HYSTEROSALPINGOGRAPHY IN THE EVALUATION OF INFERTILITY: A SIX-YEAR REVIEW

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1 FERTILITY AND STERILITY Copyright 978 The American Fertility Society Vol. 30, No. 6, December 978 Printed in U.S A. HYSTEROSALPINGOGRAPHY IN THE EVALUATION OF INFERTILITY: A SIX-YEAR REVIEW JOSEPH S. SANFILIPPO, M.D.* MARVIN A. YUSSMAN, M.D. ORSON SMITH, M.D. Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of Louisville, and Department of Radiology, Methodist Evangelical Hospital, Louisville, Kentucky A series of 505 consecutive hysterosalpingograms (HSG) for the evaluation of infertility is reviewed. Two hundred and seventy-five (54.3%) were interpreted as normal. A tubal abnormality was found in 88 (37.2%) and a uterine abnormality in 42 (8.5%). The literature is reviewed. Hysterosalpingographic abnormalities in the present series are compared with those reported in studies previously published. Complications and advantages of the procedure are outlined. Analysis of the results shows a low morbidity and high return (45.7% abnormal), making HSG one of the most valuable tools in the initial evaluation of the infertile couple. Fertil Steril30:636, 978 Hysterosalpingography (HSG) was first performed in 90 by Rindfleisch, using bismuth subnitrite paste as the contrast medium. Subsequent advances in technique, fluoroscopy, and contrast material have occurred with recent studies employing either Sinografin (Squibb Pharmaceuticals, Princeton, N. J.) (meglumine diatrizoate and meglumine iodipamide) or Salpix (Ortho Pharmaceuticals, Raritan, N. J.) (sodium acetrizoate and polyvinylpyrrolidone) as contrast materials. HSG has been employed for the evaluation of tubal patency and abnormalities, uterine cavity configuration, neoplasms, dysmenorrhea, dysfunctional uterine bleeding, fistulas, pelvic pain, ectopic pregnancy, adenomyosis, 2 cervical abnormalities, and location of intrauterine contraceptive devices (IUDs). In this communication, the authors reviewed 505 consecutive HSG to assess their value as a diagnostic tool for evaluation of Received May 9, 978; revised July 3, 978; accepted August 7, 978. *Reprint requests: JosephS. Sanfilippo, M.D., Department of Obstetrics and Gynecology, University of Louisville, 323 East Chestnut, Louisville, Kentucky possible pelvic disease. Assessment of the techniques and complications of the procedure is made and compared with that previously reported in the literature. MATERIALS AND METHODS The records of 505 consecutive patients who underwent HSG between January 97 and December 977 were reviewed. All procedures were performed in a private, university-affiliated hospital. Five hundred and two patients underwent the procedure as part of their infertility evaluation. The remaining HSGs were performed for preoperative evaluation of a fistula associated with regional enteritis, molar pregnancy, IUD placement (Fig. ), and postoperative evaluation of a metroplasty. The patients were not premedicated and all studies were performed as outpatient procedures. The evaluation was scheduled to 2 weeks after a normal menstrual flow. Pregnancy tests were not deemed necessary except in the case of oligomenorrheic patients. Prior erythrocyte sedimentation rates were requested only if a history suggestive of chronic pelvic inflammatory disease was obtained. The patients' ages ranged from 8 to 43 years. 636

Vol. 30, No.6 HYSTEROSALPINGOGRAPHY IN EVALUATION OF INFERTILITY 637 FIG.. Extrauterine IUD. Aseptic technique was employed after a pelvic examination to determine uterine position.

A Kahn cannula with appropriately sized acorn was inserted into the cervical os.

