Search Results (20)

Platelet-rich plasma (PRP) is an autologous blood-derived concentrate increasingly utilized in regenerative medicine for its ability to accelerate healing and tissue repair. PRP is broadly classified by leukocyte content, fibrin architecture, and platelet concentration, with classification systems developed to standardize characterization. Preparation methods, including single- or double-spin centrifugation and buffy coat techniques, influence the final composition of PRP, determining the relative proportions of platelets, leukocytes, plasma proteins, and extracellular vesicles. These components act synergistically, with platelets releasing growth factors (e.g., VEGF, PDGF, TGF-β) that stimulate angiogenesis and matrix synthesis, leukocytes providing immunomodulation, plasma proteins facilitating scaffolding, and exosomes regulating intercellular signaling. Mechanistically, PRP enhances tissue repair through four key pathways: platelet adhesion molecules promote hemostasis and cell recruitment; immunomodulation reduces pro-inflammatory cytokines and favors M2 macrophage polarization; angiogenesis supports vascular remodeling and nutrient delivery; and serotonin-mediated pathways contribute to analgesia. These processes establish a regenerative microenvironment that supports both structural repair and functional recovery. Clinically, PRP has been applied across multiple specialties. In orthopedics, it promotes tendon, cartilage, and bone healing in conditions such as tendinopathy and osteoarthritis. In dermatology, PRP enhances skin rejuvenation, scar remodeling, and hair restoration. Gynecology has adopted PRP for ovarian rejuvenation, endometrial repair, and vulvovaginal atrophy. In dentistry and oral surgery, PRP accelerates wound closure and osseointegration, while chronic wound care benefits from its angiogenic and anti-inflammatory effects. PRP has also favored gingival recession coverage, regeneration of intrabony periodontal defects, and sinus grafting. Although preparation heterogeneity remains a challenge, PRP offers a versatile, biologically active therapy with expanding clinical utility. Full article

Premature ovarian insufficiency (POI) and diminished ovarian reserve (DOR) are two related conditions characterized by a reduced ovarian reserve. Their etiologies are multifactorial, encompassing iatrogenic causes such as chemotherapy, pelvic surgery, or radiotherapy, as well as non-iatrogenic factors including genetic and chromosomal abnormalities, environmental exposures, autoimmune mechanisms and idiopathic sources. Early recognition of these conditions is essential, as timely and appropriate management can significantly impact both reproductive potential and long-term health. In women with POI, hormone replacement therapy is required to prevent the detrimental effects of estrogen deficiency on wellbeing and overall health, while in women with DOR, management focuses on counseling, fertility preservation when pregnancy is not an immediate goal, and strategies to optimize assisted reproductive outcomes when conception is desired. In addition, emerging research into ovarian rejuvenation offers promising new avenues for future therapeutic approaches. This review summarizes current knowledge on the pathophysiology, diagnosis, and management of POI and DOR, while highlighting innovative developments in reproductive medicine. Full article

Female infertility from polycystic ovarian syndrome (PCOS) and endometriosis poses a challenge for both clinicians and women who are trying to conceive. The present clinical single case report aimed to evaluate the efficacy of multiple wavelengths of red and near-infrared (NIR) laser photobiomodulation (PBM) for increasing the potential of fertility in a woman with PCOS, endometriosis and low ovarian reserve. The observations helped to inform and establish the following: (1) any adverse effects; (2) the possibility of producing an effective PBM protocol; and (3) a healthy live birth. The case report concerns a female who failed to conceive naturally beyond five years and had experienced one unsuccessful IVF cycle. Methods: Case report of one female subject with infertility issues, which included failure to conceive naturally beyond five years. Previous conditions were recorded and then compared with outcomes from after the patient received a course of PBM treatments. PBM treatments were given at weekly and/or at two-week intervals over a 5-month period during the follicular stage of the menstrual cycle, using IR and NIR wavelengths between 600 and 1000 nm. Results: After five months a spontaneous conception was achieved. The case resulted in a full-term pregnancy and the birth of a healthy baby. Improvements in reproductive health outcomes in this case give reason to suggest that PBM helped to alleviate PCOS and endometriosis which could have been associated with a low ovarian reserve. Conclusions: The case report indicates that a multiwavelength of red and NIR-PBM laser therapy could have positively contributed to a healthy live birth in a female diagnosed with PCOS, endometriosis and a low ovarian reserve. Extensive studies with large data are warranted to validate our PBM dosimetry and treatment protocols to assess the potential impact of PBM for treating endometriosis and PCOS. Subsequently, to understand the genetic and phenotype biomarkers would be an important step further to standardise a range of PBM light dosimetry. Full article

