P-056 NOA-SERA: combined autologous progenitor cells and platelet-derived growth factors for male factor infertility due to non-obstructive azoospermia and severe oligoasthenoteratozoospermia (OATS) – a case series
Authors: Katakam D  N , Sneha G , Srinivas C , Vasanthi P 
Published: July 2024

Abstract

Study question
Can NOA-SERA be utilizing autologous progenitor cells and platelet-derived growth factors,effectively address male factor infertility in non-obstructive azoospermia (NOA) and severeoligoasthenoteratozoospermia (OATS)

Summary answer
Intra-testicular NOA-SERA transplantation of autologous progenitor cells andgrowth factors shows promise in improving spermatogenesis and fertilization potential,presenting potential breakthrough for male factor infertility.

What is known already
Male infertility affects 10–15% of couples, with non-obstructive azoospermia (NOA)diagnosed in 60% of azoospermic men. Current interventions, including platelet-rich plasma and stem cells, show variable success. This study introduces a novel protocol, NOA-SERA, combining autologous mobilized progenitor cells and platelet-derived growth factors to restore spermatogenesis. Despite advancements in assisted reproduction, male factor infertility due to primary NOA remains challenging. This case series explores the safety and efficacy of NOA-SERA, avoiding in vitro breeding risks and emphasizing intratesticular transplantation’s safety and efficacy

Study design, size, duration
his case series (March 2019–November 2023) includes 7 male factor infertility patients,consisting of 4 non-obstructive azoospermic NOA, 1 cryptozoospermia and 2 severe oligoaesthenoteratospermic (OATS, strongly desirous of pregnancy with self-gamete. All patients received NOA-SERA following written consent. One-year follow-up included hormonal profiling, semen analysis, and testicular biopsy assessment

Participants/materials, setting, methods
Seven men, with normal karyotype, underwent NOA-SERA due to male factor infertility. This intervention involved intra-testicular transplantation of autologous CD34+/CD133+ enriched peripheral blood mononuclear stem cells (MPB-MNCs) combined with platelet derived growth factors. The procedure, avoiding in vitro breeding and manipulation, prioritized safety and efficacy. Follow-up for one year included hormonal profile, semen analysis, testicular biopsy assessments, clinical pregnancy (b-hCG), sustained implantation (&gt;8 weeks), and live birth rates were followed.

Main results and the role of chance
Analysis of NOA-SERA treatment in this case series revealed positive outcomes in 70% of patients, showing increased testicular size, elevated testosterone, and reduced FSH levels. In our study, out of 4 NOA, 2 NOA remained NOA, 1 progressed to OATS, 1 progressed to normal semen analysis after 3 months. Couple conceived with intrauterine insemination (IUI) first pregnancy and they also had a subsequent natural conception. 1 Crypto progressed to OATS and 1 severe OATS remained the same and one progressed to OATS. Although no appearance of sperm in the ejaculate was observed, 2 patients displayed sperms in Testicular Sperm Aspiration (TESA) sufficient for ICSI. Couples undergoing IVF therapy post-biopsy achieved successful fertilization in two cases, leading to positive pregnancies and sustained implantation and livebirth of healthy full-term babies. Post-procedure FSH was slightly lower than pre-procedural levels, indicating hormonal improvement without observed therapy-related deterioration. The novelty lies in the intratesticular transplantation of mobilized purified autologous CD34+/CD133+ enriched MPBMNCs with platelet-derived growth factors, avoiding in vitro risks.” To summarise, 3 out of 7 achieved successful pregnancy, 2 NOA with ICSI, 1 NOA progressed to normal semen analysis and pregnancy with IUI

Limitations, reasons for caution
Despite interesting results, limitations include the self-controlled case series design and asmall patient cohort, lacking a comparison to a control group. Future studies should include more patients, stratified for age, aetiology, and other risk factors, to further elucidate this intervention’s mechanism of action

Wider implications of the findings
NOA-SERA demonstrates promise in enhancing spermatogenesis and fertilization potential, emphasizing necessity for larger randomized trials to ascertain clinical efficacy, particularly in subgroups of OATS&NOA patients. NOA-SERA emerges as safe, cost-effective adjuvant for optimizing spermatogenesis and improving IVF success and pregnancy outcomes in male factor infertility.

Trial registration number
Not applicable