- Email: [email protected]
Discriminatory Zone for Human Chorionic Gonadotropin—Level of Certainty?
development. Regardless of the available procedure, i.e., transport by intravaginal culture, in an isothermic box or even in a portable incubator, this concept will certainly help many patients to benefit from modern techniques of assisted reproduction offered by only a few specialized centers. We admit that it appears more convenient when the husband transports the oocytes immediately after aspiration of follicles instead of waiting for his wife being transferable. However, the high acceptance of the intravaginal capsule reported earlier (2) and the positive reaction of the women must be emphasized once again. Indeed, none of our patients complained or felt uncomfortable. On the other hand, we wonder about the costs for the isothermic box used by Roest et a1. Provided that a network will be established with many patients travelling from several clinics to only one microinsemination center, you will need quite a large number of "Gynotransporters (Gynotec, Amsterdam, The Netherlands)." In this respect, a plastic capsule remains the simplest and cheapest solution. Finally, there seems to be a negligible excess oflaboratory procedures if oocytes are first removed from follicular fluid; this work has to be done sooner or later, no matter at which place.
Karl Sterzik, M.D. Bernd E. Rosenbusch, Ph.D. Department of Gynecology and Obstetrics University of Ulm Ulm, Germany September 23, 1994 REFERENCES 1. Sterzik K, Rosenbusch B, Noss U. First pregnancies after
intravaginal transport and partial zona dissection of human oocytes. Fertil Steril 1993;60:582-4. 2. Sterzik K, Rosenbusch B, Sasse V, Wolf A, Beier HM, Lauritzen C. A new variation of in-vitro fertilization: intravaginal culture of human oocytes and cleavage stages. Hum Reprod 1989;4(Suppl):83-6.
Discriminatory Zone for Human Chorionic Gonadotropin-Level of Certainty?
To the Editor: Kadar et a1. (1) focused on the discriminatory heG zone for endovaginal sonography. In the discussion section of the paper the authors gave their comments on earlier reports which studied the lowVol. 63, No.3, March 1995
est heG concentration at which a gestational sac could be identified, criticizing them for being "preoccupational" and "tangential" to the issue of diagnosing ectopic pregnancy (EP). Kadar and coauthors, however, basically did the same thing, albeit in a more sophisticated study design. Their study was restricted to patients with ongoing viable pregnancies and women who delivered live infants. Those patients in whom EP should be considered from a clinical point of view, i.e., women with miscarriages, EPs and chemical pregnancies, were excluded from the study. The results of the study, therefore, do not allow solid conclusions regarding the diagnosis of EP; an important matter once pointed out by Dr. Kadar himself (2). The authors' conclusion that "if a pregnancy can be dated with a high degree of reliability, failure to detect a gestational sac when gestational age is >38 days (or >24 days postconception) should be taken as presumptive evidence of an EP," therefore, is misleading. Only indirect evidence for this conclusion was provided by the results of the study, while in our own experience, both nonvital intrauterine pregnancies and EPs should also be considered seri0usly under these circumstances (3,4). Although the authors made no recommendations for further management, we hope that they agree that serum heG measurements should be taken into account to guide further steps in these patients in order to prevent unnecessary invasive procedures.
W.M. Ankum, M.D. P.J. Hajenius, M.D. Department of Obstetrics and Gynecology Academy Medical Center University of Amsterdam Amsterdam, The Netherlands August 15, 1994 REFERENCES 1. Kadar N, Bohrer M, Kemmann E, Shelden R. The discriminatory human chorionic gonadotropin zone for endovaginal sonography: a prospective, randomized study. Fertil Steril 1994;61:1016-20. 2. Kadar N. Ultrasonography. In: Diagnosis and treatment of extrauterine pregnancies. Chapt. 6. New York: Raven Press, 1990:56. 3. Ankum WM, Van der Veen F, Hameriynck JVThH, Lammes FB. Laparoscopy: a dispensable tool in the diagnosis of ectopic pregnancy? Hum Reprod 1993;8:1301-6. 4. Ankum WM, Van der Veen F, Hamerlynck JVThH, Lammes FB. Transvaginal sonography in suspected ectopic pregnancy: analysis of the additional value ofhCG-measurements and adnexal findings. Hum Reprod 1993;8:1307-11.
