Effects of cornual catheterization on uterotubal histology and function

Effects of cornual catheterization on uterotubal histology and function Michael P. Diamond, M.D.,a Richard E. Leach, M.D.,a Kenneth A. Ginsburg, M.D.,a Diaa M. El-Mowafi, M.D.,a Elizabeth Dawe, D.V.M.,b and Richard M. Scanlan, M.D.c a c

Department of Obstetrics and Gynecology and b Surgical Research Unit, Wayne State University, Detroit, Michigan; and Department of Pathology, Oregon Health and Sciences University, Portland, Oregon

Objective: To assess histologic damage and functional impairment following coaxial tubal catheterization. Design: Prospective randomized controlled study. Setting: Research laboratory. Patient(s): Ninety-two female New Zealand rabbits. Intervention(s): Tubal cannulation and mating. Main Outcome Measure(s): Rabbits randomized for placement of unilateral catheter and guide wire (group 1), unilateral catheter and guide wire plus falloposcope (group 2), and catheterization as in group 1 or 2 but using a cage catheter (groups 3 and 4, respectively). A fifth group consisted of rabbits with tubal perforations. Rabbits were killed at 2 or 4 weeks after catheterization or after mating. The sixth group consisted of only control rabbits. Result(s): Only one catheterized tube in groups 1 and 3 showed inflammation, fibrosis, or edema. None of the tubes manifested ciliary loss. Serosal tubal adhesions were identified in two tubes in group 1, in one in group 3, in three tubes in group 5, and one in the control group. The nidation index in control and nonperforated catheterized tubes ranged from 72%–95% (not significant). Nidation index in tubes unintentionally perforated was 81%. Conclusion(s): Catheterization of the uterotubal junction and fallopian tube in rabbits does not cause long-term tubal damage or impair tubal function. (Fertil Steril威 2005;84:212–6. ©2005 by American Society for Reproductive Medicine.) Key Words: Tuboscopy, falloposcopy, tubal cannulation, nidation index

The fallopian tube lumen has sometimes been called the final frontier for gynecologic surgery. However, the last decade has witnessed an increased performance of diagnostic as well as therapeutic procedures, which have involved both antegrade and retrograde tubal evaluation. Those procedures have been given a variety of names, including tubal catheterization, tubal cannulation, tuboscopy, and falloposcopy. They have been performed for purposes including assessment of tubal patency, assessment of tubal architecture, reestablishment of tubal patency because of cornual blockage, and placement of gametes or embryos into the tubal lumen. Each of these procedures (with the exception of treatment of cornual blockage) was initially conducted in a retrograde manner beginning at the fimbria. However, such an approach was of limited value because [1] only the infundibular portion of the tube extending to approximately the ampullaryisthmic junction could be visualized because of the external diameter of the scopes and the internal lumen of the tube, [2] laparoscopy was required to gain access to the tube, and [3] the value of examination of the internal architecture of a hydrosalpinx was limited because creating a small opening in the tube was necessary to allow scope placement to judge whether to perform a neosalpingostomy (1, 2). Received September 3, 2004; revised and accepted December 15, 2004. Supported by Conceptus, San Carlos, California. Reprint requests: Michael P. Diamond, M.D., Department of Obstetrics and Gynecology, Hutzel Hospital, 4707 St. Antoine Boulevard, Detroit, Michigan 48201 (FAX: 313-745-7037; E-mail: [email protected]).

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The alternative, namely antegrade tubal evaluation beginning at the cornua using a narrow catheter or scope, as proposed by Kerin et al. (3), would potentially avoid each of the disadvantages of retrograde catheterization. However, in clinical practice, it has been difficult to perform antegrade tubal catheterization without simultaneously straightening the fallopian tube to maximize the length of tube able to be evaluated and minimize the risk of tubal perforation. Additionally, antegrade catheterization has the additional theoretical risk of injuring the narrowest portion of the tube (the cornua and isthmic segments), which would be of particular concern in patients not suspected of having proximal tubal disease. In view of these issues, this study was conducted to assess whether antegrade tubal catheterization would cause histologic or functional tubal damage. MATERIALS AND METHODS The experiment was conducted on 92 female New Zealand white rabbits of approximately 3.5 kg, in which the fallopian tube internal diameter was 0.5 to 1.0 mm. Animals were maintained on a 12-hour light/dark cycle, and provided food and water ad libidum except for fasting the evening before surgery. Treatment and housing of the rabbits was conducted in compliance with AALAC guidelines and followed approval of the Wayne State University Animal Care Committee. Rabbits were randomized into six groups: [1] catheterization of one fallopian tube with a VS catheter (Conceptus, San Carlos, CA), [2] catheterization as in group 1, followed by

Fertility and Sterility姞 Vol. 84, No. 1, July 2005 Copyright ©2005 American Society for Reproductive Medicine, Published by Elsevier Inc.

