A Medical Review of Ovarian Platelet-Rich Plasma for Fertility Enhancement

CARE Fertility & Women’s Health

June 2025

Disclaimer: Please note that this medical review is intended for informational purposes only and should not be considered as medical advice. It has been prepared with the assistance of artificial intelligence and has not undergone peer review by medical professionals. Consult with a qualified healthcare provider for personalized medical guidance and treatment. The information provided herein is not a substitute for professional medical advice.

I. Introduction to Ovarian Platelet-Rich Plasma in Reproductive Medicine

A. Defining Ovarian PRP and its Emergence as a Fertility Intervention

Platelet-Rich Plasma (PRP) is an autologous blood-derived product characterized by a platelet concentration significantly above baseline whole blood levels. This concentration renders PRP a rich reservoir of various growth factors, cytokines, and other bioactive molecules known for their roles in tissue repair and regeneration.¹ Historically, the therapeutic application of PRP gained traction in diverse medical specialties, including orthopedics for ligament and osteoarthritis treatment, dermatology for skin rejuvenation and hair loss, and dentistry for enhanced healing.¹ More recently, its potential has been explored in obstetrics and gynecology, with investigations into its utility for improving endometrial receptivity, vaginal rejuvenation, and, pertinent to this review, ovarian function.¹ Ovarian PRP, specifically, refers to the therapeutic administration of this concentrated autologous preparation directly into the ovarian tissue, typically via injection.¹

The emergence of ovarian PRP as a potential fertility intervention is largely driven by the pressing need for novel treatment strategies for women with challenging reproductive prognoses. These include individuals diagnosed with Diminished Ovarian Reserve (DOR), those exhibiting a Poor Ovarian Response (POR) to controlled ovarian stimulation, and women with Premature Ovarian Insufficiency (POI).² Such conditions are unified by a common pathophysiology: a quantitative and/or qualitative decline in oocytes, which severely curtails the success of conventional assisted reproductive technologies (ART) and often leaves oocyte donation as the sole viable path to parenthood.³ The application of ovarian PRP in these contexts is founded on the scientifically plausible, albeit still exploratory, premise that the concentrated growth factors delivered to the ovarian microenvironment can stimulate dormant follicles, enhance existing follicular development, or improve the overall health and responsiveness of the ovaries, thereby augmenting ovarian function and potentially improving fertility outcomes.²

The exploration and adoption of ovarian PRP are significantly influenced by the profound unmet needs of patients facing severely compromised ovarian function, for whom existing treatments offer limited success. The prospect of utilizing one's own oocytes, often framed by terms such as "ovarian rejuvenation," generates considerable hope and drives patient interest in such innovative, though experimental, therapies.⁶ Patients grappling with DOR, POR, and POI frequently experience substantial emotional distress and are confronted with limited, often expensive, treatment avenues, culminating in the consideration of oocyte donation. PRP, being autologous and leveraging the body's intrinsic healing capacities, presents an appealing alternative, fostering hope for achieving pregnancy with their own genetic material. This powerful patient demand, combined with the clinical impetus to offer solutions in difficult cases, can accelerate the adoption of novel therapies even when high-level scientific evidence is still nascent or in the process of evolving.² There exists a potential for a "treatment imperative," where the desire to provide some form of intervention in challenging scenarios might lead to the offering of experimental treatments outside the rigorous confines of structured clinical trials. Consequently, a critical appraisal of ovarian PRP must navigate the delicate balance between acknowledging the legitimate hope it offers to a population with few alternatives and rigorously evaluating the scientific evidence to prevent the propagation of unsubstantiated claims or premature widespread adoption.

II. Biological Basis and Putative Mechanisms of Ovarian PRP

A. Composition of PRP: The Role of Growth Factors and Bioactive Molecules

PRP is defined as a volume of plasma fraction of autologous blood having a platelet concentration above baseline.² The therapeutic potential of PRP is primarily attributed to the rich milieu of bioactive molecules stored within platelet granules, particularly the alpha granules. Upon activation, which can be triggered by various stimuli such as tissue injury, exposure to collagen, thrombin, or exogenous activators like calcium chloride, these platelets degranulate, releasing a diverse array of signaling molecules into the local environment.²

The key bioactive constituents of PRP include a wide spectrum of growth factors, such as Platelet-Derived Growth Factor (PDGF), Transforming Growth Factor-beta (TGF-β), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF), Insulin-like Growth Factor 1 (IGF-1), and Hepatocyte Growth Factor (HGF).¹ In addition to these growth factors, PRP also contains various cytokines, which can modulate inflammatory and immune responses, and adhesion molecules like fibrin, fibronectin, and vitronectin. These plasma proteins can form a provisional scaffold that supports cellular adhesion, migration, and proliferation, and may also contribute to a sustained release of growth factors.² Collectively, these molecules are integral to fundamental biological processes including cell proliferation, differentiation, chemotaxis (cell migration), angiogenesis (formation of new blood vessels), and extracellular matrix synthesis and remodeling, all of which are critical for tissue repair and regeneration.²

The specific relevance of these components to ovarian physiology is an area of active investigation. For instance, VEGF is a potent pro-angiogenic factor, and its presence in PRP is thought to enhance ovarian vascularity, thereby improving nutrient and oxygen supply to developing follicles. PDGF and TGF-β are implicated in supporting granulosa cell proliferation and differentiation, processes essential for normal folliculogenesis. IGF-1 and EGF are believed to play roles in granulosa cell survival, steroidogenesis, and the expansion of cumulus cells surrounding the oocyte, all contributing to oocyte competence and developmental potential.²

