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Postoperative danazol therapy in infertility patients with severe endometriosis*
Vol. 36 PP 460-463, October 1981 Printed in U.8A.
POSTOPERATIVE DANAZOL THERAPY IN INFERTILITY PATIENTS WIm SEVERE ENDOMETRIOSIS*
JAMES M. WHEELER, B.A. L. RUSSELL MALINAK, M.D.t Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030
The value of perioperative medical therapy in the management of infertility patients with severe endometriosis is uncertain. Previous reports of pre- or postlaparotomy danozol provide no clear direction regarding efficacy. Of 200 consecutive cases of severe endometriosis, 138 infertility patients were selected for study. One hundred nineteen patients, the control group, had laparotomy alone; 19 had laparotomy followed immediately by danozol therapy. The pregnancy rate in the control group was 30% (361119) versus 79% (15/19) in the study group, (p < 0.001). The results of this preliminary report indicate that danozol treatment in the immediate postlaparotomy period of patients with severe endometriosis significantly improves the pregnancy rate over comparable patients treated with surgery alone. It is hoped that these results will encourage other surgeons to implement a prospective surgical-medical approach, so that the most efficacious treatment for infertile patients with severe endometriosis can be determined. Fertil Steril 36:460, 1981
The value of perioperative medical therapy in the management of infertility patients with severe endometriosis is uncertain. Scattered reports of pre- and postlaparotomy danazol treatment are inconsistent in presenting stage of disease, tissue diagnosis, specific operative procedure, and dosage schedule. The pregnancy rates of these reports are uniformly IOW. 1 - 8 It is the purpose of this report to compare the pregnancy rate of infertility patients who have had severe endometriosis treated immediately after laparotomy with danazol with that of similar patients treated by laparotomy alone.
Received April 16, 1981; revised and accepted June 26, 1981. *Presented at the Thirty-Seventh Annual Meeting of the American Fertility Society, Atlanta Hilton, March 14 to 18, 1981, Atlanta, Georgia. tReprint requests: L. Russell Malinak, M.D., Associate Professor, Department of Obstetrics and Gynecology, Baylor College of Medicine, 1200 Moursund Avenue, Houston, Texas 77030.
26
METHODS
Two hundred consecutive cases of severe endometriosis were treated by laparotomy from July 1968 through April 1981. Of these, 138 patients were selected on the basis of these criteria: (1) infertility for one year or more; (2) histopathologic diagnosis of endometriosis; (3) severe disease by the classification of Acosta et al. (1973)9; (4) complete infertility investigation; (5) persistent attempt to conceive for 18 months postoperatively. These patients were divided into two groups: (1) The control group was composed of patients treated by laparotomy and conservative operation, but no perioperative suppressive therapy (N = 119). Fifty-one (43%) required unilateral salpingo-oophorectomy. The average age was 28.4 years, and the mean duration of infertility was 3.6 years. Primary infertility was present in 71%. (2) The study group was composed of patients treated since 1976 by laparotomy and conservative operation immediately followed by danazol therapy (N = 19). Fifteen (79%) required unilateral salpingo-oophorectomy. The average age was 26.6
years, and the mean duration of infertility' was 2.5 years. Primary infertility was present in 79%. Pregnancy rates were calculated, and concurrent infertility factors were compiled for each group. Statistical analysis was performed with a 2 x 2 test of independence using the chi -square distribution and Yates' correction for continuity inN < 200.10 All laparotomies with conservative procedures were carried out by the senior author and were consistent in anesthesia, operative technique, and postoperative care. l l None of the 138 patients reported herein had previous laparotomy for infertility. Danazol therapy consisted of 200 mg twice daily initiated on day of discharge from the hospital and continued for three months. The daily dose was increased by 200 mg to a maximum of 800 mg if persistent breakthrough bleeding occurred. All patients were amenorrheic for 3 months, with no patient taking the drug for a period longer than 6 months. RESULTS
Fifteen of 19 (79%) patients in the postoperative danazol group conceived. Nine of 12 (75%) patients requiring unilateral salpingo-oophorectomy conceived. Eleven patients carried to term, and one (11 %) had an early spontaneous abortion. Three patients are several weeks pregnant. The duration following danazol treatment to conception ranged from 1 to 31 months, with a mean of 8.0 months. Those patients who did not conceive were followed an average of 23 months (range = 18 to 29 months). In contrast, 36 of 119 (30%) of the patients treated with surgery alone conceived. Fifteen of 51 (29%) patients requiring unilateral salpingooophorectomy conceived. Twenty-seven patients carried to term, five (14%) had early spontaneous abortion, and two (6%) had a tubal ectopic pregnancy. The duration from surgery to conception ranged from 1 to 59 months, with a mean of 14 months. Those patients who did not conceive were followed an average of 39 months (range = 18 to 147 months). The differences in pregnancy rate between these two groups is statistically significant (P < 0.001). Four of 19 (21%) of the study group and 56 of 119 (47%) ofthe control group had one or more of the following: leiomyomata, anovulation, cervical factor, and male factor (treated with AIH or AID).
