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Histology of proximal tubal occlusion*†
Vol.
FERTILITY AND STERILITY Copyright © 1987 The American Fertility Society
48, No.3, September 1987 Printed in U.S.A.
Histology of proximal tubal occlusion*t
Patricia J. Sulak, M.D.:j:§ Gerard S. Letterie, M.D.:j:11 Charles C. Coddington, M.D.:j:~
Clifford C. Hayslip, M.D.:j:# Joan E. Woodward, M.D.** Thomas A. Klein, M.D.+tt
Walter Reed Army Medical Center, Washington, D.C.
From 1979 to 1985, 18 patients who were found to have proximal tubal obstruction by hysterosalpingography and laparoscopic chromopertubation underwent resection of the obstructed tubal segment and reimplantation or microanastomosis. Resected tubal segments were studied histologically, and in 11 of the 18 cases no tubal occlusion could be demonstrated. A variety of histologic abnormalities were noted, however, including six cases in which the tubal lumen contained an amorphous material of unknown etiology, often appearing to form a cast of the tube. Such "plugs," which the authors believe to be previously unreported, have no clearly established clinical significance at present. However, if they cause tubal occlusion, this would explain several previously published findings, and would also have implications for therapy. Fertil Steril 48:437, 1987
Tubal dysfunction is etiologic in 30% to 40% of infertility patients. 1,2 Proximal (uterotubal junction) obstruction comprises 10% to 25% of these abnormalities and often is an isolated finding with otherwise normal pelvic anatomy.2-6 The etiology
Received September 19, 1986; revised and accepted May 21, 1987. * Presented in part at the twenty-fourth annual meeting of the Armed Forces District, American College of Obstetricians and Gynecologists, New Orleans, Louisiana, October 6-10, 1985. . t The opinions and assertions expressed herein are those of the authors and are not to be construed as official or as the views of the Department of the Army, the Department of the Navy, or the Department of Defense. :j: Department of Obstetrics and Gynecology. § Present address: Obstetrics and Gynecology Service, Darnall Army Community Hospital, Fort Hood, Texas. II Present address: Department of Obstetrics and Gynecology, Tripier Army Medical Center, Honolulu, Hawaii. If Present address: Department of Obstetrics and Gynecology, Portsmouth Naval Hospital, Portsmouth, Virginia. N Present address: Department of Obstetrics and Gynecology, F. Edward Herbert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland. ** Department of Pathology. tt Reprint requests: Thomas A. Klein, M.D., Department of Obstetrics and Gynecology, Walter Reed Army Medical Center, Washington, D.C. 20307-5001. Vol. 48, No.3, September 1987
of proximal tubal obstruction (PTO) is not always clear. Infection and subsequent inflammation, fibrosis, salpingitis isthmica nodosum, endometriosis, and congenital abnormalities have been cited as causes. 3,4,6-11 However, several authors3 ,4,8,1l have commented on the lack of histologic confirmation in PTO in some patients, despite apparent functional block. This state of affairs is frustrating because the usual therapy for PTO consists of resection of the occluded segment, followed by reanastomosis or reimplantation of the remaining tube. The disappointing success rate 2,4-6,8 of such procedures is often difficult for the patient and her surgeon to accept, especially when the obstruction itself cannot be histologically explained or even documented. The present study is a histologic review of our recent experience with apparent PTO. It reports histologic findings that we believe may justify forms of treatment other than segmental resection and reanastomosis. MATERIALS AND METHODS
The infertility records at Walter Reed Army Medical Center from 1979 to 1985 were reviewed and 18 patients were found to have had bilateral Sulak et al. Histology of proximal tubal occlusion
437
tubal segmental resection and reimplantation or reanastomosis. All of these patients had PTO as diagnosed by both hysterosalpingography (HSG) and laparoscopic chromopertubation. HSG was performed in the proliferative phase of the menstrual cycle using water-soluble contrast media and image intensification. Laparoscopy was performed under general anesthesia with transcervical injection of dye via a coned cannula. Intravenous glucagon (1 mg) was administered in an effort to counteract possible tubal spasm. Patients with apparent distal patency (normal external appearance) of at least one tube were counseled and scheduled for laparotomy. At laparotomy, all patients again underwent transcervical injection of dye via an intrauterine balloon catheter, under general anesthesia. Some patients also had transfundal injection of dye and/ or retrograde tubal lavage via the fimbriated end in efforts to confirm PTO. Patients with persistent PTO, despite all of the maneuvers previously described, underwent sequential excision of the proximal fallopian tube until patency was established. These patients then underwent implantation or micro anastomosis of the remaining tube into the uterus. The resected tubal segments were studied histologically with multiple sections taken to determine the etiology of the obstruction. The tissue sections were stained with hematoxylin and eosin (H & E), as well as Masson stain, and periodic acid-Schiff (PAS) stain with and without diastase digestion. In cases where patent or normal tubes were found, further sections were taken to rule out subtle abnormalities that might have been overlooked previously. All slides were reviewed by the same pathologist.
