Abstract
Pregnant Mare's Serum Gonadotrophin (PMS) and Human Chorionic Gonadotrophin (HCG) were used in 110 anovulatory women who were suffering from various types of ovarian insufficiency. As a result, in 65 out of 110 patients (59.1%) ovulation was induced. Clinically, it was clear that larger amounts of PMS were needed in the second course than in the first course. This evidence is presumably due to the inhibition of PMS activity by anti-PMS appeared in the blood.
It has been discussed that PMS might act as an antigen in the human body because it is a heteroproteohormone. The follwoing experiments were performed immunologically : 5 c.c. of blood were obtained from sixteen patients selected randomly out of the patients treated with gonadotrophin. The sera were incubated at 56°C for 30 min. Anti-PMS titers were determined by using the haemagglutination reaction before, through, and after the treatment. The anti-PMS titers could not be detected before the treatment in all cases, and with some individual differences, at least 1 : 128 of the titers were observed in all cases and continued for about 20 weeks. The blood obtained from eleven patients treated repeatedly 8-30 weeks after the first therapy was tested with the same method. Generally, titers increased rapidly, maintained a high level and continued for a longer period than the term after the first course.
In order to investigate whether or not the anti-PMS which was detected by haemagglutination reaction could neutralize the biological activity of PMS, the following experiments were performed biologically : 1 c.c. of serum obtained from the patient, whose serum indicated the titer of 1 : 1,024, inactivated the biological activity of 2 IU of PMS completely in the uterine weight of CF#1 immature mouse. This same serum was diluted by the two fold method until 1 : 8, and was tested with the same method. As a result, it was recognized that 1 c.c. of and serum up to 1 : 64 in titer could not neutralize the biological activity of PMS 2 IU. The sera obtained from six patients who had different anti-PMS titers from 1 : 1,024 showed similar results. From these results, it can be said that anti-PMS of titer 1 : 128 neutralizes 2 IU of PMS; that is, approximately 5,000 IU of PMS injected into the human body (50 kg body weight) are inactiviated by anti-PMS of 1 : 128, and do not stimularte the ovary.
Since these results apparently indicated that anti-PMS formation in serum is a big problem in the gonadotrophic therapy, it is extremely important to devise the method of suppression of anti-PMS. The following two methods were tested : an amount of 0.5 mg of corticosteroid (dexamethasone) was administered daily for 20 days orally (total 10 mg), and 100 mg of cyclophosphamide were injected intravenously every 5 days for 5 days (total 500 mg) together with gonadotrophic therapy. As a result, anti-PMS formation was apparently suppressed, and disappeared in a short period. Although, on the application of cyclophosphamide in this field further studies are necessary, the concomitant use of corticosteroid is unquestionably favorable to induce the ovulation.
Lastly, it should be emphasized that gonadotrophic therapy with PMS in anovulatory women should be carefully carried out with corticosteroid under a rational schedule aimed at the conception.
