Lipiodol ~~F!l!l for Use in Hysterosalpingography. Allan Palmer, M.D.

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1 Lipiodol ~~F!l!l for Use in Hysterosalpingography Allan Palmer, M.D. THE diagnostic and therapeutic value of lipiodol has been reported by many investigators in the United States and Europe. Lipiodol used for hysterosalpingography in the United States, however, has been restricted to the heavy oily medium regularly available. It is not readily apparent from some of the European literature whether regular lipiodol or another form of lipiodol produced by the same manufacturer, lipiodol "F" ("ultra fluide") has been used abroad. This report deals exclusively with the use of lipiodol "F" in hysterosalpingography. It may be assumed that adverse reports on the use of lipiodol for hysterosalpingography in the United States are due to the occasional untoward effects of the highly viscous and nonabsorbable regular lipiodol. Lipiodol "F" for use in hysterosalpingography was introduced to me in 1939 by Dr. Raoul Palmer, Hopital Broca, Paris. At the time, however, I was unaware that it differed from regular lipiodol. The Riazi apparatus* with which it is used was made in France and differs from other instruments in that radiopaque media enters directly into the mechanism of the manometer. When I first used this foreign-made instrument in the United States regular lipiodol was employed. The manometer was promptly damaged by the medium and it became apparent that another medium should have been used. From the Division of Obstetrics and Gynecology, University of California Medical School. * The Riazi apparatus (more recently Riazi-Palmer) is manufactured by Collin & Cie., 6 Rue de l'ecole-de-medecine, Paris (VIe) France. It is a simple all-metal apparatus consisting of a syringe with an aneroid manometer included in a closed system by a T -way connection. Its separate parts are shown on page 171 in Raoul Palmer's "La Sterilite lnvolontaire, evaluation des methodes de diagnostic et de traitement" published in Paris by Masson & Cie. in

2 Vol. 3, No. 3, 1952] LIPIODOL "F" 211 DESCRIPTION OF CONTRAST MEDIUM Lipiodol "F"* is a straw to amber colored (different lots of it vary in appearance) oily liquid similar in appearance to olive oil but with a lower viscosity. It is produced by modifying the formula of lipiodol (iodized poppy-seed oil, 40 per cent iodine content by weight) which has long been used as a standard contrasting and therapeutic agent in radiology and iodine therapy. It is not merely a solution of iodine in poppy-seed oil, but is a stable chemical compound of these two substances. Its specific gravity is at 15 C. One cubic centimeter of lipiodol "F" contains Gm. of iodine. One gram of lipiodol "F" contains Gm. of iodine. The chemical composition of lipiodol "F" is similar to, yet distinct from, that of lipiodol. While lipiodol is a true vegetable oil, i.e., a glycerin ester, lipiodol "F" is an ethyl alcohol ester. (The specific gravity of regular lipiodol is 1.350; one cubic centimeter contains Gm. of iodine.) The substitution of the alcohol radical for glycerin in the composition of lipiodol simplifies its molecular struc~ure and greatly reduces the viscosity without appreciably affecting the other valuable properties of lipiodol. Because of its much lower viscosity lipiodol "F" is preferable to ordinary lipiodol for any radiologic exploration requiring a very fluid contrasting agent. X-ray films with lipiodol "F" give as clear pictures as with lipiodol and much better defined contrast than with the more viscous aqueous media. TECHNIC In this study hysterosalpingography was performed as an out-patient procedure during the patient's preovulatory phase (as determined from her basal body temperature record) and not less than two days after cessation of her menstrual flow. It has been observed frequently that some bleeding will occur during or after the onset of pregnancy, which cannot be distinguished by the patient from a normal menstrual period. In such cases the basal body temperature record will reveal a sustained high temperature phase, and thus enable an operator to avoid hysterosalpingography when a pregnancy may exist. The procedure was not performed if blood was exuding from the cervical os (which occasionally occurred without the patient being aware of it) or if any gross evidence of endocervicitis existed. " Through the courtesy of The Fougera Company, lipiodol "F" was imported for this study.

