By fertility experts from Spain.
IVF and IVF with donor eggs – the more additional procedures you have, the better success rates. Is this true? What is the expert’s opinion and medical evidence? Watch the recording from live webinar and Q&A session with Dr. Yadira Pallás Gálvez, an experienced embryologist from the Reproduction Unit of Hospital Clínica Vistahermosa (PreGen) in Alicante, Spain.
There is much conflicting and controversial information surrounding additional IVF procedures leaving some patients to approach these laboratory “add-ons” with caution. Questions are inevitably raised regarding the actual techniques used and whether an increase in additional treatments will actually provide an increase in pregnancy rates.
In this webinar, Dr Yadira Pallas Galvez, senior clinic embryologist at PreGen in Alicante, Spain, describes the basic IVF procedure, outlining the various additional techniques currently used and explaining when further treatment options should be recommended for patients.
The object of IVF is to fertilise eggs and create embryos outside of the body. To optimise the number of potential embryos, the first step of IVF is to increase the amount of natural eggs produced by the body, this is known as ovarian stimulation. During this stage of the IVF process, the follicles (the cavity which surrounds the oocyte) are regularly checked by ultrasound to establish the optimal time for their retrieval. An egg collection is then carried out, under sedation, and once any oocytes have been obtained, they are placed in a special incubator until the sperm has been properly prepared in the laboratory.
Finally, either IVF or ICSI is performed using the fully mature eggs. For IVF the sperm and egg are placed together in the incubator, whereas with ICSI one specially selected spermatozoa is injected into one egg; this micro injection technique is usually used in cases of male factor infertility.
After 18-20 hours the first phase of fertilisation take place and embryo cultivation begins. As they grow, all embryos are classified by the embryology team according to their development. This grading helps embryologists determine when the transfer will take place and which embryo/s should be transferred or vitrified (frozen).
Embryo transfers are not painful and do not require sedation. The embryos are inserted into the uterine cavity using a catheter and ultrasound guidance. The number of embryos transferred depends on the patient’s history, the embryonic quality and medical advice; clinics aim to transfer a single, good quality blastocyst (five-day embryo) to achieve the best results however, this isn’t always possible.
Where male infertility is a factor, Dr Galvez would recommend a MACS test. All spermatozoa have a limited viability and through the process of Magnetic Activation Cell Sorting (MACS), any apoptotic (dying cells) sperm become separated. This separation of the gametes (sperm) enables embryologists to only use sperm which is alive and healthy for the fertilisation process. Apoptotic sperm are likely to include a higher amount of DNA fragmentation which can result in abnormal embryo development. DNA fragmentation cannot be detected when using basic microscopic methods. Dr Galvez suggests MACS testing for patients who are suffering from recurrent implantation failure, a low fertilisation rate or poor embryo quality, and when male age is increased.
Research into genetics has opened up huge opportunities in the field of assisted reproduction and with the introduction of preconception genetics testing, medical teams now have the possibility of increasing the chances of a genetically healthy pregnancy. Specialists would typically test for any recessive diseases, these include conditions such as Cystic Fibrosis, Spinal Muscular Atrophy and Beta Thalassemia, which occur when both parents are determined to be carriers of mutations for the same disease. Genetics testing allows medical teams to review the compatibility of couples to determine whether they are genetically suited. For couples who are incompatible further tests and options are available and the use of donor gametes may be suggested as an alternative approach.
Genetic screening can also be carried out on embryos by using PGT-A (pre-implantation genetic testing for aneuploidies). Aneuploidy is the presence of an abnormal number of chromosomes in a cell and is the most frequent cause of implantation failure, miscarriage and congenital anomalies (birth defects). The risk is known to increase with maternal age. Pre-implantation screening can improve implantation and pregnancy rates and maximises the opportunity of transferring only euploid (chromosomally equal) embryos. The aneuploidy testing follows an embryo biopsy, where a small number of cells and removed and then analysed.
The use of time lapse technology is another additional treatment regularly offered to patients, and one which PreGen clinic has recorded a 20% pregnancy increase following their usage.
Time lapse is an optical system within the incubator which allows embryologists greater opportunity to study embryonic development throughout the entire cultivation period.
When time lapse imaging is not used by clinics, embryologists have to physically remove the embryos at least every 24 hours so that their development can be analysed. Removing the embryos from their incubator exposes them to microscopic lights, temperature and humidity changes and human manipulation. Time lapse incubators limit this exposure and instead offer constant, optimal cultivation conditions. As embryologists are afforded around the clock embryo observation, time lapse technology helps them to select only those with the highest implantation potential for transfer and freezing.
Assisted hatching and embryo glue are two other laboratory add-ons which can be performed to aid implantation. In assisted hatching a minor defect is created in the embryo membrane which potentially increases implantation potential. It would typically be recommended for embryos that have morphological issues that might make implantation more difficult. Embryo glue is used as a transfer medium and is enriched with everything an embryo needs to help it implant. As of yet, no clear data has been collated to confirm whether these two techniques have a significant impact on implantation.
Dr Galvez advises that it is important for patients to remember that these are additional treatments and are not always necessary, or applicable, for everyone. Clinics must assess all patients individually and only suggest extra lab techniques which will make a difference in each unique set of circumstances.
We think that the use of embryo glue should be general and used all the time, as it always helps. There is not anything in the embryo glue that could damage the cycles.
Yes, that’s why we use it. There is medical evidence and bibliographies reporting the embryo glue use.
We do not use it at the moment, as there is no medical evidence for it.
All of them are useful, only when medically necessary. It doesn’t work in a way that “the more you do, the better”—there has to be a medical indication for it.
