Blog - Fertility Fact Checker

8 Questions You Need to Ask When Choosing a New Fertility Clinic

When choosing a new fertility clinic either for the first time or because you have decided to move on from your old clinic there is always a sense of urgency, a bit of a rush. After all, you wanted your baby, like, yesterday. If you have got any patience left in you at all though it pays to take a little bit of time and try and suss out the answers to at least some of these questions. Not only will you know what to expect but it could save you a lot of hassle and time if you decide before you even attend that first appointment that a particular clinic is not going to be right for you.

Having fallen into the trap of going to the first clinic that crossed my path here is my list of the top 8 things you need to ask any prospective new fertility clinic…remember although we are thankful to them for hopefully helping us make that baby, they are also lucky to have us as their patient!

Will I see the same doctor for each of my appointments and procedures?

Quite often the doctors in fertility clinics work in teams. The doctor who you sit down and have your initial appointment with often is not the doctor who will make the day to day decisions to change your medications as you go through your cycle and may not be the doctor who does your egg pick up or embryo transfer. Instead, the doctors seem to work on a rotating roster and which doctor is doing what on the day is pot luck (well, it seems that way!). I get it. This is understandable and with so many patients and some clinics being open 7 days a week, your one doctor can’t be waiting for you to ovulate all the time.

Having a team of doctors should be ok though as long as they have good handover procedures and regular review meetings. When they are just making the day to day standard clinical decisions as long as these procedures are in place you should be in safe hands and they should have a good understanding of your medical history.

In my opinion, what isn’t ok though is when there is no continuity of who you see for your review appointments. I have heard of some fertility patients who see a different doctor every time they go for a review appointment. Although we are not kidding ourselves into believing that we are all best friends, it is important to have that therapeutic relationship build over time and more importantly, you also you need to know who is responsible for your care when things don’t work out the way you wanted it to. Additionally, by having one key doctor you should also be able to discuss the ‘next steps’ and both be on the same page knowing when it is time to try a different protocol for example and for what reasons. For these reasons and many more, I think that having just one doctor carry that clinical continuity is one of the most important things over the course of your ‘journey’.

Who can I contact with clinical questions during my cycle?

Often the only people you will actually see whilst you are taking your medications during the first half of your cycle is the receptionists and nurses. Although the nurses are incredibly knowledgeable they do not make the clinical decisions. If it is important to you to be able to speak, or email, the decision makers directly ask your clinic if direct contact with your doctors is possible (HINT: it should be 😉 obviously not on a stalking, daily basis, and don’t expect to get a response all the time, but you should be able to feel like your concerns are being heard by those making the decisions). Saying that though, some clinics are set up so that you have a main nurse to contact throughout your cycle, she (forgive the gender role pronouns used here – has anyone actually encountered a male fertility nurse?!) ends up acting as a kind of case manager. In this instance you have more reassurance that your direct concerns will get to your doctor but its still a question you need to consider.

How long do I need to wait to get a review appointment?

Some clinics operate so that there are ring fenced appointments only for new patients. This is great for the new patients as it means that they can get in and get those initial questions answered (and also great for the clinic who are bringing in those new patients) but not so great for down the track when you want to see your doctor again for a review appointment. After every cycle (and hopefully you won’t have to do too many) you will need to see your doctor to decide on what the next treatment options are. It can be incredibly frustrating and will hold up your treatment considerably if you need to wait a couple of months just to get this review appointment.

Where and when are bloods collected?

During the cycle you will be visiting the clinic first thing in the morning 2 – 3 times a week. It is important that you are able to make the blood collection times as, at the risk of sounding dramatic, it could significantly impact on the success of your cycle if you don’t attend for blood collections as required. This is because depending on your blood test results your medication may need to be increased or decreased to optimise those, hopefully numerous if doing IVF, follicles that are developing. People who do shift work or need to travel for work need to pay particular attention. Some clinics have arrangements with various pathology labs allowing for the bloods to be collected at centres other than at your fertility clinic which could make it a lot easier for you to get to work on time. The downside to this though is that the results are often delayed in getting to your clinic and could delay any medication alterations.

How much does it cost?

This seems like an obvious one and one that you should be able to pin down pretty quickly. Depending on the clinic, your type of cycle and your level of health insurance though, there could be little ‘extra’s’. These extras may include use of an EmbryoScope, special sperm preparation, medications and possible hospital fees.

