What to do after failed cycles and miscarriages?

Dr Alexandra Eissler
Fertility Specialist

Failed IVF Cycles, Miscarriages and RPL

From this video you will find out:
  • What are the common causes of failed IVF cycles, particularly egg quality?
  • What solutions or strategies are available to improve egg quality after failed cycles?
  • Are there specific treatments or interventions that can enhance the health of the endometrium to increase the chances of a successful pregnancy?
  • In cases where male factors contribute to fertility challenges, what concepts should be taken into account, and what solutions are available to address these issues?
  • What other causes can lead to a failed IVF cycle and miscarriages?

What to do after failed cycles and miscarriages?

Dealing with failed fertility cycles and miscarriages can be emotionally challenging. Watch the webinar led by Dr Alexandra Eissler, a Fertility Specialist, who provided helpful information on the next steps after facing failed cycles and miscarriages and how they can be prevented.

The importance of diagnostic evaluation

Before starting any treatment, it’s essential to find the cause of infertility, why miscarriages are happening, and why implantation is not occurring. We want to discover this before attempting another treatment because there may have been previous treatments in other clinics, and we can learn from them. We can learn from every failed cycle, implantation, or miscarriage, but we have to study them and understand what happened.

There are various reasons for treatment failure, with the most important ones being egg quality, the uterine lining, and male factors. There are other reasons as well that will be addressed later on.

Evaluating egg quality and quantity

Egg quality is crucial in the treatment process. We need to have an adequate number of eggs, and ovarian reserve decreases with age, so this is an individual consideration. We also measure the Anti-Müllerian hormone (AMH) level in the blood to understand the ovarian reserve better. Additionally, the number of follicles in a scan is counted to assess the cycle. Age is essential, not only for the number of eggs but also for their quality, as older patients may have a higher risk of chromosomal abnormalities in embryos.

To address issues with egg quality, we can consider various options. Individualized priming may be necessary for patients who need more time to develop eggs. Pre-implantation genetic testing of embryos can be performed to check if embryos have the correct number of chromosomes. Other genetic tests for specific conditions can also be considered. Personalized stimulation protocols can be developed based on past treatment experiences. Platelet-rich plasma (PRP) treatment is a new method that has shown promising results in improving egg quality and quantity.

In the end, we need to decide whether IVF is the right treatment or if egg donation might be a better option. This decision should be made in consultation with the patient, considering the advantages and disadvantages.

Optimizing the uterine lining

The uterine lining is a dynamic tissue that changes regularly. There are several factors we can consider, to improve the chances of successful implantation. We can test the implantation window to ensure the lining is at its most receptive state. Immunology is also crucial, as the body has natural defense mechanisms. We test for natural killer cells, T-helper cells, and their ratios. We can treat any issues found in these tests with medication. Testing for endometritis, a chronic inflammation of the endometrium, is also essential, as it can be bacterial or non-bacterial. This can be treated with antibiotics if necessary.”

To determine these factors, we conduct an endometrial biopsy, a relatively painless procedure done without anesthesia in most cases. It’s done in our consulting room, and we analyze the tissue to get more information about the lining’s condition. In some cases, it might be necessary to consider going a little further and testing for receptors, as well as HLA-C genotyping. However, this is reserved for special cases and needs to be considered individually.

Exploring male factor and sperm quality

Let’s take a closer look at the male factor. The male factor primarily concerns sperm quality, and there can be various issues associated with it. I’ve listed a few potential diagnoses that can result from a spermogram. In simpler terms, it can involve having too few sperm cells in the sample, reduced mobility, abnormal forms that make it challenging to find normal sperm cells, or even a complete absence of sperm cells in the sample. In such cases, we need to investigate whether it’s due to an obstructive or other factors.

These issues can be directly observed in the sperm sample. Additionally, we examine sperm DNA fragmentation to identify potential problems with DNA destruction and assess apoptosis to determine how many sperm cells are self-destructing after ejaculation. Various mechanisms can influence sperm quality, and we can offer medications and vitamins to improve it. If these measures don’t suffice, testicular sperm aspiration (TESA) might be an option. TESA involves puncturing the testicle to obtain higher-quality sperm cells because sperm can encounter oxidative stress during their journey out of the testicle, potentially damaging them.

The quality of sperm is crucial for fertilization. Different techniques are used, such as IVF, IUI, IMSI, or PICSI. The choice of technique depends on the laboratory’s evaluation and the specific situation.

Investigating other causes

Miscarriages, implantation failures, or cycle failures can have other causes. To address these issues, we may examine your karyotype, assess chromosome abnormalities, and investigate immunological factors, thyroid health, and autoimmune diagnoses. Circulation and thrombosis risks are also assessed to ensure a safe pregnancy.

Before starting treatment, we evaluate the best individual approach based on various tests and diagnoses. Typically, treatment begins with ovarian stimulation or preparation for embryo transfer, depending on the selected treatment plan. We provide guidance on medication, dosages, and schedules, customized to your needs and test results.

Once the embryos are obtained, we proceed with embryo transfer. This process requires specific preparation, and we might conduct an endometrial biopsy or a mock cycle to optimize the uterine lining for implantation. We follow up until the end of the first trimester, monitoring progesterone levels and providing guidance on post-transfer medication.