There is no statistically significant difference between the groups in incidence of associated infertility factors. Six of 19 (32%) patients completed their medical regimen on the 200 mg danazol twice daily for 3 months. Thirteen (68%) required increase in dose or duration of treatment to achieve 3 months of amenorrhea.
DISCUSSION
Macroscopic implants of endometriosis obscured by the dense adhesions of severe disease, as well as microscopic foci, can be overlooked at surgery.12 Microscopic foci have been postulated as etiologic in patients with unexplained infertility who have subsequently conceived after danazol. 13 Postoperative danazol therapy may thus complement standard conservative surgery, with improved pregnancy rates. Review of the literature does not demonstrate a clear advantage for postoperative danazol therapy. Eight papers have presented patients treated after laparotomy with danazol. l -8 However, only three reported the histologic diagnosis. I -3 Four studies grouped results of patients treated with laparotomy with those patients diagnosed by laparoscopy.2,4-6 Only one study of three patients specified procedure at laparotomy, confirmed endometriosis histologically, staged extent of disease as severe, and reported a single pregnancy (33%).3 For comparison, Dmowski and Cohen published a 38% pregnancy rate in patients with severe endometriosis treated with danazol after diagnostic laparoscopy.14 There is no published data on pregnancy rates following prelaparotomy danazol treatment, although there has been recent speculation about its potential benefit. 15, 16 It is generally recognized that medical suppression alone is inadequate therapy for severe endometriosis. 5, 16, 17 This concept is reasonable, considering that extensive and often dense adhesions attendant with severe disease will not respond to medical therapy.4 This observation has been made at laparoscopy following danazol treatment. 1 Thick, avascular walls of endometriomata are similarly refractory.14, 16 Reports of pregnancies following operative management alone have not been analyzed relative to extent of disease until recent years. When severe endometriosis has been managed by surgery alone,15, 18-21 the pregnancy rates range 27
from 0%18- to 56%,15 with the majority of reports in the lower percentages. When a combination of medical and surgical therapy is utilized, opinions differ as to the timing of each. Danazol is currently the medication of choice. 16 Some surgeons favor preoperative treatment on theoretical grounds,15 while others oppose it.I2 More surgeons prescribe postoperative danazol,12,16 though some have a contrary opinion. 15 Yet others remain noncommitted, suggesting danazol before and/or after operation. 7 Operative laparoscopy with perioperative danazol therapy has been advocated for management of severe endometriosis. 17, 22 It is our opinion that this method should be used rarely, if ever, because of the increased surgicalrisk and likelihood of incomplete surgical management. This point is well illustrated by the necessity of unilateral salpingo-oophorectomy in 48% of our patients; similar to an earlier reported rate of 45%.20 Severity of disease was clearly documented with the most utilized classification of endometriosis. While subclasses of severe endometriosis might be associated with varying prognoses, sufficient data are not yet available to substantiate this. 23 The-use of a uniform classification in both study and control groups lends clinical relevance to statistical significance. The frequency with which the danazol regimen had to be altered attests to the lack of knowledge as to proper dosage. The concept that persistent amenorrhea must be accomplished to achieve maximum results must be questioned. Published regimens of danazol use in endometriosis have ranged from 50 mg2 to 1000 mg24 daily, and duration of treatment has varied widely. The results of this preliminary report indicate that danazol treatment in the immediate postlaparotomy period of patients with severe endometriosis significantly improves the pregnancy rate over comparable patients treated with surgery alone. It is important to stress that none of these 138 patients had a previous laparotomy for infertility. Repeat laparotomy has been clearly demonstrated to adversely affect prognosis for conception. 3, 21 Postoperative danazol therapy is unlikely to alter that fact. It is hoped that the results of this study will encourage other surgeons to implement a similar protocol, so that the most efficacious treatment for infertile patients with severe endometriosis can be determined.
