The limited value of hysterosalpingography in assessing tubal status and fertility potential

FERTILITY AND STERILITY Copyright

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Vol. 63, No.6, June 1995

1995 American Society for Reproductive Medicine

Printed on acid·free paper in U. S. A.

The limited value of hysterosalpingography in assessing tubal status and fertility potential

Vishvanath c. Karande, M.D. * Donna E. Pratt, M.D. Douglas S. Rabin, M.D. Norbert Gleicher, M.D. The Center for Human Reproduction and the Biological Studies Section, The Foundation for Reproductive Medicine, Inc., Chicago, Illinois

Design: To determine whether the diagnostic accuracy and prognostic value ofhysterosalpingography (HSG) could be improved if routine spot films were replaced by an on-line recorded gynecoradiologic study. Setting: Medical school-affiliated private infertility center. Patients: In 1992, a review of 152 infertile women with infertility who demonstrated a normal HSG, by standard criteria of spot film evaluation, in 117 (77%). They were further investigated by gynecoradiologic study if the HSG revealed asymmetrical tubal filling, an increased perfusion pressure, and/or evidence for abnormal tubal spill. In 1993, 47 women with normal HSG by spot film criteria underwent bilateral selective salpingography and were subdivided into those with normal (group I, n = 23) and abnormal (group II, n = 24) tubal perfusion pressures. Intervention: Patients in both study groups then were treated for their infertility independently of pressure perfusion measurements. Main Outcome Measure: Clinical pregnancy rates (PRs) over the ensuing 6 to 10 months. Results: Among 117 women with apparently normal spot film HSG, 64 (55%) demonstrated asymmetrical tubal filling, 32 (27%) demonstrated abnormal spillage into the peritoneal cavity, and 55 (47%) demonstrated abnormally elevated injection pressures. Among 98 women who underwent bilateral selective salpingography, 43 (44%) demonstrated bilaterally normal tubal perfusion pressures and 55 (56%) showed an abnormally elevated pressure in at least one oviduct. Of 47 women that were followed prospectively in 1993, patients with normal perfusion pressure (group I) demonstrated a significantly higher PR than women with elevated tubal pressure (group II) from 2 months and on after the procedure. Conclusions: Routine spot film HSG is oflimited value in assessing tubal status beyond the determination of tubal patency. Especially with regard to fertility potential, HSG should be replaced by gynecoradiologic study. Fertil Steril1995;63:1167-71 Key Words: Hysterosalpingography, selective salpingography, perfusion pressure, gynecoradiology

Hysterosalpingography (HSG) has been a routine procedure in the evaluation of females with suspected fertility problems for decades (1). We estimate that a minimum of 200,000, and probably more, HSG procedures are performed annually in the United States. The overwhelming majority are performed today as they were 10, 20, or 30 years Received June 13, 1994; revised and accepted January 13, 1995. * Reprint requests: Norbert Gleicher, M.D., The Center for Human Reproduction, 750 North Orleans Street, Chicago, Illinois 60610 (FAX: 312-649-9655). Vol. 63, No.6, June 1995

ago. Specifically, HSG is done routinely through the manual injection of contrast media. One therefore can expect considerable differences in injection volume and injection speed. These variations translate into significant differences in injection pressures and thus create conditions that, not surprisingly, result in considerable differences in outcome assessment between investigators (2). An increase in injection pressure can have therapeutic consequences. It now has been well established that higher injection pressures, whether during HSG or selective salpingography, can achieve tubal patency in previously

