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Use of corticosteroids as an adjuvant in terminal salpingostomy
FERTIUTY AND STERILITY Copyright " 1983 The American Fertility Society
Vol. 40, No.6, December 1983 Printed in U.8A.
Use of corticosteroids as an adjuvant in terminal salpingostomy
Wesley J. Harris, M.D. James F. Daniell, M.D.* Center for Fertility and Reproductive Research (C -FARR), Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee
Between the years 1977 and 1980, 26 women underwent terminal salpingostomy with a standard operative procedure at Vanderbilt University Medical Center. The term pregnancy rate was 23%, and the ectopic pregnancy rate was 13%. Fourteen patients received dexamethasone perioperatively; and of these, 3 had term pregnancies (21%). Of the 12 patients not receiving dexamethasone, there were also three term pregnancies (25%). It is concluded from this small series that perioperative corticosteroids do not improve the term pregnancy rate for terminal salpingostomy. Fertil Steril40:785, 1983
Much attention has been focused in the past on various methods to prevent adhesions postoperatively in infertility surgery. Promethazine, corticosteroids, l and 32% dextran 702 have all been touted to decrease adhesion formation. The problem in interpreting clinical data in this area arises from the fact that it is difficult to provide adequate control groups for comparison. The severity of preexisting disease is the major determinant of success, and it is difficult to find two groups of patients with similar tubal disease. Similarly, in few studies has the usefulness of a single adhesioprophylactic agent been evaluated in patients undergoing a single operative procedure. In the past 4 years, approximately half of our patients undergoing terminal salpingostomy received corticosteroids, and the other half did not. These groups were similar with respect to age, race, and duration and extent of disease.
Received December 20, 1982; revised and accepted March 30,1983. *Reprint requests: James F. Daniell, M.D., Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee 37232. Vol. 40, No.6, December 1983
According to the nomenclature proposed at the Ninth World Congress on Fertility and Sterility,3 salpingostomy refers to the repair of a totally occluded tube and can be classified as "terminal," "midampullary," or "isthmic." Furthermore, fimbrioplasty refers to the partially occluded tube, which is repaired by (1) deagglutination and/or dilatation of fimbria; (2) incision of peritoneal ring; or (3) incision of the tubal wall with freeing of the fimbria. 3 In this report we review cases of terminal salpingostomy with distal occlusion proven by hysterosalpingographic studies and laparoscopic visualization with injection of dye. MATERIALS AND METHODS
Between the years 1977 and 1980 at Vanderbilt University Medical Center, 26 pure terminal salpingostomies were performed by one of us (J. D.). All patients had distal fimbrial occlusion documented by hysterosalpingography (HSG) and at laparoscopy. Patients whose pathologic condition consisted of phimotic tube(s) secondary to peritoneal bands or with fimbrial agglutination were excluded, as were patients with associated proximal tubal disease and those with endometriosis. Harris and Daniell Corticosteroid use in salpingostomy
785
Cases in which only one tube underwent a terminal salpingostomy with a different procedure being performed on the other tube, i.e., fimbrioplasty or salpingo-oophorolysis, were not included in this review. All patients underwent a standard infertility workup, which included documentation of ovulation, semen analysis, postcoital testing, and HSG. On several occasions, laparoscopic visualization of dye constituted the only preoperative evaluation of the tubal factor. Patients were given cefamandole nafate preoperatively, 1 to 2 gm intravenously, and every 6 hours postoperatively for 48 hours. Promethazine was given postoperatively, 50 mg every 4 hours for a total of 48 hours. Those receiving corticosteroids were given dexamethasone, 20 mg intravenously every 4 hours for 36 hours, beginning intraoperatively. Standard microsurgical technique was used in the method described by Gomel and McComb,4 with magnification provided in all cases by loupes or an operating Zeiss OM 7 microscope (Carl Zeiss, Inc., New York, NY). Meticulous salpingooophorolysis was accomplished and hemostatis was achieved with saline lavage and unipolar cautery. The tube was distended with dye, and the dimple was identified where the ostium had scarred and obstructed the tube. This point was then opened with needle cautery and a Teflon probe or a glass rod was inserted. Radial incisions were then made with unipolar needle cautery, looking "from inside out" to determine planes of fibrosis and scarring along which to make the incision. The fimbriated ends were then pinned back to the serosal surface with 7-0 Dexon (Davis and Geck, Manati, PR). Before closing the peritoneum, 100 to 200 ml 32% dextran 70 was poured into the abdominal cavity. Hydrotubation was performed on the first postoperative morning unless uterine bleeding was present, using sterile saline without adjuvants. A similar office hydrotubation was performed after the first menstrual cycle at the first postoperative visit. In those patients where follow-up was adequate and pregnancy had not occurred, HSG was performed 6 months postoperatively. Beginning in 1979, we began to recommend an early "second-look" laparoscopy to selected patients, and eight were performed. Since the institution is a referral hospital for middle Tennessee, the majority of our patients were referred from a radius of 200 miles. Those patients were primarily followed by their local 786
Harris and Daniell Corticosteroid use in salpingostomy
gynecologists or family physicians, although we made an attempt to see them on at least a yearly basis and perform their follow-up HSG and second-look laparoscopy. An estimation of the size of the hydrosalpinx, the condition of the fimbria, and the degree of peritubal adhesions was made at the time of the procedure and recorded in the operative notes. Some of the patients who were referred for surgery had their preoperative hysterosalpingograms done elsewhere, and they were not available for review. In approximately half the cases, the screening laparoscopy and definitive operative procedure were performed at the same time.