tures. In 3 patients, the tubes were completely normal without occlusion. Eight patients had patent tubes with some identifiable histologic abnormality, such as fibrosis or inflammation. In only 7 of the 18 patients was tubal occlusion, either fibrous obliteration or salpingitis isthmica nodosum, documented histologically. In 6 of the 18 patients, an amorphous material was observed in the tubal lumen, appearing to form a cast frequently including inflammatory cells (Figs. 1 to 4). This material had H & E staining characteristics diagnostic of calcification in 2 cases. It stained faintly blue with Masson stain, suggestive of early fibrosis, and was diastase-resistant PAS-positive (mucin-positive). All 6 of these patients had histologic evidence of tubal fibrosis or inflammation, with occlusion in 3 and apparent patency in the other 3. All 6 patients had abnormal gross pelvic findings, 3 showing unilateral chronic salpingitis and the other 3 with pelvic adhesions but externally normal tubes. DISCUSSION
Our review of 18 patients with PTO has confirmed many findings of other investigators. The results reported are similar to those of Green-Armytage 6 and those of Fortier and HaneylO in that a large percentage of patients had grossly normal pelvic organs and frequently presented with secondary infertility. Histologic studies of our excised
RESULTS
The age range of the 18 patients was 22 to 34 years, with a mean of 27.4 years. Fourteen patients had secondary infertility and 4 had primary infertility. The average duration of infertility was 4.2 years (range, 2 to 11 years). Seven patients had a history of prior pelvic infection. Two had used an intrauterine device in the past. Six of the 18 patients were noted to have completely normal gross pelvic anatomy. Pelvic adhesions were noted in 9 patients, but the tubes were otherwise normal. In 3 patients, there was evidence of chronic salpingitis affecting the distal portion of one tube. The 18 patients who underwent proximal tubal resection demonstrated a variety of histologic fea438
Sulak et al.
Histology of proximal tubal occlusion
Figure 1 Amorphous material forming a cast of the tubal lumen (XSO). Fertility and Sterility
Figure 2 Amorphous material forming a cast of the tubal lumen (X80).
tubal segments were similar to the findings of others in that we were frequently unable to document tubal occlusion and, in some patients, found completely normal tubes. In 1971, Grant wrote, "We have been considerably frustrated by the reports received from the pathologist. . . as he failed to find a block in many segments examined."4 We believe this to be the first report of an amorphous material in the tubal lumen, possibly form-
Figure 3 Calcified material (arrow) in the tubal lumen with cellular deb)."is (X175). Vol. 48, No.3, September 1987
Figure 4
Organizing exudate in the tubal lumen (XSO).
ing a cast. The etiology ofthis material is unknown, but the staining characteristics are consistent with the conjecture that it might represent partially organized inflammatory exudate, partially calcified in some cases. The fact that the six patients in whom this material was found all had gross and histologic evidence of prior pelvic inflammation supports this conjecture. Green-Armytage 6 frequently found a history of a prior induced abortion or infected pregnancy in her patients with PTO. Both the incidence and clinical significance of tubal casts are also speculative. The amorphous material we have described may be artifactual or a common feature of the tubal lumen, not causing obstruction or perhaps doing so only in tubes already narrowed by disease. It is true that our histologic evidence (Figs. 1 to 4) does not show the "casts" actually adhering to the tubal lumen. However, we have not observed such material in a large number of grossly normal tubes excised at hysterectomy from women without histories of pelvic inflammation or infertility. Furthermore, the shape of the "casts" conforms to that of the tubal lumen (Figs. 1 to 4), and we therefore believe the apparent lack of adherence is a result of tissue processing. In addition, the results of many previous studies are consistent with the hypothesis that infertility may be caused by tubal "plugs." The pregnancy rate after HSG has been reported as 13% to 55%.12-14 Suggested mechanisms have included separation of mild agglutinations of the tubal folds, dislodging Sulak et al.
