Recurrent pregnancy loss (RPL), determined as two or more consecutive abortions by some authors, are seen in 1-3% of couples; an underlying cause, however, is only found in up to 50% [
1]. These include embryonic factors, like poor quality embryos with or without karyotype abnormalities, as well as maternal factors, such as uterine malformations, general maternal infections, as well as local inflammation [
2], hormonal abnormalities, immunogenic abnormalities (like thyroid antibodies, cardiolipin antibodies or antinuclear antibodies), genetic imbalances and thrombophilic diseases [
3].
However, when none of these factors are evident, the recurrent pregnancy losses are classified as idiopathic, because the underlying mechanisms are not well understood. The functional expression of endometrial genes and proteins have been examined, because they compromise the endometrial microenviroment and may therefore contribute to an abnormal foetal-maternal interaction, resulting in pregnancy failure [
4]. Furthermore synchronisation between embryonic development and endometrial decidualisation is found to be essential for adequate implantation [
5]. Many authors have studied the embryo-endometrium interface in order to elucidate the pregnancy failure [
6,
7]. Global gene expression analysis [
8,
9] has determined the adequate endometrial gene and protein expression during the short endometrial receptive stage in the mid-secretory phase, the so-called window of implantation (WOI) [
10]. One of these proteins is the αvβ3 integrin [
11]. The combined integrin αvβ3 acts as an adhesion promoter via cell-cell interactions and it has been very well characterized within the human endometrium [
12]. The αvβ3 integrin is expressed in the glandular epithelium during the window of implantation and translocates into endometrial stroma, if pregnancy occurs [
13]. Reduced expression of αvβ3 has been related to unexplained infertility [
11] and in women with endometriosis [
14]. Xu
et al., in a recent publication, did not find any difference in β3 integrin expression in women with RPL compared to normal fertile women [
15]. However, these authors analysed the expression of β3 integrin in formalin fixed paraffin embedded (FFPE) samples. It is known that β3 integrin expression in FFPE produces artefacts and should be avoided [
16]. In order to find a more accurate expression of β3 integrin subunit in cases with RPL, would be necessary to use frozen sections of endometrial biopsies, instead of FFPE. Other authors reported the expression of avβ3 integrin in endometrial-frozen section and did not find any difference between groups [
17,
18]. Contrary, other authors found a reduction of αvβ3 integrin during the implantation window in patients with recurrent pregnancy loss, compared to controls, either in frozen sections [
19], or in microarray studies [
7]. Possible discrepancies among studies could be related to technical differences. Our group has been using the SSA6 antibody to identify the β3 integrin subunit, and the expertise developed in our group to evaluate β3 immunostaining has been validated using NIH software image analysis [
20]. This study has two objectives: a) to examine the expression of the αvβ3 integrin in women with RPL compared to healthy controls, b) to compare integrin expression with morphologic dating of the endometrium, which has been widely used to judge the endometrial development and receptivity.