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Ovarian rejuvenation and PRP – process and outcomes explained

Natalia Szlarb, MD, PhD
Gynaecologist & Fertility Specialist, UR Vistahermosa

Category:
Advanced Maternal Age, Low Ovarian Reserve, PRP & Ovarian Rejuvenation

ovarian-rejuventation-prp-process-explained
From this video you will find out:
  • What is PRP?
  • How is PRP used for IVF and other fertility Treatments?
  • Who should consider PRP fertility treatment & when should it be indicated?
  • Are there any side effects of PRP treatment?
  • What are its main advantages?

Ovarian rejuvenation and PRP – process and outcomes explained

During this session, Dr Natalia Szlarb, Gynaecologist & Fertility Specialist at UR Vistahermosa discussed ovarian rejuvenation treatment options, its main indications, how it works, and outcomes.

We have to be aware that PRP has been used in medicine for quite a while. Whole blood is rich in red blood cells, white blood cells, and platelets. When centrifuged, the cells settle at the bottom of the tube, while the serum is usually in the upper area. By adding special factors to this blood, platelets release beneficial nutrients such as cell growth factors, cytokines, and vascular growth factors. PRP has been used in regenerative medicine, especially in orthopaedics for knee injuries, which are common in cold countries like Germany where skiing is popular.

The use of PRP in mesotherapy for advanced-aged women has shown improvements in skin quality. Collagen in the skin’s connective tissue becomes disorganized with age, but after PRP injections, collagen regains its organized structure, enhancing skin quality. Gynaecology has also adopted PRP in 3 specific indications: premature ovarian failure, low ovarian reserve patients, and endometrial regeneration.

PRP in reproductive medicine

The platelets in PRP, after a special centrifuge preparation, release nutrients that positively impact the uterus lining, especially in cases of thin endometrium, poor growth, implantation failure, premature ovarian failure, or low ovarian reserve due to age. Platelets release growth factors, insulin growth factors, tissue growth factors, and vascular factors, improving endometrial and ovarian responses.

For patients with ovarian failure, PRP injections have shown an increase in the number of undrafted follicles, improved cortex volume, and enhanced angiogenesis. These improvements allow hormones injected in subsequent cycles to penetrate the ovary better, leading to a better ovarian response. In cases of Asherman syndrome, PRP cannot be considered a treatment. However, for less severe cases where parts of the endometrium are still viable, PRP can be used to reduce pro-inflammatory factors, improve endometrial thickness, and target the remaining viable areas during embryo transfer.

It’s important to note that PRP is not used daily for endometrial growth, unlike estrogen. It is reserved for selected severe cases, such as Asherman syndrome, ovarian regeneration in premature ovarian failure, and patients with advanced maternal age and low ovarian reserve.
Assessing ovarian reserve is crucial before undergoing an IVF cycle.
Low ovarian reserve and premature ovarian failure are two separate conditions. Menopause occurs naturally between 45 and 55 years old when women stop producing eggs. Premature ovarian failure is the condition where women stop producing eggs before the age of 45. PRP can be used in cases of premature ovarian failure if the AMH levels are dropping.

It is important to plan pregnancies earlier due to the postponement of maternity. Freezing eggs at a younger age or considering PRP treatment in advanced maternal age with a low ovarian reserve can be beneficial. If PRP doesn’t work, egg donation is another option.

PRP may not be suitable for patients who have undergone strong chemotherapy or have AMH levels of 0.2 or 0.0. When your AMH is more than 2 nanograms per millilitre, you have a good ovarian reserve. When your AMH is between 1 and 2, you have diminished ovarian reserve. When your AMH is under 1 nanogram per millilitre, you have a low ovarian reserve. In patients with low ovarian reserve, the aim is to increase the number of untraveled follicles through ovarian rejuvenation. For them, one additional egg or follicle is a blessing, especially when they travel to Spain from another part of the world.

There are two separate entities: low ovarian reserve and premature ovarian failure. Premature ovarian failure occurs when women experience the cessation of egg production in their ovaries before the age of 45. This condition is also known as premature menopause. These patients, develop problems with infertility at an early age due to the lack of egg production. In cases of low ovarian reserve or premature ovarian failure, we offer PRP treatment. However, it’s important to note that we cannot expect miracles from PRP. For example, after strong chemotherapy, such as for breast cancer or leukaemia, PRP is not the best solution. Before chemotherapy, it is advisable to freeze eggs for future use after the oncological disease is under control. If we naturally observe a drop in AMH indicating premature ovarian failure, this is the moment when we can consider using PRP.