Infertility remains a major global health concern, with diminished ovarian reserve (DOR), premature ovarian insufficiency (POI), polycystic ovary syndrome (PCOS), and impaired endometrial receptivity representing key contributors to poor assisted reproductive technology (ART) outcomes. Platelet-rich plasma (PRP), an autologous blood-derived concentrate enriched with growth factors and cytokines, has emerged as a promising regenerative therapy with angiogenic, anti-apoptotic, and proliferative properties. In reproductive medicine, intraovarian PRP has been evaluated for its potential to restore ovarian function in women with DOR and POI, improve oocyte competence and embryo euploidy, and promote ovulation in PCOS. Similarly, intrauterine PRP infusion or subendometrial zone injections has shown encouraging results in women with recurrent implantation failure and thin endometrium, enhancing endometrial thickness, receptivity, and implantation potential. Evidence from preclinical animal models and early clinical studies suggests multi-level mechanisms of action, including modulation of endocrine pathways, reduction in oxidative stress, activation of dormant follicles, and improvement of endometrial angiogenesis and receptivity. Despite these promising findings, results remain inconsistent due to heterogeneity in PRP preparation protocols, administration routes, timing, and study designs. Even though robust randomized controlled trials with standardized methodologies are needed to determine the efficacy and long-term reproductive outcomes of PRP in infertility treatment and anovulation in PCOS, PRP represents a novel and potentially transformative adjunct in reproductive endocrinology. Full article

Background: Infertility remains a significant global health challenge, affecting approximately 15% of couples worldwide. In vitro fertilization (IVF) has transformed reproductive medicine; however, challenges such as low success rates in older patients, ovarian insufficiency, endometrial dysfunction, and male infertility continue to limit outcomes. Objective: This review aims to summarize the principles of IVF and explore the potential role of stem cells in enhancing IVF outcomes, with particular attention to applications in both women and men, as well as the accompanying ethical considerations. Summary: Stem cell research has introduced novel therapeutic opportunities, including ovarian rejuvenation, endometrial regeneration, sperm quality enhancement, and the development of synthetic embryo models. Mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) demonstrate regenerative properties that may help to overcome current reproductive limitations. Despite encouraging findings from preclinical and early clinical studies, challenges such as tumorigenesis, genetic instability, and ethical controversies remain major barriers to translation. Conclusions: IVF continues to serve as a cornerstone of assisted reproductive technology (ART). Stem cell-based approaches represent an exciting frontier that could expand the therapeutic possibilities of IVF. Careful clinical validation, international regulatory harmonization, and robust ethical oversight will be essential to ensuring safe and equitable implementation. Full article

Advancements in assisted reproductive technologies (ARTs) have led to the development of various add-on techniques aimed at improving oocyte quality and enhancing embryo implantation potential. These techniques target critical stages of both oocyte and embryo physiology, including oocyte growth and maturation, fertilization, chromosomal status, and embryo development. Key approaches involve the optimization of in vitro fertilization (IVF) protocols, recruiting capable follicles giving rise to dynamic oocytes to evolve, culture media supplementation, preimplantation genetic testing (PGT), and mitochondrial replacement therapy (MRT), all of which are designed to enhance oocyte competence through its function and metabolism. The use of PGT has been promising in selecting embryos suitable for transfer, thus optimizing implantation success. Emerging technologies, such as platelet-rich plasma treatment (PRP), time-lapse imaging (TLI), and hyaluronan-rich (HA) culture media, claim to improve ovarian rejuvenation and uterine receptivity, embryo selection, as well as embryo implantation potential, respectively. Evidence for certain add-on approaches remains limited, but ongoing research suggests that the use of such treatments may lead to increased clinical pregnancies and live birth rates, especially in poor-prognosis patients. The present review describes the current state of the add-on innovations, their mechanisms of action, as well as their possibilities to increase ART success rates. Full article

