When autoimmune disorder occurs, the body’s own immune system works against healthy cells. Unfortunately, women (and men!) with existing autoimmune conditions may be at a higher risk for infertility. Can anything be done about this problem?
From this webinar you will know:
- what to do in case of autoimmune disorder
- what tests should be done
- what are the chances of overcoming infertility issues with IVF
- what can be done to prevent a higher risk of miscarriage .
In this #IVFWEBINARS , dr. Emma María Adsuar, fertility gynaecologist from UR Vistahermosa (PreGen) in Alicante (Spain), is explaining whether the combination of an autoimmune diseases and infertility is a possible obstacle to overcome at all.
Explaining the problem
The first thing to understand is the definition of autoimmune disease. It is the disease that occurs when the immune system functions produce an erroneous attack against health cells and tissues of the patient, triggering an inflammatory and self-destructive response. In short, it means that our immune system simply does not recognise some parts of our body. Dr. Emma María Adsuar lists the most common autoimmune diseases, such as e.g. Addison’s disease, celiac disease, Hashimoto’s thyroiditis, Diabetes type I and Antiphospholipid Syndrome. Most of them occur when patients are in their mid 20s or mid 30s.
All these diseases are important regarding fertility as they may have some antibodies against ovaries and – as a result – provoke the so-called primary ovarian insufficiency, also known as premature ovarian failure. It means that woman’s ovaries contain only very few follicles. Premature ovarian failure affects 1 in 250 women below the age of 35 and 1 in 100 women over the age of 40 – and it is much more common in women suffering from one of autoimmune diseases.
Another way how autoimmune disease can affect women’s fertility is alteration in the hypothalamic-pituitary-gonadal (HPG) axis. Dr Adsuar explains that in order for the valuation to take place, the synchronisation between the hypothalamus, the pituitary gland (or hypophysis) and the ovary. If there is a blockage or any kind of impairment in any part of this axis, the dysfunction may occur in the ovary or – what is worse – the ovary may stop functioning. All of this happens more frequently with autoimmune diseases, too.
Autoimmune disease can also influence fertility through effects of medications on ovarian function. It happens so because these medications can alter DNA of the cells located in the ovary, provoking ovarian fibrosis and – as a result – causing a depletion of progesterone and estrogens. At this point, dr Adsuar reminds us that not only ovaries can be affected by autoimmune diseases – but the testicles as well. It is important to remember that autoimmune diseases can influence male fertility as well.
Preventing the problem
After making us familiar with all the adverse effects of autoimmune disease on fertility, dr. Emma María Adsuar goes on to the most important issue: the possible solutions. Fortunately, there are two ways to deal with the problem: to prevent it and/ or act on it. When it comes to preventing, the preservation of fertility may be the answer. When women are diagnosed with e.g. Hashimoto disease, a good idea is to freeze their eggs before starting the medication. The doctors usually try to hyper stimulate the ovary to collect as many eggs as possible. The eggs are then retrieved under anaesthesia and frozen using the vitrification method. Dr. Adsuar assures us that the eggs’ fertility rate is not being diminished no matter how long the storage is. When it comes to the vitrification, the survival rate of eggs is 85-90%. However, the doctor tells us that for a 50% chance of having a child, a 36-year old woman should freeze at least 10 eggs. 3 years later (at the age of 39), a woman would need to freeze 16 eggs.
When it comes to men affected by an autoimmune disease (that, for example, reduces the number of sperm produced), there is an option of a testicular biopsy. During the procedure, the sperm sample is taken from a testicle, frozen and stored (just like in case of eggs). The thawed sperm may be used afterwards when doing IVF.
Solving the problem with IVF
In case you did not think earlier of reserving your fertility, the problem can be acted upon by the use of fertility treatment. Dr. Adsuar says that if you’re less than 35 years old and your autoimmune disease is not severe, you may use the technique called intrauterine insemination (IUI). It involves injection of the partner’s washed sperm into the uterus with a catheter. For more advanced autoimmune diseases, IVF treatment is recommended. In case of the treatment with own eggs, the success rates depend on the patient’s age (if it is less than 35 years old or more). When it comes to egg donation, the latter makes no difference as donors as usually less than 30 years old.
Regardless of a fertility procedure chosen, the basic thing is to stabilise the disease before starting the treatment as the pregnancy success depends on it.
Supporting the treatment
Apart from fertility treatments, there are additional new techniques that may support pregnancy in patients with autoimmune diseases. Depending on the type of the disease the patient is developing, doctors may use anticoagulant therapy (which has been proved effective in people who have antiphospholipid syndrome), intralipds and corticosteroids. The latter act as a treatment for recurrent pregnancy loss. Dr. Adsuar admits that, apart from lower ovarian reserve and problems with getting pregnant, women with autoimmune diseases suffer from recurrent miscarriage more often than the rest of the population.
