In this webinar, Dr. Arianna D’Angelo, MD, Consultant in Assisted Reproduction at Wales Fertility Institute, ESHRE UK Clinician National representative; a member of the ESHRE Ethics Committee has talked about how the ovaries are stimulated and prepared for egg collection as well as explained how the embryo transfer is done.
It very much depends on the stage of the embryo when you had your embryo transfer. If you had an embryo transferred on day-5, the embryos at the blastocyst stage, then it takes around 48 hours for the embryo to implant. So, after 10 days, if you have a blood test, you will have some evidence for pregnancy. If you had an embryo transferred on day-2 or day-3, then perhaps it will need a couple of days more. With the urine pregnancy test, we suggest waiting 14 to 16 days. Some of the urine tests are not as sensitive to pick up the pregnancy. The blood test definitely after 10 days will be fine.
Normally, as part of the IVF treatment, we offer an early pregnancy scan, and that is usually a viability scan just to make sure that the pregnancy is in the right place, is diable, and there is a baby’s heart. After that usually, we refer the patients to the obstetrician, there are a series of blood tests and an early screening test that can be done even at 10 weeks of pregnancy like the Chorionic villus sampling (CVS). The scan usually, in the first trimesters around 10-12 weeks would identify some problems. It depends on what birth defects we’re talking about because the spectrum is quite broad. In terms of genetic defects, the best thing to do is either have the blood test for the non-invasive genetic test or associated with the nuclear translucency measurement for the identification of Down Syndrome, and then obviously, if you want to have more precise answers, it’s the Chorionic CVS between 10 and 12 weeks, otherwise, wait for the second trimester, but it becomes more invasive for the pregnancy in a way and the mother as well because finding out about this while the pregnancy is advanced can have quite a lot of consequences emotionally. The problems with herniation or hydrocephalus can be identified at 10-12 weeks, but obviously, these kinds of defects are a little bit more advanced. Normally, there would be an ultrasound scan done at 20 weeks, and that is the anomaly scan where we look specifically at each organ inside the baby’s body, at the brain, blood, a heart, so some defects can be already found at the 20 weeks scan.
The gas we don’t tend to use. We do the embryo transfer very close to the lab, and we don’t know if this gas is toxic for the embryos and eggs, so I don’t think it’s recommended. The general aesthetic we don’t use either. For sedation, we usually give some Propofol or Morphine. Some Morphine or a little bit of Valium, and so it is called conscious sedation basically, the patient is awake and can tell the anesthetist if she requires any more painkillers. The whole idea is really to relax the pelvic area, and we find that when the patient is relaxed, the only instrumentation that we use, like the speculum, goes in nicely, and it makes the procedure easier from a technical point of view as well. Some anxious patients, so tend to contract the pelvic floor muscles, and that is even something that they can’t control, then they will benefit from having some conscious sedation. Occasionally, we also prescribe some Valium to take perhaps the night before or the morning of the embryo transfer just again to relax a little bit before the procedure takes place.
The future is going to be artificial gametes, which I’m not going to talk about because I don’t know much about it, but we hope in the future, we’ll be able to create eggs and sperm in the lab so that we don’t need anything else, but that’s a little bit far future, and we just have to be realistic. Two things are very important. First, is education, we have to start educating our young generation that it’s very important to look after your eggs, so don’t smoke, don’t drink too much, think about these things because the eggs stay with us for all our lives, and when we reach age 40-44, the eggs have been there for 44 years, so they are the reflection of what we’ve been through in our life if we’ve been having lots of nights out, lots of drink, lots of smoke, lots of drugs also, so unhealthy lifestyle, unhealthy diet, these are all things that day by day are seen in the eggs.
That’s why it’s important to do fertility education, which is something that is happening more and more now, and I’m really glad to see that happening also in high school alongside family planning. The second thing that we can do is also to start thinking that things that we see in the press are not always through, so all these celebrities that are getting pregnant in their late 40s-50s having children at any point in life, most of them are having egg donation, which is a perfectly acceptable option when you don’t have eggs when the eggs are not of good enough quality, but they don’t tell that. Obviously, the message goes out there that you can get pregnant at any point in life, but unfortunately, when we are not at the stage that we can have an egg on demand in a way, we need to do some more research. My message to all women is just to look after their eggs as much as they can.
That’s quite a lot of supplements. I can see that they are all very useful supplements, so I don’t think they will be too much or contraindicated. What is evidence-based is the folic acid, so the folic acid, it’s a must, we all have to advise our patients to start taking folic acid the moment they want to start conceiving because that is being proved that it does reduce the incidence of spina bifida, so neural tube defects in the baby. There is also more and more evidence about vitamin D, so it’s very important to take that as well. These prenatal vitamins I believe that means that they all contain all the vitamins that are required in pregnancy like vitamin B, D, C, iron, the ferrous sulfate iron is important. In regards to fish oil and probiotics, I don’t know, but I think they are all good for a healthy lifestyle. If you’re a vegetarian or vegan, and you don’t get much intake of proteins, perhaps that is why you need more supplements.
