Autologous platelet-rich plasma ovarian injection was associated with increased oocyte acquisition in patients with poor ovarian response: a retrospective propensity-matched study.

A total of 1833 oocyte retrieval cycles met the inclusion criteria. Following propensity score matching (PSM), 91 oocyte retrieval cycles in patients who had received autologous platelet-rich plasma ovarian injections were matched with 261 cycles in the control group (Fig.  1 ). After PSM, all the baseline characteristics, including female age, infertility type, etiology of infertility, infertility duration, body mass index(BMI), basal hormonal concentrations, AMH and antral follicle count(AFC) were well-balanced between the two groups.(Table  1 ). Fig. 1 Ovarian stimulation cycle characteristics Ovarian stimulation cycle characteristics Table 1 Baseline characteristics PRP group control group P -value Number of cycles 91 261 Female ages(years) 38.85 ± 5.13 38.33 ± 5.08 0.405 Infertility type 0.226 Primary infertility 40 96 Secondary infertility 51 165 etiology of infertility 0.607 POR 27 73 POR combined with tubal factor 14 56 POR combined with endometriosis 5 16 POR combined with male factor 20 42 POR and combined factor 25 74 Infertility duration(years) 4.89 ± 3.77 4.74 ± 3.60 0.741 Body mass index(kg/m 2 ) 22.36 ± 2.90 22.77 ± 3.13 0.282 AMH (ng/ml)) 0.30 ± 0.21 0.29 ± 0.21 0.641 Antral follicle count 2.43 ± 1.32 2.5 ± 1.49 0.693 Basel FSH (IU/L) 11.84 ± 5.39 11.63 ± 5.53 0.746 Basel LH (IU/L) 5.15 ± 2.45 5.48 ± 3.54 0.416 Basel oestradiol (pg/ml) 42.11 ± 26.24 49.63 ± 42.73 0.116 Baseline characteristics Table  2 summarizes the ovarian stimulation cycle characteristics. No significant differences were observed in the stimulation protocol, total gonadotropin dose, length of stimulation, or peak estradiol concentrations. However, the number of follicles ≥ 14 mm on the trigger day was significantly higher in the PRP group compared to the control group (2.96 ± 1.79 vs. 2.26 ± 1.44, P  < 0.001). Table 2 Comparison of cycle characteristics between the PRP and control groups PRP group control group P -value Number of cycles 91 261 Number of previous cycles 5.26 ± 3.27 3.79 ± 2.81 < 0.001 Stimulation protocol 0.057 Progestin-primed ovarian stimulation 26 87 Microstimulation 15 50 Antagonist protocol 43 82 Agonist protocol 3 13 Natural cycle 4 29 Total length of stimulation (days) 8.30 ± 3.64 7.66 ± 4.26 0.203 Total gonadotropin dosage (IU) 2204.26 ± 1271.83 1997.51 ± 1407.63 0.217 Trigger day characteristics Peak estradiol (pg/ml) 781.14 ± 530.89 725.62 ± 565.90 0.414 Number of follicles ≥ 14 mm 2.96 ± 1.79 2.26 ± 1.44 < 0.001 Procedure 0.103 IVF 58 190 ICSI 33 71 Number of initiated cycle cancellations 0 0 Comparison of cycle characteristics between the PRP and control groups Table  3 summarizes the cycle outcomes. The PRP group had significantly higher numbers of oocytes retrieved (2.86 ± 1.88 vs. 2.07 ± 1.78, P  < 0.001) and normally fertilized zygotes (1.73 ± 1.42 vs. 1.37 ± 1.44, P  = 0.044) compared to the control group. Although the numbers of transferable embryos (1.34 ± 1.21 vs. 1.07 ± 1.26, P  = 0.079) and high-quality embryos (1.09 ± 1.16 vs. 0.83 ± 1.13, P  = 0.066) were higher in the PRP group, the differences did not reach statistical significance. However, the proportion of cycles without transferable cleavage-stage embryos was significantly lower in the PRP group compared to the control group (25.27% vs. 38.31%, P  < 0.001). Table 3 Comparison of cycle outcomes between the PRP and control groups PRP Group ( n  = 91) Control Group ( n  = 261) P -value Number of oocytes retrieved 2.86 ± 1.88 2.07 ± 1.78 < 0.001 Number of normal fertilized zygotes 1.73 ± 1.42 1.37 ± 1.44 0.044 Number of transferable cleavage embryos 1.34 ± 1.21 1.07 ± 1.26 0.079 Number of high-quality cleavage embryos 1.09 ± 1.16 0.83 ± 1.13 0.066 Rate of cycles without transferable cleavage embryos 25.27%(23/91) 38.31%(100/261) < 0.001 Number of cycles with a transfer 43 93 - Type of transplantation cycle 0.503 Fresh embryos transfer 20 49 Thawed embryos transfer 23 44 Type of embryo transferred 