Embryo transfer - how to prepare
Patients going for IVF would do as much they can to increase their chances of getting pregnant. However, is it at all possible to improve assisted reproductive techniques results? In this webinar, dr Magdalena Golańska-Wróblewska and dr Bogna Sobkiewicz from Polish IVF clinic Salve Medica prove that it is!
According to dr Magdalena Golańska-Wróblewska, leading a healthy lifestyle and avoiding extremes, both in a physical and chemical sense, may significantly increase IVF success rates. Moreover, there are additional aids available that have a positive effect on embryo implantation success. These are e.g. all sorts of drugs modulating the immune response or preventing uterine contractions. Last but not least, the way a patient behaves and is taken care of after the transfer is also very important.
Lifestyle does matter
In fact, a patient’s chances for pregnancy may be affected by a number of factors, both internal or external. These include age, diet, lack of exercise, drinking alcohol, smoking or taking drugs. There are also the so-called occupational factors, such as excessive physical exertion, shift work (where night shifts may affect one’s cardiovascular system and cause hormone secretion disorders) and exposure to chemical or biological agents. Operations that a patient has undergone can also have an impact – especially when we talk about oncological treatment and the removal of ovaries or the fallopian tube.
When it comes to the most important factors influencing a woman’s infertility, age surely plays the most significant role. Dr Golańska-Wróblewska admits that in women, the age effect on fertility is more marked than in the case of men. However, the truth is that ovarian reserve decreases with age – it is manifested in a reduced pool of ovarian follicles. Moreover, when a woman ages, the number of mature oocytes decreases while the number of errors in cell divisions increases. The latter may influence the risk of genetic diseases (such as Down syndrome). The risk of other diseases (e,g, achondroplasia or Aper syndrome) increases, on the other hand, with the father’s age.
Dr Golańska-Wróblewska says that it is crucial to follow a balanced diet if you want to be successful in your IVF treatment. Whilst an elimination diet is not necessary, it is important to maintain proper body weight. High BMI not only reduces the chances of pregnancy but it also is a risk factor for adverse events during pregnancy. Besides, the higher the body weight, the greater the potential for vitamin D deficiency. And according to dr Golańska-Wróblewska, proper levels of vitamin D positively affect fertility – both in women and men. Another factor helpful in maintaining proper BMI (and thus, increasing the chances for successful IVF treatment) is frequent physical activity. Regular daily exercise (at least 30 minutes a day) reduces the risk of metabolic diseases and also helps in relieving stress which can be very beneficial in the process of infertility treatment.
While it is easy to change our diet and introduce more physical activity into our lives, it is not always possible to avoid occupational factors that have a lot of impact on our reproductive health. Although we all seem to know that exposure to ionising radiation can cause infertility (or even sterility), not all of us realise that contact with pesticides, high temperature or chemical factors may cause a decrease in the number, motility and percentage of normal sperm and as a result, negatively influence its fertilising capacity. Similarly harmful are drugs – it refers both to those used in treating oncological diseases or peptic ulcers and the antipsychotics and antidepressants prescribed by psychiatrists. In all of these cases, it is advisable to wait a few weeks after the drug therapy to undergo an IVF procedure.
Embryo transfer – a major determinant of IVF success
Leading a healthy lifestyle is one way to increase patients’ chances of getting pregnant. Fortunately, there are also some additional medical procedures that may turn out to be helpful in one’s fertility journey. One of them is scratching which has a proven positive effect on subsequent embryo implantation. And the latter is surely one of the most critical steps in determining the success of an IVF cycle.
Embryo transfer is a complex process, depending on many variables. Dr Bogna Sobkiewicz reminds us to always differentiate fresh embryo transfer from frozen embryo transfer. Both of them have their pros and cons. The frozen one is used when there is the risk of developing ovarian hyperstimulation syndrome, when doctors conduct pre-implantation genetic diagnosis and when late-follicular progesterone is elevated. What’s the most important, It can boast higher pregnancy rates. The fresh embryo transfer, on the other hand, is less extended in time but one always has to consider the so-called ‘embryo-endometrial asynchrony’ due to supraphysiological hormone levels after the necessary hormone stimulation.