RESULTS The makeup of the patient population was as follows: of 26 patients, 23 were Caucasian and 3 were black. Nine patients had primary infertility, and 17 had secondary infertility. Three patients had had prior tuboplasty procedures of the same type. The mean duration of infertility was 3 years. A total of 8 of 26 patients conceived, for an overall pregnancy rate of 31%. Seven patients had intrauterine pregnancies (27%), and six women gave birth to seven full-term infants for a term pregnancy rate of 23%. Three women had ectopic pregnancies, for a 13% ectopic pregnancy rate. Interestingly, two of the three ectopic pregnancies came after prior intrauterine pregnancies. The median surgery-to-conception interval was 20 months, with a range of 4 to 25 months. A higher percentage of secondary infertility patients (29%) achieved term pregnancies, as compared with primary infertility patients (11%). Of the 17 secondary infertility patients, 11 did not receive steroids and 6 did. Of the nine primary infertility patients, eight received steroids and one did not. Of patients who did not have term pregnancies, three underwent subsequent hysterectomy for pelvic pain, one requested birth control pills after a tubal pregnancy, one patient divorced, and another requested birth control pills after undergoing surgery for a benign cerebellar tumor. Thus, of the 20 patients attempting to conceive and followed for a minimum of 24 months, 7 conceived (35%) and 6 (30%) delivered full-term infants. Of the 18 patients who did not conceive, 4 had other documented infertility problems. One couple was using artificial insemination by husband Fertility and Sterility
Table 1. Results of Terminal Salpingostomy Overall
No. of patients Median age (yr) Median duration of infertility (mo) Median surgery-conception (mo) Median follow-up (mo) Primary infertility Secondary infertility Patency by HSG Term pregnancy Ectopic pregnancy
Nonsteroids
Steroids
26 26 3
12 25 3
14 27 3
20
14
20
35 9 17 75% 23% 13%
31 1
36 8 6 60% 21% 25%
11
100% 25% 0%
due to the husband's hypospadias, before being lost to follow-up. One woman became anovulatory postoperatively; and before this condition could be adequately evaluated and treated, she underwent a hysterectomy elsewhere for pelvic pain. Two other women with anovulation and a luteal phase defect were treated effectively with clomiphene citrate and progesterone suppositories, respectively. Follow-up HSG showed a patency rate of 75% for all tubes repaired. Additionally, eight patients had second-look laparoscopy, at which time adhesions were lysed when possible. On several occasions, an attempt was made to bluntly enlarge the ostium with the laparoscopic instruments at the time of the second-look laparoscopy. Fourteen patients received steroids perioperatively. Of those 14, there were five pregnancies resulting in three viable full-term infants. Of the 12 patients not receiving steroids, there were three pregnancies, all full-term (Table 1). Of the eight patients receiving second-look laparoscopy, six received steroids and two did not. Five of the six patients receiving steroids had significant adhesions or recurrence of hydrosalpinx. Both of the patients not receiving steroids had recurrence of hydrosalpinx. DISCUSSION
Corticosteroids have been shown to inhibit fibroblastic migration, proliferation, and organization, and may also have a role in decreasing histamine release, thus decreasing vascular permeability.1 Both intraperitoneal and systemic doses are theoretically plausible routes of administration. There has been much controversy, however, over the effectiveness of steroids for reducing postoperative adhesions both in experimental animals and in clinical trials. Vol. 40, No.6, December 1983