Anticoagulant therapy is usually started with low doses of Adiro (Aspirin) and followed with Heparin subcutaneous injections. Sometimes, in case of antiphospholipid syndrome, both medications are used at the same time. Dr Adsuar says it has been proved to diminish the probability of having clots, increase the uterine flow and enhance the embryo implantation.
Another type of treatment used for patients with autoimmune disease is the use of intralipids. Intralipids are nutritional supplements that contain purified soya oil that gives energy and essential fatty acids. This therapy is believed to stabilise cellular membranes and suppress the activity of natural killer cells that contribute to repeated implantation failure. Intralipids are administered intravenously in 3 doses: one week before the embryo transfer, when embryo heist activity is proven and at 12 weeks of pregnancy. However, dr Adsuar reminds us that there are some contraindications for using the intralipid therapy – and these include e.g. allergies to its components (soya, egg, peanut), severe hyperlipemia or severe liver insufficiency.
Corticosteroids, the third way to increase the probability of embryo implantation in autoimmune patients, increase endometrial receptivity, immune tolerance and vascular adaption. Additionally, dr Adsuar mentions the endometrial scratching technique that can be helpful in supporting the embryo implantation. It is believed to promote the renewal of the cells and it should be done a month before the beginning of any fertility treatment.
Dealing with a special case
Dr. Emma María Adsuar devotes a part of her presentation to antisperm antibodies which occur when a cellular structure in the testes called the blood/testis barrier is damaged (by physical or chemical injury or infection). This barrier separates the developing sperm cells from the blood and prevent immunologic stimulation. When it’s destroyed, sperm antigens come in direct contact with blood elements which produce sperm antibodies such as Immunoglobulin G (IgG), Immunoglobulin A (IgA) and Immunoglobulin M (IgM). These launch an immunologic attack that can affect sperm in several negative ways – for example, by causing it to agglutinate. Agglutinated sperm is unable to migrate through the cervix into the uterus. There are several risk factors for anti-sperm antibodies development, such as testicular torsion, varicocele, seminal infections and surgical procedures as the reversal of vasectomy.
Fortunately, there are ways to diagnose antisperm antibodies. Dr Adsuar mentions the immunobead test (specific but expensive) that allows doctors to recognize where the antibodies are located – if they’re in the head of the sperm or in the tail of the sperm. Another way is the MAR test that detects one part of the immunoglobulin antibodies that attack the sperm. It is much cheaper than the immunobead test so most of the time it is the first test that doctors do.
When it comes to antisperm antibodies treatment, it may involve either corticosteroids or IUI/IVF techniques. Dr Adsuar admits that the former is a long-term therapy involving high doses of steroid hormones and resulting in frequent side effects – that’s why it is not used on a daily basis.
Considering egg donation
However, it may happen that we have tried all of the above mentioned options and none of them worked. When autoimmune disease is really severe and it seriously affects our chances of being a mother with own gametes, dr Adsuar recommends going one step ahead and trying gamete donation. It can be either only egg donation, sperm donation or double donation – meaning that both oocytes and sperm are taken from donors. Donors undergo thorough medical testing and psychological evaluation what assures the best quality of their genetic material. Dr Adsuar encourages patients to take the possibility of donation into account and treat it as just another way of realising the dream of becoming parents.
Autoimmune disease and infertility. Do I have any chances to have a baby? – Q&A:
I would like to know of your clinic offers polar body diagnosis (PBD) with egg from a donor. I am 44-year old woman. My first attempt with egg donation failed. My doctor said this was due to chromosomal issues of a donor egg.
No, in our clinic we do not do a polar body biopsy because it hasn’t been proved that it is really 100% accurate. What we offer is PGT-A. It is a biopsy that we do in the embryo when the embryo reaches the blastocyst stage. In the clinic, we have a genetic team that can process the sample in less than 12 hours. So most of the time we don’t have to delay the transfer.
I don’t have an autoimmune disease diagnosis but I was found to have high natural killer cells on Chicago blood tests and on endometrial biopsy. Is this something your clinic treat and if yes, what would be the treatment?
Yes, I was describing it in my presentation before. I suppose you have high natural killer cells because you were undergoing fertility treatment. Am I right? What we do in our clinic to diminish the activity of natural killer cells is to use intralipid therapy. We also use a corticoid as a supplement. As I said before, that suppresses natural killer activity. So far we have had really good success rates.
I’ve been told I need intravenous immunoglobulin and Humira injections for my high natural killer cells. Would you consider these treatments?
We can consider them but to tell you the truth, it’s not the treatment we’re using here on a daily basis. We prefer to use the other kind of treatment I explained before.
If I am undergoing anticoagulant therapy, would you recommend both Asprin and Heparin or one or the other?
Everything has to be individualised. If you have antiphospholipid syndrome, most of the time we combine Asprin and Heparin. If you’re using anticoagulant therapy to diminish the probabilities of recurrent miscarriages, without being associated with antiphospholipid syndrome, most of the time we only give Heparin.
What is a polar body?
