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Histopathology of the fallopian tube after local instillation of hyperosmolar glucose solution for unruptured tubal pregnancy
FERTILITY AND STERILITY Copyright
©
Vol. 59, No.6, ,June 1993
1993 The American Fertility Society
Printed on acid-free paper in U.S.A.
Histopathology of the fallopian tube after local instillation of hyperosmolar glucose solution for unruptured tubal pregnancy
Werner Honigl, M.D.* Hellmuth Pickel, M.D. Karl Tamussino, M.D. Peter F. Lang, M.D. Department of Obstetrics and Gynecology, University of Graz, Graz, Austria
Although the clinical safety and effectiveness of local hyperosmolar glucose for treatment of selected tubal pregnancies has been reported (1, 2), there have been no histopathologic studies of tubes after glucose treatment to address whether the tubal mucosa might be damaged by the hyperosmolar solution. We report the histopathology of an oviduct showing an intact endosalpinx and a resolving ectopic pregnancy (EP) after instillation of hyperosmolar glucose solution 12 days earlier. CASE REPORT
A 28-year-old gravida-2 para-1 was admitted to the hospital on cycle day 55 with a serum hCG level of 1.122 miU/mL (conversion factor to SI unit, 1.00) for treatment of an ectopic gestation. Laparoscopy showed a right-sided unruptured ampullary tubal pregnancy measuring 6.0 X 2.5 em without active bleeding. The left adnexae were normal. After 180 mL of blood and clots were removed from the pelvis, 20 mL of 50% glucose solution were injected into the tubal gestation as described elsewhere (1). The serum hCG level was 200 miU /mL on day 4, 133 miU/mL on day 6, and 68 miU/mL on day 11 after laparoscopy. On postoperative day 12, when the serum hCG had declined to 37 miU /mL, the patient reported cramping pelvic pain and increased vaginal Received October 13, 1992; revised and accepted February 11, 1993. * Reprint requests: Werner Honig!, M.D., Department of Obstetrics and Gynecology, University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria.
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bleeding. The blood pressure, pulse rate, and red blood cell count were normal. Pelvic examination showed right-sided adnexal tenderness, and transvaginal sonography showed intra-abdominal fluid and echo-dense structures suggestive of blood clots. Relaparoscopy showed that the distension of the right tube had decreased markedly since the first procedure. Sixty milliliters of blood and clots were suctioned out of the pelvis. The right tube showed slight bluish discoloration and swelling but no active bleeding, adnexal adhesions, or signs of tubal rupture. The diagnosis of incomplete tubal abortion was made, and the tube was removed in toto at the patient's request. After fixation, serial sections of the oviduct were stained with hematoxylin and eosin (H and E) and studied with light microscopy. The postoperative course was uneventful. The trophoblast had spread mostly in the lumen of the fallopian tube. Most placental villi showed hyalinization or were necrotic (Fig. 1). Embryonic parts were not seen. The tubal folds showed signs of acute and chronic inflammation and were pressed to the tubal wall by an intraluminal hematoma containing necrotic trophoblastic tissue. Apart from the site of implantation, the epithelial surfaces of the tubal folds were intact. The tubal wall contained perivascular inflammatory infiltrates and some hemorrhagic foci within the muscularis but only isolated residual nonvillous cytotrophoblast cells invading blood vessels. The tubal arteries near the implantation site showed accumulation of foam cells under the proliferated intima. There were no signs of inflammation on the serosal surface. The blood
Fertility and Sterility
Figure 1 Vanishing trophoblastic villus with signs of necrobiosis in the vicinity of a vital tubal fold containing inflammatory cells and showing an intact epithelial lining (H and E, X250).
