Center for Human Reproduction

Abstract Study question Does intraovarian platelet-rich plasma (PRP) improve embryo quality, ovarian biomarkers, or pregnancy outcomes compared with platelet-poor plasma (PPP) in women with diminished ovarian reserve (DOR)? Summary answer PRP did not improve embryo quality, ovarian response, hormone markers, or pregnancy outcomes compared with PPP. What is known already Autologous PRP has been promoted as a potential strategy to improve ovarian function and fertility in women with DOR, based largely on uncontrolled case series and biologic plausibility related to growth factors release. Reported improvements in hormone levels, follicular development, and oocyte yield remain inconsistent, and few randomized controlled data exist. Additionally, the absence of appropriate control groups and standardized preparation protocols limits interpretation of published studies and has contributed to wide clinical adoption despite limited evidence. Study design, size, duration Randomized, quadruple-blinded, placebo-controlled trial with planned enrollment of 90 participants; 68 randomized to date; 65 initiated a post-randomization IVF attempt. Recruitment began February 2020 and was halted following an interim analysis indicating a low likelihood of treatment benefit. Participants/materials, setting, methods Women aged ≤44 years with DOR (FSH >12 IU/L, AMH <1.0 ng/mL, and <6 oocytes in a prior cycle) were randomized to intraovarian PRP or PPP prepared using RegenLab centrifugation. Primary endpoint was ≥1 day-3 eight-cell embryo with <5% fragmentation obtained from the first IVF cycle. Cancelled cycles due to lack of response were analyzed as failures; true dropouts were excluded. Hormone levels and pregnancy outcomes were assessed exploratorily. Trial registration number ClinicalTrials.gov identifier: NCT04278313 Main results and the role of chance Sixty-five participants initiated post-randomization IVF (PRP n = 32; PPP n = 33); 14 cycles were cancelled (failed); 52 completed cycles were evaluable for embryo quality (PRP n = 26; PPP n = 26). No PRP participant achieved the primary endpoint of ≥ 1 high-quality day-3 embryo, compared with one participant in the PPP arm (0/26 vs 1/26; Fisher’s exact p = 1.00). A sensitivity analysis incorporating day-4 embryos yielded identical results. Median usable embryo yield was numerically similar or slightly higher in PPP than PRP (median 9 vs 5 embryos), with no difference in the proportion achieving any usable embryo (81% PRP vs 76% PPP; p = 0.77). Baseline and post-treatment AMH, FSH, and estradiol did not differ between groups. No signal favoring PRP was observed for clinical pregnancy or live birth. Overall, effect estimates showed no evidence of efficacy or biological effect for PRP, with observed differences consistent with random variation. Limitations, reasons for caution The primary endpoint was rare in this severe DOR population, limiting power to detect small effects. Some hormone data were incomplete, and long-term reproductive outcomes remain limited by sample size. Wider implications of the findings These findings do not support routine clinical use of intraovarian PRP for DOR. Rigorous randomized data suggest limited biological efficacy, emphasizing the need for caution before adopting costly or invasive ovarian “rejuvenation” interventions. Trial registration number Yes

STUDY QUESTION:Has the efficiency of IVF cycles in the USA declined between 2012 and 2021? SUMMARY ANSWER:National U.S. data show a continuous linear decline in IVF cycle efficiency between 2012 and 2021. WHAT IS KNOWN ALREADY:Previous studies reported that live birth rates after IVF increased until 2010 but subsequently declined, potentially due to the introduction of IVF 'add-ons' and changes in clinical practice. STUDY DESIGN SIZE DURATION:Retrospective cohort study, using publicly available national U.S. IVF outcome data reported annually to the Centers for Disease Control and Prevention (CDC) for the period 2012-2021. PARTICIPANTS/MATERIALS SETTING METHODS:CDC annual reports were used as a data source. Extracted variables included a number of IVF cycle starts, embryo transfers, embryo banking cycles, and live births. IVF 'treatment efficiency' was calculated as the proportion of live births per initiated cycle (intent-to-treat analysis). MAIN RESULTS AND THE ROLE OF CHANCE:Over the study period, IVF cycle starts increased by 234.7% (176 274 to 413 776), embryo transfers by 150.3% (134 471 to 202 121), and embryo banking cycles by 902.3% (18 585 to 167 689). Live births increased by 179.2% (51 286 to 91 906). However, cycle efficiency declined from 29.1% in 2012 to 22.2% in 2021, a relative reduction of 23.4%, with an approximately linear decline across the decade. LIMITATIONS REASONS FOR CAUTION:The study is based on aggregate CDC data without patient-level granularity. Therefore, analyses could not control for confounding factors such as parity, infertility diagnosis, or detailed age subgroups. Embryo banking practices also complicate year-to-year comparisons of live birth rates. WIDER IMPLICATIONS OF THE FINDINGS:These findings suggest that despite substantial growth in IVF cycle numbers, treatment efficiency has progressively declined in the USA over the last decade. This decline coincided with a rapid increase in the use of embryo banking and other IVF 'add-ons'. The results raise concern about current clinical practices and highlight the need for critical re-evaluation of routine interventions in IVF. STUDY FUNDING/COMPETING INTERESTS:No external funding was received for this study. NG and DHB hold patents related to androgen treatment in females (DHEA) with numbers US8067400B2, US8501718B2, and US9375436B2 (listed in USPTO/public records and assigned to American Infertility of New York). They also receive royalties from Nutraceuticals LLC, which has helped commercialize DHEA as a nutritional supplement. TRIAL REGISTRATION NUMBER:N/A.

RESEARCH QUESTION:Is the routine practice of triggering ovulation at a fixed follicle size (18-22 mm) in IVF optimal across all age groups? DESIGN:An analysis of 109 autologous IVF cycles with fresh embryo transfer performed in 2025 was undertaken at the authors' New York fertility centre, following the approach of trigger-timing optimization from a 10-year experience with the Highly Individualized Egg Retrieval (HIER) protocol. HIER is based on the longitudinal understanding of age-related changes in follicular dynamics and oocyte maturity, involving lowering follicle size thresholds for triggering with advancing ovarian age - often to less than 12-14 mm in patients over 43 years of age - combined with routine rescue in-vitro maturation (rIVM) of all immature oocytes. The main outcome was clinical pregnancy rate, both global (median age 42.8 years, range 26.6-51.9 years) and over age 43 (median age 46.9 years, range 44.0-51.9 years), a decade after implementation of HIER with rIVM. RESULTS:In 2025, a 12% overall clinical pregnancy rate per transfer was achieved in women with a median age of 42.8 years, and 8% in the subset of patients aged 44 years or older. CONCLUSIONS:The universal application of a fixed follicle size (18-22 mm) for ovulation triggering may be outdated. Age-adjusted protocols such as HIER optimize IVF success, especially in older or poor-prognosis patients in whom there tends to be a rapid acceleration of premature luteinization. This warrants further validation for broader clinical adoption.