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Termination of early pregnancy by a single-dose 3.0 mg 15-methyl PGF2alpha methyl ester vaginal suppository.

The abortifacient effect of a single-dose, long-acting vaginal suppository containing 3.0 mg of 15-methyl PGF2 alpha methyl ester was investigated in 104 early pregnancies. The pregnancy was terminated in 91 per cent of the cases. The abortion was uncomplicated in 79 patients, while 12 patients experienced prolonged bleeding. In 21 uncomplicated cases, VabraR curettage done 4 weeks after therapy revealed necrotic residual tissue in 16 patients and nonspecific endometritis in 20 patients. Residual tissue was found in about 50 per cent of the patients curettaged after 1st menstruation, but no residua was found after 2nd menstruation. In patients with prolonged bleeding, substantial amounts of necrotic residual tissue was found in all patients curettaged 4 weeks after therapy. The decline of serum hCg and plasma progesterone levels was significantly slower in these patients as compared with uneventful abortions.

Abortifacient Agents↗

The use of a radioreceptorassay of human chorionic gonadotropin for the diagnosis and management of ectopic pregnancy.

The radioreceptorassay of human chorionic gonadotropin (hCG), with a sensitivity of 50 pg or 3 mIU/ml of plasma, has provided almost 100% reliability in detecting pregnancy after the first missed cycle. This test may be performed within 1 hour and is ideally suited to the clinical detection of ectopic pregnancy, especially in patients who require immediate surgical intervention. Thirteen patients with suspected ectopic pregnancy were evaluated by the radioreceptorassay, one of whom was followed with four separate determinations. The results of the assay were subsequently compared with those of hemagglutination pregnancy tests, clinical symptoms, and pathologic findings. All of the patients were diagnosed accurately by the radioreceptorassay, even when hemagglutination tests yielded a false indication of pregnancy. By this assay, the hCG levels during ectopic pregnancies are generally lower than those found during a normal intrauterine pregnancy; in addition, pregnancy may be detected much earlier (prior to the rupture) than is possible by hemagglutination tests. Furthermore, the diagnosis of ectopic pregnancy may be excluded for patients admitted to the hospital with acute abdominal emergencies.

Acromegaly↗

A simple and sensitive nonradioactive method for the detection of urinary human chorionic gonadotropin and diagnosis of early human pregnancy. I. Multiple-unit test.

A simple, sensitive, and reproducible method for the detection of urinary human chorionic gonadotropin (hCG) and diagnosis of early human pregnancy is reported. A 5-ml aliquot of filtered early-morning urine sample was concentrated in a microconcentrator (M) to 0.1 ml of retentate which was diluted with 0.4 ml of distilled water and tested in a hemagglutination inhibition test (M-HIT). Also, a 0.1-ml aliquot of filtered unconcentrated urine sample was diluted with 0.4 ml of distilled water and tested in the same hemagglutination inhibition test (HIT). Urine samples from women of reproductive age; from perimenopausal, menopausal, and proteinuric women; and from adult males were tested in the HIT and M-HIT. Some of these urine samples were also tested in the mouse ovulation bioassay (MOB). The M-HIT was significantly more reliable than the HIT for diagnosis of early pregnancy 25 to 55 days after menses. Correct negative results with the M-HIT were obtained in urine samples of most of the nonpregnant cycling, perimenopausal, and menopausal women, and adult males. Urine samples from subjects with severe proteinuria gave false-positive types of reactions in the M-HIT. Positive results were obtained in the MOB with a number of urine samples from pregnant, perimenopausal, and menopausal women. A properly conducted M-HIT should be very valuable in diagnosing pregnancy as early as the 26th day of the cycle in regularly menstruating women.

Chorionic Gonadotropin↗

Late luteal administration of the antiprogesterone RU486 in normal women: effects on the menstrual cycle events and fertility control in a long-term study.

Twelve regularly cycling women, with contraindications to other methods of contraception, received RU486 (Roussel UCLAF, Romainville, France), once a month as a method of fertility control. The study was designed for 18 consecutive cycles. Each patient recorded basal body temperature, detected urinary luteinizing hormone peak, and collected saliva samples during each luteal phase for progesterone (P) determinations. A single dose of RU486, 600 mg, was given on the day before the expected date of the menses and 8 days later in case of continuing pregnancy after the first dose. Blood samples were collected for estradiol, P, and beta-human chorionic gonadotropin analyses on these two occasions. The compliance was poor and the results of only 137 cycles were obtained. The menstrual cyclicity was not significantly modified during this long-term study. Of the 137 cycles, 22 pregnancies occurred (16%), and 4 (18.2%) were not interrupted by the second dose of RU486. Thus, because of the high failure rate, use of RU486 at the time of the natural P withdrawal cannot be advocated as a "once-a-month" contragestive agent.

