Clinical value of pregnancy-specific beta 1-glycoprotein (SP1) and beta-hCG determination in serum in suspected ectopic pregnancy

We compared the clinical value of pregnancy-specific beta 1-glycoprotein (SP1) determination in serum by means of a highly sensitive enzyme-linked immunosorbent assay (ELISA) versus that of beta human chorionic gonadotropin (beta-hCG) determination in suspected ectopic pregnancy. The study comprised 58 women admitted consecutively with suspected ectopic pregnancy but without signs warranting immediate surgical intervention. Both SP1 and beta-hCG were found in 11 patients with ectopic pregnancy and in 8 patients with early intra-uterine pregnancy, whereas beta-hCG was detected in 4 and SP1 in 7 of 8 women with a recent abortion. Of 31 women presenting a non-pregnant condition, 2 were positive for both SP1 and beta-hCG. The measurement of SP1 in serum thus appears to be an alternative to beta-hCG measurement when ectopic pregnancy is suspected.     

Serum estradiol as an aid in the diagnosis of ectopic pregnancy.

The value of serum beta-hCG measurement in the diagnosis of ectopic pregnancy is well established, and there have been recent studies on the use of serum progesterone levels. However, we have been unable to find any reports on the potential application of serum estradiol (E2) assays in the diagnosis of ectopic pregnancy. We therefore concurrently measured serum E2, progesterone, and beta-hCG in 100 women with ectopic pregnancies, as well as in 69 controls with normal intrauterine pregnancies and 36 women with threatened abortion. The mean (+/- standard deviation) E2 levels for ectopic-pregnancy patients, the normal controls, and the women with threatened abortion were 281.1 +/- 115.6, 788.2 +/- 45.5, and 788.8 +/- 40.6 pg/mL, respectively; the mean levels in the ectopic group were significantly different (P less than .0001) from those of the other two groups. All but one of the ectopic pregnancies had values below 650 pg/mL for E2 and 23 ng/mL for progesterone, and all but one of the normal intrauterine pregnancies had values above these levels. Our data suggest that the addition of the estradiol assay, with or without progesterone, to the early evaluation of patients suspected of having an ectopic pregnancy may be helpful in diagnosis.     

Predicting pregnancy outcome after in vitro fertilization and embryo transfer using estradiol, progesterone, and human chorionic gonadotropin beta-subunit

Two hundred twenty consecutive in vitro fertilization (IVF) conception cycles were studied prospectively in order to examine the predictive value of serum human chorionic gonadotropin beta-subunit (beta-hCG), estradiol (E2), and progesterone (P) in predicting pregnancy outcome between 2 and 4 weeks after oocyte collection. To examine the predictive value of each hormone in predicting clinical pregnancy outcome, each patient's result at each week was assigned a scoring system based on the 25th percentile value of the concentration of beta-hCG, E2, and P in ongoing singleton IVF pregnancies for each week of the study. All but one ectopic pregnancies had scores of 0 or 1 points between 2 and 4 weeks after oocyte collection. The scores in successful pregnancies were significantly higher than in unsuccessful pregnancies 2 weeks after oocyte collection. Ninety percent of women scoring 3 points 2 weeks after oocyte collection had ongoing IVF pregnancies. The authors conclude that determination of serum beta-hCG, E2, and P concentrations between 2 and 4 weeks after oocyte collection provides clinically useful information not only in the prediction of ectopic IVF pregnancy, but also, conversely, in the identification of IVF pregnancies that are destined to be ongoing.     

The predictive value of hCG beta subunit levels in pregnancies achieved by in vitro fertilization and embryo transfer: an international collaborative study

Serial human chorionic gonadotropin (hCG) beta subunit measurements of 300 pregnancies achieved by in vitro fertilization (IVF) were obtained by 15 IVF centers worldwide. Hormonal curves were established for 164 normal singleton pregnancies, 25 normal multiple gestations, 60 chemical pregnancies, 41 first-trimester spontaneous abortions, and 10 ectopic pregnancies. In comparison to the normal singleton pregnancy curve, chemical pregnancies and spontaneous abortions showed statistically lower hCG levels. hCG levels of ectopic pregnancies, compared with normal singleton gestations, were lower from days 7 to 14. It is concluded that beta-hCG determinations of in vitro fertilized pregnancies allow pregnancy diagnosis as early as 7 to 9 days after embryo transfer (ET) and will permit early discrimination between normal and abnormal IVF pregnancies. A single beta-hCG determination on day 9 after ET may discriminate chemical, ectopic pregnancy or impending miscarriage from a normal gestation. An hCG determination on day 17 will predict early normal development of an IVF pregnancy.     

