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Norplant implants: the mechanism of contraceptive action.

OBJECTIVE: To determine if fertilization occurs unnoticed among Norplant users who are ovulatory. DESIGN: Serial blood samples were obtained during 1 month from sexually active Norplant users experiencing regular menstrual bleeding patterns and a control group of noncontracepting women trying to conceive. The sequential blood samples were assayed for the presence of human chorionic gonadotropin (hCG). SETTING: All samples were obtained from women receiving contraceptive service and health care at the Center for Research and Services in Human Reproduction and Contraception, Santo Domingo, The Dominican Republic. Assays for hCG were performed at the Department of Biomedical Sciences, University of Tampere, Finland. PATIENTS, PARTICIPANTS: A total of 32 women using Norplant implants were enrolled in the treatment group, and 20 women of proven fertility who were attempting to conceive served as a control group. INTERVENTIONS: Duration of Norplant use was as follows: 4 in the 2nd year of use, 13 in the 3rd year, 11 in the 4th year, 3 in the 5th year, and 1 in the 7th year. MAIN OUTCOME MEASURE: The determination of pregnancy was based on the presence of hCG in the luteal phase, using a sensitive and specific immunoenzymatic assay that can detect dimeric hCG as early as 7 days after ovulation. RESULTS: Nine pregnancies were detected. All were in the control group trying to conceive. Six of these advanced to clinical pregnancies, and three did not proceed beyond the next expected menses. None of the Norplant users had evidence of hCG production, whether the observed cycles were anovulatory or ovulatory. The probability of finding no pregnancies in the ovulatory months at risk among Norplant users is between 1 in 50 and 1 in 150,000. The null hypothesis that Norplant users conceive at a natural rate can be rejected at the 0.05 level. CONCLUSION: Interruption of early pregnancy (menstrual abortion) does not play a role in the mechanism of action of Norplant contraceptive implants.

Chorionic Gonadotropin↗

Application of the radioreceptor assay for human chorionic gonadotropin in pregnancy testing and management of trophoblastic disease.

A commercially prepared radioreceptor assay (RRA) for human chorionic gonadotropin (hCG) has been evaluated as a pregnancy test and in a quantitative assay to follow patients with hydatidiform mole. The RRA demonstrated almost 100% agreement in comparison with radioimmunoassay (RIA) and urinary hCG tests. In the quantitative assay, a limiting reliable concentration of 70 mIU/ml of hCG in serum could be obtained. Extremely good correlation was achieved between the RRA and RIA test for hCG in 2 patients with hydatidiform mole over a span of 3 months of followup after evacuation of the mole. The usefulness of the RRA as a replacement of RIA tests for hCG is discussed.

Chorionic Gonadotropin↗

Performance and sensitivity of modern home pregnancy tests.

We have studied the performance of three currently available home pregnancy tests. The Advance is a test based on monoclonal antibodies in an enzyme immunoassay format that specifically detects hCG in urine. The positive results are determined by the presence of a blue color in a color stick (30 minutes). The Daisy 2 and FACT are tests based on monoclonal antibodies that specifically detect hCG in urine in a hemagglutination inhibition assay; positive results are demonstrated by the deposition of a dot ring at the bottom of the test tube (45 minutes). Thirty-five patients who eventually became pregnant in that cycle collected the first morning urine specimens from day of ovulation (determined by ultrasound) in artificial insemination donor (AID) cycles, or from the date of gamete intrafallopian transfer (GIFT) for 16 consecutive days. In each specimen, the Advance, Daisy 2, and FACT tests were performed; in addition, beta-hCG levels were determined by radioimmunoassay. All the home pregnancy tests studied can detect pregnancy as early as 9 or 10 days post-conception, and they give positive results at the time of the expected onset of menses in 70%, 95%, and 88% of cases for Daisy 2, Advance, and FACT, respectively. The sensitivity of the these home pregnancy tests was determined to be about 200 mIU/mL of urine after correlating their positive or negative results with the concentrations of urinary beta-hCG determined by radioimmunoassay.