Do you have counsellors attached to your clinic?

Although you may feel like you have it in the bag and are emotionally strong there will inevitably be a day when you just want to talk it out with someone who ‘gets it’. Although you could quite easily find an independent counsellor to talk to finding one that understands the unique challenges that being a fertility patient brings and understands the way your clinic works is another story. And then they often have waitlists anyway – not helpful when having a nervous breakdown! Having a counsellor that you know you can easily book into is a relief and reassurance that you aren’t going to be wasting your money on someone who just doesn’t have the experience. What’s even better is when clinics have counsellors you can easily get into for FREE!!

Is your doctor open to new research and ideas?

This is a bit of a funny question and obviously, no doctor is going to answer ‘no’. For some women though the road to motherhood is a bit more twisted and long winded than anticipated. If this happens it is important to know that your doctor is up to date with the latest evidence based research and isn’t just trying the same thing on you that he has been doing for the past 20 years. Though saying that, 20 years of clinical experience can also be a good thing! What is key here is making sure that you feel your doctor is respecting your situation and is willing to try new approaches as is appropriate for you.

If we need to use a donor is there a waiting list?

Like the wait times on needing to get review appointments, some clinics will have different waiting times for donor egg, sperm and embryo. If you know in advance that this is something that you need to consider it definitely does not hurt to ask the question. Similar to this is needing to know if there are certain ‘start times’ for your cycles. Some clinics prescribe the contraceptive pill so that they can control when ‘Day 1’ is and then start a batch of women cycling at the same time. Easier for the clinic but is it better for you?

These are only some of the major questions that you should ask before signing up with a clinic. Other questions might include where does the egg pickup take place and is it under general anaesthetic, does my partner always need to come to my review appointments and what is the process for freezing ‘left over’ embryos?

Although it might delay your first appointment by a week or two whilst you are collecting the answers to these questions it is much easier and less stressful to cover these questions early than randomly choose a clinic only to find it isn’t going to work for you and to have to move clinics in the future.

Antinuclear Antibodies and Infertility

Antinuclear antibodies (ANA’s) is a grey area in infertility. Some doctors will tell you testing positive for ANA’s it doesn’t make any difference to your fertility, some believe it may be the reason why you still don’t have that take home baby and others may try you on some medication, just…because.

Testing for ANA’s comes under the umbrella of testing for ‘immune problems’ and seems to be a growing area of interest. And whilst for some a diagnosis of ‘unexplained’ is exactly that, for others ‘unexplained’ may sometimes become explained when immunological issues are investigated.

Without sounding too hippie, there seems to be many more allergy suffers today then there was of days gone by. An allergy is ‘a damaging immune response by the body to a substance, especially a particular food, pollen, fur, or dust, to which it has become hypersensitive.’ Especially with today’s chemicals, sprays, laundry detergents! and extreme levels of cleanliness in general it is difficult to know exactly what allergens people may be allergic to and what impact it is having on the body. Having these allergies can trigger immune responses in the body which can also be associated with infertility.

The doctors willing to consider immune issues in infertility seems to be growing. There is also a growing amount of research and literature further investigating immunology problems and its negative impact on fertility. Regardless of this though, it still seems as if it is not necessarily routine to have all your immunology tests completed at the outset. If you take nothing else out of this blog post, take away this:

make sure you discuss immunology problems as a possible source of infertility with your doctor and that they have requested the relevant blood tests.

Sometimes in fertility, the problem you initially thought that was the cause of your infertility spirals and spirals until you don’t know what is going on. For the sake of a blood test, it is well worth ruling this one out.

There are lots of different markers and factors to consider in immunology. There are antisperm antibodies, antiphospholipid antibodies, natural killer cells and leukocyte antibodies and a whole heap more that I haven’t even heard of. Each of these should be tested and evaluated by your doctor. Then there is my favourite: antinuclear antibodies.

A…N… what??

