When did our most challenging cases get a happy end?
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IVF Success Stories with a Happy End

It was once said that challenges are meant to be met and overcome and this holds true for modern medicine pretty well. In the field of reproductive medicine it is no different.

Dr Stavros Natsis, Head fertility specialist at Gennima IVF, during this #IVFWEBINARS, talks about some cases which seemed to be pretty obvious from the beginning but turned out to be complete miracles. He starts with an uplifting message: never lose your hope and remember that there is always some light at the end of the tunnel.

Couple (39 years old), 8 years of natural pregnancy attempts, 5 miscarriages

The first case Dr Natsis talks about is a young couple (both 39 years old) who experienced 8 years of natural pregnancy attempts that resulted in 5 miscarriages (with no heartbeat detected at – usually – 6 weeks of pregnancy). Their karyotype test results were completely normal. The main problem was the fact that the woman had a condition called complete bicornuate uterus which was detected in 2013. It is a type of uterine duplication anomaly which is characterised by the presence of the septum starting from the fundus of the uterus and reaching up to the cervix. Although the patient had 3 attempts of hysteroscopy to dissect it, none of them was successful. This was one of the reasons why the embryos did not implant – there was not a healthy area for the placentation. Additionally, the patient had low levels of both AMH and FSH.

IVF – real patients stories

Based on the patient’s medical history, doctors at Gennima IVF decided that a metroplasty with hysteroscopy was needed again in order to make sure that the uterine septum would go away. After the dissection of the septum, they wanted to let the patient try for another six months – but not more than that, due to the low AMH levels.

Dr Natsis recalled that in March 2018, the patient underwent the first hysteroscopy (metroplasty) at Gennima IVF and during that procedure, the doctors dissected approximately 70% of the septum. Then in August 2018, the second and final hysteroscopy followed – together with a biopsy of the lining of the womb. The sample was sent to the French lab that Gennima IVF collaborates with, in order to assess the immune system of the endometrium and to decide what sort of medication should be given to support the pregnancy.

Following the second hysteroscopy, the patient had a natural conception 3 months later. The pregnancy was closely monitored. The doctors advised the couple to perform a cervical cerclage during the 14th week of the pregnancy. Because of multiple surgeries the patient had undergone, they were afraid that the cervix would be incompetent. Finally, after an uneventful pregnancy, a patient delivered a healthy baby girl. Such a successful ending made the whole Gennima IVF medical team very happy!

Recurrent IVF failures, multiple miscarriages and very low ovarian reserve

The second couple that Dr Natsis analyses in his webinar is an example of recurrent IVF failures, multiple miscarriages and very low ovarian reserve. When they first came to the Gennima IVF clinic, they were 41 years old and had a 3-year history of pregnancy attempts . The woman’s AMH was very low – approximately 0.3 ng. She had IVF short protocol performed three times – she had 2 modified natural cycles with the fertility drug Clomid as well as 10 natural cycles with no medication at all. The results were: 1 miscarriage at the 8th week of pregnancy (although the baby’s karyotype was tested and classified as a normal one) and 3 biochemical pregnancies. A thorough medical screening that a patient was subjected to, revealed that she had a Von Willebrand disease. It’s a condition that impairs the blood clot and puts a patient at an increased risk of bleeding. However, the screening did not reveal any abnormal level of NK cells nor any significant pathology of the endometrium.

During a medical review, the doctors at Gennima IVF found out that the fundus of the uterus had a mild septum. This – in their opinion – could cause some difficulty in the embryo implantation. The treatment plan included a hysteroscopy with creating implantation cuts that would be immediately followed with an IVF treatment. Because of the patient’s age and her low AMH level, there was not much time to wait for a natural conception. There was also the possibility of the endometrium biopsy taken into account – in order to determine the immunology profile and the post-implantation treatment.

