Cortisone in the Treatment of Tubal Occlusion Caused by Healed Genital Tuberculosis

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1 Cortisone in the Treatment of Tubal Occlusion Caused by Healed Genital Tuberculosis ISAC HALBRECHT, M.D. THERE IS a general agreement on the importance of the tubal factor in sterility. In certain geographic areas, tubal tuberculosis is a major cause of tubal occlusion, especially in women suffering from primary sterility.1-4 In 135 out of 325 patients with primary sterility ( 41 per cent), we were able to detect the tuberculous nature of the tubal occlusion either by endometrial biopsy or by cultures of the menstrual discharge and, in some patients, by means of the histologic examination of the tissues discarded during a plastic operation on the tubes. Moreover, on the grounds of the radiographic as well as the clinical findings, we believe that even in those in whom no active tuberculosis of the genital organs was discovered, healed tuberculosis might be the cause of tubal occlusion in primary sterility. The purpose of this article is to report on the results of the use of cortisone (with antituberculous drugs) in the treatment of tubal occlusion caused either by spontaneously healed, or therapeutically healed, genital tuberculosis. MATERIAL AND METHODS In 42 patients in whom bilateral tubal occlusion was diagnosed by means of at least one salpingogram and repeated tubal insufflation, combined cortisone and antituberculous drug treatment was instituted. In 30, genital tuberculosis had previously been diagnosed and treated with antibiotics and chemotherapeutics. In the 12 other patients no active genital tuberculosis had ever been detected, but there was enough radiographic and clinical evidence to warrant the assumption of spontaneously healed tubal tuberculosis. The treatment consisted of daily administration of 50 mg. of cortisone or 5 mg. of meticorten,o 250 mg. of isoniazid, and 12 gm. of PAS, and 1 gm. streptomycin 3 times a week over a period of 4 months. All 42 patients were initially admitted to the hospital for at least 1 week From the Department of Obstetrics and Gynecology, Hasharon Hospital, Petah Tikva, Israel. *Schering Corp., Bloomfield, N. J. 371

2 372 HALBRECHT FERTILITY & STERILITY during which they were thoroughly studied and treatment was initiated under strict clinical observation. Thirty were discharged from the hospital and allowed to continue treatment on an ambulatory basis under the supervision of their own physician. In 12 additional patients a tuboplasty was performed, anti-tuberculous drugs were begun immediately after the operation, and cortisone was added 4-5 days later. The combined therapy was continued for a period of 6-8 weeks. In all patients hysterosalpingography was done routinely 4 months later with the following results: Of the 42 patients who received combined therapy without tuboplasty 10 showed definite improvement of the fibrotic lesions of the tubal walls, as evidenced by greater permeability to the radiopaque substance. Complete restitution of tubal patency was demonstrated by X-ray in 7 patients. In 3 others, tubal insufhation gave positive results, but no radiopaque substance could be seen to enter the peritoneal cavity on salpingography. Three patients became pregnant immediately after treatment. Two had intrauterine pregnancies and have since delivered healthy full-term children. One has been operated twice for an ectopic pregnancy. In 2 of the 12 in whom tuboplasty was done, patency was definitely restored, but no pregnancy has occurred.. In the following cases the results of the cortisone treatment were particularly conspicuous and sufficiently instructive to be reported in detail. CASE REPORTS Case 1. C. R. had been treated for primary sterility for 5 years. Tubal insuffiation was done twice with negative results. Salpingography revealed an occlusion of the right tube at its cornual end. The left tube appeared coiled and filled out to its fimbria. Some extravasation of the radiopaque material occurred in the vicinity of the abdominal ostium of the left tube, but none was visible free in the peritoneal cavity. Vaginal examination revealed a sinistroposition of the uterus and shortening of the left parametrium. Endometrial biopsy and cultures of the menstrual discharge gave negative results for tuberculosis. On the basis of these clinical and radiographic findings, which we consider pathognomonic for the existence of either active or healed genital tuberculosis, we assumed that this patient had had tubal tuberculosis which had healed. A combined cortisone-antibiotic treatment was administered for 4 months. Salpingography done following treatment showed both tubes filled to the fimbriated end and the radiopaque material was seen free in the abdominal cavity. (Fig. 1-3) Immediately after termination of treatment the patient conceived and since has delivered a normal full-term baby. Case 2. B. P. had been suffering from primary sterility for 6 years. The endometrial biopsy showed a normal secretory phase but no tuberculosis. Repeated tubal