Shikata, 5 using experimental animals, found intraperitoneal steroids useful in decreasing adhesion formation after abrading bowel serosa. Clinical support for this was supplied by Swolin, 6 who found decreased pelvic adhesions at the time of second-look procedures in patients treated with intraperitoneal hydrocortisone during various infertility procedures. Of 33 nontreated controls, 32 had adhesions noted, whereas only 11 of 33 treated patients had adhesions. 6 Experimental evidence by Glucksman,7 however, indicated no decrease in adhesion formation in dogs treated with intraperitoneal steroids after serosal abrasion. Furthermore, Surrey and Friedman8 have recently noted hydrocortisone plaques in a significant number of patients at second-look laparoscopy who had previously received intraperitoneal hydrocortisone. They commented that systemic use could accomplish the same beneficial antiinflammatory effects without subjecting the patient to risks of plaques and subsequent adhesion formation. However, the beneficial effects of systemic corticosteroids have also not been clearly demonstrated. Replogle and co-workers 9 initially showed decreased adhesion formation in dogs with systemic corticosteroid use after bowel abrasion. Home's cooperative study1 gave tremendous clinical impetus to the use of systemic corticosteroids with his group's report of greatly increased fertility rates using promethazine, dexamethasone, and antibiotics. Unfortunately, he did not have a control group in this study, and many different types of infertility procedures were included from multiple centers. Seitz et al.,l0 using monkeys, could find no benefit with systemic corticosteroids in decreasing adhesion formation. This was confirmed by diZerega, 2 also using monkeys. In this small clinical series,2 the term pregnancy rate was 3 of 14, or 21 %, with corticosteroids and 3 of 12, or 25%, without corticosteroids, suggesting that corticosteroids did not increase the term pregnancy rate. Also, there appeared to be no benefit for the limited number of patients who received second-look laparoscopy. There are theoretic risks of administering steroids, including retardation of wound healing and increased incidence of infection. l l • 12 While this is well proven in experimental animals, it has not been a clinically significant factor in infertility surgery. Our term pregnancy rate of 23% and ectopic pregnancy rate of 13% is in the range reported by Harris and Daniell Corticosteroid use in salpingostomy
787
Table 2. Results of Terminal Salpingostomy: Recent Reports Term EctQpic No. of pre,nan- .p~nanpatients Patency Cles Cles
Swolin (1967)6 Gomel (1978)13 DeCherney and Kase (1981)18 Harris and Daniell (1982) (present study)
%
%
33 41 54
Nsa NS 90%
24 27 26
18 12 12
26
75%
23
13
aNS, not stated.
various investigators for terminal salpingostomy (Table 2). In retrospectively evaluating cases, it is often difficult to separate out fimbrioplasty procedures, because phimotic tubes have a much greater pregnancy rate-Patton reported 68%. 3 Furthermore, these patients have a shorter interval between surgery and conception; 44% in Patton's series conceived within 3 months. Our median interval to conception of 20 months compares well with Gomel's observation 13 that 60% of his patients conceived more than 1 year following terminal salpingostomy. The difference in the surgery-to-conception interval has been thought to arise from the need for damaged endothelial tissue to regenerate after terminal salpingostomy.13 The fallopian tube being repaired in a fimbrioplasty procedure is only partially occluded and theoretically does not have the degree of damaged endothelium present in the totally occluded hydrosalpinx. It is sometimes difficult to decide whether a tube is totally or partially occluded. Phimotic tubes that retain some patency can still be dilated proximally to the phimosis stimulating hydrosalpinx on inspection. We have considered all cases where dye flowed easily through the fallopian tube to be fimbrioplastyprocedures regardless of the degree of dilatation. We included in our series, however, several patients who had been found at laparoscopy to have hydrosalpinx, which slowly distended with dye and then with considerable pressure leaked a small amount. It is our contention that these tubes were functionally occludedas far as physiologic secretions were concerned. However, with added hydrostatic pressure from retrograde injection, the adhesions that sealed the ostium separated and allowed the intraperitoneal spill of the distending fluid. It is of interest that even with less follow-up time, our pregnancy rate in 1980 was somewhat 788