clots removed from the pouch of Douglas contained hyalinized chorionic villi. DISCUSSION
The effects of hyperosmolar glucose on the tubal wall have not been studied and there has been concern that the substance damages the tubal mucosa. The histopathologic findings in the patient reported here, who had a resolving EP and incomplete tubal abortion after intraluminal glucose instillation, showed an intact epithelial surface. Tubal gestations can show a variety of histologic features (3). Appropriate controls to study the effect of local medical treatment are difficult to obtain (3). Three weeks after methotrexate (MTX) injection, the histopathology of an oviduct was reported completely normal apart from a light local inflammatory reaction with granulocytes and some edema (3). However, sonographic evidence of prolonged tubal distension after heG levels had declined to undetectable levels after MTX injection has been reported (4). The histopathologic findings of acute and chronic inflammation of tubal folds and the endarteritic changes of tubal arteries reported here have been described in tubal gestations before the era of local medical treatment (5); it is not known whether endarteritis because of thrombosis, organization, and recanalization is more frequent after local instillation of hyperosmolar glucose. Penetration of the underlying tissue by interstitial extravillous cytotrophoblast cells and invasion of blood vessels occurs early in tubal gestation; these
Vol. 59, No.6, June 1993
cytotrophoblast cells are nonreactive with antibodies directed against heG. Isolated foci of trophoblast cells within the tubal wall probably remain after most conservative procedures (6), but these remaining cells are supposed to degenerate after the major trophoblastic mass has been removed surgically (6) or devitalized medically. Though trophoblastic foci may survive leading to persistent EP (1, 6), the syndrome of persistence is related mostly to remaining chorionic villi; these villi contain heG within the syncytiotrophoblast layer. Three oviducts removed because of persistent EP in an earlier series (1) showed no signs of tubal damage attributable to the hyperosmolar glucose solution. However, tubal damage because of a greater biologic effect of the hyperosmolar stimulus is conceivable in tubal pregnancies in which extensive necrosis of the trophoblast has been induced. In the patient reported here, the decline of serum heG to <4% of the preoperative level within 12 days was considered adequate (1). With local medical treatment, the products of conception and tubal hematoma are left in the fallopian tube to be spontaneously absorbed or aborted. Degenerating EPs are mostly associated with an indolent clinical course, but tubal abortion of necrotic trophoblastic tissue and clots can be associated with pelvic pain. Tubal abortion may be more frequent in large tubal gestations. Intratubal bleeding leading to tubal distension and rupture have occurred even in patients with low and declining heG levels (4) or after disappearance of serum heG below detectability. However, in the presence of stable circulatory parameters symptomatic patients strictly desiring tubal conservation can be managed expectantly under strict clinical observation. SUMMARY
Because of an incomplete tubal abortion, salpingectomy was performed in a patient 12 days after glucose instillation into an ampullary tubal gestation. Serum heG levels had progressively declined from 1.122 mIU/mL at first intervention to 37 mID/ mL at the second operation. Histopathology showed marked necrosis of trophoblastic tissue but no discernible damage of the tubal epithelium and tubal wall attributable to the hyperosmolar solution applied 12 days before. This case offers histopathologic evidence that intraluminal glucose instillation for treatment of unruptured tubal pregnancies does not lead to persisting damage of the tubal mucosa.
Honig} et al.
Communications-in-brief
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Key Words: Histopathology, tubal pregnancy, medical treatment, hyperosmolar glucose. REFERENCES 1. Lang PF, Tamussino K, Honig! W, Ralph G. Treatment of unruptured tubal pregnancy by laparoscopic instillation of hyperosmolar glucose solution. Am J Obstet Gynecol 1992;166:1378-81. 2. Honig! W, Lang PF. Intrauterine pregnancy in a patient with a sole remaining tube after local treatment of tubal pregnancy with hyperosmolar glucose. Fertil Steril 1992;58:625-6.
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3. Kooi S, van Etten FHPM, Kock HCLV. Histopathology of five tubes after treatment with methotrexate for a tubal pregnancy. Fertil Steril1992;57:341-5. 4. Tulandi T, Atri M, Bret P, Falcone T, Khalife S. Transvaginal intratubal methotrexate treatment of ectopic pregnancy. Fertil Steril 1992;58:98-100. 5. Blaustein A, Shenker L. Vascular lesions of the uterine tube in ectopic pregnancy. Obstet Gynecol1967;30:551-5. 6. DiMarchi JM, Kosasa TS, Kobara TY, Hale RW. Persistent ectopic pregnancy. Obstet Gynecol 1987;70:555-8.
Note. Additional references are available upon request from the author.
