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Efficacy of Laser Laparoscopy in Minimal Endometriosis?
served that integrins are closely related to endometrial morphology and therefore may prove to be useful markers of the window of implantation. Indeed, two of these integrins, a4.B1 and av.B3 are coexpressed only during the narrow window of time permissive to embryo implantation. While we suggest that these integrins may play a role in nidation, their greatest utility appears to be as markers of endometrial maturation and uterine receptivity. The loss of one of these integrins, av.B3, is highly associated with infertility and missing in patients suffering from luteal phase deficiency (2), endometriosis (4), and hydrosalpinges (Lessey BA, Castelbaum AJ, Riben M, Howarth J, Tureck R, Meyer WR, abstract 0-91). As these integrins are consistently present in fertile control subjects, we believe that av.B3 may be a useful marker of normal uterine receptivity. The second interesting finding in this paper, as well as the paper by Ruck et aI., is the observation that the decidua also undergoes dynamic alterations in integrin expression. While many of the changes are seen in epithelial cells appear to be regulated by steroid hormones, we suspect that growth factors play a greater role in stromal integrin expression, possibly originating in the trophoblasts. Thus, we agree that the distribution of cell adhesion molecules in epithelia and decidua provides a potential insight into endometrial trophoblast interaction. The use of integrins to investigate the endometrium and implantation is an evolving and promising area with many likely applications for the evaluation and treatment of the infertile couple.
Bruce A. Lessey, Ph.D., M.D. Division of Reproductive Endocrinology Department of Obstetrics and Gynecology University of North Carolina Chapel Hill, North Carolina Art Castelbaum, M.D. Northern Fertility and Reproductive Associates, P. C. Meadowbrook, Pennsylvania December 7, 1994 REFERENCES 1. Ruck P, Marzusch K, Kaiserling E, Horny H-P, Dietl J, Geiselhart A, et al. Distribution of cell adhesion molecules in decidua of early human pregnancy: an immunohistochemical study. Lab Invest 1994;71:94-101. 2. Lessey BA, Castelbaum AJ, Buck CA, Lei Y, Yowell CW, Sun J. Further characterization of endometrial integrins during the menstrual cycle and in pregnancy. Fertil Steril 1994; 62:497 -506. 3. Lessey BA, Damjanovich L, Coutifaris C, Castelbaum A, AlbeIda SM, Buck CA. Integrin adhesion molecules in the huVol. 63, No.6, June 1995
man endometrium. Correlation with the normal and abnormal menstrual cycle. J Clin Invest 1992;90:188-95. 4. Lessey BA, Castelbaum AJ, Sawin SJ, Buck CA, Schinnar R, Wilkins B, et al. Aberrant integrin expression in the endometrium of women with endometriosis. J Clin Endocrinol Metab 1994;79:643-9.
Efficacy of Laser Laparoscopy in Minimal Endometriosis?
To the Editor: I read with interest the article by Drs. Sutton et al. "Prospective Randomized, Double-Blind, Controlled Trial of Laser Laparoscopy in the Treatment of Pelvic Pain Associated with Minimal, Mild, and Moderate Endometriosis" (1). The authors are to be commended for demonstrating that appropriately controlled studies of operative laparoscopic procedures are indeed feasible. Unfortunately, the authors oft-repeated conclusion that the study "confirms that laser laparoscopy is effective for alleviating symptoms associated with endometriosis," is not supported by their data. Specifically, their study suffers from one significant methodological problem which is that patients were not randomized to laser laparoscopy of endometriosis versus expectant management; rather, they were randomized to laser laparoscopy of endometriosis plus laparoscopic uterosacral nerve ablation versus expectant management. As the authors may know, laparoscopic uterosacral nerve ablation has been shown to result in an 80% response rate for dysmenorrhea in randomized blinded prospective trials involving women without endometriosis (2). Intentionally or not, the authors have not provided a controlled trial of laser laparoscopic treatment of pelvic pain associated with endometriosis, but rather a confirmatory trial of laparoscopic uterosacral nerve ablation for dysmenorrhea. The authors state in the discussion that "enthusiasts of the medical treatment of endometriosis can no longer claim that laser laparoscopy has not been subjected to a placebo-controlled study." In order to have fulfilled this worthwhile goal, the present study should have either included an additional treatment arm (namely expectant management versus laser of endometriosis versus laser of endometriosis plus laparoscopic uterosacral nerve ablation) or should have randomized patients to expectant management versus laser of endometriosis only. Finally, the fact that the authors observed a poor response rate in women with minimal disease raises questions as to whether minimal endometriosis is causally or incidentally asLetters-to-the-editor Letters-to-the-editor
1355
--sociated with significant dysmenorrhea, which is present in 50% ofthe general population (3). For this reason, I would recommend caution against recommending laser laparoscopy of minimal endometriosis in this setting.