3 212 PALMER [Fertility & Sterility One of the three sizes of Colvin self-retaining cannulae was used in most of the patients. This permitted removal of the vaginal speculum so that the outline of the endocervical canal could be seen in the film. In the rare instance where a lacerated or patulous cervix would not permit the use of a Colvin cannula, a short tipped Mathieu cannula, Cotte cannula, or Foley catheter and tenaculum were used. A radioparent aluminum speculum was employed in these patients so that the outline of the cervical canal could still be perceived in the film. The injection was made with manometric but without fluoroscopic control. A preliminary film was exposed; then a second skiagram was made after an injection of 5 cc. of lipiodol "F." The pressure was raised to mm. Hg. In the cases of normal bilateral tubal patency, the pressure fell immediately to below 60 mm. Hg. The wet film was viewed within two minutes and if both tubes were seen to "fill," the apparatus was removed. TABLE 1. Indications for Hysterosalpingography Diagnosis Infertility Menorrhagia Dysmenorrhea Amenorrhea Menopause ToTAL No. of patients l 206 No. of examinations l l 295 The procedure was finished except for a twenty-four-hour follow-up film to establish whether or not "spill" into the peritoneal cavity had occurred. If both tubes did not "fill," further increments of 2 cc. of lipiodol "F" were injected and successive films exposed until tubal patency was established or until the patient's limit of tolerance to discomfort was reached. It was observed in cases of unilateral tubal patency that the pressure did not fall below 90 mm. Hg and usually rose above 100 mm. Hg before it began to fall. Few patients complained of any discomfort at pressures of less than 200 mm. Hg. Tubes have "filled" and "spill" has occurred when the pressure has been increased as high as 350 mm. Hg. Above this point the intrauterine pressure ejected the cannula from the cervix into the vagina. Lipiodol "F" has been used 295 times in 206 patients during the past five years. Table 1 shows the selection of patients studied and the reason for the procedure.

4 Vol. 3, No.3, 1952] LIPIODOL "F" 213 Hysterosalpingograms were repeated only on infertile patients. Table 2 shows the frequency with which the procedure was repeated. Skiagrams were repeated for the following reasons: 1. For mechanical therapy in patients with bilateral or unilateral tubal occlusion. 2. For mechanical clearing of webs, secretions, and kinks in the tubes of patients in whom pregnancy intervened between injections. 3. For postoperative control after surgical intervention upon the tubes. TABLE 2. Numbers of Hysterosalpingograms Taken on 196 Infertile Patients TOTALS No. of examinations made on each patient No. of patients examined No. of skiagmrns made COMMENT Lipiodol "F" has been found to be superior to all other radiopaque media used for hysterosalpingography by this author. It has caused no discomfort, pain, or subjective peritoneal irritation. It is completely absorbed from the peritoneal cavity in three to four months except for an occasional minute droplet within the pelvis. No toxic effects have been observed. Patients prefer the procedure to uterotubal insufflation with carbon dioxide or air. Discomfort was produced by dilating the cervix to introduce the cannula or by raising the pressure above 200 mm. Hg. The patient's tolerance to pain determined the height to which the pressure was raised. ~Hid febrile reactions which may have been the result of the procedure were observed on three occasions. A low-grade pelvic peritonitis occurred in 2 patients, in both of whom hysterosalpingography had been pedormed elsewhere with the use of another medium, presumably regular lipiodol, more than a year previously. Both patients developed an acute pelvic inflammation, bilateral hydrosalpinges, and pelvic inflammatory masses after the first hysterosalpingogram. Preliminary films taken before the use of lipiodol "F" revealed residual quantities of opaque medium still present in each of these patients. The inflammation which occurred in the first of these patients (Case 15) fifteen days after the use of lipiodol "F" was mild and responded promptly to penicillin. In the second patient (Case 120) the reaction ap-

5 214 PALMER [Fertility & Sterility peared forty-seven days after the use of lipiodol "F" during the second menstrual cycle after the procedure. She also responded promptly to the administration of penicillin. She had received a single 300,000 unit dose of penicillin prophylactically at the time of the procedure. The third patient (Case 23) sustained a febrile reaction due to a mild pelvic inflammation nine days after the use of lipiodol "F." On February 21, 1949, following the intrauterine injection of 5.5 cc. lipiodol "F" with pressure to 200 mm. Hg, the uterine cavity was outlined but neither tube filled. A month later, when the procedure was repeated with 6.5 cc. of lipiodol "F" at 200 mm. Hg pressure, the left tube as well as the uterine cavity filled. Follow-up films showed the lipiodol "F" localized, presumably as an "hydrosalpinx," in the region of the fimbriated end of the left tube. The follow-up film nine days later, at the time of her pelvic inflammatory disease, revealed a spreading of the lipiodol "F." She, too, responded promptly to a single dose of penicillin. Since this incident, it has been my custom to administer a single prophylactic dose of 300,000 units of penicillin intramuscularly at the time of the procedure whenever more than 100 mm. Hg pressure has been required for the injection. With the exception of the questionable delayed reaction described in Case 120 above, no febrile reactions have been encountered during the past three years in 183 patients who received more than 250 intrauterine injections of lipiodol "F." There were many other patients who exhibited unilateral or bilateral hydrosalpinges in this study who sustained pressures up to 350 mm. Hg without ill effects. In the beginning, serial films were not always viewed while still wet. The seventh patient in this study, whose skiagrams showed neither tube filled after an injection of lipiodol "F" at 300 mm. Hg pressure, returned for the second injection a month later. Bilateral tubal patency was then demonstrated after a pressure of 280 mm. Hg. Inadvertently the procedure was done on the fourth day of her cycle. She had stopped menstruating less than twenty-four hours previously. There was a massive injection of the titerine lymphatics in the right side which was not seen until after the twenty-fourhour film was taken and all of the films viewed together. Migration of the lipiodol "F" could be traced to the pelvic lymph nodes by X-ray. None reached the chest. There were no ill effects. Because of this incident more temerity was exercised in subsequent patients. Injection of lymphatics has occurred in 9 patients ( 4.3 per cent) without ill effects. Follow-up studies on the 9 patients whose pelvic lymphatics had been