Harris and Daniell Corticosteroid use in salpingostomy
better (three of seven) than in 1977 (one of four). Although a few minor technicologic and surgical advances have been made in that time, the clinical arrival in our department of in vitro fertilization and embryo transfer (IVF-ET) has changed our surgical decision making. At other institutions a pregnancy rate as high as 21% has been reported. 14 Our initial rate in IVF-ET is currently being evaluated15 but does not yet approach 20%. In 1977, a patient with adnexa that would be classified as severe by Rock et al. 16 would have undergone salpingostomy. By contrast, in 1980 the same adnexa necessitated no surgery or salpingectomy along with ovarian suspension for future attempts at IVF-ET. The patients in this study were not classified by etiology or severity of disease because individual variations made it difficult to divide them into groups. Some methods of prognostic grading techniques may have applicability, such as tubal mucosal biopsy and electron-microscopic evaluation as discussed by Brosens and DeGraef17 or the recording of rugae by HSG. 18 In conclusion, our pregnancy rates after terminalsalpingostomy roughly parallel those reported by other investigators, with a term pregnancy rate of 23% and an ectopic pregnancy rate of 13%. In two groups of patients equivalent with respect to age, race, and duration and extent of disease, the use of corticosteroids perioperatively did not alter our term pregnancy rate.
REFERENCES 1. Horne W: The prevention of post-operative pelvic adhesions following conservative operative treatment for human infertility. Int J Fertil 18:109, 1973 2. diZerega GS: Prevention of post-operative tubal adhesions. Am J Obstet GynecoI136:173, 1980 3. Patton GW Jr: Pregnancy outcome following microsurgical fimbrioplasty. Fertil Steril 37:150, 1982 4. Gomel V, McCombP: Microsurgery in gynecology. In Microsurgery, Edited by SJ Silber. Baltimore, Williams & Wilkins Co., 1979, p 143 5. Shikata J: The role of topically applied dexamethasone in preventing peritoneal adhesions: experimental and clinical studies. World J Surg 1:389, 1977 6. Swolin K: Die einwirkung von grossen intraperitonealen dosen glukokortikoid aut die bildung von postoperativen adhasionen. Acta Obstet Gynecol Scand 46:1, 1967 7. Glucksman DC: The effect of topically applied corticosteroids in the prevention of peritoneal adhesions. Surgery 60:352, 1966 8. Surrey MW,Friedman S: Second-look laparoscopy after reconstructive pelvic surgery for infertility. J Reprod Med 27:658, 1982 Fertility and Sterility
9. Replogle RL, Johnson R, Gross RE: Prevention of postoperative adhesions with combined promethazine and dexamethasone therapy. Ann Surg 163:580, 1966 10. Seitz HM Jr, Schenker JG, Epstein S, Garcia C-R: Postoperative intraperitoneal adhesions: a double-blind assessment of their prevention in the monkey. Fertil Steril 24:935, 1973 11. Zacharie L: Hydrocortisone acetate applied intraperitoneally. Acta Endocrinol (Copenh) 19:275, 1955 12. Hinshaw DB: Effects of cortisone on the healing of disrupted abdominal wounds. Am J Surg 101:189, 1961 13. Gomel V: Salpingostomy by microsurgery. Fertil Steril 29:380, 1978 14. Jones HW Jr, Jones GS, Andrews MC, Acosta A, Bundren C, Garcia J, Sandow B, Veeck L, Wilkes C, Witmyer J, Wortham JE, Wright G: The program for in vitro fertilization at Norfolk. Fertil Steril 38:14, 1982
Vol. 40, No.6, December 1983
15. Wentz AC, Daniell JD, Maxson WM: Unpublished data 16. Rock JA, Katayama P, Martin EJ, Woodruff JD, Jones HW Jr: Factors influencing the success of salpingostomy techniques for distal fimbrial occlusion. Obstet Gynecol 52:591, 1978 17. Brosens lA, DeGraef R: Microbiopsy of the fallopian tube as a method for clinical investigation of tubal function in infertility. Int J Fertil 20:55, 1975 18. DeCherney AH, Kase N: A comparison of treatment for bilateral fimbrial occlusion. Fertil Steril 35:162, 1981
Harris and Daniell Corticosteroid use in salpingostomy
789
Vol. 40, No.6, December 1983 Printed in U.8A.