In January 2019, the patient underwent the hysteroscopy during which the small septum was dissected and the implantation cuts were created. There was also a biopsy performed and the sample was sent to the lab in France (as in the previous case study). The biopsy result showed abnormal uterine cytokine equilibrium as well as increased uterine Natural Killers. It is important to mention here that the patient had had an evaluation of peripheral blood NK cells done in one of the previous clinics – which turned out to be normal. According to Dr Natsis, it only proves that this kind of test – although vastly popular – does not have any clinical significance.

Based on the biopsy results, the doctors created the post-implantation treatment protocol for the patient. In February 2019, the patient underwent a modified natural cycle with Clomid – especially helpful in case of patients with low ovarian reserve. 2 eggs were collected and fertilised and one good quality day 3 embryo was transferred. The pregnancy test was positive. Again, the doctors performed a cervical cerclage in the 14th week of the gestation.

Dr Natsis says that the patient could not believe she was pregnant and consequently needed a lot of psychological support. Finally, she delivered a healthy baby boy at 39 weeks of pregnancy through a C-section.

Woman 37, 30 IVF attempts during 8 years

The third case Dr Natsis discusses is extraordinary. The couple he treated had experienced approximately 30 IVF attempts – the largest number they have ever had at Gennima IVF clinic! When Dr Natsis met them, they were only 37 years old and already had 8-year experience of IVF attempts. The female patient underwent 6 IVF cycles with short protocol and 25 natural cycles – and the only result was one miscarriage in the 9th week of pregnancy and 2 biochemical pregnancies (!).

The review of medical notes revealed that the patient had two surgeries for possible endometriosis (laparoscopic surgery) as well as double hysteroscopy – in order to deal with her polyps and endometrial adhesions. She also had low ovarian reserve. Another issue the doctors had to help with was the unsatisfying result of the male partner’s sperm analysis, meaning both low count and low motility. Additionally, just like the previous two case studies the hysteroscopy conducted at Gennima IVF revealed the presence of a small septum.

Due to the 30 unsuccessful IVF attempts, the doctors assumed the patient had a very serious problem with the quality of her eggs and they suggested egg donation. However, the patient opted for the last final attempt with her own eggs – and the doctors agreed with her wish.

In November 2014, a hysteroscopy was conducted and during that procedure the uterine septum and adhesions were dissected. Three months later, the doctors collected 3 eggs during the short IVF protocol and 2 out of those 3 eggs were fertilised with ICSI. On day 3, two good quality embryos were transferred and the woman became pregnant. Similarly to the previously mentioned patient, she needed a lot of psychological support during her pregnancy as she could not believe she was pregnant. In December 2015, she gave birth to a healthy baby boy.

Woman 44 years old – 7 years of IVF attempts

This case perfectly shows that women who have multiple medical conditions can become pregnant if they get right treatment. Dr Natsis recalls that the patient was 44 years old (with 7 years of attempts) when she came to Gennima IVF clinic for the first time. In her history, she had one natural conception but the pregnancy had to be terminated – the child had a genetic syndrome which was picked up in a nuchal translucency scan. Additionally, the woman’s BMI was 37 at that time, she suffered from hypertension and diabetes and she had undergone 2 strokes. Her history of pregnancy attempts included clomiphene stimulations and IVF-ICSI. She also had a hysteroscopy with polyps removal performed and her partner suffered from obstructive azoospermia. While reviewing the patient’s hysteroscopy DVD, Dr Natsis and his colleagues found a small septum in the uterus, too.

The doctors’ plan was to assure the perfect state of the womb lining in order for it to accept the embryos. Firstly, they asked the patient to adopt a more healthy lifestyle and lose weight. Secondly, the woman was reviewed by a cardiologist, endocrinologist and neurologist to make sure that she would go through pregnancy without problems. The patient decided on egg donation.

The doctors performed a hysteroscopy to dissect the uterine septum in March 2018 and six months later (in September 2018), the perfect phenotypically matched donor was found. The donor produced sufficient number of eggs in the second cycle and 4 of them were fertilised with the sperm of the woman’s partner – through the use of ICSI. The embryos were cultured until day 5 in a modern incubator called Embryoscope+, allowing for non-invasive prenatal screening and helping to choose the embryos with the best chances of success. Two embryos were transferred and the woman got pregnant successfully. After a closely monitored but uncomplicated pregnancy, she delivered a completely healthy baby girl and now she is considering a second child.