Table 1: Key Bioactive Components in Platelet-Rich Plasma and Their Postulated Roles in Ovarian Function

B. PRP Preparation and Activation Techniques

The preparation of PRP is a multi-step laboratory process that begins with the collection of autologous peripheral blood from the patient. This blood is then subjected to centrifugation to separate its components based on density, allowing for the isolation and concentration of platelets.¹ Various protocols exist, which may involve single or double centrifugation steps, different centrifugation speeds and durations, and the use of various anticoagulants, all of which can influence the final composition of the PRP product.¹

Following the concentration of platelets, an activation step is often employed. Activation aims to induce platelet degranulation, thereby releasing the stored growth factors and other bioactive molecules from the alpha granules into the plasma supernatant.² Common activators include calcium chloride, calcium fluoride, or thrombin.⁷ There is some evidence to suggest that the therapeutic efficacy of PRP may be dependent on this activation step, with one report indicating that the injection of resting (non-activated) platelets for intraovarian use might reduce or even negate the desired post-treatment response.⁷

The variability in PRP preparation and activation protocols presents a significant challenge in the field. PRP is not a standardized pharmaceutical agent; its final composition, including platelet concentration, leukocyte content (which can also influence outcomes), and the profile of released growth factors, is highly dependent on both patient-specific hematological parameters and the precise details of the preparation protocol used. This inherent variability makes it exceedingly difficult to compare outcomes across different studies and to establish a clear dose-response relationship. If different studies utilize distinct PRP formulations, any observed discrepancies in efficacy could be attributable to variations in the PRP product itself, rather than other clinical or patient-related factors. Furthermore, the lack of detailed reporting on the specific characteristics of the PRP used (e.g., precise platelet counts, concentrations of key growth factors, presence or absence of leukocytes) in many published studies further exacerbates this problem, effectively creating a "black box" around the intervention.⁹ This methodological heterogeneity is a major impediment to the establishment of definitive evidence for ovarian PRP and the identification of optimal, reproducible protocols. Consequently, there is a pressing need for standardization in PRP preparation and characterization, as well as comprehensive reporting of these details in future research, to enhance comparability and facilitate the translation of findings into reliable clinical practice. A meta-analysis, for instance, has reported differential clinical pregnancy and live birth rates based on whether platelets were activated prior to injection, underscoring the critical impact of such procedural details.¹⁰

C. Hypothesized Effects on Folliculogenesis, Oocyte Maturation, and the Ovarian Microenvironment

The rich cocktail of growth factors and cytokines contained within PRP is believed to exert a range of beneficial effects on ovarian physiology through multiple, potentially synergistic, pathways:

1. Follicular Activation and Development: A primary hypothesis is that PRP can stimulate dormant primordial follicles to enter the growth phase, thereby increasing the pool of developing follicles. Growth factors such as TGF-β and PDGF are specifically implicated in supporting the proliferation and differentiation of granulosa cells, which are somatic cells surrounding the oocyte that play indispensable roles in folliculogenesis, steroidogenesis, and oocyte maturation.²

2. Angiogenesis: Enhanced ovarian perfusion is another proposed mechanism. VEGF, a key component of PRP, is a potent stimulator of angiogenesis. By promoting the formation of new blood vessels within the ovarian stroma, PRP may improve the delivery of oxygen, nutrients, and hormones to developing follicles, creating a more supportive environment for their growth and survival.²

3. Ovarian Microenvironment Modulation: PRP is thought to foster a regenerative microenvironment within the ovary. This may involve reducing local inflammation and oxidative stress, both of which can be detrimental to follicular health and oocyte quality. The immunomodulatory properties of PRP, including its ability to decrease the production of pro-inflammatory cytokines, contribute to this effect.² Paracrine signaling initiated by the released factors is central to this modulation.

4. Oocyte Competence: Several growth factors in PRP, notably IGF-1 and EGF, are known to be involved in critical aspects of oocyte development, including granulosa cell survival, steroid hormone production, and the expansion of cumulus cells (specialized granulosa cells that directly surround and support the oocyte). These processes are vital for the acquisition of oocyte competence, which is its capacity to undergo fertilization and support normal embryonic development.²

Preclinical evidence lends some support to these hypotheses. For example, studies conducted in mouse models of diminished ovarian reserve induced by chemotherapy have demonstrated that intraovarian PRP administration can mitigate some of the chemotherapy-induced alterations in ovarian stromal architecture and follicle morphology. Interestingly, while PRP did not necessarily lead to an increase in the yield of mature (Metaphase II) oocytes in these models, it was associated with improvements in subsequent embryological outcomes. Specifically, PRP-treated mice showed increased numbers of 2-cell embryos, higher fertilization rates, improved blastocyst formation rates, and a greater quantity of good-quality blastocysts. These findings suggest that PRP may exert a beneficial effect on oocyte and embryo quality, possibly mediated through local paracrine signaling within the ovary that enhances the developmental potential of existing oocytes.¹¹

