P-371 Subendometrial administration of selectively enriched angiogenic precursor cells and growth factors derived from peripheral blood and bone marrow optimizes endometrialthickness and pregnancyoutcomes in thin-endometrium patients
Authors: Sharmila J , Aruna R , Vasanthi P , Shrinivas C , Parthasarathy A , Chandrasekaran M , Anandraj R K , Venkatabaskaran S , Ashokan M 
Published: June 2023

Abstract

Study question
Can hysteroscopic instillation of 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 and growth factors significantly improved endometrial thickness (EMT) and pregnancy outcomes in women with refractory thin endometrium

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, 50 patients with persistent refractory thin endometrium were included and underwent frozen embryo transfer from September 2019-January 2023 at A4 fertility center, Chennai. Out of 50 patients, 43 were treated with peripheral blood and 7 were treated with bonemarrow derived cells and growth factors.

Participants/materials, setting, methods
50 patients with EMT&lt;6mm and &gt;2 canceled cycles included. Two doses of subcutaneous G-CSF was given on Menstrual Cycle Days 3&4, followed by 60ml venous blood or bone marrow aspirated on MCD-5. Seragen’s selective enrichment protocol was used to prepare circulating endothelial progenitor cells and growth factors concentrate. With a 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
EMT increased significantly following bone marrow and peripheral blood cells 5 days after sub-endometrial injection (5.8 ± 0.71 vs. 7.12 ± 0.8; P = 0.0001), with average increase of 1.30mm and 1.80mm respectively and considered optimal improvement when EMT≥ 7mm. 33 (66%) had an optimal response and there was a significant improvement in the endometrial thickness(mm).Cycle cancellations were significantly lesser in both peripheral blood and bone marrow group and LBR was significantly improved (p &lt; 0.05). There was no significant difference in CPR, IR and LBR between peripheral blood and bone marrow groups (p &gt; 0.05). Overall, clinical pregnancy and LBR reached up to 40% and 30%, respectively. No adverse reactions were reported. There was statistically significant probability of achieving pregnancy (p &lt; 0.01) when treated with both peripheral blood and bone marrow derived cells. Likewise, there was also a statistically significant probability of getting pregnant (p &lt; 0.05) when embryo transfer was planned in the subsequent cycle. While bone marrow group showed 100% HCG positive in all 5 out of 7 patients underwent embryo transfer and 57% (4/7) of clinical pregnancy, the sample size was small compared to peripheral blood group.

Limitations, reasons for caution
Further research is needed to provide opportunity for women with refractory thin endometrium to conceive without surrogacy. Clinician expertise in patient recruitment, dosage personalization support, and administration is paramount. Our study provides promising information for future randomized, controlled trials with large sample size in this field.

Wider implications of the findings
We have validated feasibility and efficacy of mobilized peripheral blood cells for improving endometrial pathologies when bone marrow aspiration is a challenge. Our findings show targeted delivery of personalizeddosage from minimally invasive autologous source could be new rayof hope in females failto improve despite all possible treatment options recommended surrogacy.

Trial registration number
Not applicable