IVF add-ons such as PGT-A, ERA and immunological treatments could be a great option for you, helping you to improve chances. And sometimes your problem may be that your doctor doesn't  recommend add-ons at all; perhaps the clinic doesn’t offer them due to tradition or regulation. But it also happens that (profit-driven) clinics recommend add-ons even though research doesn’t support that it will improve your chances. Most add-ons are recommended for certain patient groups, not as a standard treatment. 

When all you want is a solution, you want to try it ALL. But costs (financial and physical) may not always outweigh the potential - at least at every stage of the treatment. No matter how frustrating it is, treating infertility often is a “trial and error” process where you have to try a few things and learn along the way. 

Having said that, there’s no right or wrong decision; only you and your doctor can agree on what the next step should be. But no matter the outcome it always feels better if you’ve asked the right questions to be able to make an informed decision. So here’s a few tips on questions you can ask to have a better discussion with your doctor. Bring this check-list to your appointment...

1. Why do I need this add-on? Do you recommend it to all patients or are there certain things that make it suitable for me?

2. What will happen if I don’t add this to my treatment or if I wait a while?

3. Are there any alternatives I should know about?

4. Are there any risks or side effects involved? How likely are they to occur?

6. In your opinion - do the potential benefits outweigh the risks and costs for me?

This checklist and many other are found in Tilly's app - bring them to your doctor's appointment and tick the questions you've asked. Feeling in control can make a big difference 💪

Checklist: Questions to ask when your doctor suggests an IVF add-on

An individual miscarriage is unfortunately quite common and is most often due to the embryo having abnormal chromosomes - something you can't do anything about. But when several miscarriages occur in a row, you may need treatment and identifying the underlying cause is therefore crucial.

Dr Hassan Shehata runs two clinics in UK that specialise in helping women who suffer from recurrent miscarriages or repeated (IVF) implantation failures - Center for reproductive immunology and pregnancy. He is a Consultant Obstetrician and Gynaecologist and a subspecialist in Maternal Medicine, and has managed and treated over 5,000 patients at the CRP Clinic with 80% success rate.

Most individual miscarriages are due to the fact that the embryo was not healthy; it didn’t have normal chromosomes. No one has only healthy eggs and sperm, so when the doctor says your miscarriage was "bad luck", he/she basically means that you were unlucky enough to get pregnant with an egg and/or a sperm that was not chromosomally normal.

If you have several miscarriages in a row, the probability that it's "bad luck" decreases, and in the event of more than three miscarriages in a row, you are diagnosed with what is called "recurrent miscarriages". I that case a miscarriage investigation should be done to try to identify the reason, and if tests show anything, treatment is available. But the fact is that classic miscarriage investigations quite seldom identify an issue. In other words, the cause of most cases of recurrent miscarriages remain undiagnosed.

Through his research, Dr. Shehata has established that the factors tested in a classic investigation only cause a minority of cases. So there are basically gaps in our knowledge and research; we just don't know that much about recurrent miscarriages yet.

Why is the immune system relevant to consider?

That the immune system plays a role during pregnancy is well established. If you receive a donated  kidney or heart, you must take immunosuppressant drugs for the body not to repel these genetically foreign body parts. But even though an embryo always consists of 50% genetically foreign material from the man (and sometimes 100% when donated eggs are used), the generally body doesn’t reject it. The immune system thus adapts in one way or another to support a pregnancy. 

So a logical theory is that if a woman's immune system somehow doesn't work as it should, her body could repel embryos causing miscarriages. The immune system could be overactive, there could be an abnormal presence of different antibodies and/or the woman could have an autoimmune disease.

The view on to what extent the immune system and miscarriages are related and what we can do about it, varies from country to country. In som countries (e.g. Sweden) doctors don't think we know enough to do immunological testing or treatment while it's common in many other countries. Dr Shehata is an example of a doctor who does research on the topic and also treats women with immunological issues at his clinic.

1. What immunological investigations and treatments do you do in case of repeated miscarriages?

In the event of repeated miscarriages, I do six different investigations that can lead to different treatment strategies.