0.973 Cleavage embryo 38 82 Blastocyst 5 11 Number of embryo transferred per cycle 1.63 ± 0.54 1.62 ± 0.51 0.965 Pregnancy outcomes per transfer Biochemical pregnancy rate 25.58% (11/43) 31.18% (29/93) 0.505 Clinical pregnancy rate 18.60% (8/43) 24.73% (23/93 0.653 Miscarriage rate 37.5% (3/8) 30.43% (7/23) 0.713 Comparison of cycle outcomes between the PRP and control groups In both groups, only a portion of the embryos were transferred, with 43 cycles in the PRP group and 93 cycles in the control group, while the remaining embryos were cryopreserved. There were two patients in each group who underwent twice transfers using embryos from the same cycle. Specifically, one patient in the PRP group underwent twice frozen-embryo transfers, while the others each had one fresh-embryo transfer and one frozen-embryo transfer. The characteristics of embryo transfer cycles—including type of transplantation cycle, type of embryo transferred, and number of embryos transferred per cycle—were comparable between the two groups (Table  3 ). Following embryo transfer, no significant differences were observed between the PRP group and the control group in biochemical pregnancy rate (25.58% vs. 31.18%, P  = 0.505), clinical pregnancy rate (18.60% vs. 24.73%, P  = 0.653), or early miscarriage rate (37.5% vs. 30.43%, P  = 0.713). A liner regression analysis was performed to evaluate the impact of autologous platelet-rich plasma (PRP) ovarian injection on the number of oocytes retrieved (Table  4 ). After adjusting for potential confounding factors, autologous PRP ovarian injection was found to be significantly associated with an increased number of oocytes retrieved(regression coefficient[B] 0.701, 95% confidence interval [CI] of B 0.324–1.079, P  < 0.001). Additionally, AMH (B 1.825, 95% CI of B 0.949–2.701, P  < 0.001) and the total dosage of gonadotropin(B < 0.001, 95% CI of B < 0.001–0.001, P  = 0.004)were identified as independent predictors influencing the number of oocytes retrieved. Table 4 Linear regression analysis for the number of oocytes retrieved Regression coefficient(B) Standard error t 95% confidence interval of B P -value Group 0.701 0.192 3.655 0.324–1.079 < 0.001 AMH 1.825 0.445 4.096 0.949–2.701 < 0.001 Antral follicle count 0.072 0.062 1.161 −0.050-0.195 0.246 Basel FSH −0.029 0.017 −1.711 −0.062-0.004 0.088 Female ages −0.019 0.017 −1.173 −0.052-0.013 0.242 Total dosage of gonadotrophin < 0.001 < 0.001 2.899 < 0.001–0.001 0.004 Total length of stimulation 0.008 0.044 0.856 −0.079-0.094 0.856 constant 1.57 0.732 2.145 0.130–3.009 0.033 Linear regression analysis for the number of oocytes retrieved

This retrospective propensity-matched study was conducted at the reproductive center of the Sixth Affiliated Hospital of Sun Yat-sen Universitiy between August 2022 and December 2023.The research proposal was approved by the Ethics Committee at the Sixth Affiliated Hospital of Sun Yat-sen University(E2022233) in accordance with the Declaration of Helsinki. Informed consent was waived due to the retrospective nature of this study. Included infertile women with poor ovarian response (POR) according to the Bologna criteria [ 10 ] had to have at least two of the following three features: (i) Advanced maternal age (≥ 40 years) or any other risk factor; (ii) history of cycle cancellation, equal or less than 3 oocytes retrieved after conventional stimulation protocol. (iii) antral follicle count (AFC) of 5–7 follicles or anti-Mullerian hormone (AMH) of 0.5–1.1 ng/ml. Additionally, any spouse with chromosomal abnormalities, pre-implantation genetic diagnosis and single ovary only will be excluded. The enrolled patients were divided into two groups according to whether or not autologous platelet-rich plasma ovarian injections were performed prior to the IVF/ICSI cycle.The cycle would be included in PRP group when it was the first cycle performed within six months after the injection of patient’s autologous PRP into both ovaries. But other cycles of patients in the PRP group would be excluded from both groups. The method of preparing PRP from autologous blood