Fertility and Genital Tuberculosis

Transcription

1 Fertility and Genital Tuberculosis JOHN STALLWORTHY, F.R.C.S., F.R.C.O.C., F.A.C.S. (Hon.) REFERENCES TO PREGNANCY following treatment of genital tuberculosis are increasing in world literature. Including the cases reviewed for the first time in this paper the delivery of at least 61 viable infants from patients so treated has been recorded since 1952, when Rabau reported the first posttreatment conception. In addition there has been a tragic series of abortions and extrauterine pregnancies although in one instance reported by Snaith and Barns an extrauterine gestation of 39 weeks duration in an elderly primigravida yielded a healthy infant of 2~f kg. In spite of the encouragement provided by these successes, or perhaps it would be more correct to say because of the encouragement provided by these apparent successes, a healthy scepticism has from time to time challenged the validity of claims that have been made. This is a good thing. Schaefer: who has made many valuable contributions to the subject, stated in 1956 that intrauterine pregnancy occurring in the presence of genital tuberculosis was extremely rare and it remained to be seen whether antituberculous treatment would alter this. Already, however, by 1956 cases of intrauterine gestations had been reported by Rabau, Kullander, Barns and Snaith, Pastor, Mac Donald, Hallum and Thomas, and ten Berge. Those reported by Rabau and Barns and Snaith ended in abortion. In the next 3 years, , further reports of a total of 32 successful pregnancies were published by Norburn and Walker, Schmid, Kirchoff, Drasnar, Halbrecht, Dietel, Bobrow, Sutherland, Kese, Earn, and Greenhill. In spite of these reports Schaefer, speaking at the Royal Society of Medicine in London in 1959 issued a warning against unsubstantiated claims by stating that in many of the reported cases the diagnosis of genital tuberculosis may have been incorrect. His reason for this supposition was that chest physicians were occasionally reporting pulmonary infections which appeared clinically and radiologically to be tuberculous but were associated with mycobacteria which could not be identified as either human or bovine organisms. The implication of his comment, not unreasonably, was that a similar infection simulating genital tuberculosis might occur in the pelvis. There Presented at the Ninth Annual Meeting of the Canadian Society for the Study of Fertility, Oct. 26 and 27, 1962, Ottawa, Canada. 284

2 VOL. 14, No.3, 1963 FERTILITY AND GENITAL TB 285 would seem little evidence, however, for the conclusion he drew, namely "that this error in diagnosis is responsible foj; a number of published reports of pregnancies following the treatment of alleged pelvic tuberculosis." As far as the cases reported from Oxford are concerned the possible errors referred to by Schaefer do not apply. All the organisms isolated from these patients were mycobacteria tuberculosis. As yet none of the other strains of mycobacteria have been isolated from pelvic lesions in Oxford and we are unaware of any reports of their discovery from these sites. Strains such as M ycobacterium fortuitum and anonymous are being isolated with increasing frequency in association with pulmonary and surgical lesions resembling tuberculosis. The behavior of these strains on culture and their sensitivity to drugs varies considerably and an experienced bacteriologist can identify them. Schaefer has raised an interesting point, and research into the possible occurrence of this type of pelvic infection and its clinical significance is indicated. His criticism implies a reasonable admonition that in future reports the initial diagnosis of tuberculosis be established beyond dispute. Since 1959 a further 10 successful pregnancies have been reported by Denniss, Johnston and Liggett, Sharman,3o and Snaith and Barns. This brings the total to 61 successful pregnancies following the treatment of genital tuberculosis (Table 1). Some of these reports have been from the Soviet sphere, as with Drasnar's 5 successes, and it is probable that other pregnancies either have not been reported or have not been traced in the literature. Recently, in a letter to the British Medical Journal, Mulligan and his colleagues expressed further doubts on whether genital tuberculosis could be followed by pregnancy. The query was the more significant because it came from workers engaged in the study of infertility and therefore well aware of the literature claiming successes during the last 10 years. They had no personal knowledge of post-treatment successes, but as pelvic tuberculosis is allegedly relatively rare in North America it is possible that the material available to them was inadequate for clinical appraisal. It should be remembered, however, that wherever pulmonary tuberculosis exists there is the probability of finding unsuspected genital tuberculosis if it is looked for. Greenhill was able to report 4 successful post-treatment pregnancies in 135 patients with proven disease in his unit in Chicago. It is worth remembering that 20 years ago the disease was seldom diagnosed in Great Britain, Scandinavia, or other parts of the world from which so many cases have since. been reported. When unsuspected it is easily missed and when provisionally diagnosed on clinical evidence it is not always easy to confirm bacteriologically at the first attempt. Stallworthy discussed the surgical treatment of genital tuberculosis in a