In Spain, there is an interesting trend in maternal age and pregnancy planning. In the northern part of Spain, maternal age is around 32–31 years old, while in the southern part, there are younger mothers. In big cities in the north, where people are more educated, and women are more independent, they tend to postpone maternity and focus on growing their careers. In such cases, it is recommended to freeze eggs before the age of 35 or consider PRP treatment if advanced maternal age with low ovarian reserve is a concern. If PRP treatment works, it can be amazing, but if it doesn’t, the only remaining option is egg donation. It is crucial not to wait too long and take action before the age of 35.

I have seen cases where patients experience recurrent implantation failure after undergoing DNC (dilation and curettage) due to restrictive legislation in countries like Germany. In such cases, the tissue of the embryo, which likely has poor genetic quality, is removed during DNC. However, frequent DNCs can lead to problems with the thickness of the uterine lining necessary for embryo transfer. PRP has shown improvement in uterine lining thickness due to its rich nutritive factors from platelets.

There have been cases where it took months to grow a good lining, but with PRP, improvement was observed. It is worth mentioning that after the delivery of the first child, trying for a second child is often less difficult as the body has been trained, and the growth of the uterine lining is smoother.

Implantation failure is another challenge in reproductive medicine. Even after transferring the best quality embryos from egg donors or patients’ eggs, sometimes it doesn’t work. Various immunological protocols are implemented to reduce the activity of NK cells, but if everything has been tried and it’s still not working, flushing the lining with PRP can be considered to improve implantation.

We always examine patients and perform a uterus scan and ovarian scan. We review the protocols used in your previous treatments in other clinics to find a solution and identify areas for improvement during your treatment with us. We also evaluate hormonal results such as AMH (anti-Müllerian hormone) and TSH (thyroid-stimulating hormone) to provide our honest opinion. It’s important to note that even with our honest opinion, success cannot be guaranteed.

Dosage Adjustment and Endometrial Regeneration

The dosage of hormonal stimulation, such as FSH and LH, is adjusted based on the patient’s AMH level. Lower AMH levels require a lower dose of medication to avoid overstimulation of the ovaries. In endometrial regeneration, we use vasodilators like Viagra (sildenafil) and adrenaline, but please note that this is not commercial Viagra and should not be taken orally. The vasodilators are taken vaginally in combination with high doses of estrogen and PRP flushing to improve the thickness of the uterine lining. However, it often takes months to see improvements in the lining thickness.

PRP Preparation Process

For endometrial rejuvenation, two syringes of blood (10 millilitres each) are needed, and from this, plasma is prepared to contain growth factors and platelets. The platelets are activated with calcium fluoride to release cytokines and growth factors. For ovarian rejuvenation, more blood is required, and four syringes of blood (10 millilitres each) are collected. Three millilitres of PRP are then injected into each ovary. These procedures are performed in the lab, and the upper part of the plasma, which contains the beneficial components, is taken for the therapy.

PRP Treatment Timing and Organization

The timing of the PRP treatment can vary depending on the complexity of the case. In some cases, it is given on the 8th or 9th day of the cycle, while in selected cases, it may be administered for the entire cycle. The scheduling can be challenging, especially for patients travelling from other parts of Europe. We strive to provide convenience by organizing the workflow efficiently. On the day of the first appointment, we send the consent, medication protocol, and prescriptions to ensure everything is in order. We understand that patients have different needs, so the medication plan can be adjusted accordingly.

Benefits of PRP

PRP offers advantages in complicated cases and is an autologous treatment, meaning it comes from the patient’s own body and reduces the risk of rejection. The PRP procedure does not typically cause allergic reactions. It can be beneficial for cases where egg donation is not yet suitable, aiming to increase the number of follicles. It can also improve the thickness of the uterine lining and potentially enhance pregnancy rates. However, in severe cases of Asherman syndrome or extensive adhesions, PRP may not be effective, and alternative treatments may be necessary.

