- Email: [email protected]
Power Enough?—Confidence intervals for uncertainity: Reply of the Authors:
in their ultrasonography-guided group compared to the control group (59.9% vs. 55.1% and 30.6% vs. 26.3%, respectively), although the differences were not statistically significant. We urge the authors to continue with their study to eliminate the possibility of type II error. Hassan N. Sallam, M.D., F.R.C.O.G., Ph.D. (London) Sameh Saad-el-Din, M.D. Department of Obstetrics and Gynaecology The University of Alexandria Alexandria, Egypt October 28, 2002
References 1. Garcia-Velasco A, Isaza V, Martinez-Salazar J, Landazabal A, Requena A, Remohi J, et al. Transabdominal ultrasound-guided embryo transfer does not increase pregnancy rates in oocyte recipients. Fertil Steril 2002;78:534 –9. 2. Sallam HN, Agameya AF, Rahman AF, Ezzeldin F, Sallam AN. Ultrasound measurement of the uterocervical angle before embryo transfer: a prospective controlled study. Hum Reprod 2002;17:1767–72. 3. Sallam HN, Saad-el-Din S. Performing embryo transfer under ultrasound-guidance—a meta-analysis of randomized trials. Fertil Steril 2002;78(Suppl 1):S46.
doi:10.1016/S0015-0282(02)04933-6
significant role in the outcome of ET, only well-selected prospective randomized trials should be included in a metaanalysis, to reach clear conclusions. Most of the data on transabdominal ultrasonography– guided ET come from retrospective data analysis. A few randomized controlled trials later appeared. We await meta-analysis or cumulative metaanalysis. Until then, we are performing a harmless technique that has not proved to be beneficial in terms of pregnancy rates but does increase patient confidence and satisfaction. Juan A. Garcia-Velasco, M.D. Carlos Simon, M.D. Instituto Valenciano de Infertilidad Madrid, Spain November 14, 2002
References 1. Garcia-Velasco A, Isaza V, Martinez-Salazar J, Landazabal A, Requena A, Remohi J, et al. Transabdominal ultrasound-guided embryo transfer does not increase pregnancy rates in oocyte recipients. Fertil Steril 2002;78:534 –9. 2. Mansour RT, Aboulghar M. Optimizing the embryo transfer technique. Hum Reprod 2002;17:1149 –53.
doi:10.1016/S0015-0282(02)04934-8
Reply of the Authors: We thank Dr. Meldrum, as well as Dr. Sallam and Dr. Saad-el-Din, for their compliments and interest in our recent publication that attempted to investigate further whether a single intervention, such as transabdominal ultrasonography– guided embryo transfer would significantly increase implantation and pregnancy rates (1). We agree with Dr. Meldrum that comparison of techniques is difficult, especially after recent publications claiming that such minor issues as the distance from the top of the uterine cavity to the tip of the catheter or the volume of medium accompanying the embryos play a crucial role in the final outcome (2). In our patients who had blind ET, we did not perform the transfer using a fixed distance from the tip to the external cervical os. Because previous randomized, controlled trials showed a 15% increase in the current pregnancy rate, we decided to test the same intervention in a different sample with less confounding variables as those in oocyte recipients, who all undergo similar endometrial priming and receive only goodquality embryos from young donors. We therefore designed a study with the classic parameters of 80% power and a 5% chance of rejecting the null hypothesis. Our results did not reach significant differences; thus, the trend we observed could be due to chance and not to a real effect of the intervention. As both authors pointed out, meta-analysis will improve statistical power. At the time of our publication, the study by Sallam and Saad-el-Din was not available, so we could not comment on it. Because so many different variables play a
Editorial Commentary
Power enough? Confidence intervals for uncertainty The study by Garcia-Velasco and colleagues is an important addition to discussions of the relative merits of “blind” versus ultrasonography-guided embryo transfer. The group in back of this study headed by Antonio Pellicer and Carlos Simon is now located in Madrid. One can be certain, with narrow confidence intervals, that this study will be frequently cited in the future literature on this topic. However, both Doctors Meldrum and Sallam caution as to the dangers of misinterpretation of nonsignificant results, when the analysis of the sample data is unable to document the difference statistically. It is obvious that one of the difficulties of clinical testing is defining the study power that is necessary to detect real, clinically worthwhile differences. With a  of 0.20, an effect size of 15%, and a corresponding power of 80%, the authors have taken a reasonable protection against a type II error. In his letter, Doctor Sallam suggests that the sample size estimates were overly optimistic in expecting to have an 80% probability of detecting a difference of 15% or greater between the two groups. The quantitative boundary designed to establish superiority seems to be large. One wonders if an effect size of 15% with a possible overall success rate of 65% is beyond the inherent efficiency of most assisted reproductive programs. A smaller effect size would require more patients and may have influenced the prestudy power calculations. It is normal for researchers to feel uncertain about advance power calculations because the Vol. 79, No. 4, April 2003
1040
References 1. Garcia-Velasco A, Isaza V, Martinez-Salazar J, Landazabal A, Requena A, Remohi J, et al. Transabdominal ultrasound-guided embryo transfer does not increase pregnancy rates in oocyte recipients. Fertil Steril 2002;78:534 –9. 2. Sallam HN, Agameya AF, Rahman AF, Ezzeldin F, Sallam AN. Ultrasound measurement of the uterocervical angle before embryo transfer: a prospective controlled study. Hum Reprod 2002;17:1767–72. 3. Sallam HN, Saad-el-Din S. Performing embryo transfer under ultrasound-guidance—a meta-analysis of randomized trials. Fertil Steril 2002;78(Suppl 1):S46.
