By fertility experts from Spain.
When an 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?
In this #IVFWEBINAR, Dr Emma María Adsuar, fertility gynaecologist from UR Vistahermosa (PreGen) in Alicante (Spain), explains whether the combination of autoimmune diseases and infertility is a possible obstacle to overcome at all.
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 a premature ovarian failure. It means that a 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 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 the 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.
After making us familiar with all the adverse effects of autoimmune disease on fertility, Dr Adsuar goes on to the most important issue: possible solutions. Fortunately, there are two ways to deal with the problem: to prevent it and or to address it. When it comes to preventing, the preservation of fertility may be the answer. When women are diagnosed with Hashimoto disease, for instance, 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.
In case you did not think earlier about 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 an injection of the partner’s washed sperm into the uterus with a catheter. For more advanced autoimmune diseases, IVF treatment is recommended. In the 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.
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 experiencing, doctors may use anticoagulant therapy (which has been proved effective in people who have antiphospholipid syndrome), intralipids and corticosteroids. The latter acts 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 the 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 (soy, 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.
Dr Adsuar devotes 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 is 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 are 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 is why it is not used on a daily basis.
There are occasions however where none of these interventions work. When an 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.
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’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 the case of the latter, we would have double donation.
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.
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 of 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.
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.
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.