According to World Health Organization (WHO) data, 16% of people are affected by infertility across the globe. One underlying factor is the age-related decline of ovarian reserve (DOR), which can lead to a higher chance of infertility and has no widely accepted treatment currently. Specific supplements and moderate exercise have been shown to improve fertility; however, there is no consensus to date on the type of exercise providing the best results. Our goal is to develop a novel exercise program combined with natural supplements for the improvement of fertility. We also propose a single-centered, randomized, open-label clinical trial using our newly developed exercise in the intervention group, compared to walking and no exercise in the other groups, to investigate the benefits of this exercise program in the future. In this study, we developed a structured, novel combination of exercises focusing on the pelvic and ovarian regions, core strengthening and improvement of blood circulation in this region. The 70 min full body “reproductive gymnastics”, includes strengthening, stretching, and relaxation exercises combined with yoga-inspired moves and diaphragmatic breathing with meditation elements to activate the parasympathetic pathway and stress relief. We believe we can improve fertility through the combination of natural supplements and our targeted, moderate physiotherapy program in women with DOR. Full article

Background/Objectives: Female infertility due to unexpected causes exhibits a great challenge for both clinicians and women who are trying to conceive. The present clinical case series study aimed to evaluate the efficacy of multiple wavelengths of red and near-infrared (NIR) laser photobiomodulation (PBM) for increasing the potential of fertility in women and improving reproductive health in unexplained infertility issues. The objectives were to assess the following: (1) any adverse effects; (2) the possibility of producing an effective PBM protocol; (3) and healthy live birth. The inclusion criteria were to related to females who failed to conceive naturally beyond two years, multiple miscarriages, molar pregnancy, non-viable embryos from in vitro fertilisation (IVF) cycles, and failure to complete successful implantation of viable pre-implantation genetic tested (PGT-A) embryos. Methods: Case series of three female subjects with unexplained age-related infertility issues, which included a failure to conceive naturally beyond two years, multiple miscarriages, molar pregnancy, non-viable embryos from IVF cycles, and failure to complete successful implantation of viable pre-implantation genetic tested (PGT-A) embryos. In each case, previous conditions were recorded and then compared with outcomes after the patient received a course of PBM treatments. In every case, fertility outcomes improved. Three cases resulted in a full-term pregnancy and the birth of a healthy baby. PBM treatments were given at weekly and/or at two-week intervals using IR and NIR wavelengths between 600 nm and 1000 nm in the lead up to natural conception, IVF oocyte retrieval, blastocyst/embryo implantation, and/or the production of viable embryos. Results: In every case, fertility outcomes improved. Improvements in reproductive health outcomes in each case give reason to suggest that PBM may help to improve unexplained age-related infertility. Conclusions: Our study demonstrated that multiwavelength of red and NIR PBM with either an LED or laser, or a combination, improved female fertility and reproductive health and contributed to healthy live births in females diagnosed with unexplained age-related infertility. Extensive studies with robust data are warranted to validate our PBM dosimetry and treatment protocols. Moreover, understanding the genetic and phenotype biomarkers is important to standardise a range of PBM light dosimetry. Full article

Background/Objectives: Infertility constitutes a significant challenge for couples around the world. Ovarian dysfunction, a major cause of infertility, can manifest with anovulatory cycles, elevated follicle-stimulating hormone levels, and diminished ovarian reserve markers such as anti-Müllerian hormone (AMH) levels or the Antral Follicle Count (AFC). Blood-derived therapies including platelet-rich plasma (PRP) have been used in fertility treatments in women with low ovarian reserve or premature ovarian insufficiency. This prospective clinical cohort study aims to assess the effects of intraovarian PRP therapy on ovarian function in women diagnosed with anovulatory cycles. Methods: The preliminary findings of this prospective cohort study are based on the first 32 patients enrolled. In this study, patients over 40 years old with anovulatory infertility were included. Venous blood samples were collected from each participant for the preparation of autologous platelet-rich plasma (PRP). Each participant received two courses of intraovarian PRP injections using a transvaginal ultrasound-guided approach. Serum levels of reproductive hormones before and after PRP intervention were measured. Results: This study’s results demonstrate a significant improvement in ovarian physiology following transvaginal ultrasound-guided PRP infusion. A 75% increase in Antral Follicle Count (AFC) was observed, which was statistically significant. Furthermore, statistically significant reductions in follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels were observed. Serum Vitamin D 1–25 levels were substantially increased after the injection. Conclusions: These findings highlight the beneficial impact of intraovarian PRP injection in optimizing ovarian function and other metabolic parameters. However, the published literature on this subject is limited and further clinical studies should be conducted to confirm the role of intraovarian PRP in fertility treatments. Full article