The proposed mechanisms suggest a nuanced interplay where PRP could act directly on follicular cells (e.g., by stimulating quiescent follicles or promoting granulosa cell function) and/or indirectly by optimizing the overall ovarian milieu (e.g., by improving vascularity or reducing inflammation). The findings from the aforementioned mouse study¹¹, where embryo quality improved even without an increase in oocyte quantity post-chemotherapy, are particularly illustrative of a potential qualitative benefit derived from microenvironmental enhancement. This distinction is important because the term "ovarian rejuvenation" often implies a fundamental reversal of ovarian aging, leading to both more and better-quality oocytes, akin to a younger ovarian state. In contrast, "ovarian reactivation," a term suggested by some researchers⁶, implies the stimulation of already present but quiescent follicles to grow, potentially increasing oocyte quantity without necessarily altering their intrinsic quality. If PRP's primary benefit, especially in severely damaged or aged ovaries, is to improve the supportive stromal environment, reduce inflammation, or enhance vascularity, this could lead to better development and quality of the few remaining follicles, without necessarily increasing their absolute number from a depleted primordial pool or fundamentally altering age-related aneuploidy rates. This nuanced understanding is vital for setting realistic expectations and for designing future studies aimed at dissecting these differential effects. PRP's benefits might not solely be about increasing oocyte numbers; improving the quality and developmental potential of oocytes by fostering a healthier ovarian environment could be an equally, if not more, important contribution, particularly in contexts like mitigating gonadotoxic damage.

D. Exploring Cellular Plasticity and Epigenetic Influences

Beyond the direct effects of growth factors on cell proliferation and microenvironment, more speculative but scientifically intriguing theories propose that ovarian PRP might induce deeper, more fundamental cellular changes, potentially involving mechanisms of cellular plasticity and epigenetic reprogramming.⁷ These proposed mechanisms differ conceptually from traditional hormonal ovarian stimulation, which primarily acts on existing G-protein coupled receptors on follicular cells to promote the growth of already committed follicles.⁷

The rationale for exploring these deeper mechanisms stems from observations that activated platelet releasate contains factors capable of promoting signaling networks associated with cell pluripotency.⁷ In experimental models using bone marrow-derived mesenchymal stem cells, exposure to PRP has been shown to upregulate the expression of key pluripotency-associated transcription factors, such as Oct4, Sox2, Sall4, and Nanog. These genes are recognized for their roles in maintaining stem cell identity and, in some contexts, reprogramming somatic cells towards a more pluripotent state. Concurrently, PRP exposure in these models led to a reduced expression of β-galactosidase, a known biomarker of cellular senescence.⁷ Furthermore, Oct4 expression has been observed in human testicular cells cultured in vitro with PRP, suggesting the possibility of a parallel response occurring in adult ovarian tissues following the introduction of activated platelet-derived cytokines.⁷

Epigenetic modifications, which are heritable changes in gene expression that do not involve alterations to the underlying DNA sequence, are central to these theories. Processes such as DNA methylation and various histone modifications (e.g., acetylation, phosphorylation) play crucial roles in regulating gene activity and cellular identity.⁷ PRP is known to contain a variety of microRNAs (miRNAs), many of which are packaged within platelets and released upon activation. These miRNAs are small non-coding RNAs that can post-transcriptionally regulate gene expression, and some have been shown to influence the activity of DNA methyltransferases, enzymes that catalyze DNA methylation. It is therefore hypothesized that PRP-derived miRNAs could contribute to an "epigenetic reset" by altering DNA methylation patterns within ovarian cells.⁷ Additionally, the Piwi-interacting RNA (piRNA) pathway, which is crucial for maintaining genome stability by suppressing the activity of mobile transposable elements (whose dysregulation can contribute to genomic instability and cellular senescence with age), is also an area of emerging interest in ovarian biology, with preliminary characterization in adult human ovarian tissue.⁷

These advanced mechanistic theories, hinting at pluripotency induction and epigenetic reprogramming, suggest the possibility that PRP might induce a partial "reset" of cellular programs associated with ovarian aging or dysfunction. This would represent a significant conceptual shift from merely supporting existing ovarian function to actively remodeling or recalibrating it at a more fundamental level. However, it is crucial to emphasize that these concepts are, at present, highly theoretical and largely extrapolated from preclinical models or biological systems distinct from the human ovary. The human ovary is an exceedingly complex organ, and ovarian aging is not only a process of decline but is also considered by some to be an evolved tumor-suppression mechanism.⁷ Attempting to override such deeply embedded biological programs, if indeed possible with PRP, carries unknown and potentially significant risks, including the theoretical concern of inducing pathological overgrowth or even malignancy if cellular safeguards against uncontrolled proliferation are inadvertently bypassed. Therefore, while these hypotheses offer a tantalizing glimpse into potential future understandings, they must be approached with considerable caution. The review of such mechanisms underscores the frontier nature of this line of inquiry and highlights the critical need for extensive research to validate (or refute) these ideas in the human ovarian context, with a strong emphasis on long-term safety.

III. Clinical Applications and Patient Selection for Ovarian PRP

A. Target Populations: Diminished Ovarian Reserve (DOR), Poor Ovarian Response (POR), and Premature Ovarian Insufficiency (POI)

Ovarian PRP is primarily investigated as a therapeutic option for women experiencing specific challenging fertility conditions characterized by a compromised quantity or quality of oocytes. The main target populations include:

1. Diminished Ovarian Reserve (DOR): DOR is characterized by a reduction in the number and, often, the quality of remaining oocytes in the ovaries relative to age-matched peers. This can be an age-related phenomenon or can result from genetic predispositions, previous ovarian surgery, or exposure to gonadotoxic treatments such as chemotherapy or radiotherapy.² Women with DOR typically have low levels of Anti-Müllerian Hormone (AMH) and a low Antral Follicle Count (AFC).

