DOI: 10.1093/humrep/deaf097.1105 ISSN: 0268-1161

P-801 Sub-Endometrial Administration of Angiogenic Precursor Cells and Growth Factors Enhances Endometrial Thickness and Pregnancy Outcomes in Refractory Thin Endometrium

R Vernekar, Y Rashmi, R Rupa, N Niveditha, C Srinivas, P Vasanthi

Abstract

Study question

Does hysteroscopic instillation of autologous blood-derived progenitor cells and platelet-derived growth factors improve endometrial thickness and pregnancy outcomes in patients with refractory thin endometrium?

Summary answer

This procedure significantly improved endometrial thickness, achieving optimal response in 92% of patients. The β-HCG positivity rate reached 71.3%, leading to 33.3% full-term healthy deliveries.

What is known already

Recurrent thin endometrium presents a significant barrier to successful assisted reproduction, often leading to canceled cycles and recommendations for surrogacy. Standard therapies, including hormonal and vascular agents, frequently fail to achieve optimal endometrial receptivity. Regenerative approaches utilizing stem cells and platelet-derived growth factors have demonstrated potential in enhancing tissue regeneration and vascularization. Sub-endometrial delivery of blood-derived progenitor cells and concentrated growth factors targets local tissue remodeling and angiogenesis, offering a novel solution for patients with refractory thin endometrium. This approach aims to restore endometrial thickness and receptivity, thereby improving implantation and pregnancy success rates.

Study design, size, duration

This retrospective, self-controlled study was conducted from August 2023 to October 2024, involving 150 patients with refractory thin endometrium (EMT <7 mm) and more than three failed or canceled cycles. All participants underwent frozen embryo transfer (FET) following sub-endometrial administration of autologous progenitor cells and platelet-derived growth factors.

Participants/materials, setting, methods

Patients received two doses of subcutaneous G-CSF on menstrual cycle days 3 and 4, followed by venous blood aspiration on day 5. Autologous peripheral blood-derived progenitor cells and growth factors were isolated using Seragen’s selective enrichment protocol. The prepared concentrate was hysteroscopically injected into the sub-endometrial layer of all four uterine walls. Endometrial thickness, vascularity, and pregnancy outcomes were assessed before and after the procedure.

Main results and the role of chance

The study included 150 patients with an average age of 33.5 ± 4.4 years, BMI of 25.7 ± 2.9 kg/m², and infertility duration of 5.9 ± 2.2 years. Post-treatment, EMT increased significantly from 7.3 ± 2.3 mm to 9.2 ± 2.0 mm (P = 0.0001), with an average improvement of 1.9 mm. An optimal response (EMT ≥7 mm with vascularity across all three zones) was observed in 138 patients (92%).Following embryo transfer, 107 patients (71.3%) tested positive for β-HCG. Among these, 50 patients (33.3%) delivered healthy full-term babies, and 44 (29.3%) had ongoing pregnancies beyond 24 weeks. Eight patients (5.3%) experienced miscarriage, and 5 patients (3.3%) had biochemical pregnancies. 22 patients(15%) were recommended surrogacy conceived and delivered fullterm babies. The sustained implantation rate was 42%. Compared to subendometrial PRP studies, this approach demonstrated superior outcomes in endometrial receptivity and pregnancy success.These results suggest that combining angiogenic progenitor cells with platelet-derived growth factors effectively improves both endometrial thickness and pregnancy outcomes in refractory cases. However, further research with larger randomized trials is needed to confirm these findings and optimize treatment protocols.

Limitations, reasons for caution

This study is limited by its non-randomized self controlled design and relatively small sample size. Further large-scale controlled trials are needed to confirm efficacy and assess long-term outcomes. Success depends on clinician expertise in patient selection, dose personalization, and precise administration techniques.

Wider implications of the findings

This innovative approach provides a transformative alternative to surrogacy for women with refractory thin endometrium. By improving endometrial receptivity and implantation rates, combining autologous progenitor cells and growth factors offers new hope for achieving conception and live birth in challenging infertility cases.

Trial registration number

No

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