2 Vol. 30, No.6 HYSTEROSALPINGOGRAPHY IN EVALUATION OF INFERTILITY 637 FIG.. Extrauterine IUD. Aseptic technique was employed after a pelvic examination to determine uterine position. A vaginal speculum was used to visualize the cervix, which was cleansed with betadine and grasped with a single-toothed tenaculum. A Kahn cannula with appropriately sized acorn was inserted into the cervical os. Vaginal leakage of contrast material was prevented by obtaining a tight seal by inserting the tip of the cannula a distance of 3 em into the cervical canal. To decrease distortion of the endometrial cavity, the tenaculum and cannula were retracted posteriorly with equal force. Sinografin at room temperature was used as the contrast medium because of its high image intensity and low viscosity. The latter property was considered beneficial because it produced minimal discomfort when injected. One milliliter of contrast medium provided good uterine cavity visualization; larger quantities tended to obscure subtle defects. A constant flow-low pressure technique was employed during injection. Patient response was considered a good indication for subsequent rate of introduction of contrast material. Significant abdominal pain was an indication to abandon further evaluation. A - to 2-minute rest period was employed when possible bilateral cornual obstruction was noted. Subsequent injection of contrast material showed alleviation of the obstruction in most instances. Repeat studies for this problem were necessary in less than 0.5% of cases. Fluoroscopic time up to 2 minutes was utilized. Anteroposterior and right and left oblique films were obtained as well as a 0-minute delay film for assessing tubal function. Radiation dosage varying from 7 5 to 550 mrads was delivered to the ovaries. The details of the radiographic technique have been previously reported.3 The variation in fluoroscopic time accounted for the differences in total radiation exposure. RESULTS Two hundred and seventy-five (54.3%) of the HSGs performed for infertility evaluation were considered normal. A tubal abnormality was found in 88 (37.2%). A uterine abnormality was found

638 SANFILIPPO ET AL. December 978 Fro. 2. Deeply arcuate uterus with proximal obstruction on one side and hydrosalpinx on the other. in 42 (8.5% ). In 7 cases (7.

Two of the latter were associated with an IUD. Unilateral disease was confirmed by laparoscopy and/or laparotomy in eight cases. Bilateral cornual obstruction was observed in 27 (5.3%) cases.

3 638 SANFILIPPO ET AL. December 978 Fro. 2. Deeply arcuate uterus with proximal obstruction on one side and hydrosalpinx on the other. in 42 (8.5% ). In 7 cases (7.3% of the individual totals) there were both uterine and tubal abnormalities. Twenty-four (4.7%) patients had bilateral hydrosalpinges and 36 (7.%) had a unilateral hydrosalpinx (Fig. 2). Two of the latter were associated with an IUD. Unilateral disease was confirmed by laparoscopy and/or laparotomy in eight cases. Bilateral cornual obstruction was observed in 27 (5.3%) cases. Each exhibited marked resistance to injection of contrast material. Four of these were confirmed by laparoscopy and/or laparotomy; two had a history suggesting chronic pelvic inflammatory disease. Unilateral cornual obstruction was noted in 27 cases (5.3%). None reported a history of tuberculosis or IUD placement. Isthmic obstruction occurred in 27 patients (5.3%): 6 were bilateral and 2 unilateral. Obstruction at the isthmic-ampullary junction or in the ampulla was observed in 24 (4.7%): 6 were bilateral and 8 unilateral. Distal obstruction without evidence of hydrosalpinx was identified in 5 (2.9% ). Surgery was performed in 8 of the group with isthmic obstruction and in of the group with isthmic ampullary blockage, at which time obstruction was confirmed. One unusual finding was that of a fistula between the sigmoid colon and the left tube, the result of regional enteritis (Fig. 3). Lymphatic and venous intravasation was seen in four cases (0.8%) in our series. "Beaded ampulla," shortened tube (postsalpingoplasty), and narrowed ("pipestem") tube with spillage of dye were also observed (Table ). The abnormalities of the uterine cavity are listed in Table 2. The most common findings were eight cases (.6%) of submucous leiomyomas, seven cases (.4%) of a bicornuate uterus (Fig. 4), seven cases (.4%) which were interpreted as unusually large endometrial cavities, five cases (.0%) of uterus didelphys, and three cases (0.6%) ofintrauterine synechiae (Asherman's syndrome). Complications included one patient with iodine hypersensitivity, manifested by urticaria and syncope, and four cases of uneventful intravasation of contrast material. Two patients were hospitalized for severe abdominal pain associated with marked bradycardia. Both patients responded quickly to analgesics.

