**3. Markers related to tubal implantation**

## **3.1. Markers of compromised tubal musculature markers**

These markers reflect the disruption of the integrity of the tubal circular smooth muscle layer, which can happen in an ectopic implantation. These markers of muscle damage have been investigated as biomarkers for diagnosing EP.

**1.** Creatine Kinase (CK)

Creatine Kinase is the enzyme released from damaged muscles, which is currently used in the diagnosis of myocardial infarction. Lavie et al found serum CK levels to be significantly higher in patients with tEP as compared to those with missed abortion or normal IUP [104]. Similar findings were observed by Birkhahn et al and Duncan et al [105,106]. In a study conducted in our population, we found that the optimal cut-off for total CK, CK-MM and CPK-MB% as predictors of ruptured EP were 147 IU/L, 135 IU/L and 10%, respectively, with the former two having higher specificity, and latter high sensitivity [107]. On the contrary, several independ‐ ent study groups found CK to be inadequate in diagnosing EP [108-112]. Recently, Safdarian et al studied the role of CK-1 as an indicator for differentiating between the successful and unsuccessful treatment groups in EP, but failed to find any relation between initial CPK serum levels [113].

## **2.** Smooth muscle heavy-chain myosin (SMHC) & Myoglobin

Smooth muscle heavy chain myosin and myoglobin are markers of smooth muscle damage. As the ectopic pregnancy grows to invade the muscular layer of the fallopian tube, markers of muscle damage should also rise. Birkhahn et al studied serum myoglobin and smooth muscle heavy-chain myosin and observed a statistically significant elevation in the serum levels of SMHC, but did not find it useful in the screening for EP [105,114]. As there is paucity of data regarding the usefulness of these markers in the screening of EP, their clinical utility is limited.