3 286 STALL WORTHY FERTILITY & STERILITY TABLE 1. Reports from the Literature of Successful Pregnancy (Living Infant) after Treatment for Genital Tuberculosis Author Year Number of pl'egnancies Kullander Garcia Pastor MacDonald Hallum & Thomas ten Berge3tl Norburn & Walker Schmid Kirchoff Drasnar Halbrechtll, Dietel Bobrow Sutherland Kese Earn Greenhill Denniss Johnston & Liggett Sharman29, Snaith & Barns Stallworthy paper read to the Thirteenth British Congress of Obstetrics in He referred to the two major complications of high primary mortality and high postoperative fistula incidence, hitherto associated with the surgery of pelvic tuberculosis, and demonstrated how these could be avoided. This was in the pre-antibiotic era. As radical surgery was then essential to success, sterility was the price of cure. Early apparent cures with streptomycin and P.A.S. were already being reported by the time the paper was presented and it was obvious that an important new milestone had been reached both in the treatment of pelvic tuberculosis and in the study and treatment of infertility. The possibility of the new drug not only curing the disease but leaving tubes patent and functional was envisaged. It was clear that surgery, still less radical surgery, should no longer be the primary treatment of choice in those patients whose only complaint was infertility, in the investigation of which unsuspected tuberculosis had been revealed. As far as these patients were concerned an important page in medical history had been turned. Nonetheless, a specialist as eminent as Knaus, in 1962, advocated bilateral

4 VOL. 14, No.3, 1963 FERTILITY AND GENITAL TB 287 salpingectomy as the treatment of choice. This was not new advice, for Solomons, as early as 1935, stated that the removal of tuberculous Fallopian tubes would cure tuberculous endometritis, and other writers have made similar claims. Sharman/V however, reported at the Royal Society of Medicine in 1961 that he had deliberately treated 4 patients in this way (by salpingectomy) and the endometritis had persisted. He had made a similar statement in As one who was among the first to advocate radical surgery before effective drug therapy was developed I regret the thought of any woman now being made permanently sterile by surgery before modern therapy is given a fair trial. If this paper does no more than give at least some woman a chance which she might otherwise be denied it will achieve its purpose. The advice from a surgeon as experienced as Knaus was evidence of his belief that the prospects of pregnancy following medical treatment were remote. This is a view with which we can no longer agree, but the dangers as well as the opportunities must be assessed critically. The need for a subsequent but delayed analysis of results achieved by the new technics was apparent even in 1952, when Stallworthy stated "The time is premature for dogmatic claims regarding treatment and prognosis, and a further review will be required within the next ten years before the value of ideas at present held can be assessed fairly." It seems appropriate, therefore, that in 1962, just 10 years later, with claims for success and reasoned doubts in mind an attempt would be made to review the present position regarding the prospects of pregnancy in tuberculous pelvic disease. PRESENT STUDY The clinical material available to anyone worker is necessarily limited. I have personal experience of only 169 infected patients investigated and treated in the Area Department at Oxford since The early ones in the series were diagnosed prior to the development of modern technics and have been reported previously.34 In addition, as a member of the Research Committee in Great Britain whose results have been reported by Sutherland it has been possible to follow progress over a wider clinical field. For the purpose of this analysis only those patients treated at Oxford since the advent of modern drug therapy are included. From experience gained from these, and where relevant from reports published from other centers, an attempt will be made to answer two basic important questions: 1. Can conception occur in the presence of active pelvic tuberculosis? 2. Can cure of uterine and tubal infection be followed hy pregnancy?