2. Poor Ovarian Response (POR): POR refers to a suboptimal response of the ovaries to exogenous gonadotropin stimulation during ART cycles. Various criteria are used for definition, with the Bologna criteria being widely recognized. According to these criteria, POR may be diagnosed if at least two of the following three features are present: (i) Advanced maternal age (e.g., ≥40 years) or any other risk factor for POR; (ii) A previous POR cycle where ≤3 oocytes were retrieved with a conventional stimulation protocol; (iii) An abnormal ovarian reserve test (e.g., AMH <0.5–1.1 ng/mL, or AFC <5–7 follicles).¹

3. Premature Ovarian Insufficiency (POI): POI is defined by the loss of ovarian activity before the age of 40. It is characterized by amenorrhea (or oligomenorrhea), sex steroid deficiency (low estrogen levels), and elevated gonadotropin levels (FSH), indicating impaired follicular development or accelerated follicular depletion.² POI leads to infertility and symptoms of premature menopause.

While these categories define the broad indications, some evidence suggests that the degree of residual ovarian function may influence the potential for benefit. For instance, it has been suggested that PRP may not be suitable for patients with extremely low or undetectable AMH levels (e.g., 0.0–0.2 ng/mL) or for those who have undergone particularly aggressive chemotherapy regimens, implying that a certain baseline level of ovarian follicular presence or stromal responsiveness might be necessary for PRP to exert an effect.⁸

It is important to recognize that DOR, POR, and POI, while often grouped as indications for PRP, represent a heterogeneous spectrum of ovarian dysfunction. This spectrum ranges from a reduced but still present level of follicular activity to a state of near-complete follicular depletion. This heterogeneity has significant implications for treatment expectations and outcomes. For example, predictors for a favorable response to PRP in women with POI have been reported to include better baseline ovarian reserve markers (higher AMH, higher AFC, lower FSH) and a shorter duration of amenorrhea.² This observation strongly suggests that PRP requires some existing ovarian substrate – such as dormant primordial follicles, responsive granulosa cells, or a receptive stromal environment – upon which its growth factors can act. If the ovarian reserve is almost entirely exhausted, as might be the case in long-standing POI with no detectable antral follicles, the growth factors delivered by PRP may have limited targets, and the potential for significant "reactivation" or "rejuvenation" would likely be minimal. This implies that a "one-size-fits-all" approach to PRP across the entire spectrum of poor ovarian reserve is unlikely to be effective. Nuanced patient selection within these broad diagnostic categories is therefore paramount. Future research should focus on identifying precise biomarkers or clinical profiles that can more accurately pinpoint which individuals within the DOR, POR, and POI populations are most likely to derive a clinically meaningful benefit from ovarian PRP therapy.

B. Intraovarian Administration: Protocols and Procedural Aspects

The administration of PRP to the ovaries is typically performed via direct intraovarian injection, aiming to deliver the concentrated growth factors to the target tissue.¹ The most commonly reported route for this procedure is transvaginal, performed under ultrasound guidance, a technique familiar to reproductive specialists as it mirrors the approach used for oocyte retrieval in IVF cycles.¹ Laparoscopic administration has also been described, particularly if PRP injection is planned concurrently with another surgical intervention.¹

The volume of PRP injected per ovary and the total dosage can vary between protocols. For example, some studies report injecting 3–4 mL of PRP into each ovary⁵, while others describe using 3 mL per ovary, prepared from an initial blood draw of approximately 40 mL.⁸ To manage any discomfort associated with the needle puncture and injection, the procedure is often performed under minimal sedation or with the administration of local anesthetics.¹

The timing of PRP administration relative to subsequent ART cycles or attempts at natural conception is a critical aspect of the protocol, though consensus is lacking.

• PRP may be administered following a previously unsuccessful IVF cycle, with the aim of improving ovarian response in a subsequent attempt.¹

• A waiting period is often observed after PRP injection to allow for potential biological effects to manifest. For instance, an 8-week period of anticipatory management has been described, during which spontaneous ovulation, menstruation, or pregnancy might occur before initiating further fertility treatments.⁵ Hormonal reassessment (e.g., AMH, FSH) may be performed at various intervals post-PRP to monitor for changes in ovarian reserve markers, although very early reassessment⁵ is unlikely to capture significant functional changes related to new follicular growth.

• There is emerging evidence suggesting that the interval between PRP administration and the initiation of an IVF cycle could influence outcomes. Some data indicate that commencing an IVF cycle within a specific timeframe, such as within 90 days post-PRP, might be more beneficial.⁹

• A point of significant discrepancy and importance concerns the optimal timing for oocyte retrieval after PRP if an increase in oocyte yield is anticipated. One report highlighted that while no significant increase in oocyte numbers was observed at 24 days post-PRP, a statistically significant increase was noted when oocyte retrieval was performed 49 days after PRP administration.⁶

