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Uterine fibroids—impact on IVF and outcome of IVF pregnancies
FERTILITY AND STERILITY威 VOL. 82, NO. 3, SEPTEMBER 2004
LETTERS TO THE EDITOR
Copyright ©2004 American Society for Reproductive Medicine Published by Elsevier Inc. Printed on acid-free paper in U.S.A.
Paul G. McDonough, M.D. Associate Editor
Uterine fibroids—impact on IVF and outcome of IVF pregnancies To the Editor: The conclusions of Oliveira et al. (1) in the article regarding the influence of large intramural fibroids on fertility misrepresent the data presented. We applaud the authors for undertaking a much-needed investigation of this subject and for writing an excellent report. However, they state that the outcome with large fibroids was worse than with smaller fibroids and suggest that it might be reasonable to remove such fibroids before IVF/intracytoplasmic sperm injection. The appropriate comparison should be how women with large fibroids compare with the control group (245 women with no fibroids). Our analysis of these data show that the 41 women who had intramural fibroids between 4 and 7 cm and not impinging on the endometrial cavity had pregnancy rates not statistically different from those of the control group (odds ratio ⫽ 0.578, Wald 95% confidence interval 0.248 – 1.042, P⫽0.0887). Delivery rates, the only important issue for patients, were not provided for women with fibroids ⬎4 cm, but the delivery rates for all women with fibroids were no different than for women without fibroids, nor did premature delivery rates differ. Additionally, this study might not have had the statistical power to demonstrate a difference even if there was one. To achieve that goal with an ␣ ⫽ 0.05 and power ⫽ 80%, a relative sample size of 6 controls to 1 fibroid patient, and the pregnancy rates seen in this study, the required sample size would be 91 in the fibroid group and 546 controls. More importantly, demonstrating a lower pregnancy or live birth rate in the presence of 4 –7-cm myomas does not demonstrate that their removal improves success; for that, a properly designed and analyzed treatment trial would be needed. The authors rightly refer to the risks of adhesions, blood loss, and infection associated with myomectomy. Issues of recovery, cost, and delay in pursuing fertility should be considered. A meta-analysis (2) found no association between intramural myomas and fertility and failed to find support for improvement in fertility after myomectomy. We thus have no evidence at present to support myomectomy for intramural, non– cavity-distorting fibroids of any size. As Oliveira and others suggest, it is time that a prospective, randomized, controlled investigation of this important issue be performed. Perhaps the Society for Reproductive Surgeons could organize such a study. In that 36,000 myomectomies are performed in the United States per year (and
many more worldwide), it should not take long to obtain guidance for physicians and the women with fibroids for whom they provide care. William H. Parker, M.D. University of California Los Angeles Santa Monica, California Elizabeth A. Pritts, M.D. David L. Olive, M.D. Department of Obstetrics and Gynecology University of Wisconsin Medical School Madison, Wisconsin May 10, 2004 doi:10.1016/j.fertnstert.2004.06.002
References 1. Oliveira F, Abdelmassih V, Diamond M, Dozortsev D, Melo N, Abdelmassih R. Impact of subserosal and intramural uterine fibroids that do not distort the endometrial cavity on the outcome of in vitro fertilizationintracytoplasmic sperm injection. Fertil Steril 2004;81:582–7. 2. Pritts E. Fibroids and infertility: a systematic review of the evidence. Obstet Gynecol Surv 2001;56:483–91.
doi:10.1016/j.fertnstert.2004.06.002
Reply of the Authors: To begin with, we would like to thank Dr. Parker and collegues for the important considerations concerning our study, focused on such a controversial subject. Our main goal was to assess whether uterine leiomyomas (subserosal or intramural, without distortion of the endometrial cavity) ⬍7 cm (mean diameter) had any impact on IVF-intracytoplasmic sperm injection (ICSI) outcomes. To answer this question, we compared the IVF-ICSI outcomes of patients with such uterine fibroids to patients without any fibroids. Both groups were submitted to a transvaginal ultrasound scan before starting the treatment. The patients were retrospectively matched by age and number of retrieved oocytes to control for other variables (1). On the basis of our results, we suggested that patients with leiomyomas ⬍4 cm (mean diameter) probably would not benefit from myomectomy before ICSI because they had outcomes similar to those of patients without such fibroids. The appropriate counseling and the correct management of patients with fibroids with a mean diameter of 4 –7 cm was not clear because they had lower pregnancy rates, lower implantation rates, and, obviously, lower live birth rates than patients with fibroids ⬍4 cm and their respective controls 763
LETTERS TO THE EDITOR
Copyright ©2004 American Society for Reproductive Medicine Published by Elsevier Inc. Printed on acid-free paper in U.S.A.
