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PRP (uterine & ovarian rejuvenation) – indications and prospects

Dr Estefanía Rodríguez
Medical Co-Director, Head of Research Unit & Gynaecologist, specialised in Assisted Reproduction

Category:
Low Ovarian Reserve, PRP & Ovarian Rejuvenation

ovarian-uterine-rejuvenation-indications-prospects
From this video you will find out:
  • What is platelet-rich plasma (PRP) and what are PRP injections?
  • What are the endometrial indications for PRP treatment?
  • What are the ovarian indications for PRP treatment?
  • How is the procedure performed?
  • What are the success rates after the use of PRP?

PRP (uterine & ovarian rejuvenation) – indications and prospects

During this session, Dr Estefanía Rodríguez, Medical Co-Director, Head of the Research Unit & Gynaecologist, specialised in Assisted Reproduction discussed PRP treatment, the aim of ovarian and uterine rejuvenation and explained which group of patients it is recommended.

Dr Estefanía Rodríguez began with a brief overview of the concept of PRP and how it works. Then, also explored the effects of PRP on tissues, its application, and its objectives. Next, she delved into the candidacy for PRP therapy and the preparation of this treatment. Lastly, the event was focused on ovarian PRP procedures and Dr Rodríguez touched on the recommended strategy of embryo banking, followed by a discussion on endometrial PRP procedures and treatments.

Understanding PRP

PRP is an autologous plasma enriched with growth factors extracted from the patient’s peripheral blood platelets. It was first used in 1987 during open-heart surgery and has since found extensive applications in various medical procedures, including traumatology, surgery, and now, gynaecology. PRP can be used in both the uterus and ovaries to achieve rejuvenation.

The Effects of PRP

PRP promotes angiogenesis and vascularization in tissues. It stimulates cell migration and increases cell proliferation while reducing inflammation. Additionally, it stimulates the autocrine and paracrine secretion of growth factors. Numerous studies have demonstrated that PRP can enhance the proliferation and motility of endometrial fibroblasts, leading to an increase in endometrial thickness. This improvement in endometrial function can enhance implantation rates, ultimately aiding in achieving pregnancy.

Indications and Objectives

The use of PRP in the endometrium and ovary serves different objectives. In the endometrium, PRP can improve endometrial thickness, promote growth factor expression by endometrial cells, and enhance the function of the endometrium. This can be beneficial in cases of adhesions, atrophic endometrium, chronic endometriosis, implantation failure, and repeated miscarriages.

In the ovary, PRP can improve angiogenesis and vascularization, enhance follicular functionality, stimulate cell migration, and promote the autocrine and paracrine secretion of growth factors. This can be particularly useful in patients with low ovarian reserve, premature ovarian failure, perimenopausal issues, and menopausal symptoms. By reactivating follicular function, PRP can improve hormone production and overall quality of life for patients.

Contraindications and Evaluation

Before implementing PRP treatment, it is crucial to evaluate patients for permanent and temporary contraindications. Permanent contraindications include severe health diseases, a history of hepatitis B or C, active infections, and severe uterine abnormalities such as fibroids or an oncological history. Temporary contraindications may involve bacterial infections, blood disorders, autoimmune disorders, or generative diseases. Each patient’s case needs to be evaluated individually to determine the suitability of PRP therapy.

PRP Protocol for Ovarian Stimulation

When considering patients with conditions such as fibroids or a history of oncological or autoimmune diseases, careful evaluation is necessary to determine the suitability of PRP treatment. The PRP protocol involves stimulating the patient multiple times to introduce PRP into the ovaries. The menstrual cycle is typically initiated with hormone administration, followed by stimulation for the extraction of liquid from the follicles. Subsequently, PRP is introduced into the ovary. PRP preparation is performed in the clinic using a blood sample obtained from the patient. The centrifugation process separates the plasma and platelets from the blood, ensuring a safe treatment with minimal side effects. After PRP injection into the ovary, a one-month waiting period ensues, followed by the evaluation of ovarian markers through hormonal testing and ultrasound examinations. If positive changes are observed, indicating improved follicular function, a second stimulation can be initiated. However, if the results are not favourable, a wait of another month is recommended before reassessing the ovarian markers and repeating the ultrasound.