The observation of a temporal delay between PRP administration and discernible biological or clinical effects is recurrent in the literature. This includes the common practice of an observation period post-injection⁵, the gradual rise in AMH levels over one to three months¹², the differential oocyte yield based on timing post-PRP⁶, and the suggestion of an optimal window for subsequent IVF.⁹ Folliculogenesis, the complex process of follicle development from the primordial stage to a mature, ovulatory follicle, is a protracted biological journey that can span several months. If PRP's mechanisms involve the activation of very early-stage (primordial or primary) follicles or require substantial remodeling of the ovarian microenvironment (e.g., through angiogenesis or stromal changes), its impact would not be immediate but would manifest over a period of time as these newly recruited follicles progress through development or as the ovarian environment becomes more conducive to follicular growth. This implies the existence of a "lag phase" following PRP administration, during which initial biological changes are occurring, followed by a potential "window of opportunity" when subsequent fertility interventions, such as ovarian stimulation for IVF, might be most effective. The conflicting data on oocyte yield at different time points post-PRP⁶ strongly underscore this concept. If oocyte retrieval is timed too early, any potential benefit from newly activated follicles might be missed; if timed too late, the therapeutic effect might have waned. The current variability in protocols regarding this waiting period and the timing of subsequent ART contributes significantly to the heterogeneity of reported outcomes and makes it challenging to draw firm conclusions about efficacy. Therefore, understanding and optimizing these temporal dynamics is critical. Future research must systematically investigate the optimal interval between PRP administration and subsequent fertility treatments to maximize potential efficacy, forming a key area for protocol standardization.

IV. Critical Appraisal of Clinical Efficacy

A. Impact on Ovarian Reserve Markers (AMH, FSH, AFC)

A frequently reported outcome following ovarian PRP administration is a change in biomarkers associated with ovarian reserve. These markers, including Anti-Müllerian Hormone (AMH), Follicle-Stimulating Hormone (FSH), and Antral Follicle Count (AFC), are routinely used in clinical practice to estimate a woman's remaining follicular pool and predict response to ovarian stimulation.

Anti-Müllerian Hormone (AMH): AMH is a glycoprotein hormone produced by the granulosa cells of small, growing (preantral and small antral) follicles. Serum AMH levels are considered to reflect the size of the primordial follicle pool. Several systematic reviews and meta-analyses have reported statistically significant increases in serum AMH levels following ovarian PRP treatment. For instance, a large meta-analysis encompassing 2,256 women with DOR demonstrated mean increases in AMH of 0.20 ng/mL at 1 month, 0.26 ng/mL at 2 months, and 0.36 ng/mL at 3 months post-PRP administration.¹² Another meta-analysis focusing on POR patients also found higher AMH levels at 1 and 2 months post-treatment.¹⁰ These findings are supported by trends observed in individual prospective studies.³

Follicle-Stimulating Hormone (FSH): FSH is a pituitary hormone that stimulates follicular growth. Elevated basal FSH levels are indicative of diminishing ovarian reserve, as the pituitary gland increases FSH production in an attempt to stimulate less responsive ovaries. Corresponding to the rise in AMH, significant decreases in serum FSH levels have been reported post-PRP. The same large meta-analysis in DOR women showed mean FSH decreases of -10.20 IU/L at 1 month, -7.02 IU/L at 2 months, and -8.87 IU/L at 3 months.¹² Other meta-analyses and studies have reported similar trends of FSH reduction.³

Antral Follicle Count (AFC): AFC refers to the number of small (2–10 mm) antral follicles visible on transvaginal ultrasound at the beginning of a menstrual cycle. It is a direct measure of the cohort of follicles available for growth in response to FSH. An increase in AFC is a relatively consistent finding across several meta-analyses, with reported mean differences in the range of approximately 1.1 to 1.6 additional antral follicles per patient following PRP treatment.³

While these statistically significant improvements in AMH, FSH, and AFC are encouraging and suggest some level of biological response within the ovary, the clinical meaningfulness of these shifts warrants careful consideration, particularly in the context of patients with severely compromised ovarian reserve. A statistically significant result indicates that the observed effect is unlikely to have occurred by chance. However, this does not automatically translate to a clinically important benefit that will substantially alter a patient's overall fertility prognosis or, more importantly, lead to a live birth. For example, an increase in AMH from a very low baseline of 0.1 ng/mL to 0.3 ng/mL represents a 200% relative increase and may achieve statistical significance in a large cohort of patients. However, an AMH level of 0.3 ng/mL still signifies severely diminished ovarian reserve and is typically associated with a very poor prognosis for success with IVF. Similarly, an increase of one or two antral follicles, while a positive change, may not drastically alter the clinical outcome if the baseline AFC is extremely low (e.g., zero or one). Furthermore, the sustainability of these observed changes is a pertinent concern. One meta-analysis noted that the improvements in AMH and FSH levels might not remain statistically significant by 6 months post-PRP, suggesting that the effect of a single PRP treatment on these surrogate markers could be transient.¹⁰ Therefore, while changes in ovarian reserve markers are valuable indicators of a potential biological response, they should be interpreted with caution and their impact on harder clinical endpoints, such as live birth rates, must be clearly demonstrated. The potential transience of these effects also raises questions about the need for repeat treatments or precise timing of subsequent interventions.

B. Influence on Oocyte Retrieval, Oocyte Quality, and Embryological Outcomes

Beyond changes in ovarian reserve markers, the impact of ovarian PRP on outcomes directly related to ART cycles, such as the number and quality of oocytes retrieved and subsequent embryological development, is of paramount importance.

