The aim of this study was to evaluate the efficacy of hysteroscopically controlled injections of autologous platelet-rich plasma (PRP) and autologous endometrial cells as a treatment for infertile women with thin endometrium. The study enrolled 115 patients with thin endometrium (< 7 mm at implantation window) and infertility, who were divided into groups: Group 1 (the control) underwent conservative therapy; Group 2 received intraendometrial PRP injections instead of the conservative therapy; Group 3 received identical injections after conservative therapy; Group 4 received injections of the autologous endometrial cells suspended in PRP. A single injection dose of PRP contained 0.6–0.7 × 1011 of platelets. The levels of PDGF-BB and VEGF in PRP were increased compared with ordinary plasma. The autologous endometrial cells, obtained from pipelle biopsies, constituted heterogeneous cell populations containing stromal and epithelial cells. Intraendometrial PRP injections had significant impact on endometrial thickness and local microcirculation in Group 2 and Group 3. In Group 4, injections of PRP reinforced with endometrial cells also facilitated a significant increase in endometrial thickness. This work describes a novel approach for infertility treatment in patients with refractory thin endometrium. PRP injections and injections of the endometrial cells suspended in PRP into endometrium enhanced cell proliferation and angiogenesis.
Abnormal uterine bleeding (AUB) is one of the most common indications for hysteroscopy. Most of the AUB cases occur due to endometrial or myometrium pathology. Among it, endometrial polyps (EP) and chronic endometritis (CE) prevalent in reproductive age, while endometrial hyperplasia (EH) and EP dominate in perimenopause. It was determined that EP and CE are characterized with menorrhagia and metrorrhagia approximately equally, whereas EH reveals AUB with oligomenorrhoea. Verification of exact endometrial pathology by ultrasound examination is hindered, that results in deviations of ultrasound and histological diagnosis. The usage of ultrasound data and AUB’s characteristics may improve the diagnostic accuracy on preadmission period.
Background Platelet-rich plasma (PRP), which represents a valuable source of growth factors, is increasingly being applied in regenerative medicine. Recent findings suggest the feasibility of using PRP in the treatment of infertility secondary to refractory thin endometrium. Mesenchymal stem/stromal cells (MSCs) of the endometrium are an essential cellular component responsible for extracellular matrix remodeling, angiogenesis, cell-to-cell communication, and postmenstrual tissue repair. Using a rat model, we examine the effects of autologous PRP on MSCs isolated from the uterus and compare them with the effects of autologous ordinary plasma (OP) and complete growth medium. Methods MSCs were isolated from uterine tissues via enzymatic disaggregation. Flow cytometry immunophenotyping of the primary cell cultures was complemented by immunocytochemistry for Ki-67 and vimentin. The ability of MSCs to differentiate in osteo-, chondro-, and adipogenic directions was assessed using differentiation-inducing media. The levels of autophagy and apoptosis markers, as well as the levels of matrix metalloproteinase 9 (MMP9) and estrogen receptor α, were assessed by western blotting. Results After 24 h incubation, the proliferation index of the PRP-treated MSC cultures was significantly higher than that of the MSC cultures treated with complete growth medium. PRP treatment elevated production of LC3B protein, an autophagy marker, while OP treatment upregulated the expression of stress-induced protein p53 and extracellular enzyme MMP9. The results indicate practical relevance and validity for PRP use in the treatment of infertility.
OBJECTIVE: The study aims to evaluate the effectiveness of autologous platelet-rich plasma (PRP) injection during histeroscopy in infertile patients with thin endometrium which is refractory to conventional treatment.DESIGN: Prospective interventional study. MATERIALS AND METHODS: All patients signed informed consent for medical intervention and participation in the study. The study included 42 patients aged 18-38 years (34.9 (3.6) years) with an endometrial thickness (EMT) of %7 mm during the mid-luteal phase of menstrual cycle, who had a history of implantation failures or canceled embryo transfer (ET) cycles due to a thin endometrium. During the mid-luteal phase transvaginal ultrasound was performed to all patients to assess the EMT, as well as Doppler examination, and endometrial aspiration biopsy to further assess its receptivity. PRP was prepared from 400 (50) ml of autologous blood by two-stage centrifugation and reinfusion of the patient's autoerythrocytes. All patients were injected 40 (5) ml of autologous PRP into the most altered areas of endometrium with an endoscopic needle with a diameter of 0.6/1.16 mm through the operating channel of the hysteroscope to a depth of 0.2-0.3 mm on the 6th -8th day of the proliferative phase of the menstrual cycle preceding the ET. The duration of the intervention was on average 15 minutes. In the new menstrual cycle, patients took orally administered estradiol valerate, starting from the 3rd-4th day with initial dose of 4 mg per day with subsequent correction according to the endometrial response. The daily maximum dose was 10 mg. In the mid-luteal phase patients underwent a control ultrasound examination by the same specialist to assess the EMT. Patients who reached the optimal EMT were transferred one good quality embryo. Posttransfer support was performed by 600 mg of micronized progesterone intravaginally per day until the results of serum b-chorionic gonadotropin were obtained. Numerical parameters were presented as M (SD) and Me (Q1; Q3). Statistical significance was determined at p<0.05.RESULTS: In study population 71.4% of patients (30/42) had a history of cancellation of ET cycles due to inadequate endometrial growth. The mean EMT on the previous-cycle mid-luteal phase was 5.4 (4; 6) mm. After PRP treatment, EMT was 7.5 (7; 9), which was significantly thicker than initial values (P<0.001). The clinical pregnancy rate was 33.3% (14/42) after ET. Three patients had a livebirth after ET, 3 patients had a miscarriage at 7-8 weeks, and 8 pregnancies develope normally in accordance with the gestation period. There were no cases of transmission/allergic reactions or infectious complications in any patient. The study is ongoing, and Doppler parameters and endometrial receptivity are being evaluated.CONCLUSIONS: The study has demonstrated for the first time a new approach to the treatment of women with infertility caused by thin endometrium which is refractory to conventional hormonal and "vascular'' treatment methods. Further research is needed to provide the opport...
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