First data on in vitro fertilization and blastocyst formation after intraovarian injection of calcium gluconate-activated autologous platelet rich plasma

Abstract

Platelets modulate clinically relevant yet incompletely understood tissue regeneration processes, and platelet rich plasma (PRP) has been previously used with some success in various non-reproductive medical contexts. Here, we extended PRP application to ovarian tissue with a view to document impact on ovarian reserve among women attending for infertility treatment. PRP was freshly isolated from patients (n= 4) with diminished ovarian reserve as determined by at least one prior IVF cycle canceled for poor follicular recruitment response or estimated by serum AMH and/or FSH, no menses for ≥1 year. Immediately following substrate isolation and activation with calcium gluconate, approximately 5 mL of autologous PRP was injected into each ovary under direct transvaginal sonogram guidance. For each study subject, AMH, FSH, and serum estradiol data were recorded at two-week intervals post-PRP and compared to baseline (pre-PRP) values. In this pilot group, mean (±SD) patient age was 42 ± 4 years with infertility duration reported as 60 ± 25 months. Following this protocol of intraovarian PRP administration, increases in serum AMH (p = .17), decreases in FSH (p < .01), or both, were observed in all cases, sufficient to permit retrieval of 5.3 ± 1.3 MII oocytes. IVF occurred 78 ± 22 (range =  59–110) days after activated PRP injection, and results appeared independent of patient age, infertility duration, baseline platelet concentration or pretreatment antral follicle count. Each patient had at least one blastocyst suitable for cryopreservation. While autologous PRP has been successfully applied therapeutically to various tissues to accelerate healing and wound repair, this is the first description of direct injection of activated PRP into the human ovary of poor prognosis IVF patients. Evidence of improved ovarian function was noted in all who received intraovarian PRP, possibly as early as two months after treatment. Additional research is needed to clarify (and enhance) which PRP components are responsible for altered ovarian function, and to identify predictive characteristics for patients most likely to benefit from this intervention.

Chinese abstract

血小板调节临床相关但尚未完全了解的组织再生过程, 并且富含血小板的血浆（PRP）先前已在各种非生殖医学环境中取得了一些成功。在这里, 我们将PRP应用扩展到卵巢组织, 以记录对不孕症治疗女性卵巢储备的影响。PRP从卵巢储备减少的患者（n = 4）中新鲜分离出来, 这些病人至少有一个先前因卵泡募集反应不良而被取消的IVF周期或通过血清AMH和/或FSH估计、1年没有月经。在用葡萄糖酸钙进行底物分离和活化后, 立即在直接经阴道超声波指导下将约5mL自体PRP注射到每个卵巢中。对于每个研究受试者, 在PRP后每两周间隔记录AMH, FSH和血清雌二醇数据, 并与基线（PRP前）值进行比较。在该试验组中, 平均（±SD）患者年龄为42±4岁, 不孕持续时间为60±25个月。按照该卵巢内PRP给药方案, 在所有病例中观察到血清AMH（p =0 .17）的增加, FSH降低（p <0.01）或两者均降低, 足以允许回收5.3±1.3个MII卵母细胞。激活PRP注射后IVF发生在78±22天（范围= 59-110）, 结果与患者年龄、不孕持续时间、基线血小板浓度或治疗前窦卵泡计数无关；每位患者都至少有一个适合冷冻保存的胚泡。尽管自体PRP已经成功地应用于各种组织以加速愈合和伤口修复, 但这是将活化的PRP直接注射到预后不良的IVF患者的人卵巢中的第一个描述。所有接受卵巢内PRP治疗的人都记录到卵巢功能改善的证据, 可能在治疗后两个月开始出现。需要进一步研究以澄清（和增强）哪些PRP组分有改变卵巢功能的作用, 并确定最有可能从这种干预中受益的患者的预测特征。

Keywords:

• Platelet rich plasma
• ovary
• senescence
• fertility potential
• stem cells
• regeneration

Disclosure statement

None of the authors report any conflict of interest with this research.