Discussion
infertilityNon-invasive intrauterine, endometrial insufficiency, platelet aggregation, infertility
EVENTS, PATHOLOGY
Successful pregnancy onset requires both the fully functional, receptive endometrium and a good quality embryo. The opportunities of influencing the embryonic factor are limited (the only means is selection), whereas the uterine factor is more manipulable. The literature contains multiple lines of evidence on the strong association of endometrial thickness with the rates of clinical pregnancy and live birth in ART programs.First our step was estimation of patients’ endometrium. Statistically significantly higher expression of CD34 in the endometrium of patients with pregnancy reflects the pathological state of the endometrial stroma. Such a state of the stromal component, even with the unchanged glandular component of the uterine mucosa, may be an expression of immunophenotypic pathology preceding the occurrence of histologically verifiable abnormalities. It should be noted that data on increased CD34 expression in patients with various causes of infertility were also obtained by Mai et al., who assigned stromal cell pathology a leading role in the development of infertilityNon-invasive intrauterine instillations with 1–2 mL autologous PRP represent a promising therapeutic option for thin endometrial infertilityHere we firstly describe injections of PRP into endometrium under hysteroscopic control in patients with the uterine factor infertility. We applied autologous PRP prepared in accordance with the manufacturing and quality control standards, with mandatory functional assessment of the product (platelet counts, growth factor content) immediately before the use. To maximize the curative effects of PRP, optionally with an admixture of autologous minimally manipulated cells, the medication was injected into endometrium via endoscopic needle, to the depth of 2–3 mm, under direct hysteroscopic visualization. This technique afforded a decisive improvement in many patients with refractory thin endometrium and a history of ET cancellations due to habitual endometrial insufficiency even under high doses of estrogens.The curative effects of PRP are mediated by growth factors contained in platelet granules and released in response to activating stimuli. Platelet-derived growth factors (PDGFs) constitute a family of secreted dimeric polypeptides, which exert strong mitogenic action on cells of mesenchymal originPlatelet degranulation is triggered by specific stimuli. The process of receiving these stimuli and their interpretation by a platelet is termed 'activation'. In the context of clinical use of PRP, exact time point(s) of platelet activation are critically important. The activation status of PRP can be measured by relative counts of CD63 and P-selectin signals in the pool of CD61 positive events. CD61, also known as platelet glycoprotein IIIa, resides at the surface of platelets, both resting or activated. In a dimeric complex with CD41, it promotes platelet aggregation through interactions with plasma proteins, notably fibrinogen. By contrast, tetraspanin CD63 and P-selectin epitopes are confined within the granules — their relocation to the surface indicates degranulation. P-selectin is contained in α-granules and externalized faster than CD63. High levels of CD63–P-selectin+ platelets correspond to early stages of activation; the uniformity of this condition (observed for all PRP samples in the study) suggests that degranulation occurs upon injection (which is optimal, considering the short half-lives of growth factors).In addition to the major part of the cohort receiving injections of unadmixed PRP or no injections at all (Groups 1–3), a small group of patients (Group 4) received injections of autologous PRP reinforced with eutopic autologous stem cells isolated from endometrial biopsies. Immunophenotyping of the minimally manipulated cell products revealed > 50% positivity for CD90 и vimentin. CD90 (which belongs to immunoglobulin superfamily of cell surface receptors) is expressed on MSCs, fibroblasts and endothelial cellsThe ultimate moment of truth for the infertility treatment efficacy is provided by pregnancy rates. In our setting, the estimated reproductive impact of autologous PRP injections in patients with refractory thin endometrium was positive. Both pregnancy and live birth rates in PRP-treated groups were higher compared with the control. It is important to emphasize that the patients had a history of unresponsiveness to standard therapies involving basic and add-on approaches.