The PSP (Speck) Test for Tubal Patency

Transcription

1 The PSP (Speck) Test for Tubal Patency S. Leon Israel, M.D., and Charles R. Freed, M.D. SPECK recently advocated the intra-uterine instillation of phenolsulfonthalein as a test of the patency of the fallopian tubes. He based his suggestion "... upon animal and human experiments" in which, he stated, "... it was found that PSP is not easily absorbed (if at all) from the normal vaginal mucosa, endometrium, or endosalpinx, but is readily absorbed from the peritoneum." By colorimetrically assaying a specimen of urine obtained by catheter thirty minutes after the PSP solution had been slowly injected into the uterine cavity, Speck was able to determine for each of 24 patients whether or not the instilled dye had traversed the fallopian tubes, been absorbed from the peritoneal cavity, delivered to the kidneys, and had thus been excreted. The reported accuracy of the test-judging by the uniformly consistent correlation with uterosalpingography, transuterine insuffiation, or surgical observations in the 24 patients-as well as the relative simplicity of the proposed test, seemed to warrant further investigation. The present study comprises a series of three different applications of the basic principles of the PSP test, namely, that the rate of absorption of the dye from the peritoneal cavity far overshadows the rate attained from the uterus and tubes. Each of the following experiments was so planned as to permit comparison of the absorption and subsequent urinary excretion of variously placed PSP. Thus, the three groups of subjects were such as to leave no doubt concerning the actual placement of the PSP-20 women known positively to have occluded tubes because of previous bilateral cornual excision ( Falk operation), 15 patients into whose peritoneal cavity PSP was introduced during the course of an abdominal operation, and 15 From the Department of Obstetrics and Gynecology, Graduate School of Medicine, University of Pennsylvania, Philadelphia, Pa. 328

2 CO. ~ Vol. 1, No. 4, 1950] TUBAL PATENCY 329 subjects who were given the PSP test under the direct vision afforded by the Decker culdoscope. The only form of selection of patients exercised in this study was that imposed by any existing contraindication to intra-uterine or intratubal manipulation. The untoward complications which occasionally follow tubal studies may generally be traced either to poor timing, or to carelessness in selection of patients. To avoid such unfavorable reactions, the following conditions were regarded as strict deterrents to the intrauterine instillation of PSP: ( 1) any suspicion of active genital infection, including chronic cervicitis and Trichomonas vaginalis vaginitis, and ( 2) an imminent menstrual flow or the presence of uterine bleeding. The monosodium salt of phenolsulfonthalein, the customary commercial variety of phenol red or PSP, was employed in these tests. It is available in aqueous solution in a 1 cc. ampule containing.006 Gm. of the substance. The solution, made separately for each test, except in the Group II experiment, consisted of 2 cc. ( 2 ampules) of PSP and 18 cc. of isotonic saline, totalling 20 cc. and embodying 12 mg. of the dye. However, only half of that quantity, 10 cc., or 6 mg. of the PSP, was injected for the test. This allowed a few cubic centimeters of solution to fill the cannula prior to its passage and permitted comparison to the color standards in use for the universally employed PSP excretion test wherein 6 mg. is the quantity administered intravenously. When the phenol red reaches the blood stream either directly or through absorption, most of it will be bound to plasma proteins until it reaches the distal tubules of the kidney, whence it is liberated into the urine. 2 Its presence therein will be undetected until alkali is added. When that is done, the resulting color varies froni deep red in concentrated solutions to a violet-tinted pink in dilute solutions. The alkali employed in this study was that recommended by Speck: a 10 per cent solution of sodium hydroxide. It was determined in preliminary dilution experiments, by comparison with the laboratory standards for PSP excretion tests, that the "pink or red" end-point considered by Speck to be a positive test-peritoneal absorption of the dye permitted by patent tubes-represented distinct quantitative variations in the urinary content of PSP. A violet-pink hue was found to occur in alkalinized urine when it contained less than 5 per cent of the PSP. A distinctly pink or a clearly red color appeared when at least 5 per cent of the substance was present. Most of the urinary color reactions observed in this investigation were sharply delineated, being either red, representing a content of more than 5 per cent of