Oocyte Yield: Meta-analyses of available studies, which often include a mix of randomized and non-randomized designs, generally report a statistically significant, albeit modest, increase in the number of oocytes retrieved following ovarian PRP treatment. For example, one meta-analysis reported a mean difference (MD) of 0.81 more oocytes retrieved¹², while another found an MD of 1.073 more Metaphase II (MII, mature) oocytes.¹⁰ Some individual studies also support an increase in oocyte yield.³

Embryo Numbers: Consistent with an increase in oocyte yield, an increase in the number of embryos created post-PRP is also commonly reported in meta-analyses. Mean differences have been reported in the range of 0.91 to 0.946 additional embryos.⁸

Oocyte and Embryo Quality: This aspect is more complex and controversial, with conflicting evidence.

Some meta-analyses and reviews suggest that PRP may lead to "improved embryo quality".³ Preclinical data from a mouse model of chemotherapy-induced ovarian damage indicated that PRP administration, while not increasing the MII oocyte yield, did improve fertilization rates, the proportion of 2-cell embryos, and the rates of blastocyst formation and good quality blastocysts.¹¹ This suggests a potential qualitative benefit on oocyte developmental competence, at least in the context of mitigating gonadotoxic damage.¹¹

However, the critical question of whether PRP improves oocyte euploidy (chromosomal normality) remains highly contentious. A commentary discussing two Randomized Controlled Trials (RCTs) published in 2024 stated that both trials concluded that PRP administration was not associated with an increase in the percentage of euploid blastocysts.⁶ It is noteworthy that one of these RCTs did report an increased oocyte count when retrieval was timed 49 days post-PRP, whereas the other did not, highlighting the potential influence of procedural timing on oocyte quantity.⁶

The discrepancy between reported increases in oocyte/embryo numbers and the more uncertain, and in some recent RCTs, negative findings regarding oocyte/embryo quality (particularly euploidy) represents a critical point of discussion. For patients with DOR, especially those of advanced maternal age or with conditions predisposing to poor oocyte quality, aneuploidy is a primary driver of implantation failure, miscarriage, and reduced live birth rates. Therefore, simply retrieving a marginally higher number of oocytes is only beneficial if those oocytes are developmentally competent and chromosomally normal. An increase in the number of aneuploid oocytes will not improve live birth outcomes of healthy infants. The term "ovarian rejuvenation" strongly implies an improvement in oocyte quality to a more youthful, and therefore presumably more euploid, state. The findings from the 2024 RCTs cited in ⁶, indicating no improvement in euploid blastocyst rates, directly challenge this core tenet of "rejuvenation." If PRP does not enhance the chromosomal integrity of oocytes, its ability to truly "rejuvenate" ovarian function at a fundamental, qualitative level is questionable. It is plausible that PRP might "reactivate" dormant follicles, leading to an increase in oocyte quantity, without altering the intrinsic age-related or condition-specific aneuploidy risk of the oocytes contained within them. The positive findings on embryo quality in the mouse model¹¹ occurred in a specific scenario of mitigating chemotherapy-induced damage. This context might not be directly generalizable to age-related ovarian decline or idiopathic DOR, where the underlying etiologies of poor oocyte quality may differ. This distinction is pivotal for managing patient expectations and for accurately positioning the potential role of ovarian PRP in fertility treatment.

C. Reported Pregnancy Rates (Spontaneous, Biochemical, Clinical) and Live Birth Rates

The ultimate measure of success for any fertility treatment is the achievement of a healthy live birth. The reported impact of ovarian PRP on pregnancy and live birth rates is varied and warrants careful interpretation based on study design and patient population.

Meta-Analyses (often including observational studies and non-randomized trials):

• One systematic review and meta-analysis indicated that PRP treatment was associated with significant increases in natural pregnancy rates, assisted reproductive pregnancy rates, and live birth rates.³

• A large meta-analysis focusing on 2256 women with DOR reported a spontaneous pregnancy rate of 7% (95% Confidence Interval [CI]: 0.04–0.12), a biochemical pregnancy rate of 18% (95% CI: 0.15–0.22), and a live birth rate (LBR) of 11% (95% CI: 0.07–0.15) following ovarian PRP.¹²

• Another meta-analysis centered on patients with POR found a clinical pregnancy rate (CPR) of 25.4% (95% CI: 13.1%–39.9%) and an LBR of 16.6% (95% CI: 8.8%–26.1%).¹⁰ This particular review also highlighted a significant finding: CPR and LBR were substantially higher in the subgroup of studies where platelets were activated prior to injection compared to those where non-activated PRP was used.

Individual Studies and Commentaries on RCTs:

• A pre-post study involving 234 women with POR reported a 9% spontaneous pregnancy rate after PRP. Among those who subsequently underwent IVF, the CPR per embryo transfer was 39.6%, and the ongoing pregnancy/live birth rate per transfer was 36.8%.⁵

• In contrast, a commentary on two 2024 RCTs concluded that PRP treatment does not improve pregnancy rates per oocyte retrieved.⁶

• A retrospective study evaluating PRP in women with POI and POR found no significant difference in LBRs before versus after PRP in the POR group (0% vs 4.7%, p=0.296). No pregnancies resulted in the POI group in that particular study.⁹

• A review concerning POI reported spontaneous pregnancy rates of 7.4–10% after PRP. It also cited a prospective trial in 311 women with POI that found a 22.8% pregnancy rate following embryo transfer. However, caution is urged when interpreting some reports of very high LBRs (e.g., 69-100%) in POI case series, as these are often based on very small sample sizes and are susceptible to significant bias.²

The reported pregnancy and live birth rates following ovarian PRP exhibit considerable heterogeneity across the literature. Meta-Analyses that include a substantial proportion of observational studies often present a more optimistic view³ compared to individual, more stringently designed studies or commentaries on recent RCTs.⁶ The exceptionally high LBRs noted in some small POI case reports² should be viewed as statistical outliers, likely influenced by small numbers and potential publication bias.

