- Email: [email protected]
Diagnosis of endometriosis: utility of MRI?
and cleavage stages compares favourably with day 5 blastocyst transfer. Hum Reprod 2002;17:1852–5. 5. Fisch JD, Rodriguez H, Ross R, Overby G, Sher G. The graduated embryo score (GES) predicts blastocyst formation and pregnancy rate from cleavage-stage embryos. Hum Reprod 2001;16:1970 –5. 6. Milki AA, Hinckley MD, Gebhardt J, Dasig D, Westpal LM, Behr B. Accuracy of day 3 criteria for selecting the best embryos. Fertil Steril 2002;77:1191–5.
doi:10.1016/S0015-0282(03)01130-0
Reply of the Authors: We appreciate Drs. Correa-Pe´ rez and Ferna´ ndez-Pelegrina’s interest in our work. We do not disagree with the spirit of their comments, but we wish to clarify some of the details. A prospective study, in which transfers are randomly assigned to day 3 or day 5, would be a better way of comparing these two techniques. Several investigators (1–3) have done this, but not specifically for patients older than 40 years of age. We believe that our study provides valuable preliminary data, that may encourage a randomized prospective study in this age group. During the study, we had no good feel for what technique worked best and offered either day 3 or day 5 transfer to patients older than 40 with four or more 8-cell embryos. This process may have introduced an unintended selection bias. The suggestion to assign patients with a minimum number of zygotes to either day 3 or day 5 transfer would be a reasonable approach for a prospective study. In clinical practice, however, we have found it more relevant to assess the number of good embryos on day 3 before making a decision. It is not uncommon for patients with multiple zygotes, especially older patients, to fail to produce 8-cell embryos and accordingly become poor candidates for extended culture (4). The alternative suggestion is “to compare patients who made their choice on day 3 but were similar in terms of number and quality of embryos transferred.” We did compare patients who were similar in number of 8-cell embryos available; however, the number of embryos transferred was significantly higher on day 3, as one would expect, given the lower implantation rate of cleavage-stage embryos compared with blastocysts (1, 3–5). As we discussed, the risk of not conceiving rather than the risk of “overconceiving” is the major gamble among women with a mean age of 41.6 years, and in most U.S. programs, the transfer of a high number of day 3 embryos is justified. This prevailing tendency leads to significantly fewer cycles with excess embryos available for cryopreservation and may decrease the cumulative pregnancy rate. Use of stringent selection criteria that follow the embryo through pronuclear morphology and early 2-cell cleavage on day 1, day 2 multinucleation, and day 3 morphology may sharpen our ability to select the best cleavage-stage embryo. There is no consensus, however, about the accuracy of these FERTILITY & STERILITY威
criteria. In addition, their implementation requires individual embryo culture and multiple thorough examinations outside the incubator. We believe that if several good-quality embryo are available, blastocyst culture is a practical and more reliable tool for selecting the best for transfer. The information gained from extended culture may be an added benefit in older women by shedding light on embryo quality and more clearly guiding future therapy, including oocyte donation. Amin A. Milki, M.D. Mary D. Hinckley, M.D. Barry Behr, Ph.D. Department of Gynecology and Obstetrics Stanford University School of Medicine Stanford, California May 30, 2003
References 1. Gardner DK, Schoolcraft WB, Wagley L, Schlenker T, Stevens J, Hesla J. A prospective randomized trial of blastocyst culture and transfer in human in vitro fertilization. Hum Reprod 1998;13:3434 –40. 2. Coskun S, Hollanders J, Al-Hassan S, Al-Sufyan H, Al-Mayman H, Jaroudi K. Day 5 versus day 3 embryo transfer: a controlled randomized trial. Hum Reprod 2000;15:1947–52. 3. Karaki RZ, Samarraie SS, Younie NA, Lahloub TM, Ibrahim MH. Blastocyst culture and transfer: a step toward improved in vitro fertilization outcome. Fertil Steril 2002;77:114 –8. 4. Racowsky C, Jackson KV, Cekleniak NA, Fox JH, Hornstein MD, Ginsburg ES. The number of eight-cell embryos is a key determinant for selecting day three or day five transfer. Fertil Steril 2000;73:558 –64. 5. Milki AA, Hinckley MD, Fisch JD, Dasig D, Behr B. Comparison of blastocyst transfer with day 3 embryo transfer in similar patient populations. Fertil Steril 2000;73:126 –9.