Adult↗

[Treatment of tubal pregnancy with prostaglandins: a multicenter study].

In this prospective multi-centre-study, the new treatment of tubal pregnancies by means of local prostaglandin (PG) F2 alpha and systemic PG E2 application was compared to the usual surgical technique of eliminating the conceptus. In 71 patients treated with PG, the method proved to be successful in 81%; 21 patients (19%) required surgical intervention later. With an initial beta-hCG level of 2500 mIE/ml, the success rate increased to 88%. The duration of hospitalisation was significantly reduced in the PG group compared to the patients treated by primary operation (3 +/- 1 versus 6 +/- 2 days). In the PG-group, only 2 of 24 hysterosalpingograms showed tubal occlusions after treatment, whereas occlusion was present in 3 of 8 patients of the surgically treated group. Four subsequent intrauterine pregnancies in the PG-group occurred compared to none in the surgical group. PG treatment of tubal pregnancy in patients with a low initial beta-hCG value (less than 2500 mIE/ml) revealed promising results with regard to reduced postoperative morbidity and future fertility.

Abortifacient Agents↗

Effect of oral prostaglandin E2 on uterine contractility and outcome of treatment in women receiving RU 486 (mifepristone) for termination of early pregnancy.

It has been shown that the antiprogestin RU 486 (mifepristone) increases the sensitivity of the early pregnant human uterus to the stimulatory action of synthetic prostaglandin E (PGE) analogues. To examine if RU 486 also increases uterine sensitivity to the naturally occurring PGE2 given orally, two investigative approaches were used in the present studies: (i) direct registration of uterine contractions before and after PGE2 administration in untreated and RU 486-treated early pregnant women; and (ii) a double-blind, randomized, controlled efficacy trial involving treatment of pregnant women (amenorrhoea of less than or equal to 49 days) with RU 486 (25 mg twice daily for 4 days) and PGE2 (1 mg once or twice) or placebo on the last day of RU 486 treatment. The results indicate that oral PGE2 at the doses employed had little or no stimulatory effect on uterine contractility and that it did not improve the rate of complete abortion achieved with RU 486 alone. Overall, 25 of 42 women (59%) had a complete abortion, 15 women (36%) did not abort and the remaining two had incomplete abortions. Women with complete abortions had significantly lower pretreatment levels of progesterone and a longer duration of induced bleeding than those who did not abort. Thus oral PGE2, when given in clinically acceptable doses, is not a suitable alternative to synthetic PGE analogues for use in combination with RU 486 for termination of early pregnancy.

Abortifacient Agents↗

Local prostaglandin treatment of ectopic pregnancy.

Eleven women with small unruptured tubal pregnancies were treated by laparoscopically guided injection of prostaglandin F2 alpha in the oviduct and in the ovary which contained the corpus luteum. They had no side effects of the treatment and were discharged from hospital 1-3 days later. In 10 women the serum concentration of human chorionic gonadotrophin (HCG) decreased to less than 20 IU/l in a median time of 7.5 days, the range being 1-46 days. One woman required an operation 6 days after the treatment as her serum HCG level was stationary and she continued to have abdominal pain. Hysterosalpingography 3 months after the treatment showed patency of the oviduct on the side of the pregnancy in seven of the eight women who have been examined. We conclude that the injection of prostaglandin F2 alpha seems to promote the resolution of selected tubal pregnancies.

Chorionic Gonadotropin↗

Cigarette smoking in pregnancy results in marked decrease in maternal hCG and oestradiol levels.

We have examined serum levels of oestradiol (E2), sex-hormone binding globulin (SHBG) and human chorionic gonadotrophin (hCG) during early pregnancy in relation to smoking status at the time of sampling in a series of 147 women. Smoking was associated with significantly depressed serum levels of E2, SHBG and hCG: in smokers, E2 levels were on average 17.6% lower (P = 0.037), SHBG levels were 12.4% lower (P = 0.15), and hCG levels were 21.5% lower (P = 0.044). There appeared to be a steady decline in these values with increasing cigarette consumption. These lower hormone levels in smokers may explain certain adverse effects of smoking in pregnancy.