5 288 STALL WORTHY FERTILITY & STERILITY Diagnostic Criteria Before considering each of these in more detail it is essential to establish criteria of diagnosis likely to be accepted by the most critical observer. Failure to do this in the past has been responsible for any confusion which at present exists and has led to the doubts which Schaefer and others have expressed. The protean manifestations in both symptoms and signs of genital tuberculosis have been discussed in many publications and are irrelevant to the problem we have set ourselves except insofar as it is necessary to declare the belief that no combination of these is in itself justification for more than a provisional diagnosis. The final proof of active infection must rest on more certain data. These consist of bacteriologic and histologic evidence and no patient has been included in the Oxford series unless bacteriologic proof of infection was established. Many of the doubts expressed concerning the validity of claims made for cure and for successful pregnancy have arisen understandably enough because some writers have relied solely on histologic evidence of infection, or in their reports have not made it clear whether this or bacteriologic proof was obtained. All who are familiar with the investigation and treatment of these patients know the errors which can arise when only one diagnostic technic is used. The experienced pathologist examining endometrium from many infected patients is unlikely to mistake talc or other foreign body granulomata for tubercles, as described by Bourne, Rouchy, Roberts, Burne, and others. A positive diagnosis in competent hands should be accurate. A negative histologic diagnosis is almost worthless, however skilled the pathologist may be. An exception would be when prolonged amenorrhea thought to be due to fibrocaseous endometritis was shown to be associated with an endometrium without histologic evidence of infection. Generally speaking, however, negative tests are useless. The implications of a negative histologic report can be serious, and to base the opinion of cure on a post-treatment negative histologic report or even repeated negative reports is as unscientific as to exclude a primary diagnosis of tuberculosis because no tubercles are found in the material examined. The reason for this is that in most cases tubercles are discrete and may be few in number, with healthy endometrium between. This explains why random sections and even many serial sections can be negative just as would be the case if healthy skin or interstinal wall were sectioned in the neighborhood of a tuberculous ulcer without including a portion of the ulcer itself. Mistakes will be fewer if the endometrium is studied in the late premenstrual phase of the cycle. If a biopsy specimen is negative, all the material obtained at a subsequent curettage should be sent for pathologic and

6 VOL. 14, No.3, 1963 FERTILITY AND GENITAL TB 289 bacteriologic examination. Except where there is diffuse tuberculous infiltration many serial sections may require examination before one tubercle is found. Bacteriologic proof is obtained by growing the organism from prepared specimens of suspected material, by guinea pig inoculation, or rarely by demonstrating the stained Mycobacterium in a histologic preparation. No method is foolproof. Error will be in relation to negative reports. Mistakes on culture are lessened if two different media such as Loewenstein-Jensen and Kirschner are used simultaneously. Vollum reported 12 specimens which gave a positive culture with Kirschner medium, although negative with Loewenstein-Jensen medium. Some bacteriologists, like some gardeners, have green thumbs and have a much higher success rate on culture than have others of their colleagues. Vollum's experience with known infected material was that histologic evidence was positive in 51%, culture in 52%, and guinea pig inoculation in 58%. Schaefer has thrown doubt on the value of culture as a diagnostic procedure and regards guinea pig inoculation as the final arbiter. Vollum, who is in charge of the bacteriologic laboratories at Oxford and has a wide experience and an international reputation in this field, agrees with this view. Cultures are tested for pathogenicity by guinea pig and, where necessary, rabbit inoculation and are reported positive only when confirmed in this way. In the Oxford series we have accepted either a positive culture or positive guinea pig test as proof of an active lesion, but we have not included patients in whom these were both negative even though the histologic picture suggested the diagnosis. In such a case a repeat premenstrual curettage was performed and bacteriologic investigation repeated. Negative the first time, they could be positive later when there was adequate histologic evidence to suggest the possibility or probability of infection. On the other hand, this emphasis on the importance attached to bacteriologic evidence has resulted in an inevitable reduction in the number of positive histologic reports in the Oxford series. The explanation of this is simple. The proportion of positive results in endometrial specimens will vary according to the number of sections examined from each. The preparation and staining of serial sections is laborious and is not encouraged by busy departments of pathology. If the clinician relies primarily on bacteriologic proof it is unreasonable (apart from research projects) to request serial studies, and the result is that the histologic report will be given on a random sample with the corresponding high risk of it being negative. Attempts to assess the value of histology in diagnosis by comparing the incidence of positive histological reports published by different authors is of little value unless information is given of the extent to which serial sections