It depends on the experience of the doctor as well to make sure that we go at the right time, and that’s one of the challenges of our job to make sure that we don’t go to collect the eggs when it’s too early or when it’s too late. Sometimes, this is a bit of a learning curve, each woman is different, each patient is different, and the difference is not just between the patients, but it’s also between the same patients in different cycles, so some patients react to a drug in a certain way, and then the same patients react to a different drug or the same drug differently. There is a minimum number of days that it would be advisable for stimulation and to go too early with the stimulation. It’s not just a problem with the eggs, it’s also a problem with the endometrium. Don’t forget that those eggs produce hormones, and the hormones will prepare the lining of the endometrium for the pregnancy, so there must be enough exposure to the endometrium to the estrogens, otherwise, we end up having an embryo, which goes into the endometrial cavity, to an environment, which is not synchronized with the age of the embryo, and that is one of the reasons why embryos don’t implant if the endometrium is not well prepared. There have to be at least 10 days of stimulation to allow the good maturation of the lining, and then the decision is usually taken together, it’s not just the follicular size, but it’s also the thickness of the lining and the appearance of the lining. Once we get those eggs out, we expect some of them to be immature, so not all the eggs are mature maybe, 20-10% of the eggs can be immature, very rarely they are over mature, but sometimes if they are over matured possibly, it’s because we left it too late to collect, and in some protocols, this can happen because they don’t get released. After all, you’re taking the drugs to stop you from releasing the eggs, nevertheless, they pass that stage, and they’re just not good enough to be fertilized.
There is non-invasive fetal testing, which usually is done in the first trimester. It’s the sampling of the cells in the maternal blood to see if there is any problem. That can also be associated with standardized tests that are usually done around 14-15 weeks. Then as I said, there could be other tests, but they are invasive, so I wouldn’t recommend it and then a series of scans to check the baby’s growing well associated with the doppler study as well of the vascular, of the cord, and just to make sure the baby is feeling well. This is done as part of fetal medicine. I don’t do obstetrics, so I don’t have any specific details, but there is a blood test, a non-invasive blood test that can be done to find out about genetic abnormalities, and then a series of scans through the pregnancy. When we do the PGD, we usually advise doing some antenatal testing to make sure that the actual PGD was right so they will look at the genetic abnormalities like Down Syndrome, Turner Syndrome, or monosomy, anything that can be genetic just, to confirm the PGD.
Pergoveris is a bit different, it’s the same make as Gonal-F left, but the actual drug is different. Gonal –F is the only follicular stimulating hormone, which means that it just contains one type of hormone to stimulate the follicles. Pergoveris contains two hormones, so it’s partly follicular stimulating hormone and part luteinized hormone, so LH activity, which is always very good to give. There is no enough evidence to say which one works best, but there are some protocols that can be given to people who had perhaps several failures or a low egg reserve, which implies starting with Gonal-F the first week and then from day 8 onwards adding the Pergoveris, so switching to Pergoveris, so that you add that LH activity which is that extra hormone that might just give the eggs that extra boost to become more competent and more mature. This is called a sequential protocol, so it’s a combination of the two drugs. These are different drugs, so I wouldn’t say that Pergoveris is better than Gonal-F, I would say that they are different, and it can be used either as an alternative from the very beginning of the stimulation or in an addition to the Gonal-F in the sequential protocol.
Sometimes, we withdraw the FSH injections, so the stimulation drugs even for more than 18 hours, even for 2 or 3 days if there is a high risk of hyperstimulation sometimes, we do something called casting, which means withdrawal of the FSH until the trigger is done, and normally, it’s to allow the reduction of the hormone level to a safe level so that the risk of hyperstimulation is reduced. However, I have to say that recently the new protocols with the antagonist have the possibility of using a trigger shot, which is the agonist. By giving that, we reduce the risk of hyperstimulation quite dramatically, so that’s a rescue way. It depends on which protocol has been used, in this case. If it is a long protocol, sometimes the FSH has to be stopped because if the risk of hyperextension is too high, then that is the only option to reduce the exposure to the estrogens. Sometimes, we also don’t give the stimulation in a short protocol, it depends on each case, but perhaps the follicles were already quite big, and they didn’t want to grow them too much, so that is when you don’t take the FSH injection and take the suprecur or the drugs to stop you from ovulating and then have the trigger shot.
If two cycles are fresh, so you’re going to stimulate the ovaries again. Then we usually recommend having a couple of periods to give the time to the body to reset a little bit, and then you can start again. If you had a fresh cycle, and then if you have some frozen embryos, you can go back even the following month. Between 2 frozen cycles, there is no need to wait. When we’re talking about frozen cycles, you can go for one after the other, but some cycles are quite intense emotionally, as well. Not just for the woman, but also the partner. Sometimes, it’s better to have a bit of a break, but it is very much depending on how you feel. A couple of periods should be enough.