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removal of the falloposcopy wire and placement of a falloposcope (Conceptus), [3] catheterization as in group 1 but using a cage catheter (Conceptus) instead of the straight catheter, [4] catheterization as in group 3, followed by removal of the guide wire and placement of a falloposcope, and [5] rabbits with tubal perforation, and [6] control animals (no surgery done). Randomized assignment to group 6 was performed just before anesthesia for catheterization; group 6 animals thus underwent no surgery. The external diameter of the VS and cage catheters was 1.02 mm. The surgeons remained blinded to catheter group assignment (VS catheter in groups 1 and 2 vs. cage catheter in groups 3 and 4) until just before initiation of tubal catheterization and remained blinded to use of the falloposcope (group 1 vs. group 2 and group 3 vs. group 4) until after completion of catheterization of the tube. If any tube perforated in any group, the animal was removed from the group to which it was originally randomized and placed in a separate (fifth) group for tubal perforations. The protocol called for an additional group of rabbits with intentional perforation of the tube in 14 animals, if this number of unintentional perforations did not occur. Additionally, each rabbit undergoing catheterization was randomized to have one tube catheterized and the contralateral tube to serve as an uncatheterized internal control. This allowed creation of an extended control group, which includes the rabbits randomized to the control group plus the noncatheterized contralateral tubes in groups 1 through 5. Surgery was conducted under sterile conditions after shaving the abdominal wall and cleansing with betadine. Rabbits were preanesthetized with ketamine and rompum, and then placed on a respirator with surgery performed under isoflurane anesthesia. A midline laparotomy was performed approximately 3– 4 inches long and the uterine horns exposed. Each horn was punctured approximately 1 cm from the uterine bifurcation. The appropriate catheter with the guide wire advanced 2 cm was then threaded through the horn to the tubal cornua. The catheter was then advanced through the fallopian tube as far as possible. In groups 2 and 4, the falloposcopy guide wire was removed and the falloposcope placed. Following completion of the catheterization procedure, the catheters were removed. The abdomen was then closed with 3-0 Vicryl suture, and the skin with staples. Skin staples were removed 2 weeks after surgery. Within each group of animals, the rabbits were also randomized to be killed 2 weeks postoperatively, 4 weeks postoperatively, or after mating. The latter group was included so as to allow determination of a nidation index in each horn. The surgeon was blinded to these group assignments throughout the surgical procedure. Autopsy was performed by an individual unaware of group assignment or which tube was catheterized, except that the gestational sacs could identify pregnant animals. At the time of autopsy, all adhesions and other pathology were identified. Catheterization holes were not identified in any animal. The horn, tube, and ovary on each side were excised en bloc, and placed in 10% paraformaldehyde. Fertility and Sterility姞

Histologic analysis, as well as counting of corpora lutea and gestational sacs, was performed by an individual blinded to assignment of group, presence or absence of perforation, whether the tube was catheterized or noncatheterized, and the time interval between surgery and necropsy. The fallopian tubes were processed and microscopically evaluated for inflammatory changes in a manner similar to that described previously (4). Briefly, each fallopian tube was submitted in its entirety, sectioned longitudinally, and stained with hematoxylin and eosin. The tubes were then examined microscopically for the presence of inflammation, fibrosis, ciliary loss, edema, and abnormal secretory activity. The latter was identified when the scattered secretory cells that are usually inconspicuously dispersed throughout the tubal ciliated columnar epithelial cells have become irritated and developed large unilocular secretory vacuoles that give them the appearance of goblet cells. Inflammation was scored on a scale of 0 (absent) to 3⫹ (severe). Fibrosis, ciliary loss, edema, and abnormal secretory findings were evaluated as either present or absent. Breeding was performed 4 weeks after surgery. Rabbits were observed to mate and pregnancy was confirmed by abdominal palpation approximately 10 days later. Any rabbits that did not mate were placed with another buck until mating occurred. Any rabbit that was not noted to be pregnant by palpation was remated. Rabbits that failed to conceive after two matings (n ⫽ 1) were excluded from the nidation index analysis but were included in the histologic analysis. Data analysis was conducted by QST Consultants (Allendale, MI). Statistical analysis was performed by ␹2 analysis and Mann-Whitney U test as appropriate. Significance was defined as P⬍.05. RESULTS Surgery was conducted in a total of 92 animals to obtain the 87 rabbits included in the study. The 5 animals excluded had injuries to bowel or mesentery vessels during entry into the abdominal cavity, which required their exclusion, which was done before randomization to a group. At the time of autopsy, tubal serosal adhesions were identified in only 7 rabbits, 6 of which had been catheterized, 3 of which were in rabbits intentionally perforated. Of the remainder, 2 were in tubes unintentionally perforated with the VS catheter, 1 was unintentionally perforated with the cage catheter, and 1 was in a noncatheterized tube. In total there were 4 rabbits with unintentional perforations; thus group 5 was composed of 15 animals total, 11 of which had intentional perforations. Only 1 animal failed to conceive after two matings. Histologic analysis demonstrated that the control tube in this animal had mild inflammation. Identification of abnormal findings at 2, 4, and 7 weeks after surgery is shown in Table 1. There was a total of eight, seven, and nine abnormalities at 2, 4, and 7 weeks, respectively. There were no abnormal findings in the control group. There was no significant difference in abnormalities following use of the VS catheter as opposed to the cage catheter; exchanging the fallo213

