PRP Treatment – Ovarian Rejuvenation
OVARIAN PLATELET RICH PLASMA (PRP) TREATMENT
The success of fertility treatment hinges on the number and quality of oocytes. In women with diminished ovarian reserve, this poses an enormous challenge. Despite the development of modern IVF techniques that overcame male infertility factors, options for women with oocyte issues are limited to either doing repetitive treatments or resorting to donor oocytes. While poor numbers and quality of the oocytes is mostly associated with advancing age >37 years, it may also affect younger women. It is estimated that approximately 1% of women of reproductive age have severe decrease in ovarian reserve, contributing to intractable infertility.
Oocytes have a relatively long lifecycle starting from fetal stage and while the ovaries are endowed with millions of oocytes during the fetal stage, the numbers dwindle to 1 million at birth and to <300-400 thousand at puberty and only about 400-500 oocytes are destined to ovulate. Most follicles in the human ovary either undergo attrition or atresia or may remain dormant throughout the female life span and eventually become atretic. Previous studies have also encouraged a belief that the adult ovaries may in fact have stem cells that can develop into oocytes.
For over two decades, research is underway to activate the dormant primordial follicles as well as ‘oogonial stem cells’ with the hope of activating them to generate mature oocytes. One such approach could be the use of platelet rich plasma (PRP) with the purpose of delivering beneficial factors to promote the growth and development of the dormant follicles to generate oocytes with good quality. PRP research in fertility has led to it being offered in fertility clinics in areas of California such as San Francisco, Oakland and Modesto.
What is platelet rich plasma?
Platelet rich plasma (PRP) is a blood-derived product, characterized by high concentrations of growth factors and chemokines that are known to be beneficial in the healing process. PRP is produced by centrifuging a small quantity of the patient’s own blood and extracting the active, platelet-rich fraction. The platelet-rich fraction is introduced to the human body typically by injection. PRP is used for therapeutic purposes in different medical areas ranging from orthopedics to plastic surgery, for its putative ability to stimulate and facilitate cell proliferation and thereby tissue differentiation and regeneration.
In the context of reproductive medicine, PRP has been proposed to increase pregnancy rates after uterine flushing in women with recurrent implantation failure or thin endometrium. Intra-ovarian injection of PRP has also been proposed to activate dormant ovarian follicles pre-IVF-treatment in cases of idiopathic low ovarian reserve, premature ovarian insufficiency or ovarian depletion because of advanced maternal age. Recent studies highlight the benefits of ovarian PRP injections that increase AMH, and contributing to spontaneous as well as assisted reproduction. Several randomized placebo-controlled trials are underway; although considering its overall safety profile and minimal invasiveness, PRP injection treatments can become clinically available to select group of patients including those with diminished ovarian reserve or poor ovarian response (POR) or to those women with premature exhaustion of oocytes related to ovarian insufficiency and are interested in attempting conception using own oocytes.
Who are the candidates that will benefit?
Overall, most fertility clinics that offer PRP injections for ovarian ‘rejuvenation’ offer it for women with diminished ovarian reserve, who desire to achieve a pregnancy with the use of own rather than donor oocytes. These include women with age-factor infertility, previous unsuccessful IVF cycles with low oocyte numbers and poor oocyte/embryo quality or chromosomally abnormal embryos, and those with premature ovarian failure. In order to streamline the indications, they are presented below.
- Severely diminished ovarian reserve
- Serum AMH < 0.5 ng/ml at screening visit
- Antral follicular count (AFC) in both ovaries ≤ 5 (at screening visit and in the absence of OC or sex-steroid intake)
- Spontaneous, regular or occasionally irregular menstrual cycles
- Body mass index (BMI) ≥18 kg/m2 and ≤40 kg/m2
- One or both ovaries must be visible on transvaginal ultrasound and deemed accessible for needle puncture
- Consent to undergo the procedures, understanding the relatively newly introduced procedure with unproven benefit
- The patient and partner must agree to follow-up for ultrasound and blood work and/or fertility treatment outcome
Who would not be suitable?
- Menopause with Serum value of FSH ≥25 IU/l
- History of abnormal bleeding or platelet count < 100.000 platelets/µl at screening
- Presence of significant structural or numerical chromosomal abnormality in cytogenetic analysis (Exception of Turner Mosaics)
- Severe systemic disease that contraindicates pregnancy and/fertility treatment
- Presence of active or indolent pelvic infection (fever, tenderness, leukocytosis)
- Current or recent febrile illness (including influenza, Covid-19 etc.)
- Current or recent sexually transmitted infection (an STD screening will be performed at baseline)
- History of malignancy and systemic chemotherapy or pelvic radiation
- Severe endometriosis (stage III-IV) (Relative contraindication)
- Inaccessible or poorly accessible ovaries located outside the pelvic cavity
- Presence of untreated hydrosalpinx (will need to be addressed separately)
- Relevant endocrine disorders such as hypothalamic-pituitary disorder or thyroid dysfunction (except substituted Hashimoto’s thyroiditis or latent hypothyroidism)
- Untreated Clotting disorders: Congenital or acquired thrombophilia
- Contraindication for transvaginal ovarian puncture (such as previous major lower abdominal surgery and known severe pelvic adhesion)
- Uterine malformations or pathologies (such as sub mucosal fibroid(s), endometrial hyperplasia, endometrial fluid accumulation, or endometrial adhesions) (Relative contraindication)
- Inability to consent: e.g., mental disability or any other major health issue as deemed unfit for IV sedation/anesthesia or surgical procedures.
How is Ovarian PRP injection performed?
The ovarian PRP injection involves transvaginal ultrasound guided technique and can be performed in a procedure room under IV sedation or local anesthesia. The platelet enriched plasma can be prepared from freshly drawn autologous blood in clinic. The risks of ovarian PRP injection are minimal, especially when performed by experienced REI physician providers in fertility clinics.