In this project, we will characterize the effects of fertility limiting diseases of pelvic organs on the receptivity of the endometrium. The primary aim of the project is the characterization of endometrium in patients with infertility suffering from AD, UF and DE, and compare it with infertile patients with minimal or mild endometriosis but no AD or UF (ETRS group), and with healthy women with only male factor of infertility (CTRL group, controls). The proper infertility treatment of patients with AD,UF and endometriosis is controversial and lacking clear evidence based algorithms. Despite their topical character, especially AD and DE (and UFs as well if present as multiple lesions) can be classified as systemic diseases in relation to women´s fertility. The presumed impact of these pathologies to endometrial receptivity (no matter they do not occur in the uterine cavity itself) can beseen as a fascinating hypothesis. Eradication of these diseases could have a potential to increase the prognosis of these women fundamentally.
The project will be studied in two parts - laboratory and clinical. In the laboratory part, the parameters of endometrial receptivity will be specified in women with UF, AD, DE, minimal and mild endometriosis and in healthy controls. These parameters will be also compared in surgically treated patients before and after the procedures. This data will also be compared with patients from both control groups (ETRS, CTRL). First, we will perform bulk RNA Sequencing (RNA-Seq), to characterize the main differences in RNA expression of the endometrium between women with successful and unsuccessful conceptions. The candidate genes will be used for choosing the RTqPCR controlled set of samples for single-nucleus RNA-Seq (snRNA-Seq) profiling of the endometrial tissue. The results will be validated using RT-qPCR. In the clinical part, we will analyse the reproductive results of surgical and conservative management of infertility associated with AD and UF. Collectively, our data will provide information for the development of new diagnostic tools for better investigation and choice of treatment for patients with infertility. This project is not a clinical trial.
Study Type
OBSERVATIONAL
Enrollment
236
All women chosen for the study will be divided into the groups (AD, UF, DE, ETRS, CTRL) based on the inclusion/exclusion criteria (Table 2).A meticulous concern will be dedicated to patients´ education on advantages and disadvantages (including the eventual risks) of surgical and conservative management of AD and UF. These patients will be allocated into surgical or conservative arm of the study based on their inclinations: either to fertility saving surgical procedure (FSS) with subsequent IVF, or directly to IVF. This phenomenon of the importance of patients´ preferences in controversial clinical situations is the usual part of the management of infertile patients with AD or UF.
Sampling of endometrium (Hysteroscopy) The samples will be collected using hysteroscopy, scheduled into the secretory phase of endometrial cycle. During hysteroscopy, the uterine cavity will be observed and described in the surgical protocol (capacity, symmetry, presence of intrauterine pathologies, internal ostia of the tubes). The 3.2 mm wide hysteroscope will be used. Its usage usually does not require any anaesthesia. The endometrium will be taken using biopsy forceps (7 French / 2.3 mm) and immediately frozen on dry ice and stored at -80 °C until processing. Two pieces of endometrium per patient will be collected - one for isolation of RNA and bulk RNA-Seq and/or RT-qPCR and the second one for isolation of nuclei and snRNA-Seq or validation using snRT-qPCR. If some unexpected findings would be observed during hysteroscopy (especially some interfering with fertility), they would be hysteroscopically removed and endometrial sampling postponed.
General Hospital in Prague
Prague, Czechia
RECRUITINGloss of endometrial receptivity
frequency of patients with loss of receptivity
Time frame: 12 weeks
pregnancy rate
the percentage of all attempts that leads to pregnancy
Time frame: 2 years
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