4 evaluated 73 HSGs for infertility and found 44 (60%) to be interpreted as normal. Pontifex et al.,s in a review of 3697 HSGs for primary and secondary infertility, found 35.8% of the former and 22.

4 Vol. 30, No.6 HYSTEROSALPINGOGRAPHY IN EVALUATION OF INFERTILITY 639 FIG. 3. Tubo-ovarian abscess with rupture into the sigmoid colon. DISCUSSION Comparing our data with those previously published in the literature, we noted that 275 (54.3%) of our HSGs were normal. Yune et al. 4 evaluated 73 HSGs for infertility and found 44 (60%) to be interpreted as normal. Pontifex et al.,s in a review of 3697 HSGs for primary and secondary infertility, found 35.8% of the former and 22.6% of the latter to be normal. The purpose of their evaluation was to investigate the frequency and etiologic significance of HSG findings in patients with infertility. Tubal abnormalities were noted in 88 (37.2%) of our cases as compared with 38.8% in a series of 000 HSGs for infertility reviewed by Siegler. 6 Gabos 7 evaluated HSG and endoscopy and found tubal abnormalities in 54' of 7 HSGs ( 46% ); of 409 cases in Hutchins' series 8 comparing laparoscopy and HSG, 23.8% had tubal abnormality on HSG (Table 3). In evaluating specific HSG findings, bilateral cornual obstruction was noted in 27 cases (5.3%) in our series as compared with 5 of73 cases (6.8%) in the series reported by Yune et al.4 We found the

5 640 SANFU.IPPO ET AL. December 978 Hydrosalpinx Bilateral TABLE. Tubal Abnormalities Abnormality Cornual obstruction Bilateral Proximal one-third obstruction Bilateral Midtube obstruction Bilateral Distal obstruction (nonhydrosalpinx) Fistula between sigmoid colon and left tube Beaded right ampulla Previous tuboplasty with removal of distal one-half of tube Bilateral narrowed tube with spillage Lymphatic and venous intravasation With right cornual obstruction With left hydrosalpinx Otherwise unremarkable No. of cases incidence of a bicornuate uterus to be.4%, leiomyomas.6%, and polyps 0.4%. The patient population and criteria for interpretation of the bicornuate uterus and other congenital anomalies may well account for the percentage difference in our series and that ofpontifex et al. 5 The incidence of polyps is difficult to explain (Table 4}. However, air bubble defects can mimic polyp formation. Intrauterine synechiae were noted in three cases (0.6%) in our series. This entity is discussed in depth by Siegler. 9 In 7 cases there were both uterine and tubal abnormalities. This compares with 4.2% in the entire series of Pontifex et al. 5 Twenty-seven of our cases had a different tubal abnormality on either side. This has not been previously evaluated in the literature. Unilateral hydrosalpinx currently has received much attention as a complication of the IUD. It is of interest that our series indicates that unilateral hydrosalpinx is not an.uncommon entity. Two of thirty-six cases were associated with an IUD. Laparoscopic confirmation was obtained in eight cases. In our series. leiomyomas, an abnormally enlarged uterine cavity, and a bicornuate uterus were among the most frequent fundal abnormalities. These entitites are rarely responsible for inability to conceive but rather are problems in maintaining gestation. Keirse and V andervellen 0 compared HSGs and laparoscopy in a selected group of infertile patients. Tubal patency was agreed upon in 76% of 50 patients. Nickerson evaluated infertility and uterine contour in 90 patients with primary infertility. Each had patent tubes and no obvious cause for infertility. This analysis is of a selected group with subclassification of endometrial cavity abnormalities. Sobrero et al. 2 compared uterotubal insufllation with HSG in 500 patients and found that in 4% the x-ray showed pathologic findings that would not have been discovered otherwise. Many complications of hysterosalpingography have been reported. Infection, in 2% of cases, 3 is apparently related to preparation and antiseptic application prior. to beginning the procedure, retrograde cervical infection, and exacerbation of latent tubal infection. In following our series of patients, none had an exacerbation of chronic salpingitis. Perhaps this was related to the requirement for a normal erythrocyte sedimentation rate before the HSG was performed. Antibiotic therapy is indicated if infection occurs. Intravasation of contrast material continues to be a problem. Timing of the study with respect to the menstrual cycle is of utmost importance in preventing this problem since blood vessel and lymphatics are easily penetrated by contrast material. Etiologic factors include accidental instrument penetration of the uterine wall with subsequent injection of material TABLE 2. Uterine Cavity Abnormalities Abnormality Bicornuate uterus Uterus didelphys Submucous leiomyoma Synechiae Septum Endometrial polyps Stenosis Abnormally enlarged uterine cavity Molar pregnancy Missed abortion Probable adenomyosis IUD Unicornuate uterus No. of cases

