Specific Protocols for Recurrent IVF Failure

At the recent Fertility Show Africa 2023, Medfem Fertility Clinic’s Dr Antonio (Tony) Rodrigues was among the leading fertility experts who spoke at the FSA2023 Expert Talks programme.

Based on Medfem Fertility Clinic’s more than 30 years of IVF experience, Dr Tony shared ways in which couples can boost their chances of IVF success, and explained the specific protocols Medfem Fertility Clinic has in place for those patients with recurrent IVF failure.

To boost chances of IVF success Dr Tony recommends the following is done before a cycle of IVF treatment: lifestyle changes for improved egg and sperm health, and treating existing medical conditions known to affect fertility, including hormone imbalances, fibroids and endometriosis. You can read more about these suggestions the our article: What You Can Do To Boost Your Chances Of IVF Success.

During his talk, Dr Tony also explained the specific protocols Medfem Fertility Clinic has in place for those patients with recurrent IVF failure, which we share below.

Recurrent IVF failure in numbers

Dr Tony explained that if one looks at the worldwide statistics, the chances of having recurrent IVF failure are around about 10%. However, over three cycles of IVF treatment with tested embryos, the pregnancy rate increases to as high as 92.6%. It is also important to realise that the chances of success increases – not decreases – with each IVF cycle.

So, recurrent IVF failure is not something that happens to every couple receiving IVF treatment, but only to a small group of IVF patients who experienced three failed embryo (fertilised eggs) transfers with high quality tested embryos.

The emphasis is on “high quality tested” embryos because most IVF failures are often a result of abnormal embryos which results in failed implantation in the lining of the uterus.

The challenge is that fertility specialists do all the preparation possible, but until there is an embryo, there is no way of knowing whether it’s going to be fine or not. However, based on decades of IVF experience, Medfem follows the following protocols for those patients experiencing recurrent IVF failure.

What we do at Medfem when you’ve had failed IVFs?

After an IVF treatment cycle that did not result in a pregnancy, our team at Medfem turn our collective efforts to achieve a better outcome. The entire fertility team goes back to the drawing board.

Stimulation for egg retrieval

For example, where a patient has undergone stimulation for egg retrieval and the embryo is of poor quality due to poor egg quality, we know from experience that it is possible to improve egg quality by, for example, paying attention to the stimulation for that individual and unique patient. Where poor egg quality is the problem, we tailor the stimulation specifically for that patient. In women over the age of 38, donated eggs are also a next possible step to consider.

Fresh vs frozen embryos

After recurrent failure, we also have a specific protocol that we follow when deciding whether to do fresh embryo transfers or frozen. We believe that fresh and frozen embryos are equal, and that what is more important than fresh vs frozen is the timing of the transfer. So, if you have a fresh embryo, but the parameters that determine the timing of the transfer indicates that the time is not right, then it would be recommended to wait and do a frozen embryo transfer.

However, in some cases, some patients do better with fresh embryos than frozen embryos, so if frozen embryos were used during the first treatment cycle, we might recommend a fresh embryo transfer depending on the unique circumstances.

Pre-genetic testing

Pre-genetic testing the five-day-old embryo is another process we use at Medfem Fertility Clinic to improve the chances of IVF success after recurrent failures.

After the egg is fertilised with the sperm, it grows in the lab for five days to form a blastocyst – the beginning of an embryo. The laboratory staff will then do a biopsy and remove about six to eight cells, which are then prepared in a special way. From there, the cells go to a genetic laboratory for assessment of all the chromosomes – 22 pairs of chromosomes plus the X and Y chromosomes – are tested for everything that can help us ensure we transfer only an embryo that is normal. Pre genetic testing is generally recommended to patients over the age of 35.

Preparing the uterus

At Medfem Fertility Clinic, we also pay special attention to preparing the uterus before the embryo transfer, especially in the case of recurrent IVF failures. The preparation of the uterus can be done in two ways: in a natural cycle or by medical induction. Using the natural cycle means monitoring the female partner during a natural cycle to know when the egg is ovulated or released. This triggers the necessary changes in the uterus naturally. The second method is to stimulate the uterus to prepare for an embryo by giving the patient oestrogen. Generally, the natural cycle is preferred to transfer tested embryos, but in some cases, it may be better to use oestrogen.

The uterus microbiomes

In the uterus, there are microbiomes, and these include a bacteria called Lactobacillus. It is a very important bacteria in women, because it protects the vagina, it protects the cervix and it protects the uterus. If the microbiomes are out of balance, bacteria are allowed into the uterus and those bacteria then will prevent the implantation of an embryo.

The there are ways of measuring this and it can often be picked up on a hysteroscopy, during which the specialist will see that there is something wrong where there is inflammation in that uterus. This can fortunately be treated up front and the treatments is a simple antibiotic therapy.

Managing natural killer cells

Another step we take to prepare the uterus and achieve a better success rate is to manage for elevated natural killer cells. At the time when an embryo implants, there are complex physical processes taking place and immune factors play an important role.

This is because the embryo that must implant in the lining of the uterus is made up of half of another person. The body picks up that there are male genes present in the uterus and believes it to be a foreign body that must be defended against. It is a very complicated immune reaction, and in order for this embryo – which is considered by the body to be a foreign body – to implant, it needs antibodies that surround it. These are called blocking antibodies and they protect the embryo so it can implant in the uterus.

There is a very specific group of patients who have a problem higher natural killer cells. It is called tumor necrosis factor in the uterus and it is treatable with immunotherapy.

