The demand for fertility treatment is increasing and therefore those responsible for the treatment and care of patients need to ensure that the services they provide are the best and most effective available. This article based on a webinar led by Dr Ahmet Ozyigit from North Cyprus IVF
outlines options for women over 40 including ovarian PRP (Platelet Rich Plasma) treatment.
Reproductive medicine is always looking for ways to improve pregnancy rates as more people turn to assisted reproduction to have a child. Demand for fertility treatments is rising due to a number of factors including career orientation, the increased age of couples getting married and a greater awareness of the options available for those having difficulty in conceiving or maintaining a pregnancy. However, a significant number of people are also delaying the decision to try for children and this can be both problematic for the patient and the treatment provider.
Age is not the sole factor which determines fertility problems. One factor which can have devastating consequences is so-called Premature Ovarian Failure which can affect women in twenties or thirties. These women have very low AMH (Anti-Mullerian Hormone)
levels and very high FSH (follicle-stimulating hormone) levels as well as practically no antral follicles. Ovarian reserve, as well as ovarian function and activity declines naturally with age but premature ovarian failure can mean that women need some assistance in getting pregnant very much earlier in life. Fortunately, there are a number of treatment options available for women who experience premature ovarian failure including cytoplasmic IVF treatment, embryo banking with or without PGS, IVF using donor eggs (or double donation) and ovarian PRP treatment.
As Dr Ahmet Ozyigit explains, the latter has a lot to offer.
What is PRP?
Dr. Ozyigit starts the webinar by introducing PRP. Platelets (also known as thrombocytes) are a part of our blood involved in wound healing and tissue regeneration. Platelet-rich plasma (PRP) is the blood product where the blood sample of an individual is subjected to specific laboratory techniques and equipment to separate the platelet-rich part from the part that is platelet poor.
In terms of platelet function, we know they have a lot of growth factors and proteins in them which play a specific role. All of them work in a collective manner in key parts of tissue regeneration such as cell growth, proliferation and differentiation in addition to improved oxygen delivery and circulation. PRP helps with growth and proliferation but since this is a concentrated platelet-rich plasma, it is also is equipped with certain elements (growth factors) that reduce the inflammatory response.
How does PRP work?
The idea of using platelet rich plasma to rejuvenate is not a far-fetched one. This is something we all witness in our daily life. It happens when we cut or knock ourselves – an initial bruise becomes inflamed with the same oedema. Later on, a yellowish layer is formed that consists of white blood cells, blood clots, platelets and growth factors. All of this helps prevent bleeding and infection and also helps to regenerate connective tissue and repair the damaged area. Dr Ozyigit explains that in assisted reproductive medicine the part of the process which doesn’t cause inflammation is isolated. It focuses on introducing dormant stem cells into ovaries to activate them in order that they go through follicular genesis or oogenesis which means oocyte development.
PRP applications have been shown to have proliferative effects as well as anti-inflammatory effects while working on tissue repair. Currently, PRP is being used in a number of fields and these include anti-ageing, hair growth, dental applications, soft tissue regeneration and endometrial and ovarian rejuvenation.
According to Dr Ozyigit, PRP application has also been associated with increased progesterone receptor activity. Progesterone receptors are the main actors that help maintain a thick and healthy endometrial lining which helps with embryo implantation.
What can you expect from PRP?
Dr Ozyigit observes that up until recently, it was widely believed that women were born with a limited ovarian reserve which depleted in a non-reversible way. However, recent evidence points to the existence of dormant stem cells in the ovaries. Although it is not sure why they exist, they have been shown to have the potential for activation. This gave the idea of possible ovarian rejuvenation. If these stem cells could be activated to produce new oocytes, menopause could then be potentially stalled allowing a greater opportunity for a woman to achieve a pregnancy.
Based on what is known about platelets and the growth factors involved, Dr Ozyigit explains what to expect from the PRP application. It is increased vascularisation and improved blood supply. Additionally, growth factors in platelets can stimulate the activation of ovarian stem cells which have the potential to mature into oocytes.
The stem cells in the ovary are located in the cortex. For the purpose of PRP treatment, it is very important to know exactly where these stem cells are to target the treatment directly towards them.
Main considerations in PRP treatment
According to Dr Ozyigit, the first thing to consider is the method itself. PRP isolation is, for example, one of the main factors that determine success in ovarian PRP treatment. It involves a number of considerations, such as anticoagulation of the blood sample to avoid premature activation of the platelets, appropriate isolation protocols to obtain a highly isolated sample and last but not least – correct timing of activation.
Location in PRP treatment is equally important. As mentioned before, stem cells are found in the ovarian cortex. Therefore, any treatment which involves activation or/and differentiation of these cells, needs to involve the cortex.
When injecting the PRP, oogenesis is the most important consideration of all. If one doesn’t know how eggs grow, how they develop and go into ovulation, then the whole procedure is not going to be successful. In terms of oocyte development, timing is everything. Dr Ozyigit reminds us that the timeline to grow oocytes from scratch is four months.
One more thing which is very important is supportive treatment. When initiating the growth of cells, we need to support them at the cellular level. Dr Ozyigit says they use a human growth hormone which helps to increase the number of the preantral follicles from the primordial ones. They also use aromatase inhibitors to suppress the estrogen and lock the negative feedback mechanism between the ovaries and the brain. At a later stage, they also include gonadotropins to produce more eggs than in a natural cycle.
Success rates and PRP
Dr Ozyigit admits that in terms of success rates, it is too soon to tell if the method has the potential to be ground breaking. It usually works for women with premature ovarian failure who still have primordial follicles. However, it has low success rates in women who are over 50 years of age and after menopause. According to Dr Ozyigit, there is a considerable difference between the first IVF cycle before the PRP and the second IVF cycle after the PRP. The difference is not seen just in terms of the number of collected eggs but also in the AMH measurements as well as the number of antral follicles seen in the ultrasound scan. The antral follicle count before the PRP and after the PRP varies greatly. However, this still does not guarantee a successful pregnancy. Dr Ozyigit concludes, PRP treatment is still a work in progress and there are a lot of modifications and improvements which will need to be introduced and made in the future.
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