Accumulation of Stimulation Cycles and Embryos

In cases where multiple stimulation cycles are required, the embryos can be accumulated for better outcomes. The protocol involves performing oocyte retrieval on the day of follicle collection and then storing the embryos until the fifth day of development, as this provides higher chances of good-quality embryos. The ultrasound image shows the collection of liquid through a vaginal ultrasound. The extracted liquid is used to obtain the oocytes, and PRP is introduced into the ovaries. Although it is preferable to stimulate the ovaries before introducing PRP, in some cases, where no follicular activation is present, the liquid can still be introduced without prior stimulation.

Endometrial Preparation and PRP Application

When using PRP for endometrial improvement in patients with already existing embryos, the uterus is prepared for transfer. PRP is prepared using a blood sample and stored in the clinic. Once the uterus is prepared, PRP is introduced directly into the uterus or behind the endometrium using a hysteroscopy. The specific application method depends on the individual case. This procedure is usually performed three times, although the frequency may vary depending on the patient’s response. Multiple studies and protocols exist regarding PRP introduction, making it essential to continue gathering information and refining the treatment approach. Proper patient selection is crucial, and the current recommendation is to undergo PRP treatment three times, but adjustments can be made based on the ultrasound findings and endometrial thickness.

Embryo Banking Strategy

To optimize outcomes in women with low ovarian reserve, an embryo banking strategy is recommended. This strategy involves stimulating the ovaries two to four times over a period of two to four months. The goal is to collect between four and eight high-quality embryos. By studying the genetics of these embryos, the chances of transferring a chromosomally normal embryo with a high implantation rate can be significantly increased.

Conclusion

The use of PRP in fertility treatments holds promising potential. The team at IVF Life San Sebastián and Donostia specializes in utilizing PRP in various protocols to improve ovarian and endometrial function. Ongoing research and data collection are crucial for refining these protocols and providing better outcomes for patients.

- Questions and Answers

Does PRP work with women in perimenopause or menopause? Are there any studies about introducing this kind of treatment inside the ovary with menopause or perimenopause?

There are some studies about introducing this kind of treatment inside the ovary during menopause or perimenopause. The objective of PRP is to activate the dormant eggs to improve the function of the ovaries.

When is the best time to do endometrial PRP for IVF, and when is the best time to do it for IUI?

For IVF, we have to wait a little bit before the transfer, just before the embryo is implanted inside the endometrium. So, we try to do it a maximum of two days before the endometrial transfer. We usually start with the installation and try to do three installations, depending on the cycle. The last one is done two or three days before the transfer to improve the endometrial function. As for IUI, I don’t have experience with PRP in intrauterine insemination. However, I believe we have to bear in mind the same timing as with embryo transfer. So, if we do this procedure, it should be done just before the embryo implantation, which is typically a few days around the insemination.

Did I understand correctly? Do women in menopause still have eggs in a dormant form? Meaning, could they get pregnant with their own eggs?

Yes, women in menopause still have eggs in a dormant form. It is not impossible for them to get pregnant with their own eggs. However, the quality of the eggs is the main concern. While it is possible for a woman in her younger years to have good-quality eggs, as the woman ages, the quality and genetics of the eggs may not be good for producing embryos. It depends on the age of the woman and her specific circumstances.

Can you clarify the term “premenopausal”?

Premenopausal is the term used when there are problems with the menstrual cycles, a decrease in the number of eggs, and the body’s inability to prepare for ovulation. The onset of menopause typically occurs around 50 years of age, but it can vary. Some women may reach menopause at 60 years, while others may experience it as early as 25 years. It depends on the individual and their specific menstrual cycles rather than their age.

Is there a deadline when you can’t do PRP post-menopause? Would the eggs be okay?

It depends on the age. With women over 43 years old, it becomes quite difficult to obtain good quality eggs genetically. If there aren’t many eggs available, it becomes like a lottery to find a good quality egg. The chances of success are quite difficult for menopausal women who can only produce one egg.

My uterine lining is 6 millimeters. To improve the lining, I’m thinking of doing PRP uterine rejuvenation. What are the risks? Is it okay to do it as PRP or treat the thin uterine lining when doing IVF?