Conclusion

PRP in reproductive medicine is still considered experimental, and more research is needed to fully understand its effects on ovarian and uterine tissue. It is not used routinely but is reserved for selected cases. While PRP has shown benefits in uterine lining growth, better protocols are required to achieve more consistent results in ovarian rejuvenation.

- Questions and Answers

How long after ovarian PRP will you notice a change in ovarian function for patients with lower ovarian reserve?

If you use a protocol that is implemented in our patients, it’s usually a month or two after PRP. Then, you can either perform an IVF cycle with low-dose stimulation or opt for a natural cycle. We don’t want you to wait two to three months after PRP. It’s usually done in one month, and we will know if it’s working or not.

When do you suggest starting the IVF cycle after PRP?

One to two months after PRP, I wouldn’t wait long. There comes a moment in your life when you have to make decisions. If PRP treatment is successful, great! If not, we have to switch the strategy accordingly.

Can one go for ovarian fertility induction using Clomid or Femara after PRP?

Sure, you can go for it. Personally, I’m not a big fan of Clomid because it works for one or two cycles and then can deplete your ovaries. But if your AMH is very low, some people prefer stimulation with Clomid. It’s worth trying if you want to see how your cycle monitoring progresses and then have timed intercourse.

Is PRP used for adenomyosis, and if so, how often should it be done?

We do not use PRP for adenomyosis. Adenomyosis is the presence of endometrial tissue in the uterine wall. The classical standard is to undergo downregulation for two to three months to shrink the uterus and eliminate the bulky, inflammatory-like sponge endometrial tissue in the uterine wall. PRP is not used for this condition.

I have lower ovarian reserve likely due to endometriosis, and I also have issues with lining thickness. Is PRP used in these cases?

If you’re 35 or younger, you still have a good ovarian reserve. I would suggest performing one to two cycles to create multiple embryos through a process called embryo banking. The goal is to have at least five or six embryos, keeping in mind that statistically, at age 35, only three of them will be genetically normal. This approach allows for the transfer of genetically normal frozen embryos to the lining, which may require longer preparation time. Flushes with PRP can be performed to enhance lining growth.

Does calcium activation or endometrial PRP preparation have any benefits?

The PRP preparation is done by our lab, and we are not directly involved in the process. It’s similar to cooking. We cannot provide specific details about the preparation method, but our lab handles it. As far as I know, the platelets are activated with calcium.

What about after one round of egg freezing if you are before the age of 38 and you want to maximize the number of eggs in order to freeze?

It depends. What AMH do you have? If you have AMH 5.2 nanograms, you don’t need PRP. But if your AMH is around 1 or 0.8, or you know, around 1, should I say, try PRP.

How often should PRP be performed after implantation failure and several early miscarriages before a cryo transfer and new IVF with PGT-A?

Implantation failure is a very complex problem. In order to solve this puzzle, we have to be a little bit obsessive-compulsive, which means we have to check all the pieces of the puzzle: genetic normal embryos, implantation window verified by good uterus lining biopsy, where we see serious activity, where we see infections, where we see a lot of stuff. Okay, where we can even see the immunology? And the third problem is NK cells, HLA matching. I don’t want you to think that with the uterus lining flushing with PRP, we can solve the implantation failure. Medicine is a game of exclusion, it’s a puzzle which is the game of exclusion. You have to exclude one, two, three, genetics, quality lining, and biopsy, and then you can look for help in alternative medicine, which is PRP uterus lining flushing. And we usually perform in this kind of case at least two flushings, tend of a cycle, 90% of a cycle where we check the uterus lining thickness, and then 48 hours when people are on progesterone, 40 hours before we transfer. So it’s done twice in the transfer cycle.

What do you know if you know combining the use of PRP with hyaluronic acid is a generation?

I’ve never heard about hyaluronic acid in reproductive medicine. So I’ve seen a lot of cases in aesthetic medicine, and I know that it improves the collagen in the skin. I’m not sure if there’s anything published about ovaries and the lining.

I have fibroids and was told they didn’t interfere with implantation, unfortunately never worked for me. I am now 45, almost menopausal. Is embryo donation okay with PRP?