Some types of NK cells are found naturally in the uterus, but another group of NK cells (CD16 +, CD56 +, CD69) can cause miscarriage when they attack the uterus. NK cells can also prevent embryos from attaching during an IVF treatment. This can be treated by calming these cells with immunosuppressant, reducing their effect. 

Elevated levels of TH1 / TH2 cytokines can lead to a miscarriage. Cytokines are small proteins that are crucial in controlling the growth and activity of other immune system cells and blood cells, and affect the growth of all blood cells and other cells that help the body's immune and inflammation responses. The activity of cytokine cells can be TH1 (pro-inflammatory) or TH2 (anti-inflammatory). The pro-inflammatory cells are needed when the blastocyst is to attach in the uterus and blood vessels are formed between the embryo and the woman, but if they become too many or remain for too long, they can instead become harmful. The treatment to inhibit this is different types of immunosuppressive drugs.

People who have the autoimmune disease SLE have ANA, and may have an increased risk of miscarriage. However, people who do not have SLE can also have an immune system that behaves in a similar way. Therefore, we investigate whether women have these antibodies, and if it's the case, treat them with Prednisolone (cortisone).

In case of thyroid disfunction, you're often considered treated if you have antibodies against the thyroid gland (TPO-ak, Tg-ak or TRAK) and the right dose of a medicine (e.g. Levaxin). In my opinion, the risk of miscarriage is greater if antibodies remain, so I give further treatment with Prednisolone (cortisone).

These antibodies are found in those who have celiac disease (gluten allergy). Even if you don't show symptoms of gluten intolerance, these antibodies can occur and be the cause of repeated miscarriages. It's treated with a lifestyle change that involves a gluten-free diet.

Anticardiolipid antibodies (APS) - "Sticky blood"

Anticardiolipid antibodies make the blood thicker and thus increase the risk of blood clots, especially in pregnant women, which can cause miscarriage both late and early. However, it is not a common cause of miscarriage (only 0.83% according to one of my  studies). The treatment entails blood thinners - a low dose of acetylsalicylic acid, which you start taking before pregnancy, and then injections of heparin.

2. Why are immunological causes of miscarriage still so debated?

Immunology is very complex if we talk clinical evidence. Even for general autoimmune diseases, tests very often don't deliver clear answers. For example, for a well-known autoimmune disease like rheumatism, tests only show positive in less than 20% of patients who carry the disease. Therefore, doctors have to look at symptoms like e.g. a swollen joint rather than just blood tests. And this makes it complicated when it comes to miscarriages and failed IVF attempts.

The lack of clear clinical evidence, is what complicates the debate. There is undeniably a strong correlation between pregnancy and the immune system, and although it has historically been seen as controversial to believe that the immune system can cause miscarriage, nowadays most people are convinced that there is a connection. The main debate regards how we test and treat, rather than why we test and treat. It's a discussion that will continue and the most important thing is that continued research is done within the area.

3. Is there an increased risk of miscarriages if you have rheumatism or another autoimmune illness? 

In general, yes, if you have an autoimmune issue then there is an increased risk of miscarriages and it’s important to be tested for the cells related to your particular illness. There are certain immune disorders that are particularly associated with a much higher risk of miscarriage such as Lupus Disease.

Briefly explained, an autoimmune disease means that the body attacks itself. Antibodies are present in the body to protect us from viruses and bacteria. They are formed by different types of immune cells. For people who have an autoimmune disease, the body's immune system instead begins to break down cells that we need. The immune system mistakenly believes that these cells are invaders in the body. 

About 5-7% of the population in the western world is affected by some type of autoimmune disease, and women are affected much more often than men. Examples of autoimmune diseases are type 1 diabetes, Hashimoto's (hypothyroidism / underactive thyroid), SLE (Lupus), rheumatoid arthritis (rheumatoid arthritis), celiac disease (gluten intolerance), Crohn's disease, Sjögren's disease and Addison's disease.

5. Can immunological disorders cause repeated implantation failure? 

Yes, implantation failure could be considered a very early miscarriage and if the issue is not the embryo or anatomical abnormalities it is worth looking into. 