was detailed as reported previously [ 11 ]. Approximately 30 ml of blood was taken from the patient’s peripheral vein and the platelet count was checked.The patient’s blood was centrifuged twice to remove the red blood cells and the platelet count was rechecked.Finally, 4—5 ml of PRP was obtained per patient and could be stored at room temperature for less than 2 h. After preparation of autologous PRP, it was activated by mechanical oscillation and then injected 2—2.5 ml into the stromal region of each ovary by transvaginal ultrasound (TVS) guidance under intravenous anesthesia by one expert infertility fellow and using needle number 18 for ovarian puncture on the day of egg collection or between 3 and 7 days after menstruation. A controlled ovarian stimulation (COS) protocol was chosen based on individual patient characteristics such as AMH levels, baseline FSH, LH, E2, and antral follicle count (AFC) on days 2–3 of the menstrual cycle. The protocols used included progestin-primed ovarian stimulation (PPOS), microstimulation, antagonist protocol, agonist protocol, and natural cycles. For all protocols except the natural cycle, ovarian stimulation was performed using 150–300 IU of gonadotropins per day. Antagonists or progesterone were administered to prevent premature LH surges. When the diameters of three follicles reached ≥ 17 mm or two dominant follicles reached ≥ 18 mm, human chorionic gonadotropin (hCG) was administered, and oocyte retrieval was performed 36–38 h later. In most cases, fresh embryo transfer was carried out on day 3. However, in cases involving the PPOS protocol, severe adenomyosis, ovarian endometriotic cysts, advanced maternal age with only one embryo, thin endometrium, or elevated progesterone levels, all embryos were frozen. Cleavage-stage embryos were assessed based on Scott’s criteria [ 12 ], with grades I and II embryos having ≥ 4 cells considered usable, and those with ≥ 6 cells considered of good quality. Blastocysts (day 5 or 6) were evaluated using Gardner’s system [ 13 ], where grade 3–6 blastocysts with inner cell mass and trophectoderm grades of AA, AB, BA, AC, CA, BB, BC, or CB were considered usable embryos, and those with AA, AB, BA, and BB were considered good quality. Luteal phase support was provided with oral or vaginal progesterone until 8–10 weeks of gestation. The primary outcome was the number of oocytes retrieved. Secondary outcomes assessed included the estrogen level and number of follicles no less than 14 mm in diameter on trigger day, number of two-pronuclear (2PN) embryos, usable cleavage embryo number, and good-quality cleavage embryo number. Pregnancy results after embryo transfer in partial cycles were also shown in Results.In terms of pregnancy outcomes, biochemical pregnancy rate, clinical pregnancy rate and early abortion rate were evaluated. Clinical pregnancy was defined as the observation of gestational sac(s) through a transvaginal probe. Propensity score-matching analysis was conducted with R version 4.3.2. Data analyses were carried out using IBM SPSS Statistics (version 26.0; IBM, USA).To Limit confounding effects, we used propensity scores that incorporated a range of baseline covariates and were estimated with Liner regression models. Patients of the study group and the control group were randomly matched with the 1:3 nearest neighbor matching method. The covariates included female age, AMH, AFC, and the total dosage of gonadotropin. Continuous variables were expressed as the means ± standard deviation (SD), which were compared using the Student’s t-test (normal distribution) or Kruskal–Wallis test (non-normal distribution). Categorical variables were described as counts (percentages) and compared by Pearson Chi-square test. Liner regression analysis was used to assess the association between autologous platelet-rich plasma ovarian injection and the number of oocytes retrieved after adjusting for potential confounders, including female age, basel FSH, AMH values, AFC, total dose of gonadotropins and total length of stimulation. P  < 0.05 was regarded as statistically significant.

