Abstract

Abstract Study question Does intraovarian injection of autologous platelet-rich plasma (PRP) improve oocyte yield in young patients with poor ovarian response (POR)? Summary answer Intra-ovarian PRP injection did not result in increased number of oocytes retrieved or improvement of any other relevant measured outcomes. What is known already POR is one of the major hurdles to overcome in patients undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Several methods have recently emerged to attempt follicular reactivation in these patients with a poor prognosis. One of them, the intra-ovarian injection of autologous PRP, demonstrated promising results in retrospective and prospective cohort studies. Study design, size, duration This was a multi-center, randomized controlled trial (RCT) to evaluate the efficacy of PRP in improving IVF outcomes in women with POR. Patients who met inclusion criteria (<38 years, two or more prior cycles with < 3 oocytes retrieved, and without single gene disorders, prior ovarian surgery, endometriomas, BMI >35, or severe male factor infertility) were randomized to either receive an autologous intra-ovarian PRP injection (PRP group) or no intervention (control group) prior to COH. Participants/materials, setting, methods A total of 83 patients were randomized to PRP group (n = 41) or control group (n = 42). After treatment, patients underwent COH, oocyte retrieval, intracytoplasmic sperm injection (ICSI), preimplantation genetic testing for aneuploidy (PGT-A), and single frozen euploid embryo transfer. Number of MII oocytes obtained was the primary outcome. Secondary outcomes included ovarian reserve tests (antral follicle count [AFC] and anti-Mullerian hormone [AMH]), blastocyst and euploid blastocyst yields, and sustained implantation. Main results and the role of chance No significant differences were observed in number of MII oocytes retrieved (3.1 ± 3.3 vs 2.8 ± 2.4 in PRP vs control, respectively; p = 0.9), blastocysts (1.3 ± 2.1 vs 1.0 ± 1.3, p = 0.8), or euploid blastocysts (0.9 ± 1.6 vs 0.8 ± 1.1; p = 0.5) per cycle. Similarly, no differences were observed in the likelihood of obtaining at least one euploid blastocyst (37 vs 45%, p = 0.4; relative risk [RR], 95% confidence interval [CI] 0.9, 0.6-1.2) or the rate of sustained implantation (29 vs 31%, p = 0.9; RR 1.0, 0.7-1.3). Pre- and post-treatment AFC in both groups (PRP: from 5.2 ± 3.2 to 7.9 ± 4.5, p < 0.0001; control: from 5.6 ± 3.3 to 6.8 ± 4.8, p = 0.02) were statistically significantly different, whereas AMH was different in the PRP group only (PRP: 0.73 ± 0.46 to 0.99 ± 0.98, p = 0.02; control: 0.70 ± 0.59 to 0.73 ± 0.57, p = 0.59). Limitations, reasons for caution Oocyte retrieval took place the cycle immediately following treatment; therefore, we could not evaluate long-term effects of PRP on ovarian reserve or response. Lack of a placebo group would limit interpretability had a difference between groups been observed. The effect of PRP on patients >38 years old was not studied. Wider implications of the findings Intra-ovarian PRP injection did not improve reproductive outcomes by any relevant measure. Our findings do not support wide utilization of PRP to improve IVF outcomes in women with POR. Trial registration number NCT04163640

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