3 ISRAEL & FREED [Fertility & Sterility the injected PSP, or colorless, indicating the absence of PSP. A few of the end-points, however, were violet-pink. Having observed that such a color indicated, according to the standards in use, the presence of less than 5 per cent of PSP, we thought it best to consider these few as equivocal results. RESULTS Group I The sub;ects of this experiment were 20 women of childbearing age, each of whom had previously undergone bilateral cornual resection ( Falk operation) because of repeated attacks of salpingitis. The interval between the bilateral tubal excision and the reported experiment varied from 4 to 12 months, but each patient had thoroughly recovered from the laparotomy. The technic of the PSP test in this group of patients was that described by Speck. A bivalve vaginal speculum, two catheters, cotton-tipped applicators, cervical tenaculum, uterine sound, self-retaining screw-type cannula with flexible stem, and 20 cc.-syringe containing the diluted PSP ( 2 cc., or 12 mg., of the dye and 18 cc. of isotonic saline) were placed within reach of the operator, following sterile technic. The patient was placed in the lithotomy position, catheterized, and a bimanual gynecologic examination performed to ascertain the position of the uterus and to exclude the presence of any newly acquired pelvic disorder. The cervix was then exposed by means of the bivalve speculum, painted with antiseptic solution, and its anterior lip grasped by the tenaculum. The uterine sound was gently and briefly introduced into the uterine cavity to determine the direction and length of the cervical canal. The cannula was now connected to the 20 cc. syringe, filled with the PSP solution, and rotated tightly into the cervical canal. About three minutes were allowed to elapse, permitting any uterine spasm evoked by the manipulation to subside, and 10 cc. of the remaining PSP solution was slowly injected into the uterine cavity. The syringe was removed from the cannula but replaced by a stopper, thus preventing the instilled dye from being lost by reflux. In ten minutes, the cannula was removed and a tampon inserted into the vagina. The patient was made comfortable but remained on the examining table. Twenty minutes laterthirty minutes after the intra-uterine injection of the dye-the patient was again catheterized, the urine being carefully collected and sent to the hospital's laboratory for PSP assay. There, a medical technician, one un-

4 Vol. 1, No. 4, 1950] TUBAL PATENCY 331 familiar with the clinical aspects of the study but accustomed to PSP analysis of urine, performed the colorimetric test. Ten per cent solution of sodium hydroxide was slowly added to the urine specimen, the resulting color recorded as being colorless, violet-pink, or red, and the PSPpercentage-content noted by comparison to known standards. In 6 instances, a second specimen of urine was obtained thirty minutes later and tested in like manner. The results observed in these 20 women are summarized in Table 1. Each of them, known to have bilaterally occluded tubes because of previously performed cornual resections, showed no urinary excretion of PSP thirty minutes after its intra-uterine instillation-a negative Speck test. Of the TABLE 1. Results of PSP Test in 20 Women Previously Subjected to Bilateral Cornual Excision (Falk Operation) Time after Intra- No. of Results uterine I n;ection of PSP Patients Positive Equivocal Negative 30 minutes minutes Violet-pink color: less than 5 per cent of the injected PSP in urine. I~ L I ~,., 6 subjects in whom a second specimen of urine was tested for PSP thirty minutes later, or sixty minutes after its injection, only 1 yielded an equivocal response. The latter must be attributed to slight absorption of the PSP through the endometrium, a possibility anticipated by Speck when he chose the thirty-minute interval for the test. The ability of these patients to excrete intravenously injected PSP was not tested. It seems unlikely, however, that 20 negative tests could be so explained. None of the 20 patients experienced any untoward reaction during or following the test. The colic produced in some by the distention of the uterine cavity seemed minimal. Group II The subjects of this experiment were 15 women of child-bearing age, who were undergoing some form of elective abdominal operation. The objective was to study the absorption and excretion of PSP solution placed directly into the peritoneal cavity. Speck had reported that in female rabbits such

