The Effects of Intraovarian Injection of Autologous Menstrual Blood-Derived Mesenchymal Stromal Cells on Pregnancy Outcomes in Women with Poor Ovarian Response

Abstract

Background The major obstacle associated with assisted reproduction is poor ovarian response (POR) to controlled ovarian stimulation. Consequently, mesenchymal stem cell therapy has been proposed as a potential treatment for female infertility and/or restoration of ovarian function in POR women. The initial phase of the study showed an increase in pregnancy rate for women with POR who received menstrual blood-derived-mesenchymal stromal cells (MenSCs) into their ovaries. The objective was to evaluate whether this treatment could improve ovarian reserve parameters and pregnancy outcome in a larger population with POR. Method This study included 180 infertile individuals with reduced ovarian reserve who declined oocyte donation. The participants were separated into two groups according to their preference: those who received bilateral MenSCs intraovarian injection and those who did not receive any intervention. These two groups were further divided into two age categories (≤ 40 years and > 40 years). The primary outcomes assessed included a comparison of serum FSH, AMH, and AFC levels pre- and post-treatment. Secondary outcomes evaluated were the quantity and quality of oocytes and embryos, biochemical/clinical pregnancy rates, live birth rates. Results The treatment of MenSCs was found to be generally well-tolerated and free of safety issues. At the 2-4-month follow-up, there was a significant improvement in AMH (P = 0.0007) and AFC (P < 0.001) among the women treated with MenSCs, while the control group experienced a notable decrease in these values (P < 0.0001 and P < 0.001, respectively). A subgroup analysis based on age (≤ 40 years) revealed that 12 (27.3%) patients in the MenSCs group and just 2 (4.5%) patients in the control group had spontaneous pregnancies within 3 to 4 months (P = 0.003). Similarly, 8 people from the MenSCs group (27.6%) and 2 from the control group (4.8%) became pregnant after ICSI (P = 0.009). Conclusion The injection of MenSCs is an efficacious and safe methodology to improve markers of low ovarian reserve, particularly in women aged forty or younger. This treatment has been found to significantly increase the number and quality of oocytes, the embryo quality, the fertilization rate, and the pregnancy rate, particularly spontaneous pregnancies, and boost the live birth rate. Trial registration: ClinicalTrials.gov Identifier: NCT05703308. Registered 01/26/2023, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05703308. IRCT, IRCT20180619040147N4. Registered 08/01/2020.