Use of hCG stimulation test in women immunized with beta-hCG vaccine.

Eleven normally menstruating women, who had earlier been immunized with NII beta-hCG vaccine but had no detectable anti-hCG antibody titres, were selected as controls for the hCG challenge test using 1000/2000 I.U. The test was repeated in five of them after a booster immunization, which raised antibody titres to 18-450 ng/ml. Stimulation of serum progesterone secretion was used as an index of corpus luteum (CL) response to the I.V. hCG. In the control group, the progesterone (P) secretory response following hCG stimulus showed peak levels which were significantly higher than basal levels in all except 2 subjects. The non-responsiveness in 2 subjects cannot be easily explained but may be dose-related. No significant difference was noted between the two dose levels. Length of luteal phase was increased by 4-5 days in 6 out of 20 cycles studied. The results of this test in 5 women before and after the vaccine boosters were encouraging as peak P levels appeared higher than basal levels in controls, but not so in the immunized group. However, these results could not be confirmed statistically. Nonetheless, this study is suggestive that the antibodies generated by this vaccine were capable of intercepting the effect of exogenous hCG in the human female. Further studies with more subjects and higher dosage of hCG are called for.

Analysis of menstrual records of women immunized with anti-hCG vaccines inducing antibodies partially cross-reactive with hLH.

Menstrual data of 13 control subjects and 88 subjects immunized with three beta-hCG-based vaccine formulations were analysed. Immunization did not change the menstrual regularity; bleeding days were normal (3-7 days) and 89% of the menstrual cycles were within the normal range of 22-35 days. Irregular (short or long) cycles were observed in both immunized and control groups. These were, however, unrelated to prevailing anti-hCG antibody titres or to cross-reactivity of antibodies with hLH.

Phase I clinical trials with three formulations of anti-human chorionic gonadotropin vaccine.

Comparative phase I clinical trials were carried out in 5 centres with three formulations of beta-hCG-based vaccines inducing antibodies against human chorionic gonadotropin. The objectives of these trials were to determine their relative immunogenicity, duration, reversibility and safety. A total of 116 tubal ligated women volunteers were enrolled in the study and 101 subjects were followed-up for one year or more until the antibody titres declined to near zero levels. Every woman receiving the vaccine produced anti-hCG and anti-tetanus antibodies. Clinical examination carried out at intervals of 4-6 weeks revealed no abnormality. No serious side effects or adverse reactions were reported with any of the formulations during primary immunization with three monthly injections of the vaccine. Eleven women, however, demonstrated hypersensitivity to test dose at the time of the booster injection. The reaction was to tetanus toxoid; gonadotropin subunits conjugated to another carrier did not evoke any such reaction. Progesterone in bleeds taken at midluteal phase, as well as complete progesterone and estradiol done in two immunized women, indicated normal ovulatory cycles. Immunization with these formulations had no significant effect on haematological, clinical chemistry and other metabolic parameters. In summary, the results indicate that none of the three beta-hCG-based contraceptive vaccines had any adverse effects clinically, on endocrine status and metabolic parameters. Formulations A and B induced comparatively higher anti-hCG titres than M. Thus, further work can be undertaken to study the efficacy of these vaccines in humans for preventing pregnancy.

Hypothyroidism in children/adolescents. Clinical and hormonal profiles.

This paper describes the clinical, hormonal and radiologic profiles in 282 children evaluated for hypothyroidism. Short stature, mental retardation or puberal disturbances were often the presenting features in the older age group, whereas in the 1-5 years age group medical opinion was usually sought for symptomatology suggestive of thyroid hypofunction. Children in the 0-1 year group were suspected on the basis of psychomotor dysfunction. Skeletal immaturity was found in 93.0% of patients with overt hypothyroidism and in 36.6% cases with normal thyroid profiles but associated with malnutrition. High TSH levels were noted in 70.9% of the cases studied. 4.9% and 7.3% patients with normal TSH had low T3, and T4 levels respectively. FSH, testosterone and PRL levels were also affected in some patients with overt hypothyroidism. Therapeutic responses based on at least 1 year follow up were available in 170 cases. The results are discussed.

Klinefelter's syndrome. An immunological disorder.

Immunological study was carried out in 10 cases of Klinefelter Syndrome against sperm antigen. Sperm antibody in serum was present in one of ten cases but cell mediated immunity on the basis of leukocyte migration inhibition test was positive in all the ten cases showing a strong link between chromosomal disorders and immunological tolerance.

Contraceptive efficacy of norethindrone acetate (ENTA) implant: its release rate and fertility potential.