For some women, including myself, having high levels of antinuclear antibodies (ANA’s) can be the, or one of the, reasons behind difficulty conceiving. Although many people can have higher ANA’s then normal and be completely healthy it can also be an indicator of an autoimmune response where your body is producing a type of antibody that starts attacking the nuclei in the cells of your normal tissue. As my specialist described it, its like your immune system is constantly switched on and is possibly considering an embryo as a foreign body that needs to be eliminated. But there are different levels of ‘high’ ANA’s, or ANA positives.

You may get a ANA positive result of 1:160 and because ANA results are reported in titres, what this means is that when 1 part of your blood was mixed with 160 parts of a diluting substance laboratory staff are still able to detect the ANA’s. Different labs have different ways of reporting when is considered ‘positive’ and when they stop diluting. For me, I had ANA of 1:2560 which means that when 1 part of my blood is mixed with 2560 parts of another substance they can still detect the antinuclear antibody, which as far as I am aware is as high as the scale goes. Mixing your blood with so much of the other substance you would expect to not see any of the ANA’s at this point. This is going to sound contradictory to what I have said, but being ANA positive in itself is not a diagnosis or an indicator that anything is necessarily wrong. In a review done in 2009 (1) it was found that having low titre antibodies (for example around 1:160) does not impact IVF success rates. Depending on your clinical symptoms, what being ANA positive can be though is an indicator to do further immunological testing for things such as lupus or connective tissue conditions, like rheumatoid arthritis. Positive ANA’s can also be present in a healthy population as well so just because you receive a positive result does not necessarily mean anything is wrong per se.

When getting your results back regarding ANA’s there may also be information on what pattern is present, such as homogenous or speckled. Different patterns can be associated with different autoimmune conditions and your own situation needs further discussion with your specialist or GP.

ANA +ve + TTC = ?

Despite it seemingly being a bit of a ‘Wild West’ topic to some fertility specialists and the fact that it does not necessarily always mean something is wrong, there does seem to be a link between being ANA positive and experiencing infertility issues.

One study investigating the presence of immunological markers in IVF patients noted that in the general population 5% of people have elevated ANA’s where as in their infertile cohort, 30% of patients undergoing IVF were ANA positive (2).

That is there are a lot more ANA positive people in those that are known to be reproductively challenged then those in the general population. Another study looked at 560 Iranian women who had experienced 3 or more miscarriages. They found that 13% of women who had experienced recurrent miscarriage were ANA positive and only .9% of their control group, that is the healthy population who did not experience recurrent miscarriage, were ANA positive (3). It should be noted that about half of these ANA positive women also had antibodies associated with Lupus – so when you get your test results back, make sure you aren’t jumping to conclusions or worrying without getting more of the picture.

From the above studies it appears that there does seem to be some association with being ANA positive and having difficulty either conceiving or continuing a pregnancy (at least in the early stages of pregnancy).

The different areas of fertility ANA’s can impact

Premature Ovarian Failure

ANA’s can possibly have an impact fertility at various stages – whether that be by affecting implantation rates to having an impact on oocyte, or egg, quality. Carp and colleagues (4) speculate that autoimmune conditions can be responsible for premature ovarian failure to implantation failure and pregnancy loss. And the boys aren’t ‘immune’ either by the way, with Carp also mentioning that autoimmune conditions could be responsible for testicular failure as well. Carp mentions that 10 – 30% of women with premature ovarian failure (when the ovaries fail before the age of 40) have some type of concurrent autoimmune condition. There are many other reasons for premature ovarian failure and often a reason is not found. When it is associated with an autoimmune condition however, it is usually associated with high levels of follicle stimulating hormone, anti-muellerian hormone and inhibin – measurements that many women with infertility will be familiar with (4). The good news here is that if you do experience premature ovarian failure due to autoimmune conditions then with addressing the autoimmune conditions at play, along with any subsequent hormonal conditions such as diabetes, then recovery of ovarian function may occur (4). Unfortunately though it is not the magical answer and even if your autoimmune complications are resolved, if the damage has already occurred and there are no eggs remaining then it is suggested, in this study at least, that donation is the only option in the cases of severe premature ovarian failure (4), but like always discuss your options with your doctor.