Use of corticosteroids as an adjuvant in terminal salpingostomy
Wesley J. Harris, M.D. James F. Daniell, M.D.* Center for Fertility and Reproductive Research (C -FARR), Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee
Between the years 1977 and 1980, 26 women underwent terminal salpingostomy with a standard operative procedure at Vanderbilt University Medical Center. The term pregnancy rate was 23%, and the ectopic pregnancy rate was 13%. Fourteen patients received dexamethasone perioperatively; and of these, 3 had term pregnancies (21%). Of the 12 patients not receiving dexamethasone, there were also three term pregnancies (25%). It is concluded from this small series that perioperative corticosteroids do not improve the term pregnancy rate for terminal salpingostomy. Fertil Steril40:785, 1983
Much attention has been focused in the past on various methods to prevent adhesions postoperatively in infertility surgery. Promethazine, corticosteroids, l and 32% dextran 702 have all been touted to decrease adhesion formation. The problem in interpreting clinical data in this area arises from the fact that it is difficult to provide adequate control groups for comparison. The severity of preexisting disease is the major determinant of success, and it is difficult to find two groups of patients with similar tubal disease. Similarly, in few studies has the usefulness of a single adhesioprophylactic agent been evaluated in patients undergoing a single operative procedure. In the past 4 years, approximately half of our patients undergoing terminal salpingostomy received corticosteroids, and the other half did not. These groups were similar with respect to age, race, and duration and extent of disease.
Received December 20, 1982; revised and accepted March 30,1983. *Reprint requests: James F. Daniell, M.D., Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee 37232. Vol. 40, No.6, December 1983
According to the nomenclature proposed at the Ninth World Congress on Fertility and Sterility,3 salpingostomy refers to the repair of a totally occluded tube and can be classified as "terminal," "midampullary," or "isthmic." Furthermore, fimbrioplasty refers to the partially occluded tube, which is repaired by (1) deagglutination and/or dilatation of fimbria; (2) incision of peritoneal ring; or (3) incision of the tubal wall with freeing of the fimbria. 3 In this report we review cases of terminal salpingostomy with distal occlusion proven by hysterosalpingographic studies and laparoscopic visualization with injection of dye. MATERIALS AND METHODS
Between the years 1977 and 1980 at Vanderbilt University Medical Center, 26 pure terminal salpingostomies were performed by one of us (J. D.). All patients had distal fimbrial occlusion documented by hysterosalpingography (HSG) and at laparoscopy. Patients whose pathologic condition consisted of phimotic tube(s) secondary to peritoneal bands or with fimbrial agglutination were excluded, as were patients with associated proximal tubal disease and those with endometriosis. Harris and Daniell Corticosteroid use in salpingostomy
785
Cases in which only one tube underwent a terminal salpingostomy with a different procedure being performed on the other tube, i.e., fimbrioplasty or salpingo-oophorolysis, were not included in this review. All patients underwent a standard infertility workup, which included documentation of ovulation, semen analysis, postcoital testing, and HSG. On several occasions, laparoscopic visualization of dye constituted the only preoperative evaluation of the tubal factor. Patients were given cefamandole nafate preoperatively, 1 to 2 gm intravenously, and every 6 hours postoperatively for 48 hours. Promethazine was given postoperatively, 50 mg every 4 hours for a total of 48 hours. Those receiving corticosteroids were given dexamethasone, 20 mg intravenously every 4 hours for 36 hours, beginning intraoperatively. Standard microsurgical technique was used in the method described by Gomel and McComb,4 with magnification provided in all cases by loupes or an operating Zeiss OM 7 microscope (Carl Zeiss, Inc., New York, NY). Meticulous salpingooophorolysis was accomplished and hemostatis was achieved with saline lavage and unipolar cautery. The tube was distended with dye, and the dimple was identified where the ostium had scarred and obstructed the tube. This point was then opened with needle cautery and a Teflon probe or a glass rod was inserted. Radial incisions were then made with unipolar needle cautery, looking "from inside out" to determine planes of fibrosis and scarring along which to make the incision. The fimbriated ends were then pinned back to the serosal surface with 7-0 Dexon (Davis and Geck, Manati, PR). Before closing the peritoneum, 100 to 200 ml 32% dextran 70 was poured into the abdominal cavity. Hydrotubation was performed on the first postoperative morning unless uterine bleeding was present, using sterile saline without adjuvants. A similar office hydrotubation was performed after the first menstrual cycle at the first postoperative visit. In those patients where follow-up was adequate and pregnancy had not occurred, HSG was performed 6 months postoperatively. Beginning in 1979, we began to recommend an early "second-look" laparoscopy to selected patients, and eight were performed. Since the institution is a referral hospital for middle Tennessee, the majority of our patients were referred from a radius of 200 miles. Those patients were primarily followed by their local 786
Harris and Daniell Corticosteroid use in salpingostomy
gynecologists or family physicians, although we made an attempt to see them on at least a yearly basis and perform their follow-up HSG and second-look laparoscopy. An estimation of the size of the hydrosalpinx, the condition of the fimbria, and the degree of peritubal adhesions was made at the time of the procedure and recorded in the operative notes. Some of the patients who were referred for surgery had their preoperative hysterosalpingograms done elsewhere, and they were not available for review. In approximately half the cases, the screening laparoscopy and definitive operative procedure were performed at the same time.