28
Acknowledgments. We thank Kim Goldenfarb and Wanda Pancamo for secretarial assistance and Carolyn Hayball, R.N., and Lisa Wheeler for research assistance. REFERENCES 1. Dmowski WP, Cohen MR: Treatment of endometriosis with an anti-gonadotropin, danazol. Obstet Gynecol 46: 147, 1975 2. Lauerson NH, Wilson KH, Birnbaum S: Danazol: an antigonadotropin agent in the treatment of pelvic endometriosis. Am J Obstet Gynecol 123:742,1975 3. Ingerslev M: Experience with danazol in severe and extensive endometriosis. J Int Med Res [Suppl 3] 5:81, 1977 4. Noble AD, Letchworth AT: Preliminary observations on the use of danazol in endometriosis compared to estrogen! progesterone combination therapy. J Int Med Res [Suppl 3] 5:79, 1977 5. Chalmers JA, Shervington PC: Proceedings of a symposium: Danazol: follow-up of patients with endometriosis treated with danazol. Postgrad Med J 55:44, 1979 6. Greenblatt RB, Tzingounis V: Danazol treatment of endometriosis long-term follow-up. Fertil Steril 31:237, 1979 7. Hirschowitz JS, Soler NC, Wortsman J: Sex steroid levels during treatment of endometriosis. Obstet Gynecol 54: 448, 1979 8. Ronnberg L, Ylostalo P, Jarvinen PA: Proceedings of a symposium: Danazol: effects of danazol in the treatment of severe endometriosis. Postgrad Med J [Suppl 5]55: 21, 1979 9. Acosta AA, Buttram VC, BeschPK, Malinak LR, Franklin RR, Vanderheyden JD: A proposed classification of endometriosis. Obstet GynecoI42:1, 1973 10. Sokal RR, Rohlf FJ: Introduction to biostatistics. San Francisco, W. H. Freeman, 1977, p 300 11. Malinak LR: Management of endometriosis in the infertile female. In The Infertile Female, Edited by JR Givens. Chicago, Year Book Publishers, 1979,p 359 12. Cohen MR: Laparoscopic diagnosis and pseudomenopause treatment of endometriosis with danazol. Clin Obstet Gynecol 23:3, 1980 13. Greenblatt RB: Danazol in the treatment of infertility. Drugs 19:362, 1980 14. Dmowski WP, Cohen MR: Antigonadotropin (danazol) in the treatment of endometriosis: evaluation of post-treatment fertility and three year follow-up data. Am J Obstet Gynecol 130:41, 1978 15. Buttram VC, Betts JW: Endometriosis. Curr Prob Obstet Gynecol 19:331, 1980 16. Chalmers TA: Danazol in the treatment of endometriosis. Drugs 19:331, 1980 17. Mettler L, Semm K: Clinical and biochemical experience with danazol in the treatment of endometriosis in cases with female infertility. Postgrad Med J [Suppl 5] 55:27, 1979 18. Hammond CB, Rock JA, Parker RT: Conservative treatment of endometriosis: the effects of limited surgery and hormonal pseudopregnancy. Fertil Steril 27:758, 1976 19. Garcia CR, David S: Pelvic endometriosis: infertility and pelvic pain. Am J Obstet GynecoI129:740, 1977
20. Sadigh H, Naples JD, Batt RF: Conservative surgery for endometriosis in the infertile couple. Obstet Gynecol 49: 651, 1977 21. Schenken RB, Malinak LR: Reoperation after initial treatment of endometriosis with conservative surgery. Am J Obstet Gynecol 131:416, 1978 22. Audebert AJ, Larrue-Charlus S, Emperaire TC: Proceedings of a symposium: Danazol: endometriosis and infertility: a review of sixty-two patients treated with danazol. Postgrad Med J [SuppI5]55:10, 1979
23. Rock JA, Cusick DS, Sengos C, Schweditsch M, Sapp KC, Jones HW: The conservative surgical treatment of endometriosis: evaluation of pregnancy success with respect to the extent of disease as categorized using contemporary classification systems. Fertil Steril 35:131, 1981 24. Lind T, Cook DB: Letter: How does danazol work? Lancet 2:1401, 1976
29
POSTOPERATIVE DANAZOL THERAPY IN INFERTILITY PATIENTS WIm SEVERE ENDOMETRIOSIS*
JAMES M. WHEELER, B.A. L. RUSSELL MALINAK, M.D.t Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030
The value of perioperative medical therapy in the management of infertility patients with severe endometriosis is uncertain. Previous reports of pre- or postlaparotomy danozol provide no clear direction regarding efficacy. Of 200 consecutive cases of severe endometriosis, 138 infertility patients were selected for study. One hundred nineteen patients, the control group, had laparotomy alone; 19 had laparotomy followed immediately by danozol therapy. The pregnancy rate in the control group was 30% (361119) versus 79% (15/19) in the study group, (p < 0.001). The results of this preliminary report indicate that danozol treatment in the immediate postlaparotomy period of patients with severe endometriosis significantly improves the pregnancy rate over comparable patients treated with surgery alone. It is hoped that these results will encourage other surgeons to implement a prospective surgical-medical approach, so that the most efficacious treatment for infertile patients with severe endometriosis can be determined. Fertil Steril 36:460, 1981
