Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency

Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency: A Randomized Controlled Trial

60 cases with premature ovarian insufficiency will be randomized to either receive PRP or saline injection in their ovaries. Then follow up by hormonal & ultrasound & clinically to monitor any changes

Study Overview

• Status: Not yet recruiting
• Conditions: Premature Ovarian Failure
• Intervention / Treatment: Biological: platelet rich plasma; Drug: Normal saline

Detailed Description

In this pilot study, 60 patients will be included. All patients will have a premature ovarian insufficiency (PORs) who meet at least two of the following three Bologna criteria.

The following data will be registered for all the cases: age, weight, height, menstrual history, previous pregnancies and their outcome, no. of living children and age of the youngest, history symptoms, married for how long, infertility duration and whether primary or secondary. Estimation of Antral Follicle Count (AFC) will be done for all the patients by transvaginal ultrasound (TVUS). Finally, a blood sample will be withdrawn for the following lab. Investigations: FSH, LH, E2, AMH, TSH, Prolactin before inclusion of the patients in the study.

A written consent form will be signed by all patients after complete explanation of the procedures and the expectations of the trial. Patients will be randomized into 2 groups (A& B). All will undergo a transvaginal intervention through an ovum pickup needle 17 G for the procedure. The group A consists of 30 patients, who will receive a PRP (autologous platelet-rich plasma injection) with activation with calcium chloride. The group B consists of 30 patients, who will receive a normal saline inj. 0.9% Nacl.

Sample preparation of the PRP:

According to the classification proposed by Ehrenfest, 4 different types of PRP are defined, depending on the content of cells and the presence of fibrin. In regards to the Classification of PRP in this case study, it is used as a commercial type of PRP with the lower concentration (2.5 x 3 times) system, Ycellbio PRP. The process will be carried out under strict aseptic conditions as well as optimum temperature regulations, i.e., 21-24°C. PRP will be prepared according to the manufacturer's guidelines. Draw 1 CC anticoagulant (sodium citrate) into a 20 CC syringe. Coat the inside walls of the syringe with the drawn anticoagulant. Then draw 14 CC blood under complete aseptic condition into a 20 CC syringe. Swing the syringe slowly to mix blood and anticoagulant well. Inject the blood slowly into the Ycellbio tube. Straighten the tube when the blood reaches the Y-funnel. Inject the blood into the Ycellbiotube to the appropriate level as indicated by the lines. Close the Ycellbio tube with silicon stopper using a forceps. Centrifuge at 3500 RPM at time 5 min. After the 5 min. spin, the Buffy coat is well visible. Twist the controller to adjust the height of buffy coat to the marked line. Twist the controller to adjust the height of buffy coat to the marked line. Prepare a 18 G ½ needle and a 3 CC syringe for PRP harvest. Open the silicone stopper using an alcohol soaked cotton. Extract 2.0 CC PRP while slowly swirling the needle in the area of the PRP into a 3 CC syringe. The same process is done for another 3 blood samples to have a total of 8 ml PRP to be used for both ovaries.

In the last step, the volume immediately above the erythrocyte layer will be collected. Calcium gluconate in conc. 1:9 will be used as an activator. After activation, in a period less than 2 min, approximately 4 ml of the PRP will be injected into each ovary by TVUS.

Monitoring & follow up:

The changes in the hormones at day 3 of the menstrual cycle: FSH, LH, estradiol, AMH will be closely monitored,after the application of the procedure in each group after 3 months. The investigators will also monitor the number of antral follicles & changes in the menstrual cycles & spontaneous ovulation before and after 3 months.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ahmed S Saad, phd, MD; Phone Number: 01221709989; Email: drahmedsaad@live.com
• Study Contact Backup: Name: Mohamed F Elsherbiny, phd.MD; Phone Number: 01094070920; Email: mohfarag171@gmail.com

Study Locations

• Egypt
  • Qalyubiya
    • Banhā, Qalyubiya, Egypt, 13512
      • Benha University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 42 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• PORs who meet at least two of the following three Bologna criteria
• AMH: 0.1-1 ng/ml.

Exclusion Criteria:

• ovarian insufficiency due to gonadal dysgenesis and -
• chromosomal abnormalities,
• immunoglobulin A deficiency,
• the use of anticoagulants,
• psychotropic medicaments,
• psychiatric disorders,
• carcinomas or
• a history of chronic pelvic pain.
• Women with present infection,
• haemoglobin lower than 11 g/L or
• platelets lower than 150 x 10ʒ/μL were excluded from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group A: PRP group; Preparation of PRP sample fro the patient own blood then the volume immediately above the erythrocyte layer was collected. Calcium gluconate in conc. 1:9 will be used as an activator. After activation, in a period less than 2 min, approximately 4 ml of the PRP will be injected into each ovary by TVUS.	Biological: platelet rich plasma; blood will be withdrawn from the patient then separation of the platelet rich layer and then injection in the ovary
PLACEBO_COMPARATOR: Group B: saline group; consists of 30 patients, who will receive 4 ml of a normal saline inj. 0.9% Nacl. then injected into each ovary by TVUS.	Drug: Normal saline; 0.9% normal saline will be injected in each ovary; Other Names: saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FSH hormonal changes	The changes in the hormones at day 3 of the menstrual cycle: FSH monitored	3rd day of the 3rd menstrual cycle after the procedure
vaginal ultrasound monitoring of the ovaries	monitor the number of antral follicles.	3rd day of the 3rd menstrual cycle after the procedure
clinical follow up	changes in the menstrual cycle by history taking & questionnaire	3rd day of the 3rd menstrual cycle after the procedure
LH hormonal changes	serum LH at day 3 of the menstrual cycle	3rd day of the 3rd menstrual cycle after the procedure
E2 hormonal changes	serum E2 at day 3 of the menstrual cycle	3rd day of the 3rd menstrual cycle after the procedure
AMH hormonal changes	serum AMH	3rd day of the 3rd menstrual cycle after the procedure

Collaborators and Investigators

• Sponsor: Ahmed Saad
• Collaborators: Hawaa Fertility Center
• Investigators: Study Director: Mohamed F Elsherbiny, phd.MD, Professor of OB & GYN

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 20, 2021
• Primary Completion (ANTICIPATED): December 1, 2021
• Study Completion (ANTICIPATED): December 30, 2021

Study Registration Dates

• First Submitted: May 19, 2021
• First Submitted That Met QC Criteria: June 5, 2021
• First Posted (ACTUAL): June 10, 2021

Study Record Updates

• Last Update Posted (ACTUAL): June 10, 2021
• Last Update Submitted That Met QC Criteria: June 5, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: PRP; poor responders; premature ovarian failure; poor ovarian reserve
• Additional Relevant MeSH Terms: Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Primary Ovarian Insufficiency; Menopause, Premature
• Other Study ID Numbers: Hawaa-9

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: the protocol the excel sheet
• IPD Sharing Time Frame: 6 months
• IPD Sharing Access Criteria: 6 months
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No