Antibodies, Monoclonal↗

The development and evaluation of Sevatest ELISA hCG Micro I. kit as a test for pregnancy.

The enzyme-linked immunosorbent assay (ELISA) method of sandwich type for determination of human chorionic gonadotropin (hCG) in serum or urine using horseradish peroxidase as an enzyme label and microtiter ELISA plates (or polystyrene microtubes respectively) as a solid phase support for antibody was developed. Test sensitivity of 200 mIU hCG per milliliter is approximately sixfold greater than the available hemo- or latex agglutination tests; quantitative hCG ELISA method has sensitivity of 6 mIU hCG per milliliter. In order to evaluate the usefulness of the method for early pregnancy detection 5,000 urine samples were prospectively collected and results correlated with outcome of pregnancy. Reliability of the test performed on routine basis at the Institute for the Care of Mother and Child in Prague proved to be 97.2% for intrauterine pregnancy detection, in 2.52% the test result was "+ -", and only in 0.28% the results were erroneous. For samples sent with the diagnosis of suspected extrauterine pregnancy 93.5% of correct results, 4.35% of "+ -" and 2.17% of erroneous results was found.

Chorionic Gonadotropin↗

Interference of exogenous HCG on pregnancy tests.

New urinary tests of pregnancy have recently been developed that are exceptionally sensitive to HCG. Our study was undertaken to explore the possibility that exogenous HCG, administered to induce ovulation, may interfere with these low-threshold tests of pregnancy. Six healthy volunteers participated in our study. Each woman received three sequential 5,000-U doses of HCG by im route on days 3, 5, and 7 after ovulation. Blood and urine for HCG assay were taken daily from each subject. Urine specimens were subjected to a traditional high-threshold pregnancy test (sensitivity limit = 2000 U/L) and to a low-threshold pregnancy test (sensitivity limit = 50 U/L); HCG in plasma and urine was determined by ELISA assay. Plasma HCG levels increased gradually under HCG dosing and attained a peak on day 8 (average = 73.7 U/L; range 24-124 U/L). As regards urinary HCG levels, the average value on days 8, 9, and 10 was above the 50-U/L detection limit of the low-threshold test, which was in fact positive in the majority of patients. Also on days 11 and 12, however, urinary HCG levels were above this limit in a certain proportion of subjects (day 11, 2/6; day 12, 1/6); accordingly the low-threshold pregnancy test was positive with a frequency of 2/6 on day 11 and of 1/6 on day 12. By contrast, the traditional high-threshold pregnancy test was negative in urine samples of all subjects. Our study indicates that the increased sensitivity of modern low-threshold pregnancy tests may cause false positive results in those cases where exogenous HCG has been administered during the luteinic phase.

Adult↗

[Studies on the viability of trophoblast after termination of various kinds of pregnancies (author's transl)].

Although normal value of hCG (LH level) does not necessarily indicate eradication of viable trophoblast, its confirmation has been demonstrated as a clinically useful guide for the probable prevention of choriocarcinoma after hydatidiform mole by Takeuchi et al. Choriocarcinoma preceded by other pregnancies than hydatidiform mole which has the highest risk for choriocarcinoma has drawn more attention than before in connection with the decrease of postmolar choriocarcinoma. So that I have studied the regression rate of urinary gonadotropin (hCG) after the termination of various kinds of pregnancies. In 2,433 cases of induced abortion, 695 cases of spontaneous abortion, 1,724 cases of term delivery and 43 cases of hydatidiform mole, their urinary hCG were determined to the level of physiological range of LH. The rate of hCG regression was in the order of term delivery, spontaneous abortion, induced abortion and hydatidiform mole. The younger was the gestational age of trophoblast, the slower was the regression of hCG. At one month after the termination of pregnancy, 80.1%, 11%, 0.3%, 8% and 4.1%, and at two month 55.8%, 1.6%, 0.5%, 4% and 0.5% for hydatidiform mole, induced abortion of less than 12 week of gestation, spontaneous abortion of less than 12 week of gestation, spontaneous abortion of between 13 and 20 week of gestation respectively still showed abnormal hCG value. One percent of induced abortion at 5 month, 4% of spontaneous abortion at 3 month, 0.3% of term delivery at 4 month still maintained abnormal titer. No malignant sequelae in patients under the investigation have ever been observed in the follow up period between 3 and 8 years.