TABLE 1 Gross anatomic abnormal findings at varying intervals between surgery and autopsy. Time between surgery and autopsy Catheter Falloposcope Perforation n 2 wk 4 wk 7 wk Total

Treatment groups 1

2

3

4

5

6

Extended controla

Total

VS ⫺ ⫺ 14 5 3 1 9

VS ⫹ ⫺ 15 1 0 1 2

Cage ⫺ ⫺ 15 0 3 0 3

Cage ⫹ ⫺ 15 0 0 0 0

Either ⫺ ⫹ 14 N/A N/A 5 5

Neither ⫺ ⫺ 15 0 0 0 0

Neither ⫺ ⫺ 103 2 1 2 5

8 7 9 24

Note: N/A ⫽ not applicable. a Group 6 tubes plus control tubes from groups 1–5. Diamond. Histology of tubal cannulation. Fertil Steril 2005.

poscope for the guide wire did not increase abnormalities. Interestingly, among the nonperforated tubes, following breeding the control and catheterized tubes each had two abnormalities. All of the abnormalities in the perforated group occurred in tubes intentionally perforated. Histologic findings are summarized in Table 2. Inflammation was noted in four tubes: in one rabbit in group 1 sacrificed at 2 weeks, one rabbit in group 3 sacrificed at 3 weeks, one control tube from one rabbit in group 3 that failed to conceive, and one rabbit in the perforated group that conceived. In the latter rabbit the nidation index on the intentionally perforated side was 20%, while it was 40% on the contralateral side. Rabbits identified to have fibrosis were killed at 2 weeks (group 1) and 4 weeks (group 3); ciliary loss was identified in one control tube in a rabbit killed 2 weeks after surgery, and edema in one tube in a rabbit killed 2 weeks after surgery. Abnormal secretory findings were identified in 10 tubes in eight rabbits; in group 1, one rabbit was killed at 2 weeks, two at 4 weeks, and one after breeding. This latter rabbit had a 100% nidation index on the catheterized side as compared with 40% on the control side. In group 2, one rabbit was killed at 2 weeks and one after breeding; the nidation index was 100% on each side. In group 5, the perforated tube had no pregnancies while the contralateral nidation index was 33%. Two of the control tubes were the contralateral tubes from rabbits in groups 1 and 2 killed at 4 and 2 weeks, respectively, and the third was from a rabbit in group 2 with nidation indexes of 100% on each side. None of the histologic findings were statistically significantly different. Tubal function was assessed by the number of corpora lutea and fetuses and by the calculated nidation indexes, as shown in Table 3. In each group, there was no significant difference in nidation index between the catheterized and noncatheterized tubes; additionally, there was no difference in the nidation index of all catheterized tubes and the control group. Combining all 214

Diamond et al.

Histology of tubal cannulation

the uncatheterized tubes, the mean nidation index was 87.4% and in unperforated catheterized tubes 89.1% (not significant). In the perforated tubes, those unintentionally perforated (n ⫽ 4) had a nidation index (81.2%), which was no different from the control tubes, whereas intentionally perforated tubes (n ⫽ 9) had a nidation index of 55.4%. DISCUSSION Examination of the fimbria and serosal surfaces of the fallopian tube at laparotomy or laparoscopy provides a basis for prediction of eventual pregnancy outcome. Intraluminal tubal examination provides additional information, not identifiable by external examination alone, that can improve the ability to predict the initiation of pregnancy and its eventual outcome (5–7). Furthermore, identification of intraluminal pathology may identify candidates for surgical treatment and/or allow identification of women who are at low probability for establishment of a viable pregnancy (8 –11), thereby allowing them to pursue other options including assisted reproductive technologies or adoption. The potential value of viewing the tubal lumen can be enhanced if it can be achieved without the morbidity or expense of procedures that traverse the abdominal wall. As demonstrated by Kerin et al. (3, 8) and others (2, 5–7, 12, 13), it is now feasible to conduct examinations of the fallopian tube following cornual catheterization. Such procedures can be conducted by direct visualization hysteroscopically or under fluoroscopic or ultrasonographic guidance. In any case, the intramural and isthmic portions can often be catheterized and viewed. However, retrograde extension into the ampullary segment is most often prohibited unless performed concurrently with transabdominal tubal manipulation to allow straightening of the tube, thereby minimizing the likelihood of tubal perforation. Vol. 84, No. 1, July 2005

TABLE 2 Histologic findings following tubal catheterization with regard to (a) inflammation, (b) fibrosis, (c) ciliary loss, (d) edema, and (e) abnormal secretory findings. (a) Inflammation Treatment groups

Total

Histologic findings

1

2

3

4

5

Extended controla

No.