Follicular Fluid and oocyte (egg) quality

Just as ANA’s can show up in your blood, they can also show up in follicular fluid. Follicular fluid is the fluid that surrounds the oocyte, or the egg, in its follicle. You will recall that when you have an egg collection, follicles are extracted from your ovaries and from the follicles eggs are extracted. Recently follicular fluid has been recognised as being a key indicator of the environment that eggs are housed in and the substances that are in the fluid can impact egg quality and hence subsequent fertilisation and pregnancy rates (5). For women where ANA’s have been detected in follicular fluid, this has been associated with typically producing smaller amount of embryos. Not only is there less quantity produced but it seems that those that are produced are generally also of lower quality than ladies who are ANA negative (ie have normal levels of antinuclear antibodies.

Implantation and pregnancy rates

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Assuming that by running the gauntlet so far you have kick started your ovaries into action as well as produced some fantastic quality embryo’s. So far so good. Before we get too ahead of ourselves unfortunately elevated ANA’s can also influence implantation and overall success rates even where good quality embryo’s are produced. One study done in 2012 (2) compared the overall implantation and success rates of women experiencing infertility who were ANA positive (ie had more antinuclear antibodies then normal) to those that were ANA negative. Although there sample size was quite small only comparing 96 cycles for the ANA positive women to 285 cycles of ANA negative women it was enough to significantly indicate that women who were ANA positive had lower numbers of embryo’s and a lower proportion of good quality embryos. Additionally in this group the pregnancy rate for ANA positive group was 28% compared to 46% in the ANA negative group. This understandably lead the authors to conclude that the

‘presence of ANAs significantly interfere with the oocyte and embryo development, as well as reduce implantation and pregnancy rate in patients undergoing IVF treatment’ (2).

Some good news

Although this study was done back in 2003 and was only a small sample size it had some interesting findings (6). Essentially what the researchers did was assess the IVF success rates of women testing positive for ANA’s and for those testing negative. In the first cycle women testing positive achieved lower pregnancy rates then those that were ANA negative. This is what we would expect given all of the above. The cumulative pregnancy rates though were not significantly different. AND that’s without the ANA positive women even taking specific medications to address their ANA. As the authors note

This indicates that the mechanisms of implantation failure by ANA could be solved, and effective and safe medication should be developed for better implantation rates

The treatment for ANA’s seems to vary and if you look at the notice boards you will find women taking different medications. Treatment will depend on your lab results and the type of patterning found. Prednisolone together with aspirin before conception and into pregnancy seems to be common treatment; however, again, discuss what will be best for you with your doctor.
INTERPRET IN CONTEXT OF OTHER TESTS

It is important to be mindful that when interpreting your ANA results that is only in the context of a ‘bigger picture’ taking into account other symptoms you may or may not be having and other blood tests that your practitioner completes. For example, in my case the fact that the ENA Panel (extractable nuclear antigen test) was negative, and the anti-DNA was also negative was an indicator that there were not necessarily any other autoimmune conditions under the surface and that by treating the impact of the ANA’s themselves that success may be just around the corner. And it was.

Being ANA positive is only one of many other antibody tests out there that may or may not impact on fertility. These can include antiphospholipids and immunoglobulins (IgA, IgG and IgM) and are also worth discussing with your specialist.

It is also important to remember that as previously highlighted being ANA positive can come in varying degrees. For example 1:80 indicates that there are far few antibodies in the blood then a result of 1:640. Having only ‘mildly’ positive ANA result may be less of an issue then a very high result and may influence you and your specialists decision as to whether or not the side effects of any treatment is more detrimental then not treating at all.

THE TAKE HOME ANA MESSAGES

Being ANA positive does NOT necessarily indicate that you have an underlying autoimmune condition or that anything is wrong, perfectly healthy, fertile people can be ANA positive
There is some research though that indicates being ANA positive is more common in women that need to receive fertility treatments
The presence of excessive ANA’s may be implicated in premature ovarian failure, embryo quality, implantation and recurrent miscarriage.
More research in this area is required and many fertility specialists do not believe that the presence of ANA’s on their own are worth treating

I am always worried about ‘scare mongering’ when I mention to my friends who are having fertility treatments to get their ANA’s (and other autoimmune markers) checked. There are so many things to worry about in the fertility world and just because this was one of my problems, it may not be yours. But given that the presence of excessive ANA’s does appear in a significant proportion of women yet to conceive, for the inconvenience of a blood test and a chat with your doctor its certainly something worth considering.

