Maclyn E. Wade

First-trimester chorionic gonadotropin measurements as an aid in the diagnosis of early pregnancy disorders.

Abstract In order to evaluate the usefulness of serial human chorionic gonadotropin (hCG) levels as a first-trimester placental function test, we prospectively collected 685 serum samples from 256 women during the first 100 days of gestation. Dating of the samples was based upon the thermal shift in the basal body temperature (BBT). Human chorionic gonadotropin was measured by use of a sensitive and relatively specific radioimmunoassay, and the results were correlated with the outcome of pregnancy. The 90 per cent tolerance limits for normal serum hCG levels were established by measurements made on 489 samples obtained from 187 pregnancies. A pregnancy was judged to be abnormal if two or more serum samples collected at two-week intervals showed hCG levels above or below the 90 per cent tolerance limits 14 or more days after the BBT shift. Using this criterion, 1.6 per cent of normal pregnancies, 57.6 per cent of pregnancies which terminated in a spontaneous first- or second-trimester abortion, 100 per cent of ectopic pregnancies, and 60 per cent of pregnancies complicated by multiple gestations showed abnormal first-trimester serum hCG levels. The predictive value of serial hCG measurements was further demonstrated by a second prospective study in 28 patients for whom the outcome of the pregnancy was predicted based upon the normal range. All of the normal pregnancies were correctly identified, while 88.9 per cent of the pregnancies resulting in spontaneous abortions and all of the ectopic pregnancies were correctly predicted to be abnormal. These results indicate that the majority of patients with ectopic pregnancies or those whose pregnancies are destined to terminate in a first- or second-trimester spontaneous abortion will have abnormally low serum hCG levels. We conclude that serial first-trimester serum hCG determinations are useful for distinguishing between normal and abnormal trophoblastic function.

Presence in Normal Human Testes of a Chorionic-Gonadotropin-like Substance Distinct from Human Luteinizing Hormone

The high rate of human chorionic gonadotropin production by testicular tumors caused us to investigate the possibility that normal human testes contain small amounts of that substance. Extracts of human testes obtained at autopsy demonstrated parallel inhibition curves to the human chorionic gonadotropin standard in a radioimmunoassay specific for the hormone. The immunoreactive material was adsorbed onto concanavalin A, a reaction characteristic of glycoproteins, and was eluted within the chorionic gonadotropin range on Sephadex G-100 column chromatography. Solubilized receptor proteins for the hormone could not be identified in the extracts. The demonstration that the normal human testes contain a glycoprotein similar or identical to human chorionic gonadotropin suggests that the fetal genome responsible for production of the hormone during pregnancy is not completely suppressed in the adult. Excessive productton of this glycoprotein may account for the high levels of human chorionic gonadotropin reported in the serum of patients with germ-cell tumors of the testes.

Early third-trimester ultrasound screening in gestational diabetes to determine the risk of macrosomia and labor dystocia at term

The purpose of this study was to determine whether an early third-trimester fetal abdominal circumference measurement can be used in patients with gestational diabetes to predict the presence or absence of macrosomia and labor dystocia at term. The predictive accuracy of a 30- to 33-week abdominal circumference measurement was tested, using the ninetieth percentile as the discriminant point. The study consisted of 201 patients with gestational diabetes who maintained weekly fasting glucose levels less than 100 mg/dl and 2-hour postprandial glucose levels less than 120 mg/dl with dietary management alone. The predictive accuracy of a 30- to 33-week fetal abdominal circumference measurement was 96.4% for ruling out macrosomia and 56.3% for predicting macrosomia. Patients with fetal abdominal circumference measurements greater than the ninetieth percentile at 30 to 33 weeks had a significantly increased incidence of cesarean section for failure to progress, shoulder dystocia, and birth trauma, whereas patients with abdominal circumference measurements less than or equal to the ninetieth percentile were at no greater risk than the general population. These results suggest that patients with non-insulin-dependent gestational diabetes with fetal abdominal circumference measurements less than or equal to the ninetieth percentile at 30 to 33 weeks are not at increased risk for macrosomia, cesarean section, or birth trauma at term, as long as their weekly glucose testing remains within normal limits. Efforts to decrease the incidence of macrosomia and its attendant risks should focus on those gestational diabetic patients whose fetal abdominal circumference greater than the ninetieth percentile at 30 to 33 weeks.

The efficacy of starting postterm antenatal testing at 41 weeks as compared with 42 weeks of gestational age

Postterm antenatal fetal surveillance has traditionally begun at 42 completed weeks of gestation. However, recent data have shown that a significant percentage of cases of perinatal asphyxia occurs between 40 and 42 weeks of gestation. We compared the perinatal outcome of fetuses with antenatal surveillance beginning at 41 weeks to those starting at 42 weeks of gestation. The study groups consisted of 908 patients who began antenatal testing at 41 weeks and 352 who began testing at 42 weeks. Antenatal testing consisted of twice-weekly amniotic fluid assessments and nonstress tests (including evaluation for late and variable decelerations). Between 41 and 42 weeks, the group whose testing started at 41 weeks had an overall incidence of intrapartum fetal distress of 2.7%, no stillbirths, and no infants with major neonatal morbidity. Patients without antenatal testing who delivered between 41 to 42 weeks did not have a significantly increased incidence of fetal distress (3.3%; p = 0.07). However, this group had a significantly increased incidence of adverse outcomes (p less than 0.05), including three stillbirths and seven cases of major neonatal morbidity. Beyond 42 weeks, the group whose testing started at 41 weeks had a 2.3% overall incidence of fetal distress. This was significantly less (p less than 0.01) than the group whose testing started at 42 weeks (5.6%). Neither of the groups had any stillbirths or infants with major neonatal morbidity. These findings suggest that starting antenatal testing at 41 weeks of gestation may result in decreased postterm perinatal mortality and morbidity as well as a decreased incidence of intrapartum fetal distress.