doi:10.1016/S0015-0282(03)01131-2
Diagnosis of endometriosis: utility of MRI? To the Editor: In the study by Stratton et al. (1), magnetic resonance imaging did not appear to offer a reliable alternative to diagnostic laparoscopy across the spectrum of endometriosis. However, if endometriosis on peritoneal surfaces is a consequence of abnormal uterine contractility secondary to different patterns of neurologic dysfunction, perhaps some clearer relationships might be established. Advanced nulliparous endometriosis (American Fertility Society stage IV) is regularly observed in women who have sustained expulsive efforts to achieve defecation and can be demonstrated by both diagnostic techniques. Minor parous endometriosis is frequently observed some time after difficult obstetric episodes (e.g., after prolonged or premature maternal voluntary efforts) and may lead to reduced specificity for both techniques. Myofascial injuries during parturition, including damage to the uterosacral and transverse cervical ligaments, are associated with denervation and subsequent reinnervation of the uterus (2). Uncoordinated activity of subserosal and endometrial–myometrial nerve plexi may be expected to result in abnormal uterine contractility (3). Gamete transport and 1071
disordered menstrual function are direct consequences, with endometrium being deposited at sites of intraperitoneal damage—for example, hyperplastic uterosacral ligaments in nulliparous women who strain to evacuate their bowels or the scarred vaginal insertions of the uterosacral ligaments after difficult intrapartum episodes. Chronic pain is the consequence of progressive reinnervation of myofascial supports over the medium term. Intrinsic damage to uterine innervation, as by a single asymmetric uterine leiomyomata, or extrapelvic damage to uterine innervation, as by accidents, falls, or traffic accidents may cause different presentations. Disordered uterine contractility associated with aberrant neural repair in and around uterine myofascial supports may account for many of the manifestations of “endometriosis.” If this hypothesis is confirmed, diagnostic techniques might be tailored to address clinical issues that will vary with the specific etiology and subsequent natural history of the condition. Martin Quinn, M.D., M.R.C.O.G. Richard Slade, F.R.C.S., M.R.C.O.G. Hope Hospital Salford, Manchester, United Kingdom May 15, 2003
References
Reply of the Authors: The purpose of our study was to determine whether currently available MRI technology was useful in diagnosing endometriosis (1). In this context, MRI had limited utility because we could not determine the extent of disease or identify small peritoneal lesions. Drs. Quinn and Slade present some interesting implications about the potential for neurologic dysfunction or fascial damage in the etiology of endometriosis. The issue of etiology or coincident conditions of endometriosis alluded to in this letter, is beyond the scope of our paper. On the basis of Drs. Quinn and Slade’s suggestion, perhaps additional studies should be considered. Pamela Stratton, M.D. Craig Winkel, M.D. Ahalya Premkumar, M.D. Catherine Chow, M.D. Jan Wilson, R.N. Rhonda Hearns-Stokes, M.D. Sun Yeong Heo, Ph.D. Maria Merino, M.D. Lynnette K. Nieman, M.D. Warren G. Magnusen Clinical Center National Institutes of Health Bethesda, Maryland May 28, 2003
1. Stratton P, Winkel C, Premkumar A, Chow C, Wilson J, Hearns-Stokes R, et al. Diagnostic accuracy of laparoscopy, magnetic resonance imaging, and histopathologic examination for the detection of endometriosis. Fertil Steril 2003;79:1078 –85. 2. Quinn MJ, Kirk N. Differences in uterine innervation at hysterectomy. Am J Obstet Gynecol 2002;187:1515–20. 3. Kunz G, Beil D, Huppert P, Leyendecker G. Structural abnormalities of the uterine wall in women with endometriosis and infertility visualized by vaginal sonography and magnetic resonance imaging. Hum Reprod 2000;15:76 –82.
