In this online event, Dr Rami Wakim, Reproductive Medicine Consultant, explains what you can expect when undergoing IVF treatment and what tests and studies are available to investigate difficult patient cases.
Starting with male fertility, the basic analysis is a straightforward semen analysis, and this is more than enough in most cases. Even if the numbers are a bit lower, there are ways to improve semen quality through your lifestyle, by quitting smoking and alcohol, having a healthy diet, avoiding toxins, exercising and so on. You can also improve your semen with the help of supplements in the form of sachets or tablets. Nowadays, more tests are available, for example, tests for seminal oxidative stress that can be done prior to antioxidant therapy, and sperm DNA fragmentation test, which can be helpful in cases of recurrent miscarriage, and unexplained infertility. Thanks to this test, it’s possible to see if there is any damage to the DNA in a sperm sample. The main indications for sperm DNA testing are varicocele, unexplained infertility, recurrent pregnancy loss, IVF and ICSI failure and lifestyle risk factors. According to ESHRE guidelines from 2017, the main cause of DNA damage is oxidative stress which can be exacerbated by smoking, and obesity, therefore, sperm DNA damage and oxidative stress testing should be offered to couples following even a single miscarriage. Couples should be advised on how to have a healthy lifestyle, so men would be advised to test semen, and oxidative stress before embarking on additional dietary antioxidant supplementation.
Fertility chips are more and more used and are very promising, potentially, those can help the embryologist choose the right sperm to have higher fertilization potential. PESA, TESA, TESE, and microTESE are also useful depending on each case and its indications.
There are 2 parameters to assess the egg, one is the quantity, and the other is the quality. The quantity is assessed by 2 things, a blood test (AMH), and the antral follicle count (AFC) scan, those help with the prediction of ovarian reserve. The AMH testing does not mean that if it is low, for example, e you are going to have your menopause very early or you cannot ovulate, or you cannot get pregnant on your own, it doesn’t mean anything like that, it just helped the clinicians to predict your ovarian response and to tailor your medication accordingly and an IVF cycle for example. The Anti-Müllerian hormone is the best single predictor because this is an objective test, and it doesn’t have to be related to the period, you can do it any time of the month, and it doesn’t have to be related to day 1, 2, 3 like what it was done with the FSH.
The quality is another issue, and the quality is directly proportional to age. Is it possible to improve your egg quantity? Unfortunately not, what you have is what you got. The other thing is regarding the age, how can I improve the quality of your eggs? Yes, there are ways, and the most important one is fertility cryopreservation. Why is that? If you freeze your eggs in time, let’s say at 30, they remain 30, even if you have to use them when you are 35 or 37, your eggs will behave exactly like 30. All your statistics will be based on age 30. Other options to improve poor quality include still experimental techniques such as mitochondrial transfer (three-parent baby), there is also the autologous transfer of ovarian tissue or ovarian tissue cryopreservation up to an ovarian transplant. Some centres are very advanced in this, and they do ovarian transplants to use it at a later stage.
The majority of euploid embryos (normal chromosomes) do implant, on the other hand, the aneuploid embryos (abnormal chromosomes) do not implant, however, there is also a grey area because some euploid embryos do not end in implantation. The first failure can happen, the second time can be just bad luck, and the third time means there is something wrong and it should be thoroughly checked. There are many tests available that can help with finding the cause of recurrent implantation failure. These include the ERA test (endometrial receptivity test), but also endometrial scratch, which according to HFEA doesn’t have robust scientific evidence to prove it actually works, as well as EmbryoGlue. Another useful tool is EndomeTRIO: ERA (Endometrial Receptivity Analysis) +EMMA (Endometrial Microbiome Metagenomic)+ALICE (Analysis of Infectious Chronic Endometritis) tests.
The uterine cavity is full of good and bad bacteria, if we adjust the microbiome, especially, the lactobacillus possibly we can improve things.
Nowadays, a lot of people ask about DHEA (Dehydroepiandrosterone)supplementation, and in 2015, the papers suggested that there is an absence of good-quality evidence of the risk and benefits of DHEA therefore it is not recommended. In 2020, a Cochrane review revealed a higher ongoing pregnancy rate and live births following DHEA use, however, the benefit was not statistically significant. There was also a very famous study called DHEA Intervention to treat ovarian ageing, it was a single-centre randomized control study which failed to demonstrate any benefit from the use of DHEA in women with diminished ovarian reserve.
Regarding antioxidants including CoQ10, in 2015, a paper came up where it was stated that further evidence is required before CoQ10 can be recommended for all low responders. It was shown that COQ10 improves the oocyte and cumulus cells’ quantity and quality, however, a recent study failed to demonstrate any improvement in clinical outcome. Another important thing to remember is that the excessive formation of reactive oxygen species (ROS) can induce oxidative stress and lead to some damage or death. However, both extremes whether you use more oxidative or more antioxidant are both counterproductive.
Artificial oocyte activation (AOA) is a good concept to activate the oocyte artificially, however, it has been only limited to scientific files, so it cannot be recommended clinically.
When we’re talking about heparin, there is conflicting evidence to establish its potential in recurrent miscarriage without Thrombophilia. However, there is growing evidence that other than its antithrombotic effect, the use of heparin can favour reproductive outcomes via different mechanisms of action.
A Cochrane review of 13 randomized controlled trials has suggested that the administration of aspirin did not improve the pregnancy rate for IVF patients. More recently, a Cochrane review of studies in women with recurrent miscarriage, whether associated with Thrombophilia or not, did not find any benefit of the use of aspirin alone or in a combination of Low-molecular-weight heparin (LMWH).