1240 Correspondence
hope we all hold for the vaginal probe (which cannot be prejudged), refinements in the use of serial hCG testing are required if such cases are to be optimally managed. Ultrasound is, quite simply, not always diagnostic, and given the history there was a high probability that adhesions would have prevented adequate inspection of the pelvic organs had one proceeded straight to laparoscopy. There is, therefore, a firm place for serial hCG level testing in the management of a minority of cases suspected of having an ectopic pregnancy. This in no way removes the clinician's obligation to take account of the clinical situation, nor is the necessity to consider the complete picture an argument against serial hCG testing.
What is a mistake is to rely on qualitative impressions of "tests" rather than to establish objective criteria for such tests, so that their utility and reproducibility can be tested in the community at large. We refer here to terms such as "plateauing" and "falling" hCG levels that are being used increasingly with diagnostic implications. No definition of what constitutes a plateau in paired blood samples has been established, and although a fall in hCG levels identifies a pregnancy as nonviable, it remains to be determined whether the rate of fall, as determined in paired samples, helps to separate ectopic pregnancy and spontaneous abortion. If it does not, that too needs to be documented. Neither our attempt to address these issues, nor the great deal of attention that has recently been focussed on the diagnostic value of serial hCG testing in cases of suspected ectopic pregnancy should be taken to indicate that we consider this to be appropriate in more than a minority of cases, perhaps 10% to 20%.
Nicholas Kadar, MD Department of Obstetrics and Gynecology Hahnemann University Broad and Vine Streets Philadelphia, PA 19102-1192
Roberto Romero, MD Department of Obstetrics and Gynecology Yale-New Haven Hospital New Haven, CT 06510
REFERENCES
l. Kadar N, Romero R. hCG determinations in early pregnancy. Fertil Steril1987;47:722.
2. Kadar N, DeVore G, Romero R. Discriminatory hCG zone: its use in the sonographic evaluation for ectopic pregnancy. Obstet Gyneco11981;58:158.
3. Legarth J, Nielsen PL. Freeze microscopy of the endometrium in ectopic pregnancy. Acta Gynecol Scand 1980;59:505.
Reply To the Editors:
Our report has generated a most interesting response from Drs. Kadar and Romero. In our study human chorionic gonadotropin (hCG) was measured with a commercially available immunoradiometric monoclonal antibody kit, Tandem-R-HCG (Hybritech Inc.,
May 1988 Am J Obstet Gynecol
San Diego, Calif.). This assay has been standardized to the World Health Organization First International Reference Preparation (1RP #75/537). Thus a concentration of 5620 miU/ml would not have exceeded the discriminatory zone on July 20, before tubal rupture. Endometrial curettage would have failed to demonstrate chorionic villi. As Drs. Kadar and Romero point out, this would not have ruled out the possibility of a spontaneously resolving intrauterine pregnancy, because by their estimate only 10% of these demonstrate chorionic villi on curettage. The presence of chorionic villi obviously speaks for itself in ruling out an extrauterine pregnancy and therein would lie its value. In this patient the ectopic pregnancy ruptured while on the way to the operating room for dilation and curettage.
Dr. Gretz and I fully agree that the significance (or lack thereof) of the rate of decline in hCG levels must be documented and reported. We also agree that ultrasound has its limitations (as demonstrated in this report) and await more information on the usefulness of the vaginal probe in early pregnancy disorders. Until then, clinicians will undoubtedly continue to pay attention to the rate of decline in hCG levels and to make clinical decisions (as we did) based upon it.
We look forward to Drs. Kadar and Romero resolving this issue for us one way or the other.
John Quagliarello, MD Department of Obstetrics and Gynecology New York University School of Medicine New York, NY 10016
Clarification of the College's stand on universal screening
To the Editors: It has come to my attention that in the May issue an
article by Weiner et a!. regarding the diagnosis of gestational diabetes (Weiner CP, Faustick MW, Burns J, eta!. Diagnosis of gestational diabetes by capillary blood samples and a portable reflectance meter: Derivatives of threshold values and prospective validation. AM J 0BSTET GYNECOL 1987;156:1085-9) indicates that the College recommends universal screening. This is not the case. The AGOG Standards for Obstetric/Gynecologic Services recommends that because maternal age does become a significant risk factor at age 30 years, routine screening should be instituted by this time. The presence of other risk factors, of course, would indicate screening at an earlier age.
Harold A. Kaminetzky, MD The American College of Obstetricians and Gynecologists 600 Maryland Ave., SW Washington, DC 20024-2588
Reply To the Editors:
Dr. Kaminetzky has identified an error in the introduction to our recent report on the use of capillary
Volume 158 Number 5
glucose measurements for the diagnosis of gestational diabetes. We apologize for misleading the readers on the position of the American College. Perhaps a separate issue is whether or not age 30 years is an appropriate recommendation. At the University oflowa, 74% of patients with gestational diabetes are under 30 years old. 1 Furthermore, there is no significant increase in the percentage of patients with a positive glucose tolerance test by age group until after age 36 years. Additional information supporting the importance of screening all patients is contained in The Proceedings of the Second International Workshop-Conference on Gestational Diabetes Mellitus? Thus the threshold of age 30 years may be in need of reconsideration.