Histology of proximal tubal occlusion
439
mucus, and opening fimbrial adhesions. 15 The therapeutic value of multiple uterotubal insufHations has been described in several earlier studies with success rates of20% to 60%.2,16-18 It seems plausible to us that these findings may be explained by the dislodging of tubal "plugs." The histologic findings reported here, and their implications, have led us to attempt more direct methods of relieving apparent PTO by applying increased pressure to the tubal ostia. Our experience with two patients in whom tubal patency was restored by hysteroscopic cannulation of the ostia is reported in a separate article. 19
8.
9. 10. 11.
12.
13. REFERENCES 1. Speroff L, Glass RH, Kase NG: Clinical Gynecologic Endo· crinology & Infertility, 3rd edition. Baltimore, Williams & Wilkins, 1983, p 469
2. Arronet GH, Eduljee SY, O'Brien JR: A nine-year survey of fallopian tube dysfunction in human infertility: diagnosis and therapy. Fertil Steril 20:903, 1969 3. Siegler AM, Hellman LM: Tuboplastic surgery: a retrospective study of 50 cases. Am J Obstet Gynecol 86:448, 1963 4. Grant A: Infertility surgery of the oviduct. Fertil Steril 22:496, 1971 5. Umezake C, Katayama KP, Jones HW Jr: Pregnancy rates after reconstructive surgery of the fallopian tubes. Obstet GynecoI43:418, 1974 6. Green-Armytage VB: Tubo-uterine implantation. Br Med J 1:1222, 1952 7. Musich JR, Behrman SJ: Surgical management of tubal
440
Sulak et al.
Histology of proximal tubal occlusion
14.
15. 16.
17. 18.
19.
obstruction at the uterotubal junction. Fertil Steril 40:423, 1983 Rock JA, Katayama KP, Martin EJ, Rock BM, Woodruff JD, Jones HW Jr: Pregnancy outcome following uterotubal implantation: a comparison of the reamer and sharp cornual wedge excision techniques. Fertil Steril 31:634, 1979 Levinson CJ: Implantation procedures for intramural obstruction. J Reprod Med 26:347, 1981 Fortier KJ, Haney AF: The pathologic spectrum ofuterotubal junction obstruction. Obstet Gynecol 65:93, 1985 Siegler AM: Evaluation of tubal factors in infertility and management of tubal obstruction. Clin Obstet Gynecol 22:81,1978 DeCherney AH, Kort H, Barney JB, DeVore GR: Increased pregnancy rate with oil-soluble hysterosalpingography dye. Fertil Steril 33:407, 1980 Maathuis JB, Horbach JGM, Van Hall EV: A comparison of the results of hysterosalpingography and laparoscopy in the diagnosis of fallopian tube dysfunction. Fertil Steril 23:428, 1972 Horbach JGM, Maathuis JB, Van Hall EV: Factors influencing the pregnancy rate following hysterosalpingography and their prognostic significance. Fertil Steril 24:15, 1973 Pauerstein CJ: The Fallopian Tube: A Reappraisal. Philadelphia, Lea & Febiger, 1974, p 110 Vessell M: Multiple uterotubal insuffiations in cases of sterility due to tubal occlusion. Am J Obstet Gynecol 68:810, 1954 Rutherford RN: The therapeutic value of repetitive tubal insuffiations. West J Surg 54:145, 1948 Rubin IC: Uterotubal insuffiations: value in the treatment of tubal obstruction to ovular migration. Fertil Steril 5:311, 1954 Sulak PJ, Letterie G, Hayslip CC, Coddington CC, Klein T A: Hysteroscopic cannulation and lavage in the treatment of proximal tubal occlusion. Fertil Steril In press, 1987
Fertility and Sterility
FERTILITY AND STERILITY Copyright © 1987 The American Fertility Society
48, No.3, September 1987 Printed in U.S.A.