Finally, for those women who are interested in exploring ANA’s and other immunology issues there is a book by Dr Alan Beer entitled ‘Is Your Body Baby Friendly’. Dr Beer was an incredibly respected fertility specialist in California and assisted many women who had given up their fertility dreams to go on and get that take home baby. In his book it states that there is no such thing as ‘unexplained’ infertility and for everyone there is a reason. The book goes into some details about the different immunological problems that exist and also have some very inspiring case studies. A word of caution though the book is not necessarily for the faint hearted and may get you self diagnosing all sorts of issues! If you have run out of conversation or options with your fertility specialist though it may just very well give you a few things to discuss with them and for that reason is very well worth a look.

If you are doing or are thinking about doing IVF, don’t forget to get your free IVF guide with 19 evidence based ways that are designed to increase egg quality, implantation rates and hopefully IVF success!

References

1. Cline, A. & Kutteh, W. 2009. Is there a role of autoimmunity in implantation failure after in-vitro fertilization? Current Opinion Obstetrics and Gynecology. 21(3):291-5

2. Ying Ying, Yi-ping Zhong, Can-quan Zhou, Yan-wen Xu, Qiong Wang, Jie Li, Xiao-ting Shen, and Hai-tao Wu 2012. Antinuclear Antibodies Predicts a Poor IVF-ET Outcome: Impaired Egg and Embryo Development and Reduced Pregnancy Rate. 41 (5): 458-468 (doi:10.3109/08820139.2012.660266)

3. Molazadeh M., Karimzadeh, H. & Azizi M. 2014. Prevalence and clinical significance of antinuclear antibodies in Iranian women with unexplained recurrent miscarriage. Iranian Journal of Reproductive Medicine 12(3): 221 – 226.

4. Carp, H. Selmi, C. & Shoenfeld, Y. 2012. The autoimmune bases of infertility and pregnancy loss. Journal of Autoimmunity (38)J266 – J274

5. Revelli, A., Delle Piane, L., Casano, S., Molinari, E., Massobrio, M. & Rinaudo, P. 2009. Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics. Reproductive Biology and Endocrinology 7:40

6. Kikuchi, K., Shibahara, H., Hirano, Y., Kohno, T., Hirashima, C., Suzuki, T., Takamizawa, S. & Suzuki, M. 2003. Antinuclear antibody reduces the pregnancy rate in the first IVF-ET treatment cycle but not the cumulative pregnancy rate without specific medication. American Journal of Reproductive Immunology. 50 (4):363 – 7

ICSI IVF… What Is It About?

For some ICSI is just that next step down the fertility path when traditional IVF fails. For others their clinic ONLY fertilises eggs by using ICSI and there is no way around it. One thing is apparent though and that is that ICSI is gaining ground on IVF and becoming more and more common. Here are some answers to those common questions regarding ICSI.

What is ICSI?

ICSI, pronounced ‘ick-see’ stands for intra-cytoplasmic sperm injection. It is when the embryologist selects one sperm from the semen sample that has been provided and this single sperm is then injected directly into the egg. There are different methods and techniques that the embryologist can use to select the best sperm such as using an extra high magnification microscope or putting the sperm into substances that mature sperm then bind to and then picking one of these. For the purposes of this article we will just lump all these different methods together (as is mostly done in the literature).

There are strict rules set by various overseeing bodies that dictate which sperm is suitable for ICSI. For example sperm must be mature and of a particular size and shape. This is reassuring as it again attempts to ensure that only healthy, mature sperm are injected – though if they weren’t healthy, mature sperm the egg probably wouldn’t fertilise rather than having adverse outcomes for your baby.

Although it is a different procedure ICSI comes under the umbrella of IVF and sometimes your lab might interchange the term ICSI with IVF.

ICSI is different to IVF, which as you are likely to know is where the egg and the sperm are placed together in a dish and the sperm are left to their own devices to penetrate the shell of the egg and fertilise the egg that way. As a new patient in the fertility world IVF can seem a little bit more natural then ICSI because at least some sort of natural selection is taking place, right? That is in traditional IVF the best sperm still has to win at the end of the day, albeit in a manufactured environment. On top of injections and ‘harvesting’ your eggs ICSI can seem like yet another intervention.

Why is ICSI used?

