**2.4. Markers related to normal uterine implantation**

These biomarkers are released into the circulation as a result of normal interaction between the pregnancy and the uterine decidua. As the normal process is disrupted in EP, these surrogate markers can be used to diagnose EP.

**1.** Leukemia inhibitory factor (LIF)

LIF is a cytokine of interleukin-6 family with a key role in implantation [88]. Wegner et al observed that women with ectopic pregnancy had low serum concentrations of LIF and could diagnose it with moderate sensitivity and specificity [89]. However, Daponte et al failed to find any difference in LIF concentrations in patients with ectopic pregnancy and other abnormal intrauterine pregnancy [41]. A further attempt in validation of LIF has yielded conflicting results. Mueller et al found LIF levels to be undetectable in serum of patients with ectopic pregnancy and viable intrauterine pregnancy [38], whereas Iyibozkurt AC et al found increased levels of LIF in patients with EP compared to IUP [90]. Increased immunohisto‐ chemical expression of LIF in fallopian tube was found to be increased in EP compared to non –pregnant and healthy pregnant controls, indicating its role in ectopic implantation of embryo [91]. Similarly it was observed that LIF expression was increased in inflamed fallopian tube and might be one of the reasons of increased susceptibility of salphingitis patients to EP [92].

**2.** Glycodelin (Placental protein 14)

Glycodelin is secreted from endometrium and fallopian tube, with immunomodulatory role in implantation. Its serum concentration increases during early first trimester of pregnancy, till 8-10 weeks of gestation and then progressively declines [93, 94]. Foth et al found signifi‐ cantly lower levels of serum glycodelin in patients with ectopic pregnancy compared to IUP and incomplete abortion with a study population of 169 subjects [95]. Out of the three groups, who studied glycodelin in a multiple marker setting, two had found glycodelin levels to be decreased in EP, while one observed no significant difference between EP and abnormal IUP [28, 38, 41]. Further studies are required to validate the use of this marker in EP.