Robert C. Reiter, M.D. Department of Obstetrics and Gynecology University of Iowa College of Medicine Office of Outcomes Evaluation and Management University of Iowa Hospitals and Clinics November 14, 1994
metriosis but some other condition causing the subtle peritoneal changes (3). Nevertheless we have found when performing second-look procedures on patients who did not have any ablative treatment that the disease invariably progressed, so this alone may be a rationale for vaporizing these peritoneal lesions, especially since there was no added hazard in our hands.
Christopher J. G. Sutton M.B., B.Ch. Royal Surry County Hospital Waterden Road Clinic Guildford, Surrey, United Kingdom January 12, 1995
REFERENCES 1. Sutton CJ, Ewen SP, Whitelaw N, Haines P. Prospective, randomized, double-blind, controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal, mild, and moderate endometriosis. Fertil Steri11994; 62:696700. 2. Lichten EM, Bombard J. Surgical treatment of primary dysmenorrhea with laparoscopic uterine nerve ablation. J Repro Med 1987;32:37-41. 3. Ylikorkala 0, Dawood YM. New concepts in dysmenorrhea. Am J Obstet Gynecol 1987; 130:833-40.
Reply of the Author: Thank you for allowing me the opportunity to reply to Dr. Reiter's criticisms of our study (1). He states that our conclusion that "laser laparoscopy is effective for alleviating symptoms associated with endometriosis" is not supported by our data. I refute this suggestion because all the patients in our study had dysmenorrhoea as their main complaint, often associated with noncyclical pelvic pain and dyspareunia. Because the aim of our laser laparoscopic treatment is to alleviate symptoms, it would be nonsensical to exclude laparoscopic uterine nerve ablation since the use of this technique is an integral part ofthe alleviation of the dominant symptom. We made this perfectly clear in our description of the methods and are at the moment in the middle of a similar study comparing laser vaporization of the endometriotic peritoneal implants with and without laparoscopic uterosacral nerve ablation. It is quite wrong to say that laparoscopic uterosacral nerve ablation has been the subject of a randomized, blinded, prospective trial in endometriosis associated with dysmenorrhea because the study of Lichten and Bombard (2) dealt only with a few patients, was performed using electrosurgery, and was entirely for patients with primary dysmenorrhea with no associated pathology. Finally, I would agree that the response was poorest with those with minimal disease and it may be that many of those patients did not in fact have endo1356
Letters-to-the-editor Letters-to-the-editor
REFERENCES 1. Hughes EG, Yeo J, Claman P, YoungLai EV, Sagle MA, Daya S, et al. Cigarette smoking and the outcomes of in vitro fertilization: measurement of effect size and levels of action. Fertil Steril 1994; 62:807 -14. 2. Lichten EM, Bombard J. Surgical treatment of primary dysmenorrhoea with laparoscopic uterine nerve ablation. J Repro Med 1987;32:37-41. 3. Martin DC. Therapeutic laparoscopy. In Martin DC, editor. Laparoscopic appearance of endometriosis. 2nd ed. Vol. 1. Memphis: Resurge Press, 1990:21-9.
Role of Postmenopausal Ovaries in Androgen Production?
