Autologous Intraovarian Platelet Rich Plasma Treatment in Women With Poor Ovarian Response

Study Overview
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Brief Summary
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Reproductive age women diagnosed with poor ovarian response (POR) based on Bologna criteria with a history of at least two prior failed ICSI cycle will be recruited for the study. Antral follicle count (AFC), serum anti-mullerian hormone (AMH), and early follicular phase serum follicle stimulating hormone (FSH) levels will determined at baseline. Autologous blood obtained from peripheral vein will be used to prepare PRP following standard protocols and will be injected to both ovaries. Ovarian reserve parameters and ICSI outcomes will be determined.

Detailed Description
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Reproductive age women diagnosed with POR based on Bologna criteria with a history of at least two prior failed intracytoplasmic sperm injection (ICSI) cycle will recruited for the study. Antral follicle count (AFC), serum anti-mullerian hormone (AMH), and early follicular phase serum follicle stimulating hormone (FSH) levels will be determined at baseline. Autologous blood obtained from peripheral vein will be used to prepare PRP following standard protocols. PRP injection will be performed under sedation anesthesia, using a 11.8 inch (30 cm) single lumen 21G needles under transvaginal ultrasound guidance. On the 2 to 4th days of the first three menstrual cycles following the procedure, AFC, AMH, and FSH levels will be re-assessed. Patients with at least one antral follicle will be started on ovarian stimulation for ICSI, followed by embryo transfer. Biomarkers of ovarian reserve (AFC, FSH, AMH), and ICSI outcome parameters (number of metaphase II (MII) oocytes, blastocyst embryos, fertilization rate, oocyte and embryo quality) will be followed.

Official Title
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Effects of Autologous Intraovarian Platelet Rich Plasma in Women With Poor Ovarian Response

Conditions
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Poor Ovarian Reserve

Intervention / Treatment
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* Biological: Autologous ovarian PRP injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with POR based on Bologna criteria and with a history of at least two prior failed ICSI cycles A previous assisted reproductive technology cycle with less than 3 oocytes (conventional stimulation protocol) and AFC < 7 The same ovarian stimulation protocol before and after the PRP treatment Exclusion Criteria: Age over 46 years, Body mass index (BMI) ≥ 30 kg/m2, Presence of pregnancy Uncontrolled endocrine disorders (polycystic ovary syndrome and others) Parental genetic and chromosomal disorders, Immunological disorders Cancer diagnostics

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 46 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: After the women are recruited for the study, Antral follicle count (AFC), serum anti-mullerian hormone (AMH) and follicle stimulating hormone (FSH) levels will be determined at baseline and will be repeated beginning with the first menstrual cycle after treatment. Approximately 22 ml of blood sample will be collected under sterile conditions, and PRP will be prepared. The same day, within 1 hour of sample preparation, PRP injection will be performed transvaginally under ultrasound guidance and under sedation anesthesia into both ovaries. Ovarian reserve (AFC, FSH, AMH), and ICSI outcome parameters (number of MII oocytes, fertilization rate, oocyte and embryo quality) will be followed up to three months after the intervention.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ovarian Reserve<br>Patients with diminished ovarian reserve or premature ovarian insufficiency | Biological: Autologous ovarian PRP injection<br>* The same day, within 1 hour of sample preparation, PRP injection will be performed transvaginally under ultrasound guidance and under sedation anesthesia into both ovaries using 11.8 inch (30 cm) single lumen 21G needles. The ovaries will be reached using needle guide preventing vascular or other structures rupture. The needle will be advanced into the centre of the ovarian medula without rotation. The correct tip placement will be confirmed by ultrasound. The activated PRP will be slowly introduced during careful retraction of the needle across the previously traversed ovarian cortex. The final PRP volume will be deposited under the ovarian capsule and the needle exit the ovary. Approximately 0.5 ml of the PRP solution will be injected into each ovary. After the procedure, the patients will be taken to the recovery room and will be observed for 30 minutes and also be discharged home on the same day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oocyte number | Number of Metaphase II oocyte yield. | 3 months | 
| Oocyte quality | Oocytes will be classified based on morphological assessment and enumeration of extracytoplasmic anomalies. | 3 months | 
| Embryo number | Number of produced embryos per cycle. | 3 months | 
| Embryo quality | Morphological evaluation of the cultured embryos will be conducted 120 or 144 hr following sperm injection. Blastocysts scoring will be performed on day 5 or 6 depending on the blastocoel cavity expansion and on the inner cell mass and trophectoderm cells integrity. | 3 months | 
| Fertilization rate | Fertilization rate will be calculated as the percentage of transformation of the injected oocytes into two pronuclei. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antral follicle count (AFC) | Number of Antral Follicles determined by pelvic sonogram on day 2 or 3 of the cycle. | 3 months | 
| Serum anti-mullerian hormone (AMH) | Serum concentration of anti-mullerian hormone determined on day 3 of the cycle by an electrochemiluminescent (ECLIA) immunoanalyzer. | 3 months | 
| Serum follicle stimulating hormone (FSH) | Serum concentration of follicle stimulating hormone (FSH) levels determined on day 3 of the cycle by an electrochemiluminescent (ECLIA) immunoanalyzer. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Platelet-Rich Plasma, Poor Ovarian Reserve, Oocyte Quality, Embryo Quality