Recurrent pre-clinical pregnancy loss is unlikely to be a 'cause' of unexplained infertility

Koot, Yvonne E; Boomsma, Carolien M.; Eijkemans, Marinus J.C.; Lentjes, Eef G.W.M.; Macklon, Nick S.

doi:10.1093/humrep/der217

Cited by 31 publications

(19 citation statements)

References 20 publications

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“…There is some clinical evidence that this, indeed, occurs as monosomic embryos can develop to blastocysts that look normal but are never found in later products of conception, suggesting failure at or soon after implantation. By contrast, some women recurrently fail to become pregnant when 'good quality' embryos have been transferred after IVF, and do not show overt evidence of miscarriage (Koot et al, 2011). Embryos initially form tenuous and reversible attachments to epithelial cells.…”

Section: Epithelial Polarity and Gene Expressionmentioning

confidence: 99%

Embryo–epithelium interactions during implantation at a glance

Aplin

Ruane

2017

Journal of Cell Science

181

134

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At implantation, with the acquisition of a receptive phenotype in the uterine epithelium, an initial tenuous attachment of embryonic trophectoderm initiates reorganisation of epithelial polarity to enable stable embryo attachment and the differentiation of invasive trophoblasts. In this Cell Science at a Glance article, we describe cellular and molecular events during the epithelial phase of implantation in rodent, drawing on morphological studies both in vivo and in vitro, and genetic models. Evidence is emerging for a repertoire of transcription factors downstream of the master steroidal regulators estrogen and progesterone that coordinate alterations in epithelial polarity, delivery of signals to the stroma and epithelial cell death or displacement. We discuss what is known of the cell interactions that occur during implantation, before considering specific adhesion molecules. We compare the rodent data with our much more limited knowledge of the human system, where direct mechanistic evidence is hard to obtain. In the accompanying poster, we represent the embryo-epithelium interactions in humans and laboratory rodents, highlighting similarities and differences, as well as depict some of the key cell biological events that enable interstitial implantation to occur.

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Section: Epithelial Polarity and Gene Expressionmentioning

confidence: 99%

Embryo–epithelium interactions during implantation at a glance

Aplin

Ruane

2017

Journal of Cell Science

181

134

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“…It has been estimated that between 30% and 50% of all implanting embryos fail before reaching viability (19)(20)(21)(22), rendering miscarriage, preclinical or not, the most common complication of pregnancy. A series of uncontrolled studies demonstrating an increased incidence of spontaneous abortion in women with endometriosis led to the inclusion of the disease on the list of possible causes of miscarriage (23,24).…”

Section: Obstetrical Complications Associated With Endometriosismentioning

confidence: 99%

Risks of adverse pregnancy outcome in endometriosis

Brosens¹,

Brosens²,

Fusi³

et al. 2012

Fertility and Sterility

115

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“…Although definitions of recurrent implantation failure (RIF) vary (Coughlan et al, 2014;Polanski et al, 2014), it is clear that embryo transfer commonly leads to a biochemical pregnancy [human chorionic gonadotropin (hCG) detected but no embryonic sac] or no detectable pregnancy at all. RIF appears distinct from recurrent miscarriage; that is, there is a group of women in whom pregnancy repeatedly fails very early on (Koot et al, 2011). This might be accounted for by the repeated transfer of karyotypically abnormal embryos or, alternatively, by a lack of adequate receptivity in the endometrium.…”

Section: Introductionmentioning

confidence: 99%

miR-145 suppresses embryo-epithelial juxtacrine communication at implantation by modulating maternal IGF1R

Kang

Lees

Matthews

et al. 2015

Journal of Cell Science

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Successful implantation requires the synchronization of viable embryonic development with endometrial receptivity. The mechanisms allowing for the initiation of crosstalk between the embryo and the endometrium remain elusive; however, recent studies have revealed that there are alterations in endometrial microRNAs (miRs) in women suffering repeated implantation failure and that one of the altered miRs is miR-145. We assessed the role of miR-145 and its target IGF1R, in early implantation. miR-145 overexpression and IGF1R knockdown were achieved in Ishikawa endometrial cells. Quantitative PCR, western blotting and 39UTR luciferase reporter assays confirmed that IGF1R is a direct target of miR-145 in the endometrium. Attachment of mouse embryos or IGF1-coated beads to endometrial epithelial cells was used to study the effects of altered miR-145 and/or IGF1R expression on early implantation events. miR-145 overexpression or specific reduction of IGF1R impaired attachment in both cases. An IGF1R target protector prevented the miR-145-mediated reduction in IGF1R and reversed the effect of miR-145 overexpression on attachment. The data demonstrate that miR-145 influences embryo attachment by reducing the level of IGF1R in endometrium.

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Recurrent pre-clinical pregnancy loss is unlikely to be a 'cause' of unexplained infertility

Abstract: Our data do not support the hypothesis that recurrent EPL may present as unexplained infertility. Post-implantation failure is therefore unlikely to contribute significantly to the presentation of subfertility.

Cited by 31 publications

References 20 publications

Embryo–epithelium interactions during implantation at a glance

Embryo–epithelium interactions during implantation at a glance

Risks of adverse pregnancy outcome in endometriosis

miR-145 suppresses embryo-epithelial juxtacrine communication at implantation by modulating maternal IGF1R

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