ICSI has been traditionally used when there is significant male factor infertility and we can’t really go further without first briefly touching on sperm count. You might remember that the normal sperm count in a healthy man is around 40 million per ‘go’ (or ejaculate in case I wasn’t clear). Don’t forget though that sheer numbers is not enough and the sperm themselves need to be healthy with good motility, that is the need to have the ability to move around and get to where they need to and good morphology, meaning that they look the part with one tail and one head, for example. When a semen sample is provided, the embryologist will prepare the sperm, taking out all these stragglers leaving behind only the best of the best. Or as I have heard one consultant say SAS sperm.

Low Sperm Count

It has previously been mentioned that in instances of male factor infertility if the SAS sperm count is greater than 10 million it might be worth attempting IUI, if the count is between 5 – 10 million try IVF and anything less than this just use ICSI as the likihood of fertilisation without it would be relatively low. It is in these very low sperm counts that ICSI was first intended.

Previous Zero Fertilisation Rate

In addition to the reason of having low sperm count, another reason that ICSI might be used is if you have previously completed a cycle where there was zero fertilisation. This can happen in 10 – 20% of couples (Chen et al as cited in 1). Instead of having to live that one again, your embryologists may recommend that you skip plain old IVF and head straight to ICSI in order to give the egg and sperm the best chance to meeting and the egg fertilising. Remember though, that just because the sperm has been injected right into the egg, a little something special still has to happen and it doesn’t automatically guarantee fertilisation. It can in some instances improve it though which is why some clinics opt for ICSI as standard, though other clinics believe that with normal, healthy sperm ICSI is just not required and with mother nature not actually intending for a needle to necessarily be shoved in her eggs side they are quite possibly correct.

Rescue ICSI

ICSI may also be performed in ‘rescue’ situations. That is when traditional IVF has been attempted but no fertilisation has occurred after a certain amount of time. In this case the embryologist will inject the egg with sperm in an attempt to make it easier for fertilisation to occur. When rescue IVF is needed research shows that the sooner it is done the better. One small study shows that fertilisation rates for rescue ICSI performed after 6 hours has a fertilisation rate of 70%, compared with only 48% when rescue ICSI was performed after 22 hours (1). This 70% fertilisation rate is in line with the general fertilisation rates of standard IVF (Nagy et al as cited in 1) so this is a very good outcome. The 6 hour rescue ICSI, as opposed to 22 hour rescue ICSI also has better implantation, pregnancy and live birth rates. It should be noted that in some instances clinics do not always like to practice rescue ICSI due to the risk of more than one sperm being inserted into the egg and the complications this can cause (though there are ways technician can try and see if an egg has fertilised to reduce this from happening, for example by looking at the polar body of an egg, so this doesn’t happen very often).

Extra Testing or Surgical Collection

ICSI can also be recommended if you are planning on doing embryo testing or if sperm has needed to be collected surgically through means such as Percutaneous Epididymal Sperm Aspiration (PESA), Micro-Epididymal Sperm Aspiration (MESA) or Testicular Sperm Extraction (TESE).

Does ICSI cause higher rates of birth defects?

Generally speaking, the news is good. It seems that if you are comparing IVF to ICSI there is no correlation between the use of ICSI over IVF and birth defects.

This was recently covered in a metaanalysis completed by some researchers in Europe (2). They reassuringly found that there was no difference between ICSI conceived babies and IVF conceived babies and this has also been reported elsewhere (3).

Although this study is getting a little old now (Bonduelle et al 2003, as cited in 3) research was also done assessing children’s development at two years of age which is a welcome study to have given that a lot of research stops following the babies at birth. By completing standardised testing it was found that at two years the psychomotor and cognitive development of children were the same irrespective of whether the child was conceived using IVF or ICSI.

The Centre for Disease Control reports nearly 70,000 ICSI cycles were completed in America in the year 2012. This is a number that has been steadily increasing since the introduction of ICSI and we can be forgiven for thinking that there may be some safety in numbers. With all the checks and scrutiny that IVF clinics are rightfully held to, if ICSI was causing an increase in children with birth defects it would have come to light by now. And with the first ICSI babies being conceived in the early 90’s, this provides around 25 years of longitudinal data to have had scrutinised.