6. Could a donated egg cause immune reactions from the body?

Recurrent miscarriages & Immunology - Q&A with Dr Shehata

When you step into the world of infertility and IVF, the amount of new things and terms you have to learn may make your head spin. So let’s go through some of the major acronyms that tend to come up when you meet your doctor or turn to Dr Google. 

IUI, or intrauterine insemination, is a fertility treatment in which your partner’s or donated sperm is being directly placed inside your uterus to facilitate fertilization. Sperms are “washed” to find the strongest ones and then injected through a catheter up through the cervix directly into the uterus,This is a cheaper and less invasive procedure in comparison to IVF. Sometimes ovulation is induced by medications such as Clomid or Letrozole, sometimes its done in a natural cycle. 

Invitro fertilization, commonly abbreviated as IVF, is a widely known technique to help people with infertility problems. At the simplest level it entails an egg being combined with sperm ‘in vitro’, i.e. ‘in glass’ (or today more accurately in a ‘plastic Petri dish’) outside of the body. For this to happen you take hormonal medications to stimulate follicle growth so that several eggs can be retrieved to be fertilised. 

A frozen embryo transfer, often abbreviated as FET, is a part of an IVF treatment referring to when a frozen embryo is transferred into your uterus. The embryo can come from a previous IVF cycle or donor egg cycle when it was frozen and to be thawed and transferred in a future cycle. (The alternative is a fresh transfer when an embryo is transferred in the same cycle as the egg retrieval.)

ICSI is an abbreviation for intracytoplasmic sperm injection, which is one of the IVF techniques used to improve chances in case of male infertility issues. A live single sperm, chosen by your embryologist, is directly injected into the center of your egg to be fertilized and then hopefully grown into an embryo that can be transferred to your uterus. (The alternative is to just place several sperm with the egg and let one find its way just like when fertilisation happens inside a woman’s body.)   

Physiological intracytoplasmic sperm injection (PICSI) is essentially ICSI with an extra step. It involves adding a special enzyme to the sperm to enhance insemination chances during an IVF treatment where there are  male infertility issues. The enzyme is called hyaluronan and is a natural compound in the body that attracts healthy strong sperm. The sperm binds with hyaluronan and then isolated to be used for ICSI.

TTC stands for trying to conceive is an abbreviation used on social media and fertility forums basically referring to people who are trying to get pregnant. 

Pregnant Until Proven Otherwise or PUPO is a common slang used on social media and fertility forums that describes your status after undergoing IVF and an embryo has been transferred to your uterus. Technically you are considered pregnant but this is not confirmed until the implantation has successfully happened. 

The two-week-wait (2WW) is the time (approx 14 days) between your ovulation and your next expected period.The term is very common between women who are trying to get pregnant (trying to conceive, TTC), especially those undergoing IVF, so it actually rather refers to the time between your ovulation and when you can take a pregnancy test.

Deciphering infertility acronyms: IUI, IFV, ICSI, PICSI, TTC… what do they all mean?

IVF or ‘In Vitro Fertilisation’ is one of the techniques that can help people who have fertility issues. In this Q&A our expert Dr Evangelia Elenis has responded to your questions about this treatment. Dr Elenis is an MD and PhD specialised in Reproductive Medicine. She is an affiliated researcher at Uppsala University with postdoctoral studies at Harvard Medical School. She is also a mother who has gone through IVF herself and has a strong passion for improving the patient experience. 

What is considered a normal fertilisation rate? And if it’s lower, is low sperm quality always the reason?

Average fertilisation rate, that is the proportion of mature oocytes that end up becoming fertilised by sperm, lies around 70% after regular IVF (conventional insemination). But rates down to 50% can be considered normal. It is when rates fall below 40% that most clinics use ICSI in order to improve pregnancy chances.  

A lower fertilisation rate can be the result of lower sperm concentration, quality or the origin of the sperm (that is depending if it is ejaculated sperm or after surgically extracting sperm from the testicles or the epididymis). But also issues with the eggs such as lower egg quality or a hardened, difficult to penetrate surrounding membrane called zona pellucida. Whether eggs are fresh or frozen can also play a role. So although sperm seems to account for most of the cases of lower fertilisation, it doesn’t seem to be the only factor that plays a role.