7 290 STALLWORTHY FERTILITY & STERILITY were used. In illustration of this is the fact that, in the Oxford series in the group under review, with bacteriologically proved infection, only 18% had a definitely positive histological picture, while in another 18% it was suspicious. Conversely, in 64% there was no pathologic evidence of endometrial infection in the random sections studied. This was in spite of the fact that bacteriologic tests had confirmed activity. Halbrecht,l1 as early as 1950 reported that from 84 infertile women he had made 287 cultures from menstrual blood and in 5 grew MycobF!Cterium although in none was the endometrial biopsy positive. In summary, therefore, it is established that there is considerable potential error in each diagnostic technic and that these relate mainly to negative reports. A positive guinea pig inoculation is accepted as proof of tuberculosis by all bacteriologists, pathologists, and clinicians. A positive culture if confirmed by guinea pig inoculation is also beyond dispute. There are some who will not accept as proof of activity positive cultures unless guinea pig inoculation is subsequently made from these, and there are more who dispute the value of histologic evidence alone. THE BASIC QUESTIONS With this as a background and applying only the undisputed diagnostic criteria of guinea pig inoculation it is possible to answer briefly the two basic questions. Can Conception Occur in the Presence of Active Genital Tuberculosis? The usual answer to this question is "no," but the available evidence does not justify a categorical denial. It merits careful appraisal. It should be emphasized, as has been done repeatedly in the literature, that pelvic tuberculosis whether unsuspected or not is a serious and potentially fatal disease and for this reason should always be treated when diagnosed. The question of whether pregnancy can occur before treatment or after is important but irrelevant to the main issue, which is the necessity for effective treatment. The only death in the Oxford series of 169 patients was that of a woman in 1940 complaining of infertility and found to have unsuspected endometrial infection. She refused to accept the diagnosis, had no treatment, and died a year later of meningitis and miliary tuberculosis. Nonetheless, the question of whether pregnancy can occur before treatment is of great practical importance. It could well be that if conception is possible in spite of activity failure to recognize this possibility has delayed a better understanding of the disease and its relation to infertility. In the Ox-

8 VOL. 14, No.3, 1963 FERTILITY AND GENITAL TB 291 ford series before modern therapy was available no patient with active infection conceived during the time she was under observation, in spite of the fact that 50% had patent tubes. More recently, Snaith and Barns observed no pregnancies in 47 untreated patients during a total of 169 patient years although 46% had patent tubes. Schaefer in 1956 stated that intrauterine pregnancy occurring in the presence of genital tuberculosis was "extremely rare." This implied that it was possible but unlikely. The evidence from Newcastle and Oxford might be interpreted as confirming the view often expressed that pregnancy does not occur in the presence of active tuberculous infection, but there is a possible if not probable fallacy in such a deduction. The patients reviewed in these series were selected insofar as they had complained of infertility, menstrual disorders, or other symptoms. Only on investigation had unsuspected tuberculosis been revealed. Fifty per cent of women with genital tuberculosis have no menstrual disturbance and many are in apparent excellent health, without even a raised E.S.R. They are not therefore normally investigated. There is no justification for declaring that pregnancy cannot occur in this group because it has not been observed in the other. Three case histories are of interest in this connection. Case Reports Case 1. Mrs. K. A., aged 30, had pulmonary tuberculosis at the age of 22. Her first child was born 3 years prior to this when she was aged 19. Two years after her pulmonary lesion she had a therapeutic abortion which was "infected." There is no record of investigation which could have revealed the nature of the genital tract infection. At the age of 25 and 27 she again was delivered normally at term but 3 years later when aged 30 she had a criminal abortion which was "infected." Investigation revealed endometrial tuberculosis as confirmed by positive histology and positive guinea pig inoculation. This infection was obviously present during the pregnancy which was terminated by abortion and there is no evidence to exclude the possibility that it was present throughout the earlier pregnancies following the pulmonary lesion at the age of 22. Case 2. C. L., aged 32, para 3, was admitted to the hospital in 1943, 36 hr. after a normal term delivery with extreme distention of the abdomen due to an extensive paralytic ileus. She had a temperature of 99 and a pulse rate of 120. Her hemoglobin was only 52%, with a red count of 2,800,000. There was marked ascites. There was no clinical or radiological evidence of a pulmonary focus. A straight X-ray of the abdomen showed extensive gaseous distention of the bowel and the suggestion was made that there was probably an obstruction in the rectosigmoid region. Laparotomy was decided upon and was performed 48 hr. after the patient had been admitted. It revealed an extensive subacute tuberculous peritonitis with