From a medical point of view, treatment options would include using cortisone, as well as immunoglobulins and intralipids. At Medfem Fertility Clinic, we like to use immunoglobulins under the skin instead of intravenously, and we believe it has the same benefits intralipids. We generally offer this for recurrent failures – and 15% of our patients test positive in the tests we like to do upfront – anti-thyroid antibodies, anti-nuclear antibodies and anti-phospholipid antibodies. Where necessary, our team provide the prophylactic treatment on the first IVF.

Treating blood clots

Another protocol we include in our treatments for patients with recurring IVF failure is to check for and treat blood clots. There is a group of patients that have a higher chance of having clots. It is usually a genetic thing – these patients often have a family history of having clots in the legs or pulmonary embolus. That’s a very specific group of patients. There is also a very specific set of tests that needs to be done. But if you are having recurrent miscarriages, it is a good set of tests to do because clots are known to cause recurrent miscarriages. For this group of patients, we provide treatment in the form of blood thinners to improve the chances of successful implantation.

Patients can choose not to use it, but it is a treatment we don’t even use on a diagnosis basis, we use it routinely. In fact, at Medfem Fertility Clinic, we have a protocol that every patient takes Ecotrin tablets – which prevent blood cells sticking together and forming a blood clot – during the IVF treatment cycle. We’ve done it for years, and we will certainly continue to do so, because we believe it makes a positive difference to our success rates.

We also continue the treatment beyond implantation and right up until 12 weeks of pregnancy. Where the fetal medicine specialist believes the treatment should be continued, the Ecotrin can be taken for the rest of the pregnancy.

EmbryoGlue

At Medfem Fertility Clinic, we also pay attention to endometrial receptivity and how we can improve the way the endometrial layer inside the uterus allows the embryo to implant, in addition to other than the immune therapy described above.

One option is EmbryoGlue(r) which is made with a substance – hyaluronan – that makes the embryo more likely to stick to the lining of the womb. It is actually not a glue. It is a culture medium that hyper stimulates the area of the endometrial lining and hyper stimulates stem cells, and changes some of the cells’ immunity and allows that embryo to implant. At Medfem Fertility Clinic, we believe in it and we have used it for a long time. Our studies show that we have increased pregnancy rates by using EmbryoGlue(r).

ERA test

One of the latest and increasingly popular treatments is called the ERA test, which stands for Endometrial Receptivity Assay test. It was developed by a genetic company to improve the likelihood of the embryo implanting in the uterus for women who have had several failed embryo transfers. It is a genetic test that can be used to assess when the lining of the womb is most receptive to the embryo. This allows the specialists to pinpoint on which day it would be best to put back the embryo.

This treatment is unfortunately quite expensive, so not many patients have access, but where necessary it can also be done by the Medfem Fertility Clinic team.

Assisted hatching

Assisted hatching is something we believe in at Medfem Fertility Clinic because we have witnessed the positive impact it has on the chances of a successful outcome.

In order to implant into the uterine lining, the embryo must hatch out of its shell, the zona pellucida. If hatching does not occur the embryo cannot implant and pregnancy will not occur. A common cause of difficulties with hatching is that the shell is too thick or too hard.

In assisted hatching a small break is made in the zona pellucida to weaken it just prior to blastocyst transfer. In specific cases this results in increased implantation of the blastocyst into the endometrium and increased pregnancy rates.

We offer this to patients over the age of 38, as well as during transfers when using both fresh and frozen embryos.

Even further options to consider

There are even other treatments that may be beneficial for patients experiencing recurrent IVF failures, which are not specifically part of the protocol at Medfem Fertility Clinic, but are still available to patients, such as Platelet-rich plasma (PRP) therapies and G-CSF.

Platelet-rich plasma (PRP) therapies use a patient’s own platelets to promote tissue healing and growth, including endometrium. It basically means that specialists can take some of your blood and create plasma. We do not specifically do this at Medfem Fertility Clinic but there are studies that show that it may be effective for patients who have a very thin lining and unable to fall pregnant. In general, we would not offer this unless there is damage to the endometrial lining.

Another therapy that may be helpful is G-CSF (granulocyte-colony stimulating factor) – a type of protein called a growth factor. G-CSF stimulates the bone marrow to make more blood cells, and increases the number of some types of white blood cells in the blood that protect from infection. It’s most often used with chemotherapy. It can also increase the number of stem cells.

Where to turn after recurrent IVF failure

If you have experienced recurrent IVF failure, our team at Medfem Fertility Clinic would like to share this message with you: just hold on to hope – there are so many options to help you have the baby you want even after a number of failed IVF cycles!

Our IVF clinic treats over a thousand patients each year with success rates that have consistently remained high and well above the national averages. In fact, our success rates are consistent with the highest reported amongst clinics worldwide. We are proud to have played a role in bringing more than 18,000 babies into the world.

At Medfem we believe in helping you reach your family dream through:

* World-Class Fertility for Everyone – we believe in making world-class fertility treatments available for everyone

* A Positive Fertility Journey – It is our joy and commitment to give you a positive outcome to your fertility journey

* Delivered With Empathy & Caring – So you may have a fond memory, of a feeling of empathy, caring and being part of the Medfem family

If you would like to meet one of our fertility specialists at Medfem Fertility Clinic, simply click here to book an initial consultation or contact us telephonically on +27 (11) 463 2244.

Our Fertility Specialists can also meet with You During a Virtual Consultation Via Zoom or Skype. Click here to book a virtual consultation now.

We look forward to meeting you at Medfem Fertility Clinic!