IVF lab procedures and techniques to boost the success rates
Inconsistent, sometimes unproven information and price of laboratory add-ons may cause confusion and make patients some kind of suspicious. Are there any chances to boost IVF success rates with use of LAB techniques and procedures? Or is it just false hope? Is it true that the more additional procedures we use, the more chances of success we have? These are the fundamental questions that Elena Gonzálvez Albaladejo, head of the IVF laboratory at Phi Fertility, tried to answer in her webinar presentation.
Elena Gonzálvez Albaladejo starts with reminding us that embryos are very sensitive to the lab conditions. Over the years, IVF scientists have worked on improving lab conditions to make them imitate the female uterus and help embryos implant after the transfer. In order to achieve that goal, it is very important to closely control lab environment and pay attention to factors like humidity, oxygen, CO2 and luminosity. Additionally, there are all the new IVF techniques that can improve implantation rates. However, as Elena Gonzálvez Albaladejo says, they can work differently for different patients.
Generally, the success of embryo implantation depends mainly on the quality of eggs and sperm. However, there are a lot of factors that may influence the mentioned quality and these include patient’s age, medical and family background, chronic diseases, wrong diet (overweight or malnutrition), stress, bad habits (smoking or drinking) or even environment pollution.
More over, IVF lab is one of the most important issues in any IVF treatment. These are the lab incubators that are responsible for providing right conditions to the embryos. Controlling temperature and levels of CO2, O2 and humidity in the incubator is critical to the embryo culture. The correct incubation humidity is 95% and the ideal level of both CO2 and oxygen is 5%. Embryologist should also take care of good lab cleaning and they are recommended to wear sterile clothes and shoes. What is interesting, they are not allowed to wear make-up and perfumes while performing lab procedures.
Elena Gonzálvez Albaladejo goes on to explain some IVF techniques that may improve the embryo quality. First of them is a time-lapse system – the incubator with integrated continuous embryo monitoring capabilities. It provides individualised and undisturbed incubation environment. Thanks to time-lapse, it is not necessary to remove the embryo from the incubator during the cultivation. The system takes photos and videos of the embryo development that embryologist can see on their computers. In result, an embryo experiences less fluctuations in temperature, humidity and pH. And what’s the most important, time-lapse can help embryologists to evaluate the embryos by indicating them with different colours. In this way, the embryologists can choose the best embryos to transfer.
Another IVF technique for improving the success rates is choosing the best day for an embryo transfer. Elena Gonzálvez Albaladejo says that a few years ago, it was common to transfer embryos on day 2, 3 or 4 of their development. However, it often turned out that some of them were not ready to implant as they had lower implantation potential. So in spite of the fact that earlier in the embryo culture process there are more embryos available, it does not mean that a patient is more probable to get pregnant. Instead, she may be subjected to more treatments, more costs and – consequently – more emotional stress.
Nowadays it is more usual to conduct the embryo transfer on day 5 or 6 of the embryo development. In fact, it is not earlier than on day 3 when the embryo starts to develop itself and show its true potential. Thanks to a later embryo transfer, embryologist can make sure that they use only really good embryos. Additionally, it allows them for choosing one embryo instead of two. And this significantly decreases the risk of multiple pregnancies. Elena Gonzálvez Albaladejo admits that the day embryologists choose for the embryo transfer depends on a patient’s individual case – but according to hers and her colleagues’ experience, it is generally recommended to conduct transfers on the last stages of embryo culture.
The next important IVF lab factor that Elena Gonzálvez Albaladejo discusses is embryo culture medium. There are 2 different types of such media: sequential and global. With the sequential medium, embryos are grown from day 1 to day 3 in a first growth medium and then, on day 3, they are moved to a second medium in which they stay up to day 5. On day 3, embryologists have to change the environment the embryos are being cultured in and because of that, the embryos remain outside their incubators for about 3 minutes. As it involves fluctuations in media conditions and greater light exposure, there is an increased risk of generating stress and free radicals.