Will I lose eggs faster if I take fertility drugs that result in multiple eggs ovulating and releasing each month?

Although that sounds reasonable it doesn’t seem to be the case. IVF doesn’t lead to running out of eggs earlier and doesn’t bring on premature menopause.  Even in a normal cycle you lose more than the one egg you ovulate. What happens with IVF, is that by taking high doses of fertility drugs, such as FSH injections, all follicles that have started to grow during that cycle but would otherwise be wasted during a natural cycle can continue to grow and fully mature.  We can in this way make use of them with IVF. The remaining egg reserve is not affected negatively by fertility treatment.

More eggs is not always better! Large studies performed after thousands of IVF cycles show that pregnancy chances and live birth increase as the number of eggs retrieved rises. That is easy to understand since more eggs retrieved translates to higher chances for more fertilised eggs and more genetically normal embryos to transfer. However, that improvement reaches its peak when we collect around 15 eggs. When retrieving 15-20 eggs or more the pregnancy chances remain stable or somewhat decrease. The reason is not clear but one of the hypotheses is that more eggs produce higher estrogen levels; high estrogen in turn affects the uterine lining in a negative way and therefore the likelihood that the embryo will implant. Another hypothesis is that the large number of eggs might lead to immature eggs or eggs of lower quality but that has been largely debated and not confirmed by newer studies.

Is there any advice you would give a couple before starting IVF?

An IVF treatment is a process that is both physically and emotionally demanding, not only for the woman undergoing the stimulation and egg retrieval but also for her partner. Regarding the physical part I would recommend to the woman to start taking prenatal vitamins, and to the couple to quit smoking and cut back on alcohol. Also - make sure to establish a good dialogue with your doctors so that you feel you get the information you need to feel in control. 

Also, the couple’s psychological well-being  is equally important as the physical one! My advice would  be to try to manage the stress and anxiety, using tools that YOU like. It could be meditation, yoga or journaling. Both partners are going through a demanding phase in life so it’s important to always have an open dialogue with each other. Don’t be afraid to ask for help from your friends and relatives or a professional (such as the fertility clinic’s psychologist! Being also part of a fertility forum, communicating with women that go through similar difficulties, and sharing, can also help. Remember - you are not alone in this!

I’ve done many failed IVFs, never retrieved eggs that developed into embryos. Now moving on to donor eggs. Is the IVF-process different for the donor or same as I did? Does my husband have to leave a sperm sample on the day of her retrieval?

An embryo donation cycle is carried out in a similar way as a regular IVF. The egg donor will go through the same steps of egg stimulation with fertility drugs and egg retrieval that you did. On the scheduled day of egg retrieval the male partner leaves a sperm sample and depending on the quality of the sperm, the lab personnel fertilise the eggs either through regular IVF or through ICSI. The fertilised eggs will then hopefully grow in the incubator for 2-5 days and the best embryos will afterwards be selected for transfer or to be frozen. Usually, during the stimulation period of the donor, the recipient, that is you, receives fertility medications, such as estrogen and progesterone, in order to tune her uterus lining with the embryo and therefore maximize the chances that the embryo(s) will implant after they are transferred. Sometimes, the embryos are frozen / thawed and transferred in a natural unstimulated cycle, happening at a later phase. 

In which cases is transferring an embryo on day 2 or 3 better than waiting for a blastocyst?

Nowadays most fertility clinics choose to transfer embryos at the blastocyst stage compared to cleavage stage embryos (day 2 or 3). That is because embryos that manage to survive until day 5 have generally a superior quality compared to the ones that didn’t make it. A transfer of a blastocyst has therefore a higher chance to lead to a pregnancy (around 40-50%) compared to that of a cleavage stage embryo (25-35%). However if the number of eggs after a retrieval is relatively low (for example 1- 4 eggs) or if embryos from prior IVF-treatments didn’t reach the blastocyst stage despite adequate number of eggs collected, we might opt for a day 2-3 embryo instead. From our experience, a small number of embryos that would not qualify as blastocysts according to our strict lab criteria, could nevertheless thrive in the uterus and lead to a pregnancy. The human body can sometimes be a better “incubator” than that of the lab.