27-year old girl, 50-year old partner with azoospermia

The last case that Dr Natsis deals with involves severe male infertility. The couple that came to Gennima IVF clinic was a 27-year old girl and a 50-year old man who suffered from azoospermia – the condition in which a man does not produce any spermatozoa in his semen. When discussing the treatment plan with the couple, the doctors suggested a series of sperm analysis. The intention was the following: if during such a screening some spermatozoa were identified, they would be cryopreserved for later use. If no sperm was to be identified, the doctors would decide to do a testicular biopsy.

The sperm analysis conducted in February 2018 showed 5 healthy and moving spermatozoa – the specimen was cryopreserved. The sperm analysis was repeated a month later and then 8 more spermatozoa was found and cryopreserved as well. Dr Natsis notes here that during both tests, the embryologists had to process each sample for unbelievably long time – 12 hours! However, thanks to their effort, the man was spared an uncomfortable and painful testicular biopsy.

After the sperm was secured, the woman underwent the so-called ‘short protocol’ and 7 eggs were collected. One of them was fertilised through ICSI with thawed specimen and after 3 days, one good quality embryo was transferred. Again, the pregnancy was classified as uncomplicated and it finished with the delivery of a healthy baby boy.

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Conclusion

Summing up, Dr Stavros Natsis addresses all the couples who are now in the middle of IVF treatments – especially those experiencing multiple failures. Firstly, they should never lose their hope and never give up looking for possible solutions. In case of repeated failures, it’s advisable to search for a new clinic that may look at their medical history from the ‘fresh’ perspective. At most clinics, multidisciplinary meetings are held during which many fertility experts meet and try to tailor the clinic services to the patients’ needs. Dr Natsis also believes in the use of the latest technologies, like e.g. EmbryoScope+, and the fertility education of the patients. The latter is helpful in making them understand what is needed and necessary to be done. The cooperation between doctors and patients is crucial – it is much more valuable than just following the medical instructions blindly.

Dr Stavros Natsis finishes with a great quote by Nelson Mandela:

It always seems impossible… until it’s done. A perfect message and an ideal beacon of light in the darkness – for all those facing fertility issues every day.

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Questions and Answers from the event

In patient 2, how was the medication modified based on the result showing elevated NK cells?

Actually this new biopsy that we perform it gives us an idea of what is the immune profile of the uterus. Does it have lower activation when the baby goes inside or does it have overactivation when the baby goes inside? When the Natural Killers actually level is higher than the desired one, they can become quite aggressive towards the embryo. In that case, patients usually would have to take steroids, possibly 20 milligrams of Cortisone, up to the 12th week of pregnancy. There is a group of patients that has to take another form of immunosuppressant drugs called intralipids. These are medications that we usually give a few days prior or the embryo transfer. They can help with the immunosuppression locally in the uterus. This kind of medication needs to be repeated in the first week after the embryo transfer and two weeks later. There was a very good study that done in in France where they tested approximately 400 women who had multiple IVF failures and miscarriages. They found out that almost 340 of those women had problems with the immune profile of the uterus. It’s something that we also strongly believe in because not every patient had the same reason for a miscarriage. Every patient is different and I believe it’s something that other clinics could consider doing as well.

After multiple missed miscarriages at approximately 8 to 10 weeks, would you suspect immune issues as the cause of these miscarriages?

Yes, we would definitely suspect immune issues. Of course it would be better if I had a little more information regarding the patient’s age and the previous surgical history. But just for you to know – 70% of miscarriages are caused by an embryo that doesn’t have the right chromosomes. The reason of 25 % of miscarriages is usually the receptivity of the uterus and this is where we can actually intervene. 5% is thrombophilia and other more rare conditions. So if you had multiple miscarriages at 8 to 10 weeks of pregnancy, I don’t believe that all of those had to do with karyotype issues of the embryos. The doctors should definitely look more into the receptivity of the uterus. There are many tests that you could perform. If you need a more detailed information, I would be happy to answer in an email.