The value of perioperative medical therapy in the management of infertility patients with severe endometriosis is uncertain. Scattered reports of pre- and postlaparotomy danazol treatment are inconsistent in presenting stage of disease, tissue diagnosis, specific operative procedure, and dosage schedule. The pregnancy rates of these reports are uniformly IOW. 1 - 8 It is the purpose of this report to compare the pregnancy rate of infertility patients who have had severe endometriosis treated immediately after laparotomy with danazol with that of similar patients treated by laparotomy alone.
Received April 16, 1981; revised and accepted June 26, 1981. *Presented at the Thirty-Seventh Annual Meeting of the American Fertility Society, Atlanta Hilton, March 14 to 18, 1981, Atlanta, Georgia. tReprint requests: L. Russell Malinak, M.D., Associate Professor, Department of Obstetrics and Gynecology, Baylor College of Medicine, 1200 Moursund Avenue, Houston, Texas 77030.
26
METHODS
Two hundred consecutive cases of severe endometriosis were treated by laparotomy from July 1968 through April 1981. Of these, 138 patients were selected on the basis of these criteria: (1) infertility for one year or more; (2) histopathologic diagnosis of endometriosis; (3) severe disease by the classification of Acosta et al. (1973)9; (4) complete infertility investigation; (5) persistent attempt to conceive for 18 months postoperatively. These patients were divided into two groups: (1) The control group was composed of patients treated by laparotomy and conservative operation, but no perioperative suppressive therapy (N = 119). Fifty-one (43%) required unilateral salpingo-oophorectomy. The average age was 28.4 years, and the mean duration of infertility was 3.6 years. Primary infertility was present in 71%. (2) The study group was composed of patients treated since 1976 by laparotomy and conservative operation immediately followed by danazol therapy (N = 19). Fifteen (79%) required unilateral salpingo-oophorectomy. The average age was 26.6
years, and the mean duration of infertility' was 2.5 years. Primary infertility was present in 79%. Pregnancy rates were calculated, and concurrent infertility factors were compiled for each group. Statistical analysis was performed with a 2 x 2 test of independence using the chi -square distribution and Yates' correction for continuity inN < 200.10 All laparotomies with conservative procedures were carried out by the senior author and were consistent in anesthesia, operative technique, and postoperative care. l l None of the 138 patients reported herein had previous laparotomy for infertility. Danazol therapy consisted of 200 mg twice daily initiated on day of discharge from the hospital and continued for three months. The daily dose was increased by 200 mg to a maximum of 800 mg if persistent breakthrough bleeding occurred. All patients were amenorrheic for 3 months, with no patient taking the drug for a period longer than 6 months. RESULTS
Fifteen of 19 (79%) patients in the postoperative danazol group conceived. Nine of 12 (75%) patients requiring unilateral salpingo-oophorectomy conceived. Eleven patients carried to term, and one (11 %) had an early spontaneous abortion. Three patients are several weeks pregnant. The duration following danazol treatment to conception ranged from 1 to 31 months, with a mean of 8.0 months. Those patients who did not conceive were followed an average of 23 months (range = 18 to 29 months). In contrast, 36 of 119 (30%) of the patients treated with surgery alone conceived. Fifteen of 51 (29%) patients requiring unilateral salpingooophorectomy conceived. Twenty-seven patients carried to term, five (14%) had early spontaneous abortion, and two (6%) had a tubal ectopic pregnancy. The duration from surgery to conception ranged from 1 to 59 months, with a mean of 14 months. Those patients who did not conceive were followed an average of 39 months (range = 18 to 147 months). The differences in pregnancy rate between these two groups is statistically significant (P < 0.001). Four of 19 (21%) of the study group and 56 of 119 (47%) ofthe control group had one or more of the following: leiomyomata, anovulation, cervical factor, and male factor (treated with AIH or AID).
