Implantation issues and possible solutions when IVF cycle fails

Infertility is not only a clinical problem. It is an overwhelming and demanding process for couples who desire to have children. Starting IVF treatment isn’t the end of the journey it is only one of a number of hurdles which need to be overcome before a successful pregnancy.

In this webinar, Dr Natalia Szlarb tries to explain what to do if IVF failures happen to us and, at the same time, gives some hints on how we can increase the chance of embryo implantation.

It is common that women plan to have their children much later than they used to. The problem is that women’s biological clock is not aware of these changes. With age, both the number of eggs and their quality decrease.

There are three factors of a woman’s ovarian reserve: her age, Anti-Müllerian hormone (AMH) and antral follicle count (AFC). In every clinic, with every patient, they have to calculate how many good eggs the woman generates. This number depends solely on a woman’s age. AMH says how many eggs a woman is able to produce – but it doesn’t say anything about their quality. AFC is a transvaginal ultrasound that tells how many astral follicles (so – in other words – potential eggs) there are in the ovaries. According to criteria suggested by the American College of Obstetricians and Gynaecologists, ideal patients to work with own eggs are women under 40 years old with AMH 1-2 ng/ml and with at least 6 antral follicles in both ovaries. As a woman gets older her AMH reduces as well as the number of genetically healthy embryos that she is able to generate. This number is only stable until the age of 35 years old. About 10 years later, there are almost no good embryos left. That’s why women over 45 are usually recommended to go for egg donation treatment.

Dr Natalia Szlarb admits that up to recently, medicine has associated bad embryos that women generate only with Down syndrome. Now thanks to next-generation sequencing (NGS) we know that from the age of 35 there is a higher rate of other chromosomal abnormalities, too.

Pregnancy rates in women between 35 – 40 years old (without genetical testing of embryos) are under 20%. When technology is applied to the way embryos are developed and selected, the rate increases up to 70% per transfer and is age-independent. If a woman is young (around 35) 50% of her embryos are healthy. With a good quality partner’s sperm, out of 20 egg cells, Dr Szlarb expects 8-10 blastocysts (embryos on day 5 of development) – only 5 of them are genetically healthy euploid embryos.

At a certain age, the key to achieving certain success rates is blastocyst culture. In order to select the best embryos and assure implantation success, an IVF cycle with PGS (pre-implantation genetic screening) has to be performed. First, the biopsy is administered. An embryo biopsy removes about 3-8 cells from each day 5 embryo (a blastocyst). After the biopsy, the embryo is typically frozen while PGS testing is performed. For a biopsy to be successful, a skilled and well-trained senior embryologist is required. Screening for both genetic diseases and chromosomal defects with a single biopsy improves pregnancy rates. In fact, with a euploid, genetically normal blastocyst (after the biopsy), pregnancy rates are as high as 70% per transfer.

Here Dr Szlarb makes a point that the majority of embryos do not implant just because they are ‘good-looking’. Doctors have no idea if these amazing embryos are genetically healthy or not unless they perform genetic testing.

According to Dr Szlarb, the duty of every doctor is to explain to a patient her success rates. The latter is not only related to AMH and the number of eggs that a woman generates but also the effort her body puts into achieving pregnancy. sometimes, even if AMH is low (and in this case diminished ovarian reserve), a woman can still generate blastocysts. When working with genetic testing of embryos, the desired number is 6 blastocysts. Then, according to a patient’s age, doctors may predict the number of healthy blastocysts they’re going to generate. Statistically, from the age of 44-45 years old onwards, every patient is a candidate for egg donation. However, Dr Szlarb admits she always listens to patients and allows them to have one IVF cycle with own eggs to help them understand that all eggs they produce are genetically abnormal. Then they may psychologically prepare themselves to either adopt a child or allow themselves for egg donation.

Dr Szlarb says that egg donation is the final step in infertility treatment that doctors can offer to a patient. However, sometimes even with the best, healthy donors and their detailed qualification process, things may not go according to plan. After the first unsuccessful transfer with donor eggs, Dr Szlarb suggests patients do receptivity testing. It may turn out that the problem lies in a patient’s body, and it is her endometrium that does not accept even good embryos.

It took medicine quite a while to define what is exactly going on in the implantation process. Implantation may be described as a dialogue between the embryo and the endometrium. The endometrium is known to accept only healthy and genetically normal embryos. Through progesterone, the endometrium undergoes immunological changes and the creation of immune cells that allow for immune modulation and better blood flow to the lining. The lining accepts blastocysts only at a certain time. The endometrium is made the best to accept the embryos after 5-5,5 days of progesterone intake. There are some women that have their implantation window moved. It needs another average of 6-7 days of progesterone to open the implantation window. Before transferring for the second time, doctors double-check the receptivity. An endometrial receptivity map checks how many hours is needed for the lining to have the best receptivity.

In some cases, on the day when the receptivity testing is performed, there is also immunological testing conducted. In cases where there are too many Natural Killer Cells (NKs) in the lining, Intralipid treatment is prescribed. Immunological testing is also used for detecting e.g. antiphospholipid syndrome, KIR polymorphism or placenta antibodies. The solution for immunological issues is the uterus lining biopsy.

Of course, infertility is not only a woman’s problem. According to the new data, 40% of infertility cases are due to a male factor. There is genetic testing of sperm available, too. It is the so-called FISH test. If a man is over 50 years old and his FISH test results are pathological, he may not generate as many healthy embryos as a younger man. However, there is still a chance of generating at least 1-2 euploid blastocysts per cycle.

Dr Szlarb says that a sperm analysis is performed during the first appointment for every patient. It helps to establish sperm quality according to the World Health Organisation criteria, such as volume, concentration, motility and morphology. Dr Szlarb advises performing additional DNA fragmentation and apoptosis testing as well. If there are some issues indicated, IMSI is also performed, as well as a testicular aspiration biopsy.

According to Dr Szlarb, there are two key elements for successful IVF. It is the new technology that helps to find the cause of your implantation issue and the best fertility experts who believe in personalised treatments and are at your side throughout your patient journey.