Adult↗

Induction of abortion in early pregnancy with mifepristone.

Seventy women requesting first trimester abortion and with amenorrhea of less than 42 days were treated with a single 600-mg dose of mifepristone. Mifepristone is a synthetic 19-norsteroid with strong progesterone receptor antagonist properties. Complete abortion was achieved in 56 women (80%), 2 women (3%) had an incomplete abortion and 12 women (17%) had a continuing pregnancy. No relationship between rate of success and gestational age could be demonstrated. There was no serious side effects and the treatment was favorably received by the women concerned. It is concluded that this treatment is a safe and very acceptable alternative to vacuum aspiration for termination of early pregnancy.

Abortion, Induced↗

Diagnosis of pregnancy in chimpanzees using the nonhuman primate pregnancy test kit.

The usefulness of The Nonhuman Primate Pregnancy Test kit for diagnosis of pregnancy in chimpanzees was determined. This hemagglutination inhibition test for urinary chorionic gonadotropin accurately indicated conception by positive responses in 151 to 153 specimens collected between 20 and 133 days after the estimated day of fertilization. The rate of false positive responses did not exceed 1%.

Animals↗

Studies on in vitro synthesis and secretion of human chorionic gonadtropin and its subunits.

Human chorionic tissues were cultivated in vitro in they presence of 3H-proline in order to study the synthesis of the hCG and its subunits by the placenta. After terminating the culture, tissue extracts and media were individually gel-filtrated on Sephadex G-100. The eluted fractions were radioimmunoassayed for hCG, hCGalpha and hCGbeta and were measured for 3H-radioactivity. Label incorporation was determined by immunoprecipitation. Elution profiles of tissue extracts showed the existence of large immunologic forms of hHCG, hCGalpha and hCGbeta emerging near the void volume. The amounts of these large immunologic species in chorionic tissue gradually decreased during the course of cultivation. 3H-proline was almost exclusively incorporated into the large immunologic forms of hCG, hCGalpha and hCGbeta within the chrionic tissue during the 5-hour exposure. A great quantity of hCGalpha was found in the media after the 3-day culture, while the amount of hCGbeta found in the media was minute. After a 15-minute pulse, the 3H-radioactivity peak within the chorionic tissue appeared in the void volume, conicidental with hCG immunoreactivity. During the chase period, there was shift of the 3H-radioactivity peak associated with hCG immunoreactivity from the void volume to the more retarded area. In the media until after the 60-minute chase, no labeled hCG and its subunits appeared. Within the media after 3-hour chase, no labeled hCG peak associated with 3H-radioactivity was more retarded on Sephadex G-100 than that within the tissue extract after the 15-MINUTE pulse. These results suggest that the large immunologic forms of hCG, HCGalpha and hCGbeta are synthesized as the earliest detectable biosynthetic forms and that the may then be converted to small molecule species. In the culture of molar trophoblastic tissues after a 15-minute pulse, considerable amounts of hCG and its subunits accompanied by high 3H-radioactively had already been secreted into the media. These observations suggest that protein synthesis by molar trophoblastic tissue is markedly enhanced as compared with that by normal chorionic tissue and that immunoreactive materials synthesized in molar trophoblastic tissue may be secreted more radily than those synthesized a in normal chorionic tssue.

Chorionic Gonadotropin↗

The significance of human chorionic gonadotropin in blood serum for the early diagnosis of ectopic pregnancy.

Determination of human chorionic gonadotropin (HCG) values in the serum by the radioimmunoassay technique, was performed in 23 women with suspected ectopic pregnancies. In 16 cases the values of HCG were high and the diagnosis of ectopic pregnancy was verified by laparoscopy and laparotomy. In 7 cases low HCG values were found and ectopic pregnancy was excluded. The detection of HCG in the serum was found to be an excellent tool for the early diagnosis of ectopic pregnancy, thus helping to prevent the dangerous sequelae which follow the late diagnosis of this condition.

Chorionic Gonadotropin↗

Growth hormone secretion during termination of pregnancy. Further evidence of a placental variant.

Serum profiles of growth hormone (GH), hPL and hCG were recorded in 5 pregnant women during termination of pregnancy at cesarean section and legal abortion. Two monoclonal antibodies directed against different epitopes on the GH molecule were used to distinguish the pituitary 22K-GH from the placental GH variant. After placental removal at cesarean section, a rapid fall in GH as well as in hPL and hCG concentrations was recorded. On the other hand GH levels were unaffected when early pregnancy was terminated by legal abortion. The importance of an intact placental function for the maintenance of high GH levels lends further support to the concept that a placental GH variant is produced during late pregnancy.