Vol. 30, No.6 HYSTEROSALPINGOGRAPHY IN EVALUATION OF INFERTILITY 64 FIG. 4. Bicomuate uterus. into sinuses; Polyps, tuberculous endometritis, and submucous leiomyomas are.

A distinct effort to coordinate the menstrual cycle with timing ofthe examination may well account for the low incidence of this entity.

6 Vol. 30, No.6 HYSTEROSALPINGOGRAPHY IN EVALUATION OF INFERTILITY 64 FIG. 4. Bicomuate uterus. into sinuses; Polyps, tuberculous endometritis, and submucous leiomyomas are.predisposing factors to intravasation. If oil-soluble contrast material is employed, granuloma formation may result. In our series four cases of intravasation occurred. A distinct effort to coordinate the menstrual cycle with timing ofthe examination may well account for the low incidence of this entity. Pain has been reported in up to 80% 4 of patients undergoing the procedure; It has been associated with pre-existing dysmenorrhea, is more common with tubal blockage, and can be reduced by injecting contrast medium slowly. Chemical irritation of the peritoneum reportedly contributes to the pain. 4 It occurs more commonly with watersoluble contrast material. 5 This was not specifically evaluated in our study, although two cases requiring hospitalization were dramatic evidence of its occurrence. Urticaria and syncope following the injection of TABLE 3. Comparison of Tubal Obstructions Reference Tubal obstruction Present Keirse and study Gabos 7 " Siegler" HutchinsH. u Vandervellen HI." Comual Bilateral 5.3% 8.5% 5.3% 2.7% 8% Unilateral 5.3% 3.7% 5.2% 2.5% 2% Total 0.6% 22.2% 20.5% 5.2% 20o/o Mid tube Bilateral.2% 0.8% 2.0% Unilateral 3.6% 4.9% 0.7% 8% Total 4.8% 5.7% 2.7% a HSG findings only.