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occluded oviducts (2-4). A standardization of injection parameters therefore is essential if gynecoradiologic studies are to be compared between individual patients and investigators. Hysterosalpingography also is performed routinely using spot films. What this means is that the operator obtains documentation of contrast flow at totally arbitrarily chosen moments during the study. Such a technique permits adequate determination of anatomic contours and determination of tubal spill but is obviously quite limited beyond that. For example, spot filming does not permit assessment of tubal filling, especially as it reflects symmetry between both tubes. Spot films also do not permit a slow observation of uterine filling, which at times can greatly contribute to the diagnosis of uterine pathology (Fig. 1). A radiologic system that permits on-line documentation of flow, replay from memory, and, possibly, digitalized enhancement features therefore can be expected to improve the diagnostic capabilities of spot film HSG beyond the obvious limitations of the naked eye to follow a fluoroscopic event on the screen. We have demonstrated that in a standardized system injection pressures during HSG and selective salpingography can be defined as normal or abnormally high (5). Although pressures during HSG are of limited value because they reflect the tube of lesser resistance, perfusion pressures during selective salpingography appear to correlate to tubal disease (5). Whether they also correlate to pregnancy potential, however, has not been determined. This study was designed to determine whether a gynecoradiologic study based on [1] standardized contrast injection; [2] on-line continuous flow monitoring and digitalized enhancement capabilities; and [3] the evaluation of perfusion pressures during HSG and selective salpingography would be superior in diagnostic capabilities to standard spot film HSG and could be used as a valid predictor of fertility potential. MATERIALS AND METHODS

In 1992, 152 consecutive females underwent a radiologic investigation of uterine and tubal status as part of a routine infertility evaluation at the Center for Human Reproduction in Chicago. Written consent was obtained from every patient. Among those, 117 (77%) demonstrated normal findings, defined as a normal uterine cavity, normally appearing tubes, and bilateral spill into the peritoneal cavity. Under spot film conditions, all ofthese patients would qualify as normal HSG studies. However, because their roentgenogram procedure was done with utilization of a fully digitalized C-arm system (Stenoscop-2 C1l6~

Figure 1 Standard HSG with margin enhancement feature. Frame 003 demonstrates the right horn of a mildly bicornuate uterus and a properly filling right tube (R). A filling defect at the base ofthe left horn (arrows) is suggestive of a submucous myoma, which prevents filling of the left uterine horn and left tube. Only a split second later (frame 004) the intrauterine pressure is high enough to separate anterior and posterior walls of the uterine cavity in a more pronounced fashion. The contrast bypasses the myoma and fills the left uterine horn and left tube (Ll. Without sequentially recorded time studies, this myoma would not have been diagnosable.

arm; General Electric Medical Instruments, Milwaukee, WI), with 100 frame memory and various enhancement capabilities, each study was documented on-line, recorded, and printed out on heatsensitive paper. This allowed the detailed documentation of asymmetrical tubal filling and of rather minimal uterine abnormalities (Fig. 1). It also permitted the diagnosis of fimbrial tubal abnormalities and of abnormal patterns of tubal spill. Standardization of contrast injection was achieved as described before (5), except that a fully computerized system was used to record and document pressure curves during HSG and selective salpingography. In short, a double balloon HSG catheter (Uterine cannula; Bard Reproductive Systems, Tewksbury, MA) was placed in the cervix. This effec-

Karande et al. Hysterosalpingography versus gynecoradiology

Fertility and Sterility

Figure 2 Gynecoradiologic study demonstrating perfectly normal contrast and pressure findings. The top panel demonstrates a normal HSG with symmetrical fill and spill of both tubes and a normal perfusion pressure curve. Middle and bottom panels demonstrate left and right selective salpingography, respectively. The pressure curves to the right once again are entirely normal.

tively seals the endometrial cavity. A selective salpingography catheter (same manufacturer) then is threaded through the main channel of the HSG cannula until its tip reaches the tip of the cannula, as indicated by a marker. The distal end ofthe selective salpingography catheter is connected with polyethylene tubing to a preset injection pump and, by three-way stopcock, to a pressure sensitive chip, which relays pressure information to a computer. As contrast is injected by the pump, the computer screen displays the encountered resistance in the form of a pressure curve on the screen and provides a hard copy print out (Fig. 2). The selective salpingography catheter thus was used for HSG as well as selective salpingography. If a selective salpingography was to follow a HSG, the selective salpingography catheter was advanced under fluoroscopic guidance into the desired cornua (5). All studies were performed using water-soluble contrast medium (Renografin-60; Squibb Diagnostics, Princeton, NJ) at a constant rate of 15 mLimin. Based on previously published data, 350 mm Hg of pressure was considered the upper limit of a normal perfusion pressure for both HSG and selective salpingography (5). An apparently normal HSG (by spot film criteria) was considered abnormal (by gynecoradiologic studies criteria) if tubal opacification occurred asymmetVol. 63, No.6, June 1995