When conducting IVF treatment, doctors always have to decide whether to use a patient’s natural cycle or hormone replacement treatment. Oestrogen supplementation surely helps to achieve endometrial proliferation and follicular growth suppression whilst by taking progesterone, it is easier to promote the final phase of endometrial preparation. In case of natural cycle, endometrial preparation is conducted by using only endogenous steroids (what excludes the risks of exogenous hormones) and the whole procedure requires no medical or pharmacological intervention, except for endocrine and ultrasound monitoring to schedule the transfer. And what’s interesting, when it comes to results, a recent multi-center study did not show any significant difference between the natural cycle and hormone replacement treatment in regards to live birth and clinical or ongoing pregnancy rates.
Improving implantation rates
One of the factors deciding of the success of the embryo transfer is the day it is conducted. Dr Sobkiewicz says that in Salva Medica clinic they suggest to perform it on day 5. Such a solution allows selecting more viable and stronger embryos that have demonstrated the potential to develop and differentiate. In fact, embryo selection is probably of the highest importance when it comes to improving the cycle implantation rates.
Another question to answer while preparing to embryo transfer is how many embryos to transfer. Data from various countries indicate a general tendency to transfer individual embryos to the uterine cavity – and in case of failure, repeat the whole procedure in the next cycle. This successfully excludes the risk of multiple pregnancy which may entail various complications.
There are of course other ways doctors can use to improve patient’s implantation rates. They can, for instance, introduce additional drugs (e.g. Intralipid, Atosiban, Accofil). As these are not routine procedures, there are always extra consultations needed to indicate the real benefit of their use. Other medications that doctors can make use of for patients’ benefit are folic acid, Heparin, Encorton and acetylsalicylic acid.
Assuming the embryo transfer was successful, there are various indications of how to behave afterwards in order to increase one’ own chances of pregnancy. Dr Sobkiewicz mentions the necessity to continue the use of medications (in some cases almost until the end of pregnancy), bed rest straight after the procedure and refrain from sexual intercourse until the first pregnancy test. A patient should always take exceptional care of their own emotional state, too. It is advisable to use stress relieving techniques, maintain one’s own social life at its current level and focus on other aspects of life (such as job, friends, hobbies, etc.) to avoid constant uncertainty and depressive thoughts. Differentiating between anxiety and depression is also highly important as each requires different psychosocial interventions, including consultations with specialists.
The presentation and answers to all the questions from attendees were given by experts:
Dr Magdalena Golańska-Wróblewska – MD, graduated from the medical department at Medical University of Lodz, in 2010. Finishing PhD studies in Endocrinology Clinic in Medical University in Łódź. Her attention is focused on diagnosis and treatment of infertility, endocrinology, gynaecological procedures, ultrasonography.
Dr Bogna Sobkiewicz – MD, graduated from the medical department at Medical University of Lodz, in 2013. Finishing the specialisation of gynaecology and obstetrics. Her attention is focused on endoscopy, small procedures and counselling.
Questions and Answers from the event
Can holding an iPad by your stomach after the embryo transfer affect the success of the transfer?
There is no such study. However, we recommend our patients not to take any cell phones or other mobile devices into the room during the embryo transfer. But afterwards, patients do use their cell phones to e.g. relax or just to have some fun during bed rest. We also don’t have our phones with us as we’re afraid of some interference.
Why is the pregnancy rate higher for frozen embryo transfer than fresh embryo transfer?
I think you mean drugs we use during the procedure. We use Heparin and acetylsalicylic acid very often and there are no side effects. Besides, these drugs vanish from the blood very quickly so they cause no problems. We stop to take some of them on the 44th day of gestation. We also stop giving Acofil earlier so you do not have to wait until your system will be cleaned.