Infertility remains a formidable challenge within the realm of reproductive medicine, attributed to a myriad of etiological factors that impede conception. Among these, poor ovarian response (POR) represents a particularly arduous condition to address. It is delineated by a diminished yield and quality of oocytes during the processes of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles. The Bologna criteria serve as the standard for identifying women afflicted with POR, who consequently experience diminished success rates in assisted reproductive technology (ART) cycles [ 1 ]. Despite the strides made in ART, the quest for efficacious interventions for POR continues, often culminating in outcomes that fall short of expectations. In recent years, autologous platelet-rich plasma (PRP) has been posited as a viable intervention for ovarian rejuvenation. PRP, a plasma fraction enriched with platelets, harbors a plethora of growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), and vascular endothelial growth factor (VEGF), which are implicated in tissue regeneration and repair [ 2 ]. The deployment of PRP within the domain of reproductive medicine is aimed at augmenting ovarian functionality and, by extension, enhancing ART cycle outcomes for women grappling with POR. A body of research has begun to shed light on the potential of PRP in ameliorating ovarian reserve markers and bolstering ART outcomes. Notably, a prospective pilot study indicated an upward trend in implantation and live birth rates (LBRs) among patients administered PRP, in contrast to their untreated counterparts [ 1 ]. Furthermore, evidence from another study suggests that the application of PRP in conjunction with gonadotropins, through whole-dimension subcortical ovarian administration, can rejuvenate ovarian function and elevate the likelihood of pregnancy in women experiencing early menopause [ 2 ]. These insights underscore the potential of PRP as a beacon of hope for enhancing reproductive outcomes in women with compromised ovarian reserve. Nevertheless, the integration of PRP into clinical practice for reproductive medicine remains nascent, necessitating further investigation to validate its effectiveness and safety. In the existing literature, several studies have explored the effects of autologous PRP on patients with POR, as defined by the Bologna criteria. However, these investigations have been limited by small sample sizes [ 3 , 4 ]. Conversely, larger studies have tended to group patients with POR, premature ovarian insufficiency (POI), and menopausal women together, analyzing the results collectively, which could dilute the specificity of findings related to POR alone [ 5 ]– [ 6 ]. Additionally, while some research has focused on POR patients, the inclusion criteria have occasionally aligned with the Poseidon criteria rather than the Bologna criteria, introducing variability in patient selection [ 7 , 8 ]. Moreover, certain studies have evaluated the impact of autologous ovarian PRP treatment on ovarian reserve without assessing subsequent effects on assisted reproductive technology (ART) outcomes, further limiting the applicability of their findings [ 3 , 9 ]. Given these limitations, the reliability of existing evidence remains questionable, highlighting the need for further, more rigorous studies. Our research addresses these gaps by employing a detailed analysis through propensity score matching (PSM). This methodological approach aims to minimize selection bias and ensure comparability between the treatment and control groups, thereby enhancing the robustness of our findings.The clinical implications of our study are particularly significant for women with POR, as diagnosed by the Bologna criteria, who are undergoing IVF/ICSI. For these women, whose fertility prospects may be notably diminished, this study aims to investigate the impact of autologous PRP ovarian injection on oocyte retrieval numbers and other reproductive indices in IVF/ICSI cycles. By conducting a retrospective propensity score-matched study, we seek to provide robust evidence on the efficacy of PRP in enhancing ovarian response and improving ART outcomes.

In summary, our study demonstrates that autologous PRP ovarian injection has a positive impact on the number of oocytes retrieved and other related reproductive outcomes in IVF/ICSI cycles for women with POR.The findings suggest that PRP administration can significantly increase the number of oocytes retrieved and improve secondary outcomes. However, future research should aim to include larger, multicenter cohorts and employ prospective randomized controlled trial designs to validate these findings and explore the long-term impact of PRP on ovarian function and reproductive outcomes. Additionally, further investigations into the underlying mechanisms of PRP’s action on the ovary are warranted to optimize its therapeutic potential and ensure its safe and effective application in clinical practice.