RESULTS The makeup of the patient population was as follows: of 26 patients, 23 were Caucasian and 3 were black. Nine patients had primary infertility, and 17 had secondary infertility. Three patients had had prior tuboplasty procedures of the same type. The mean duration of infertility was 3 years. A total of 8 of 26 patients conceived, for an overall pregnancy rate of 31%. Seven patients had intrauterine pregnancies (27%), and six women gave birth to seven full-term infants for a term pregnancy rate of 23%. Three women had ectopic pregnancies, for a 13% ectopic pregnancy rate. Interestingly, two of the three ectopic pregnancies came after prior intrauterine pregnancies. The median surgery-to-conception interval was 20 months, with a range of 4 to 25 months. A higher percentage of secondary infertility patients (29%) achieved term pregnancies, as compared with primary infertility patients (11%). Of the 17 secondary infertility patients, 11 did not receive steroids and 6 did. Of the nine primary infertility patients, eight received steroids and one did not. Of patients who did not have term pregnancies, three underwent subsequent hysterectomy for pelvic pain, one requested birth control pills after a tubal pregnancy, one patient divorced, and another requested birth control pills after undergoing surgery for a benign cerebellar tumor. Thus, of the 20 patients attempting to conceive and followed for a minimum of 24 months, 7 conceived (35%) and 6 (30%) delivered full-term infants. Of the 18 patients who did not conceive, 4 had other documented infertility problems. One couple was using artificial insemination by husband Fertility and Sterility
Table 1. Results of Terminal Salpingostomy Overall
No. of patients Median age (yr) Median duration of infertility (mo) Median surgery-conception (mo) Median follow-up (mo) Primary infertility Secondary infertility Patency by HSG Term pregnancy Ectopic pregnancy
Nonsteroids
Steroids
26 26 3
12 25 3
14 27 3
20
14
20
35 9 17 75% 23% 13%
31 1
36 8 6 60% 21% 25%
11
100% 25% 0%
due to the husband's hypospadias, before being lost to follow-up. One woman became anovulatory postoperatively; and before this condition could be adequately evaluated and treated, she underwent a hysterectomy elsewhere for pelvic pain. Two other women with anovulation and a luteal phase defect were treated effectively with clomiphene citrate and progesterone suppositories, respectively. Follow-up HSG showed a patency rate of 75% for all tubes repaired. Additionally, eight patients had second-look laparoscopy, at which time adhesions were lysed when possible. On several occasions, an attempt was made to bluntly enlarge the ostium with the laparoscopic instruments at the time of the second-look laparoscopy. Fourteen patients received steroids perioperatively. Of those 14, there were five pregnancies resulting in three viable full-term infants. Of the 12 patients not receiving steroids, there were three pregnancies, all full-term (Table 1). Of the eight patients receiving second-look laparoscopy, six received steroids and two did not. Five of the six patients receiving steroids had significant adhesions or recurrence of hydrosalpinx. Both of the patients not receiving steroids had recurrence of hydrosalpinx. DISCUSSION
Corticosteroids have been shown to inhibit fibroblastic migration, proliferation, and organization, and may also have a role in decreasing histamine release, thus decreasing vascular permeability.1 Both intraperitoneal and systemic doses are theoretically plausible routes of administration. There has been much controversy, however, over the effectiveness of steroids for reducing postoperative adhesions both in experimental animals and in clinical trials. Vol. 40, No.6, December 1983