There is no statistically significant difference between the groups in incidence of associated infertility factors. Six of 19 (32%) patients completed their medical regimen on the 200 mg danazol twice daily for 3 months. Thirteen (68%) required increase in dose or duration of treatment to achieve 3 months of amenorrhea.
DISCUSSION
Macroscopic implants of endometriosis obscured by the dense adhesions of severe disease, as well as microscopic foci, can be overlooked at surgery.12 Microscopic foci have been postulated as etiologic in patients with unexplained infertility who have subsequently conceived after danazol. 13 Postoperative danazol therapy may thus complement standard conservative surgery, with improved pregnancy rates. Review of the literature does not demonstrate a clear advantage for postoperative danazol therapy. Eight papers have presented patients treated after laparotomy with danazol. l -8 However, only three reported the histologic diagnosis. I -3 Four studies grouped results of patients treated with laparotomy with those patients diagnosed by laparoscopy.2,4-6 Only one study of three patients specified procedure at laparotomy, confirmed endometriosis histologically, staged extent of disease as severe, and reported a single pregnancy (33%).3 For comparison, Dmowski and Cohen published a 38% pregnancy rate in patients with severe endometriosis treated with danazol after diagnostic laparoscopy.14 There is no published data on pregnancy rates following prelaparotomy danazol treatment, although there has been recent speculation about its potential benefit. 15, 16 It is generally recognized that medical suppression alone is inadequate therapy for severe endometriosis. 5, 16, 17 This concept is reasonable, considering that extensive and often dense adhesions attendant with severe disease will not respond to medical therapy.4 This observation has been made at laparoscopy following danazol treatment. 1 Thick, avascular walls of endometriomata are similarly refractory.14, 16 Reports of pregnancies following operative management alone have not been analyzed relative to extent of disease until recent years. When severe endometriosis has been managed by surgery alone,15, 18-21 the pregnancy rates range 27
from 0%18- to 56%,15 with the majority of reports in the lower percentages. When a combination of medical and surgical therapy is utilized, opinions differ as to the timing of each. Danazol is currently the medication of choice. 16 Some surgeons favor preoperative treatment on theoretical grounds,15 while others oppose it.I2 More surgeons prescribe postoperative danazol,12,16 though some have a contrary opinion. 15 Yet others remain noncommitted, suggesting danazol before and/or after operation. 7 Operative laparoscopy with perioperative danazol therapy has been advocated for management of severe endometriosis. 17, 22 It is our opinion that this method should be used rarely, if ever, because of the increased surgicalrisk and likelihood of incomplete surgical management. This point is well illustrated by the necessity of unilateral salpingo-oophorectomy in 48% of our patients; similar to an earlier reported rate of 45%.20 Severity of disease was clearly documented with the most utilized classification of endometriosis. While subclasses of severe endometriosis might be associated with varying prognoses, sufficient data are not yet available to substantiate this. 23 The-use of a uniform classification in both study and control groups lends clinical relevance to statistical significance. The frequency with which the danazol regimen had to be altered attests to the lack of knowledge as to proper dosage. The concept that persistent amenorrhea must be accomplished to achieve maximum results must be questioned. Published regimens of danazol use in endometriosis have ranged from 50 mg2 to 1000 mg24 daily, and duration of treatment has varied widely. The results of this preliminary report indicate that danazol treatment in the immediate postlaparotomy period of patients with severe endometriosis significantly improves the pregnancy rate over comparable patients treated with surgery alone. It is important to stress that none of these 138 patients had a previous laparotomy for infertility. Repeat laparotomy has been clearly demonstrated to adversely affect prognosis for conception. 3, 21 Postoperative danazol therapy is unlikely to alter that fact. It is hoped that the results of this study will encourage other surgeons to implement a similar protocol, so that the most efficacious treatment for infertile patients with severe endometriosis can be determined.