3 VOL. 13, No. 4, 1962 TUBAL OCCLUSION TREATMENT 373 Fig. 1. Case 1. Before chemotherapy and cortisone-antibiotic treatment, the left tube appears coiled and fills to its abdominal end. There is some extravasation of contrast medium in the vicinity of the ostium of the left tube. There is no contrast medium free in the peritoneal cavity. Fig. 2. Case 1. Normal filling of both tubes to abdominal ostia after treatment. Fig. 3. Case 1. Contrast medium freely dispersed in peritoneal cavity 24 hours after injection. insufhations and salpingography showed bilateral tubal occlusion. Bimanual vaginal examination revealed a sinistroposition of the uterus and shortening of the left parametrium; healed genital tuberculosis was therefore suspected. Combined cortisone-antituberculous drugs were given for a period of 4 months. Salpingography done after treatment showed both tubes filled to the abdominal ostia and dilatation of the ampular portions (hydrosalpinx). Radiopaque substance

4 374 HAL BRECHT FERTILITY & STERILITY was visible, free in the peritoneal cavity (Fig. 4-6). Two months later the patient conceived and has since delivered a healthy full-term baby. Case 3. A. N. had been treated for primary sterility for 3 years when genital tuberculosis was discovered by means of an endometrial biopsy and cultures of menstrual discharge. She first received purely antituberculous drug therapy: 1 gm. of streptomycin 3 times weekly and 250 mg. of isoniazid daily for 5 months. Repeated endometrial biopsies and 15 cultures of the menstrual discharge, done after irutia- Fig. 4. Case 2. Defective filling of uterine cavity (adhesions?), and normal filling of tubes up to abdominal ostia. After chemotherapy and antibiotics without cortisone. No contrast medium is visible in the free abdominal cavity. Endometrial tuberculosis was diagnosed by endometrial biopsy and culture of menstrual discharge. Fig. 5. and Fig. 6. Case 2. Dilatation of the ampular portions of both tubes, with contrast medium freely dispersed in the peritoneal cavity after combined chemotherapy and cortisone-antibiotic treatment. Uterine cavity is normal.

5 VOL. 13, No.4, 1962 TUBAL OCCLUSION TREATMENT 375 tion of treatment, gave negative results for tuberculosis. Salpingography showed occlusion of the right tube at the uterine cornu and a conglomeration of calcified glands, probably in the cecal region. The left tube was occluded at the fimbriated end. A combined cortisone-antituberculous drug treatment was given for 4 months. Salpingography after treatment showed narrow coiled tubes, both open (Fig. 7-9). Three months afterward she was operated for a first ectopic pregnancy and ten months later for a second one. Fig. 7. Case 3. Left tube filled to the abdominal end, and complete occlusion of right tube before cortisone therapy, but after chemotherapy and antibiotic treatment of endometrial tuberculosis. No contrast medium is free in the peritoneal cavity after 24 hours. There is conglomeration of calcified glands in the cecal region. Fig. 8 and 9. Case 3. Filling of both tubes to their abdominal ends after combined chemotherapy and cortisoneantibiotic treatment. Freely dispersed contrast medium is in the peritoneal cavity after 24 hours.

6 376 HALBRECHT FERTILITY & STERILITY Fig. 10. Case 4. Defects in the filling of the uterine cavity before cortisone therapy. Both tubes are IDled to their abdominal ostia, but with multiple strictures in the ampular portions. Fig.1l. Case 4. No defects in the filling of the uterine cavity after chemotherapy and cortisone-antibiotic treatment. Filling of the tubal lumen better than shown in Fig. 10. Contrast medium is in the peritoneal cavity. Case 4. G. A. has been suffering from primary sterility for 2 years. Endometrial tuberculosis was diagnosed by means of endometrial biopsy. She received 1 gm. of streptomycin 3 times weekly, 12 gm. of PAS and 250 mg. of isoniazid daily, for 6 months. Repeated endometrial biopsies, done during the 2 years following treatment, showed healing of the endometrial tuberculosis. Salpingography showed occlusion of both tubes at the abdominal ends with multiple strictures in the ampular portions. After this a combined cortisone-antituberculous drug treatment was given for 4 months. A repeat salpingography then revealed complete restoration of tubal patency, as well as a normal configuration of the tubal lumen. DISCUSSION During the past 12 years we have treated more than 160 female patients suffering from genital tuberculosis with antituberculous drugs. Treatment consisted of 1 gm. streptomycin 3 times weekly, 12 gm. of PAS and 250 mg.