We have to see your AMH (Anti-Mullerian Hormone); it’s always about the ovarian reserve. I’m so proud of you that you are looking for embryo or egg donation. You can imagine that in 2015, one of the biggest statistics was published about the average quality due to age. And my statistics regarding egg donors were a part of this project. So, after 45, we have no genetically normal embryos. Zero, okay? So, you need an egg donation. If you need a sperm donor, go for it. Don’t think that PRP is going to be a cure for everything or fix everything. Try a good-quality embryo or a quality euploid embryo. We have this kind of embryo frozen in our bank here in UR Vistahermosa. So, if you need them, we do have embryos from double donation genetically examined to be sure that they are healthy. If the lining has issues growing, try hormone therapy. If the lining is good and the thickness is between 7–12 millimetres, you don’t need PRP. But sometimes, the problem could be your immunology, where your egg and sperm donor have to be immunologically matched to you. So, try one spontaneous good cycle with good-quality embryos. If it’s working, great! If not, dig deeper into your immunology. That could be an answer to why this is not working.

I am 43 years old, FSH 18, AMH 0.7. With this, is PRP an option, or should I go for donor eggs?

The oldest patient that I ever had with a genetically normal embryo was 45. It was a Chinese lady in London. We used to rent an office in London’s Harley Street before Brexit, which I loved. And the lady was 45, and she had one genetically normal embryo in my whole career. And she got pregnant until eight weeks of pregnancy, and then she miscarried. Probably the embryo was metabolically weak, not strong enough to develop into a baby. And then our papers were published about the mitochondrial quality of embryos, mitochondrial age, and this kind of story. So, if you are 43 and you probably have some IVF story behind you, go for an egg donation, and I’ll be more than happy to help you.

Will PRP work for me? I have an AMH of 0.01, and an FSH of 80, visualizing my ovaries is usually hard. Will PRP give me a chance?

No matter how old you are, if your FSH is more than 20, it’s super difficult to make it happen. I have a couple of cases in my life because the ovarian reserve is not only your AMH; it’s the combination of three factors: age, AMH, and antral follicle count. So if I have somebody with that low AMH, and this lady is 20 years old because she’s in premature ovarian failure, she has the chance to have three cells and one of them is healthy. If I have somebody with this low AMH and at the age of 40, there will be no good eggs and there will be a low number of eggs. Okay, so with FSH 18, I have never seen anybody generating the next. I’m sorry, you need an egg donation.

Vaginal Viagra is not available in the UK. Do you use a special operation or can the oral tablets be inserted eventually?

The same Viagra that men take for fun orally, we can use vaginally. There isn’t a difference between oral and vaginal Viagra. There are no specially composed vaginal pastes or Viagra. It’s the same one. Viagra can be quite expensive, but there are other generic brands which can be useful.

I’ve been told I don’t ovulate anymore due to low estrogen and progesterone, but I still have periods. Is this something I should consider?

When I see a patient, ovarian reserve is the key. AMH (Anti-Mullerian Hormone), antral follicle count. I’m like a broken record, it’s always the same. Your low estrogens are probably a reflection of low ovarian reserve. When you have a low ovarian reserve, you have to make decisions. If you have low amounts but are young, unified under 35-38, we can try to look for treatment with your own eggs. But if you have low ovarian reserve, and low estrogens, and you are over 40, then you need an egg donor. So, you need an appointment and an assessment with somebody who won’t just look for the end products of Reproductive Medicine, which are estrogen and progesterone. I can give you oral estrogens. From estrogens, 30 units, I can have 200 units in 3 days. The question is your own eggs or donor eggs and your AMH or AMH of your donor. Take it one step at a time. Get yourself an appointment, and we’ll be more than happy to help you.

How long does the effect of PRP last?

2 months, 3, not more. So, the answer is if you do PRP, get yourself 1 to 2 months before you perform IVF. If somebody suggests a Clomid cycle or treatment with IVF or a natural cycle, the dosage of medication injected will differ.

I’m 40 and collected 5 eggs on the last cycle. As you said, quality is linked to age. Would PRP be appropriate?