Diagnosis of ectopic pregnancy by vaginal ultrasonography in combination with a discriminatory serum hCG level of 1000 IU/1 (IRP)

Summary. The diagnostic value of vaginal sonography in combination with a discriminatory serum hCG level of 1000 iu/1 (International Reference Preparation) was tested prospectively in 200 pregnant women suspected of having an ectopic pregnancy. An ectopic pregnancy was diagnosed in 68 women (34%), a miscarriage in 56 (28%) and a normal pregnancy in 76 (38%). On admission, an intrauterinc sac was seen in 89% of the intrauterinc pregnancies, but in none of the ectopic pregnancies. Detection of an adnexal mass separate from the ovaries was diagnostic of ectopic pregnancy with a sensitivity of 93%, a specificity of 99%, a positive predictive value of 98% and a negative predictive value of 96%. Tn 19 patients (9%) the initial sonogram was non-diagnostic and the final diagnosis was obtained after a repeated scan within 6 days. Five of these women had an ectopic pregnancy, 12 a miscarriage and two a normal pregnancy. On admission the hCG level exceeded 1000 iu/1 in 77% of all patients and in 67% of those with ectopic pregnancies. In patients with an initial level exceeding 1000 iu/1, an intrauterine sac was found in all the intrauterine pregnancies but in none of the ectopic pregnancies. The use of this threshold in combination with sonographic detection of an adnexal mass was diagnostic of ectopic pregnancy with a sensitivity of 97%, a specificity of 99%, a positive predictive value of 98% and a negative predictive value of 98%.     

A contemporary approach to suspected ectopic pregnancy with use of quantitative and qualitative assays for the beta-subunit of human chorionic gonadotropin and sonography

Although assays for the beta-subunit of human chorionic gonadotropin (beta-hCG) and ultrasonography have become popular diagnostic aids in the approach to patients with a suspected ectopic pregnancy, their true utility has not been clearly defined; in fact, the beta-hCG assay is so sensitive that proper clinical interpretation is sometimes difficult. A recent study describing a "discriminatory zone" (beta-hCG level of 6000 to 6500 mIU/ml), which correlates beta-hCG levels with appearance of a gestational sac on ultrasound scans, has been reported to be of diagnostic benefit. A prospective study of 103 women with suspected ectopic pregnancy was undertaken utilizing an algorithm which included beta-hCG assays (quantitative as well as qualitative) and ultrasonography. Seventy-three patients were found not to be pregnant, and seven had a normal pregnancy, 14 patients ultimately had a spontaneous abortion, and seven ectopic pregnancies were identified. The following conclusions were drawn: (1) a qualitative beta-hCG assay with a sensitivity of 25 mIU/ml is an effective test in screening for ectopic pregnancies; (2) the concept of a "discriminatory zone" is valid but not of frequent clinical utility, since most patients suspected of having an ectopic gestation have beta-hCG levels below this zone; (3) serial monitoring of beta-hCG values is an important diagnostic aid; (4) culdocentesis is still an important contemporary diagnostic test for the patient suspected of ectopic pregnancy.     

Diagnosis of ectopic pregnancy by vaginal ultrasonography in combination with a discriminatory serum hCG level of 1000 IU/l (IRP)