9 292 STALL WORTHY FERTILITY & STERILITY ascites and miliary tubercles throughout the abdomen. Both tubes and ovaries were involved in multiple adhesions to the back of the uterus. The left tube was freed and a portion was removed for biopsy purposes and the diagnosis of tuberculous sillpingitis was confirmed histologically. The patient was transferred to a sanatorium where she made good progress; she was discharged after 4 months. Two years later, in 1945, at the age of 34 she was referred back to the gynecological department because of severe menorrhagia which had been present ever since the salpingectomy in A curettage was performed and revealed histological tuberculous endometritis. The patient went back to the sanatorium for 2 months but her menorrhagia persisted and an endometrial biopsy taken at the end of this time gave a positive guinea pig test but a negative culture. A total hysterectomy with bilateral removal of the adnexa and an appendectomy were therefore performed by the technic described in The pathologist reported a secretory endometrium with typical tuberculous infection. Both tubes and both ovaries were also tuberculous. As the subacute manifestation of salpingitis and peritonitis occurred 36 hi. after delivery, it is obvious that this patient had an infection during her pregnancy. There is of course no proof that it antedated conception. Case 3. M. T., at the age of 22, was referred to the gynecological department because of progressive menstrual irregularity over a period of 2~~ years. At one stage there had been 6 months of amenorrhea. She was nulliparous. A calcified focus was found in the infraclavicular zone of the left lung. This was in A diagnostic curettage revealed scanty endometrium, which was reported upon as showing histologic evidence of hypertrophied nonsecretory endometrium with considerable stromal fibrosis. A year later the patient married; she was still having menstrual irregularity and sought further gynecological advice. Her uterus had a cavity of 2~~ in. and endometrial biopsy again revealed only scanty endometrium, which once more was reported upon as being hypertrophied and nonsecretory. There was no evidence of infection. Cyclical hormone therapy was given for 2 months and was followed by two normal periods, the last being on Dec. 23, On Feb. 11, 1947, the patient reported back for infertility testing. The postcoital test revealed only a few nonmotile sperms. The uterus was small, but tubal patency was demonstrated by insufration. An endometrial biopsy again revealed scanty endometrium. The patient was next seen in August 1949 when she reported back because of over 5 months of amenorrhea. She stated that her periods had been extremely irregular, with spells of amenorrhea varying from 3 to 8 months since she had last been seen. Her general health was good. She was also complaining of deep dyspareunia and examination revealed an ovary prolapsed into the pouch of Douglas. Pressure on it reproduced the pain of which she complained. Arrangements were made for repeating her infertility tests, and this time the postcoital test was strongly positive. An endometrial biopsy was taken for culture and histology and it was decided that if these were negative she was to have a further course of cyclical hormone therapy. This was not necessary because when the reports were received the biopsy disclosed

10 VOL. 14, No.3, 1963 FERTILITY AND GENITAL TB 293 the presence of an early pregnancy by demonstrating a few chorionic villi in a small fragment of decidua. Later the culture was reported positive for Mycobacterium tuberculosis. In spite of the unfortunate trauma of the biopsy the pregnancy continued uneventfully to term when preeclamptic toxemia developed. Surgical induction was followed by delivery of a healthy 5-lb. IS-oz. male child. There was no histologic evidence of tuberculosis in the placenta. Re-examination of the chest showed no change in the infraclavicular focus. Unfortunately, at this stage the patient left the Oxford area and we have not seen her since. In this unusual case tuberculous infection existed in the endometrium at the time of the onset of pregnancy. As to date there has been no subsequent investigation of this patient and therefore no confirmation of the diagnosis made in the early weeks of pregnancy there may be reluctance to accept the evidence of the one positive culture. Sharman 30 reported a Glasgow woman who became pregnant at the age of 38 after 17 years of infertility during which tuberculous endometritis had been diagnosed. Eight years after the last histologic diagnosis of chronic endometritis the patient conceived without receiving treatment in the meantime. It does not follow that her lesion had remained active but extensive experience of these patients in the pre-antibacterial era proved that spontaneous cure rarely occurred. More recently tuberculous endometritis was diagnosed 12 days after an abortion at 20 weeks in a case presented in the British Medical Journal by Fisher. In the light of the available evidence it would seem at least justifiable to use the Scottish verdict of "not proved" in answer to the question of whether active infection precludes the possibility of pregnancy. It would be foolish to dogmatize from the one case recorded above in which the evidence seemed conclusive that pregnancy occurred in spite of an active endometritis, but further research is indicated on the decidua or puerperal endometrium of women with a known or suspected pulmonary or surgical tuberculosis. Can Pregnancy Follow the Treatment of Genital Tuberculosis? This question is easier to answer. The reply is unequivocally in the affirmative. Not only is this so, but the prospects are much better than are commonly realized. Seven of the Oxford patients who subsequently conceived and produced 9 healthy infants had a positive guinea pig test when the infection was first diagnosed or a positive endometrial culture confirmed by animal inoculation (Table 2). Two of these also had one abortion each. Five other patients conceived and either aborted or had one or more extrauterine gestation (Table 3). This makes a total of 12 patients who conceived following treatment of a bacteriologically proven infection. The number of infertility patients treated at Oxford for pelvic tuberculosis since the advent of modem

