of anomalies as a function of level of elevated maternal serum alpha-fetoprotein.

OBJECTIVE: Most neural tube defects risks are not actual but mathematical extrapolations. We sought to evaluate this risk and to compare actual performance. STUDY DESIGN: This was a retrospective study of a referral population with elevated maternal serum alpha-fetoprotein results between 1987 and 1992. Ultrasonography results, delivery records, and autopsy results were compared with entry levels of maternal serum alpha-fetoprotein, and the percentage of fetal anomalies detected in this study was evaluated. RESULTS: A total of 773 patients with elevated maternal serum alpha-fetoprotein levels were evaluated. There was a progressive increase in the incidence of anomalies as a direct function of the level of the maternal serum AFP, varying from 3.4% at a level of 2.5 to 40.3% at a level > 7.0. CONCLUSION: Data from this study support the correlation of maternal serum AFP levels with the risk of neural tube defect and ventral wall defects.

Microscopic neuroblastoma in a fetus with a de novo unbalanced translocation 3;10.

We report on a fetus with a de novo unbalanced translocation 3;10 and a microscopic neuroblastoma. The fetus had the karyotypic and phenotypic manifestations of partial dup (3q). The finding of a constitutional chromosomal abnormality and a microscopic neuroblastoma, although possibly coincidental, supports Knudson's two hit hypothesis for development of neuroblastomas and other embryonal tumors. In this case the first mutation is represented by the constitutional abnormality, possibly resulting in the microscopic neuroblastoma. A second mutation affecting the abnormal cells, which may be more prone to mutagenesis, may trigger a neuroblastoma.

Early prenatal diagnosis of polycystic pancreas with narrow thorax and short limb dwarfism.

We describe the ultrasound findings of polycystic pancreas with short rib dwarfism in the early second trimester. Radiologic, morphologic, and histologic examination after pregnancy termination confirmed the findings and also disclosed dysplastic kidneys. The skeletal anomalies are similar to those in Verma Naumoff type of short rib polydactyly, but the extraskeletal malformations have never been reported before in this syndrome.

Fetal drug therapy.

Fetal drug therapy encompasses several areas, including the prevention of external genital masculinization in 21-hydroxylase deficiency syndrome (congenital adrenal hyperplasia), biochemical amelioration of methylmalonic acidemia, and biotin-responsive multiple carboxylase deficiency. The correction of cardiac arrhythmias has become relatively commonplace, and a reduction in the risks of neural tube defects is now possible with the use of preconceptual and early conceptual folic acid. Similarly, fetal function can be altered by the induction of fetal lung maturity using a number of agents; corticosteroids are the most common fetal pharmaceutic agent, and a number of other agents have also been tried. The most common route of administering pharmaceutic agents is through the mother and the placenta, although the direct administration of certain agents is becoming more common.

The value of Doppler ultrasonography in prolonged pregnancies.

One hundred forty-two gravid women at term were followed prospectively by a non-stress test, estimation of amniotic fluid volume and Doppler velocimetry of the umbilical and uterine arteries. Adverse perinatal outcome was detected in 12 women (8.5%). Abnormal antepartum tests were detected in 26 women (17%). Seven women had an abnormally elevated resistance index (RI) in the umbilical artery; but only two had an abnormal outcome. Seven women had an abnormally elevated RI in the uterine artery, but only two had abnormal outcome. Three out of 11 women with oligohydramnion had abnormal perinatal outcome. Only one out of seven women with an abnormal non-stress test had abnormal perinatal outcome. In six women, more than one antepartum test was abnormal. The various surveillance methods demonstrated a low sensitivity (the highest was obtained by estimating amniotic fluid volume: 25%) and a low positive predictive value (the highest obtained by measuring the resistance index in either the umbilical or the uterine arteries: 28.6%). By considering any abnormal test as a positive test result for a given patient, a substantial improvement in sensitivity (66.7%) and positive predictive value (33.3%) are obtained. Doppler velocimetry adds very little in itself to the follow-up of patients with post-term gestations. However, when combined with additional antepartum tests, it may increase our ability to predict the compromised fetus in this condition.

A new model for investigating in real-time the existence of chemotaxis in human spermatozoa.

OBJECTIVE: To suggest a new approach to the research of chemotaxis between various media and human spermatozoa to solve the riddle of its existence. DESIGN: Laboratory experiments in which chemotaxis between human spermatozoa and follicular fluid (FF) as well as N-formyl was investigated. SETTING: Male physiology laboratory and in vitro fertilization program unit. PATIENTS: Follicular fluid was collected from 15 patients and used either fresh or after storage at -5 degrees C for less than 2 weeks. High-quality semen specimens were obtained from normal donors and underwent one-step washing with Ham's F-10 solution (Biological Industries, Kibbutz Beth Haemek, Israel). TECHNIQUES: Assays were performed in real time by direct microscopical observation and quantitative determination of the disturbance in random movements of human spermatozoa caused by the tested media. Spermatozoa and tested media, including FF and N-formyl-Met-Leu-Phe were placed in a sealed minichamber and photographed with the aid of the multiple exposure photography technique. RESULTS: By analyzing photographed tracks of more than 80,000 moving spermatozoa, a physiologically insignificant deviation from randomness, corresponding to a 95% confidence interval of -0.57 +/- 0.46%, was found when spermatozoa swam along the concentration gradient of the tested media. The average velocity of spermatozoa swimming toward the test media was slightly lower (less than 5%) than that for spermatozoa swimming away, indicating, if anything, negative chemoattraction. CONCLUSIONS: Despite the high sensitivity of the model, neither natural FF nor synthetic N-formyl exerted any chemotaxis on human sperm. The advantages and potential use of this model for investigating chemotaxis by other biological and synthetic media are discussed.

Prototype of a fully automated device for determination of bacterial antibiotic susceptibility in the clinical laboratory.

A completely automated system for the performance of antibiotic susceptibility tests in the clinical laboratory is described. With a modicum of personnel involvement, data on 40 specimens tested against 13 antibiotics are obtained every hour after an initial 3-hr period. The step by step explanation of the functioning of this prototype system, based on a thoroughly tested manual model, is presented. The system compares well with the standard diffusion test and has a potential for application to other endeavors of the clinical microbiology laboratory with a comparable saving in time and labor.