How are embryos graded? Heard it can be a bit subjective?

In order to increase pregnancy chances after IVF we have to choose wisely which embryo(s) to transfer. That is done by using embryo grading as a tool. Embryo grading is mainly based on the embryo's number of cells, their appearance in a high-power microscope as well as their growth rate. The scoring varies depending if the embryo is on day 2-3 (a cleavage stage) or on day 5-6 (a blastocyst).  In addition to these universal criteria, some fertility clinics have even developed their own systems to select how many and which embryos to transfer. 

So yes, individual judgement is important and the assessment is thus, at least partly, subjective.

My AMH is 0,2. Which type of stimulation protocol would you try? Know there are no guarantees.

This is a hard question to answer. No treatment protocol has been shown to be better than the rest for women with low egg reserve - it might therefore be necessary to test some of the “regular” IVF protocols to see what would suit you, such as the long agonist, the short antagonist or the short flare-up agonist protocol. Lately several fertility clinics have started testing mild IVF or natural modified IVF for women with low egg reserve, that is using low dose fertility injections in addition to ovulation pills during an IVF. The rest of the IVF steps are similar. The data thus far show similar success rates compared to regular IVF but lower medication cost, fewer side effects reported and potentially better quality of the embryos obtained.  

Who would you recommend an ERA-test to? 

ERA stands for Endometrial Receptivity Analysis (or Array) and  is a genetic test carried out during IVF in order to check whether your endometrium and your embryos are synchronized or your “wind of receptivity”. The test is done by taking cells from the endometrium through a biopsy on a specific day of the menstrual cycle and performing genetic analyses of over 200 genes. By evaluating the endometrium on the time it’s supposed to be receptive, you confirm whether that is the case or whether the endometrium is at an earlier or later stage than expected. In that case the timing of the embryo transfer should be pushed forward or back. The ERA test is relatively new, costly and hasn’t proven to be effective for all women that undergo IVF. However it may hold promise for women that have repeated failed IVF attempts, 3 or more failed embryo transfers that is. Especially if the embryos have been tested and proven to be genetically healthy (have normal chromosomes), meaning you’ve excluded the possibility that low embryo quality is the reason for your failed transfers.

How important is it to assess the correct day 1 of the period? It sounded very important that menstruation started properly with red bleeding. And depending on whether it came before or after 12 o'clock, it was decided what was day 1. Then start some with the simulation meds on day 2 and others on day 3? Why is that?

During IVF treatment, especially when using the short antagonist protocol, which is the most commonly used treatment, women start using stimulation meds at the beginning of their menstrual cycle. This has two main reasons. Firstly because we’re trying to take advantage of the natural FSH produced by a woman’s pituitary when it is at its highest. We can in this way increase the response from the ovaries. Furthermore, timing is essential! We synchronise the artificial stimulation period to the one otherwise happening naturally. That  ensures that the other involved organs are correctly tuned, the uterus for example. Women with shorter cycles would therefore need to start one day earlier in order to lower the risk of something being out of phase.

After 4 failed transfers with high quality embryos, what would you suggest? I've not done an ERA or a hysteroscopy.

When 3 or more IVF attempts with good quality embryos have been made and failed, we usually talk about repeated implantation failure (RIF). Several studies have been done on RIF but the results on the efficacy of treatments and the necessity of the evaluation are still conflicting. Before presenting what we know on the matter, I would therefore urge you to make an informed decision after talking with your fertility specialist on whether such tests and/or treatments might positively affect YOUR chances of success. Unfortunately, despite doing various tests, which can be both costly and sometimes painful, we don’t always find a reason. 

