Injections of Autologous PRP in Women With Primary Ovarian Insufficiency

Premature ovarian failure is a loss of normal function before age 40, leading to infertility
and hypoestrogenism. While POI is sometimes called premature menopause, it is not the same
thing as menopause. Women with POI may still have occasional irregular periods and may even
occasionally achieve a pregnancy. Symptoms of POI include: irregular menses or amenorrhea,
infertility, hypoestrogenic symptoms and decreased libido. POI may be caused by Chromosomal
defects such as mosaic Turner's syndrome, exposure to toxins (chemotherapy or radiation),
autoimmunity, genetic factors (FMR1) and other unknown factors.

Autologous Platelet Rich Plasma (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. In this study A-PRP will be
prepared using Regen Lab PRP Kit which is approved by US-FDA for preparation of PRP.

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 only adult women with a diagnosis of POI. Consenting participants
will receive injections of autologous Platelet RIch Plasma (A-PRP) in one randomly selected
ovary under ultrasound guidance performed after induction of IV sedation. Randomization will
determine whether the right or left ovary will be treated. The result of randomization will
not be recorded in the participants clinical chart, but will be maintained in the research
database with blinding to all clinical participants. The physician performing the A-PRP
administration will not perform post procedure follow-up of those patients. In case of a
complication, possibly related to treatment, the case will be unblinded.

The study will be powered to detect a 20% response in the treated ovary (every patient's 2nd
ovary will serve as control). This will require 68 ovaries and 34 patients. The study, thus,
does not involve randomization of patients because each patient's second ovary functions as
control ovary, although which ovary will receive treatment in a given patient will be
determined by computer randomization.

Inclusion Criteria:

- Signed and dated informed consent

- Women 40 years of age and younger with documented primary ovarian insufficiency.

- Normal Karyotype

- FSH > 30

- AMH not detectable

- No evidence of follicles > 4mm

- Must have two ovaries of approximately equal volume.

- No Aspirin or any NSAID (e.g. Motrin) for approximately one week before treatment

- Willingness to undergo further fertility treatment, including IVF if there is evidence
of response

Exclusion Criteria:

- Premature ovarian failure due to a genetic origin, such as Turner's Syndrome or
chromosomal abnormality

- Marked thrombocytopenia

- Blood diseases

- Hypofibrinogenemia

- Hemodynamic instability

- Anticoagulant or antiaggregant treatment

- Oncological diseases (specially, skeletal system and blood)

- Sepsis

- Acute and chronic infectious diseases

- Autoimmune diseases, for example, lupus erythematosus, etc.

- Active substance abuse or dependence

- Major Mental health disorder