IVF failure – What’s next?

Ioannis Koutoulakis, MD
Consultant Gynecologist & Clinical Director

Failed IVF Cycles

IVF failure and what’s next?
From this video you will find out:
  • What are the common reasons behind IVF failure?
  • What options are available for patients experiencing repeated IVF failure?
  • How does male factor infertility contribute to IVF failure?

Failed IVF cycles: What’s next?

What are the symptoms of IVF failure? What are the reasons for IVF failure? Should I try again with donor eggs? What if I have IVF donor egg failure or a history of repeated IVF failure? How many cycles are enough? Are there any additional tests I can take? How to get pregnant after IVF failure? Can natural pregnancy happen after IVF failure?

These are the questions that many fertility patients ask – find out the answers in this webinar. Watch the recording above for the presentation by Dr Ioannis Koutoulakis, a Consultant Gynaecologist at fertility clinic Serum IVF in Athens, Greece. Dr. Koutoulakis has experience with working with patients after IVF failure and is able to recommend other solutions.

What if my IVF cycle failed?

It’s an incredibly sad fact, but IVF isn’t a given; it can, and indeed does, fail, sometimes repeatedly. Unsuccessful cycles often leave patients feeling disheartened and confused, wondering what their next steps might be, in order to conceive, and fulfil their dreams of becoming a parent. It can be an overwhelming time, searching for answers and trying to find the solutions, which could lead to a healthy pregnancy and live birth.

In this webinar, Dr Yannis Koutoulakis, Clinical Director of Serum IVF, in Greece, discusses the range of options available, for anyone experiencing the devastation, failure of IVF treatment brings.

In order to conceive, either naturally or with assistance, three things are required; good quality oocytes (eggs); good quality sperm and an embryo “friendly” endometrial cavity. These all need to happen in conjunction, taking place at the same time, with Dr Koutoulakis stating that, in addition to these three elements, “a matter of luck” is also required, for human reproduction.

There are, of course, many factors that play a role in achieving the optimum quality of eggs, sperm and uterine cavity; the immunological and hormonal health, of both parties, any chromosomal abnormalities and medical history, to name just a few. Fortunately, clinics can now run a whole range of tests, with screening taking place, in order to help provide answers and create a tailormade programme, for each couple, after many failed attempts.

Following a cycle of IVF, Dr Koutoulakis advises that medical specialists are able to understand, with greater clarity, the condition of a woman’s eggs, by looking at the appearance of the oocytes retrieved, how many were collected and how they fertilised. This information can then be used to form a more detailed medical picture, around a woman’s fertility, and determine whether any different, or additional, protocols should be suggested, for future rounds of IVF.

Egg quality and age

If egg quality has decreased, due to, perhaps, maternal age, medical conditions or illness, it can, sometimes, be improved, with supplements, such as folic acid and / or melatonin. However, Dr Koutoulakis warns not to expect miracles, and advises that in cases, where oocyte quality is diminished, and IVF has repeatedly failed, the use of donor oocytes are an option, for a successful pregnancy.

Female’s uterine cavity

The female’s uterine cavity should be screened for macroscopic disorders, such as fibroids or polyps, which are known to cause problems with embryo implantation. If diagnosed, these are likely to be correctable, and couples may go on to conceive, with IVF. Dr Koutoulakis would also suggest an intrauterine biopsy or period bleeding test, to screen for the presence of NK (natural killer) cells, or any bacterial secrete toxins, which could also hinder implantation. Again, he advises that, if discovered, these conditions can, usually, be treated, either by medication or surgery, depending on the individual circumstances of patients. It’s also advisable for couples to undergo immunology screening.

Male factor and IVF

Currently, the usual fertility investigations do tend to focus, predominantly, on the woman. However, Dr Koutoulakis is keen to point out that male infertility does pose problems, and Serum IVF treats many couples, requiring assisted conception, due to male factors.

As sperm carries the paternal DNA, which is used in the creation of an embryo, any problems, with the seminal fluid, will have a detrimental effect on the outcome of fertility treatments.

Classic sperm tests provide medical teams with information including, the number; count, appearance; morphology, and how they move; motility. Additional sperm DNA fragmentation and oxidation tests can also offer further insights into a couple’s fertility. In cases of lower quality sperm, supplements and / or medication may be prescribed, as part of a sperm improvement protocol. If no progress is noted, then, once again, Dr Koutoulakis advises that using a donor may be presented as a viable alternative.