Letters-to-the-editor
683
I Reply of the Author: I would like to thank Drs. Ankum and Hajenius for their interest in our work. I disagree with their conclusion that the point of our paper was to study the "lowest hCG concentration at which a gestational sac could be identified," except with more sophisticated techniques. In the language ofprediction intervals, information that pertains to when gestational sacs are first detectable ultrasonographically correspond, roughly, to the 1st to 10th centile range and has no diagnostic relevance. It is precisely for this reason that our analysis focused on the other end of the distribution curve. I agree entirely that it is not possible to deduce how predictive of an ectopic pregnancy (EP) the failure to detect a gestational sac at a particular hCG is from a study of normal pregnancies alone, nor did I say that one could. I simply suggested that failure to detect a gestational sac above a certain gestational age or hCG concentration should be taken as presumptive evidence of an EP. This conclusion is based not only on our own findings but on the collective evidence and experience that pseudosacs are not detected with a significantly greater frequency with a vaginal ultrasound (US) than with an abdominal one, and the absence of any evidence that abortions might lead to a greater frequency of erroneous diagnoses of EPs if a vaginal rather than an abdominal US is used. In other words, in drawing our conclusions from these data I did not consider them in isolation from other evidence. Thus, the wedge the authors seem to wish to drive between this and my earlier comments is mendacious for when I drew attention to the need to study abnormal pregnancies as well as normal ones in 1989, there was comparatively speaking, still little experience with vaginal US. The situation is somewhat different 5 years later. A meaningful, ethical randomized study involving abnormal pregnancies is simply not feasible in a democratic society. Even if it were, it is doubtful, given the information already available on this subject, that it would lead us to a different conclusion. Parethetically, had patients with abortions or EPs been included in our regression analysis, the conclusions of the study would not have been affected.
Nicholas Kadar, M.D. The Gynecologic Institute Neptune, New Jersey September 8, 1994 684
Letters-to-the-editor
e..... "'"
a..
~
Before Oophorectomy
•
After Oophorectomy
400
2000
300
1500
e 200
~ 1000
100
500 0
0
ANDROSTENEDIONE
TESTOSTERONE
e.,. .....
40
40
30
30
e
20
~
a..
20 10
10
0
0
ESTRONE
ESTRADIOL Erratum
To the Editor: Re: Adashi, KY. The Climacteric Ovary as a Functional Gonadotropin-Driven Androgen-Producing Gland. Fertil Steril 1994;62:20-28. Former Figure 3 in the above article was erroneously inserted instead of a related but distinctly different figure. The affixed figure is the correct one and should be regarded as Figure 3.
Eli Y Adashi MD Departments of Obstetrics/Gynecology and Physiology University of Maryland School of Medicine Baltimore Maryland October 4, 1994 Erratum
To the Editor: Re: Lanzone A, Fulghesu AM, Villa P, Guida C, Guido M, Nicoletti MC, et al. Gonadotropinreleasing hormone agonist versus human chori0nic gonadotropin as a trigger of ovulation in polycystic ovarian disease gonadotropin hyperstimulated cycles. Fertil Steril 1994;62: 35-41. Fertility and Sterility
Karl Sterzik, M.D. Bernd E. Rosenbusch, Ph.D. Department of Gynecology and Obstetrics University of Ulm Ulm, Germany September 23, 1994 REFERENCES 1. Sterzik K, Rosenbusch B, Noss U. First pregnancies after
intravaginal transport and partial zona dissection of human oocytes. Fertil Steril 1993;60:582-4. 2. Sterzik K, Rosenbusch B, Sasse V, Wolf A, Beier HM, Lauritzen C. A new variation of in-vitro fertilization: intravaginal culture of human oocytes and cleavage stages. Hum Reprod 1989;4(Suppl):83-6.
Discriminatory Zone for Human Chorionic Gonadotropin-Level of Certainty?
To the Editor: Kadar et a1. (1) focused on the discriminatory heG zone for endovaginal sonography. In the discussion section of the paper the authors gave their comments on earlier reports which studied the lowVol. 63, No.3, March 1995
est heG concentration at which a gestational sac could be identified, criticizing them for being "preoccupational" and "tangential" to the issue of diagnosing ectopic pregnancy (EP). Kadar and coauthors, however, basically did the same thing, albeit in a more sophisticated study design. Their study was restricted to patients with ongoing viable pregnancies and women who delivered live infants. Those patients in whom EP should be considered from a clinical point of view, i.e., women with miscarriages, EPs and chemical pregnancies, were excluded from the study. The results of the study, therefore, do not allow solid conclusions regarding the diagnosis of EP; an important matter once pointed out by Dr. Kadar himself (2). The authors' conclusion that "if a pregnancy can be dated with a high degree of reliability, failure to detect a gestational sac when gestational age is >38 days (or >24 days postconception) should be taken as presumptive evidence of an EP," therefore, is misleading. Only indirect evidence for this conclusion was provided by the results of the study, while in our own experience, both nonvital intrauterine pregnancies and EPs should also be considered seri0usly under these circumstances (3,4). Although the authors made no recommendations for further management, we hope that they agree that serum heG measurements should be taken into account to guide further steps in these patients in order to prevent unnecessary invasive procedures.