Maternal serum human chorionic gonadotropin concentrations and fetal sex prediction.

The feasibility of using maternal serum human chorionic gonadotropin (hCG) concentrations for prenatal sex prediction was examined. hCG was mesured in 822 serum samples from 560 women with uncomplicated pregnancies. Significantly higher hCG concentrations were found in the serum of women bearing female fetuses than in the serum of women bearing male fetuses during the third trimester, especially during the 10th lunar month. The data were utilized to construct probability graphs for fetal sex prediction based upon a single maternal serum hCG determination during the third trimester and during the 10th lunar month. However, the utility of these graphs is limited by the small proportion of pregnant women with serum hCG concentrations that were high or low enough to allow a prediction with high probability.

Treatment of vulvar carcinoma in situ with the CO2 laser

Between January 1960 and December 1982, 142 patients with carcinoma in situ of the vulva were treated at Cedars-Sinai Medical Center and UCLA Medical Center. Primary treatment consisted of wide excision in 45 patients; vulvectomy in 23 patients; topical chemotherapy in 9 patients; and CO2 laser therapy in 42 patients. Twenty-three patients were also treated with the CO2 laser for recurrent disease. Multifocal disease was present in 59% of the cases. Lesions involving the posterior vulva recurred most commonly, for both initial and recurrent disease. Results utilizing the CO2 are compared with the other methods of treating carcinoma in situ of the vulva. The CO2 laser is well suited for treatment of both multifocal and unifocal vulvar lesions, as it allows for maximal retention of vulvar integrity with no decrease in therapeutic efficacy.

Antepautum predictors of fetal distress in postterm pregnancy

The purpose of this study was to determine the efficacy of combining nonstress testing with ultrasound assessment of amniotic fluid volume for the antenatal evaluation of the postterm fetus. Postterm patients (884) were managed with amniotic fluid assessments and nonstress tests (including evaluation for variable and late decelerations) twice a week. There were no perinatal deaths or major neonatal morbidity. However, the antenatal testing sensitivity, specificity, negative, or positive predictive values were not improved by combining the two tests. Individually, amniotic fluid assessment was just as accurate a predictor of fetal well-being and was a significantly more sensitive test than the nonstress test. In addition, antenatal predictors of fetal distress and intrapartum signs of fetal distress were almost exclusively those reflective of umbilical cord compromise. These findings stress the importance of antenatal screening for signs of umbilical cord compromise as an early indication of potential fetal compromise. Although the results also suggest that amniotic fluid assessment is superior to the nonstress test, they do not conclusively support the use of amniotic fluid assessment as the sole parameter for postterm antenatal surveillance.

SERUM GLYCOPROTEIN HORMONE ALPHA SUBUNIT LEVELS IN PATIENTS WITH CANCER

The serum glycoprotein hormone alpha subunit concentration was measured in 957 nonpregnant patients with benign disorders and 683 patients with unselected malignancies. Postmenopausal women had significantly higher alpha levels than premenopausal women or men. When the patients were subdivided according to age, sex or disease sites, significant population differences were found for women less than 50 years of age and patients with cancers of presumed neural crest origin. However, individual serum alpha levels in patients with benign disorders or malignancies demonstrated considerable overlap. No population differences in serum alpha concentrations were demonstrated between patients grouped according to stage of disease, suggesting that serum alpha were not directly related to tumor burden. Similarly, there was no statistical association between clinical improvement or deterioration and change in the serum alpha subunit concentration. These results indicate that measurement of the glycoprotein hormone alpha subunit concentration in the serum is not useful for screening patients for cancer or for monitoring the clinical course of patients with the vast majority of cancers.

Removal of intra-abdominal intrauterine contraceptive devices through a peritoneoscope with the use of intraoperative fluoroscopy to aid localization.

The article describes the use of peritoneoscopy to locate displaced IUDs and gives 4 case histories, 2 of which include concomitant use of fluoroscopy. Peritoneoscopy obviates the use of colpotomy or laparotomy, both of which entail lengthy hospitalization and greater hazards. A radiolucent operating table is recommended to facilitate fluoroscopic examination. After localization of the IUD, the device is freed from any serosal attachment with a biopsy forceps inserted through a cannula; if necessary electrodesiccation can be used to aid incision. When free, the device is pulled through the lower midline trocar under direct visual supervision when the sleeve is large enough. The case histories stress that the longer the IUD is displaced in the abdominal cavity, the more difficult the removal; thus, each patient should be reexamined several months after insertion. Only radiopaque IUDs should be inserted to permit X rays in the event of complications.

Presence of an hCG-Like Substance in Non-Pregnant Humans

In 1972, Vaitukaitis and co-workers developed a radioimmunoassay that was relatively specific for hCG. This assay utilized an antiserum generated against the purified beta subunit of hCG, radioiodinated hCG or its beta subunit as a labeled ligand, and a highly purified preparation of hCG as a standard. With this method, serum concentrations of hCG as low as 1 ng (5 mIU)/ml could be measured in the presence of physiologic quantities of luteinizing hormone (LH), including those found during the mid-cycle LH surge in premenopausal women and the large concentrations found in the serum of postmenopausal women (Vaitukaitis et al., 1972). Following the introduction of this assay, a number of investigators examined the sera of patients with a variety of nontrophoblastic neoplasms for the presence of immunoreactive hCG (Braunstein, 1978; Braunstein, 1979). The combined data from all of these studies indicated that immunoreactive hCG is found in the sera of approximately 20% of patients with cancer (Braunstein, 1979).