Abortion, Induced↗

Termination of early pregnancy with RU 486 (mifepristone) in combination with a prostaglandin analogue (sulprostone).

The antiprogestin RU 486 (mifepristone) has been shown to induce abortion when administered in early pregnancy, but the rate of incomplete abortion is high, around 40%. As blockage of the progesterone receptor increases the myometrial sensitivity to prostaglandins, a combination of RU 486 and a prostaglandin E2-analogue was tested for termination of pregnancy. One hundred and sixteen women, with a gestational length of less than 49 days from the first day of the last menstrual period, were treated with a daily dose of 50 or 100 mg RU 486 for 3 to 6 days, complemented with an intramuscular dose of 0.25 mg sulprostone (16-phenoxy-PGE2-sulfonylamide) on the last day of RU 486 treatment. The results confirmed that a reduction of treatment duration to 3 days is just as effective for inducing abortion (91% complete abortion) as a 4-6-day treatment regimen (95% complete abortion). Six patients had an incomplete abortion and in one the pregnancy continued unaffected. Side effects included intense uterine pain after the prostaglandin administration (16%), vomiting associated with the antiprogestin intake (9%) and after the prostaglandin administration (9%). One woman needed emergency curettage due to heavy bleeding. Six percent of the treated patients had a decrease in hemoglobin exceeding 20 g/l during the first week but no patient needed blood transfusion. No serious side effects were recorded.

Abortifacient Agents↗

The effect of the anti-progestin mifepristone (RU 486) on plasma prostaglandin metabolite levels in early pregnancy and its influence on pregnancy termination.

The effect of a single dose of RU 486 (600mg) on prostaglandin metabolite levels has been studied over a 48 h period in 20 women undergoing medical termination of early pregnancy. The results were compared with controls of similar gestation who were treated surgically. The mean (SD) PGEM levels at 0 and 48 h in the RU 486 group were 13.7 (2.7) and 13.2 (2.2) pg/ml respectively, which was not significantly different from the values of 11.7 (1.1) and 11.3 (0.4) pg/ml measured in the control patients. Similarly the mean (SD) PGFM values of 22.3 (14.7) and 17.0 (7.2) pg/ml at 0 and 48 h were not significantly different from the corresponding control values of 21.9 (13.8) and 23.8 (7.2) pg/ml. In 10 of the study patients, there were no significant changes in PGEM and PGFM concentrations prior to and at 4, 24 and 48 h after RU 486 administration. Although all pregnancies were successfully terminated with the combination of RU 486 and subsequently a vaginal pessary containing PGE1, no stimulation of prostaglandin production could be demonstrated.

Abortion, Induced↗

Preliminary studies on the indium slide immunoassay for estimation of human chorionic gonadotropin and antihuman chorionic gonadotropin antibody.

Human chorionic gonadotropin (hCG) is synthesized and secreted as early as 170 hr after fertilization and has been used as an index for pregnancy. Neutralization of hCG with a beta-subunit hCG vaccine(s) has been proposed as a contraceptive technique. To monitor the duration of effectiveness of the vaccine, it will be necessary to monitor the anti-hCG antibodies, especially those responsible for inhibiting the hCG bioactivity. We report a simple, rapid technique using an indium slide immunoassay for the qualitative estimation of hCG and to monitor a bioeffective anti-hCG antibody. The sensitivity of the indium slide assay to measure hCG ranged from 1 microgram/ml to 1 ng/ml, depending on the format of the assay. The indium slide assay also detected anti-hCG antibodies generated against a specific determinant on hCG recognized by a neutralizing monoclonal antibody (P3W80) in women immunized with a contraceptive vaccine.

Antibodies↗

Rapid hCG-specific radioimmunoassay for menstrual aspiration.

Fifty-one women with missed periods ranging from 5 to 14 days who suspected a pregnancy underwent an aspiration curettage with a flexible soft-tipped cannula attached to a Karman-type syringe. Sera from these women were measured for human chorionic gonadotropin (hCG) by a rapid 2-hour solid phase radioimmunoassay using an antibody with a specificity for the beta subunit of hCG. The sensitivity and specificity of this assay insured detection of bCG with 100% accuracy at the time of the missed period. Of the 51 women, 33 (64.7%) were found to have hCG in their serum, and 29 (56.8%) had histologic evidence diagnostic of pregnancy.

Abortion, Induced↗