Correspondence
Correction
Ectopic Pregnancy
N Engl J Med 1994; 330:712-714March 10, 1994
- Article
To the Editor:
In their review of ectopic pregnancy (Oct. 14 issue),1 Carson and Buster propose an algorithm for early diagnosis based on progesterone measurement. In many areas of the country, including our own, progesterone measurement is not available either daily or during initial assessment. This limits the usefulness of the test as a starting point for the routine diagnosis of ectopic pregnancy.
Abnormal serum progesterone levels or serial values for the beta subunit of human chorionic gonadotropin (β-hCG) are not specific to ectopic pregnancy. According to the data of Stovall and Ling,2 only 24 percent of patients with progesterone levels below 5 ng per milliliter had ectopic pregnancies, and only 56 percent of the patients with such pregnancies had levels below 5 ng per milliliter. Although Figure 1 of Carson and Buster implies that patients with intermediate progesterone levels have either viable intrauterine pregnancies or ectopic pregnancies, this clearly omits failing intrauterine pregnancies, which account for over 70 percent of pregnancies in this group. In other reports,3 it seems that the best use of serum progesterone measurement has been to eliminate the need for sonography in the 57 percent of patients whose initial levels are 25 ng per milliliter or more. Sonography is readily available in most centers and may provide valuable data at the first visit or within 24 hours.
For the majority of centers in which rapid progesterone measurement is not available, we propose the following. (1) In patients in stable condition, transvaginal ultrasonography or a β-hCG measurement of 50,000 mIU per milliliter or more (International Reference Preparation) will reveal a viable intrauterine pregnancy2. (2) In the absence of a clear diagnosis of an ectopic or intrauterine pregnancy by ultrasonography, serial observations and measurement of hCG are indicated. (3) If the β-hCG level falls or rises by less than 50 percent in two days, the possibility of an ectopic pregnancy can be excluded in many patients by performing dilation and curettage, which will identify a failed intrauterine pregnancy. (4) If the diagnosis is still unclear, serial observations and aggressive follow-up are indicated.
Critical to early diagnosis of ectopic pregnancy is consideration of the diagnosis in any woman with vaginal bleeding or pain in the first trimester, careful instructions to the patient, and the use of modern sonographic techniques correlated with measurement of β-hCG. The benefit of routinely adding serum progesterone measurement to the algorithm has yet to be established.
3 ReferencesJean Abbott, M.D.
University of Colorado School of Medicine, Denver, CO 80262Jedd Roe, M.D.
Denver General Hospital, Denver, CO 802041
Carson SA ,Buster JE . Ectopic pregnancy. N Engl J Med 1993;329:1174-1181
Full Text | Web of Science | Medline2
Stovall TG ,Ling FW . Ectopic pregnancy: diagnostic and therapeutic algorithms minimizing surgical intervention. J Reprod Med 1993;38:807-812
Web of Science | Medline3
Stovall TG ,Kellerman AL ,Ling FW ,Buster JE . Emergency department diagnosis of ectopic pregnancy. Ann Emerg Med 1990;19:1098-1103
CrossRef | Web of Science | Medline
To the Editor:
Carson and Buster state that a serum progesterone level less than or equal to 5 ng per milliliter can identify nonviable pregnancies with 100 percent sensitivity. A test with 100 percent sensitivity would be able to identify every such pregnancy. Sensitivity is determined by dividing the number of patients with a diagnosis and a positive test by the total number of patients with the diagnosis.1 Since the authors state “with progesterone values above 5 and below 25 ng per milliliter, viability must be established by ultrasonography,” a low progesterone level will not identify 100 percent of nonviable pregnancies. What they should have said, and probably meant, was that a serum progesterone value of 5 ng per milliliter or less will identify nonviable pregnancies with 100 percent specificity, indicating zero false positive tests in the diagnosis of nonviable pregnancy.