What kind of criteria are you looking for in case of an egg donor?

Our first aim is to make a very good phenotype matching for the patient. When we say phenotype, we mean that the donor and the recipient have a lot of similar characteristics like the hair colour, the smile, the eyes, height, BMI (body mass index), etc. Actually, we try to find almost an identical twin. After we find the person that looks like the recipient, we have to do a lot of screening to make sure that the donor does not have any chromosomal problems and genetic conditions like cystic fibrosis, thalassemia, etc. We also do screening for for sexually transmitted diseases like hepatitis, syphilis, AIDS. We take a very thorough medical history to make sure that they don’t have any genetic conditions or history of psychiatric disorders. Once we tick all these boxes, we feel that we have found a good donor. Of course she needs to be young – up to the age of 30-35 the most. In case of a 22-year old girl, 1 egg out of 4 is healthy so we try to find young girls and collect as many eggs as we can. So these are some of our criteria.

How long must you wait after CS (cesarean section) before trying for second child?

We believe that 9 months should be the minimum. The uterus needs to heal because when you do a C-section there is some scar tissue formation. Our biggest worry is that if a woman becomes pregnant earlier, the scar tissue will open as the uterus distends. So usually we would suggest 9 months as the smallest time interval for someone before going ahead for another pregnancy.

Is there anything one can do about improving sperm results (like motility, etc.)?

Over the last few months there is a lot of discussion here about a new test called sperm oxidative stress. It’s actually a sperm analysis that can measure oxygen free radicals that live in the male sperm. If these free radicals are above a certain level, they become they can become poisonous and actually destroy the genetic material that the sperm is carrying. In our clinic we do that test quite a lot and if we find that this level is elevated, we usually give a combination of antioxidative vitamins, like e.g. vitamin E or zinc. This can play a crucial role in the improvement of the quality sperm. But we have to remember that taking vitamins without knowing if you have elevated oxidative stress can give the opposite effect. It can cause some problems in the sperm and it can make it worse actually. So we would advise you to do the more detailed sperm analysis and if there are signs of elevated oxidative stress, then you can take some vitamins. But if no, then we wouldn’t recommend that.

I want to have IVF treatment but I must have a baby letter from a baby doctor in the UK. Is there any clinic aboard that could do the test and scan together before the treatment? Would your clinic do this for me? I’m 53 years old in December and I want twin babies. How much does this cost in your clinic?

The European law says that we cannot perform any IVF treatment here in Greece if a woman is above the age of 50. This is a European regulation and it’s very strict. There are some places where they could help you, like e.g. clinics in Russia or North Cyprus. But unfortunately, it is not at our clinic as we have to follow the European rules. There is some discussion here in Greece about increasing the age limit to 52 or 53 years – but it’s still just a discussion. So, unfortunately, we wouldn’t be able to help you. Maybe you could do some research on the internet and look for clinics in other countries.

Does viagra help in growing the endometrium lining after the start of progesterone?

Yes, viagra can actually help because it can stimulate locally the blood supply. When you are going to transfer thawed embryos in women whose lining is not growing well, then you add some viagra. But after you start progesterone, then there is a very little effect of viagra. So usually it is given it before you start progesterone. Progesterone is generally administered once the lining of the home has reached the level of 8-9 millimetres. So the answer is: yes, it helps but not after you start progesterone. We would give it prior to progesterone.

What is the cut-off age for an egg donation patient?

In Greece, you can do the embryo transfer one day before the patient becomes 50 years old. I think in other parts of Europe it is 45 years of age. Outside the European Union, there are clinics that accept patients who are 50-53 years old. But in Europe, the cut-off age is 50 years old.

We transferred 2 5AA embryos on 11/14, but our HCG seems at lower end – around 90 (11 dpt, 5 dt). Do you have any suggestions for a successful pregnancy going forward?