7 642 SANFILIPPO ET AL. December 978 TABLE 4. Comparison of Uterine Abnormalities Uterine abnormality Bicornuate uterus Uterus didelphys Submucous leiomyomas Synechiae Septum Endometrial polyps Stenosis Enlarged cavity "Primary infertility statistics only. bhsg findings only. Present study.4%.0%.6% 0.6% 0.2% 0.4% 0.4%.4% Sobrero et al % 0.2% 3.8% 0.8% Reference Keirse and Pontifex et ap a Vandervellen 0 'tj Nickerson 2.9%.58% 2.% 2.0% 6.0% 3.5% contrast material occurred in one patient. Treatment consisted of intravenous hydrocortisone and Benadryl with no apparent sequelae. Cardiac response during hysterosalpingography has been previously reported. 6 Patients with a history of reaction following intravenous pyelograms or intravenous cholangiograms, allergies to seafood, or other evidence of iodine sensitivity should be carefully evaluated prior to performing hysterosalpingography. Other reported complications of hysterosalpingography include hemorrhage and shock,t 7 pulmonary and retinal embolus formation, 8 9 peritoneal hemangioendotheliomatosis, 20 cilia damage, 2 and death. 22 Water-soluble contrast material has decreased the incidence of embolus formation. 8 None of these complications occurred in our series. The importance ofhysterosalpingograms as therapy for tubal disease has been suggested. Pregnancy rates of 30%, 23 45%, 23 and 75% 24 have been reported following this radiologic procedure. Rates are influenced by age and duration of infertility. Postulated factors responsible for this phenomenon include therapeutic tubal lavage, breaking down of peritubal adhesions, kinocilial stimulation, and a bacteriostatic effect of the iodine in the contrast materiaj.2 5 Only one patient in our series conceived during the cycle in which the HSG was performed. The low morbidity and high return ( 45.7% abnormal) make HSG one of the most valuable tools in the initial evaluation of the infertile couple. Acknowledgments. The authors wish to thank Douglas Haynes, M.D., and John T. Queenan, M.D., for their cooperation in this study, and express appreciation to Arthur Boerner, M.D., for his contribution to the organization of the data. REFERENCES. Rindfleisch W: Darstellung des Cavum Uteri. Klin Wochenschr 47:780, Fullenlove TM: Experience with over 2,000 uterosalpingographies. Am J Roentgenol 06:463, Sheikh H, Yussman M: Radiation exposure of ovaries during hysterosalpingography. Am J Obstet Gynecol24:307, Yune H, Klatte E, Clearly R, Peterson L: Hysterosalpingography in infertility. Am J Roentgenol 2:642, Pontifex G, Trichopoulous D, Karpathios S: Hysterosalpingography in the diagnosis of infertility. Fertil Steril 23:829, Siegler A: Hysterosalpingography, Second Edition. New York, Medcome Press, 974, p Gabos P: A comparison of hysterosalpingography and endoscopy in evaluation of tubal function in infertile women. Fertil Steril 27:238, Hutchins C: Laparoscopy and hysterosalpingography in the assessment of tubal patency. Obstet Gynecol 49:325, Sieger A: Hysterosalpingography, Second Edition. New York, Medcome Press, 974, p Keirse M, Vandervellen R: A comparison of hysterosalpingography and laparoscopy in the investigation of infertility. Obstet Gynecol 4:685, 973. Nickerson C: Infertility and uterine contour. Am J Obstet Gynecol 29:268, Sobrero A, Silberman C, Post A, Ciner L: Tubal insuffiation and hysterosalpingography. Obstet Gynecol 8:9, Measday B: An analysis of the complications ofhysterosalpingography. J Obstet Gynaecol Br Commonw 67:663, Marshak R, Poole C, Goldberger M: Hysterography and hysterosalpingography. Surg Gynecol Obstet 9:82, Cron R: Hysterosalpingography and infertility. Aust NZ J Obstet Gynaecol 5:2, Sheikh H, Yussman M: Electrocardiographic monitoring during hysterosalpingography. Obstet Gynecol 48:90, Ottow B: Uber violente Cervix Performation gei der Hysterosalpingographie. Abl Gynaekol 60:54, Hodge J, Price A: The management of massive pulmonary embolism following hysterosalpingography. J SC Med Assoc 65:35, 969

8 Vol. 30, No.6 HYSTEROSALPINGOGRAPHY IN EVALUATION OF INFERTILITY Charawanamuttu A, Hughes-Nurse J, Hamlett J: Retinal embolism after hysterosalpingography. Br J Ophthalmol 57:66, Casper J: Periotoneal hemangioendotheliomatosis after salpingography with Thorotrast. Ann NY Acad Sci 45:789, Holmes C: Infertility investigated by hysterosalpingogram. Radiotherapy 38:87, Chuang J, Hewett W, Hreschchyshyn M: Death after hysterosalpingography in choriocarcinoma with pelvic abscess. Obstet Gynecol 37:543, Horbach J, Maathuis J, VanHall E: Factors influencing the pregnancy rate following hysterosalpingography and their prognostic significance. Fertil Steril 24:5, Palmer A: Ethiodol hysterosalpingography for the treatment of infertility. Fertil Steril :3, Gillespie H: The therapeutic aspects of hysterosalpingography. Br J Radiol 38:30, 965