28
Acknowledgments. We thank Kim Goldenfarb and Wanda Pancamo for secretarial assistance and Carolyn Hayball, R.N., and Lisa Wheeler for research assistance. REFERENCES 1. Dmowski WP, Cohen MR: Treatment of endometriosis with an anti-gonadotropin, danazol. Obstet Gynecol 46: 147, 1975 2. Lauerson NH, Wilson KH, Birnbaum S: Danazol: an antigonadotropin agent in the treatment of pelvic endometriosis. Am J Obstet Gynecol 123:742,1975 3. Ingerslev M: Experience with danazol in severe and extensive endometriosis. J Int Med Res [Suppl 3] 5:81, 1977 4. Noble AD, Letchworth AT: Preliminary observations on the use of danazol in endometriosis compared to estrogen! progesterone combination therapy. J Int Med Res [Suppl 3] 5:79, 1977 5. Chalmers JA, Shervington PC: Proceedings of a symposium: Danazol: follow-up of patients with endometriosis treated with danazol. Postgrad Med J 55:44, 1979 6. Greenblatt RB, Tzingounis V: Danazol treatment of endometriosis long-term follow-up. Fertil Steril 31:237, 1979 7. Hirschowitz JS, Soler NC, Wortsman J: Sex steroid levels during treatment of endometriosis. Obstet Gynecol 54: 448, 1979 8. Ronnberg L, Ylostalo P, Jarvinen PA: Proceedings of a symposium: Danazol: effects of danazol in the treatment of severe endometriosis. Postgrad Med J [Suppl 5]55: 21, 1979 9. Acosta AA, Buttram VC, BeschPK, Malinak LR, Franklin RR, Vanderheyden JD: A proposed classification of endometriosis. Obstet GynecoI42:1, 1973 10. Sokal RR, Rohlf FJ: Introduction to biostatistics. San Francisco, W. H. Freeman, 1977, p 300 11. Malinak LR: Management of endometriosis in the infertile female. In The Infertile Female, Edited by JR Givens. Chicago, Year Book Publishers, 1979,p 359 12. Cohen MR: Laparoscopic diagnosis and pseudomenopause treatment of endometriosis with danazol. Clin Obstet Gynecol 23:3, 1980 13. Greenblatt RB: Danazol in the treatment of infertility. Drugs 19:362, 1980 14. Dmowski WP, Cohen MR: Antigonadotropin (danazol) in the treatment of endometriosis: evaluation of post-treatment fertility and three year follow-up data. Am J Obstet Gynecol 130:41, 1978 15. Buttram VC, Betts JW: Endometriosis. Curr Prob Obstet Gynecol 19:331, 1980 16. Chalmers TA: Danazol in the treatment of endometriosis. Drugs 19:331, 1980 17. Mettler L, Semm K: Clinical and biochemical experience with danazol in the treatment of endometriosis in cases with female infertility. Postgrad Med J [Suppl 5] 55:27, 1979 18. Hammond CB, Rock JA, Parker RT: Conservative treatment of endometriosis: the effects of limited surgery and hormonal pseudopregnancy. Fertil Steril 27:758, 1976 19. Garcia CR, David S: Pelvic endometriosis: infertility and pelvic pain. Am J Obstet GynecoI129:740, 1977
20. Sadigh H, Naples JD, Batt RF: Conservative surgery for endometriosis in the infertile couple. Obstet Gynecol 49: 651, 1977 21. Schenken RB, Malinak LR: Reoperation after initial treatment of endometriosis with conservative surgery. Am J Obstet Gynecol 131:416, 1978 22. Audebert AJ, Larrue-Charlus S, Emperaire TC: Proceedings of a symposium: Danazol: endometriosis and infertility: a review of sixty-two patients treated with danazol. Postgrad Med J [SuppI5]55:10, 1979
23. Rock JA, Cusick DS, Sengos C, Schweditsch M, Sapp KC, Jones HW: The conservative surgical treatment of endometriosis: evaluation of pregnancy success with respect to the extent of disease as categorized using contemporary classification systems. Fertil Steril 35:131, 1981 24. Lind T, Cook DB: Letter: How does danazol work? Lancet 2:1401, 1976
29