I hope that your beta HCG will rise. I don’t know whether the embryos you transferred were thawed embryos or fresh cycle embryos. In the thawed embryos, beta HCG usually starts lower and I’m sure it will pick up later. Or maybe beta HCG starts very low because you had the pre-genetic screening when they took some cells from the embryos. I don’t have full information here. But if we assume that it’s a normal cycle and you just transferred two embryos with low beta HCG, unfortunately, there’s not much to do now – apart from adding some progesterone to help with the implantation. If this doesn’t go well, in that case, there are a few blood tests that you can perform to check the immune activation of your body, thrombophilia or the condition called anntiphospholipid syndrome. Sometimes you can treat those with some blood thinner injections or Aspirin, but only after you get confirmation that this medication would be helpful. So we keep our fingers crossed and maybe your beta HCG will pick up later, which is something that we have seen quite often.

What do you think would be the success rate of an euploid 5 days blastocyst 4BB? Would it be the same if the euploid blastocyst 5AB was day 6?

The first thing that I don’t know is the age of the person that produced the blastocyst. The success rate of the embryo depends a lot on the age of the woman who produced the embryo. If we had the 4BB blastocyst and the patient was 32 years old, I would tell you that we had a 40-50% chance of success. But if the patient has a 4BB blastocyst and she is 42 years old, then the success rate drops to 20%. When we have a day 6 euploid blastocyst, usually the success rate is lower. If it takes the embryo 6 days to reach the stage of blastocyst (instead of 5 days), it means that the baby is very slow in its development. So we wouldn’t have a lot of hope for the day 6 blastocysts – even if they look good. They don’t usually have the same success rate as day 5 blastocysts.

I have been trying for 5 years, I have had 2 failed IUI’s and 1 failed IVF with egg donation in October. So I needed this presentation to give me some more hope – which it did.

Well, definitely my advice is don’t stop believing in yourself and don’t stop trying – and you will succeed. The only person that doesn’t succeed is the one that he doesn’t try. Don’t give up your hope.

Is a biochemical pregnancy loss a concern if it happened to a young 22-year old lady one year after she delivered a healthy baby? What is your recommendation?

A biochemical pregnancy wouldn’t concern me a lot. It’s something very very common and the majority of the women will have a biochemical pregnancy during their life. They will just never find out about it. The guidelines usually recommend doing some additional tests if you had three biochemical pregnancies or more. I don’t think you should do anything more about that – unless, of course, there is a second one. In that case, some clinics can recommend doing some blood tests and some screening. The only thing I don’t know is whether the lady delivered a baby through normal delivery or a cesarean section. C-sections can sometimes cause some problems but I think it’s a very rare condition. So I would just wait and see if that happens again.

What are some of the tests to check the receptivity of the endometrium for implantation?

There are multiple tests available to test the receptivity of the endometrium. In our clinic, we perform some blood tests and we try to see whether they are positive and you have some of the antibodies, like e.g. the lupus antibody. It’s a condition that could show some autoimmunity which suggests that your body can become a little more aggressive towards an embryo. Apart from that, we have much more detailed tests, like the hysteroscopy. It is a very good test because you can actually see the lining of the womb and check whether there is a small septum or small polyps that could impair the implantation. Of course, there are also some more difficult tests to perform, like the one that we send to France. In this test, you need to take a biopsy from the lining of the womb during the implantation window. The implantation window is actually only four days during your cycle. And then we send the sample to France. We also test the uterine Natural Killers and some other elements that are called cytokines – they help with the implantation and the formation of blood vessels for the embryo. Additionally, there is the ERA test which helps to identify the ideal implantation window when your endometrium is more receptive. So we have quite a lot of tests. I would suggest starting with something mild (like the blood test to check for autoimmune antibodies) and if the results are positive, proceed with other tests.

My husband has a sperm sample from 2007 from Sydney Australia that we want to use with our last 11th IVF attempt. Has sperm freezing changed over the years? I think it was the so-called ‘slow freezing’. From what I understand, vitrification of sperm is not done? Has the vitrification of eggs and embryos changed as the norm now?

