PRP and POR

PRP and POR

The most rigorously designed trial of intraovarian PRP (to date) demonstrated no improvements in # of mature oocytes obtained or in # of live births versus placebo.

Study Background

WHAT

  • Comparison of intraovarian platelet-rich plasma (PRP) to placebo for improving the number of mature oocytes (MII) obtained after controlled ovarian stimulation in women with a history of poor ovarian response (POR) with in-vitro fertilization (IVF)

WHY

  • Low to modest quality research has shown promising results with PRP for POR

  • High-quality study is needed to assess the impact of PRP in IVF for POR

WHERE/WHEN

  • Two academically affiliated reproductive centers (one in the USA and one in Turkey)

  • January 2020 - November 2022

WHO

Inclusion Criteria:

  • females ages 18-37 with POR defined as at least two IVF cycles cancelled due to poor follicle growth or just 0-2 follicles developing despite max FSH daily injections or 0-3 mature oocytes retrieved

  • male partner must have 100k or greater total motile sperm count

Female Exclusion Criteria:

  • BMI >35 kg/m2, surgically obtained sperm, or continued use of adjuncts that could result in improved ovarian response to treatment (specified CoQ10, DHEA, but presumably others per clinician’s discretion)

  • for additional exclusion criteria, see p 2 within article

HOW

  • Randomized at each site in 1:1 ratio via computer-generated block schema to PRP or no injection (control)

  • Unblinded: patients + physicians performing PRP administration

  • Blinded: physicians performing oocyte retrievals + physicians performing ultrasounds for antral follicle count (AFC) + all involved embryologists

  • PRP group

    • sedated then received intraovarian 1 mL PRP injected into four ovarian sites between days 6-10 of menstrual cycle in cycle after study enrollment

    • Received (unspecified) antibiotics to prevent surgical infection

    • Estrace (oral estradiol) 2 mg BID x 25 days started on POD1 + Prometrium (oral progesterone) 200 mg BID x 10 days taken started 15 days later

  • Control group started Estrace day after randomization and Prometrium 15 days later

  • Embryos from both groups included ICSI, day 3 hatching, TE biopsies on Days 5-6-7 with subsequent PGT-A samples

  • Euploid embryos transferred via frozen embryo transfer in subsequent menstrual cycle

  • Pregnancies monitored at IVF clinic through eight weeks

Statistics (Briefly)

  • Used intention-to-treat analysis (ITT); tests varied by normality of distibution of variables

  • Primary outcome = 0 for randomized patients who withdrew from study, who lacked mature oocytes, or had cycles cancelled

Results

  • Characteristics: 224 screened —> 112 eligible —> 87 enrolled —> 83 randomized into the two groups —> 76 proceeded with oocyte retrieval (PRP = 39, control = 37)

  • Efficacy: no improvements found in markers of ovarian reserve (AMH, AFC), # mature oocytes retrieved, # blastocysts formed, or implantation rates with PRP vs. control

  • Safety: no women experienced infections or hematomas with the PRP injection, though most of them were in mild discomfort for three days after getting PRP

Authors’ Thoughts & Conclusions

  • Increased rigor of this study design (inclusion of control group + randomization) may explain results that differ from previous PRP studies

  • Additional strengths were validated PGT-A platform, strong patient adherence/retention, and stringent inclusion criteria

  • Study limitations were PRP prep is not necessarily universally generalizable (though used commercially available product), PRP composition was not analyzed, randomization method might have been predictable, and results not generalizable beyond POR

  • PRP will not improve IVF results in POR

    Conclusions

This is the highest-quality PRP trial conducted thus far, which randomized, blinded, and compared PRP injections to no injections in infertile women with poor ovarian response. Results showed that PRP does not improve fertility markers nor outcomes compared to not giving the PRP. Future studies should be conducted with similar methodology (but recruiting additional participants at more study sites) to confirm results, especially since the results from this study conflict with previous, albeit lower-quality studies.

Resources

Cakiroglu Y, Yuceturk A, Karaosmanoglu O, et al. Ovarian reserve parameters and IVF outcomes in 510 women with poor ovarian response (POR) treated with intraovarian injection of autologous platelet rich plasma (PRP). Aging (Albany NY). 2022;14(6):2513-2523. doi:10.18632/aging.203972

Herlihy NS, Cakiroglu Y, Whitehead C, et al. Effect of intraovarian platelet-rich plasma injection on IVF outcomes in women with poor ovarian response: the PROVA randomized controlled trial. Hum Reprod. Published online May 9, 2024. doi:10.1093/humrep/deae093

Food and Drug Administration. BK210591 - Platelet-Rich Plasma (PRP) Procedure Pack. Accessed September 7, 2024. BK210591 - Platelet-Rich Plasma (PRP) Procedure Pack | FDA

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