Carl P. Weiner, MD Division of Maternal-Fetal Medicine Department of Obstetrics and Gynecology University of Iowa College of Medicine Iowa City, lA 52242
REFERENCES 1. Weiner CP, Fraser MM, Burns JM, Schnoor D, Herrig J,
Whitaker LA. Cost efficacy of routine screening for diabetes in pregnancy: 1-h versus 2-h specimen. Diabetes Care 1986;9:255-9.
2. National Diabetes Data Group. Second summary and recommendations of the international workshop-conference on gestational diabetes mellitus. Diabetes 1985;34(suppl2): 123-66.
Diabetes and spontaneous abortion To the Editors:
We read with interest the recent article by H. Kalter, "Diabetes and spontaneous abortion: A historical review" (AMJ 0BSTET GYNECOL 1987;156:1243-53). Dr. Kalter is unconvinced that there is a higher incidence of abortion in the diabetic pregnancy. We would like to address a few issues in his article.
Dr. Kalter was concerned that one study excluded congenital malformations in the calculation of abortion rates. However, studies of "normal" populations routinely exclude malformations in calculation of the abortion rate. Thus the "problem" appears moot. Congenital malformations may reflect a different form of maternal insult and it is not inherently apparent that malformation rates should be mixed with abortion data. Nevertheless, in a recent study malformed fetuses were not excluded, and the statistical significance of the findings did not change. 1
Dr. Kalter is concerned that women who "experienced increased risk of reproductive mishap" would enter a diabetes study and potentially bias the results. However, in the study mentioned above, 1 primiparous women only were analyzed separately and the results were similar.
Dr. Kalter also wonders about the randomness of the composition in the Cincinnati studies2
·1 because "the
ratios of the White classes in the American reports are somewhat different." If Dr. Kalter had done careful statistical analysis on these numbers, he would have
Correspondence 1241
found that the ratios of the White classes in the studies did not differ significantly from one study to the other.
Dr. Kalter quotes the article by Mills5 that reports no differences in frequencies of spontaneous abortion between control pregnancies and diabetic pregnancies. This publication, which was abstracted in Diabetes in 1984, has not been published yet.
Finally, we are surprised that in his extensive review, Dr. Kalter neglected completely the literature on experimental animals, which shows clearly that diabetes per se is a significant cause of fetal loss. As an example, there is in the pregnant rat with streptozotocin-induced diabetes a fetal resorption rate of 35%, compared with 5% in controls.6
In summary, we believe that both the animal data and the significant relationship between glycemic control and the rate of abortions in human insulindependent diabetes mellitus give evidence that insulindependent diabetes is an additional independent risk factor for spontaneous abortion.
Menachem Miodovnik, MD Francis Mimouni, MD
Reginald C. Tsang, MB, BS Jane Holroyde, BS
Department of Obstetrics and Gynecology University of Cincinnati Medical Center 23 I Bethesda Ave. Cincinnati, OH 45267-0526
REFERENCES I. Mimouni F. Miodovnik M, Tsang RC, et a!. Decreased ma
ternal serum magnesium concentration and adverse fetal outcome in insulin-dependent diabetic women. Obstet Gynecol 1987;70:85-8.
2. Miodovnik M, Lavin JP, Knowles HC, et al. Spontaneous abortion among insulin-dependent diabetic women. AM J 0BSTET GYNECOL 1984;150:372-5.
3. Miodovnik M, Skillman C, Holroyde JC, et a!. Elevated maternal hemoglobin A 1 in early pregnancy and spontaneous abortion among insulin-dependent diabetic women. AM j 0BSTET GYNECOL 1985; 153:439-42.
4. Miodovnik M, Mimouni F, Tsang RC, et a!. Glycemic control and spontaneous abortion in insulin-dependent diabetic women. Obstet Gynecol 1986;68:366-9.
5. Mills J. A prospective study of fetal losses in diabetic and control pregnancies from the third week post conception. Diabetes 1984;33:46A.
6. Eriksson U, Dahltrom E, Larsson S, et a!. Increased incidence of congenital malformations in the offspring of diabetic rats and their prevention by maternal insulin therapy. Diabetes 1982;30:1-6.
Reply
To the Editors: The authors of the preceding letter, in the final anal
ysis, fail to give any reason to dispel my doubt that there is an elevated frequency of spontaneous abortion in insulin-dependent diabetic pregnancies.
One of their rejoinders apparently reflects a misunderstanding of a point of mine: namely, that a pregnancy that eventuates in a child with a malformation is obviously not an abortion, and hence cannot be omitted