Can you give me any advice on what to eat before in-vitro?
You should be on a normal diet, without any restrictions. You just should take Omega 3 and anti-inflammatory supplements. We are not dieticians so we’re not the best persons to be asked that question. However, you should surely eat a lot of vegetables and fruit, whole grain bread, maybe less meat. In other words, you should eat according to the food pyramid and avoid fast food.
How much effect can age have? Is late forties too late?
It depends on your ovarian reserve and the quality of eggs. As I said before, the biological age does not correspond to one’s metrical age. So it may not be too late. It depends on your ovarian reserve and the response of ovaries to the stimulation. Of course, it is sure that late forties are not like early twenties. At the age of 45, the quality of oocytes diminishes. But we can never say that late forties do not allow us to have children from own oocytes. However, the chances are decreased for sure. But if we do not have our own eggs in the late forties, we can use donated eggs and undergo the whole procedure. Sometimes we even recommend using donor eggs because in the early 40s we do not have enough time to wait and be stimulated many times. The time is running very fast then so we recommend going for donors as that procedure will surely have higher success rates. It is especially important to us because in Poland the maximum woman’s age for IVF treatment is 49.
Is it possible to have an embryo transfer with my partner? I mean: can the partner be present during the procedure at your clinic in the theatre?
No, we do not allow anyone to enter the theatre. We are very strict in terms of hygiene and the environment in our theatre. We have special ways to keep it very clean to create the best environment for our embryos. We try to do it as quickly as possible because we know that the more time passes before we put embryos in the uterus, the more harmful it is to them. So we are very focused on the procedure, we do not talk during it. We also ask our patient not to talk or laugh or move her stomach because it makes it more difficult for us to put the catheter into the uterus. Time is important to us as we always want to achieve success. That is why we do not allow the partner into the theatre. However, afterward when our patient is lying down and resting, her partner can join them.
Regarding the scratching – is that done in the cycle before the transfer? If the transfer fails, would the scratching be repeated?
Yes, the scratching is performed during the cycle before the transfer. Of course if the transfer fails, the scratching is going to be repeated. The scratching increases the rates of embryo implantation so we need to repeat it before the next transfer. We also recommend it because usually the fact that it is the second transfer means we should put more effort to be successful. We want to do as much as we can.
I understood scratching can help pregnancy. When the scratching needs to be done? During the embryo transfer cycle or before the transfer cycle?
Always before the transfer cycle. Otherwise, it doesn’t make any sense. It has to be done in the cycle before. And yes, it really helps.
What percentage of transfers are successful first time?
I’m sorry but we do not have any such data. We always count it as the whole procedure, we do not divide it into first, second or third transfer.
I have adenomyosis, fibroids and endometriosis. Please advise what is the best IVF protocol, i.e. natural, mild or long antagonist. Do I need to have any pre- or post-treatment before the IVF cycle to increase success rates?
It is difficult to answer this question as we need more information on your medical history. What kind of treatment did you undergo? Was there any procedure at all? Was it successful? It would be better for us to contact privately or meet for the consultation.
Does it make sense to make a double embryo transfer after a failed single embryo transfer?
It depends on embryo quality and your age. If you are less than 35-38 years old, we do not recommend a double embryo transfer after a failed single embryo transfer. But in case you’re older and you’ve already had more than one failed single embryo transfer, then we recommend to have a double embryo transfer because it’s more successful. However, you have to be aware that there is a higher risk of multiple gestation. A multiple pregnancy is always more complicated and the risk of other complications is much higher, too. So we can recommend it but the final decision always belongs to the patient.
Which protocol/procedure prior to the transfer do you recommend for patients with an autoimmune diseases such as Hashimoto?
First of all, you have to see your endocrinologist who will give you medicines for your disease. Then we can start stimulation with the standard procedure. This does not require a special protocol. Sometimes when the hormone levels are ok but you have an autoimmune disease, we recommend to have small doses of L-thyroxine.
