When women are born, they have a certain number of quality eggs in their ovaries. Because of the social revolution which has taken place over recent decades and many both personal and professional factors, more women postpone their maternity. The bad news is that the older they get, the lower the quality of embryos they are generated. It is these embryos, as well as the endometrium and the so-called ‘implantation window, which play a crucial role in the successful outcome of any IVF treatment. In this webinar, Dr Natalia Szlarb talks in detail about these factors and explains how they depend on each other.
Dr Szlarb starts by reminding us that young women under 35 years old generate about 50%-60% of genetically healthy embryos. The magic number to work with one’s own eggs is until 40 years old. Between 40 and 43 years old, the majority of embryos are unfortunately genetically abnormal. The most common genetic abnormalities are the ones like trisomy 21 (Down syndrome), trisomy 18 (Edwards’ syndrome) or trisomy 13 (Patau syndrome). If we do not apply pre-implantation genetic screening of blastocysts in women over 35 years old, the pregnancy rates are only 18%. When genetic testing and embryo selection are performed, the pregnancy rates are about 60%.
There are different methodologies in the embryo selection process. Generally, after pre-implantation genetic tests (PGD – preimplantation genetic diagnosis and PGS – preimplantation genetic screening), pregnancy rates are cumulatively very high. Embryos generated with donor eggs and selected with Time-Lapse technology can achieve even 70% of pregnancy rates.
Selecting embryos is the most sensitive methodology. However, these perfectly healthy, genetically normal blastocysts have to be put on perfect ground. Dr Szlarb highlights that it is the main reason why every patient is thoroughly examined during the first appointment with a doctor. Among others, they perform a transvaginal ultrasound scan. If on the basis of the transvaginal ultrasound, doctors are not sure what is going on with the uterus lining, they follow up with a hydrosonography. It is an intrauterine instillation of a saline solution aimed at improving the diagnostic accuracy in detecting uterine abnormalities. In other words, it is possible to see if there are polyps or fibroids in the uterus. These are basic anatomical pathologies that have an impact on the uterus lining and they have to be removed before the embryo transfer.
According to Dr Szlarb, another issue to focus on is the thickness of the lining. The standard thickness lining should be 7 millimetres, according to medical literature. It is common to perform the so-called test cycle that mimics a patient’s natural cycle. It includes progesterone and oestrogen supplementing and is conducted in order to see how thick the uterus lining is. It shows what dose of hormones is needed to grow the lining to the desired 7 millimetres and thanks to it, it is easier for the doctors to determine how to proceed with hormone supplementing in the transfer cycle.
However, hormone supplementing is sometimes not enough to achieve the desired thickness of the endometrium. Dr Szlarb says that in such a case, the lining growth has to be supported in an alternative way. We have undertaken an endometrium regeneration study aimed at treating patients with a history of transfer cancellation or failed transfers because of thin endometrium. Doctors are microinjecting patients’ platelet-rich plasma to support the uterus lining growth. It is believed that platelet-rich plasma allows endometrium to regenerate and highly improves its quality – not only in the current cycle but in future cycles as well.
Next, Dr Szlarb focuses on the importance of physiology. In fact, the question of how the uterus lining is working seems to be one of the most important issues. It happens that despite a visually perfect 10 mm thick lining and genetically normal embryos transferred, the patient is still not pregnant. Then in case of recurrent implantation failure (3 unsuccessful transfers), it is indicated for a patient to undergo a uterus lining biopsy. There are different ideas on why the endometrium is receptive or not.
According to Dr Szlarb, around the 19-21 days of a cycle is the moment when the cells of the uterus lining undergo specific changes – the receptors of progesterone are being expressed on the surface of the cells. It would not be possible to discover if not for microarray genetic technology that enabled the development of tests like a receptivity essay or endometrial receptivity map (ER Map). Thanks to these it is easier to determine if the endometrium is ready to accept the embryo or not. The results of the ER Map test are either receptive, pre-receptive or post-receptive. The pre- or post-receptive results are usually corrected by prolonging or shortening the progesterone supplementation. And then the doctors either follow up with a transfer or perform a confirmatory biopsy to know exactly when the receptivity window is.
The endometrium is extremely important in embryo transfer. However, if the doctors see that the combination of the correct implantation window, good uterus lining and genetically normal embryos does not result in a positive pregnancy test, it is time to move on to egg donation. Egg donation is performed in about 600 patients annually. The first step of the egg donor selection process is the confirmation of donors’ availability. The law in Spain allows for egg donation anonymity. Donors are screened for infectious diseases as well as genetic or heart diseases. The computer programme matches the donors and the recipients on the basis of a phenotype (eyes, hair and skin colour) as well as height and weight. For complicated cases with genetic diseases, we offer to test to match a donor with the recipient genetically. In order to exclude male factor infertility, a sperm analysis is conducted as well. In the case of patients over 35 years old with low ovarian reserve, where AMH is low, and the antral follicle count is less than 6, Dr Szlarb sometimes recommends so-called embryo banking. In such cases, 3 embryos before the blastocyst stage are generated in one cycle, they undergo biopsy and are frozen afterwards. After 3-4 months of the recovery time required for the patient’s body, another cycle is performed.
Summing up, the key to successful implantation and pregnancy is embryo selection. Genetic testing is the most sensitive method and when it is combined with effective endometrium receptivity mapping (ER Map) and reliable determination of the implantation window, the pregnancy rates may be as high as 80%.
According to Dr Szlarb, the biggest advantage of all of these factors is the possibility to “erase” a patient’s age and in this way make pregnancy rates completely age independent.
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