1 ReferencesBrian Budenholzer, M.D.
Group Health Northwest, Spokane, WA 99206To the Editor:
Transvaginal ultrasonography provides a definitive diagnosis in approximately 90 percent of women at risk for ectopic pregnancy1. Unfortunately, the algorithm of Carson and Buster (their Figure 1) does not direct the care of the 10 percent who have ultrasonograms with indeterminate findings and require further diagnostic evaluation. Women with indeterminate ultrasonograms and β-hCG measurements within the “discriminatory zone” -- that is, values above the level at which all intrauterine pregnancies would be diagnosed on transvaginal ultrasonography -- should be presumed to have ectopic pregnancies. Women whose values fall below the discriminatory zone remain the most difficult cohort with respect to diagnosis. In their study of vaginal ultrasonography, in which they used the value of 1000 mIU of β-hCG per milliliter (International Reference Preparation) as the cutoff for the discriminatory zone, Cacciatore et al. found that 26 percent of women with indeterminate ultrasonograms (5 of 19) had ectopic pregnancies and, of these, 40 percent (2 of 5) had β-hCG values of less than 1000 mIU per milliliter1.
Contrary to the algorithm presented, the possibility of ectopic pregnancy cannot be completely excluded when the serum progesterone level exceeds 25 ng per milliliter or the β-hCG level is greater than 100,000 mIU per milliliter. Stovall et al. reported that 3.1 percent of ectopic pregnancies (5 of 161) were associated with progesterone levels over 25 ng per milliliter2. In our collective experience at San Francisco General Hospital and Boston City Hospital, 0.7 percent of ectopic pregnancies (2 of 297) involved β-hCG levels greater than 100,000 mIU per milliliter.
2 ReferencesTom Scaletta, M.D.
Beth C. Kaplan, M.D.
University of California, San Francisco, San Francisco, CA 941101
Cacciatore B ,Stenman UH ,Ylostalo P . Diagnosis of ectopic pregnancy by vaginal ultrasonography in combination with a discriminatory serum hCG level of 1000 IU/l (IRP). Br J Obstet Gynaecol 1990;97:904-908
CrossRef | Medline2
Stovall TG ,Kellerman AL ,Ling FW ,Buster JE . Emergency department diagnosis of ectopic pregnancy. Ann Emerg Med 1990;19:1098-1103
CrossRef | Web of Science | Medline
To the Editor:
In their otherwise excellent review of ectopic pregnancy, Carson and Buster state “Transvaginal ultrasound visualizes many ectopic gestations; intrauterine pregnancies may also be imaged, thus ruling out ectopic pregnancy.” The finding of an intrauterine pregnancy does not rule out a coexisting ectopic pregnancy. Coexisting ectopic and intrauterine pregnancies were once considered very rare, occurring in only 1 in 30,000 pregnancies, but recent literature suggests a much higher incidence (1 in 4000)1. The increase is due primarily to the use of exogenous pituitary gonadotropin to treat sterility2 and the rising use of in vitro fertilization3,4. In addition, the increasing incidence of sexually transmitted diseases and pelvic inflammatory disease puts women at higher risk for ectopic pregnancy. Establishing the existence of an intrauterine pregnancy by ultrasonography does not rule out a coexisting ectopic pregnancy5.
5 ReferencesMarc R. Salzberg, M.D.
Baystate Medical Center, Springfield, MA 011991
Ben-Rafael Z ,Carp HJ ,Mashiach S ,Blankstein J ,Serr DM . The clinical features and incidence of concurrent intra and extra uterine pregnancies. J Acta Eur Fertil 1985;16:199-202
Medline2
Dietz TU ,Haenggi W ,Birkhaeuser M ,Gyr T ,Dreher E . Combined bilateral tubal and multiple intrauterine pregnancy after ovulation induction. Eur J Obstet Gynecol Reprod Biol 1993;48:69-71
CrossRef | Web of Science | Medline3
Chang JC ,Sun TT ,Lin YC . Simultaneous ectopic pregnancy with intrauterine gestation after in vitro fertilization and embryo transfer. Chang Keng I Hsueh 1991;14:197-201
Medline4
Rizk B ,Tan SL ,Morcos S , et al. Heterotopic pregnancies after in vitro fertilization and embryo transfer. Am J Obstet Gynecol 1991;164:161-164
Web of Science | Medline5
Hayes HR ,Haley EC . Intrauterine and ruptured tubal ectopic pregnancy: a diagnostic challenge. Ann Emerg Med 1984;13:355-358
CrossRef | Web of Science | Medline
To the Editor:
Carson and Buster fail to mention that ectopic pregnancy can result in Rh sensitization of an Rh-negative woman due to fetomaternal hemorrhage. Rh antigens have been detected on fetal red cells as early as 38 days after conception,1 and Rh sensitization after tubal pregnancy has been reported in the Journal2. All patients with ectopic pregnancies should undergo blood sampling for typing. Those who are Rh-negative should receive Rho(D) immune globulin (unless the father is known to be D-negative) according to the current recommendations of the American College of Obstetricians and Gynecologists3.