Histology of proximal tubal occlusion*t
Patricia J. Sulak, M.D.:j:§ Gerard S. Letterie, M.D.:j:11 Charles C. Coddington, M.D.:j:~
Clifford C. Hayslip, M.D.:j:# Joan E. Woodward, M.D.** Thomas A. Klein, M.D.+tt
Walter Reed Army Medical Center, Washington, D.C.
From 1979 to 1985, 18 patients who were found to have proximal tubal obstruction by hysterosalpingography and laparoscopic chromopertubation underwent resection of the obstructed tubal segment and reimplantation or microanastomosis. Resected tubal segments were studied histologically, and in 11 of the 18 cases no tubal occlusion could be demonstrated. A variety of histologic abnormalities were noted, however, including six cases in which the tubal lumen contained an amorphous material of unknown etiology, often appearing to form a cast of the tube. Such "plugs," which the authors believe to be previously unreported, have no clearly established clinical significance at present. However, if they cause tubal occlusion, this would explain several previously published findings, and would also have implications for therapy. Fertil Steril 48:437, 1987
Tubal dysfunction is etiologic in 30% to 40% of infertility patients. 1,2 Proximal (uterotubal junction) obstruction comprises 10% to 25% of these abnormalities and often is an isolated finding with otherwise normal pelvic anatomy.2-6 The etiology
Received September 19, 1986; revised and accepted May 21, 1987. * Presented in part at the twenty-fourth annual meeting of the Armed Forces District, American College of Obstetricians and Gynecologists, New Orleans, Louisiana, October 6-10, 1985. . t The opinions and assertions expressed herein are those of the authors and are not to be construed as official or as the views of the Department of the Army, the Department of the Navy, or the Department of Defense. :j: Department of Obstetrics and Gynecology. § Present address: Obstetrics and Gynecology Service, Darnall Army Community Hospital, Fort Hood, Texas. II Present address: Department of Obstetrics and Gynecology, Tripier Army Medical Center, Honolulu, Hawaii. If Present address: Department of Obstetrics and Gynecology, Portsmouth Naval Hospital, Portsmouth, Virginia. N Present address: Department of Obstetrics and Gynecology, F. Edward Herbert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland. ** Department of Pathology. tt Reprint requests: Thomas A. Klein, M.D., Department of Obstetrics and Gynecology, Walter Reed Army Medical Center, Washington, D.C. 20307-5001. Vol. 48, No.3, September 1987
of proximal tubal obstruction (PTO) is not always clear. Infection and subsequent inflammation, fibrosis, salpingitis isthmica nodosum, endometriosis, and congenital abnormalities have been cited as causes. 3,4,6-11 However, several authors3 ,4,8,1l have commented on the lack of histologic confirmation in PTO in some patients, despite apparent functional block. This state of affairs is frustrating because the usual therapy for PTO consists of resection of the occluded segment, followed by reanastomosis or reimplantation of the remaining tube. The disappointing success rate 2,4-6,8 of such procedures is often difficult for the patient and her surgeon to accept, especially when the obstruction itself cannot be histologically explained or even documented. The present study is a histologic review of our recent experience with apparent PTO. It reports histologic findings that we believe may justify forms of treatment other than segmental resection and reanastomosis. MATERIALS AND METHODS
The infertility records at Walter Reed Army Medical Center from 1979 to 1985 were reviewed and 18 patients were found to have had bilateral Sulak et al. Histology of proximal tubal occlusion
437
tubal segmental resection and reimplantation or reanastomosis. All of these patients had PTO as diagnosed by both hysterosalpingography (HSG) and laparoscopic chromopertubation. HSG was performed in the proliferative phase of the menstrual cycle using water-soluble contrast media and image intensification. Laparoscopy was performed under general anesthesia with transcervical injection of dye via a coned cannula. Intravenous glucagon (1 mg) was administered in an effort to counteract possible tubal spasm. Patients with apparent distal patency (normal external appearance) of at least one tube were counseled and scheduled for laparotomy. At laparotomy, all patients again underwent transcervical injection of dye via an intrauterine balloon catheter, under general anesthesia. Some patients also had transfundal injection of dye and/ or retrograde tubal lavage via the fimbriated end in efforts to confirm PTO. Patients with persistent PTO, despite all of the maneuvers previously described, underwent sequential excision of the proximal fallopian tube until patency was established. These patients then underwent implantation or micro anastomosis of the remaining tube into the uterus. The resected tubal segments were studied histologically with multiple sections taken to determine the etiology of the obstruction. The tissue sections were stained with hematoxylin and eosin (H & E), as well as Masson stain, and periodic acid-Schiff (PAS) stain with and without diastase digestion. In cases where patent or normal tubes were found, further sections were taken to rule out subtle abnormalities that might have been overlooked previously. All slides were reviewed by the same pathologist.