Several factors contribute to this variability. Firstly, the hierarchy of evidence dictates that RCTs generally provide more reliable data than observational studies due to a reduced risk of bias, including selection bias and confounding variables. Meta-analyses are powerful tools for synthesizing data, but their validity is intrinsically linked to the quality and homogeneity of the included primary studies. Pooling data from numerous small, potentially biased observational studies can sometimes amplify a weak or even non-existent effect. Secondly, publication bias, where studies with positive findings are more likely to be published than those with negative or null results, can skew the overall picture if not adequately addressed in systematic reviews. Thirdly, the commentary on recent RCTs⁶ is particularly pivotal: if well-conducted RCTs are not demonstrating improved pregnancy rates per oocyte retrieved, this challenges the broader claims of efficacy derived from lower-quality evidence. Fourthly, the finding that activated PRP yields significantly better pregnancy and LBRs than non-activated PRP¹⁰ is a crucial mechanistic insight that could explain some of the outcome variability if activation status is not consistently applied or reported across studies. Finally, nuances within patient populations are critical; an 11% LBR in a large DOR cohort¹², while based predominantly on observational data, is noteworthy for this typically poor-prognosis group. However, for POI patients, especially those with prolonged amenorrhea and minimal or no follicular activity, the chances of success appear to be substantially lower.²

Therefore, a highly nuanced interpretation of pregnancy and LBR data is essential. The source and quality of evidence underpinning different claims must be clearly delineated, with appropriate weight given to findings from robust RCTs. While some pooled data show promise, definitive, high-quality evidence of a substantial and consistent LBR benefit, particularly from well-powered RCTs, is still largely awaited or, in some recent instances, not supportive.

D. Synthesizing Evidence: From Case Reports to Meta-Analyses

The body of scientific literature pertaining to ovarian PRP is diverse, spanning a wide range of study designs. It includes anecdotal case reports detailing individual patient experiences¹, small observational case series, larger prospective cohort studies⁵, and an increasing number of systematic reviews and meta-analyses that attempt to synthesize the accumulating data.³ The level of scientific rigor and, consequently, the reliability and generalizability of the findings, vary significantly across these different types of studies.⁶

Typically, the evolution of evidence for a novel medical intervention begins with promising case reports and small series, which can generate initial enthusiasm and hypotheses. These are often followed by more structured observational studies and, eventually, by comparative trials, including RCTs, which are designed to provide more definitive evidence on efficacy and safety. Meta-analyses play a crucial role in this process by statistically combining the results of multiple studies to provide a more precise estimate of the treatment effect. However, the conclusions of a meta-analysis are heavily dependent on the quality, homogeneity, and potential biases of the primary studies included.

Table 2: Summary of Findings from Major Systematic Reviews and Meta-Analyses on Ovarian PRP Efficacy

This table provides a comparative overview of aggregated evidence, allowing for an assessment of consistency and divergence in findings across different reviews and patient populations. It underscores the evolving nature of the evidence base and the critical need for high-quality RCTs to provide more definitive answers.

V. Safety Profile and Risk Considerations of Intraovarian PRP

The safety profile of intraovarian PRP administration is a critical consideration, encompassing both immediate procedural risks and potential long-term consequences.

Short-Term Safety and Procedural Aspects:

A key purported safety advantage of PRP therapy is its autologous nature. Because PRP is derived from the patient's own blood, the risks of alloimmunization (immune reactions against foreign tissues) and the transmission of blood-borne infectious diseases, which could be concerns with allogeneic (donor-derived) products, are inherently minimized.¹

The administration procedure itself, typically involving a transvaginal ultrasound-guided needle puncture into the ovaries, is similar to oocyte retrieval performed during IVF. This procedure is associated with some degree of discomfort or mild pain. However, this is generally reported as minimal and can be effectively managed with the use of local anesthetics or light sedation.⁴ The initial blood draw required for PRP preparation is a standard phlebotomy procedure with well-established, low risks.

Regarding reported adverse events, the available literature, including a meta-analysis that cited four reports, suggests that clinically significant acute adverse reactions directly attributable to ovarian PRP administration are infrequently observed or reported.³ Most studies describe the procedure as well-tolerated.

Theoretical and Long-Term Risks:

Despite the generally favorable short-term safety profile, several theoretical and long-term risks warrant serious consideration, primarily due to the biological nature of PRP and the current lack of extensive long-term follow-up data.

1. Oncogenic Potential: A significant theoretical concern revolves around the introduction of a high concentration of various growth factors directly into ovarian tissue. Growth factors, by their fundamental biological action, stimulate cell proliferation, angiogenesis, and tissue growth – processes that are also hallmarks of tumor development and progression.⁹ The ovary is a hormonally responsive and mitotically active organ, and concerns exist that exogenously administered growth factors could potentially promote the growth of pre-existing occult neoplastic cells or, more speculatively, contribute to de novo malignant transformation over time. The long-term effects of such interventions are currently unknown.

