Autologous Platelet Rich Plasma Intraovarian Infusion for Poor Responders

Study Overview
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Brief Summary
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Autologous platelet rich plasma (PRP) intraovarian infusion may improve ovarian response to controlled ovarian stimulation as well as the hormonal profile of poor ovarian response infertile women subjected to intracytoplasmic sperm injection (ICSI) treatment.

Detailed Description
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Despite recent advances in reproductive medicine, poor ovarian response (POR) management is still considered to be very challenging. Commonly, POR patients present with reduced ovarian reserve and poor ovarian stimulation performance. The POR cycles are characterized by a very limited number of retrieved oocytes, subsequently leading to poor embryo formation and thus to high cycle cancelation rate. Despite the fact that POR constitutes a multifactorial condition, it is well demonstrated that advanced maternal age (AMA) is the most significant contributor of POR. As maternal age increases, reduction of neo-angiogenesis in ovaries is observed, leading to accelerated follicular loss. Considering that PRP contains several growth factors such as vascular endothelial growth factor (VEGF) and cytokines, it has been proposed that intraovarian infusion of autologous PRP could restore the ovarian niche microenvironment, increasing ovarian response to external gonadotropin stimulation. However, limited data are available with regards to PRP efficiency in POR patients, which are mainly originating from pilot or small cohort studies. This interventional non-randomised open-label study aims to investigate the effect of autologous PRP intraovarian infusion on improving POR patient performance by studying a large and well-controlled POR population.

Official Title
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Investigating the Efficiency of Autologous Platelet Rich Plasma Intraovarian Infusion on Improving Ovarian Functionality in Poor Ovarian Response Patients

Conditions
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Poor Response to Ovulation Induction, Infertility, Female, Ovarian Insufficiency, Ovarian Failure, Reproductive Sterility, Ovary; Anomaly

Intervention / Treatment
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* Biological: Autologous platelet rich plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Poor Ovarian Response according to Bologna Criteria (fulfilling 2 out of 3 of the following): Age ≥ 40 years AMH < 1.1 ng/ml OR AFC < 7 ≤ 3 oocytes with a conventional stimulation protocol Discontinuation of any complementary/adjuvant treatment including hormone replacement and acupuncture, for at least three months prior to recruitment. Willing to comply with study requirements Exclusion Criteria: Any pathological disorder related to reproductive system anatomy Cycle irregularities Amenorrhea Endometriosis Adenomyosis Fibroids and adhesions Infections in reproductive system Current or previous diagnosis of cancer in reproductive system History of familiar cancer in reproductive system Severe male factor infertility Prior referral for Preimplantation Genetic Testing (PGT) -Ovarian inaccessibility -Endocrinological disorders (Hypothalamus- Pituitary disorders, thyroid dysfunction, diabetes mellitus, metabolic syndrome) BMI>30 kg/m2 or BMI<18.5 kg/m2 Systematic autoimmune disorders

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 47 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Experimental: Group of participants receiving PRP treatment Women presenting with POR, treated with autologous PRP intraovarian infusion in the mid-luteal phase of the menstrual cycle, undergoing a subsequent stimulated fresh Embryo Transfer-Intracytoplasmic Sperm Injection (ET-ICSI) cycle on the first menstrual cycle following PRP treatment. Control Group: Group of participants receiving standard management Women presenting with POR undergoing a stimulated fresh ET-ICSI cycle
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Group of participants receiving PRP treatment<br>Women presenting with POR, treated with autologous PRP intraovarian infusion during the mid-luteal phase, undergoing a subsequent stimulated fresh ET-ICSI cycle on the first month following PRP infusion | Biological: Autologous platelet rich plasma<br>* Preparation of PRP will be performed immediately following blood sample collection. Blood samples will be collected from the median antebrachial vein. PRP will be prepared according to the manufacturer's instructions employing a Regen Autologous Cellular Regeneration (ACR®-C) Kit (Regen Laboratory, Le Mont-sur-Lausanne, Switzerland). Approximately 60 mL of the patient's peripheral blood will be required in order to yield the required volume of PRP. The goal concentration of platelets in PRP is approximately 1.000.000 platelets/µL. The technique of PRP intraovarian infusion resembles the transvaginal paracentesis performed during the oocyte pick-up procedure. Briefly, both ovaries are visualized via transvaginal ultrasound monitoring, and they are intramedullary injected on multiple sites using a 17-gauge single lumen needle, with the patient under inhaled minimal sedation.<br>* Other names: PRP;|
| No Intervention: Control Group: Group of participants receiving standard protocol<br>Women presenting with POR undergoing a stimulated fresh ET-ICSI cycle | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of oocytes retrieved | Number of oocytes retrieved following controlled ovarian stimulation in the first fresh ICSI-ET cycle performed on the first menstrual cycle following intervention | 34-36 hours following ovulation triggering | 
| Anti-Müllerian Hormone Levels (AMH) | Serum anti-müllerian hormone (AMH) levels evaluated in the first menstrual cycle following intervention | On day 2-3 of the first menstrual cycle post intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate | Clinical pregnancy rate, following the first fresh ET-ICSI cycle performed on the first menstrual cycle after intervention | 6-7 weeks following last menstruation | 
| Antral Follicle Count (AFC) | Antral Follicle Count (AFC) evaluated in the first menstrual cycle following intervention | On day 2-3 of the first menstrual cycle post intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous platelet rich plasma intraovarian infusion, Assisted reproduction, PRP, In vitro fertilization, Ovarian functionality improvement