The second type of embryo culture medium is the global one. It provides all the nutrients for embryo growth until day 5. Because an embryo stays in an incubator uninterrupted, its culture conditions are stable. According to Elena Gonzálvez Albaladejo, embryologists, basing on their experience, always recommend global culture medium.
PGT-A, pre-implantation genetic testing, is another technique that may significantly boost the success rates. Formerly known as PGS (preimplantation genetic screening), it is a genetic study of the embryo produced during IVF treatment to identify numerical chromosome aneuploidies (imbalances). One has to remember that all women are at risk of producing chromosomally abnormal embryos. PGT-A is especially indicated in case of advanced maternal age (38-40 years and above), repetitive miscarriages or IVF failures (two or more). However, as this is quite an invasive procedure (a biopsy) and it requires a significant number of good quality embryos to be tested, it is not recommended for everyone.
As Elena Gonzálvez Albaladejo mentioned at the beginning, the sperm quality also plays an important role in increasing the pregnancy rates. Fortunately, there are a lot of different IVF lab techniques that enable embryologists to select the best sperm. These include MACS (magnetic-activated cell sorting), SpermSlow, PICSI (phisiological ICSI), IMSI (Intracytoplasmic Morphologically Selected Sperm Injection) and Fertile Chip. All of them are recommended when sperm test results show low concentration or mobility, high level of fragmentation or bad morphology. The embryologists should evaluate each patient’s case individually and choose the best technique.
The last technique Elena Gonzálvez Albaladejo focuses on in her webinar presentation is the embryo transfer medium, which is known under different names, such as e.g. EmbryoGlue® or UTM™. It is a hyaluronan-enriched medium that, thanks to its chemical composition, may help the embryo in its adherence to the uterus lining. It is especially recommended in patients with the history of repetitive miscarriages or implantation failures.
In conclusion, Elena Gonzálvez Albaladejo highlights the importance of treating each patient as a single case. One should bear in mind that the embryo quality won’t improve simply because of applying all of the available IVF techniques. A patient should always evaluate costs against real benefits and remember that the mentioned techniques are only as good as the experienced and professional staff using them.
Questions from the event
I had IVF and collected 7 mature eggs but only one was fertilised and it was abnormal by day 2 so I did not get any embryos… Is there anything the lab can do to help fertilisation and egg activation? I used donor sperm so that was not the problem. I am 39 years old.
Maybe the factor here was the eggs. You are only 39 years old but the eggs may not be of good quality. Every month we have several different eggs so maybe in the next treatment the situation will be different. But the age may be a negative factor here, too.
My husband has 100% abnormal sperm morphology… Does this really mean all his spermatozoa are bad or can you find some good cells?
The morphology results often depend on the embryologist who watches the sample. But with 100% abnormal sperm morphology, it is difficult to find one good sperm cell. So I recommend your husband to do the test again but in another clinic. If the situation is the same, start thinking about other methods, such as a sperm donor. Maybe you will have better results with donor’s sperm than with the sample of your husband’s sperm.
I have 5 frozen embryos. I am due for a transfer in January. Is there anything I can do to increase my chances for a successful implantation? This will be my first time!
From the IVF lab point of view – no, there isn’t anything you can do. Maybe if you ask your gynaecologist, you can receive some vitamins or supplements. But when it comes to the quality of the embryos, there’s nothing that can be done.
I am 39 and had failed IVF with own eggs. We did not test embryos and I wonder if you could tell by just looking at eggs if they are mature? Or is testing the only way to know it?
We, the embryologists, can see if eggs are mature or not – and sometimes we can also know the quality of the eggs thanks to morphology. But it is very difficult to predict the quality of the embryos.
I have also read about mosaic embryos. What is your opinion and practice at the clinic?
We can identify mosaic embryos by making PGT-A testing. The mosaic embryos are difficult to explain. These are not unhealthy embryos but we do not have certainty that they are healthy either. They are risky because they can give us a false answer during the analysis. I don’t like doing PGT-A testing in all the cases. But we may have mosaic embryos and then I can’t transfer them. It’s the risk of the technique.