The diagnostic value of vaginal sonography in combination with a discriminatory serum hCG level of 1000 iu/l (International Reference Preparation) was tested prospectively in 200 pregnant women suspected of having an ectopic pregnancy. An ectopic pregnancy was diagnosed in 68 women (34%), a miscarriage in 56 (28%) and a normal pregnancy in 76 (38%). On admission, an intrauterine sac was seen in 89% of the intrauterine pregnancies, but in none of the ectopic pregnancies. Detection of an adnexal mass separate from the ovaries was diagnostic of ectopic pregnancy with a sensitivity of 93%, a specificity of 99%, a positive predictive value of 98% and a negative predictive value of 96%. In 19 patients (9%) the initial sonogram was non-diagnostic and the final diagnosis was obtained after a repeated scan within 6 days. Five of these women had an ectopic pregnancy, 12 a miscarriage and two a normal pregnancy. On admission the hCG level exceeded 1000 iu/l in 77% of all patients and in 67% of those with ectopic pregnancies. In patients with an initial level exceeding 100 iu/l, an intrauterine sac was found in all the intrauterine pregnancies but in none of the ectopic pregnancies. The use of this threshold in combination with sonographic detection of an adnexal mass was diagnostic of ectopic pregnancy with a sensitivity of 97%, a specificity of 99%, a positive predictive value of 98% and a negative predictive value of 98%.     

The use of transvaginal ultrasonography in the diagnosis of ectopic pregnancy

Despite advances in diagnosis made by the introduction of serum beta-subunit of human chorionic gonadotropin determinations and transabdominal ultrasonography, ectopic gestations still present a major diagnostic challenge. The increased resolution of the transvaginally introduced high-frequency ultrasound transducer probes seems to solve this diagnostic problem. In this study 145 patients were referred for ultrasonographic workup because of a suspected ectopic gestation. In 38 patients a diagnosis could be made with classical transabdominal scanning. One hundred seventeen patients required additional transvaginal scanning with a 5.0 and a 6.5 MHz probe. In 98 patients a diagnosis was made during the first transvaginal scan; nine patients were rescanned within 3 days for the final diagnosis. In 56 patients, ectopic pregnancy was successfully ruled out by transvaginal scanning. Thirty-nine ectopic pregnancies were diagnosed. Only one false-positive identification was made. The sensitivity of diagnosing ectopic pregnancy by high-frequency transvaginal sonography was 100%; the specificity was 98.2%. The positive predictive value of this method was 98%, and the negative predictive value was 100%. The rate of the beating fetal heart was seen in the tube (23%). The high number of unruptured tubal pregnancies in this series (66%) suggests the possibility of an early diagnosis that may have therapeutic implications. The use of higher-frequency transvaginal transducer probes improves the diagnosis of the ectopic gestation.     

beta-Subunit of human chorionic gonadotropin, ultrasound, and ectopic pregnancy: a prospective study

This prospective study shows that the beta-subunit of human chorionic gonadotropin (beta-hCG) "screen" and ultrasound provide for nearly 100% clinical accuracy in diagnosing ectopic pregnancy in suspected cases. During the 14 months from February, 1981, to April, 1982, 81 consecutive patients believed to have ectopic pregnancies were screened. Fifty-six had a negative beta-hCG screen, thus ruling out early pregnancy complications. No false negative results were found. Twenty-seven patients had a positive screen, and 16 of these had an ectopic pregnancy. Twenty of the 27 patients with a positive beta-hCG screen underwent pelvic ultrasound examination. All of those with a positive beta-hCG screen and no intrauterine pregnancy on ultrasound had ectopic pregnancies. With the use of these clinical aids, morbidity and tubal damage are reduced because delay in operating upon those with ectopic pregnancy is avoided. Unnecessary operation is avoided in those patients who do not have an ectopic pregnancy.     

Diagnosis of ectopic pregnancy: value of the discriminatory human chorionic gonadotropin zone

A prospective study was conducted to test the hypothesis that the absence of an intrauterine gestational sac when the serum level of human chorionic gonadotropin (hCG) is above 6500 mIU/mL is indicative of ectopic pregnancy. A total of 383 patients who were clinically suspected to have ectopic pregnancies had pelvic ultrasound examinations with serum hCG determinations on the day of the scan. There were 217 (57%) intrauterine gestations, 104 (27%) ectopic pregnancies, and 62 (16%) spontaneous abortions. Forty-one percent of patients had an hCG level above 6500 mIU/mL. The absence of an intrauterine gestational sac at an hCG concentration above this level had a sensitivity of 100%, a specificity of 96%, a positive predictive value of 86%, a negative predictive value of 100%, and was 98% efficient, based on a 19.4% prevalence of ectopic pregnancies among this group.     

Hysteroscopic diagnosis of ectopic pregnancy.

