Sheldon Schlaff

Serial β-Subunit Human Chorionic Gonadotropin Doubling Time as a Prognosticator of Pregnancy Outcome in an Infertile Population*

Prospective evaluation through the use of radioimmunoassay of the beta-subunit of human chorionic gonadotropin (beta-hCG) in blood samples obtained during the first 30 days of gestation was performed on an infertile population at high risk for pregnancy loss. Four hundred and fourteen samples in 281 pregnancies were analyzed. On the basis of single, random beta-hCG samples in asymptomatic patients, 77% of successful pregnancies and 59% of abortions were correctly identified. On the basis of beta-hCG doubling time (mean 2.2 days +/- 1.0 [2 SD]) computed from serial sampling, again in asymptomatic patients, 88% of successful pregnancies and 76% of abortions were correctly identified. beta-hCG doubling time appears to provide a reliable method of evaluating early pregnancy prognosis with significantly greater ability to identify problem pregnancies within the first 30 days of gestation than does single random hCG values.

Landmarks during the first forty-two days of gestation demonstrated by the β-subunit of human chorionic gonadotropin and ultrasound

Prospective pregnancy evaluation through the combined use of a radioimmunoassay (RIA) for the beta-subunit of human chorionic gonadotropin (beta-hCG) and ultrasound during the first 42 days of gestation after ovulation was performed on a population asymptomatic for first-trimester spontaneous abortion. One hundred forty-six ultrasonic observations in 98 pregnancies were made with simultaneous beta-hCG RIA performed in 80 patients. The following landmarks of normal gestational growth were identified: (1) Before 26 days, beta-HCG RIA permits definitive diagnosis of growing trophoblastic tissue, and serial samples allow doubling time computation for prognosis while ultrasound shows a nonspecific increasing decidual response within the uterus; (2) between 26 and 36 days after ovulation, serial beta-hCG samples continue to give doubling time results while ultrasonic demonstration of a gestational sac is normally seen by 28 days after ovulation; (3) the lack of fetal heart motion by 42 days after ovulation or within a gestational sac with a mean diameter of greater than 30 mm was prognostic of abortion; (4) the absence of a gestational sac by 28 days after ovulation or with a beta-hCG RIA greater than 1,000 ng/ml is suggestive of an ectopic pregnancy until proved otherwise.

Sex selection by sperm separation and insemination

The Ericsson albumin filtration technique was used to collect a fraction rich in Y sperm for selective insemination in couples desiring a male infant. Of 35 conceptions in which sex was known at delivery or spontaneous abortion, there were 28 males (80%). Twelve pregnancies were achieved after separation of sperm in a Sephadex gel filtration system designed to allow for collection of a fraction enriched in X sperm. Seven pregnancies have resulted in females, two in males, and one in twins of each sex. One patient aborted, and one is still pregnant. While selection for either sex can be done electively, on the basis of sociologic preference, female selection has, as an additional indication, avoidance of male offspring to carriers of sex-linked diseases.

Gonadotropin-releasing hormone radioimmunoassay and its measurement in normal human plasma, secondary amenorrhea, and postmenopausal syndrome

A sensitive and specific double antibody radioimmunoassay for gonadotropin-releasing hormone (GnRH) has been developed for measurement in ethanol extracts of human plasma. Iodinated hormone was prepared with the use of the chloramine-T method, and antibodies were developed in rabbits over a six-month period with a GnRH synthetic copolymer immunogen. A Scatchard plot revealed at least three species of antibody. The assay can measure conservatively at the 5 pg. per milliliter level and shows no cross-reactivity with other available hypothalamic and pituitary hormones. The releasing hormone was quantitatively recovered from human plasma with immunologic identity to native hormone. Unextracted plasma could not be used because of nonspecific displacement. The measurement of GnRH in individuals receiving 100 mug of intravenous bolus infusions of the synthetic decapeptide show extremely elevated values with two half-lives: one of two to four minutes and another of 35 to 40 minutes. In our experiments, we have found measurable GnRH in patients with secondary amenorrhea and at the midcycle in normal women. In the normal cycling woman during the follicular and luteal phases, GnRH was undetectable. In postmenopausal women with extreme hypoestrogenism and markedly elevated luteinizing hormone values, GnRH was also undetectable. No bursts of GnRH could be detected in normal men when sampled every ten minutes over a two-hour period and every two hours throughout the day.

Preconceptual female gender selection

While most techniques of prenatal sex gender determination have focused on male preference as a function of societal or cultural customs the identification of roughly 200 sex-linked diseases in the medical literature argues for a reliable method of enhancing the female/male birth ratio as a form of prenatal medical therapy. To date none of the apocryphal methods of prenatal sex selection including douches diet and coital timing has proven successful when subjected to close scientific scrutiny. Therefore the efforts of Steeno et al. And Quilivan et al. in obtaining X-enriched populations of sperm were of great interest to us. This communication concerns what we believe to be the first human pregnancy achieved with X enrichment by gel filtration reported in the literature. (authors)

Prostaglandin F2a, an ovulatory intermediate in the in vitro perfused rabbit ovary model☆

PGF2a has been proposed as a mediator of mammalian ovulation. To elucidate further the role of PGF2a in the process of ovulation, PGF and PGF2a metabolite were measured by radioimmunoassay in the perfusate of an in vitro perfused rabbit ovary preparation. Perfusion medium samples were collected over a 10 to 12 hour period from ovaries perfused with tissue culture M199 (total volume 150 ml, sample volume 3 ml) to which varying amounts of hCG had been added. [The PGF2a antisera a 40% cross reaction with PGF1a, hence total PGF was measured with this antisera.] Both PGF and PGF2a metabolite showed a linear increase with time and numbers of ovulations. PGF media accumulation was 575 pg/ovary/ovulation/hr and PGF2a metabolite accumulation was 367 pg/ovary/ovulation/hr. Medium prostaglandin content could be correlated with numbers of ovulations, ovulatory efficiency (number of ovulations/total follicles) but not total follicles. These data best fit a model of independent ovulatory units producing PGF2a without recruitment or interaction between them. We infer that PGF and PGF2a metabolites in this system can be used as a direct index of the ovulation process.

A life-table analysis of pregnancy yield in fixed low-dose menotropin therapy for patients in whom clomiphene citrate failed to induce ovulation

Forty-nine patients in whom clomiphene citrate failed to induce ovulation were treated for 177 cycles with a fixed low dosage of menotropin. Among these 49 patients, there were 24 pregnancies. Among these pregnancies were two that were multiple and three spontaneous abortions. In only one treatment cycle was there a hyperstimulation syndrome. These patients were divided into three clinical groups: the secondary amenorrheic patient, the oligo-amenorrheic patient, and the patient with poor corpus luteum function. There was no statistically significant difference in the pregnancy rate per month among all groups during the first three treatment cycles (average value, 0.07). However, there was a statistically significant improvement in the pregnancy rate per month in the group with secondary amenorrhea and the group with poor corpus luteum in the last three treatment cycles, as compared with the first three treatment cycles (P = 0.05; average value, 0.75). The oligo-amenorrheic patients, on the other hand, during the last 3 months of treatment, had no statistically significant increase in the pregnancy rate per month. These data suggest that menotropin therapy may have a priming effect. These data do not fit the currently accepted model of a constant pregnancy rate per month for all patients. The data suggest that caution should be exercised before combining patient groups when evaluating the results of menotropin therapy.