2. Disruption of Natural Senescence and Tumor Suppressive Mechanisms: Ovarian aging and the associated decline in reproductive function are complex biological processes. It has been proposed that ovarian senescence may, in part, represent an evolved biological safeguard against pathological overgrowth or the accumulation and transmission of genetic mutations in germ cells.⁷ Interventions that aim to "rejuvenate" or significantly "reactivate" senescent ovarian tissue might inadvertently interfere with these natural protective mechanisms, the long-term consequences of which are undetermined.

3. Unknowns of Modifying Stem Cells or Inducing Cellular Plasticity: If, as some speculative theories suggest, PRP can influence ovarian stem cell activity, induce changes in cellular plasticity, or alter epigenetic programming within ovarian cells⁷, the long-term biological and health consequences of such fundamental modifications are entirely unknown and unquantified.

The current understanding of ovarian PRP safety is characterized by a dichotomy: the immediate procedural risks appear to be low and manageable, comparable to other minimally invasive gynecological procedures like oocyte retrieval.³ However, there is a conspicuous absence in the published literature of robust, systematic, long-term follow-up data, particularly concerning oncological safety or other potential delayed complications. Theoretical concerns about the potential for growth factors to promote malignancy or disrupt natural tumor-suppressive processes in the ovary are biologically plausible and have been raised by researchers.⁷ Most current studies on ovarian PRP focus on short-term reproductive outcomes, typically assessed over months to a year or two. The latency period for many types of cancer can be years or even decades. Therefore, the existing studies are generally not designed, nor do they have sufficient duration or power, to detect any potential increase in long-term oncogenic risk. The argument that ovarian aging itself might serve as a tumor suppressor mechanism⁷ adds another layer of complexity to this concern. While the autologous origin of PRP obviates the immune and infectious disease transmission risks associated with donor products, it does not inherently negate the potential risks associated with concentrating and redirecting a patient's own potent biological mediators to a specific organ in supraphysiological amounts. Thus, it is crucial to distinguish between the generally favorable short-term safety profile and the significant, largely unquantified, long-term risks, particularly oncological. The absence of reported long-term adverse events in the current, mostly short-term, literature does not equate to proven long-term safety. This uncertainty is a critical aspect for comprehensive informed patient consent and represents a priority area for future research, potentially through the establishment of long-term patient registries or dedicated follow-up studies of treated cohorts.

VI. The "Ovarian Rejuvenation" vs. "Ovarian Reactivation" Discourse: Terminology and Managing Expectations

The terminology used to describe the purported effects of intraovarian PRP is a subject of ongoing debate within the reproductive medicine community. The choice of words is not merely semantic; it carries significant implications for patient perception, expectations, and the ethical communication of treatment possibilities.

Patients, particularly those facing the difficult prospect of diminished ovarian reserve or premature ovarian failure and considering options like oocyte donation, often find the term "ovarian rejuvenation" highly appealing.⁶ This term evokes a sense of restoring youthfulness.

Works cited

1. Enhancement of Ovarian Reserve and Oocyte Quality After Platelet ..., accessed May 22, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10910621/

2. Platelet-Rich Plasma (PRP) in Reproductive Medicine: A Critical ..., accessed May 22, 2025, https://www.mdpi.com/2227-9059/13/5/1257

3. The effect of ovarian response parameters and the synergistic effect of assisted reproduction of poor ovarian response treated with platelet rich plasma: systematic review and meta-analysis, accessed May 22, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11055225/

4. Ovarian PRP: A Glimpse into the Future of Infertility Care - Selphyl, accessed May 22, 2025, https://www.selphyl.com/post/ovarian-prp-a-glimpse-into-the-future-of-infertility-care

5. Changes in Ovarian Functions Following Platelet-Rich Plasma (PRP ..., accessed May 22, 2025, https://www.imrpress.com/journal/CEOG/52/2/10.31083/CEOG26053/htm

6. Intraovarian platelet-rich plasma injection for ovarian rejuvenation - Oxford Academic, accessed May 22, 2025, https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaf030/8045480

7. Epigenetics, ovarian cell plasticity, and platelet-rich plasma ..., accessed May 22, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9782453/

8. Ovarian Rejuvenation (PRP) - Explaining the Process, accessed May 22, 2025, https://www.myivfanswers.com/video/ovarian-rejuvenation-and-prp/

9. The effects of intra-ovarian autologous platelet rich plasma injection ..., accessed May 22, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC8907433/

10. The efficacy of platelet rich plasma on women with poor ovarian response: a systematic review and meta-analysis - ResearchGate, accessed May 22, 2025, https://www.researchgate.net/publication/377362131_The_efficacy_of_platelet_rich_plasma_on_women_with_poor_ovarian_response_a_systematic_review_and_meta-analysis

11. Intraovarian PRP injection improves oocyte quality and early embryo development in mouse models of chemotherapy-induced diminished ovarian reserve - PubMed, accessed May 22, 2025, https://pubmed.ncbi.nlm.nih.gov/39276378/

12. (PDF) Platelet-rich plasma (PRP) treatment of the ovaries ..., accessed May 22, 2025, https://www.researchgate.net/publication/380666048_Platelet-rich_plasma_PRP_treatment_of_the_ovaries_significantly_improves_fertility_parameters_and_reproductive_outcomes_in_diminished_ovarian_reserve_patients_a_systematic_review_and_meta-analysis

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