高龄DOR患者，注射富含生长因子能改善卵巢储备？

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OBJECTIVE

目的

Plasma rich in growth factors (PRGF) or platelets (PRP) contain up to 800 types of proteins, cytokines, hormones, and growth factors. Indeed, intraovarian PRP injection has been proposed to improve the reproductive performance in diminished ovarian reserve (DOR) and POI women with encouraging results promoting follicle growth. Thus, we aimed to evaluate if PRGF intraovarian optimizes the ovarian reserve but also the IVF outcomes in aged DOR patients.

富含生长因子（PRGF）或血小板（PRP）的血浆中含有高达800种蛋白质、细胞因子、激素和生长因子。事实上，已经提出通过卵巢内注射PRP来改善卵巢储备减少（DOR）和卵巢早衰POI女性的生殖能力，在促进卵泡生长方面取得了令人鼓舞的结果。因此，我们旨在评估PRGF卵巢内注射是否可以优化高龄DOR患者的卵巢储备，并改善IVF结果。

MATERIALS AND METHODS

材料和方法

Retrospective study including 348 women (25-45 years) who received intraovarian PRGF between 2020 and 2022 at IVIRMA Alicante (Spain). The study was approved by the IRB committee of La Fe University Hospital (2112-FIVI-109-SH).

Patients underwent a PRGF injection (Endoret kit; Biotechnology Institute S.L, Spain) in both ovaries and a follow up for ovarian reserve biomarkers (AFC, AMH) during 4 months after treatment, to evaluate follicular reactivation. Then, reproductive and IVF outcomes were compared with previous ovarian stimulation cycles (COS) started in our clinics, when available. Study variables were compared to basal levels with a paired t-test.

回顾性研究2020年至2022年间在西班牙阿利坎特IVIRMA接受卵巢内注射PRGF的348名女性（25-45岁）。这项研究得到了拉非大学医院IRB委员会（2112-FIVI-109-SH）的批准。

患者接受了双侧卵巢PRGF注射（Endoret试剂盒；西班牙生物技术研究所），并在治疗后4个月内随访卵巢储备生物标志物（AFC、AMH），以评估卵泡再活化情况。然后，将注射后的IVF结局与我们诊所注射前的卵巢刺激周期（COS）结局进行比较。用配对t检验将研究变量与基础水平进行比较。

RESULTS

结果

A total of 348 aged DOR patients (AMH: 0.29±0.46ng/ml; AFC0: 2.0±2.2) underwent PRGF intraovarian treatment, and showed statistically significant increases in AFC (AFC1: 4.1±3.6, p<0.0001; AFC2: 3.5±3.6, p<0.0001; AFC3 3.0±2.4, p<0.0001 and AFC4: 3.5±2.4, p=NS) during the entire follow up, compared to basal levels established before receiving the PRGF injection.

Among all the included patients, 137 of them (39.8±3.8 y.o) initiate a total of 255 COS in our clinic, after PRGF that were compared with their previous 156 COS performed before PRGF (39.7±3.1 y.o). Although AMH and E2 levels were significantly higher in their previous attempts (AMH: 0.70± 0.94 vs. 0.46±0.56, p<0.013 and E2: 274.2±359.5 vs. 149.3±318.5, p=0.016), oocyte pick up was successfully developed in 70.2% and embryos obtained in 57.6% of started COS after treatment.

With similar stimulation protocols, PRGF was able to improve the oocyte maturation (69.4% vs. 79.8% p=0.02), fertilization (64.7% vs. 75.2%,p=0.035) and implantation rates (7.1±23.9% vs. 32.4±47.47.5%, p=0.040) in these aged DOR women. Moreover, the number of vitrified embryos for future transfer (0.2±0.5 vs. 0.4±0.9, p=0.035) and the biochemical pregnancy rate (9.5% vs. 37.5%, p=0.044) were also increased. Indeed, 33.3% of the achieved pregnancies after PRGF were spontaneous.

在整个随访过程中，共有348名高龄DOR患者（AMH:0.29 ±0.46ng/ml；AFC0:2.0±2.2）接受了PRGF卵巢内注射治疗。与接受PRGF卵巢注射前确定的基础水平相比，AFC显著提高（AFC1:4.1 ±3.6，p<0.001；AFC2:3.5±3.6，p<0.0001；AFC3：3.0±2.4，p<0.0001和AFC4:3.5±2.4，p＝NS）。

在所有纳入的患者中，137名患者（39.8±3.8 y.o）接受了卵巢内注射PRGF后在我们中心总共启动了255次COS。与他们注射PRGF前进行的156次COS（39.7±3.1 y.o）相比，尽管AMH和E2水平在他们之前的COS中更高（AMH:0.70±0.94 vs.0.46±0.56，p<0.013和E2:274.2±359.5 vs.149.3±318.5，p＝0.016），但经处理后，获卵率达到70.2%，57.6%的COS获得可移植胚胎。

在相似的卵巢刺激方案情况下，PRGF能够提高这些高龄DOR妇女的卵子成熟度（69.4% vs 79.8%，p=0.02）、受精率（64.7% vs 75.2%，p=0.035）和种植率（7.1±23.9% vs 32.47±47.5%，p=0.040）。此外，将来可移植的冻胚数（0.2±0.5 vs 0.4±0.9，p=0.035）和生化妊娠率（9.5% vs 37.5%，p=0.044的0.044）也提高了。事实上，在PRGF后实现的妊娠中，33.3%是自然妊娠。

CONCLUSIONS

结论

PRGF injection promoted follicle development since the first follow-up allowing the initiation of COS cycles. Moreover, PRGF showed positive effects on reproductive outcomes by improving oocyte maturation, fertilization, implantation, and biochemical pregnancy rates.

自最初随访PRGF注射后的COS周期以来，我们发现PRGF促进了卵泡发育。此外，PRGF通过提高卵子成熟度、受精率、种植率和生化妊娠率，对生殖结果产生了积极影响。

IMPACT STATEMENT

影响声明

PRGF intraovarian injection reactivates follicle growth to perform COS and embryo obtention in a poor prognosis population of aged patients with DOR. The effects recorded in our cohort suggest that PRGF might improve quality and development potential of the obtained MII oocytes. However, large clinical trials with a proper non-intervention control group are still requested to elucidate the efficacy and mechanisms of the technique.

在预后不良的高龄DOR患者中，卵巢内注射PRGF可重新激活卵泡生长，以促进COS和胚胎获取。在我们的队列中记录的结果表明，PRGF可能提高获得的MII卵的质量和发育潜力。然而，仍需要一个适当的非干预对照组进行大型临床试验，以阐明该技术的疗效和机制。

文章来源：

INTRAOVARIAN INJECTION OF PLASMA RICH IN GROWTH FACTORS IMPROVES FOLLICLE GROWTH AND OOCYTE QUALITY AFTER COS IN AGED WOMEN WITH DIMINISHED OVARIAN RESERVE Herraiz, Sonia et al.Fertility and Sterility, Volume 120, Issue 4, e71 - e72