P-332 Management of Thin Endometrium by hysteroscopic instillation of G-CSF mobilized progenitor cells combined with platelet-derived growth factor concentrate into the sub endometrial region-A case series

Abstract

Abstract Study question Can hysteroscopic instillation of G-CSF mobilized 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 Thin endometrium is still a challenge in ART, and is considered sub-optimal for transfer and associated with lower implantation and pregnancy rates. For such patients and their treating physicians, chronically thin endometrium results in repeated expensive IVF cycles, cycle cancellations, unplanned cryopreservation of embryos and, in most extreme cases in the utilization of gestational carriers. Strategies like hysteroscopic adhesiolysis, estrogen, vasoactive chemical measures, and infusion of growth factors into the uterus, have little or no effect. Recently, many studies have successfully used stem cells or PRP alone or in combination for rejuvenation of reproductive tissues and organ failure. Study design, size, duration Case series study involving 20 patients with persistent non-responsive thin endometrium were included and underwent frozen embryo transfer over a period of 18 months from July 2020-December 2021 at A4 fertility center, Chennai Participants/materials, setting, methods 20 patients with thin endometrium and more than two implantation failures were included. Two doses of subcutaneous G-CSF were given on Menstrual Cycle Day 3&4, followed by 60ml venous blood aspirated 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 implanted in sub-endometrial zone on all four walls of cavity. Main results and the role of chance 20 patients with thin endometrium of less than 7mm and previously more than two implantation failures were included. In spite of routine HRT with Estradiol valerate and intrauterine PRP instillation, endometrium was non-responsive. After another failed attempt using letrozole for ovulation induction to improve endometrial thickness, we ventured into the option of hysteroscopic stem cell instillation. Average endometrial thickness increased from 6.35±0.6mm to 7.32±0.7mm. Out of 20 patients who underwent FET, 12(60%) became pregnant of whom 2(10%) delivered successfully. 6(30%) uneventful pregnancies are ongoing and 4(20%) had miscarriage and 8 patients didn’t conceive are recruited for ET in the next cycle. Many studies have successfully used stem cells or PRP for rejuvenation of reproductive tissues. When these growth-promoting cells and growth factor 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 to treat endometrial pathologies, main challenge is invasiveness of collection. To overcome this, we have adopted G-CSF mobilization to mobilize endothelial progenitor cells from bone marrow into circulation for easy collection and concentration. Limitations, reasons for caution Further research is needed to provide opportunity for women with refractory thin endometrium to conceive without surrogacy. Our study provides promising information for future randomized, controlled trials with large sample size in this field.This study has limitation of being small size with the women serving as their own historical controls. Wider implications of the findings We demonstrated that the proposed combination of two less invasive yet proven therapeutics combined with targeted delivery could be new ray of hope in females recommended for surrogacy or who fail to improve despite all possible treatment options and reduces emotional and financial burden associated with surrogacy and repeated IVFcycles. Trial registration number Not Applicable