Yes, actually since 2007 we have had a lot of changes in the vitrification of sperm and eggs. For the last 5 years, we have been using a new technique that helps to freeze eggs or sperm quite quickly to avoid losses during the procedure. If there is a chance, maybe you should try and use some fresh sperm of your husband. If not, then I would go with your frozen sperm sample and I’m sure that you will have some good results, too.

My husband is 54 years old and I don’t want any autism or dwarfism from an older guy – if we use his current sperm rather than his frozen sperm from 2007. What do you think of a fresh sample from an older man? As there are no tests to be done on sperm for autism/dwarfism etc., I don’t want to waste any good donor eggs.

I understand your way of thinking. It has been heard that the age of the father is somehow co-related with autism. I have to tell you that there is no study that has confirmed that. What we would do in our clinic is to use the sperm that you had in 2007 – if this sperm looks good of course. But we would definitely compare his fresh sperm with a frozen sample and see which one has better characteristics. You have to bear in mind that men produce new sperm every three months. So I’m not sure that the sperm that your husband produces now could cause autism. It’s something that it has not been proven. We would just try to see which of the two samples is better in terms of motility, oxidative stress, numbers, etc. We would choose the one that looks better to make sure that it will do the fertilisation. I wouldn’t be worried about autism and all the other things.

Who do you advise PGS testing for? Is it for all patients?

No, in our clinic we don’t routinely recommend pre-implantation genetic screening (PGS). For those of you who do not know what PGS is: we take some cells from the embryos that we have created in the lab and we test them for chromosome abnormalities. It’s a procedure that we would recommend to a couple only if they had some issues with their karyotypes. Many people don’t know that they have a condition called mosaicism. Let’s say there are people who have 95% of normal cells and 5% of cells with e.g. Down syndrome. This sort of couples would benefit from pre-implantation genetic screening. Other couples that would benefit from PGS are the ones who have some genetic conditions, like cystic fibrosis, and they don’t want to pass it to their child. There is also another case when we would recommend PGS – when we have a young 30-35-year old patient, we have transferred many blastocysts and none of those blastocysts have resulted in a pregnancy. In such a case we suspect strongly that most of the embryos have genetic abnormalities and it is advisable to proceed with pre-implantation genetic screening. But you have to bear in mind that it’s almost like a surgical procedure to the embryos. If you have a healthy embryo, you can actually delay it its development – so you should be very careful when you choose a patient for PGS. I know that in the United States they do that quite a lot – however, it is not the kind of practice that we would strongly recommend for every couple.

What are the chances of getting sperm on TESE for a man with azoospermia, chromosome microdeletion with no AZFa, AZFb and AZFc? All other blood tests are normal.

Actually, the chances are quite high. We perform a clinical examination and we try to check the epididymis which is actually like a reservoir for the sperm. If we can feel that the epididymis is full of sperm, we go ahead with TESE procedure. The procedure is about putting a needle there and trying to take some sperm from this storage. If this is not successful, then we try again with a larger needle and we take tissue from the testicles. Usually, the embryologist will find sperm there. It’s highly unlikely to proceed with the normal biopsy where you have to dissect and cut the testis. Usually, in almost 70-80 % of cases, we can take out sperm samples with these two needle techniques.

I have hypothyroidism, which was caused by ROI for hyperthyroidism and now caused problems to my fertility. I had an IVF but I couldn’t proceed because 3 oocytes that responded were ovarian cysts. Is there anything you can suggest because I really want to use my eggs? I have low ovarian reserve, low AMH and slightly higher FSH.

Definitely you shouldn’t stop trying and shouldn’t be discouraged – this is the first piece of advice. Women who are younger than 42 years old and produce even one or two eggs, usually have good chances of success. In your case, we would suggest to start using some DHEA supplements. These supplements can stimulate the ovarian reserve and maybe boost your ovaries and give us some healthier eggs. We would also recommend you to start taking vitamin D and folic acid approximately two months before your next IVF attempt. Definitely we would recommend to do an IVF attempt with very mild stimulation, maybe you could use Clomid. Giving you high doses of injections could have the the opposite effect and it could result in the formation of ovarian cysts.