No major breakthroughs have entered mainstream clinical fertility practice since egg donation and intracytoplasmic sperm injection decades ago, and oocyte deficits secondary to advanced age continue as the main manifestation of diminished ovarian reserve. In the meantime, several unproven IVF ‘accessories’ have emerged including so-called ovarian rejuvenation which entails placing fresh autologous platelet-rich plasma (PRP) directly into ovarian tissue. Among cellular responses attributed to this intervention are reduced oxidative stress, slowed apoptosis and improved metabolism. Besides having an impact on the existing follicle pool, platelet growth factors might also facilitate de novo oocyte recruitment by specified gene upregulation targeting uncommitted ovarian stem cells. Given that disordered activity at the mechanistic target of rapamycin (mTOR) has been shown to exacerbate or accelerate ovarian aging, PRP-discharged plasma cytokines combined with mTOR suppression by pulsed/cyclic rapamycin represents a novel fusion technique to enhance ovarian function. While beneficial effects have already been observed experimentally in oocytes and embryos with mTOR inhibition alone, this proposal is the first to discuss intraovarian platelet cytokines followed by low-dose, phased rapamycin. For refractory cases, this investigational, tailored approach could amplify or sustain ovarian capacity sufficient to permit retrieval of competent oocytes via distinct but complementary pathways—thus reducing dependency on oocyte donation. Full article

Platelet-rich plasma (PRP) is an ‘orthobiologic’ with recognized roles in plastic surgery, musculoskeletal disorders, dentistry, dermatology, and more recently, ‘ovarian rejuvenation’. Intraovarian PRP involves a complex secretome discharged after platelet activation, comprising multiple cytokine mediators delivered surgically to older or inactive ovarian tissue. Loss of oocyte meiotic fidelity and impaired fertilization accompanying advanced maternal age are already managed by IVF, but only with eggs provided by younger donors. However, if the observed effect of rectifying embryo ploidy error can be proven beyond case reports and small series, activated PRP (or its condensed plasma cytokines) would deliver a welcome therapeutic disruption that is difficult to overstate. Because shortcomings in ovarian function are presently addressed mainly by pharmacological approaches (i.e., via recombinant gonadotropins, GnRH analogs, or luteal support), autologous PRP would represent an unusual departure from these interventions. Given the diversity of platelet cargo proteins, the target response of intraovarian PRP is probably not confined to oocytes or follicles. For example, PRP manipulates signal networks driving improved perfusion, HOX regulation, N-glycan post-translational modification, adjustment of voltage-gated ion channels, telomere stabilization, optimization of SIRT3, and ribosome and mitochondria recovery in older oocytes. While multichannel signals operating on various pathways are not unique to reproductive biology, in intraovarian PRP this feature has received little study and may help explain why its standardization has been difficult. Against this background, our report examines the research themes considered most likely to shape clinical practice. Full article

While advanced reproductive technologies have attained remarkable increases in sophistication, success, and availability since the 1980s, clinicians always meet a therapeutic impasse when the ovarian reserve reaches exhaustion. Irrespective of fertility aspirations, the decline in and eventual collapse of ovarian estrogen output means that menopause arrives with tremendous physiologic changes and reduced overall productivity. Because more women are gaining in longevity or delaying the age at pregnancy, the number of affected patients has never been larger. As concerns regarding standard hormone replacement therapy and the limitations of IVF are confronted, a workable path to enable primordial germ cell recruitment and de novo oocyte development would be welcome. Proof-of-concept case reports and clinical studies on autologous activated platelet-rich plasma (PRP) or its condensed cytokine derivatives suggest a way to facilitate these goals. However, ovarian PRP faces vexing challenges that place ‘ovarian rejuvenation’ under caution as it enters this therapeutic space. Here, we review key features of experimental human ovarian stem cell isolation/handling and reaffirm the need to harmonize laboratory protocols. Recognizing the regenerative science borrowed from other disciplines, specimen centrifugation, platelet processing, and condensed plasma cytokine enrichment are highlighted here. As the refinement of this rejuvenation approach would promise to reprogram adult ovarian physiology, the disruption of established treatment paradigms for infertility, menopause, and perhaps overall women’s health seems likely. Emerging roles in reproductive biology and clinical practice are thus placed in a broader social and demographic context. Full article