doi:10.1016/S0015-0282(02)04933-6
significant role in the outcome of ET, only well-selected prospective randomized trials should be included in a metaanalysis, to reach clear conclusions. Most of the data on transabdominal ultrasonography– guided ET come from retrospective data analysis. A few randomized controlled trials later appeared. We await meta-analysis or cumulative metaanalysis. Until then, we are performing a harmless technique that has not proved to be beneficial in terms of pregnancy rates but does increase patient confidence and satisfaction. Juan A. Garcia-Velasco, M.D. Carlos Simon, M.D. Instituto Valenciano de Infertilidad Madrid, Spain November 14, 2002
References 1. Garcia-Velasco A, Isaza V, Martinez-Salazar J, Landazabal A, Requena A, Remohi J, et al. Transabdominal ultrasound-guided embryo transfer does not increase pregnancy rates in oocyte recipients. Fertil Steril 2002;78:534 –9. 2. Mansour RT, Aboulghar M. Optimizing the embryo transfer technique. Hum Reprod 2002;17:1149 –53.
doi:10.1016/S0015-0282(02)04934-8
Reply of the Authors: We thank Dr. Meldrum, as well as Dr. Sallam and Dr. Saad-el-Din, for their compliments and interest in our recent publication that attempted to investigate further whether a single intervention, such as transabdominal ultrasonography– guided embryo transfer would significantly increase implantation and pregnancy rates (1). We agree with Dr. Meldrum that comparison of techniques is difficult, especially after recent publications claiming that such minor issues as the distance from the top of the uterine cavity to the tip of the catheter or the volume of medium accompanying the embryos play a crucial role in the final outcome (2). In our patients who had blind ET, we did not perform the transfer using a fixed distance from the tip to the external cervical os. Because previous randomized, controlled trials showed a 15% increase in the current pregnancy rate, we decided to test the same intervention in a different sample with less confounding variables as those in oocyte recipients, who all undergo similar endometrial priming and receive only goodquality embryos from young donors. We therefore designed a study with the classic parameters of 80% power and a 5% chance of rejecting the null hypothesis. Our results did not reach significant differences; thus, the trend we observed could be due to chance and not to a real effect of the intervention. As both authors pointed out, meta-analysis will improve statistical power. At the time of our publication, the study by Sallam and Saad-el-Din was not available, so we could not comment on it. Because so many different variables play a
Editorial Commentary
Power enough? Confidence intervals for uncertainty The study by Garcia-Velasco and colleagues is an important addition to discussions of the relative merits of “blind” versus ultrasonography-guided embryo transfer. The group in back of this study headed by Antonio Pellicer and Carlos Simon is now located in Madrid. One can be certain, with narrow confidence intervals, that this study will be frequently cited in the future literature on this topic. However, both Doctors Meldrum and Sallam caution as to the dangers of misinterpretation of nonsignificant results, when the analysis of the sample data is unable to document the difference statistically. It is obvious that one of the difficulties of clinical testing is defining the study power that is necessary to detect real, clinically worthwhile differences. With a  of 0.20, an effect size of 15%, and a corresponding power of 80%, the authors have taken a reasonable protection against a type II error. In his letter, Doctor Sallam suggests that the sample size estimates were overly optimistic in expecting to have an 80% probability of detecting a difference of 15% or greater between the two groups. The quantitative boundary designed to establish superiority seems to be large. One wonders if an effect size of 15% with a possible overall success rate of 65% is beyond the inherent efficiency of most assisted reproductive programs. A smaller effect size would require more patients and may have influenced the prestudy power calculations. It is normal for researchers to feel uncertain about advance power calculations because the Vol. 79, No. 4, April 2003
1040