Intraovarian vascular enhancement via stromal injection of platelet-derived growth factors: Exploring subsequent oocyte chromosomal status and in vitro fertilization outcomes

Abstract

The inverse correlation between maternal age and pregnancy rate represents a major challenge for reproductive endocrinology. The high embryo ploidy error rate in failed <i>in vitro</i> fertilization (IVF) cycles reflects genetic misfires accumulated by older oocytes over time. Despite the application of different follicular recruitment protocols during IVF, gonadotropin modifications are generally futile in addressing such damage. Even when additional oocytes are retrieved, quality is frequently poor. Older oocytes with serious cytoplasmic and/or chromosomal errors are often harvested from poorly perfused follicles, and ovarian vascularity and follicular oxygenation impact embryonic chromosomal competency. Because stimulation regimens exert their effects briefly and immediately before ovulation, gonadotropins alone are an ineffective antidote to long-term hypoxic pathology. In contrast, the tissue repair properties (and particularly the angiogenic effects) of platelet-rich plasma (PRP) are well known, with applications in other clinical contexts. Injection of conventional PRP and/or its components (e.g., isolated platelet-derived growth factors as a cell-free substrate) into ovarian tissue prior to IVF has been reported to improve reproductive outcomes. Any derivative neovascularity may modulate oocyte competence by increasing cellular oxygenation and/or lowering concentrations of intraovarian reactive oxygen species. We propose a mechanism to support intrastromal angiogenesis, improved follicular perfusion, and, crucially, embryo ploidy rescue. This last effect may be explained by mRNA upregulation coordinated by PRP-associated molecular signaling, as in other tissue systems. Additionally, we outline an intraovarian injection technique for platelet-derived growth factors and present this method to help minimize reliance on donor oocytes and conventional hormone replacement therapy.

The Scientific and Cultural Journey to Ovarian Rejuvenation: Background, Barriers, and Beyond the Biological Clock

“…The distinction between reported methods, where superiority or equivalence has not yet been sufficiently studied, rests on ovarian injection of activated platelets or their isolated, cell free supernatant. Such growth factors can improve tissue perfusion via intrastromal angiogenesis, and after intraovarian injection (see Figure 1) this could be expected to modulate oocyte competence by tempering intraovarian reactive oxygen species and/or mRNA upregulation coordinated by PRP-associated molecular signaling [27]. In addition to numerous cytokines released by activated platelets, the releasate also includes mitochondria capable of initiating multiple physiological responses [28].…”

“…After sample placement within ovarian tissue, serum anti-Mullerian hormone (AMH) level is measured over three months to assess potential changes in ovarian reserve. Post-treatment AMH patterns appear directly correlated with baseline platelet concentration [27]. Using standard IVF equipment, bilateral ovary PRP injection may be safely performed in ≤20 min without anesthesia or sedation [7].…”

Appraisal of Experimental Methods to Manage Menopause and Infertility: Intraovarian Platelet-Rich Plasma vs. Condensed Platelet-Derived Cytokines

“…Platelets contain multiple granules which, upon activation, deliver numerous cargo proteins including platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), transforming growth factor-beta 1 (TGF-β1), insulin-like growth factor (IGF), connecting tissue growth factor (CTGF), hepatocyte growth factor (HGF), and others [9,11]. The roster of releasate contents seems ever growing; these moieties orchestrate cellular growth and directs repair following tissue injury.…”

“…Rejuvenation arrived on the gynecology stage with its (non-pharmacologic) promise to improve ovarian function [11]. Autologous PRP has also been used occasionally as an intrauterine lavage, aiming to boost endometrial receptivity and enhance embryo implantation [12].…”

Intraovarian insertion of autologous platelet growth factors as cell-free concentrate: Fertility recovery and first unassisted conception with term delivery at age over 40

“…Indeed, PRP has been shown to induce proliferation of some cell populations to improve stemness and to enhance in vitro expression of receptivity markers (18,19). Since these factors also have angiogenic properties, it is plausible that improving capillary flow and thus tissue oxygen delivery might induce beneficial ovarian effects after injection (20).…”