Shikata, 5 using experimental animals, found intraperitoneal steroids useful in decreasing adhesion formation after abrading bowel serosa. Clinical support for this was supplied by Swolin, 6 who found decreased pelvic adhesions at the time of second-look procedures in patients treated with intraperitoneal hydrocortisone during various infertility procedures. Of 33 nontreated controls, 32 had adhesions noted, whereas only 11 of 33 treated patients had adhesions. 6 Experimental evidence by Glucksman,7 however, indicated no decrease in adhesion formation in dogs treated with intraperitoneal steroids after serosal abrasion. Furthermore, Surrey and Friedman8 have recently noted hydrocortisone plaques in a significant number of patients at second-look laparoscopy who had previously received intraperitoneal hydrocortisone. They commented that systemic use could accomplish the same beneficial antiinflammatory effects without subjecting the patient to risks of plaques and subsequent adhesion formation. However, the beneficial effects of systemic corticosteroids have also not been clearly demonstrated. Replogle and co-workers 9 initially showed decreased adhesion formation in dogs with systemic corticosteroid use after bowel abrasion. Home's cooperative study1 gave tremendous clinical impetus to the use of systemic corticosteroids with his group's report of greatly increased fertility rates using promethazine, dexamethasone, and antibiotics. Unfortunately, he did not have a control group in this study, and many different types of infertility procedures were included from multiple centers. Seitz et al.,l0 using monkeys, could find no benefit with systemic corticosteroids in decreasing adhesion formation. This was confirmed by diZerega, 2 also using monkeys. In this small clinical series,2 the term pregnancy rate was 3 of 14, or 21 %, with corticosteroids and 3 of 12, or 25%, without corticosteroids, suggesting that corticosteroids did not increase the term pregnancy rate. Also, there appeared to be no benefit for the limited number of patients who received second-look laparoscopy. There are theoretic risks of administering steroids, including retardation of wound healing and increased incidence of infection. l l • 12 While this is well proven in experimental animals, it has not been a clinically significant factor in infertility surgery. Our term pregnancy rate of 23% and ectopic pregnancy rate of 13% is in the range reported by Harris and Daniell Corticosteroid use in salpingostomy
787
Table 2. Results of Terminal Salpingostomy: Recent Reports Term EctQpic No. of pre,nan- .p~nanpatients Patency Cles Cles
Swolin (1967)6 Gomel (1978)13 DeCherney and Kase (1981)18 Harris and Daniell (1982) (present study)
%
%
33 41 54
Nsa NS 90%
24 27 26
18 12 12
26
75%
23
13
aNS, not stated.
various investigators for terminal salpingostomy (Table 2). In retrospectively evaluating cases, it is often difficult to separate out fimbrioplasty procedures, because phimotic tubes have a much greater pregnancy rate-Patton reported 68%. 3 Furthermore, these patients have a shorter interval between surgery and conception; 44% in Patton's series conceived within 3 months. Our median interval to conception of 20 months compares well with Gomel's observation 13 that 60% of his patients conceived more than 1 year following terminal salpingostomy. The difference in the surgery-to-conception interval has been thought to arise from the need for damaged endothelial tissue to regenerate after terminal salpingostomy.13 The fallopian tube being repaired in a fimbrioplasty procedure is only partially occluded and theoretically does not have the degree of damaged endothelium present in the totally occluded hydrosalpinx. It is sometimes difficult to decide whether a tube is totally or partially occluded. Phimotic tubes that retain some patency can still be dilated proximally to the phimosis stimulating hydrosalpinx on inspection. We have considered all cases where dye flowed easily through the fallopian tube to be fimbrioplastyprocedures regardless of the degree of dilatation. We included in our series, however, several patients who had been found at laparoscopy to have hydrosalpinx, which slowly distended with dye and then with considerable pressure leaked a small amount. It is our contention that these tubes were functionally occludedas far as physiologic secretions were concerned. However, with added hydrostatic pressure from retrograde injection, the adhesions that sealed the ostium separated and allowed the intraperitoneal spill of the distending fluid. It is of interest that even with less follow-up time, our pregnancy rate in 1980 was somewhat 788