PIP: The contraceptive efficacy of norethindrone acetate (ENTA) implant was evaluated in a study of 79 healthy volunteers aged 19-30 years. The purpose of the study was to 1) relate the menstrual pattern to the average daily release rate of the hormone, 2) assess the concentration of NET in peripheral blood in cases of unintentional pregnancies and ascertain the risk to offspring in such cases, and 3) evaluate the fertility potential and menstrual pattern in the 1-year period after implant removal. In most subjects (59), the implant was removed between the 5th and 8th month. The average release rate was found to be 163.5 mcg/day in subjects with regular menstrual cycles (cycle interval of 25-32 days) compared with 190.9 mcg/day in those with an abnormal menstrual pattern (p0.05). The rate was 143.3 mcg/day in the 19 women who became pregnant during the trial, but this difference is not significant. 15 of the 19 pregnancies occurred between 4 and 8 months, suggesting that the contraceptive efficacy of this implant does not exceed 4-5 months. Mean NET concentration in the sera of the women who became pregnant was 122.5 pg/ml at the time of pregnancy diagnosis. Only 10 subjects complied with the recommendation that their pregnancy be terminated for medical indications. The remaining 9 subjects delivered 6 female and 3 male infants who appeared to clinically normal, despite the fact that 4 had been exposed to the steroid for over 6 weeks. 1 year follow-up was possible in 52 subjects. The menstrual pattern appeared to be regular during this period. 25 of the 44 women in this follow-up group who did not use contraceptive measures became pregnant during the 1st year after implant removal. Additionally, the 9 infants delivered to women during the study period were evaluated for 2-3 years. No adverse changes in growth and development have been observed. This finding suggests that reports associating teratogenicity and progestins in early pregnancy are exagerrated.^ieng

Clinical and immunological responses with Pr- beta-hCG-TT vaccine.

Six different batches of Pr-beta-hCG-TT vaccine have been evaluated in 23 women for the antibody response. The anti-sera formed against these conjugates were capable of reacting immunologically with the whole hCG in radioimmunoassays and also neutralized the biological activity of hCG in radioreceptor assays. The antibody titres attained peak levels 4-6 months after the first injection. The peak titres could not be sustained and most of the subjects showed a spiky pattern. One subject was considered as non-respective, two others had fairly low titres. Amongst the conjugates tested, batch 108 with SPLPS (sodium pthalate denatured with lipo-polysaccharides from S. entritides) seemed more promising, but the addition of the adjuvant was found to be pyrogenic and unlikely to be accepted clinically.

Use of plasma receptor test for HCG in fertility regulation.

PIP: A highly sensitive and specific pregnancy test, based on a radio-ligand assay system, is described; it was developed out of a need for more precision in pregnancy testing in a country which advocates menstrual regulation for pregnancy termination. The assay is based on identification of human chorionic gonadotropin by a plasma receptor and labeled antigen, and can be performed in about 60 minutes. Results of 428 serum samples collected from various clinical conditions were presented; these showed that the test had an accuracy of 99.7% in positive samples. Confirmation of these results was made by clinical follow-up, bioassays, histopathology, and radioimmunoassays. The only disadvantage to this test is the necessity for a radio-labeled isotope, and hence it can only be performed in areas and laboratories so equipped. The test's usefulness in cases of ectopic pregnancy, menstrual regulation, and threatened abortions is emphasized.^ieng

Metabolic and endocrine studies in women using norethindrone acetate implant.

Subcutaneously administered implant-D containing 40 mg of Norethindrone acetate in a single silastic implant was offered to 79 subjects who desired spacing of their family. The effect of constant release of steroid from this device on metabolic and endocrine functions was studied. Each subject in the pretreatment state served as her own control. The device was removed at 8 months initially and subsequently at 5-6 months. The clinical acceptability of this method was fairly high. The results reported in this study show that Norethindrone acetate administered in this way did not cause any adverse reactions on endocrine and metabolic functions as gauged by the parameters analysed.

Use of a radioreceptor test for HCG in women practicing contraception.

The importance of a simple, rapid and highly sensitive test for the diagnosis of early pregnancy cannot be overemphasized. In the present times when newer delivery systems of contraceptive agents and menstrual regulation procedures are increasingly used for fertility regulation, it is inevitable that confirmation of early pregnancy poses a severe problem. This radioreceptor test has been found to be very reliable even in early cases. A positive test was 100% accurate for pregnancy whereas the accuracy of a negative test was found to be 94.4%. Confirmation of these results was done by various other parameters like clinical, histological, radioimmunoassay for HCG and biological test for pregnancy.

PIP: An evaluation of a radioreceptor assay (RRA) for detection of early pregnancy is reported. Following delayed or irregular periods, 250 women were tested using the RRA. The test requires only .1 ml of plasma and the results are obtained within 2 hours. There were 179 positive tests, all of which were confirmed by other methods to be 100% accurate. The test was given to all but 7 of the patients within 2 weeks of the missed period. It is concluded that the RRA is more sensitive than most other immunological tests and less time-consuming than the radioimmunoassay.