7 VOL. 13, No. 4, 1962 TUBAL OCCLUSION TREATMENT 377 isoniazid daily for a period of 6-8 months. In almost 90 per cent of patients treated, the genital tuberculosis seems to have healed after such therapy, as shown by repeated negative endometrial biopsies, done at least once a year, and negative cultures of the menstrual discharge, repeated 4-8 times a year. Some patients have been under observation for as long as years and none less than 2 years. The results of antituberculous drug therapy alone were, however, much less encouraging as far as the infertility of the patients was concerned. Thirty (approximately 18.7 per cent) of the 160 treated patients have conceived and have had altogether 45 pregnancies but, unfortunately, only 9 pregnancies resulted in full-term babies; 5 ended in miscarriages and 31 were ectopic pregnancies. We think that antituberculous drug therapy solves the problem of genital tuberculosis but fails to cure the infertility which inevitably results from the former, although to some extent, at least, it improves the prognosis. The problem facing us is how to minimize the fibrotic alterations of the tube wall and how to relieve the obstruction of the tubal lumen in healed genital tuberculosis, hitherto considered irreversible. The addition of cortisone to antituberculous drug therapy has been suggested as a means of preventing the fibrotic lesions in active female genital tuberculosis. 5-7 Good results have been claimed for injection of cortisone plus antibiotics into the uterine cavity and the tubal lumen. Since this method of treatment is not completely devoid of danger, we prefer the oral-parenteral route. So far, we are unable to say whether the combined chemotherapy and cortisone-antibiotic treatment will prevent fibrotic lesions of the tubal wall and conserve tubal patency. In order to restore tubal patency, we have in our present work tried to cure the fibrotic lesions in healed genital tuberculosis with the help of cortisone. The antibiotics and chemotherapeutics which were added to cortisone served only as adjuvants and were given to prevent the eventual reactivation of any latent tuberculosis focus that might exist either in the genital or extragenital organs. The results, so far obtained, appear very encouraging. We were able to restore tubal patency in approximately 20 per cent and obtained 2 normal intrauterine pregnancies. Most of our patients have been under observation for only a relatively short time after treatment; we hope that more pregnancies will occur among them in the future. In one patient the reopening of the tubes caused by the cortisone therapy unfortunately resulted in ectopic pregnancies. We are fully aware that more of our patients face this possibility, but if the proportion between the extraand intrauterine pregnancies remains as now, we shall be satisfied. In 12 patients the combined cortisone-antibiotic treatment was tried in addition to tuboplasty. The cortisone treatment was started 4-5 days after the

8 378 HALBRECHT FERTILITY & STERILITY operation and, Sl> Lar, no untoward results have been observed as far as wound healing is concerned. Salpingography done on these, 2-3 months after operation, showed open tubes in only 2. We feel that the addition of cortisone to antibiotic chemotherapy for active genital tuberculosis in women with the hope of preventing the sclerosing effects of the healing process as much as possible, appears sufficiently promising to be tried in all such cases. The treatment of tubal occlusion in healed genital tuberculosis with cortisone, together with the protective action of the other drugs, if applied to selected patients in whom a least one tube is permeable at the abdominal end, has given encouraging results. Combined chemotherapy and cortisone-antibiotic treatment after a plastic operation for tubal occlusion in healed genital tuberculosis, also has utility. Although we were very careful to test all patients before and during cortisone treatment for sensitivity to cortisone, we were unable to prevent complications in 2. In one patient, a latent gastric ulcer perforated; the patient was operated and recovered. Another developed a few months after treatment persistent hypertension, which may have had a sequential relationship.. SUMMARY Forty-two patients with tubal occlusion caused by healed genital tuberculosis were treated with cortisone and an antibiotic-chemotherapeutic regimen. In seven patients (16.6 per cent), tubal patency was restored after the treatment. In 3 others, the tubes remained occluded but their permeability was considerably improved. Three patients became pregnant immediately after the treatment; two had intrauterine pregnancies with the delivery of normal, term infants and one had 2 ectopic pregnancies. In 12 patients a tuboplasty was done and cortisone given for 6-8 weeks thereafter, starting with the fourth to fifth postoperative day. In 2, tubal patency was restored, but neither patient has become pregnant. REFERENCES Dept. of Obstetrics & Gynecology H asharon Hospital Petah Tikva, Israel 1. HALBRECHT, I. Unsuspected genital tuberculosis as main cause of tubal occlusion. Lancet 1 :235, HALBRECHT, 1. The role of latent genital tuberculosis in the pathogenesis of female sterility. Fertil. & Steril. 2:265, HALBRECHT, I. Tubal missed abortion in active and healed genital tuberculosis. Obst. & Gynec. 14:127, 1959.

9 VOL. 13, No.4, 1962 TUBAL OCCLUSION TREATMENT HALBRECHT, I. Latent genital tuberculosis as the main cause of tubal occlusion. Internat. J. Fertil.1:363, BRET, J., and LEGROS, R. Tuberculose Utero-Annexielle. Masson, Paris, CIOTOLOMAN, H., et al. The treatment of sterility with intra-tubal injection of cortisone associated with antibiotics. Rumanian J. Obst. & Gynec. 22:224, GRUBER, A. E. Cortisone in the treatment of tubal occlusion. Geburtsh. u. Frauenh. 19:78, Fourth World Congress on Infertility (First Brazilian Congress on Infertility) The Fourth World Congress on Infertility, spons~bytheithernat.jenal Fertility Association, will be held at the Hotel Copocabana, Rio de Janeiro, Aug. 8-15, This meeting is also the First Brazilian Congress on Infertility. For further information address DR. MAXWELL ROLAND, Secretary, st Road, Forest Hills 75, N. Y., U. S. A.