P-801 Sub-endometrial administration of angiogenic precursor cells and growth factors effectively optimizes endometrial thickness (EMT) and pregnancy outcomes in women with refractory thin endometrium
Authors: Aruna R , Aparna D , Vasanthi P , Mohini S  K , Jabacks sharmila T , Sofia M , Jeyabharathi T , Chari S 
Published: July 2024

Abstract

Study question
Can hysteroscopic instillation of autologous blood derived progenitor cells combined with platelet derived growth factor concentrate into subendometrial region help patient with thin endometrium conceive?

Summary answer
Hysteroscopic subendometrial administration of stem cells represents a safe effective alternative method for patients recommended surrogacy, fail to improve despite using all possible treatment options

What is known already
Chronically thin endometrium is a challenge in ART, results in repeated expensive IVF cycles, cycle cancellations, unplanned cryopreservation of embryos and, surrogacy. Many studies have successfully used stem cells or platelet derivatives to rejuvenate reproductive tissues. When these growth-promoting cells and growth factors from platelets are delivered into basal layer which is origin of endometrial cells quality of the endometrium can be improved. While bone marrow is excellent source for obtaining stem cells main challenge is invasiveness of collection. This forms the basis for collecting mobilized endothelial progenitor cells from bone marrow into circulation for easy collection

Study design, size, duration
This study is to evaluate effect angiogenic precursor cells and growth factors derived from peripheral blood and bone marrow in improving endometrial quality and pregnancy outcomes. In the present pilot study involving 87 patients with persistent refractory thin endometrium were included and underwent frozen embryo transfer from April 2021-January 2024 at A4 fertility center, Chennai. All patients were treated with peripheral blood derived progenitor cells and platelet derived growth factors.

Participants/materials, setting, methods
87 patients with EMT&lt;7mm and &gt;2 cancelled/failed cycles included. Two doses of SC-G-CSF were given on Menstrual Cycle Day 3&4, followed by venous blood aspiration on MCD-5. Seragen’s selective enrichment protocol was used to prepare circulating endothelial progenitor cells and growth factors concentrate. With 2.9mm hysteroscope and single lumen ovum pickup needle harvested cells and growth factors were injected on all four walls of cavity.

Main results and the role of chance
In this cohort, all patients presented refractory thin endometrium during hormone replacement therapy (HRT), despite exhaustive prior medication attempts. Subendometrial injection was employed, resulting in a significant increase in endometrial thickness (EMT) post peripheral blood cell injection (6.0 ± 0.71 vs. 7.80 ± 0.8; P = 0.0001), averaging a substantial improvement of 1.80mm. An optimal response, defined as EMT≥ 7mm, was observed in 47.2% (53) of cases. Patients with improved thickness underwent embryo transfer in the subsequent cycle, displaying a significant enhancement in endometrial thickness. Out of 53 patients, 47.2% (25) tested positive for β-HCG, while 45.3% (24) tested negative. Miscarriage occurred in 9.4% (5) of patients, with 8.8% (3) delivering healthy full-term babies. Notably, 28.3% (15) sustained uneventful pregnancies, accounting for a 34% sustained implantation rate. Comparatively, when benchmarked against subendometrial platelet-rich plasma (PRP) studies, primary and secondary outcomes in our study demonstrated superiority. This favorable outcome is attributed to the combined utilization of mobilized progenitor cells and growth factors. Prior research has established that the endometrium derives its stem cell content from the bone marrow, underscoring the efficacy of this novel approach.

Limitations, reasons for caution
Future research should explore avenues for women with refractory thin endometrium, offering conception options without resorting to surrogacy. Clinician expertise in patientselection, personalized dosage, and administration is crucial. While our study offers promising insights, its limitations include small sample size and lack of randomization, emphasizing need for larger, controlled trials.

Wider implications of the findings
Our study reveals that combine use of growth factors progenitor cells enhances endometrial thickness and improves pregnancy and live birth rates. Re-evaluating need for surrogacy in nonresponsive thin endometrium may be warranted. Insights from hematopoietic stem cell research offer reliable strategy for routine use in IVF clinical practice.

Trial registration number
Not applicable