W.M. Ankum, M.D. P.J. Hajenius, M.D. Department of Obstetrics and Gynecology Academy Medical Center University of Amsterdam Amsterdam, The Netherlands August 15, 1994 REFERENCES 1. Kadar N, Bohrer M, Kemmann E, Shelden R. The discriminatory human chorionic gonadotropin zone for endovaginal sonography: a prospective, randomized study. Fertil Steril 1994;61:1016-20. 2. Kadar N. Ultrasonography. In: Diagnosis and treatment of extrauterine pregnancies. Chapt. 6. New York: Raven Press, 1990:56. 3. Ankum WM, Van der Veen F, Hameriynck JVThH, Lammes FB. Laparoscopy: a dispensable tool in the diagnosis of ectopic pregnancy? Hum Reprod 1993;8:1301-6. 4. Ankum WM, Van der Veen F, Hamerlynck JVThH, Lammes FB. Transvaginal sonography in suspected ectopic pregnancy: analysis of the additional value ofhCG-measurements and adnexal findings. Hum Reprod 1993;8:1307-11.
Letters-to-the-editor
683
I Reply of the Author: I would like to thank Drs. Ankum and Hajenius for their interest in our work. I disagree with their conclusion that the point of our paper was to study the "lowest hCG concentration at which a gestational sac could be identified," except with more sophisticated techniques. In the language ofprediction intervals, information that pertains to when gestational sacs are first detectable ultrasonographically correspond, roughly, to the 1st to 10th centile range and has no diagnostic relevance. It is precisely for this reason that our analysis focused on the other end of the distribution curve. I agree entirely that it is not possible to deduce how predictive of an ectopic pregnancy (EP) the failure to detect a gestational sac at a particular hCG is from a study of normal pregnancies alone, nor did I say that one could. I simply suggested that failure to detect a gestational sac above a certain gestational age or hCG concentration should be taken as presumptive evidence of an EP. This conclusion is based not only on our own findings but on the collective evidence and experience that pseudosacs are not detected with a significantly greater frequency with a vaginal ultrasound (US) than with an abdominal one, and the absence of any evidence that abortions might lead to a greater frequency of erroneous diagnoses of EPs if a vaginal rather than an abdominal US is used. In other words, in drawing our conclusions from these data I did not consider them in isolation from other evidence. Thus, the wedge the authors seem to wish to drive between this and my earlier comments is mendacious for when I drew attention to the need to study abnormal pregnancies as well as normal ones in 1989, there was comparatively speaking, still little experience with vaginal US. The situation is somewhat different 5 years later. A meaningful, ethical randomized study involving abnormal pregnancies is simply not feasible in a democratic society. Even if it were, it is doubtful, given the information already available on this subject, that it would lead us to a different conclusion. Parethetically, had patients with abortions or EPs been included in our regression analysis, the conclusions of the study would not have been affected.
Nicholas Kadar, M.D. The Gynecologic Institute Neptune, New Jersey September 8, 1994 684
Letters-to-the-editor
e..... "'"
a..
~
Before Oophorectomy
•
After Oophorectomy
400
2000
300
1500
e 200
~ 1000
100
500 0
0
ANDROSTENEDIONE
TESTOSTERONE
e.,. .....
40
40
30
30
e
20
~
a..
20 10
10
0
0
ESTRONE
ESTRADIOL Erratum
To the Editor: Re: Adashi, KY. The Climacteric Ovary as a Functional Gonadotropin-Driven Androgen-Producing Gland. Fertil Steril 1994;62:20-28. Former Figure 3 in the above article was erroneously inserted instead of a related but distinctly different figure. The affixed figure is the correct one and should be regarded as Figure 3.
Eli Y Adashi MD Departments of Obstetrics/Gynecology and Physiology University of Maryland School of Medicine Baltimore Maryland October 4, 1994 Erratum
To the Editor: Re: Lanzone A, Fulghesu AM, Villa P, Guida C, Guido M, Nicoletti MC, et al. Gonadotropinreleasing hormone agonist versus human chori0nic gonadotropin as a trigger of ovulation in polycystic ovarian disease gonadotropin hyperstimulated cycles. Fertil Steril 1994;62: 35-41. Fertility and Sterility