Competition PN-II-PT-PCCA-2013-4-1348Grant no. 138 / 2014

Project's objectives

The main objective of the project is the development of a highly relevant diagnostic, staging and treatment protocol based on the expression of relevant biomarkers in both eutopic and ectopic endometrial tissue in order to prevent the recurrence of active endometriotic implants and to increase the fertility of reproductive-aged women affected by this disease. This main objective will be arrived at by way of four distinct evaluations: 

a)  The evaluation of the hormonal responsiveness and aggressive potential of eutopic endometrium
In order to gauge this invasive potential of in situ endometrial cells, samples of eutopic endometrium will be obtained through Pipelle endometrial biopsies from patients with confirmed endometriosis. The abovementioned markers will be identified qualitatively and cantitatively:
    – matrixmetalproteinaze (MMPs)
    – markeri de angiogeneză – factorul de creştere al endoteliului vascular (VEGF)
    - integrine / caderine (E-cadherin, N-cadherin)

A negative control group comprising of endometrial samples obtained from hysterectomy specimens of fertile women without endometriosis or malignant gynecologic pathology will also be analysed in the same way and statistical comparisons between these two groups of samples will be made. The patient will undergo postoperative hormonal treatment and the response of the eutopic endometrium to this treatment regimen will be determined at six months after laparoscopy. Uterine curettage samples will be prelevated and the abovementioned parameters will be identified and described once more in order to identify potential markers of positive therapeutic response and endometrial receptivity to a future pregnancy.

b) The evaluation of the hormonal responsiveness and aggressive potential of ectopic endometrium
Ectopic endometrium obtained from endometrial implants removed by laparoscopy or laparotomy will also be analysed regarding to the same markers described for the samples of eutopic endometrium. A statistical comparison of these parameters between each patient’s ectopic and eutopic endometrium will be made.

c)  The evaluation of the immune cell cooperation within eutopic and ectopic endometrium as a method of elucidation of the connection between endometriosis and infertility
It has been stipulated that dysregulation of endometrial immune cell cooperation may be responsible for implantation failure leading to primary infertility in patients with low-stage endometriosis. We intend to compare the ratio of LTH1 to LTH2 lymphocytes as well as their activity in both eutopic and ectopic endometrium and also to correlate the local immunity to the stage of the illness and the aggressive potential of the eutopic endometrium, Any evidence to confirm this hypothesis would be a gateway to further research into the possible role of immune modulators to enhance fertility in these patients.

d)  A contribution towards the elucidation of the origin of endometriosis
Notable similarities between eutopic and ectopic endometrium at the cellular level in samples obtained from the same patient would make both the caelomic metaplasia and abnormal peritoneal stem cell differentiation unlikely, gearing any future research towards identifying migration paths of eutopic endometrium into the peritoneal cavity.

The findings of this two-year research project will be published in international journals in the form of at least four articles (one per phase). We will also organize a workshop for gynecologists regarding the medical and surgical therapeutic options in endometriosis during the third phase of the project. Last but not least, patient education regarding this condition, as well as its complications and management options will be done through the creation of a bilingual (English and Romanian) website dedicated to patient and physician education about endometriosis.