Paul G. McDonough, M.D. Associate Editor
Uterine fibroids—impact on IVF and outcome of IVF pregnancies To the Editor: The conclusions of Oliveira et al. (1) in the article regarding the influence of large intramural fibroids on fertility misrepresent the data presented. We applaud the authors for undertaking a much-needed investigation of this subject and for writing an excellent report. However, they state that the outcome with large fibroids was worse than with smaller fibroids and suggest that it might be reasonable to remove such fibroids before IVF/intracytoplasmic sperm injection. The appropriate comparison should be how women with large fibroids compare with the control group (245 women with no fibroids). Our analysis of these data show that the 41 women who had intramural fibroids between 4 and 7 cm and not impinging on the endometrial cavity had pregnancy rates not statistically different from those of the control group (odds ratio ⫽ 0.578, Wald 95% confidence interval 0.248 – 1.042, P⫽0.0887). Delivery rates, the only important issue for patients, were not provided for women with fibroids ⬎4 cm, but the delivery rates for all women with fibroids were no different than for women without fibroids, nor did premature delivery rates differ. Additionally, this study might not have had the statistical power to demonstrate a difference even if there was one. To achieve that goal with an ␣ ⫽ 0.05 and power ⫽ 80%, a relative sample size of 6 controls to 1 fibroid patient, and the pregnancy rates seen in this study, the required sample size would be 91 in the fibroid group and 546 controls. More importantly, demonstrating a lower pregnancy or live birth rate in the presence of 4 –7-cm myomas does not demonstrate that their removal improves success; for that, a properly designed and analyzed treatment trial would be needed. The authors rightly refer to the risks of adhesions, blood loss, and infection associated with myomectomy. Issues of recovery, cost, and delay in pursuing fertility should be considered. A meta-analysis (2) found no association between intramural myomas and fertility and failed to find support for improvement in fertility after myomectomy. We thus have no evidence at present to support myomectomy for intramural, non– cavity-distorting fibroids of any size. As Oliveira and others suggest, it is time that a prospective, randomized, controlled investigation of this important issue be performed. Perhaps the Society for Reproductive Surgeons could organize such a study. In that 36,000 myomectomies are performed in the United States per year (and
many more worldwide), it should not take long to obtain guidance for physicians and the women with fibroids for whom they provide care. William H. Parker, M.D. University of California Los Angeles Santa Monica, California Elizabeth A. Pritts, M.D. David L. Olive, M.D. Department of Obstetrics and Gynecology University of Wisconsin Medical School Madison, Wisconsin May 10, 2004 doi:10.1016/j.fertnstert.2004.06.002
References 1. Oliveira F, Abdelmassih V, Diamond M, Dozortsev D, Melo N, Abdelmassih R. Impact of subserosal and intramural uterine fibroids that do not distort the endometrial cavity on the outcome of in vitro fertilizationintracytoplasmic sperm injection. Fertil Steril 2004;81:582–7. 2. Pritts E. Fibroids and infertility: a systematic review of the evidence. Obstet Gynecol Surv 2001;56:483–91.
doi:10.1016/j.fertnstert.2004.06.002
Reply of the Authors: To begin with, we would like to thank Dr. Parker and collegues for the important considerations concerning our study, focused on such a controversial subject. Our main goal was to assess whether uterine leiomyomas (subserosal or intramural, without distortion of the endometrial cavity) ⬍7 cm (mean diameter) had any impact on IVF-intracytoplasmic sperm injection (ICSI) outcomes. To answer this question, we compared the IVF-ICSI outcomes of patients with such uterine fibroids to patients without any fibroids. Both groups were submitted to a transvaginal ultrasound scan before starting the treatment. The patients were retrospectively matched by age and number of retrieved oocytes to control for other variables (1). On the basis of our results, we suggested that patients with leiomyomas ⬍4 cm (mean diameter) probably would not benefit from myomectomy before ICSI because they had outcomes similar to those of patients without such fibroids. The appropriate counseling and the correct management of patients with fibroids with a mean diameter of 4 –7 cm was not clear because they had lower pregnancy rates, lower implantation rates, and, obviously, lower live birth rates than patients with fibroids ⬍4 cm and their respective controls 763