Do you have sperm donors? If yes – where are they from?

Actually we do not have sperm donors in our clinic, we have only egg donors. But in Greece, there is a very good sperm bank that works under the European Union laws and does a very good job. 90% of the donors there are Greeks. We also know the international sperm bank Cryos that has an excellent reputation as well.

What is the possibility of carrying a pregnancy to term after an intramural myomectomy?

The intramural myomectomy doesn’t really affect the possibility of carrying a pregnancy to term. Of course, again it depends on how big the fibroid was. It depends on the way it was taken out – was it with a laparoscopy or with open surgery? Of course, we are a little scared of the scar tissue that it’s formed when you take out the fibroid. But in general, you can carry on with your pregnancy at least up to 37th or 38th week. The majority of women who underwent the intramural myomectomy deliver with a cesarean section at approximately 38th week of pregnancy. I wouldn’t really want you to deliver earlier just because you’ve had this sort of surgery. So I think that your chances of carrying a full-term pregnancy are quite high.

What’s the ideal time duration of taking estrogen and progesterone before the embryo transfer?

The ideal duration of estrogen supplementation is approximately 12 to 15 days. It is a hormone that helps to build up the lining of the womb. There are some women who respond quite quickly to it and on day 8 or 9 of the estrogen supplementation they develop the lining of 9 millimetres. But there are other women whose response is not that quick – they might develop this type of lining on day 15. Sometimes we give it up to 20 days until we build up the lining. In case of progesterone, the duration depends on the sort of embryos you have to transfer. If you have to transfer a blastocyst, then you have to take 5 days of progesterone. If you have to transfer day 1 or day 2 embryos, then you need to start taking progesterone for two days. So it depends on the age of the embryo.

We did a spermogram that was normal except a teratospermia (2%). Do you think it is necessary to perform the DNA degradation test? My partner is fertile and has already 6 healthy children naturally. We thought about egg donation because of my age (AMH = 2 pmol/l).

To be honest, 2% is quite common to see. It depends on the other sperm characteristics, so it’s either 2% of a sperm that has 100 million spermatozoa or it is 2% of a specimen that has 3 million spermatozoa. It is very different. The fact that your partner has already 6 healthy children suggests that probably shouldn’t do the DNA degradation test. It could only give some additional information to the embryologist and tell them which technique of fertilisation to use – will they simply use IVF or will they do a microinsemination? I wouldn’t be very stressed about that. It suggests that your partner’s sperm has a very good fertilising capability. AMH of only 2 pmol/l is very low but it definitely has to do with age. If you are, let’s say, 38, then no worries – many women achieved pregnancy with low AMH at that age. But if you are 44 or 45 – then yes, it’s quite difficult. If you want to have success, we would advise going ahead for egg donation which has 80% of the success rate. But I don’t know how old you are to tell you the statistics exactly.

Is hysterosalpingography indicated for IVF with oocytes donation?

If you have decided to go ahead with oocytes donation, we wouldn’t really recommend doing that test. It’s quite painful for some women. We only perform this test as a fertility screening to see whether a couple can continue having attempts or if there is a severe blockage in the tubes and the couple should go ahead to explore other options like IVF. If you have decided to go with oocyte donation, we wouldn’t advise you to do this sort of test as it would not add any more information.

Can DNA fragmentation or FISH test be done on frozen sperm as apparently nothing was done on my husband’s frozen sperm?

Yes, in our clinic we’ve performed that a lot of times. Sometimes the embryologists are stressed that the medium they used to keep the thawed sperm can alter some of the results. We feel that the FISH test or DNA fragmentation test could give some additional information and would dictate the best technique for fertilisation. So we would do it in our lab. I do not know how they feel about it in your lab but it surely could be done.