tures. In 3 patients, the tubes were completely normal without occlusion. Eight patients had patent tubes with some identifiable histologic abnormality, such as fibrosis or inflammation. In only 7 of the 18 patients was tubal occlusion, either fibrous obliteration or salpingitis isthmica nodosum, documented histologically. In 6 of the 18 patients, an amorphous material was observed in the tubal lumen, appearing to form a cast frequently including inflammatory cells (Figs. 1 to 4). This material had H & E staining characteristics diagnostic of calcification in 2 cases. It stained faintly blue with Masson stain, suggestive of early fibrosis, and was diastase-resistant PAS-positive (mucin-positive). All 6 of these patients had histologic evidence of tubal fibrosis or inflammation, with occlusion in 3 and apparent patency in the other 3. All 6 patients had abnormal gross pelvic findings, 3 showing unilateral chronic salpingitis and the other 3 with pelvic adhesions but externally normal tubes. DISCUSSION
Our review of 18 patients with PTO has confirmed many findings of other investigators. The results reported are similar to those of Green-Armytage 6 and those of Fortier and HaneylO in that a large percentage of patients had grossly normal pelvic organs and frequently presented with secondary infertility. Histologic studies of our excised
RESULTS
The age range of the 18 patients was 22 to 34 years, with a mean of 27.4 years. Fourteen patients had secondary infertility and 4 had primary infertility. The average duration of infertility was 4.2 years (range, 2 to 11 years). Seven patients had a history of prior pelvic infection. Two had used an intrauterine device in the past. Six of the 18 patients were noted to have completely normal gross pelvic anatomy. Pelvic adhesions were noted in 9 patients, but the tubes were otherwise normal. In 3 patients, there was evidence of chronic salpingitis affecting the distal portion of one tube. The 18 patients who underwent proximal tubal resection demonstrated a variety of histologic fea438
Sulak et al.
Histology of proximal tubal occlusion
Figure 1 Amorphous material forming a cast of the tubal lumen (XSO). Fertility and Sterility
Figure 2 Amorphous material forming a cast of the tubal lumen (X80).
tubal segments were similar to the findings of others in that we were frequently unable to document tubal occlusion and, in some patients, found completely normal tubes. In 1971, Grant wrote, "We have been considerably frustrated by the reports received from the pathologist. . . as he failed to find a block in many segments examined."4 We believe this to be the first report of an amorphous material in the tubal lumen, possibly form-
Figure 3 Calcified material (arrow) in the tubal lumen with cellular deb)."is (X175). Vol. 48, No.3, September 1987
Figure 4
Organizing exudate in the tubal lumen (XSO).
ing a cast. The etiology ofthis material is unknown, but the staining characteristics are consistent with the conjecture that it might represent partially organized inflammatory exudate, partially calcified in some cases. The fact that the six patients in whom this material was found all had gross and histologic evidence of prior pelvic inflammation supports this conjecture. Green-Armytage 6 frequently found a history of a prior induced abortion or infected pregnancy in her patients with PTO. Both the incidence and clinical significance of tubal casts are also speculative. The amorphous material we have described may be artifactual or a common feature of the tubal lumen, not causing obstruction or perhaps doing so only in tubes already narrowed by disease. It is true that our histologic evidence (Figs. 1 to 4) does not show the "casts" actually adhering to the tubal lumen. However, we have not observed such material in a large number of grossly normal tubes excised at hysterectomy from women without histories of pelvic inflammation or infertility. Furthermore, the shape of the "casts" conforms to that of the tubal lumen (Figs. 1 to 4), and we therefore believe the apparent lack of adherence is a result of tissue processing. In addition, the results of many previous studies are consistent with the hypothesis that infertility may be caused by tubal "plugs." The pregnancy rate after HSG has been reported as 13% to 55%.12-14 Suggested mechanisms have included separation of mild agglutinations of the tubal folds, dislodging Sulak et al.