The objective of our study was to assess the impact of autologous platelet-rich plasma (PRP) ovarian injections on oocyte yield and additional reproductive metrics within IVF/ICSI cycles for women identified with POR, as defined by the Bologna criteria. Our data reveal that PRP administration significantly increased the number of oocytes retrieved and yielded improvements in secondary outcomes, including the count of follicles ≥ 14 mm and 2PN embryos. In our investigation, we strategically selected the initial controlled ovulation induction cycle occurring within six months after the administration of autologous PRP injections as the reference period for the PRP group. This decision was informed by a meta-analysis conducted by Máté Éliás et al., which provided a comprehensive longitudinal analysis of hormone levels at one, two, and three months following autologous PRP ovarian injections [ 14 ]. The findings from their study demonstrated a significant improvement in hormone levels at each time point assessed, underscoring the positive short-term impact of PRP therapy on ovarian function. Moreover, the efficacy of PRP therapy tends to be transient, with its beneficial effects generally subsiding by the six-month milestone [ 15 ]. In light of this evidence, our study was designed to assess the immediate outcomes post-therapy by concentrating on the first controlled ovulation induction cycle within the six-month timeframe post-PRP treatment. This methodology was deliberately chosen to enhance the probability of detecting the marked benefits of PRP therapy before any decline in its effectiveness could occur. Our findings suggest that autologous PRP ovarian injections can significantly enhance ovarian response, aligning with previous studies that highlight the benefits of PRP in improving ovarian function and reproductive outcomes in patients with poor ovarian response (POR) [ 1 , 2 ]. A recent double-blind, randomized controlled trial involving 60 patients classified under POSEIDON Group 3 and Group 4 further supports this, showing that autologous PRP ovarian injections may improve in vitro fertilization (IVF) outcomes [ 16 ]. Moreover, a comprehensive systematic review and meta-analysis confirmed the efficacy of intra-ovarian PRP injections, demonstrating not only an increase in the number of oocytes retrieved but also improvements in other ovarian reserve markers and overall assisted reproductive technology (ART) outcomes [ 17 ]. These findings position PRP as a promising adjunctive therapy for enhancing ovarian responsiveness in IVF/ICSI patients, particularly in a difficult-to-treat population. In comparison with other studies, our analysis included a relatively larger sample size, focusing primarily on patients with low ovarian response as defined by the Bologna criteria. The primary endpoints of this study were ovarian response and improved outcomes during the IVF/ICSI cycle. Importantly, we addressed potential confounding factors through propensity score matching, lending greater credibility to the results of our retrospective study. Although the precise mechanisms through which autologous PRP augments ovarian response after injection are not fully understood, several potential explanations have been proposed. PRP releases cytokines from activated platelets, which play a crucial role in facilitating communication between oocytes, granulosa cells, and thecal cells. This cytokine signaling is essential for follicular maturation, ovulation, and luteinization [ 18 ]. Furthermore, PRP’s proangiogenic properties, through factors like VEGF and PDGF, support the development of capillary networks around maturing follicles, enhancing blood flow and nutrient delivery, which are vital for ovarian health [ 19 – 21 ]. Additionally, sphingosine-1-phosphate(S1P) in PRP protects ovarian cells from oxidative stress, promoting their survival and proliferation, which is crucial in the presence of FSH and VEGF [ 22 ].S1P and its receptors, particularly S1PR1 and S1PR3, contribute to angiogenesis in ovarian tissues, potentially improving ovarian function [ 23 ]. Moreover, growth differentiation factor 9 (GDF-9) in PRP aids in oocyte maturation [ 24 ], with evidence linking it to the prevention of premature ovarian failure [ 25 ]. Finally, PRP may influence the balance between apoptosis and survival in granulosa cells, favoring follicular growth and development [ 26 ]. These comprehensive approaches to enhancing ovarian function underscore the complexity of PRP’s actions and highlight the imperative for further research to fully elucidate its mechanisms and optimize its therapeutic potential. Although our study presents a significant advancement in the field of ART, specifically focusing on the impact of autologous PRP ovarian injection on IVF/ICSI cycles in women with POR, the clinical application of PRP should be approached with caution. Although statistical significance was achieved, the absolute differences in the number of eggs and embryos obtained were relatively small. This highlights that, while the treatment demonstrates a statistically significant trend, its clinical impact may be modest. We propose that larger, multicenter studies are necessary to better evaluate the clinical relevance evaluate the clinical relevance and ascertain whether these differences result in meaningful improvements in patient outcomes. One of the primary limitations of this study is the relatively small sample size, which may affect the statistical power and generalizability of the findings. Conducting the study at a single center further limits the external validity, as the results may not be applicable to different populations or clinical settings. Additionally, the retrospective design of the study introduces potential biases in data collection and analysis, such as selection bias and recall bias, which could influence the outcomes. Fourthermore, the study’s follow-up period was also limited, preventing the assessment of the long-term safety and efficacy of autologous PRP ovarian injection.