What do you think of a 49-year old woman with adenomyosis and on Warfarin because of recurrent pulmonary embolism?

Adenomyosis is something that definitely causes some difficulty in IVF. For the people that don’t know what adenomyosis is: it’s a condition when you have thicker walls of the womb. There are some studies suggesting that due to the adenomyosis, there is some difficulty in the implantation because of some biochemical changes in the lining of the womb. Usually doing a good hysteroscopy and creating implantation cuts can help a lot with the implantation. If you decide to go ahead with egg donation because of the age, I think it could be successful. Warfarin that you take for recurrent pulmonary embolism can be definitely changed into platinum injections that many women do. I don’t really know the reason why you have been having this recurring pulmonary embolism – if you have some cardiac arrhythmia or other reason. I think that your gynecologist could have a consultation with your cardiologist and I’m sure you could go ahead with that. I don’t think it would be something to stop you from being a mother.

I was diagnosed with serve endometriosis, I had two laproscopies and removed tubes. This has resulted in multi rounds of IVF with own eggs and 3 rounds with egg donation which resulted in two miscarriages. In the last cycle I had a biopsy for endometrium lining. Would you recommend any additional tests? I’m 34 and have two frozen donor eggs left.

To be honest, you’re very young. We wouldn’t go ahead with egg donation unless you are on menopause for some reason. In the case of a 34-year-old girl, usually, one in four eggs is excellent, has good chromosomes and can lead to a healthy pregnancy. I don’t know what the lining of the endometrium showed, I think it would be very important if you sent us the results. We will be very happy to review it. I think it was good that you did this sort of test. But I would definitely recommend a hysteroscopy with creating implantation cuts – and not just doing endometrial scratching. We would also recommend some mild curettage of the lining of the womb to help it regenerate. We have seen much better receptivity following a hysteroscopy. So I would recommend you to do a good hysteroscopy this month and the next month, if you feel ready, you could transfer the frozen eggs. I’m sure you would be very successful.

Some clinics offer a synchronisation of the donor cycle with that of the recipient. Other clinics prefer not to synchronise and transfer an embryo that is already frozen. My question: are the success rates the same with frozen embryos as with the fresh embryos ?

We are one of the clinics that we prefer to synchronise the donor cycle with the recipient cycle. That would be the ideal solution because we wouldn’t put the embryo in an additional procedure to cryopreserve it and then to unfreeze it and put it back into the uterus. If we could avoid an extra step, then we would definitely do that. But I have to tell you that the success rates are almost the same, strong embryos are not affected by the cryopreservation and this is something that many clinics do – especially if they have patients that travel from far away and they want to make sure that they have embryos to transfer. Sometimes the stimulation of the donor doesn’t go according to the plan and it would be a tragedy for you to travel for e.g. 6 hours, arrive at the clinic and learn that they don’t have an embryo to put back inside. So this is the reason why many clinics prefer first to create embryos and transfer them in a later cycle to avoid having unexpected failures. But generally, the success rates are about the same so don’t worry about that.

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Stavros Natsis, MD

Stavros Natsis, MD

Dr Stavros Natsis is a fertility expert at Gennima IVF since 2017 and an associate of Dr Mantoudis, head fertility expert at Gennima IVF. He is especially interested in fertility preservation. Author of several clinical research papers. He performs monitoring scans and egg retrievals. International patients will meet Dr Natsis for their free Skype meeting and again when they come to Athens for their treatment. Dr Natsis' professional experience starts with Degree in Medicine by the University of Ioannina, MSc in High Risk Pregnancy by the University of Athens. Specialty in Obstetrics by the University of Athens. Clinical Research Fellow at the University of Oxford (Fetal Maternity Unit Department of Obstetrics and Gynaecology – High Risk Pregnancy Unit). He is also UK-trained in Gynaecological Oncology and Fertility Preservation (Senior Fellow). A warm and caring doctor with a big smile on his face. Thorough and precise, hard-working and passionate when it comes to helping our patients become parents. Fluent in English, great in communication and happy to answer all your fertility questions.
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