5 332 ISRAEL & FREED [Fertility & Sterility intraperitoneally injected PSP is recovered in the urine within thirty minutes. The technic of this experiment embodied merely the introduction of 1 cc. ( 6 mg.) of phenolsulfonthalein, to which had been added 9 cc. of isotonic saline solution, into the open peritoneal cavity and the subsequent collection of urine for testing. (Inasmuch as there was no cannula to fill in this experiment, there was no need to employ the double quantity of PSP for the initial dilution.) The 10 cc. of diluted dye was spilled into the cul-desac at the close of the operation, just prior to closing the abdominal wound. Specimens of urine were obtained by catheter thirty, sixty, and ninety minutes later, and assayed colorimetrically for PSP as described in the Group I experiment. The repeated collection of urine was necessitated by TABLE 2. The Time of Peritoneal Absorption and Urinary Excretion of PSP Immediately Postoperatively in 15 Women Time after Cul-de-Sac No. of Results Instillation of the PSP Patients Positive Equivocal Negative 30 minutes minutes minutes Six patients had a second specimen of urine assayed. the diminished urinary output in some of the patients, a variable feature of the immediate postoperative period. The results noted in these 15 women are epitomized in Table 2. Of 12 subjects who yielded sufficient urine at the thirty-minute period to permit testing for the presence of PSP by the addition of sodium hydroxide, 6 showed a red response (positive), 4 a violet-pink (equivocal), and 2 no color (negative). Each of the 4 patients yielding an initially equivocal excretion of PSP showed a positive response in a second urine specimen-3 at the sixty-minute interval and 1 at ninety minutes. Only 1 of the 2 patients who had no PSP excretion at thirty minutes was recatheterized at the sixtyminute period, showing then an equivocal response. One patient, yielding no urine at thirty minutes, showed no PSP excretion at sixty minutes but did so at ninety minutes. These observations are somewhat vitiated by the fact that the output of urine during the immediate postoperative period is poor, varying with the

6 I~ ' Vol. I, No. 4, 1950] TUBAL PATENCY 333 1l. patient's blood pressure and reaction from anesthesia, as well as with the quantity of fluid administered intravenously during the operation. It is, perhaps, significant that 10 of 12 patients excreted intraperitoneally-placed PSP within thirty minutes of operation, a period of time when the excretion of intravenously injected PSP is known to be decreased. 3 i., Group Ill The subjects of this experiment were 15 women of childbearing age who had been admitted to the hospital for culdoscopic examination. The indication for the latter procedure was either the presence of a nondescript but palpable adnexal mass or the prior demonstration of tubal occlusion by means of the Rubin test. All of the patients were ambulatory and afebrile. TABLE 3. Results of PSP Test Performed During Culdoscopic Examination in 15 Women No. of Patients 9 l 5 Visualized State of Tubes" Results Right Left Positive Equivocal p p 9 0 p NP 0 l NP NP 0 0 Negative "P: patent; NP: not patent..., The technic of the PSP test per se, including the collection of a thirtyminute specimen of urine, was the same as employed in the Group I experiment. However, the conditions were altered in that the fallopian tubes were visualized through the culdoscope during the intra-uterine instillation of the PSP. The culdoscope and the method of its use in this group of patients were those described by Decker, which we are accustomed to employing. In this procedure, accomplished without anesthesia, the tubes are clearly visualized and there is no difficulty in performing the Speck test while the patient is in the required knee-chest posture. The results observed in this group of 15 women are tabulated in Table 3. In 9 of the 15 subjects, the PSP solution injected into the uterine cavity through the cervical cannula was seen to flow from the fimbriated extremity of both tubes. In each, a specimen of urine obtained by catheter thirty minutes later yielded a positive result (red color). In 5 of the 15 women, the PSP solution was not observed to traverse the tubes; nor did it appear