For some couples, unexplained fertility is, frustratingly, diagnosed, when nothing abnormal has been found, in either the male or female, following intensive fertility testing.

From the clinic’s experience, Dr Koutoulakis explains that, when IVF failure is recurrent, and there is no confirmed reason, for the infertility, Serum IVF would then recommend treatment should proceed using donor sperm. This has shown to have a positive pregnancy outcome, for clients undergoing treatment within the clinic.

Once a full, comprehensive, fertility investigation has been undertaken, doctors can then work, with patients, in order to design a specific, and unique, treatment plan for each individual, be that medication, surgery or the use of donor gametes, in the hope of a successful cycle of IVF, and a healthy pregnancy to follow.

Related reading:

- Questions and Answers

I have had five own egg IVFs, all failed, and three natural pregnancies which all ended in miscarriage. I have had many of the tests you mentioned at Serum including two hysteroscopies and an SIS in the UK. I have also tested positive for natural killer cells. What advice would you give?

As I explained before, three things have to be optimum and in your case, after these 5 unsuccessful own egg IVF treatment and natural pregnancies, we have to investigate the egg quality first. One of the important factors in your case is the sperm and I recommend you have a denaturation sperm test. I think this is what we have to exclude.

Should my husband forgo diabetes medication and blood pressure medicine before submitting a sperm sample? Can either affect the quality? His sperm tests have always been very good.

If he forgoes his diabetes and blood pressure medication for a short period, for one or two days before submitting a sperm sample, it does not affect the results at all. But, of course, diabetes affects sperm quality.

Six IVFs, seven transfers good quality blasts, hatching blasts and then no pregnancy. I have had so many tests due to thyroid problems. What do you advise? I’ve never had implantation.

Thyroid problems can affect the implantation and we aim to stabilize the thyroid function at first. Then we have to investigate the endometrial cavity, an important factor in achieving implantation and pregnancy. Another thing you have to investigate is sperm quality because with good quality blastocysts there may be a hidden sperm issue affecting implantation. I recommend DNA fragmentation and investigating bacteria and period bleeding test.

I have had three IVF treatments using ICSI using husband’s sperm with very little fertilization with one egg each time except for the third treatment which resulted in no fertilization. We then went for another IVF using ICSI using donor sperm but none fertilized, saying egg issue. Now looking at donor eggs. I also have a thyroid problem. I never had implantation in any case.

In this case, the most important factor is the egg quality because if we don’t have fertilization on day one, we recommend using donor eggs to see the difference.

I’m currently taking antibiotics advised by Serum. What supplements should my husband and be taking? I was advised to take DHEA.

For your husband, it’s good to start taking antioxidant vitamins like vitamin C and vitamin E.  Regarding DHEA, we have some worries that there is a risk of cystic formation, as we have seen in a lot of cases.

Can stress during the two-week wait impact implantation? Can some foods positively help implantation?

Of course, stress can affect the outcomes of implantation and a healthy lifestyle can give us better results. But, as discussed before, don’t expect miracles from supplements and diet.

5 failed on own egg cycles and two failed donor egg cycles. I’m already using immune treatment and have had implantation cuts now. Anything you can suggest?

You may try a further donor egg treatment after the hysteroscopy and implantation cuts, and if this has a negative outcome, we recommend donor sperm treatment, this means donor embryo treatment. The most important factor is the uterine cavity that you have already done. A new donor egg treatment is recommended and after this, if we still have the same unsuccessful outcome, we strongly recommend using donor sperm next time.

What do you think of LIT therapy? Is there any other alternative?

For those who are not familiar with the term LIT therapy, this is a gold standard therapy for couples with recurrent miscarriages, and, after a doing a DQA match test, we check compatibility issues for the male and female. If we see they have a partial match of pathogens, then we recommend specific immunization – LIT therapy. We strongly recommend this for couples with partial incompatibility.

Do you recommend embryo adoption?

We recommend embryo adoption treatment for couples who have tried donor egg treatment more than two or three times and whose uterine investigation comes back problems free. In these cases, we recommend donor egg and donor sperm treatment – embryo adoption treatment – which has a high success rate.

Would you suggest using donor sperm or using 50/50 donor/husband sperm to get better results?

We recommend 50/50 donor sperm/husband sperm treatment for couples who have tried donor egg treatment with husband and with an optimal uterine cavity where the result comes back negative. In such a case, we would go ahead with donor embryo treatment. For diagnostic reasons, we divide the donor eggs, half with the husband sperm and half with donor sperm, to check the difference in the embryos’ progress. We recommend this treatment in cases where we suspect some hidden sperm issues.