We normally do not use it, so we do not recommend it. We think that it is better to transfer all the embryos on the same day—there is no evidence to suggest the chances will be greater to transfer fresh embryos on one day and then frozen embryos later, so we cannot answer this question. In our opinion, you can transfer two of them on day 5.
Seeing as the embryo has already been screened, and the sperm fragmentation has been solved (?-27:56), if the embryo is euploid, it does mean that there is sperm fragmentation and it’s okay, so implantation and live birth should be good.
We normally do the scratch when there is a medical indication for it. The scratch helps implantation, so it depends on your doctor—if they think that you need it, then, of course, you should have it.
This can happen with PGS, when you screen the embryos genetically because probably in the previous IVFs we don’t know if the embryos were genetically normal or not, so after performing the PGS, we are sure that the embryos which we are transferring are viable to have implantation and then a baby.
We do not recommend to do it generally. There are some embryos which have implantation capacity, so you don’t have to do assisted hatching, and there are others where assisted hatching does need to be done, so these are the cases where we perform this technique.
Yes, it definitely helps. If the womb is not ready, or if it is not prepared or receptive, it’s very difficult to achieve a pregnancy. So, all techniques to measure the womb or to measure the endometrium receptivity are quite important to be successful.
We only deal with the endometrium receptivity because it’s very difficult to measure the hormones because the hormones that we are giving are artificial.
We do not consider it a marketing issue—we think time-lapse embryo monitoring is one of the most important techniques because it gives the clinics and laboratories a lot of information about what is happening inside the incubators. In a normal incubator, you should remove the embryos every day to check how they are, and you can miss lots of things, but when you do embryo monitoring, you have everything recorded, and you have much more information, which can help the embryologist to decide which is the best embryo to be transferred. We consider it to be quite important in a clinic to have an embryo monitoring system, and all patients can benefit from it, as you don’t need a medical indication for it to be used.
There is no medical evidence for that. We choose whether or not to do it depending on the quality of the sperm, not on the source of the eggs. It helps with fertilisation when necessary, and we don’t have any medical parameters to confirm that it could cause any problems—we think it can help to achieve a pregnancy. The sperm sample will determine if we need ICSI.
Yes, of course, it is important because when you have had implantation failures or miscarriages, you should have a battery of tests—you should have a protocol of implantation failure cases. These tests include immune tests, NK cells and also others, so yes, it can give us the origin of the problem.
When we have high sperm fragmentation, what we do is MACS (magnetic-activated cell sorting)— it has a lot of medical evidence to support it. It removes most of the apoptotic sperm, that means the sperm that is damaged. After that, we do the PICSI, when we have a camera with up to 400% magnification. With that, we have very good results using the MACS + PICSI. Also, of course, you should remember the spermatic capacitation.
It’s difficult to answer this question. When you are choosing a clinic, it’s true every clinic tells you how great and beautiful they are, but when you choose the clinic, you need to choose one with experience, where you feel comfortable and one you can trust. When you feel comfortable, it means the lab is having good practice and it is serious, and once you see the clinic and you meet the team, it is not difficult to detect.
We don’t use MitoScore—we know it, it is an embryo selection technique, but we use time lapsing using an embryoscope to help us choose the best one based on the needs of the patient and we are having very good results, so we don’t think we can improve the results.
You are right—there are a lot of techniques and there are places where the techniques are always included in the treatment. As I said before, we only use the ones that we think are useful and the ones that can improve the rates and only when medically indicated and necessary. There are some techniques that are easier to be measured and others that are more difficult to be measured, but results may vary with the techniques, but the results mostly vary when you apply them when necessary.
Yes, of course, you should have a protocol for recurrent miscarriages. There are some basic things we need to check, and if none of these are positive, then we go one step further.
We feel much more comfortable with a blastomere biopsy or a trophectoderm biopsy because these are the ones which have more of a guarantee. We select them depending on the evolution of the embryo because the polar body biopsy has controversial results, so nowadays it’s not clear if it helps or not.
PGS is a guarantee before the pregnancy—it is the last step we can perform before the embryo transfer—if you have 5 frozen embryos left, then this is what you should have.
Yes, it can be done on frozen embryos.
We believe in EmbryoGlue and we have been using it for years—as we told you, there is a lot of medical evidence supporting that it helps implantation. We have no idea about using it for an hour and a half, as in our practice we normally leave the embryo in it for around 10 minutes before the embryo transfer, and that’s enough to produce good results. Regarding assisted hatching, as we explained before, we don’t use it as a standard, only when necessary depending on the morphology of the embryo.
Not at all, because we do it before the preparation cycle, so not at all.
We can do both—it is the decision of the embryologists and the geneticists. PGS can be done on day 3 or day 5 depending on the evolution of the embryos and the opinion of the professionals. Doing the biopsy on day 5 does not mean you have to freeze the embryos—it depends on how long the laboratory takes to deliver the results, but normally we would calculate it.
No, it’s only for that cycle—normally, you should have it done again if you will be doing another transfer.
When you do PGD-A, one of the main reasons is for it to help with selecting which embryo to transfer. If you have one, then the need for selection is automatically gone. There are many factors regarding the couple, for example, medical history and the economic situation, as this is not a cheap technique. It’s a difficult question to answer—we would say it depends on the patient and on the case. To observe the embryos morphologically and a medical evaluation would help to decide.
It depends on the study we need to perform, but usually, we have the results in one day.
Medication is a very personal thing—it depends on your case, on your levels of hormones. We use different brands vaginally, we use injections… There are some standard protocols, but not all patients are receptive to these protocols, so we would need to know a little more about your history to be able to advise you.
The test that you had done can orientate you, but the problem is that not all cycles for a woman are the same. That’s why we recommend you have it done when you are going to be transferring the embryos.