3 ReferencesJames W. Kendig, M.D.
Fred M. Howard, M.D.
JoAnn S. Janas, M.D.
Rochester General Hospital, Rochester, NY 146211
Bergstrom H ,Nilsson LA ,Nilsson L ,Ryttinger L . Demonstration of Rh antigens in a 38-day-old fetus. Am J Obstet Gynecol 1967;99:130-133
Web of Science | Medline2
Aborjaily AN . Rh sensitization after tubal pregnancy. N Engl J Med 1969;281:1076-1076
Web of Science | Medline3
Prevention of D-isoimmunization. Technical bulletin no. 147. Washington, D.C.: American College of Obstetricians and Gynecologists, October 1990.
Author/Editor Response
The authors reply:
To the Editor: The point of Kendig et al. is well taken. We perhaps mistakenly assumed that readers would know that Rh-negative patients require RhoD immune globulin after an ectopic pregnancy. The American College of Obstetricians and Gynecologists has widely distributed this information in its technical bulletins.
Oops! We regret using “sensitivity” for “specificity,” and thank Dr. Budenholzer for pointing out our error.
A single measurement of progesterone will identify patients at risk for ectopic pregnancy earlier than will screening with ultrasonography. Thus, the figure of 90 percent to which Scaletta and Kaplan refer is not applicable. They describe data from studies in which the ultrasonography was used as the instrument of selection -- not progesterone measurement. Indeed, they state that when the β-hCG level is 1000 mIU per milliliter or less, ultrasonography gives indeterminate results and other techniques such as curettage are required. Of course, no test is perfect. In our initial study, only 5 of 1136 patients (0.4 percent) with progesterone levels above 25 ng per milliliter had ectopic pregnancies. A single serum progesterone measurement costs about $20; an ultrasonogram costs approximately 10 times more. The radioimmunoassay for progesterone is available in commercial kits and takes four hours to perform; there is no reason that it cannot be made available daily. It is simply a matter of using it with sufficient frequency to justify the cost.
Drs. Abbott and Roe misunderstood our point regarding the use of screening progesterone levels. The single progesterone measurement is a screening test that alerts the physician to whether a patient needs diagnostic testing; the measurement is not in itself a diagnostic test. Sonography is 10 times more expensive than progesterone measurement. Furthermore, an abnormally low progesterone level alerts the physician to the possibility of an ectopic pregnancy at a time in gestation when such a pregnancy would be undetectable by ultrasonography; this has enabled our institution to reduce the rate of rupture in ectopic pregnancy from 79.2 percent to 38.8 percent.1
Although Dr. Salzberg's points are true, our review was written for the general medical community, which has found heterotopic pregnancy to be a very rare event, occurring once in 30,000 pregnancies; therefore, establishing the presence of an intrauterine pregnancy by ultrasonography will correctly rule out an ectopic pregnancy 29,999 times in 30,000. A patient undergoing gonadotropin therapy or in vitro fertilization will probably be followed by her reproductive endocrinologist until the location of the pregnancy is defined.
1 ReferencesSandra A. Carson, M.D.
John E. Buster, M.D.
University of Tennessee, Memphis, TN 381631
Stovall TG ,Ling FW ,Cope BJ ,Buster JE . Preventing ruptured ectopic pregnancy with a single serum progesterone. Am J Obstet Gynecol 1989;160:1425-1431
Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Verena T. Valley, James R. Mateer, E. James Aiman, Margaret E. Tkoma, Mary Beth Phelan. (1998) Serum Progesterone and Endovaginal Sonography by Emergency Physicians in the Evaluation of Ectopic Pregnancy. Academic Emergency Medicine 5:4, 309-313
CrossRef