Reference
doi:10.1016/S0015-0282(03)01132-4
doi:10.1016/S0015-0282(03)01133-6
1. Stratton P, Winkel C, Premkumar A, Chow C, Wilson J, Hearns-Stokes R, et al. Diagnostic accuracy of laparoscopy, magnetic resonance imaging, and histopathologic examination for the detection of endometriosis. Fertil Steril 2003;79:1078 –85.
Vol. 80, No. 4, October 2003
1072
doi:10.1016/S0015-0282(03)01130-0
Reply of the Authors: We appreciate Drs. Correa-Pe´ rez and Ferna´ ndez-Pelegrina’s interest in our work. We do not disagree with the spirit of their comments, but we wish to clarify some of the details. A prospective study, in which transfers are randomly assigned to day 3 or day 5, would be a better way of comparing these two techniques. Several investigators (1–3) have done this, but not specifically for patients older than 40 years of age. We believe that our study provides valuable preliminary data, that may encourage a randomized prospective study in this age group. During the study, we had no good feel for what technique worked best and offered either day 3 or day 5 transfer to patients older than 40 with four or more 8-cell embryos. This process may have introduced an unintended selection bias. The suggestion to assign patients with a minimum number of zygotes to either day 3 or day 5 transfer would be a reasonable approach for a prospective study. In clinical practice, however, we have found it more relevant to assess the number of good embryos on day 3 before making a decision. It is not uncommon for patients with multiple zygotes, especially older patients, to fail to produce 8-cell embryos and accordingly become poor candidates for extended culture (4). The alternative suggestion is “to compare patients who made their choice on day 3 but were similar in terms of number and quality of embryos transferred.” We did compare patients who were similar in number of 8-cell embryos available; however, the number of embryos transferred was significantly higher on day 3, as one would expect, given the lower implantation rate of cleavage-stage embryos compared with blastocysts (1, 3–5). As we discussed, the risk of not conceiving rather than the risk of “overconceiving” is the major gamble among women with a mean age of 41.6 years, and in most U.S. programs, the transfer of a high number of day 3 embryos is justified. This prevailing tendency leads to significantly fewer cycles with excess embryos available for cryopreservation and may decrease the cumulative pregnancy rate. Use of stringent selection criteria that follow the embryo through pronuclear morphology and early 2-cell cleavage on day 1, day 2 multinucleation, and day 3 morphology may sharpen our ability to select the best cleavage-stage embryo. There is no consensus, however, about the accuracy of these FERTILITY & STERILITY威
criteria. In addition, their implementation requires individual embryo culture and multiple thorough examinations outside the incubator. We believe that if several good-quality embryo are available, blastocyst culture is a practical and more reliable tool for selecting the best for transfer. The information gained from extended culture may be an added benefit in older women by shedding light on embryo quality and more clearly guiding future therapy, including oocyte donation. Amin A. Milki, M.D. Mary D. Hinckley, M.D. Barry Behr, Ph.D. Department of Gynecology and Obstetrics Stanford University School of Medicine Stanford, California May 30, 2003
References 1. Gardner DK, Schoolcraft WB, Wagley L, Schlenker T, Stevens J, Hesla J. A prospective randomized trial of blastocyst culture and transfer in human in vitro fertilization. Hum Reprod 1998;13:3434 –40. 2. Coskun S, Hollanders J, Al-Hassan S, Al-Sufyan H, Al-Mayman H, Jaroudi K. Day 5 versus day 3 embryo transfer: a controlled randomized trial. Hum Reprod 2000;15:1947–52. 3. Karaki RZ, Samarraie SS, Younie NA, Lahloub TM, Ibrahim MH. Blastocyst culture and transfer: a step toward improved in vitro fertilization outcome. Fertil Steril 2002;77:114 –8. 4. Racowsky C, Jackson KV, Cekleniak NA, Fox JH, Hornstein MD, Ginsburg ES. The number of eight-cell embryos is a key determinant for selecting day three or day five transfer. Fertil Steril 2000;73:558 –64. 5. Milki AA, Hinckley MD, Fisch JD, Dasig D, Behr B. Comparison of blastocyst transfer with day 3 embryo transfer in similar patient populations. Fertil Steril 2000;73:126 –9.