Although vaginal ultrasonography combined with plasma beta-hCG determination can provide a reliable diagnosis and location of ectopic pregnancy, the results can be difficult to interpret in the early stages when hCG levels are low. Hysteroscopy can be used in such cases to differentiate between ectopic pregnancy and non-viable uterine pregnancy when viable uterine pregnancy has been ruled out. General anaesthesia and laparoscopy are avoided. We performed 60 hysteroscopic procedures between January 1989 and December 1990 in patients with suspected ectopic pregnancies. The pregnancy had been located by means of vaginal ultrasonography in every case in which the hCG was above 1500 IU/ml and in 36% of cases in which the beta-hCG was below this level. Hysteroscopy was hindered by metrorrhagia in three cases and was inconclusive in one, necessitating laparoscopy. Diagnosis was possible in all the remaining cases, as follows: ectopic pregnancy in 41 cases, with an empty uterus and occasional bleeding from an ostium; non-viable uterine pregnancy in 18 cases, with the presence of material within the cavity. Hysteroscopy therefore confirmed the diagnosis in 55% of the cases and was itself diagnostic in a further 43% of cases. Its sensitivity for the diagnosis of ectopic pregnancy was 100% and its specificity 95%. We propose a diagnostic decision tree.     

Predictive value of hormone determinations in the first half of pregnancy

In a prospective randomized study serial hormone determinations (beta-hCG, HPL, P, 17-OHP, E2 and E3) were performed with 1125 pregnant women from the detection of pregnancy until delivery (n = 994) or abortion (n = 131). In 605 women carrying to term blood sampling started before the 16th wk of gestation, while 389 patients were admitted to hospital between the 16th and 20th wk of gestation. The first value of most of the hormone determinations at the time of diagnosis of pregnancy before the 16th wk was normal in more than 90% (beta-hCG 95%, P 94%, E3 94%, E2 92%, HPL 64%). In the case of women with abortion the first hormone determination was low in more than 50% (beta-hCG 51%, P 56%, E3 54%, E2 62%, HPL 62%). The predictive value was highest for beta-hCG (75%) and E2 (70%) and lowest for HPL (18%). In 249 women with threatened abortion blood samples were obtained at the first days of bleeding. At this time the highest sensitivity in detecting early abortions (before the 16th wk of pregnancy) was 82% for E2, followed by beta-hCG 74%, E3 65%, P 63%, 17-OHP 52% and HPL 34% (n = 112). In late abortion (after the 16th wk of pregnancy, n = 19) the sensitivity of all methods tested was below 40%. In the case of women with bleeding and continuation of pregnancy (n = 118) normal values were found in 95% by P, 94% by beta-hCG, 93% by HPL and E3, and 83% by 17-OHP respectively. Serial determinations in women with abortion revealed that in a normal population trophoblastic disorders with reduced beta-hCG concentrations were most common. Of the remaining patients with normal beta-hCG concentrations every third woman had low P or E2 values. The combined determination of all hormones allowed conclusions to be drawn on the cause of pregnancy failure. It could be established that prior to the 6th wk of pregnancy the determination of beta-hCG was most valuable. From the 7th wk onwards the measurement of E2 or E3 showed the highest sensitivity. Between the 11th and 14th wk of pregnancy the discriminating potency of all methods tested was equally high. After the 14th wk of pregnancy hormone determinations were of little diagnostic value.     

