Plasma Rich in Growth Factors (PRGF-Endoret®) for Endometrium

Plasma rich in growth factors (PRGF) is a liquid prepared from a sample of the patient’s own blood.

This PRGF is prepared according to the PRGF-Endoret® closed-technique system developed by BTI Biotechnology, and is a biomedical technology aimed at stimulating tissue regeneration through the application of growth factors and other proteins present in blood plasma. The application of Endoret® Technology (PRGF®) is a medicinal product for human use.

Platelet growth factors are a set of proteins that are involved in cell communication by modifying biological responses. These types of therapies have been widely used in many fields of medicine and dentistry and are based on Regenerative Medicine, and they aim to achieve tissue regeneration by mimicking the body’s own regeneration processes.

Suitability of the treatment in relation to its application in the endometrium

Refractory endometrium is a condition in which the endometrium, the innermost layer of the uterus where the embryo implants, does not grow properly despite appropriate hormonal treatment. If the endometrium does not grow properly, communication between the endometrium and the pre-embryo is not established, resulting in the pre-embryo not growing properly. Refractory endometrium is diagnosed by ultrasound measurement of the endometrium. It should be at least 6 to 7 mm after 10 days of hormone replacement therapy with oestrogen. Scientific studies have shown that PRGF promotes endometrial growth and is effective in repairing a damaged endometrium and improving pregnancy outcomes, hence its recommendation.

Treatment alternatives

Refractory endometrium is a difficult pathology to manage and with few effective alternatives currently described (vitamin E, vaginal sildenafil citrate and pentoxifylline), none of which have sufficient scientific evidence to be considered a form of treatment of choice.

Procedure

• After 10 days of hormone replacement therapy, if the endometrium does not grow adequately, a blood sample is taken from the patient.
• This blood sample will be prepared in a Endoret® closed system.
• There are two modes of administration:
  • As an outpatient with endometrial instillation
  • It is separated into three parts.
  • One for fresh instillation and two others that are frozen for subsequent instillation into the endometrium (at 48 and 96 hours after the fresh instillation).
  • Endometrial instillation is a simple and painless procedure performed at the doctor’s office or in the embryo transfer room through the vagina.
  • A vaginal speculum is inserted and the cervix is cannulated with an embryo transfer cannula.
• With hysteroscopy and subendometrial injections:
  • Single preparation
  • The endometrium is injected by depositing PRGF at the subendometrial level with small injections a few millimetres deep. This procedure is always accompanied by a diagnostic hysteroscopy that allows us to see the exact site of the injection and its depth, for which the corresponding informed consent for diagnostic hysteroscopy must be signed. The choice of mode of endometrial administration of PRGF will depend on a shared medical decision between you and your doctor.  The idea with subendometrial injection is to inject the factors at the level of the stem or progenitor cells and have more influence on cell growth and vascularisation. This approach has demonstrated histological changes related to endometrial regeneration.
• After the procedure the patient can return to normal life.

Contraindications

There are certain conditions in which it is not advisable to perform endometrial instillation due to a possible risk of encouraging or worsening other pathologies:

• Current or previous pelvic inflammatory disease.
• Infection.
• Active genital infection.
• Presence of any pathology that in the medical specialist’s opinion constitutes a risk or contraindication for the patient.
• Patients with reports from specialists advising against pregnancy.
• Positive serologies for the tests performed according to standard clinical practice in the IVIRMA group in Spain (HBsAg, HBcAb, HCV, HIV and syphilis).

Risks

This instillation is autologous, i.e., it comes from the patient’s own blood, so the patient is not exposed to foreign cellular material that could cause a reaction in her body.

In addition, the system used is closed, so we do not expect any contamination.

No risks or side effects are described in the literature with this procedure.

Although there is a theoretical risk of infection from introducing material into the endometrial cavity from the outside and through the vagina, this is the same risk that could occur in an intrauterine insemination or embryo transfer, which is practically zero in the thousands of these procedures performed, and prophylactic antibiotics are administered to prevent infection.

Although no long-term complications have been reported, it is possible that due to the pathogenesis of endometriosis and adenomyosis, microtrauma at the subendometrial level could favour the development of these pathologies.