%

Absent Mild Moderate Total

13 1 0 14

15 0 0 15

14 0 1 15

15 0 0 15

13 1 0 14

102 1 0 103

172 3 1 176

97.7 1.7 0.6 100

(b) Fibrosis Treatment groups

Total a

Histologic findings

1

2

3

4

5

Extended control

No.

%

Absent Present Total

13 1 14

15 0 15

14 1 15

15 0 15

14 0 14

103 0 103

174 2 176

98.8 1.2 100

(c) Ciliary loss Treatment groups

Total

Histologic findings

1

2

3

4

5

Extended controla

No.

%

Absent Present Total

14 0 14

15 0 15

15 0 15

15 0 15

14 0 14

102 1 103

175 1 176

99.4 0.6 100

(d) Edema Treatment groups

Total

Histologic findings

1

2

3

4

5

Extended controla

No.

%

Absent Present Total

13 1 14

15 0 15

15 0 15

15 0 15

14 0 14

103 0 103

175 1 176

99.4 0.6 100

(e) Abnormal secretory findings Treatment groups

Total

Histologic findings

1

2

3

4

5

Extended controla

No.

%

Absent Present Total

10 4 14

13 2 15

15 0 15

15 0 15

13 1 14

103 0 103

166 10 176

99.3 0.7 100

a

Extended control group includes rabbits assigned to the control group plus fallopian tubes from the other groups contralateral to the catheterized tube.

Diamond. Histology of tubal cannulation. Fertil Steril 2005.

In the individual with proximal tubal occlusion, tubal catheterization provides the potential for reestablishment of tubal patency and function, without the need for resection and anastomosis. However, while usually successful in esFertility and Sterility姞

tablishing tubal patency, it remains unclear whether normal tubal function is established, because pregnancy rates in these subjects tend to be lower than in reports of women undergoing tubal anastomosis (14). Furthermore, for women 215

TABLE 3 Fertility parameters following tubal catheterization: corpora lutea, fetuses, and nidation indexes. Treatment group 1 2 3 4 5 6

Catheterized tube

Corpora lutea

Fetuses

Nidation indexes (ⴛ100)

Yes No Yes No Yes No Yes No Yes No No

4.86 5.14 5.25 3.87 5.07 4.47 4.29 3.71 3.71 3.93 4.03

4.57 4.43 5.00 3.50 4.80 3.93 4.29 4.43 2.93 3.57 3.55

95.2 87.6 91.3 90.6 100 90.5 72.0 78.1 72.0 90.5 86.5

Diamond. Histology of tubal cannulation. Fertil Steril 2005.

found to have normal tubes, there exists the potential that tubal catheterization could injure the tubal mucosa, leading to inflammation, fibrosis, and/or a reduction in tubal function, thereby iatrogenically causing damage. To examine this issue, we conducted a controlled randomized study evaluating the effect of fallopian tube catheterization with two types of catheters on tubal histology and function in rabbits. The results identify that tubal catheterization with either a VS or a cage catheter had no detrimental effects on intraluminal tubal histology at 2, 4, or 7 weeks postcatheterization. These results are entirely consistent with the report of Kitamura et al. (15), in which 20 women underwent unilateral catheterization immediately before hysterectomy. The catheterized and contralateral uncatheterized control tubes were examined by light microscopy and scanning and transmission election microscopy. No significant differences in tubal histology were noted using any of these methods (15). Importantly, tubal function, as assessed by the nidation index, was not impaired by tubal catheterization. Furthermore, although uncommon, unintended tubal perforation was without demonstrable detrimental effects. In summary, tubal catheterization with a VS or cage catheter had no detrimental effects as assessed by tubal histology or function. Antegrade tubal catheterization has the opportunity to provide in-office access to the fallopian tube (without the necessity of traversing the abdominal wall) to provide women with information that could be important in determining recommendations for their prognosis and care.

1. DeCherney AH. Anything you can do I can do better ѧ or differently! Fertil Steril 1987;48:374 – 6. 2. Rimbach S, Bastert G, Wallwiener D. Technical results of falloposcopy

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