How PGS can improve success rates with chromosomally normal embryos? Is there any evidence? Should every couple consider it?
PGS (or PGT-A) doesn’t improve success rates. There’s no evidence. But thanks to PGS (PGT-A) we transfer only chromosomally normal embryos. And even if you have only one healthy embryo to transfer, it may be a good pregnancy.
After my failed IVF, I got to know that my eggs were dark – could that be because of wrong medication or wrong culture media?
We don’t know the quality of eggs before we start the treatment. We can only see them after the ’pick-up’. It’s difficult to say if here the reason was the quality, medication or culture media. If oocytes were dark at the beginning, it may be the genetic information about the health of our cells.
I am yet to start treatment. My FSH is 7.1, LH 4, AMH is 3 (0.42 ng/ml). I am nearly 44. AFC test found 4 antral follicles in each ovary. Do you recommend IVF with own eggs or egg donation?
This case should be studied with a gynaecologist. It should be evaluated if the eggs present good chances in future cycles. Sometimes even with fewer oocytes, the cycle will work out. But it is better to ask a gynaecologist.
Can I have sex while on vaginal progesterone? And how long after the embryo transfer can I have sex?
I don’t know if you can have sex while on vaginal progesterone. But we don’t recommend it after the transfer because the uterus can have contractions during sex. It might be bad for the embryo.
Are there any strict recommendations regarding the time after the embryo transfer – what to do and what not to do?
The most important recommendation is to be relaxed and not think about it. You should stay relaxed for at least 15 days until the pregnancy test.
Has PCOS influence on the quality of eggs? Do you know any statistics or could tell something from your experience? Perhaps we should increase our chances by choosing great quality semen from a donor?
A lot of things have influence on the quality of eggs and sperm cells. But I haven’t read any statistics on this subject lately. In fact, every case is different. It should be studied individually by our team or the team from your clinic. It’s different for every patient.
What is your opinion on transferring 2 or 3 embryos to increase the chances of success?
There is a lot of controversy around this subject. I do not recommend to transfer 3 embryos because there will be a high risk of multiple pregnancy. But it is difficult to decide if it should be 1 or 2 embryos. It depends on the couple, their situation, also social situation, background and history. Transferring 2 embryos will increase the pregnancy rate a little bit – but it will also increase the risk of twin pregnancy. So if the embryo is of good quality, I’d recommend to transfer just one. But if we have 2 embryos of B or C quality, it would be a good option to transfer both.
Do you recommend time-lapse systems?
I recommend them to evaluate the best embryo and help the embryologist to choose which embryo should be transferred first. But a time-lapse system does not improve the quality of the embryo much. It may improve it a little bit because in time-lapse, the embryo doesn’t have fluctuations of the conditions. But I would recommend it mainly to select the best embryos.
Is semen extracted after TESE of better quality? We got to know that the cells were immobile. Would that mean they are also of worst quality?
The semen extracted after TESE is sometimes worse than a normal sample. It’s normal to find immobile sperm cells and it’s normal to have worse results. But if there aren’t any chances of normal sperm production, we may use that technique.
Do you recommend physiological fertilisation or ICSI?
It depends on the quality of a sperm sample. But I recommend ICSI because thanks to it, I’m sure that at least one of the sperm cells is inside the egg. So it is more probable to fertilise the egg.
What should I expect on the day of my transfer? Any specific questions I should ask the embryologist?
The most important thing to ask about is how many embryos you have and what quality they are. In case you want to transfer 1 or 2 embryos in the future, it is good to say this to the embryologist because they will be frozen either one by one or two by two. And that’s all.
Microfluidic sperm sorting – does it improve the chances of pregnancy?
No, it doesn’t because when we are using IVF techniques, we separate the microfluid and the sperm cells.
What’s the average success rate of frozen donor eggs?
In our clinic, we see no differences between frozen and fresh donor eggs in terms of their quality or potential. It’s the same. When it comes to donor eggs versus own eggs, then it depends on an individual case.