11 294 STALL WORTHY FERTILITY & STERILITY TABLE 2. Data on 7 Patients who had Successful Pregnancy after Treatment for Genital Tuberculosis Patient Guinea pig test Culture '['otal successful pregnancies 1. K. A. 2. P. T. 3. H.C. 4. K. C. 5. H. R. 6. L. R. 7. M.B. TOTAL therapy is 66 so that the percentage for those subsequently conceiving is 18% and the success rate, as measured by patients who were delivered of healthy infants is 10%. Snaith and Barns reported a pregnancy rate of 12% in their series of treated patients trying to become pregnant and 20% among those in whom tubal patency was demonstrated; a figure identical with that reported by HalbrechtP Ryden, reviewing the experience of multiple authors assessed the over-all conception rate as approximately 4%, rising to 30% when tubes were patent. Conception is unfortunately never a guarantee of normal pregnancy, and in the patient who has recovered from genital tuberculosis the hazards are increased. In the Oxford series, 12 patients conceived 17 times and produced 9 living infants. There were 5 extrauterine pregnancies and 3 abortions, a success rate of 53% with an 18% incidence of abortion and a 30% incidence of ectopic pregnancy. Snaith and Barns had a successful pregnancy rate of 39% in 18 pregnancies with an ectopic incidence of 33%. Halbrecht ll 12 reported TABLE 3. Data on Patients with Unsuccessful Pregnancy after Treatment for Genital Tuberculosis Patient Guinea pig test Culture Result 1. H.K. + + Ectopic 2. P. K. + + Ectopic 3. S. J. + Abortion 4. P.T. + + Abortion'" 5. L.R. + Abortion'" 6. B.C. + Ectopic 7. B.T. + + Ectopic ligamentary pregnancy *Two subsequent successful pregnancies (see Table 2).

12 VOL. 14, No.3, 1963 FERTILITY AND GENITAL TB 295 the high ectopic rate of 72% in 22 pregnancies following the treatment of 100 patients. The abortion incidence ot 18% in the Oxford series and 33% in Snaith's series are both higher than the over-all abortion rate in Great Britain and much higher than the expected rate in selected groups of women anxious to produce children. Moreover, in Snaith's series 6 of the 7 women who produced live babies threatened to abort at some stage of pregnancy, though the reason for this is not clear. The considerably higher incidence of pregnancy in patients with apparently undamaged tubes is not surprising, but both intrauterine gestation and, to a greater extent, ectopic, pregnancy can occur when tubes are not normal. Figure 1 demonstrates a right-sided hydrosalpinx Fig. 1. Two views of patient with right-sided hydrosalpinx and typical tuberculous left tube.

13 296 STALL WORTHY FERTILITY & STERILITY and a typical tuberculous left tube in spite of which pregnancy occurred and progressed normally. There is another side to this problem which merits attention. When pregnancy is impossible and adoption is planned, careful assessment of the clinical facts of the case should be made and, before the adopted child is brought into the home, any necessary surgery should be performed so that the patient can be in the best possible health and free from the danger of recurrent pelvic disease. With modern therapy, surgery should seldom be required but is advised: 1. When the pelvic lesion fails to respond or even progresses under treatment. 2. When residual adnexal masses remain after treatment and are associated with disorganized tubes as revealed by hysterosalpingography. Only water-soluble contrast media should be used in the investigation of these patients. Oily solutions can precipitate acute reactivation of infection. Under the circumstances stated above it is advisable to perform total hysterectomy with bilateral salpingo-oophorectomy. Postoperative side effects due to ovarian removal will be avoided if a loo-mg. pellet of estradiol is left in the rectus muscle when the abdomen is closed. The following case recq)zd. illustrates the points made above. Case Report E. Me., aged 33, was nulliparous and anxious about her failure to conceive. She lived in Scotland and had come to Oxford for a second opinion. She was also troubled by a recurrent aching pain in her left iliac fossa. At the age of 29 she had a bilateral thoracoplasty for pulmonary tuberculosis, had spent a long time in the sanatorium, and had made a good recovery. Examination revealed that she was in reasonable health with no sign of pulmonary activity. Her left adnexa were palpable, slightly enlarged, a little tender, and fixed. Apart from this the pelvis was healthy. A provisional diagnosis of genital tuberculosis was made and, as the patient was returning to Scotland the following day, a full report was sent to her doctor with the recommendation that she be referred to a named consultant in Glasgow. She visited another consultant, who informed her that her pelvis was healthy. He performed a hysterosalpingogram and recorded that the tubes were blocked, suggested a repeat examination 4 months later, and told her that both tubes were then patent and normal. Five months after the first examination she was unhappy about her lack of progress and had lost 14 lb. in weight. She returned to Oxford, where the previous findings of a left adnexal pathology were confirmed. X-ray films of the patient, obtained from the consultant, in our opinion were highly suggestive of tuberculous salpingitis. We could not accept the diagnosis of normal tubes. Again the patient had to return to Scotland, so it was recommended to the specialist that he perform a curettage and look for tuberculous endometritis both bacterio-

