Markers of endometrial receptivity: a study of ultrasonographic and molecular factors

Polanski, Lukasz T. (2016) Markers of endometrial receptivity: a study of ultrasonographic and molecular factors. PhD thesis, University of Nottingham.

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The evidence suggests that alteration of the endometrial environment in women with previous failed in vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI) by inflicting endometrial injury improves the outcome of the subsequent treatment cycle. The selected population assessed in the studies supporting this statement prevents from generalizing this to all women undergoing IVF or ICSI treatment. The mechanisms responsible for alteration of the endometrial environment following biopsy remain still unclear. If proven effective, endometrial injury could serve as a beneficial adjunct for all couples undergoing assisted reproductive treatment (ART).

The hypothesis forming the basis of the work reported in this thesis was that endometrial injury in the cycle directly preceding an embryo transfer cycle, be it fresh or frozen, improves the outcome of that treatment irrespective of previous reproductive history.

In order to support or refute this hypothesis, a clinical trial of endometrial biopsy prior to IVF or ICSI treatment has been designed. Additional objectives that allow examining the mechanisms responsible for the beneficial effects of the biopsy on the endometrium included utilization of two-dimensional, three- dimensional and Spatio-Temporal Image Correlation (STIC) ultrasound and assessment of the predictive value of any sonographic indices on ART outcome. Same sonographic modalities were used to determine the effect of endometrial injury on endometrial and subendometrial blood flow. Similarly, an examination of the value of uterine natural killer (uNK) cell numbers and expression of selected molecular markers of endometrial function as a predictors of ART outcome was explored.

In this work it was not possible to clearly demonstrate a benefit of routine endometrial biopsy in all women undergoing ART on treatment outcomes, though clues, as to which population might benefit from the procedure, were identified. Extensive sonographic analysis of endometrial factors did not produce results allowing for unequivocal non- invasive identification of a receptive endometrial milieu. Triple layer endometrial pattern at oocyte collection was correlated with positive outcome and endometrial biopsy. Spatio-Temporal Image Correlation did not fulfil expectations as a non-invasive marker of endometrial receptivity and was not able to identify women that would go on to have a successful ART outcome. In a small number of patients, STIC indices were able to predict first trimester miscarriage with relatively high sensitivity and specificity. uNK cell numbers were not associated nor predictive of ART outcome, and as such not useful as a routine diagnostic tests prior to ART. An observed significant decrease in uNK cell levels following endometrial biopsy indicates a possible mechanism of action of this intervention. Limited (3) molecular cues were not able to differentiate between a receptive and non-receptive endometrium. This work, however extensive, indicates that the endometrium is a complex microenvironment requiring further investigation in order to understand and influence the mechanisms related to pregnancy establishment and development.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Raine-Fenning, N.
Campbell, B.
Keywords: Endometrial receptivity, Spatio-temporal image correlation (STIC), Assisted reproductive treatment (ART), Endometrial biopsy, Uterine natural killer (NK) cells
Subjects: W Medicine and related subjects (NLM Classification) > WP Gynecology
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 31634
Depositing User: Polanski, Lukasz
Date Deposited: 19 Jul 2016 06:40
Last Modified: 22 Oct 2016 14:04

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