6 Vol. 3, No. 3, 1952] LIPIODOL "F" 215 injected, all of whom had bilaterally occluded tubes, revealed that 3 had no further hysterosalpingograms performed. The latter were repeated on the other 6. Two obtained no benefit. Two showed partial "filling" of one tube only but no "spill." One exhibited bilateral tubal patency and 1 exhibited patency of the left tube only, followed by the onset of an intrauterine pregnancy in the second cycle after patency was established. In all of the follow-up films taken on patients whose pelvic lymphatics had been injected the distribution of the medium could be traced to discreetly identifiable lymph nodes laterally in the pelvis. There were no venous intravasations. It should be added that several patients with bilaterally occluded tubes, in TABLE 3. Pathological Findings in 295 Hysterosalpingograms Made on 206 Patients* Bilateral occlusion of tubes at uterine cornua 24 Bilateral hydrosalpinx 10 Unilateral hydrosalpinx (with or without contralateral patency) 15 Cryptic endocervicitis 42 Cervical stenosis (internal os) 33 Intrauterine tumors (myomata vs. polypi) 7 Bicornate uteri 6 Dermoid (ovary) 1 Calcified ovarian fibroma 1 Rudimentary uteri 2 Injection of lymphatics 9 * Some patients had mortl than one lesion. some of whom unilateral or bilateral patency was effected by pressures as high as 3.50 mm. Hg, sustained the injection without showing any evidence of lymphatic injection. Table 3 shows the number of patients in the study whose hysterosalpingograms revealed various pathologic findings. The absorption of lipiodol "F" by the peritoneum was evaluated from a study of those patients who received two or more intrauterine injections of the oil at varying intervals. Obviously, however, only those patients in whom one or both tubes were patent and in whom peritoneal "spill" was demonstrated were suitable for this study. Thus there were 4 patients each with one tube patent who had hysterosalpingograms during two successive menstrual cycles. The interval between injections ranged from twenty-two to thirty-five days. The preliminary film

7 216 PALMER [Fertility & Sterility taken prior to the second injection on 3 patients showed approximately 50 per cent of the oil still present as compared with that quantity seen in the twenty-four-hour film taken after the first injection. In the fourth patient, no residual oil was seen. In 3 other patients, the interval between the two injections was two menstrual cycles or fifty-six to sixty days. Residual oil in the preliminary film prior to the second injection was less than 25 per cent. In another 4 patients the interval was three menstrual cycles or eighty to one hundred and three days. No residual oil was observed in 2 and less than 1 per cent in the other 2. There were 14 additional cases where the interval was longer than three menstrual cycles (four to eighteen months), and in none of them was any residual oil observed in the preliminary films taken prior to a second injection except for an occasional minute droplet within the pelvis. ADDENDUM Since the original preparation of this report, additional follow-up films* were taken on several patients at approximately thirty, sixty, ninety and one hundred and twenty day intervals after the intrauterine injection of lipiodol "F." This was done in order to evaluate further the rate of absorption of the medium by the peritoneum. Thus in 1 patient approximately 75 per cent of the oil was present in the next cycle or thirty-eight days after the injection. In 6 patients examined two menstrual cycles or sixty to seventy-one days after the injection 25 to 50 per cent of the oil was still present. In 7 patients examined three menstrual cycles or eighty-nine to ninety-four days after the injection 4 had less than 1 per cent and 3 had from 5 to 50 per cent residual oil. In 8 patients examined approximately four months after the injection none or less than 1 per cent of the oil remained. SUMMARY Lipiodol "F" has been used for hysterosalpingography in more than 200 patients. It is one-fifth as viscous as regular lipiodol and is an equally good contrast medium. The author recommends it. REFERENCES 1. Palmer, R., Pulsford, J., and Christeas, N.: Bull. Soc. gynec. et d'obst. 27:127, Palmer, R., Pulsford, J., and Moncorge, M.: Gynec. et obst. 43:121, *I wish to thank Dr. J. Maurice Robinson, roentgenologist, for the numerous extra follow-up films taken for this study.