Is there anything I can do to help thicken the lining of my uterus so it is ready for the embryo transfer?
Yes, we use oestrogen to thicken the endometrium. However, some patients still have problems with endometrium so we use other drugs like Sildenafil or Pentoxifylline. We also use platelet-rich plasma which is a new procedure. At the moment you won’t find much data about it on Internet but it’s changing. We use it because the results encourage us to perform this procedure. It’s something new and there’s not much information about it so far. We are waiting for other clinics to share their experience in this area as well. The problem with endometrium thickness is not easy to solve because some patients do not react to our drugs. Generally, in our medical world the endometrium problem is the most difficult one to solve at the moment. It especially refers to women who have undergone some endometrial procedures like e.g. abortion.
What day of the cycle do you perform the scratching?
We do it usually between the18th and the 22nd day of the cycle. It is performed in the mid-luteal phase of the cycle before the transfer.
What are the risks of a double embryo transfer for the mother?
There is a risk of multiple gestation and everything that it involves, like pre-term birth, babies’ low birth weight, some complications such as hypertension, diabetes, anaemia connected with pregnancy and many more. These are normal multiple gestation risks.
Is it recommended to rest 2 to 3 days prior to flying back home?/Can a high number of flights and exhausting traveling impact pregnancy success?
I would suggest to stay 2 to 3 days after the embryo transfer. Generally, everything what is exhausting and stressful for the whole body will be harmful to the success of IVF treatment. We do not recommend to stay at home but we also do not recommend to overstrain your organism.
Would you recommend to proceed for IMap and ERMAP as well as Th1 and Th2 analysis in case of anomalies in a total cell population (e.g NK’s) and intake of Prednisolone before embryo transfer?
Usually our immunologist gives the indication of doing these lab tests. The use of steroid drugs is for us also an immunologist’s indication. We are gynaecologists and we have our specialists in immunology that take care of a patient’s immunological state. We operate together to adjust the best treatment.
What about hormones after the transfer (Utrogestan and Progynova)? How long should I take them during the pregnancy: till the 8th or 12th week of pregnancy?
You should take oestrogen (Progynova) till the 8th week of pregnancy and progesterone (Utrogestan) till the 12th week of pregnancy because you have to wait for the hormone shift, for the placenta to be done. The placenta starts to produce steroid hormones and when it’s done, you can stop taking Utrogestan.
What is the IVF stimulation drug for patients with endometriosis and adenomyosis? Will the drugs cause the condition to get worse?
It depends on a patient’s situation and the stage of endometriosis. The answer is not so simple because we do not have enough data to make a decision about the protocol which can be used in such a situation. But I do not think that drugs cause the condition to get worse.
What is the best day for the embryo transfer? Day 21 or day 19 of the menstrual cycle?
It depends if it is a natural cycle or hormone replacement treatment. It depends on when you start to take progesterone and how old the embryo is. If it is day 3 or day 5 embryo. The thickness of endometrium also plays an important role here.
I have 3 frozen embryos: one day 5 (2AB) and two day 6 (4BA). Which embryo do you think would have the best chance of implanting?
I suppose that the first one but I’m not an embryologist so I am not able to give you the right answer. Embryologists have much more experience with embryo quality. We always consult them when we have problems or hesitations. Together we choose the best solution for our patients.
Would you be able to tell what to do if you are a poor responder to medication during stimulation?
It depends on your age, AMH level, if you’ve had earlier procedures or not. It is difficult to answer such a question not knowing everything about the patient.
How to prepare ourselves for the day of the transfer? What is expected during the transfer?
The most important for the patient is to be relaxed. When the patient is stressed, it is always difficult to cooperate. It is also important to have a full bladder because it is much easier to put a catheter into the uterus. When it goes smoothly, it is also less stressful for us. We always try to do it as well as we can. The patient can eat before the transfer, there is no need to be fasting. In fact, there is no special preparation needed. It is enough to be relaxed and open-minded and have a positive attitude.
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