For the actual embryo transfer, it’s advisable to arrive a day before and stay for a day afterward to minimize stress. We provide all the results and support you in the initial weeks of pregnancy, as well as during the follow-up after treatment. In conclusion, the treatment process and cycle analysis are highly individual and tailored to each case to address underlying issues and improve the chances of success in subsequent attempts.

- Questions and Answers

I had a chemical pregnancy after my first cycle. Is there anything that I can do to prevent this in following cycles? Is there anything which can be done to help implantation?

Yes, I mean a chemical pregnancy is already the sign that there was a reaction of the body to the transfer, so there is something that we can see and measure. Of course, we have to see if there have been any other pregnancies in your life. Is there anything that happened before? We have to consider your medical history, the state of your womb, and how your uterine lining looked before the transfer. In this case, it’s a good idea, for example, to go for an endometrial biopsy if it hadn’t been done before to check for any issues with immunology or untreated conditions from the first transfer.

Is there any treatment protocol to improve the number of eggs?

This is a very individual question, and it’s hard to answer without knowing the specific case. There are options to improve the number of eggs, but it needs to be tailored to the specific circumstances.  

If you go to a clinic and they just have one protocol, should we not attend there anymore?

If a clinic uses the same protocol for every patient, it may not be very individualized or helpful. What works for one patient might not work for the next. It’s important to have a personalized approach.  

Is there any possibility to convert primordial follicles into antral follicles?

This depends on the specific cycle and the medication used. While we can’t change a single follicle, we can consider medications and dosages to optimize the number of antral follicles.    

What are your thoughts on MTHFR mutation, and does having it mean you have a higher risk of recurrent implantation failure?

MTHFR mutation doesn’t necessarily mean you’ll have recurrent implantation failure. The impact of genetic mutations like MTHFR on IVF outcomes can vary, and it’s essential to consult a genetic specialist to determine if specific interventions or medications are needed.  

I’ve had 8 IVF cycles, one miscarriage, and some fertilization failures. I have low AMH and stage 3 endometriosis. Have you seen good results with someone like me?

The success in your case depends on the specific AMH level, which is around 5 pmol per liter. While stage three endometriosis can pose challenges, I’ve seen successful cases. However, it’s essential to consult with specialists and explore the best approach for your unique situation.  

What should the ideal progesterone level be on the day of embryo transfer, and which form of progesterone is best (tablet, injectable, patch, or pessary)?

We typically use vaginal progesterone, but the ideal form can vary based on individual responses. In our clinic, a progesterone level of 10 or higher on the day of transfer is considered suitable. However, different clinics may have different standards.  

If I start progesterone in the morning of the 20th of November and the frozen transfer is scheduled for the 25th, what would be 5.5 days in that case?

The morning of the 20th, then the 21st is one full day, the 22nd is the second full day, the 23rd is the third full day, the 24th is the fourth full day, and the 25th is the fifth full day in the morning. So, 5.5 days would be in the afternoon or at night, depending on the hour you started the progesterone level. If you started at 9:00 in the morning, it would be 9 in the night on the 25th.

I had 4 transfers, out of them 2 were miscarriages. I have a few more embryos left in the freezer, but is there a point in going with a frozen one or starting a new cycle and creating new embryos?

This question is very individual and depends on various factors. You had 4 transfers, and 2 were miscarriages. It’s essential to consider what examinations have been done, the reasons for the miscarriages, the quality of the embryos, and your medical history. To provide a proper answer, a thorough medical consultation is needed.

Can PGT testing be done on frozen embryos, and does it affect the embryos?

Normally, PGT testing is done on day-5 embryos, known as blastocysts, which have well-defined outer cells and inner cells. Biopsy is performed on the outer cells of the embryo. Research shows that, in most cases, the embryos survive this process well, and children born from embryos with PGT testing do not experience adverse effects. PGT testing can be done on frozen embryos. You need to thaw the embryos for testing, and you can refreeze them afterward.

I have had failed implantation, had a hysteroscopy, and was put on luteal phase down-regulation for 3 months. The doctor wants to proceed with prepping me for a frozen transfer without a bleed. Is that right?

In this case, the reasons for the failed implantation, the findings from the hysteroscopy, and the purpose of the luteal phase down-regulation should be considered. It’s essential to have a complete understanding of your specific circumstances before determining the best course of action.
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Dr Alexandra Eissler

Dr Alexandra Eissler

Dr Alexandra Eissler is a Fertility Specialist at IVF-Life Alicante. She is a highly accomplished physician who began her academic studies at the prestigious Carlo-Schmid Gymnasium in Tübingen. Following her time at this institution, she completed her medical education at the University of Ulm, a period that spanned from 2012 to 2019. In addition to her academic achievements, it's worth noting her extensive language proficiency, as she impeccably masters the English, French, Spanish, and Italian languages. This valuable array of language skills undoubtedly adds an extra dimension to her remarkable academic profile. Throughout her professional journey, Dr. Eissler has accumulated an impressive range of practical experiences. Her practical training extends far beyond this, encompassing a multitude of internships in areas such as anesthesiology, gynecology, and general medicine, all of which she completed at globally renowned institutions.
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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.
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