Possible reasons behind RIF include uterine pathology (that is anatomical problems), presence of endometrial polyps or fibroids, abnormal growth of the endometrium (endometrial hyperplasia), chronic inflammation (i.e. endometritis) et.c A hysteroscopy can therefore be needed in order to confirm or exclude such a diagnosis, especially if the gynecological ultrasound exam indicates it. Furthermore, it has been discussed whether the failed implantation for women with RIF, is due to an asynchrony between the embryo and the endometrium, that is if the uterus and the embryo are not ready at the same time. So an ERA test (I’ve explained more closely in another response how that works) could potentially give an indication. All of the above however presume that the “high quality embryos”  transferred were actually chromosomally normal and thus had the potential to lead to a normal pregnancy. You can therefore also discuss with your doctor if PGT-A (i.e. a genetic test of the embryo) could be indicated in your next treatments, especially if you are above 35 years of age. There is lastly an ongoing debate on whether an overactive immune and/or coagulation system could hamper a pregnancy and if treatment adjusting these systems could positively affect the pregnancy chances.  

What can be said, in general, about how egg quality is affected by PCOS? I’ve understood there’s different types of PCOS. I’m not overweight, but I have other symptoms. 

PCOS  is a condition characterised by high levels of male hormones (such as testosterone), irregular menses and/or polycystic ovaries seen on the ultrasound. Having two of the three indicators is enough to receive the PCOS diagnosis. That means that some women might have all three features and some different combinations of those three, which is what characterises the different PCOS types. So the “picture of PCOS” can therefore look different for different women. 

Although the eggs of women with PCOS don't seem to have a worse egg quality (they actually have a similar proportion of genetically healthy eggs), we have observed a higher rate of early miscarriages in this group. One potential explanation is that the miscarriages could be the result of high androgens and/or high insulin/ insulin resistance which is common among PCOS women and not the PCOS condition itself.

IVF - Dr Elenis responds to your questions

Dr. Fatin Willendrup is a Medical Doctor with key skills in communication of medicine and problem-solving. Fatin's passion is preventive work within fertility and helping people to live healthier lives and improve fertility potential. Fatin has two children that were conceived through IVF and a third child via natural conception, so her own journey inspires her work.

Fertility is complex - both female and male fertility. But what is clear when it comes to male fertility is that good sperm quality improves chances for pregnancy. So how do you find out how good your sperm quality is? And can it be improved? We turn to Dr. Fatin Willendrup to sort out common questions and misunderstandings when it comes to male fertility.

Is it common for men to have fertility issues?

In 40% of infertility cases worldwide, male infertility is the main reason for couples not being able to conceive. 

In the Western world average sperm quality has dropped by 50% in the last 40 years and 1/3 of young men have a sperm quality so low they are likely to experience problems with fertility.

Male fertility issues could be caused by:

Blockages that prevent the delivery of sperm to the female tract

Abnormal sperm function (lack of movement, inability to fertilize the egg)

And these causes can in turn have several reasons like injuries and infections as well as lifestyle factors. 

What can I do to identify issues, do I need to go to a clinic?

I advise you to see a doctor if you have been unable to conceive a child after a year of regular, unprotected intercourse. If you have any of the below symptoms and conditions, you need to consult your doctor sooner:

Semen analysis revealing low semen quality

Erection or ejaculation problems, low sex drive, or other problems with sexual function

Pain, discomfort, a lump, or swelling in the testicle area

A history of testicle, prostate, or sexual problems

A groin, testicle, penis, or scrotum surgery

And if you want to be proactive before starting to try for a baby - to exclude risk factors and/or be able to optimize sperm health - there is no reason not to take a test earlier. You can't know how good your sperm quality is just by looking at your ejaculation. A sperm analysis like Tilly's sperm test is the only way you can evaluate sperm quality and get a real idea of your fertility status.


How can I improve my sperm health and optimize fertility? 

It’s important to focus on scientifically proven lifestyle changes that increases sperm quality. Weight management, exercise, nutrition, antioxidants intake and excluding toxins like smoking are top priorities both for men and women when trying for a baby. For men we have identified the following 10 things you can do:

When taking a sperm test with Tilly you get access to an app with personalized lifestyle programs helping you to improve sperm quality if needed.


For men who need emotional support on the road to fatherhood, it can sometimes feel incredibly lonely. But there are some organisations trying to change that. The support is out there – you just need to know where to look for it. Here are just a few of the ways you can findsupport you need – in a way that feels comfortable for you.

Via Tilly's app: Tilly: Fertility & IVF support

How to improve male fertility and sperm health. Dr Fatin answers common questions about male fertility.

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