rically, if tubal spill was judged abnormal, or if the perfusion pressure during HSG exceeded 350 mm Hg. Under any of those conditions, the HSG was followed by selective salpingography of both tubes. In 1993, 47 patients were followed prospectively based on above described criteria after bilateral selective salpingography. All underwent in routine fashion controlled ovarian hyperstimulation using either gonadotropins (Serono Laboratories, Randolph, MA) or clomiphene citrate (Serono Laboratories) under standard monitoring conditions (Table 1) (6). To maximize further conception rates and uniformity of treatment, lUIs with washed sperm were performed on the 2 days after ovulation induction with hCG (Profasi; Serono Laboratories). Thus, whether patients had normal tubal perfusion pressures (group I) or elevated pressures (group II) did not affect treatment choices. Patient characteristics for both study groups are summarized in Table l. Statistical analysis for comparisons between patient groups for age, duration of infertility, and gravidity, using t-tests, demonstrated no significant differences. Comparison between patient groups for suspected infertility etiology, using the Fisher's exact test or a x2-test when cell sizes were sufficiently large, also showed no significant differences. The occurrence of a pregnancy was recorded when the gestation was seen sonographically as an intrauterine gestational sac. All patients were followed for ~6 months from time of gynecoradiologic study (range 6 to 10 months) and pregnancies were recorded by life table analysis. The life table method was used to adjust pregnancy rates (PRs) for the variability in patient follow-up periods. P > 0.05 was considered

Table 1 Patient Characteristics in Both Prospective Study Groups (n = 23)

Group II (n = 24)

30.4 :<: 8.0 0.8 :<: 1.2 2.7 :<: 1.5

32.4 :<: 8.0 0.7 :<: 1.1 2.9:<: 2.1

7 5 7 2 3 5

9 5 4 3 3 6

15 30

35t 391'

Group I Age (y)* Gravidity* Duration of infertility (y)* Presumed etiologies Endometriosis Male factor Ovarian dysfunction Unexplained Age>40y Others Stimulation cycles Clomiphene citrate Gonadotropins

* Values are means :<: SD. t Group II underwent significantly more stimulation cycles than group I (P < 0.05), even though group I patients demonstrated significantly more pregnancies (Fig. 3). All other patient characteristics did not differ between the two study groups.

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30

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10

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23466 Months after Gynecoradiologic Study

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Figure 3 Life table analysis of PRs (%), group I patients (normal perfusion pressures) are represented by squares and group II patients (abnormal perfusion pressures) are represented by crosses. The difference in PRs was significant from 2 months on after the procedure (P > 0.01).

to represent a significant difference between study groups.

logic procedure, even if the tubal gestation in group II is considered a pregnancy success.

RESULTS

DISCUSSION

During 1992, among the initial 152 consecutively investigated females, 9 (6%) demonstrated bilateral and 26 (17%) demonstrated unilateral tubal occlusion. These patients were treated with tubal catheterization procedures (3) and thus were excluded from this study. Among 117 patients with bilateral tubal patency,64 (55%) demonstrated asymmetrical tubal filling, 32 (27%) demonstrated abnormal tubal spill, and 55 (47%) demonstrated abnormally high perfusion pressures during HSG. In this population of women with fertility problems, 98 (84%) thus demonstrated at least one of three abnormalities that on routine HSG are undetectable. Among 47 women who underwent bilateral selective salpingography during 1993 and were followed prospectively for the occurrence of pregnancy, 23 group I patients (normal perfusion pressures) established 10 pregnancies (43% PR per patient, 22% PR per stimulation cycle). They thus demonstrated significantly higher PR (P > 0.05) than 24 group II patients (abnormal perfusion pressures) who recorded three intrauterine pregnancies (13% PR) and one tubal gestation (total PR 17% per patient and 5% per treatment cycle). Figure 3 demonstrates this difference in the form of a life table analysis. The difference in PRs between groups I and II was significant from 2 months and on after the gynecoradio-