To the Editor: The recent work of Adashi (1) regarding the climacteric ovary as a viable androgen-producing site of gonadotropin action and reception strengthens the view that postmenopausal ovaries notably contribute to the steroidogenesis of androgens and through peripheral conversion to estrogens, respectively. To seek the clinical implications of these findings, we would like to discuss postmenopausal androgenproduction with regard to prophylactic oophorectomy at elective hysterectomy. A review ofthe literature on potential benefits of preserved climacteric ovaries at elective surgery reveals quite controversial data. Ohta and associates (2) found no differences in bone mineral density between natural and oophorectomized postmenopausal women, suggesting that the two groups of subjects may be managed in the same way in clinical practice. In animal models evidence has accumulated for a role of androgens in the development and expression of sexuality. However, it is not totally clear if substantially reduced active androgen levels in women after oophorectomy, with advanced ovarian age, or Fertility and Sterility
Bruce A. Lessey, Ph.D., M.D. Division of Reproductive Endocrinology Department of Obstetrics and Gynecology University of North Carolina Chapel Hill, North Carolina Art Castelbaum, M.D. Northern Fertility and Reproductive Associates, P. C. Meadowbrook, Pennsylvania December 7, 1994 REFERENCES 1. Ruck P, Marzusch K, Kaiserling E, Horny H-P, Dietl J, Geiselhart A, et al. Distribution of cell adhesion molecules in decidua of early human pregnancy: an immunohistochemical study. Lab Invest 1994;71:94-101. 2. Lessey BA, Castelbaum AJ, Buck CA, Lei Y, Yowell CW, Sun J. Further characterization of endometrial integrins during the menstrual cycle and in pregnancy. Fertil Steril 1994; 62:497 -506. 3. Lessey BA, Damjanovich L, Coutifaris C, Castelbaum A, AlbeIda SM, Buck CA. Integrin adhesion molecules in the huVol. 63, No.6, June 1995
man endometrium. Correlation with the normal and abnormal menstrual cycle. J Clin Invest 1992;90:188-95. 4. Lessey BA, Castelbaum AJ, Sawin SJ, Buck CA, Schinnar R, Wilkins B, et al. Aberrant integrin expression in the endometrium of women with endometriosis. J Clin Endocrinol Metab 1994;79:643-9.
Efficacy of Laser Laparoscopy in Minimal Endometriosis?
To the Editor: I read with interest the article by Drs. Sutton et al. "Prospective Randomized, Double-Blind, Controlled Trial of Laser Laparoscopy in the Treatment of Pelvic Pain Associated with Minimal, Mild, and Moderate Endometriosis" (1). The authors are to be commended for demonstrating that appropriately controlled studies of operative laparoscopic procedures are indeed feasible. Unfortunately, the authors oft-repeated conclusion that the study "confirms that laser laparoscopy is effective for alleviating symptoms associated with endometriosis," is not supported by their data. Specifically, their study suffers from one significant methodological problem which is that patients were not randomized to laser laparoscopy of endometriosis versus expectant management; rather, they were randomized to laser laparoscopy of endometriosis plus laparoscopic uterosacral nerve ablation versus expectant management. As the authors may know, laparoscopic uterosacral nerve ablation has been shown to result in an 80% response rate for dysmenorrhea in randomized blinded prospective trials involving women without endometriosis (2). Intentionally or not, the authors have not provided a controlled trial of laser laparoscopic treatment of pelvic pain associated with endometriosis, but rather a confirmatory trial of laparoscopic uterosacral nerve ablation for dysmenorrhea. The authors state in the discussion that "enthusiasts of the medical treatment of endometriosis can no longer claim that laser laparoscopy has not been subjected to a placebo-controlled study." In order to have fulfilled this worthwhile goal, the present study should have either included an additional treatment arm (namely expectant management versus laser of endometriosis versus laser of endometriosis plus laparoscopic uterosacral nerve ablation) or should have randomized patients to expectant management versus laser of endometriosis only. Finally, the fact that the authors observed a poor response rate in women with minimal disease raises questions as to whether minimal endometriosis is causally or incidentally asLetters-to-the-editor Letters-to-the-editor
1355
--sociated with significant dysmenorrhea, which is present in 50% ofthe general population (3). For this reason, I would recommend caution against recommending laser laparoscopy of minimal endometriosis in this setting.