Abortion, Spontaneous↗

An evaluation of four serum tests for pregnancy.

We evaluated four pregnancy tests (Biocept-G, Beta-CG, Preg/Stat, and HCG-Beta Screen), using sera from 59 nonpregnant subjects and 77 patients with serum human choriogonadotropin beta-subunit (beta-hCG) concentrations ranging from 4 to 100 000 int. units/L. The results obtained for each test were compared with the results predicted on the basis of the sample's beta-hCG concentration and the beta-hCG concentration the manufacturer claimed necessary for a positive result (the test's analytical sensitivity). Biocept-G had the best sensitivity (100%), specificity (98.9%), and accuracy (99.2%). Beta-CG had the poorest sensitivity (86.4%), Preg/Stat the poorest specificity (87.5%), and accuracy (92.6%). We confirmed the manufacturer's claimed analytical sensitivity (200 int. units/L) for the Biocept-G procedure, but our calculated analytical sensitivity for the other tests was significantly different from that claimed by their manufacturers. Best results were obtained with Biocept-G, but with its analytical sensitivity of 200 int. units/L, samples from early pregnancy will give negative results. None of the pregnancy tests evaluated here will establish the presence or absence of early pregnancy with certainty.

Chorionic Gonadotropin↗

Early embryonic mortality in women.

Measurements of human chorionic gonadotropin (hCG) have been used to assess early embryo loss in women. Urine samples obtained from a control group of sterilized women with normal ovulatory menstrual cycles enabled a concentration limit of 56 IU/l to be determined so that any nontrophoblastic hCG or other cross-reacting compounds could be accounted for. One hundred ninety-eight ovulatory cycles were collected from a normal population attempting to conceive. Fecundability was 22% to 27% for this population. The risk of pregnancy in exposed ovulatory cycles was 59.6%; however, 61.9% of conceptuses will be lost prior to 12 weeks. Most of these losses (91.7%) occur subclinically, without the knowledge of the mother.

Adult↗

Functional life span of the corpus luteum gravidarum: an estimation from the mode of fluctuation of serum hormones after artificial termination of pregnancy and succeeding exogenous hCG administration.

Concentrations of estradiol (E2), progesterone (P), 17-hydroxyprogesterone (17-OHP), hCG and hPL were measured by radioimmunoassay in sera obtained serially from 35 subjects who received artificial termination of pregnancy and 24 of them were administered 10,000 IU of hCG 3 to 5 days later when endogenous hCG had sufficiently decreased. The subjects were operated respectively at 4-11 weeks (Group A) and 12-23 weeks (Group B) of gestation. In Group B, all the hormones declined promptly showing a hyperbolic pattern. In contrast, E2, P and 17-OHP in Group A revealed a significant delay of decline although hCG and hPL decreased as fast as hormones in Group B. When hCG was administered, P and 17-OHP showed a trend to elevate in Group A, but they showed a trend to decline in Group B. When compared in percentage value, the statistically significant difference is proved in 17-OHP between the two groups. The significant delay of E2, P and 17-OHP and the significant elevation of 17-OHP in Group A as compared with Group B were clearly demonstrated. Since 17-OHP is mainly of luteal origin, these findings seem to confirm that the corpus luteum gravidarum functions as far as 11 weeks of gestation and then involutes.

Abortion, Induced↗