STUDY QUESTION Does intraovarian injection of platelet-rich plasma (PRP) change ovarian function in patients with extremely low functional ovarian reserve (LFOR) who, otherwise, would likely only have a chance of pregnancy through third-party oocyte donation? SUMMARY ANSWER No clinically significant effects of PRP treatment on ovarian function were observed over 1 year of follow-up. WHAT IS KNOWN ALREADY Several investigators have reported improved responses to ovulation induction after treatment with PRP. However, previous published reports have involved, at most, only small case series. Whether PRP actually improves ovarian performance is, therefore, still unknown. PRP is nevertheless widely offered as an 'established' fertility treatment, often under the term 'ovarian rejuvenation'. STUDY DESIGN, SIZE, DURATION We are reporting a prospective cohort study of 80 consecutive patients at ages 28-54 with LFOR, defined by anti-Mullerian hormone <1.1 ng/ml, FSH >12 mIU/ml or at least one prior IVF cycle with <= 3 oocytes within 1 year. The women were followed for 1 year after an intraovarian PRP procedure. PARTICIPANTS/MATERIALS, SETTING, METHODS PRP (1.5 ml) was injected into the cortex of ovaries with an average of 12 injections per ovary. Study participants were followed every 3 days for 2 weeks after PRP treatment with estradiol and FSH measurements and vaginal ultrasound to observe follicle growth and thereafter followed weekly. Beginning 1 month after their PRP treatment, participants underwent one or more cycles of ovarian stimulation for IVF. Outcome measures were endocrine response, and numbers of oocytes and embryos produced in response to a maximal gonadotropin stimulation before and after PRP treatment. MAIN RESULTS AND THE ROLE OF CHANCE In this study, women failed to demonstrate statistically significant outcome benefits from intraovarian PRP. However, two 40-year-old very poor-prognosis patients, with prior failed IVF cycles that never reached embryo transfer at other centers, achieved pregnancy, resulting in an ongoing pregnancy rate of 4.7% among patients who, following PRP, produced at least one oocyte (n = 42). LIMITATIONS, REASONS FOR CAUTION As an observational study of patients who performed poorly in past ovarian stimulation cycles, the improvement may be accounted for by regression to the mean. Similar considerations may also explain the occurrence of the two pregnancies. WIDER IMPLICATIONS OF THE FINDINGS This study demonstrates that, even in extremely poor prognosis patients due to LFOR, sporadic pregnancies are possible. The study, however, does not allow for the conclusion that those pregnancies were the consequence of PRP treatments. A case series, indeed, does not allow for such conclusions, even if results are more suggestive than here. This registered study, therefore, must be viewed as a preliminary report, with further data expected from this study but also from two other prospectively randomized ongoing registered studies with more controlled patient selection. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by intramural funds from The Center for Human Reproduction and the not-for-profit research Foundation for Reproductive Medicine, both in New York, NY, USA. N.G. and D.H.B. are listed as co-inventors on several US patents. Some of these patents relate to pre-supplementation of hypo-androgenic infertile women with androgens, such as dehydroepiandrosterone and testosterone and, therefore, at least peripherally relate to the subject of this manuscript. They, as well as D.F.A. , have also received research support, travel funds and speaker honoraria from several pharmaceutical and medical device companies, though none related to the here presented subject and manuscript. N.G. is a shareholder in Fertility Nutraceuticals and he and D.H.B. receive royalty payments from Fertility Nutraceuticals LLC. E.M. has no conflicts of interest to declare.