If the uterine lining is less than 6.5 millimetres, it is possible to treat it with PRP, which is a very safe treatment. We usually introduce the liquid inside the uterus before the transfer. In your case, since you’re already undergoing PRP for ovarian rejuvenation, doing both treatments at the same time is the best approach.

How long after PRP ovarian rejuvenation can one go for IVF?

We typically check ovarian markers one to two months after the injection to assess if there has been an improvement. There are no strict limits on the timing of the standard stimulation. We aim to start at the best moment, so waiting for too long may not be necessary, as we believe the improvement can’t increase significantly after a certain point.

Do you recommend PRP for the improvement of endometrial thickness on specific days of the cycle before and after embryo transfer?

We recommend doing PRP just before the transfer, ideally two to three days prior. This timing aims to avoid interfering with the endometrium during the window of implantation. Ultrasound monitoring can help determine if the thickness is improving and if the treatment is yielding positive results.

How do you activate the PRP procedure?

The PRP procedure is activated before the injection. It is done by a technical person in the clinic, depending on whether we have kept the treatment or if we are proficient with the centrifugation procedure. They prepare the PRP for us, and then we inject it.

I had 4 or 5 double transfers with no implantation at all. I was on a full immune protocol. We now suspect problems with the endometrium. Hysteroscopy came back clear, and the lining has always been above 10 millimeters. Can uterine PRP be an option for me?

Nowadays, we consider using PRP in cases like yours, where there are problems with implantation and the cause is uncertain. We can introduce this treatment in such cases with these problems.

Can this procedure help in the case of presumably low-quality oocytes due to a past history of endometrial cysts in the ovaries? Also, the ovarian reserve is low, and it presents difficulties in collecting mature oocytes, even when I did it for the first time at 36. Now I am 42. What would you say in this case?

We can’t improve the quality of oocytes (X) if the problem lies with their quality. It is important to consider the quality of embryos and also evaluate the sperm in such cases. However, with more than 38 years of age, genetic factors become crucial. We can try to retrieve a greater quantity of oocytes to improve the probability of obtaining good embryos, but not the quality.

Can we improve the quality of oocytes?

PRP is not the objective of improving oocyte quality. Some studies suggest that we may be able to retrieve more mature oocytes and thereby improve the proportion of successful fertilization, but not the overall quality or genetic factors.

Is it better to do PRP for the uterine lining or wait during IVF?

I think it varies because in some cases, if we wait a little longer and increase the days with estrogen, we may achieve a good lining thickness. However, in other cases where it’s challenging to achieve the desired thickness, PRP can be used to improve the lining.

In the case of low-quality embryos, I am 42 years old and have had three embryo transfers with the long protocol and one with the short protocol. The morphological quality was assessed as good in one instance, and a biochemical pregnancy occurred. Is there anything else you can advise?

In such cases, we can consider using PRP for the endometrium, especially when there have been pregnancy losses. However, it’s important to evaluate other factors and rule out any immunological problems. There are several considerations to take into account. We can try to improve the endometrial implantation rate with PRP. If you need to proceed with another stimulation program and have a low ovarian reserve with few embryos, you can also consider using PRP.
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Authors
Dr Estefanía Rodríguez

Dr Estefanía Rodríguez

Dr Estefanía Rodríguez, Medical Co-Director, Head of Research Unit & Gynaecologist, specialised in Assisted Reproduction at IVF-Life Donostia. Dr Estefanía Rodríguez is a renowned gynaecologist with more than 10 years of experience in the field of fertility. She graduated in Medicine in 2007 from the University of Navarra and specialised in Gynaecology and Obstetrics at the Hospital Universitario Donostia. Since completing her residency in 2012, Dr Rodríguez has continued her training, complementing her knowledge in assisted reproduction with knowledge in genetics with the Master's Degree in Genetics at the University of Granada and other training courses. Part of the team that opened IVF-Life Donostia in 2015, today she is Co-Medical Director of the clinic and is very involved in the research and development of new processes and treatments to improve our patient's satisfaction & results.
Event Moderator
Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.