Do you recommend exercise before embryo transfer with donor eggs?

We recommend exercise to relieve stress, relaxation, and a good healthy diet every time for a successful outcome.

Is your clinic, Serum IVF, closed the whole month of August?

We are closed from the 27th of July to the 26th of August.  

What’s your view on having sex after the embryo transfer?

My view is that patients should try to avoid sexual intercourse after the transfer until the test day; two weeks after a day-3 transfer or after two weeks after a blastocyst transfer.

I had two failed IVFs with my own eggs and donor sperm and they failed with no implantation. What do you recommend I am 38 years old and AFC was around 12.

In order to achieve pregnancy, we need 3 things. The first is the egg. At the age of 38, this is still in a promising age group and we would expect about a 25% to 30% chance of a positive outcome. We need to find the best appropriate protocol, depending on scan results and AFC. The second thing is the sperm. Using donor sperm, we expect the quality to be optimal. The third thing is the cavity. It’s good to investigate the cavity and exclude bacterial infection and, depending on the results, to investigate with ultrasound or hysteroscopy, if needed. This means we can adjust the protocol, depending on the age, on the hormone status and the Antral follicle count – and 12 it’s a very good number for this age group. Another thing is a full investigation of the cavity.

I have had two fresh IVF and two frozen embryo transfers. Do you think donor eggs treatment is the best option for me?

I would need more details about this case, of course. Donor eggs is not the only treatment, but it is the most promising option. However, all this is related to the quality of the sperm and the uterine cavity. If the uterus and the sperm are good, another thing we can do is to adjust the IVF stimulation protocol and try one or two more times, depending on the age group. If the patient’s age is no more than 40, the most promising option is to use donor eggs.

Like many patients, I get very stressed during the whole IVF process. What would your clinic suggest to reduce stress? My previous consultant suggested reflexology? Would this be suitable prior to treatment?

In our clinic, if the person suffers from stress during the IVF protocols, we recommend acupuncture, which seems to improve the outcomes in those with high stress. Besides acupuncture, and we recommend just enjoying life: having hobbies, visiting the islands, enjoying the sunsets. Try to enjoy the rest of life and don’t overthink the IVF treatment.

For donor egg IVF, how do you compare with other clinics in Greece in terms of successful pregnancies?

I don’t like to compare our success rates with other clinics. Our success rate using donor eggs and good quality donor sperm is around 50% to 60% with an optimal cavity, using donor or good quality sperm.

What is your success rate for 40 to 42-year-olds in your clinic for donor egg/sperm? Where can I find these results?

It is the same, about 50 to 60%. In combination with hysteroscopy, this goes up to 60 or 65% using donor eggs in all age groups.

Donor egg 4AA grade 5-day blastocyst transferred, but no implantation. Never got pregnant. Did a blood-clotting test with normal results. What tests shall I do before the next FET transfer?

This very good as we have already had the embryos and you cannot change the donors or egg quality. It’s good to focus on the uterine cavity and request tests in order to investigate bacterial infection. It is also good to arrange an aqua scan or hysteroscopy for a full investigation of the uterine cavity. If the bacterial infection comes back positive, you can have immune tests like Chicago test in order to investigate the NK cells and about the immunological panel to design an appropriate treatment before starting the preparation protocols for the lining. If there are any suspicions of endometriosis, we would start pretreatment for two weeks with anti-inflammatory medications and some steroids in order to suppress the chronic inflammation which goes with endometriosis.  As the clotting test came back normal, we don’t need to recommend a blood thinner. Of course, a blood thinner is not needed but is sometimes used during the protocol and because it increases the blood supply to the lining and protects against clots in those over 40 years old on high doses of estrogen as part of the protocol.

What is the stem cell treatment you can offer? I’m 42 and have had one pregnancy after 9 failed cycles. I’ve just tried for a sibling and had another failed cycle. The feedback is that my eggs are poor quality due to my age. Would this stem cell treatment help me with an own eggs cycle?

Autologous stem cell treatment using stem cells from the period blood is an innovative and promising treatment but is still experimental. We have seen some good outcomes in many female patients, but we have to wait to have more results in the future. Egg donation is, in this case, the most promising option at the moment.

Does weight matter with donor eggs success?

Of course, weight is an important factor for the outcome, but we don’t recommend our patients lose a lot of weight before IVF treatment. It’s good to change habits like diet or to start exercising, but we don’t recommend losing excess weight because it can have side effects; it’s a too quick change to the body and it does not help the mind as it gets stressed.