14 VOL. 14, No.3, 1963 FERTILITY AND GENITAL TB 297 logically and histologically. Further X-ray films were then taken by the consultant at a repeat hysterosalpingography; these also supported the original diagnosis of tuberculous salpingitis. Nothing more was heard of this patient until 10 months later when she was reported as having lower abdominal pain. When she arrived at Oxford she had the typical appearance of a tuberculous patient-high color and normal temperature, but a pulse rate of 98. She had a distended lower abdomen, complained of lassitude, had had only a scanty menstrual loss for some months. From the distention of her abdomen and her scanty periods she had tried to convince herself that she was at last pregnant. Examination revealed a tender mass rising from the pelvis to the size of a 14 weeks gestation. A provisional diagnosis of tuberculous pyosalpinx was made. An endometrial biopsy was taken and material sent for culture and histology, but without waiting for the report treatment was commenced with streptomycin, P.A.S., and isonicotinic acid. Six weeks later and before these reports were received it was found that in spite of the treatment the pelvic mass was considerably increased in size and the patient now looked as though she was 20 weeks pregnant. She and her husband accepted the opinion that pregnancy was now an impossibility and that in the interests of her future health it was essential for her to have the pelvic lesion cleared. Examination confirmed that there was no activity in the chest so a total hysterectomy with bilateral removal of the adnexa was performed. In closing the abdomen a 100-mg. pellet of estradiol benzoate was implanted. Pus taken from the huge pyosalpinx and a section of the wall of the pyosalpinx both grew Mycobacterium tuberculosis twice as resistant to streptomycin as the standard strain and equal in sensitivity to the standard strain in its reaction to isonicotinic acid. The patient made a smooth recovery and, before leaving hospital, had gained 3 lb. in weight. Her progress continued uneventfully. This case illustrates; 1. The necessity of pursuing relentlessly the search for tuberculosis if the initial tests are negative and there are reasonable clinical grounds for suspecting its presence 2. The fact that some patients, fortunately few, will not respond to therapy even with those drugs to which the cultured strain of Mycobacterium appears to be sensitive 3. That under these circumstances surgery is indicated and should be radical CONCLUSION Successes to date have been achieved in the early days of the development of new medical technics. There are certain to be improvements. The wider use of antibacterial and antibiotic agents of probable increasing potency, combined with steroid therapy calculated to reduce healing fibrosis and so preserve the normal anatomy and physiology of the genital tract and particularly of the tube, have yet to be assessed in clinical trial. Even more important

