Will Autologous Platelet Rich Plasma Able To Restore Ovarian Function?

Study Overview
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Brief Summary
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A-PRP (Autologous Platelet Rich Plasma) is becoming widely used in a variety of medical procedures seeking tissue remodeling and/or healing as an intervention. To date, applications in orthopedics, wound healing, dermatology and plastic surgery have gained general acceptance, primarily as the role of platelets and their activation in tissue repair and recovery has become better understood at a cellular and molecular level. This study will involve adult women with a diagnosis of Premature ovarian insufficiency (POI) willing to perform an IVF/ICSI treatment.

Detailed Description
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POI is a loss of normal function before age 40, leading to infertility and hypergonadotropic hypoestrogenism. Currently, no optimal regimen exists to ameliorate ovarian function. The options to conceive genetically related offspring, are limited. Typically, affected patients end up with egg donation or adoption as an alternative . A-PRP is plasma with a concentration of platelets above the blood baseline. A-PRP is developed from autologous blood. Within A-PRP, the concentration of platelets delivers an increased number of growth factors. PRP is becoming widely used in a variety of medical procedures seeking tissue remodeling and/or healing as an intervention. To date, applications in orthopedics, wound healing, dermatology and plastic surgery have gained general acceptance, primarily as the role of platelets and their activation in tissue repair and recovery has become better understood at a cellular and molecular level. This knowledge base provides a foundation for the present study because of the ready availability of FDA-approved kits for autologous PRP preparations and the recognition that the aging ovary acquires tissue pathologies in the form of wound healing and fibrosis as a result of repeat ovulations over the reproductive lifespan of women. Since PRP is an autologous blood product and is widely used via injection into various organs and tissues, safety concerns are minimal. This study will involve adult women with a diagnosis of Premature ovarian insufficiency (POI) willing to perform an IVF/ICSI treatment. A-PRP will be prepared using Eclipse PRP Kit which is approved by US FDA for preparation of PRP. Consenting participants will receive injections of autologous Platelet Rich Plasma (A-PRP) in one randomly selected ovary under ultrasound guidance performed under IV sedation. As it is suggested that only mechanical stimulation by biopsy/scratch could be a potentially effective method for follicle activation, the other ovary will be injected with the same amount of Saline Solution (SS) as control, to replicate the same mechanical effect. Randomization will determine whether the right or left ovary will be treated. Follow up of the participants will be performed with transvaginal ultrasound and hormonal tests including AMH, FSH, LH, estradiol and progesterone, every 10 days for the next 3 months after the injection. If ovarian activity is detected, the participant will undergo an IVF treatment.

Official Title
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Is Autologous Platelet Rich Plasma Able To Restore Ovarian Function? A Prospective Randomized Control Trial.

Conditions
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IVF, Infertility, Premature Ovarian Failure, Anti-Mullerian Hormone Deficiency

Intervention / Treatment
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* Other: autologous platelet rich plasma
* Other: saline solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent Women 40 years of age and younger with documented primary ovarian insufficiency (12). Normal Karyotype BMI </= 35 kg/m2 Oligo/amenorrhea for at least 4 months FSH > 25 IU/mL AMH </= 0,1 ng/ml No evidence of follicles > 4mm Must have two ovaries of approximately equal volume. Willingness to undergo further fertility treatment, including IVF if there is evidence of response A transvaginal scan including Doppler for arteria ovarica will be performed previously to the surgical procedure. Exclusion Criteria: Premature ovarian failure due to a genetic origin, such as Turner's Syndrome or chromosomal abnormality. Oncological diseases (specially, skeletal system and blood). Autoimmune diseases, for example, lupus erythematosus, etc. Previous treatments including radiotherapy or chemotherapy. Other conditions not suitable for surgical procedures and/or anesthesia. Anticoagulant or antiaggregant treatment. Acute and chronic infectious diseases. Active substance abuse or dependence. Major Mental health disorder.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Intervention<br>The cortex of selected ovary will be injected with 1 mL of autologous platelet rich plasma. Up to ten different sites will be injected under ultrasound guidance. In the surgical report, the surgeon will state how many punctures have been done. | Other: autologous platelet rich plasma<br>* The cortex of selected ovary will be injected with 1 mL of autologous platelet rich plasma. Up to ten different sites will be injected under ultrasound guidance. In the surgical report, the surgeon will state how many punctures have been done.<br>|
| Control<br>The cortex of contralateral ovary will be injected with 1 mL of saline solution (SS). Up to ten different sites will be injected under ultrasound guidance. In the surgical report, the surgeon will state how many punctures have been done. | Other: saline solution<br>* The cortex of contralateral ovary will be injected with 1 mL of saline solution (SS). Up to ten different sites will be injected under ultrasound guidance. In the surgical report, the surgeon will state how many punctures have been done.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Appearance of new ovarian follicles (number of follicles growing) with evidence of estradiol production. | Evaluate the difference of number of follicles growing, means values will be calculated at the two points time (baseline and 12 weeks). Means differences will be verified using the t test analysis (after confirming the normal distribution of the data by means of Kolmogorov-Smirnoff tests. If normal distribution is not confirmed a non-parametric anova test will be used. This rule will be applied to all analysis | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase in serum AMH above the baseline level | Evaluate the difference of AMH levels between time, means values will be calculated at the two points time (baseline and 12 weeks). Means differences will be verified using the t test analysis. | 12 weeks | 
| Increase in AFC above the baseline level in 12 weeks | Evaluate the difference of AFC levels between groups, means values will be calculated at the two points time (baseline and 12 weeks). Means differences will be verified using the t test analysis | 12 weeks | 
| Total number of retrieved oocytes in an IVF cycle. | Number of retrieved oocytes will be calculated in the IVF cycle: total and per groups (per ovary) | 1 day | 
| Pregnancy rates | Pregnancy rates: Biochemical pregnancy rate: Percentage of bHCG above 15 IU/ml per embryo transfer performed. Clinical pregnancy rate: percentage of pregnancies with fetal heart rate positive per embryo transfer performed. Miscarriage rate: percentage of miscarriages per embryo transfer | 40 weeks |