7 ISRAEL & FREED [Fertility & Sterility in any of the thirty-minute urine specimens of these 5 patients. The remaining patient of this group was observed to have a patent right tube, judging by the visualized unilateral passage of the PSP solution. The thirty-minute urine specimen of this patient showed a violet-pink color (equivocal). No unusual reaction occurred in any of these 15 women, an observation which parallels our clinical experience with culdoscopy. SUMMARY AND CONCLUSIONS The intra-uterine instillation of phenolsulfonthalein for the determination of tubal patency, as devised by Speck, seemed sufficiently physiologic to warrant further investigation. This corroborative study of the test followed the technic outlined by Speck, which hinges on the relatively rapid absorption of the instilled PSP from the peritoneal cavity of women with patent tubes and the end-point of which is read as a color reaction in urine obtained by catheter thirty minutes later. Fifty patients, whose tubal status was known, were subjected to the test. Twenty of the 50 subjects had previously had bilateral cornual resection ( Falk operation), 15 were patients undergoing abdominal operation for a variety of reasons, and the remaining 15 were women whose pelvic organs were studied by means of culdoscopy during the performance of the test. The results observed warrant the conclusion that the PSP test is a simple, economical, and safe method of recognizing tubal patency. It cannot, however, supplant the customary tests for determining tubal function, namely, transuterine insufflation and uterosalpingography, because it fails to give data pertaining to the degree of patency and to the localization of the occlusion. However, the test may well be applied when circumstances do not permit the use of more standard procedures. REFERENCES I. Decker, A., and Cherry, T.: Am. J. Surg. 74:40, Marshall, E. K., Jr., and Vickers, J. J.: Johns Hopkins Hosp. Bull. 34:1, Shaw, E. C.: J. Urol. 13:575, Speck, G.: Am. J. Obst. & Gynec. 55:1048, DISCUSSION WILLIS E. BROWN, M.D., Little Rock: The Speck test for tubal pregnancy in many ways is similar to some of the modifications of the Rubin test. It is designed as a quick clinical method for determining tnbal patency without recourse to

8 Vol. 1, No. 4, 1950] TUBAL PATENCY 335 x-ray studies. The present report amply confirms the original communication by Speck as to the reliability of the procedure. We have undertaken partial review of this problem. Since no adequate study of vaginal absorption was reported in this paper, this item was checked. Vaginal absorption was studied in six women by placing a saturated tampon of PSP solution in the vagina and collecting urine by catheter for three 30 minute periods. In none of these women was there any excretion of dye. After peritubal introduction the PSP was easily recognized in the urine in 30 minutes. A positive Speck test resembles shoulder pain in the tubal insufflation test, both giving evidence of some degree of tubal patency. In the study of infertile women, it is necessary to go further than the determination of tubal patency. In our experience, the most reliable method available for this procedure is the use of the various radiographic technics. In a previous report before this society, we have discussed our experience with the various radio-opaque substances and pointed out that tubal spasm would frequently be missed unless serial studies were made. Far more important, however, are the evidences of gross tubal disease in the presence of tubal patency. Patients with x-ray evidence of chronic salpingitis have little opportunity of conception, even though tubal patency is present. In summary, it would seem that the Speck test and tubal insufflation with shoulder pain are both helpful as a part of the preliminary survey of tubal patency, but should not be relied upon as the final diagnosis of the functional status of the fallopian tubes. DR. ARTHUR E. FrnsT, Philadelphia: Unfortunately, I am unable to feel as enthused over the Phenolsulfonthalein test for tubal patency as is its originator, Speck, nor as kindly toward it as is Dr. Israel. Whereas Speck in his original article describes injections into rabbit does, Dr. Israel has done a meticulous piece of investigative work in the human with reference to the absorption of this drug from the uterine cavity and peritoneum. However, in spite of all this painstaking study, I do not feel that we are justified in using the PSP test in preference to any of the other tests employed today for tubal patency. Furthermore, I am still not convinced of the complete accuracy or safety of this test. One patient of ours, with stenosed tubes, had a uterosalpingography done and it was found that the tubes were blocked at the fimbriated end on one side and at the cornu on the other side. In subsequent months, two more Rubin tests still showed complete block, yet the PSP test gave a pink reaction in 30 minutes, which is supposed to indicate tubal patency. Perhaps, the dye is at times absorbed more rapidly from the distended tubes themselves even though the fimbriated ends are closed, thus yielding a false positive. In Dr. Israel's 20 cases with correct negatives all the women had previously had cornual excisions so that no dye could get into the tubes. In several patients, we have recently injected PSP into the uterus prior to operation to determine whether any untoward effects might result. In two patients the dye was still present in a large hydrosalpinx, this distention being due to the PSP.

