Receiver Operator Characteristics and Predictive Value of Serum Cancer Antigen 125 and Creatine Kinase in the Diagnosis of Tubal Ectopic Pregnancy and Inevitable Miscarriage

Tubal ectopic pregnancy is an important cause of maternal morbidity that can be fatal if left undiagnosed due to the risk of potential tubal rupture and hemorrhage. Currently, it is diagnosed using a combination of transvaginal ultrasound and serial serum β-human chorionic gonadotrophin levels. Diagnosis is often delayed and these tests are time-consuming. Early diagnosis is the key to successful and conservative management of women with tubal ectopic pregnancy. The development of a biomarker that can differentiate a tubal ectopic from an intrauterine implantation is therefore important. Objectives: Investigate the predictive value of cancer antigen-125, progesterone, estradiol, maternal serum creatine kinase and CK-MB in the diagnosis of tubal ectopic pregnancy and inevitable miscarriage. Subjects and methods: The study was conducted during the period from September 2010 till August 2011 in the department of chemistry and biochemistry/college of medicine/ AL-Nahrain University. It includes Forty women with tubal ectopic pregnancy (EP), divided into 25 women with ruptured tubal ectopic pregnancy and 15 women unruptured tubal ectopic pregnancy, 17 with intrauterine (IU) abortion (inevitable miscarriage), and 24 women with normal IU gestation (control group). They all attended from AL-Kadhimia Teaching Hospital and Baghdad Teaching Hospital, they were diagnosed by a specialist gynecologist. Cancer antigen-125, progesterone, estradiol and Human Chorionic Gonadotropin (hCG) levels measured by commercial Enzyme Linked Immuno Sorbent Assay (ELISA) kits, total serum creatine kinase and CK-MB values were determined by a spectrophotometric methods. ABSTRACT Results: The results of the study showed that the mean of CA-125 levels were significantly lower in the group of women with tubal EP compared to women with controls (P < 0.005), and CA-125 levels were significantly higher in the group of women with intrauterine abortive pregnancy, compared to women with tubal EP (P<0.01) and women with intrauterine pregnancy (P<0.01). The Receiver Operator Characteristic (ROC) curve demonstrated a significant discriminatory ability of decreased CA-125 levels for the diagnosis of tubal ectopic pregnancy. When using a CA-125 concentration of 20.5 U/ml as a cut-off value for the diagnosis of tubal ectopic pregnancy from control groups, the sensitivity was 75.5%, specificity 100%, the positive predictive value was 100% and the negative predictive value 71.4% The mean serum creatine kinase (CK) levels were significantly higher in tubal ectopic pregnancy compared with both inevitable miscarriage (P<0.001) and normal gestations (P < 0.00005). No significant difference was observed between women with abortive intrauterine (IU) and control (P>0.05). The Receiver Operator Characteristic (ROC) curve demonstrated a significant discriminatory ability of increased total creatine kinase (CK) level for the diagnosis of ectopic pregnancy. When using total creatine kinase (CK) concentration of 22.22 IU/L as a cut-off value for the diagnosis of tubal ectopic pregnancy from control group, sensitivity was 68.4%, specificity 100%, the positive predictive value was 100% and the negative predictive value 66.66%. CK-MB levels were significantly higher in women with tubal ectopic pregnancy compared with those of women with normal pregnancy (P<0.0001) and (P <0.001) inevitable miscarriage.
Progesterone levels were significantly lower in women with tubal ectopic pregnancy, compared to those of women with IU abortion (P < 0.03) and women with normal pregnancy (P < 0.000001). Controls had significantly higher progesterone levels, compared to women with inevitable miscarriage (P < 0.0000001). CK/progesterone ratio were significantly higher in women with tubal ectopic pregnancy compared with those of women with normal pregnancy (P<0.0000001) and women with IU abortion (P <0.0001). Conclusion: Measurement of serum CA-125 and CK levels can be used in the differentiation of tubal ectopic pregnancy and its types (ruptured and unruptured) from normal intrauterine pregnancy.