Can gluten intolerance affect the results of IVF?

Gluten intolerance can affect the outcome of IVF. As we know, glucose intolerance or insulin resistance affects egg quality, as well as implantation.  In this case, for patients with gluten intolerance or with insulin resistance we recommend a low glucose index diet and Metformin for at least two to six months before starting the treatment in order to balance the glucose and insulin levels in the body.

I only have two 4AA blastocysts left. I’m 42 years old. For the next frozen embryo transfer, shall I do a single or double transfer? We have had sperm tests and fragmentation tests which have been good.

We recommend a double transfer as we don’t expect all the eggs to be optimal and we would want better chances. Of course, it would be great to investigate the cavity before arranging the next frozen transfer just to be sure everything is optimal. We would want to focus on the cavity, on microscopic findings, like bacteria, and focus on egg quality and the ovarian reserve.

If uterine problems were diagnosed, how long would it take to go on to treatment once they have been treated?

It depends on the problem. If it’s just adhesions or scar tissue, it’s good to leave it one month for a rest and to let the uterus recover and then go ahead with the next period after the hysteroscopy. If the problem is more severe, like a uterine septum or fibroids, it’s good to leave it one to three months before starting the new treatment.

I’m about to start my first donor egg cycle. I had a hysteroscopy in February with implantation cuts. Will the cuts still last?

The cuts will last at least six to eight months, sometimes a year. If it is more than a year, is good to arrange an aqua scan with an expert in order to replace the cuts, or do another hysteroscopy. If we saw from the first hysteroscopy that there was a lot of scar tissue or a septum, it’s good to investigate this again with a second hysteroscopy or an aqua scan just to reconfirm the uterine condition.

With regards to my earlier question about two fresh and two frozen transfers: I’m 37 with an AMH of 10.11 and a normal sperm sample. Also, my CRP is 18.

The age of 37 is a promising age with very good outcomes in this age group. I think this case we should focus on the uterus and the sperm.

Does the blood type matter if it is different from my donor?

No, it does not affect the outcome at all. There is no blood in the egg.

I have a question about embryo adoption. Do you recommend it? I do not mean embryo donation.

Embryo donation is the same as embryo adoption and is recommended for patients with poor egg quality and problems with the sperm, but there is a difference between frozen embryo adoption and fresh donation treatment. In frozen adoption we used two excellent quality frozen blastocysts, where with fresh donor eggs/donor sperm treatment we use fresh double donation blastocysts and maybe have more embryos for freezing, depending on the number of eggs we retrieve from the donor. Plus, with the quality of the donor sperm and egg, sometimes you have four or five blastocysts from the donor egg/donor sperm treatment instead of, in the case of embryo adoption, only two frozen excellent quality blastocysts.

Can repeated hysteroscopy cause scar tissue?

Hysteroscopy cannot cause scar tissue: hysteroscopy is to fix scar tissue. We do just superficial injuries in the lining and we don’t interrupt the base lining, which can cause scar tissue. The most common cause of scar tissue is a bacterial infection, which can kill the normal lining cells, leading to cell death and a lot of dead cells can produce this scarring. With hysteroscopy, we remove all the scar tissue and rebuild a healthy lining.

I’ve read on the Internet that children born from IVF treatment may have difficult health issues, especially when they get older. Is this true?

I’ve met children with some problem cases but there is no evidence about this and there are only just a few cases.
Understanding the Importance of Carrier Genetic Testing
Hysteroscopy before IVF:  can it improve outcomes?
Recurrent Pregnancy Loss challenges: causes and solutions
How to prepare for an embryo transfer to improve your chances: There’s more to consider than just the endometrium
Endometrial factor and recurrent failures in IVF: diagnosis and treatment
How old is too old for my IVF treatment?
Ioannis Koutoulakis, MD

Ioannis Koutoulakis, MD

Dr. Ioannis Koutoulakis is a Consultant Gynecologist at fertility clinic Serum IVF in Athens, Greece. Serum IVF has been treating infertile female and male patients and guiding them during their infertility struggle since 1989. Serum IVF experts believe egg/sperm donation and IVF are the solutions that can maximize the patients’ chances of getting pregnant regardless of their age or egg/sperm quality. Serum IVF offers oocyte donation of the highest standards of donor welfare. The patients are able to choose a donor who is the closest match to their phenotype. We know how important that is for many of them.
Have questions about what factors will affect your IVF success?
Join our live event to directly ask your questions to three IVF experts.