**4. Further research**

**2.** CA-125

62 Contemporary Gynecologic Practice

table 1.

1 Β-hCG

**Sl No**

**3.** Antibodies to C1q complement

b. 48 hours rise <53% rise

c. Mathematical models

3 Pregnancy associated plasma protein-A (PAPPA)

4 Pregnancy specific beta glycoprotein-1 (SP-1)

Conflicting results have been reported by several groups regarding the status of circulating CA-125 in EP with some groups reporting an increase, some decrease and few found no difference between viable IUP and EP [117-121]. In our experience in the cohort of patients, we found CA125 concentration to be significantly higher in woman with miscarriages compared to patients with normal IUP, but not in women with ectopic compared to IUP [Unpublished paper]. Women with **IU** abortion were found to have significantly higher CA-125 levels, compared to the other two groups. Katsikis et al also reported that when using CA-125 concentration of more than 41.9 U/ml as a threshold for the diagnosis of IU abortive pregnancy, sensitivity was 80% and specificity was 87% for discriminating it from EP [122].

C1q complement has been shown to promote trophoblast invasion of deciduas, a crucial step in normal placental development. Animal models have demonstrated that the lack of C1q is characterized by poor trophoblast invasion and pregnancy failure [123,124]. Studies based on these observations have measured the levels of antibodies to C1q complement in early pregnancy failure have been conducted. Daponte et al failed to observe any difference between normal viable IUP, EP and other abnormal IUP [116]. As new studies would be undertaken by

The biomarkers studied in ectopic pregnancy with their current status are summarized in

different groups, more information regarding this marker is likely to emerge.

**Biomarker Cut-off Sensitivity Specificity Reference**

<35% rise

a. Single serum levels <2000mIU/ml 87% 39% Shaunik et al 2011

2 Hyperglycosylated hCG 13µg/L 73% 98.1% Sutton-Riley 2006

91% 83.2%

M1 0.21 83% 88% Condous 2004 M4 - 92% 91% Condous 2007

66.6% 70.8%

31% 98% Kirk 2006 81% 89% Barnhart 2010

0.53 ng/ml 81% 54% Rausch 2011

103.3µg/ml 65% 74% Witt 1990

Barnhart 2004 Morse 2012

> Since the factors and their interplay involved in maintenance of normal viable pregnancy are not completely understood, various approaches have been explored in biomarker discovery including unbiased proteomics, shotgun proteomics [125,126]. The challenges in biomarker discovery include the variability of biomarkers with gestational age, impact of coexistent morbidities like hypertension, diabetes, chromosomal anomalies on biomarker levels and their interpretation. Other emerging markers studied in ectopic pregnancy include: Endocannibi‐ noid system abnormalities in the form of high anandamide levels and reduced receptor expression have been implicated, in women with ectopic pregnancy [127,128].

> Brown et al conducted a proteomics study and identified fibronectin has ability to discriminate EP from other pregnancy outcomes suggesting its diagnostic potential and its use as an adjunct to future multiplex EP diagnostic tests [129].

Serum Macrophage Inhibitory Cytokine-1 levels were found to be lower in women with histologically confirmed EP compared to women with definite viable intra-uterine pregnancy by Skubisz et al [130].

Another recent study by Beer et al that screened the proteome of a small group of women with EP and controls identified potential novel biomarkers, including ADAM-12 and ISM2 (Isthmin 2) as well as five specific isoforms of pregnancy-specific beta-1-glycoprotein 131].