Evaluation of leukemia inhibitory factor as a marker of ectopic pregnancy

OBJECTIVE: Our purpose was to determine the utility of measuring serum leukemia inhibitory factor, a cytokine expressed in the process of pregnancy implantation, for the diagnosis of ectopic pregnancy. STUDY DESIGN: Serum samples from 40 patients with positive serum quantitative beta-human chorionic gonadotropin levels were used for leukemia inhibitory factor determination. The serum leukemia inhibitory factor concentration was determined by enzyme-linked immunosorbent assay in the following 4 groups: (1) normal intrauterine pregnancies, (2) threatened abortions, (3) spontaneous abortions, and (4) ectopic pregnancies. RESULTS: All patients had detectable concentrations of leukemia inhibitory factor in serum, ranging from 2.44 to 8.25 pg/mL. Mean leukemia inhibitory factor concentrations for ectopic pregnancy were significantly lower (P <.05) than those of both the spontaneous abortion and threatened abortion groups by 1-way analysis of variance. When a cutoff point of serum leukemia inhibitory factor <6.2 pg/mL is assigned as diagnostic of ectopic pregnancy, leukemia inhibitory factor in patients with ectopic pregnancies versus all other groups predicted ectopic pregnancy with a sensitivity of 73%, specificity of 72%, positive predictive value of 50%, and negative predictive value of 88%. CONCLUSION: Serum leukemia inhibitory factor concentration is lowest in patients with ectopic pregnancy. A cutoff point of 6.2 pg/mL maximizes the sensitivity and specificity of the test; however, it is not sufficiently discriminatory to be used clinically for the diagnosis of ectopic pregnancy.     

Treatment of ectopic pregnancy by transvaginal intratubal methotrexate administration

Twelve women with tubal pregnancies were treated with intratubal transvaginal methotrexate injection (1 mg/kg body weight). Serum beta-hCG levels decreased in all patients, and the resolution time from injection to undetectable beta-hCG levels was 14-120 days. In spite of declining serum beta-hCG and unruptured tubal pregnancy, two patients subsequently requested definitive treatment for their ectopic pregnancies and underwent surgery. Four of six women found to have a living embryo in their gestational sacs required a repeat methotrexate injection; one of these also required a local potassium chloride injection. The tubal pregnancies resolved in nine patients treated with methotrexate alone. During resolution, we noted a gradually increasing resistance index of the blood flow in the region of the gestation, but the tube became distended to 4.4 +/- 0.4 cm before gradually decreasing in size. No complications or side effects were encountered. These findings suggest that intratubal transvaginal methotrexate administration can provide a safe alternative to surgical treatment for patients with early unruptured tubal ectopic pregnancy. However, the presence of a living embryo makes the ectopic pregnancy more resistant to methotrexate treatment.     

Diagnostic accuracy of ultrasound above and below the beta-hCG discriminatory zone.

OBJECTIVE: To evaluate clinical use and accuracy of transvaginal ultrasound for diagnosing intrauterine pregnancies, spontaneous miscarriages, and ectopic pregnancies in women who present with beta-hCG concentrations above or below an established discriminatory zone. METHODS: Ultrasound diagnosis at presentation was compared with final clinical diagnosis in 333 consecutive pregnant women who presented to an emergency department with vaginal bleeding or abdominal pain. The sensitivity, specificity, predictive value, and overall diagnostic accuracy of ultrasound were calculated. RESULTS: Transvaginal ultrasound was nondiagnostic in 59 (17.7%) of 333 subjects and 43 (67.2%) of 64 subjects with beta-hCG levels below 1500 mIU/mL at presentation. Preliminary ultrasound diagnoses were reported significantly more frequently when presenting beta-hCG levels were above 1500 mIU/mL (253 [94.1%] of 269 subjects) compared with levels below 1500 mIU/mL (21 [32.8%] of 64 subjects: P < .001; relative risk (RR) 3.4 [95% confidence interval (CI) 2.23, 5.18]). The proportion of accurate preliminary ultrasound diagnoses was significantly higher in subjects who presented with beta-hCG levels above 1500 mIU/mL (227 [91.5%] of 248 subjects) compared with levels below 1500 mIU/mL (18 [28.6%] of 63 subjects: P < .001; RR 2.9 [95% CI 2.04, 4.15]). Sensitivity of transvaginal ultrasound diagnosis of intrauterine pregnancy, spontaneous miscarriage, and ectopic pregnancy in women who presented with beta-hCG levels below 1500 mIU/mL was 33.3%, 28.2%, and 25.0%, respectively. CONCLUSION: The sensitivity, predictive value, and accuracy of transvaginal ultrasound for diagnosing complications of early pregnancy were poor when beta-hCG levels were below the discriminatory zone at presentation. Ultrasound impressions should be correlated with beta-hCG concentrations.     

