PRPPOR: Autologous Platelet Rich Plasma Intraovarian Infusion for Poor Responders

Sponsor

Genesis Athens Clinic (Other)

Overall Status

Recruiting

CT.gov ID

NCT05181748

Collaborator

National and Kapodistrian University of Athens (Other)

100

Enrollment

Location

Arms

60.3

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Poor Response to Ovulation Induction Infertility, Female Ovarian Insufficiency Ovarian Failure Reproductive Sterility Ovary; Anomaly	Biological: Autologous platelet rich plasma	Phase 2/Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention 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 cycleExperimental: 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)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 23, 2019

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Jan 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental: Group of participants receiving PRP treatment 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 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. Other Names: PRP
No Intervention: Control Group: Group of participants receiving standard protocol Women presenting with POR undergoing a stimulated fresh ET-ICSI cycle

Arm

Intervention/Treatment

Experimental: Experimental: Group of participants receiving PRP treatment

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

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.

Other Names:

PRP

No Intervention: Control Group: Group of participants receiving standard protocol

Women presenting with POR undergoing a stimulated fresh ET-ICSI cycle

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 47 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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