Fertility and Sterility
©
Vol. 59, No.6, ,June 1993
1993 The American Fertility Society
Printed on acid-free paper in U.S.A.
Histopathology of the fallopian tube after local instillation of hyperosmolar glucose solution for unruptured tubal pregnancy
Werner Honigl, M.D.* Hellmuth Pickel, M.D. Karl Tamussino, M.D. Peter F. Lang, M.D. Department of Obstetrics and Gynecology, University of Graz, Graz, Austria
Although the clinical safety and effectiveness of local hyperosmolar glucose for treatment of selected tubal pregnancies has been reported (1, 2), there have been no histopathologic studies of tubes after glucose treatment to address whether the tubal mucosa might be damaged by the hyperosmolar solution. We report the histopathology of an oviduct showing an intact endosalpinx and a resolving ectopic pregnancy (EP) after instillation of hyperosmolar glucose solution 12 days earlier. CASE REPORT
A 28-year-old gravida-2 para-1 was admitted to the hospital on cycle day 55 with a serum hCG level of 1.122 miU/mL (conversion factor to SI unit, 1.00) for treatment of an ectopic gestation. Laparoscopy showed a right-sided unruptured ampullary tubal pregnancy measuring 6.0 X 2.5 em without active bleeding. The left adnexae were normal. After 180 mL of blood and clots were removed from the pelvis, 20 mL of 50% glucose solution were injected into the tubal gestation as described elsewhere (1). The serum hCG level was 200 miU /mL on day 4, 133 miU/mL on day 6, and 68 miU/mL on day 11 after laparoscopy. On postoperative day 12, when the serum hCG had declined to 37 miU /mL, the patient reported cramping pelvic pain and increased vaginal Received October 13, 1992; revised and accepted February 11, 1993. * Reprint requests: Werner Honig!, M.D., Department of Obstetrics and Gynecology, University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria.
1316
Honig! et al.
Communications-in-brief
bleeding. The blood pressure, pulse rate, and red blood cell count were normal. Pelvic examination showed right-sided adnexal tenderness, and transvaginal sonography showed intra-abdominal fluid and echo-dense structures suggestive of blood clots. Relaparoscopy showed that the distension of the right tube had decreased markedly since the first procedure. Sixty milliliters of blood and clots were suctioned out of the pelvis. The right tube showed slight bluish discoloration and swelling but no active bleeding, adnexal adhesions, or signs of tubal rupture. The diagnosis of incomplete tubal abortion was made, and the tube was removed in toto at the patient's request. After fixation, serial sections of the oviduct were stained with hematoxylin and eosin (H and E) and studied with light microscopy. The postoperative course was uneventful. The trophoblast had spread mostly in the lumen of the fallopian tube. Most placental villi showed hyalinization or were necrotic (Fig. 1). Embryonic parts were not seen. The tubal folds showed signs of acute and chronic inflammation and were pressed to the tubal wall by an intraluminal hematoma containing necrotic trophoblastic tissue. Apart from the site of implantation, the epithelial surfaces of the tubal folds were intact. The tubal wall contained perivascular inflammatory infiltrates and some hemorrhagic foci within the muscularis but only isolated residual nonvillous cytotrophoblast cells invading blood vessels. The tubal arteries near the implantation site showed accumulation of foam cells under the proliferated intima. There were no signs of inflammation on the serosal surface. The blood
Fertility and Sterility
Figure 1 Vanishing trophoblastic villus with signs of necrobiosis in the vicinity of a vital tubal fold containing inflammatory cells and showing an intact epithelial lining (H and E, X250).