Histology of proximal tubal occlusion
439
mucus, and opening fimbrial adhesions. 15 The therapeutic value of multiple uterotubal insufHations has been described in several earlier studies with success rates of20% to 60%.2,16-18 It seems plausible to us that these findings may be explained by the dislodging of tubal "plugs." The histologic findings reported here, and their implications, have led us to attempt more direct methods of relieving apparent PTO by applying increased pressure to the tubal ostia. Our experience with two patients in whom tubal patency was restored by hysteroscopic cannulation of the ostia is reported in a separate article. 19
8.
9. 10. 11.
12.
13. REFERENCES 1. Speroff L, Glass RH, Kase NG: Clinical Gynecologic Endo· crinology & Infertility, 3rd edition. Baltimore, Williams & Wilkins, 1983, p 469
2. Arronet GH, Eduljee SY, O'Brien JR: A nine-year survey of fallopian tube dysfunction in human infertility: diagnosis and therapy. Fertil Steril 20:903, 1969 3. Siegler AM, Hellman LM: Tuboplastic surgery: a retrospective study of 50 cases. Am J Obstet Gynecol 86:448, 1963 4. Grant A: Infertility surgery of the oviduct. Fertil Steril 22:496, 1971 5. Umezake C, Katayama KP, Jones HW Jr: Pregnancy rates after reconstructive surgery of the fallopian tubes. Obstet GynecoI43:418, 1974 6. Green-Armytage VB: Tubo-uterine implantation. Br Med J 1:1222, 1952 7. Musich JR, Behrman SJ: Surgical management of tubal
440
Sulak et al.
Histology of proximal tubal occlusion
14.
15. 16.
17. 18.
19.
obstruction at the uterotubal junction. Fertil Steril 40:423, 1983 Rock JA, Katayama KP, Martin EJ, Rock BM, Woodruff JD, Jones HW Jr: Pregnancy outcome following uterotubal implantation: a comparison of the reamer and sharp cornual wedge excision techniques. Fertil Steril 31:634, 1979 Levinson CJ: Implantation procedures for intramural obstruction. J Reprod Med 26:347, 1981 Fortier KJ, Haney AF: The pathologic spectrum ofuterotubal junction obstruction. Obstet Gynecol 65:93, 1985 Siegler AM: Evaluation of tubal factors in infertility and management of tubal obstruction. Clin Obstet Gynecol 22:81,1978 DeCherney AH, Kort H, Barney JB, DeVore GR: Increased pregnancy rate with oil-soluble hysterosalpingography dye. Fertil Steril 33:407, 1980 Maathuis JB, Horbach JGM, Van Hall EV: A comparison of the results of hysterosalpingography and laparoscopy in the diagnosis of fallopian tube dysfunction. Fertil Steril 23:428, 1972 Horbach JGM, Maathuis JB, Van Hall EV: Factors influencing the pregnancy rate following hysterosalpingography and their prognostic significance. Fertil Steril 24:15, 1973 Pauerstein CJ: The Fallopian Tube: A Reappraisal. Philadelphia, Lea & Febiger, 1974, p 110 Vessell M: Multiple uterotubal insuffiations in cases of sterility due to tubal occlusion. Am J Obstet Gynecol 68:810, 1954 Rutherford RN: The therapeutic value of repetitive tubal insuffiations. West J Surg 54:145, 1948 Rubin IC: Uterotubal insuffiations: value in the treatment of tubal obstruction to ovular migration. Fertil Steril 5:311, 1954 Sulak PJ, Letterie G, Hayslip CC, Coddington CC, Klein T A: Hysteroscopic cannulation and lavage in the treatment of proximal tubal occlusion. Fertil Steril In press, 1987
Fertility and Sterility