PRP will be appropriate to improve the number of eggs, but it will not increase the number of genetically normal embryos. What you can do is something called embryo banking or you can do something called egg banking. Freeze your eggs, you know every 2 to 3 months, 5 eggs at the end after a year of work. Saw them all fertilize, develop them into 5 embryos, and develop them to the blastocyst on day 5,6 six. By then, you’ll be surprised, only 20-30% of your embryos will be genetically normal. The quality of blastocysts is due to your age, and there’s nothing we can do about it. What you can increase through PRP, as we said, is the number of antral follicles and the number of potential eggs. So, if you go through PRP before each cycle, you increase the number of eggs by 1 or 2, imagine instead of having 5 eggs in one cycle, you will have 6 or 7 after egg freezing. In 3 cycles, you would have had 15 eggs if we count 5 eggs per cycle. But if we count 7 eggs per cycle, seven times three, 21. This will increase just the number of eggs, but it doesn’t have any impact on the genetic quality of your embryos.

Do you have any experience with PRP extraction kits?

I have the luxury of working in one of the biggest hospitals in Alicante. So, my PRP extraction kit is a 10-millilitre syringe that I have to take two or four of them and send them upstairs to the lab, and then they will do their magic. So, no experience with PRP extraction kits, and the beauty is that everything is done fresh. So basically, people come at 10 o’clock in the morning, and one to two hours later, we can do PRP.

Do you indicate intravarian PRP in cases with the diagnosis of endometriosis?

I have no experience with endometriosis and PRP. I’m not a big fan of injecting anything into endometriosis. I had a couple of cases where I did a puncture of infected endometriosis cysts, and people had serious complications. So, if there is endometriosis, get rid of it, and operate it. Endometriosis doesn’t bleed outside and doesn’t bleed inside. Endometriosis doesn’t grow in your tube or your ovary. You have no cycles, no menstruation. And then, if you get it under control, perform an IVF cycle.

Is PRP ideal for recurrent implantation and no pregnancy loss (RPL)?

There is no ideal solution for recurrent pregnancy loss. You have to see the genetic quality of embryos, and endometrial quality verified by a biopsy. You can send the biopsy to Valencia or Barcelona for processing and immunological workout HLA matching of patients or donors. This is the ideal approach for recurring pregnancy loss. If obsessively compulsively, you’ve solved all the pieces of the puzzle and everything is under control, then you can try to flush the lining with PRP.

Can one use DHEA to improve ovarian reserve before an IVF cycle?

I know this American approach, the DHEA, CoQ10. It can improve ovarian reserve. There are papers published that this can improve a little bit of your ovarian reserve. I haven’t seen any papers published regarding the numbers. So, DHEA 50-75 mg for 3 months before you do a cycle, go for it. Do 1 to 2 cycles with your own eggs. And this includes vitamin D. There are some papers even published about growth hormones. So, try it. If it works, amazing. If not, call us for a first appointment, and then we have to switch gears and decide what we can do for you.

I only produce 3 eggs each cycle. With PRP be an option? I have premature ovarian failure and I am 42. I’ve had failed cycles with the maximum dosage.

Get yourself a cycle with PGT-A. Genetically normal embryos are produced. I just had a case, a girl who was 41. She had 20 eggs and 10 embryos. Everything is genetically abnormal. She was crying in front of me. I had to be a medical professional in front of her, so I couldn’t cry in front of her. But I cried at home. So, if you know that there are no genetically normal embryos, there’s nothing you can do. As I said, one of the most challenging cases I’ve ever had were 3 eggs, 2 embryos, 1 genetically normal, of somebody who’s 27. So her euploidy rate is 80. In the number of genetically normal embryos at the age of 42, the euploidy rate is less than 10%. So, out of 3 eggs, maybe 1 will be a good one. Get yourself this piece of evidence. If you’re lucky, you’ll be pregnant. If not, you need an egg donation and don’t waste time, money, or emotions on projects that we are not going to win.
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Authors
Natalia Szlarb, MD, PhD

Natalia Szlarb, MD, PhD

Dr Natalia Szlarb a Gynaecologist & Fertility Specialist at UR Vistahermosa, Alicante. She graduated from a medical university in Poland in 2002 and then worked in gynaecology and obstetrics wards at several German hospitals. She also participated in international internships in Egypt, Brazil and Poland during her medical studies. In 2011 Dr Szlarb obtained her PhD in Immunology in the United States of America. She has extensive experience in IVF with donor eggs and is known by patients as a friendly and warm doctor. Dr Szlarb speaks fluent English, Polish, German and Russian.
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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.