15 298 STALL WORTHY FERTILITY & STERILITY is the need to eradicate pulmonary tuberculosis from the community and bovine tuberculosis from the world's milk supply and to immunize every infant where there is a family history of infection. Until the day dawns when medical students study tuberculosis only as an historical disease the prognosis for child-bearing following the treatment of genital tuberculous infection should progressively improve, but its dangers must not be minimized. SUMMARY Evidence is submitted suggesting that conception can occur in the presence of tuberculous endometritis. The need for further research into this aspect of genital tuberculosis is stressed. Seventeen pregnancies occurring after the treatment of 12 patients with bacteriologically proven endometrial tuberculosis are reported and analyzed. This was the equivalent of an 18% conception rate in those infertility patients found to have genital tuberculosis. There were 9 successful pregnancies, 5 extrauterine pregnancies, and 3 abortions. The series studied is small, but the evidence is clear that healed endometrial and tubal tuberculosis can be followed by successful pregnancy. Be- cause of the increased risk of abortion and extrauterine gestation these patients require most careful antenatal supervision, particularly during the early months. Department of Obstetrics and Gynaecology Radcliffe Infirmary Oxford, England REFERENCES 1. BARNS, T., and SNAITH, L. M. ]. Obst. & Gynaec. Brit. Emp. 60: 131, BOBROW, M. L., POSNER, A. C., FRIEDMAN, S. Am. J. Obst. & Gynec. 74:1136, BOURNE, A. W. Recent Advances in Obstetrics and Gynaecology. Churchill, London, BURNE, J. C. ]. Path. & Bact. 65:101, DENNISS, R. G. ]. Obst. & Gynaec. Brit. Emp. 68:434, DIETEL, H. Deutsche med. W chnschr. 82:905, DRASNAR, J. Proceedings 2nd World Congress Fertility. 1956, p EARN, A. A. ]. Obst. & Gynaec. Brit. Emp. 65:739, FISHER, K. H. Brit. M. ]. 2: GREENHILL, J. P. Year Book of Obstetrics and Gynecology. Yr. Bk. Pub., HALBRECHT, 1. ].A.M.A. 142:331, HALBRECHT, 1. Obst. & Gynec. 10:73, HALLUM, J. L., and THOMAS, H. E. ]. Obst. & Gynaec. Brit. Emp. 62:548, JOHNSTON, J. A. L., and LIGGETT, S. W. Lancet 1:24, KESE, G. Zentral Gyniik. 80:1450, KmcHoFF, H. Milnchen med. Wchnschr. 98:975, KNAUS, H. H. Am.]. Obst. & Gynec. 83:73, 1962.

16 VOL. 14, No.3, 1963 FERTILITY AND GENITAL TB KULLANDER, S. Glasgow M. J. 33:395, MACDoNALD, C. R. J. Obst. & Gynaec. Brit. Emp. 61:514, MULLIGAN, W. J. Brit. M. J. 1:1837, NORBURN, L. M., and WALKER, S. C. H. J. Obst. & Gynaec. Brit. Emp. 63: 173, PASTOR, R. Toko-ginec. Pract 13:166, RABAU, E. J. Obst. & Gynaec. Brit. Emp. 59:743, ROBERTS, G. B. S. Brit. J. Surg. 34:417, ROUCHY, R. Ann. endocrinol. 7:1, RYDEN, A. Acta. obst. et gynec. scandinav. 37:114, SCHAEFER, G. Proc. Roy. Soc. Med. 52:947, SCHAEFER, G., BIRNBAUM, S. J. Obst. & Gynec. 7:180, SHARMAK, A. Fertil. & Steril. 3:144, SHARMAN, A. Proc. Roy. Soc. Med. 54:301, SCHMID, H. H. Zentral Gyniik. 78:2019, SNAITH, L. M., and BARNS, T. Lancet 1 :712, SOLOMONS, B. Surg. Gynec. & Obst. 60:352, STALLWORTHY, J. J. Obst. & Gynaec. Brit. Emp. 59:729, SUTHERLAND, A. J. Obst. & Gynaec. Brit. Emp. 65:450, TEN BERGE, B. Geburtsh. u. Frauenh. 15:181, VOLLUM, R. L. J. Glin. Path. 7:226, Pacific Coast Fertility Society Annual Meeting The 1963 annual meeting of the Pacific Coast Fertility Society will be held Oct. 3-6 at the Flamingo Hotel, Las Vegas, Nev. Further information is available through DR. JULIUS WINER, Secretary, 9915 Santa Monica Blvd., Beverly Hills, Calif., and DR. ERIC MATSNER, Public Relations, 450 North Bedford Dr., Beverly Hills, Calif. American Society of Cytology Eleventh and Twelfth Annual Scientific Meetings The American Society of Cytology (formerly Inter-Society Cytology Council) will hold its eleventh annual scientific meeting at The Neil House, Columbus, Ohio, Nov. 7-9, The twelfth annual meeting will be held at the Penn Sheraton Hotel, Pittsburgh, Pa., Nov , Address all correspondence to WARREN R. LANG, M.D., Secretary-Treasurer, 1012 Walnut St., Philadelphia 7, Pa.