Endometrial Stromal Cells of Women with Recurrent Miscarriage Fail to Discriminate between High- and Low-Quality Human Embryos

Abstract

BackgroundThe aetiology of recurrent miscarriage (RM) remains largely unexplained. Women with RM have a shorter time to pregnancy interval than normally fertile women, which may be due to more frequent implantation of non-viable embryos. We hypothesized that human endometrial stromal cells (H-EnSCs) of women with RM discriminate less effectively between high-and low-quality human embryos and migrate more readily towards trophoblast spheroids than H-EnSCs of normally fertile women.Methodology/Principal FindingsMonolayers of decidualized H-EnSCs were generated from endometrial biopsies of 6 women with RM and 6 fertile controls. Cell-free migration zones were created and the effect of the presence of a high-quality (day 5 blastocyst, n = 13), a low-quality (day 5 blastocyst with three pronuclei or underdeveloped embryo, n = 12) or AC-1M88 trophoblast cell line spheroid on H-ESC migratory activity was analyzed after 18 hours. In the absence of a spheroid or embryo, migration of H-EnSCs from fertile or RM women was similar. In the presence of a low-quality embryo in the zone, the migration of H-EnSCs of control women was inhibited compared to the basal migration in the absence of an embryo (P<0.05) and compared to the migration in the presence of high-quality embryo (p<0.01). Interestingly, the migratory response H-EnSCs of women with RM did not differ between high- and low-quality embryos. Furthermore, in the presence of a spheroid their migration was enhanced compared to the H-EnSCs of controls (p<0.001).ConclusionsH-EnSCs of fertile women discriminate between high- and low-quality embryos whereas H-EnSCs of women with RM fail to do so. H-EnSCs of RM women have a higher migratory response to trophoblast spheroids. Future studies will focus on the mechanisms by which low-quality embryos inhibit the migration of H-EnSCs and how this is deregulated in women with RM.

Genetic association between the HLA-G 14-bp insertion/deletion polymorphism and the recurrent spontaneous abortions in Saudi Arabian women

“…RSA is one of the most common complications associated with early pregnancy and remains a challenge in gynecology (Jauniaux et al, 2006). Different potential etiologic factors have been implicated in this condition, such as endocrine regulation, autoimmune reaction, thrombophilia, environmental, psychological, and genetic background, and viral infections (Bergant et al, 1997;Bussen et al, 1999;Li et al, 2002;Quenby et al, 2005;Weimar et al, 2012).…”

Miscarriage Definitions, Causes and Management: Review of Literature

“…Moreover, ESCs of women with RM showed prolonged receptivity (super receptivity), with low selectivity for low quality embryos [40] . A recent study showed that the migration of ESCs from RM women was similar in the presence of low-quality or high quality embryos [41] .…”

Assessing Receptivity of the Human Endometrium to Improve Outcomes of Fertility Treatment

“…The decidual milieu is overall favourable for trophoblast expansion and migration [12,13]. Recently, early decidua has been identified as a 'sensor' of human embryo quality [14,15]. It was found that the decidual cells could discriminate between 'good' and 'bad' quality embryos, except in the case of cells derived from women with recurrent pregnancy loss in whom the discriminatory capacity was absent [16].…”