9 336 ISRAEL & FREED [Fertility & Sterility In two other patients of ours with ovarian cysts, but normal tubes, the tube and affected ovary were removed 24 hours after the PSP test. Sectioning of the tube in both instances revealed evidence of acute endosalpingitis. Pathologic report stated, "Sections of the fallopian tube reveal an intact wall. The villi are edematous and contain leukocytes. The lumen of the tube contains many neutrophils, some lymphocytes, and some macrophages." Although I realize that the acute endosalpingitis in these cases may well be of a transient nature, I question the complete safety of this procedure. In his book on "Utero-Tubal Insufflation," Rubin writes "whether or not they transfer infective material into the pelvic peritoneal cavity, one objection to the use of chemical opaque solutions still remains to be overcome, namely, that they may possibly produce an inflammatory reaction that can agglutinate the lumen of normal tubes." In other words, if by the injection of a dye, such as PSP, we may still cause an endosalpingitis, we might as well employ a radiopaque medium in preference, to give us the advantage of x-ray visualization of the tubes at the same time. The tubal factor in sterility has been one of the most difficult ones to overcome. The least we can do is to use accurate criteria, such as the kymographic tracing and radiopaque oil rather than spend time on a less accurate and much longer procedure such as this. DR. SPECK, Arlington, V a.: The PSP test has been used llo times in Czechoslovakia by Dr. Palan with an accuracy of 100%. I have used the test on 45 patients with the same degree of accuracy. In 24 cases the Rubin test was done along with the PSP test. Two of the Rubin tests showed that the tubes were closed. I repeated the tests subsequently and found that the tubes were open. The PSP in both cases showed a positive test. I interpreted that to mean, and I think I interpreted it correctly, that there was tubal spasm and not that the tubes were closed. I also did 6 hysterosalpingograms. Of the 6 hysterosalpingograms one was reported as negative. The tubes were actually closed on the film but the PSP test showed that they were open. The patient subsequently became pregnant, so we know very well the tubes were open. I feel that the PSP test has so far been 100% accurate. The PSP test is not meant to supplant any of the other existing tests, but I do feel that the PSP test has a place in determining simple tubal patency. I don't feel that air should be used in any tubal patency test. I feel that air is dangerous, from personal experience and the experience of others. As for Dr. First's case, in which the PSP test was positive and the Rubin test and hysterosalpingogram were negative: I wish he had done them all at the same time. I have a patient in whom the tubes are closed during ovulation, by any test, Rubin, hysterosalpingogram, or PSP, but before the llth day and after the 17th day the tubes are open. If he had made all tests at the same time, as we always do, maybe he would have gotten another result. I was interested in his pathological slide. In my opinion I don't think that reaction, if I may say so, was due to the PSP. I should think one would see some PSP there. I believe it would be too early for a foreign body reaction, but the leukocytes or the macrophages would be trying to pick up the dye. If you look

10 . Vol. 1, No. 4, 1950] ISRAEL & FREED 337 at the slide carefully you will see that it resembles a chronic follicular salpingitis with acute exacerbation. I think this patient's tube had been damaged before. I don't think she was damaged to that extent by the PSP. The PSP test is a test which may be helpful when one cannot send the patient to a roentgenologist for a hysterosalpingogram, or cannot afford the apparatus for the Rubin test. It is economical, accurate, simple, and safe! I hope you will find some use for the test. DR. S. LEON IsRAEL: May I reiterate, that this was not an attempt to apply this test to sterility patients. This was rather an attempt to evaluate the principle of the test, namely, that peritoneal absorption is more rapid than tubal, endometrial or vaginal absorption. In response to the question raised by Dr. First, may I say that we have under way presently a study which purports to show the effect of any agent introduced through the fallopian tubes into the peritoneal cavity, the effect of any agent to that membrane in 12, 24, 48, and 96 hours. Using such a supposedly innocuous substance as Rayopake we were amazed to find, in preliminary sections, that it seemed to make a great difference whether the tube was removed and studied histologically in 24 hours or 96 hours. I hope in a year or two we will have enough data to bring the matter before you.