Poor Response to Ovulation Induction, Infertility, Female, Ovarian Insufficiency, Ovarian Failure, Reproductive Sterility, Ovary; Anomaly
Conditions
Keywords
Autologous platelet rich plasma intraovarian infusion, Assisted reproduction, PRP, In vitro fertilization, Ovarian functionality improvement
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.
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.
Interventions
BIOLOGICALAutologous 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.
Sponsors
National and Kapodistrian University of Athens
Genesis Athens Clinic
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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 cycle
Eligibility
Sex/Gender
FEMALE
Age
35 Years to 47 Years
Healthy volunteers
Yes
Inclusion criteria
Poor Ovarian Response according to Bologna Criteria (fulfilling 2 out of 3 of the following): 1. Age ≥ 40 years 2. AMH \< 1.1 ng/ml OR AFC \< 7 3. ≤ 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Greece
Contacts
Primary ContactAgni Pantou, M.D
Backup ContactKonstantinos Pantos, M.D., Ph.D
Outcome results
None listed