clots removed from the pouch of Douglas contained hyalinized chorionic villi. DISCUSSION
The effects of hyperosmolar glucose on the tubal wall have not been studied and there has been concern that the substance damages the tubal mucosa. The histopathologic findings in the patient reported here, who had a resolving EP and incomplete tubal abortion after intraluminal glucose instillation, showed an intact epithelial surface. Tubal gestations can show a variety of histologic features (3). Appropriate controls to study the effect of local medical treatment are difficult to obtain (3). Three weeks after methotrexate (MTX) injection, the histopathology of an oviduct was reported completely normal apart from a light local inflammatory reaction with granulocytes and some edema (3). However, sonographic evidence of prolonged tubal distension after heG levels had declined to undetectable levels after MTX injection has been reported (4). The histopathologic findings of acute and chronic inflammation of tubal folds and the endarteritic changes of tubal arteries reported here have been described in tubal gestations before the era of local medical treatment (5); it is not known whether endarteritis because of thrombosis, organization, and recanalization is more frequent after local instillation of hyperosmolar glucose. Penetration of the underlying tissue by interstitial extravillous cytotrophoblast cells and invasion of blood vessels occurs early in tubal gestation; these
Vol. 59, No.6, June 1993
cytotrophoblast cells are nonreactive with antibodies directed against heG. Isolated foci of trophoblast cells within the tubal wall probably remain after most conservative procedures (6), but these remaining cells are supposed to degenerate after the major trophoblastic mass has been removed surgically (6) or devitalized medically. Though trophoblastic foci may survive leading to persistent EP (1, 6), the syndrome of persistence is related mostly to remaining chorionic villi; these villi contain heG within the syncytiotrophoblast layer. Three oviducts removed because of persistent EP in an earlier series (1) showed no signs of tubal damage attributable to the hyperosmolar glucose solution. However, tubal damage because of a greater biologic effect of the hyperosmolar stimulus is conceivable in tubal pregnancies in which extensive necrosis of the trophoblast has been induced. In the patient reported here, the decline of serum heG to <4% of the preoperative level within 12 days was considered adequate (1). With local medical treatment, the products of conception and tubal hematoma are left in the fallopian tube to be spontaneously absorbed or aborted. Degenerating EPs are mostly associated with an indolent clinical course, but tubal abortion of necrotic trophoblastic tissue and clots can be associated with pelvic pain. Tubal abortion may be more frequent in large tubal gestations. Intratubal bleeding leading to tubal distension and rupture have occurred even in patients with low and declining heG levels (4) or after disappearance of serum heG below detectability. However, in the presence of stable circulatory parameters symptomatic patients strictly desiring tubal conservation can be managed expectantly under strict clinical observation. SUMMARY
Because of an incomplete tubal abortion, salpingectomy was performed in a patient 12 days after glucose instillation into an ampullary tubal gestation. Serum heG levels had progressively declined from 1.122 mIU/mL at first intervention to 37 mID/ mL at the second operation. Histopathology showed marked necrosis of trophoblastic tissue but no discernible damage of the tubal epithelium and tubal wall attributable to the hyperosmolar solution applied 12 days before. This case offers histopathologic evidence that intraluminal glucose instillation for treatment of unruptured tubal pregnancies does not lead to persisting damage of the tubal mucosa.
Honig} et al.
Communications-in-brief
1317
Key Words: Histopathology, tubal pregnancy, medical treatment, hyperosmolar glucose. REFERENCES 1. Lang PF, Tamussino K, Honig! W, Ralph G. Treatment of unruptured tubal pregnancy by laparoscopic instillation of hyperosmolar glucose solution. Am J Obstet Gynecol 1992;166:1378-81. 2. Honig! W, Lang PF. Intrauterine pregnancy in a patient with a sole remaining tube after local treatment of tubal pregnancy with hyperosmolar glucose. Fertil Steril 1992;58:625-6.
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Honigl et al.
Communications-in-brief
3. Kooi S, van Etten FHPM, Kock HCLV. Histopathology of five tubes after treatment with methotrexate for a tubal pregnancy. Fertil Steril1992;57:341-5. 4. Tulandi T, Atri M, Bret P, Falcone T, Khalife S. Transvaginal intratubal methotrexate treatment of ectopic pregnancy. Fertil Steril 1992;58:98-100. 5. Blaustein A, Shenker L. Vascular lesions of the uterine tube in ectopic pregnancy. Obstet Gynecol1967;30:551-5. 6. DiMarchi JM, Kosasa TS, Kobara TY, Hale RW. Persistent ectopic pregnancy. Obstet Gynecol 1987;70:555-8.
Note. Additional references are available upon request from the author.
Fertility and Sterility