Harris and Daniell Corticosteroid use in salpingostomy
better (three of seven) than in 1977 (one of four). Although a few minor technicologic and surgical advances have been made in that time, the clinical arrival in our department of in vitro fertilization and embryo transfer (IVF-ET) has changed our surgical decision making. At other institutions a pregnancy rate as high as 21% has been reported. 14 Our initial rate in IVF-ET is currently being evaluated15 but does not yet approach 20%. In 1977, a patient with adnexa that would be classified as severe by Rock et al. 16 would have undergone salpingostomy. By contrast, in 1980 the same adnexa necessitated no surgery or salpingectomy along with ovarian suspension for future attempts at IVF-ET. The patients in this study were not classified by etiology or severity of disease because individual variations made it difficult to divide them into groups. Some methods of prognostic grading techniques may have applicability, such as tubal mucosal biopsy and electron-microscopic evaluation as discussed by Brosens and DeGraef17 or the recording of rugae by HSG. 18 In conclusion, our pregnancy rates after terminalsalpingostomy roughly parallel those reported by other investigators, with a term pregnancy rate of 23% and an ectopic pregnancy rate of 13%. In two groups of patients equivalent with respect to age, race, and duration and extent of disease, the use of corticosteroids perioperatively did not alter our term pregnancy rate.
REFERENCES 1. Horne W: The prevention of post-operative pelvic adhesions following conservative operative treatment for human infertility. Int J Fertil 18:109, 1973 2. diZerega GS: Prevention of post-operative tubal adhesions. Am J Obstet GynecoI136:173, 1980 3. Patton GW Jr: Pregnancy outcome following microsurgical fimbrioplasty. Fertil Steril 37:150, 1982 4. Gomel V, McCombP: Microsurgery in gynecology. In Microsurgery, Edited by SJ Silber. Baltimore, Williams & Wilkins Co., 1979, p 143 5. Shikata J: The role of topically applied dexamethasone in preventing peritoneal adhesions: experimental and clinical studies. World J Surg 1:389, 1977 6. Swolin K: Die einwirkung von grossen intraperitonealen dosen glukokortikoid aut die bildung von postoperativen adhasionen. Acta Obstet Gynecol Scand 46:1, 1967 7. Glucksman DC: The effect of topically applied corticosteroids in the prevention of peritoneal adhesions. Surgery 60:352, 1966 8. Surrey MW,Friedman S: Second-look laparoscopy after reconstructive pelvic surgery for infertility. J Reprod Med 27:658, 1982 Fertility and Sterility
9. Replogle RL, Johnson R, Gross RE: Prevention of postoperative adhesions with combined promethazine and dexamethasone therapy. Ann Surg 163:580, 1966 10. Seitz HM Jr, Schenker JG, Epstein S, Garcia C-R: Postoperative intraperitoneal adhesions: a double-blind assessment of their prevention in the monkey. Fertil Steril 24:935, 1973 11. Zacharie L: Hydrocortisone acetate applied intraperitoneally. Acta Endocrinol (Copenh) 19:275, 1955 12. Hinshaw DB: Effects of cortisone on the healing of disrupted abdominal wounds. Am J Surg 101:189, 1961 13. Gomel V: Salpingostomy by microsurgery. Fertil Steril 29:380, 1978 14. Jones HW Jr, Jones GS, Andrews MC, Acosta A, Bundren C, Garcia J, Sandow B, Veeck L, Wilkes C, Witmyer J, Wortham JE, Wright G: The program for in vitro fertilization at Norfolk. Fertil Steril 38:14, 1982
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15. Wentz AC, Daniell JD, Maxson WM: Unpublished data 16. Rock JA, Katayama P, Martin EJ, Woodruff JD, Jones HW Jr: Factors influencing the success of salpingostomy techniques for distal fimbrial occlusion. Obstet Gynecol 52:591, 1978 17. Brosens lA, DeGraef R: Microbiopsy of the fallopian tube as a method for clinical investigation of tubal function in infertility. Int J Fertil 20:55, 1975 18. DeCherney AH, Kase N: A comparison of treatment for bilateral fimbrial occlusion. Fertil Steril 35:162, 1981
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