doi:10.1016/S0015-0282(03)01131-2
Diagnosis of endometriosis: utility of MRI? To the Editor: In the study by Stratton et al. (1), magnetic resonance imaging did not appear to offer a reliable alternative to diagnostic laparoscopy across the spectrum of endometriosis. However, if endometriosis on peritoneal surfaces is a consequence of abnormal uterine contractility secondary to different patterns of neurologic dysfunction, perhaps some clearer relationships might be established. Advanced nulliparous endometriosis (American Fertility Society stage IV) is regularly observed in women who have sustained expulsive efforts to achieve defecation and can be demonstrated by both diagnostic techniques. Minor parous endometriosis is frequently observed some time after difficult obstetric episodes (e.g., after prolonged or premature maternal voluntary efforts) and may lead to reduced specificity for both techniques. Myofascial injuries during parturition, including damage to the uterosacral and transverse cervical ligaments, are associated with denervation and subsequent reinnervation of the uterus (2). Uncoordinated activity of subserosal and endometrial–myometrial nerve plexi may be expected to result in abnormal uterine contractility (3). Gamete transport and 1071
disordered menstrual function are direct consequences, with endometrium being deposited at sites of intraperitoneal damage—for example, hyperplastic uterosacral ligaments in nulliparous women who strain to evacuate their bowels or the scarred vaginal insertions of the uterosacral ligaments after difficult intrapartum episodes. Chronic pain is the consequence of progressive reinnervation of myofascial supports over the medium term. Intrinsic damage to uterine innervation, as by a single asymmetric uterine leiomyomata, or extrapelvic damage to uterine innervation, as by accidents, falls, or traffic accidents may cause different presentations. Disordered uterine contractility associated with aberrant neural repair in and around uterine myofascial supports may account for many of the manifestations of “endometriosis.” If this hypothesis is confirmed, diagnostic techniques might be tailored to address clinical issues that will vary with the specific etiology and subsequent natural history of the condition. Martin Quinn, M.D., M.R.C.O.G. Richard Slade, F.R.C.S., M.R.C.O.G. Hope Hospital Salford, Manchester, United Kingdom May 15, 2003
References
Reply of the Authors: The purpose of our study was to determine whether currently available MRI technology was useful in diagnosing endometriosis (1). In this context, MRI had limited utility because we could not determine the extent of disease or identify small peritoneal lesions. Drs. Quinn and Slade present some interesting implications about the potential for neurologic dysfunction or fascial damage in the etiology of endometriosis. The issue of etiology or coincident conditions of endometriosis alluded to in this letter, is beyond the scope of our paper. On the basis of Drs. Quinn and Slade’s suggestion, perhaps additional studies should be considered. Pamela Stratton, M.D. Craig Winkel, M.D. Ahalya Premkumar, M.D. Catherine Chow, M.D. Jan Wilson, R.N. Rhonda Hearns-Stokes, M.D. Sun Yeong Heo, Ph.D. Maria Merino, M.D. Lynnette K. Nieman, M.D. Warren G. Magnusen Clinical Center National Institutes of Health Bethesda, Maryland May 28, 2003
1. Stratton P, Winkel C, Premkumar A, Chow C, Wilson J, Hearns-Stokes R, et al. Diagnostic accuracy of laparoscopy, magnetic resonance imaging, and histopathologic examination for the detection of endometriosis. Fertil Steril 2003;79:1078 –85. 2. Quinn MJ, Kirk N. Differences in uterine innervation at hysterectomy. Am J Obstet Gynecol 2002;187:1515–20. 3. Kunz G, Beil D, Huppert P, Leyendecker G. Structural abnormalities of the uterine wall in women with endometriosis and infertility visualized by vaginal sonography and magnetic resonance imaging. Hum Reprod 2000;15:76 –82.
Reference
doi:10.1016/S0015-0282(03)01132-4
doi:10.1016/S0015-0282(03)01133-6
1. Stratton P, Winkel C, Premkumar A, Chow C, Wilson J, Hearns-Stokes R, et al. Diagnostic accuracy of laparoscopy, magnetic resonance imaging, and histopathologic examination for the detection of endometriosis. Fertil Steril 2003;79:1078 –85.
Vol. 80, No. 4, October 2003
1072