Transvaginal sonographic detection of the pseudogestational sac associated with ectopic pregnancy

Fifty-seven of 261 patients (21.8%) referred with a presumptive diagnosis of an ectopic gestation had an extrauterine pregnancy. Five of the 57 ectopic pregnancies (8.8%) had a pseudogestational sac on transvaginal sonography. In four of these five cases, a single beta-hCG level had been obtained and did not help in differentiating an ectopic gestation from an early intrauterine pregnancy. A thorough assessment of the adnexa and cul-de-sac should be performed if a patient suspected of having an ectopic pregnancy has an apparent intrauterine gestational sac without a normal yolk sac or without detectable fetal cardiac activity.     

Pregnancy-specific beta 1-glycoprotein (SP1) after in vitro fertilization and embryo transfer

Recent reports indicate that SP1, a "pregnancy-specific beta 1-glycoprotein", can be used as a biological marker for very early pregnancy and occult abortion. In this investigation, SP1 serum concentrations were measured in the luteal phase of 48 menstrual cycles stimulated for in-vitro fertilization (IVF) and embryo transfer (ET). All patients received hMG for ovarian stimulation. Ovulation was induced by beta-hCG and also administered to support the luteal phase. In the 8 pregnancies arising after ET, SP1 (less than 0.5 ng/ml) was not detected before 13 to 19 days after laparoscopy. In contrast, the pregnancy-dependent beta-hCG increase was detectable earlier than SP1 despite the administration of hCG given for luteal support. However, low SP1 readings (0.5-1.1 microgram/ml) as early as 3 days after laparoscopy were observed in 11 cycles without a positive sign of beta-hCG production. Our results suggest that SP1 determinations cannot be used as a marker for occult abortion; also, positive SP1 readings without increase beta-hCG, especially during the early luteal phase after ET, have to be interpreted with caution.     

Factors that may predispose to rupture of tubal ectopic pregnancy

OBJECTIVE: The purpose of our study was to evaluate factors that may predispose to rupture of tubal ectopic pregnancy. The study included 99 cases of ectopic pregnancies that were treated during the 5-year period 1992-1996. RESULTS: It was found that: (1) tubal rupture is encountered more often in women with no history of ectopic pregnancy and in those who have full-term pregnancy, suggesting that ectopic pregnancy is less suspected in these women; (2) tubal rupture is encountered less often in lower age ectopic pregnancy; and (3) serum beta-hCG level does not predict tubal rupture. CONCLUSIONS: Rupture of the tube is more often observed in women with a history of ectopic pregnancy and in women with full-term pregnancy. Such observations suggest that ectopic pregnancy is less suspect in these cases.     

beta-1-Glycoprotein determination in normal and disturbed pregnancy

beta-1-Glycoprotein (SP1) concentration of 170 women with undisturbed pregnancy under 18th week were taken as reference. SP1 levels of 72 patients with threatening abortion but favorable outcome were compared with those of 70 patients with threatening abortion and subsequent miscarriage. Decreased SP1 levels were determined in most (88%) patients who aborted, whereas 88.8% of patients with favorable outcome had SP1 levels within normal range. The predictive value of SP1 determination in early pregnancies is emphasized.     

Persistent ectopic pregnancy following laparoscopic linear salpingostomy.

As the surgical approach for ectopic pregnancies evolves from radical to conservative procedures, the potential hazard of persistent ectopic pregnancy has become increasingly pertinent. From September 1, 1986 to August 31, 1989, 11 women with persistent ectopic pregnancy after laparoscopic salpingostomy were diagnosed and treated at Yale-New Haven Hospital. Persistent ectopic pregnancy was suspected in nine cases because of symptoms and in two because of plateauing beta-hCG titers. Ten of 11 patients underwent repeat surgery. Eight had partial or complete salpingectomy of the involved ipsilateral tube, two had repeat salpingostomies, and one was treated with methotrexate. When the 11 women with persistent ectopic pregnancies were compared with 70 patients treated successfully by laparoscopic salpingostomy using multivariate stepwise logistic regression, smaller size of the ectopic (P less than .01) and fewer days of amenorrhea (P less than .05) predicted persistent ectopic pregnancy after laparoscopic salpingostomy. Based upon our experience, we believe that earlier-treated ectopic pregnancies (ie, fewer than 42 days of amenorrhea) and/or smaller ectopics (ie, 2.0 cm or less in diameter) require treatment with particular caution and close postoperative surveillance.