Background: The intraovarian administration of autologous platelet-rich plasma (PRP) acts beneficially for the stimulation of follicle production in women presenting different forms of ovarian dysfunction. This pilot study aimed to evaluate and provide significant data regarding the efficacy of PRP to rejuvenate the ovaries. Methods: A total of 253 women aged 22–56 years, were divided into five groups, based on their status. All participants signed for informed consent for the current study. Blood sampling, preparation of PRP and intraovarian infusion of the latter were performed on all participants. The evaluation of PRP efficacy, a two-month follow-up detecting the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and anti-mullerian hormone (AMH), was performed for all participants. For women with advanced ages (>48 years), the restoration and regularity of the menstrual cycle were additionally evaluated. Results: After the two-month follow-up, the majority of the participants presented improvement in their hormonal profiles. Additionally, 17% of the women in this pilot study successfully conceived. The restoration of the menstrual cycle was detected in 15% of the women with advanced ages. Conclusions: Intraovarian infusion of autologous PRP exhibited remarkable evidence and promising results to restore ovarian insufficiency. Full article

Aging is a degenerative process involving cell function deterioration, leading to altered metabolic pathways, increased metabolite diversity, and dysregulated metabolism. Previously, we reported that human placenta-derived mesenchymal stem cells (hPD-MSCs) have therapeutic effects on ovarian aging. This study aimed to identify hPD-MSC therapy-induced responses at the metabolite and protein levels and serum biomarker(s) of aging and/or rejuvenation. We observed weight loss after hPD-MSC therapy. Importantly, insulin-like growth factor-I (IGF-I), known prolongs healthy life spans, were markedly elevated in serum. Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS) analysis identified 176 metabolites, among which the levels of 3-hydroxybutyric acid, glycocholic acid, and taurine, which are associated with health and longevity, were enhanced after hPD-MSC stimulation. Furthermore, after hPD-MSC therapy, the levels of vitamin B6 and its metabolite pyridoxal 5′-phosphate were markedly increased in the serum and liver, respectively. Interestingly, hPD-MSC therapy promoted serotonin production due to increased vitamin B6 metabolism rates. Increased liver serotonin levels after multiple-injection therapy altered the expression of mRNAs and proteins associated with hepatocyte proliferation and mitochondrial biogenesis. Changes in metabolites in circulation after hPD-MSC therapy can be used to identify biomarker(s) of aging and/or rejuvenation. In addition, serotonin is a valuable therapeutic target for reversing aging-associated liver degeneration. Full article

The first published description of intraovarian platelet-rich plasma (PRP) appeared in mid-2016, when a new experimental technique was successfully used in adult human ovaries to correct the reduced fertility potential accompanying advanced maternal age. Considering the potential therapeutic scope of intraovarian PRP would likely cover both menopause and infertility, the mainstream response has ranged from skeptical disbelief to welcome astonishment. Indeed, reports of intraovarian PRP leading to restored menses in menopause (as an alternative to conventional hormone replacement therapy) and healthy term livebirths for infertility patients (from IVF or as unassisted conceptions) continue to draw notice. Yet, any proper criticism of ovarian PRP applications will be difficult to rebut given the heterogenous patient screening, varied sample preparations, wide differences in platelet incubation and activation protocols, surgical/anesthesia techniques, and delivery methods. Notwithstanding these aspects, no adverse events have thus far been reported and ovarian PRP appears well tolerated by patients. Here, early studies guiding the transition of ‘ovarian rejuvenation’ from experimental to clinical are outlined, with mechanisms to explain results observed in both veterinary and human ovarian PRP research. Current and future challenges for intraovarian cytokine treatment are also discussed. Full article