Robert C. Reiter, M.D. Department of Obstetrics and Gynecology University of Iowa College of Medicine Office of Outcomes Evaluation and Management University of Iowa Hospitals and Clinics November 14, 1994
metriosis but some other condition causing the subtle peritoneal changes (3). Nevertheless we have found when performing second-look procedures on patients who did not have any ablative treatment that the disease invariably progressed, so this alone may be a rationale for vaporizing these peritoneal lesions, especially since there was no added hazard in our hands.
Christopher J. G. Sutton M.B., B.Ch. Royal Surry County Hospital Waterden Road Clinic Guildford, Surrey, United Kingdom January 12, 1995
REFERENCES 1. Sutton CJ, Ewen SP, Whitelaw N, Haines P. Prospective, randomized, double-blind, controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal, mild, and moderate endometriosis. Fertil Steri11994; 62:696700. 2. Lichten EM, Bombard J. Surgical treatment of primary dysmenorrhea with laparoscopic uterine nerve ablation. J Repro Med 1987;32:37-41. 3. Ylikorkala 0, Dawood YM. New concepts in dysmenorrhea. Am J Obstet Gynecol 1987; 130:833-40.
Reply of the Author: Thank you for allowing me the opportunity to reply to Dr. Reiter's criticisms of our study (1). He states that our conclusion that "laser laparoscopy is effective for alleviating symptoms associated with endometriosis" is not supported by our data. I refute this suggestion because all the patients in our study had dysmenorrhoea as their main complaint, often associated with noncyclical pelvic pain and dyspareunia. Because the aim of our laser laparoscopic treatment is to alleviate symptoms, it would be nonsensical to exclude laparoscopic uterine nerve ablation since the use of this technique is an integral part ofthe alleviation of the dominant symptom. We made this perfectly clear in our description of the methods and are at the moment in the middle of a similar study comparing laser vaporization of the endometriotic peritoneal implants with and without laparoscopic uterosacral nerve ablation. It is quite wrong to say that laparoscopic uterosacral nerve ablation has been the subject of a randomized, blinded, prospective trial in endometriosis associated with dysmenorrhea because the study of Lichten and Bombard (2) dealt only with a few patients, was performed using electrosurgery, and was entirely for patients with primary dysmenorrhea with no associated pathology. Finally, I would agree that the response was poorest with those with minimal disease and it may be that many of those patients did not in fact have endo1356
Letters-to-the-editor Letters-to-the-editor
REFERENCES 1. Hughes EG, Yeo J, Claman P, YoungLai EV, Sagle MA, Daya S, et al. Cigarette smoking and the outcomes of in vitro fertilization: measurement of effect size and levels of action. Fertil Steril 1994; 62:807 -14. 2. Lichten EM, Bombard J. Surgical treatment of primary dysmenorrhoea with laparoscopic uterine nerve ablation. J Repro Med 1987;32:37-41. 3. Martin DC. Therapeutic laparoscopy. In Martin DC, editor. Laparoscopic appearance of endometriosis. 2nd ed. Vol. 1. Memphis: Resurge Press, 1990:21-9.
Role of Postmenopausal Ovaries in Androgen Production?
To the Editor: The recent work of Adashi (1) regarding the climacteric ovary as a viable androgen-producing site of gonadotropin action and reception strengthens the view that postmenopausal ovaries notably contribute to the steroidogenesis of androgens and through peripheral conversion to estrogens, respectively. To seek the clinical implications of these findings, we would like to discuss postmenopausal androgenproduction with regard to prophylactic oophorectomy at elective hysterectomy. A review ofthe literature on potential benefits of preserved climacteric ovaries at elective surgery reveals quite controversial data. Ohta and associates (2) found no differences in bone mineral density between natural and oophorectomized postmenopausal women, suggesting that the two groups of subjects may be managed in the same way in clinical practice. In animal models evidence has accumulated for a role of androgens in the development and expression of sexuality. However, it is not totally clear if substantially reduced active androgen levels in women after oophorectomy, with advanced ovarian age, or Fertility and Sterility