It is a medical terms so I’ll try to explain it in some basic language. You know that the cells in the body are divided with mitosis. It means that a normal cell breaks into two different cells with the same chromosomal dotation. However, it doesn’t work like this with the gametes (the ovum and the sperm). The division takes place by meiosis. The gametes start having the whole karyotype (46 chromosomes) and have to end into 23 chromosomes each. When they are fertilised, they will be 46 chromosomes again. In every division of the ovum, the ovum needs to get mature. The maturity means that these 46 chromosomes get duplicated and with the first maturation, it will spill their half dotation of the chromosomes. This is the polar body. I hope I explained it correctly and you understood me.
How many days before the embryo transfer do we have to start giving corticosteroids?
It depends. If we are doing the treatment with our eggs, most of the time we start the first day we are using the medication for the stimulation of ovaries. If it’s egg donation and we have to prepare the endometrium, or if it’s a frozen transfer, most of the time we start before starting with progesterone. To summarise: it can be 15 days before the transfer or, sometimes, 6-7 days before the transfer. It also depends on the patient.
Do you perform Emma and Alice tests? Does that really give proper information about the endometrium status?
I suppose you mean ERA test. ERA test is wider while Alice/Emma tests are more specific. We don’t do it here because it hasn’t been proved that it gives us enough information. It is believed that ERA test gives you information about the endometrium in the particular cycle – and not in the following ones. That’s the reason why we don’t do it here.
Do you perform KIR-HLA matching? I mean all parties: a donor, a recipient and a man.
It depends if it’s needed. In a donor, we always do a panel of recessive diseases. If the donor is not a carrier of any disease, there is no need of doing any kind of test either with a man or a woman. It’s not necessary unless we find something really obvious.
I am 44 years old and HIV positive. I am on treatment for my HIV. My viral load is undetectable. What treatment would you recommend? My husband is 52 and and IVF negative.
I’m really happy that your load is undetectable. Because of your age, we’d recommend egg donation. It depends on the sperm of your husband. We can go for either your partner’s sperm or sperm donation. In case of the latter, we would have double donation.
Do you recommend PGT-A in egg donor treatment? Do you see difference in success rates?
We recommend PGT-A if the partner’s semen is used and we diagnose a disease in the semen itself. Before doing any fertility technique, we request a karyotype test for the parents if we’re going to use their gametes. If we’re using donor eggs, we don’t need the karyotype of the recipient. But we’ll need the karyotype of the male partner if we’re going to use his semen. Apart from that, when we’re analysing the semen and we suspect a disease, we can request a karyotype test in the semen. It’s because there’s no correlation between normal karyotype in somatic cells and the normal karyotype in gametes (sperm or eggs). In those cases, we would recommend PGT-A. If the sperm doesn’t have any kind of problem, we don’t recommend it because the age of an egg donor is less than 30 most of the time. So the probability of aneuploidy is really low. The benefit of doing PGT-A in such cases is really not shown and increases the cost of the treatment. Another situation to imagine is when the sperm is good quality, the donor is young, we check her fertility and everything is ok but we have recurrent miscarriages or we don’t have any implantation. Then of course we need to investigate further and we need to investigate the embryo just in case we have a problem with the fertilisation – the union of the egg and sperm.
So if my partner sperm is ok, karyotype came back fine, there is no need for PGT-A? We failed our first IVF with donor eggs.
Right, there’s no need for PGT-A. The sperm is ok so I suppose the spermogram is normal. As I said, IVF is not a 100% guarantee of success. Our IVF success rate is 50-59%. Success rates with egg donation are 80-85% – assuming the sperm is good quality. So it sometimes takes a while to have a baby. We wish to have only one attempt and have amazing results. But we have to be realistic and honest with you. Sometimes we need to try more than once – even with egg donation.
If we give big amounts of corticosteroids, is there a danger to over suppress the immune system by decreasing the physiological NK cells function in the implantation mechanism?
I suppose you’re talking about the implantation rate and not antisperm antibodies. The amount of corticosteroids we give for this cause is really low. The complications and adverse effects are really low so we don’t even consider them. If it was the case of antisperm antibodies, then we’d be talking about different things. We’d be causing adverse effects the moment we’d be giving corticosteroids. The reason is that the amount of corticosteroids is much greater in that case as compared to the amount we’re giving in case of the implantation failure. So no, you don’t have to be worried about that at all.
Would I qualify for a guarantee program if I failed IVF with donor eggs in other clinic?
Obviously, we have to individualise each patient’s case. It depends on the reasons that made you fail, but we can of course consider your case. I suppose you’re talking about an egg donor programme. We have some guarantee programmes at the moment – where the guarantee means ‘live birth’. We understand that patients come to our clinic not only to get pregnant – they want to have a healthy baby. So we don’t talk here about success rates in pregnancy, we’re talking about having a healthy baby. With 3 trials, we know the chances are really good. So if you do not have a baby after 3 complete cycles, we give you the money back. This is how we can summarise the guarantee programmes. We can of course individualise them as there are different options.