Hysterosalpingography is a cornerstone of routine infertility evaluation. This study demonstrates that the diagnostic capability of standard (spot film) HSG is very limited. Moreover, this study clearly suggests that the use of widely available radiology instrumentation and of easily assembled pressure registration devices can improve greatly upon the presently used techniques of tubal diagnosis. As one would expect, the continuous on-line evaluation of contrast flow is superior to spot film techniques. In fact, it is surprising that continuous flow monitoring so far has not become standard of care during gynecoradiologic procedures because it is the standard in most other medical specialties where contrast studies are performed (7). Because such instrumentation is available in most radiology departments, a proposed switch from spot film to on-line procedures should be possible without a significant increase in cost. This study also re-emphasizes the clinical value of selective salpingography and tubal perfusion pressure measurements. We previously reported that abnormal tubal perfusion pressures correlate with abnormal tubal anatomy (5). Here we are, however, able to demonstrate for the first time that elevated tubal perfusion pressures are an ominous sign with regard to future fertility potential.

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Gynecoradiologic evaluations are performed only secondarily to obtain anatomical information. The true purpose of all such studies is an assessment of fertility potential. The present study suggests that a gynecoradiologic study using the evaluation of tubal perfusion pressures is far superior to standard HSG in predicting fertility potential. Routine HSG, in fact, appears to be of very limited value in assessing tubal status beyond the determination of tubal patency. This may be the reason why HSG and laparoscopy demonstrate only limited correlation (2, 8) and, maybe more importantly, why laparoscopy has become yet another key diagnostic procedure, performed on almost all infertility patients (9). Our own experience, in fact, suggests that the routine performance of gynecoradiologic studies greatly reduces the need for diagnostic laparoscopies because, with the introduction of gynecoradiologic studies, our use of diagnostic laparoscopies as a first stage diagnostic procedure has decreased by approximately 60%. During 1993, only 23% of new infertility couples underwent laparoscopy at our institution. Gynecoradiologic studies therefore can be implemented not only in a very economic way but in fact may achieve secondary cost savings by reducing the need for laparoscopies. The observation that high tubal perfusion pressures correlate with poor pregnancy success raises the obvious question whether a reduction in tubal perfusion pressures would improve PRs. Our experience, to be reported elsewhere (Karande V, Pratt D, Gleicher D, unpublished data), suggests that at least

Vol. 63, No.6, June 1995

some elevated tubal pressures can be reduced successfully using standard transvaginal tubal catheterization techniques. Whether such a reduction, however, also improves pregnancy potential still is undetermined and presently is under investigation. REFERENCES 1. Speroff L, Glass RH, Kase NG. Investigation of the infertile couple. In: Clinical gynecologic endocrinology and infertility. Baltimore: Williams & Wilkins, 1989:513-46. 2. Maguiness SD, Djahanbakhch 0, Grudfinsuas JG. Assessment of the fallopian tube. Obstet Gynecol Surv 1992;47:587603. 3. Gleicher N, Confino E, Corfman R, Coulam C, DeCherney A, Haas G, et al. The multicenter transcervical balloon tuboplasty study: conclusions and comparison to alternative technologies. Hum Reprod 1993;8:1264-71. 4. Risquez F, Confino E. Transcervical tubal cannulation, past present, and future. Fertil SteriI1993;60:211-26. 5. Gleicher N, Parrilli M, Redding L, Pratt D, Karande V. Standardization of hysterosalpingography and selective salpingography: a valuable adjunct to simple opacification studies. Fertil Steril 1992;58:1136-41. 6. March CM, Mishell DR. Induction of ovulation. In: Mishell DR, Davajan V, Lobo RA, editors. Infertility, contraception and reproductive endocrinology. Boston: Blackwell Scientific, 1991:571-98. 7. Baum DS. Interventional catheterization techniques: percutaneous transluminal angioplasty, valvulplasty and related procedures. In: Braunwald E, editor. Heart disease. 4th ed. Philadelphia: Saunders, 1992:1365-1379. 8. Keirse M, Vanderwellen R. A comparison of hysterosalpingography and laparoscopy in the investigation of infertility. Obstet Gynecol 1973;41:685-8. 9. Jones HW, Toner J. The infertile couple. N Engl J Med 1993;329:1710-5.

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