There was one study however, that again studied babies born following ICSI conception or IVF conception (4). They found that ICSI babies generally were at higher risk of preterm birth and lower gestational weight and age (even accounting for the fact they were born earlier). It seems though that ICSI babies were more likely to be part of multiples which could very well account for this outcome as when they assessed just singletons the ICSI babies were no longer at a disadvantage. This was only one very small study however with flaws in its own methodology, but in the interests of presenting both sides of the story, I mention it briefly.

Interestingly some researchers hypothesise that it sometimes can be the reverse, that is children of IVF conceived births can fare worse off than ICSI (2). One theory of why this is is because IVF is used predominantly when the sperm is of sufficient quality and quantity, but there are still difficulties with fertility. This infers that it is due to maternal factors that infertility is experienced. That is IVF is traditionally used when there is female factor infertility and ICSI when there is male factor infertility. If this is the case and if there are slightly poorer outcomes for IVF babies, it would seem that it is more important to have a healthy mother producing good quality eggs which may be able to compensate in some way for poorer sperm quality. I should also stress that when comparing birth outcomes the researchers are generally looking at things like birth weight and gestational age and not major disabling defects, therefore if not totally ideal is most likely to be so insignificant to not change your decision to complete one procedure over another. Though like everything, your doctor will be the best person to walk you through the pros and cons.

Whilst we have established that there is no differerence between IVF conceived and ICSI conceived babies, in the course of researching I did find that it has been mentioned that ART babies in general have higher risk of birth defects. There are a number of possible reasons for this and one is that it may be that the reason couples have difficulty conceiving is the risk factor for the defect rather than the technology itself. Alternatively, it may be one or more then one of the steps involved in the IVF/ICSI process that causes this. For example it may be the medication used to stimulate cycles, growing embryos in a culture or transferring embryos into the uterus that possibly increases the risk of birth defects (though IUI is also included under the ART umbrella and in IUI the embryo is not created in the lab so this doesn’t necessarily explain it all).

These same researchers also suggests that babies that are the result of a frozen embryo transfer are generally at less risk of preterm birth and lower birth weight. This is good news for women who are already less then thrilled to be completing a frozen transfer due to the slightly lower success rates. It is suggested that this occurs because in frozen embryo cycles there is not the same amounts of medication being used and in the luteal phase (that is the phase after ovulation/ transfer) the hormones in your body more accurately reflect those in nature. But don’t worry fresh cycle ladies, there is some evidence that suggests that there is actually no relationship between the total dose of medication taken, number of eggs harvested and the health of your baby (this is low grade evidence though and further research is needed).

Remember, take all this with a pinch of salt and there is no point in getting concerned over this without discussing your individual situation with your doctor. Although when you are in the moment it may seem like the be all and end all, for example ART children are possibly more likely to have certain defects, the overall number of children experiencing these remain a very, very small number. It is up to you to determine what you are comfortable with but for most women the risk of not having a child far outweighs the relatively very small risk of a child with an abnormality. But again the exact numbers and percentage will vary according to your particular situation so it is best to discuss this with your clinic.

How much does ICSI cost?

Depending where in the world you live the cost of ICSI over IVF can be significant. Resolve, which is a leading information and support network for all things fertility related report that ICSI can cost up to an extra $1500 to the cycle for those women living in the United States of America. If you are in Australia, where there are already excellent Medicare rebates for IVF, the extra out of pocket expense for doing ICSI over IVF can be around $300 depending on your clinic.

References

1. Chen, C. & Kattera, S. 2003. Rescue ICSI of oocytes that failed to extrude the second polar body 6 h post-insemination in conventional IVF. Human Reproduction Vol.18, No.10 pp. 2118-2121

2. Pinborg A, Wennerholm UB, Romundstad LB, Loft A, Aittomaki K, Söderström-Anttila V, Nygren KG, Hazekamp J, Bergh C: Why do singletons conveived after assisted reproductive technology have adverse perinatal outcome? Systematic review and meta-analysis. Human Reproduction Update 2013, 19:87–104

3. Devroey, P. and Van Steirteghem. A. 2004. A review of ten years experience of ICSI. Human Reproduction Update, Vol.10, No.1 pp. 19±28, 2004

4. Nouri, K., Ott, J., Stoegbauer, L., Pietrowski, D., Frantal, S. and Walch, K. 2013 Obstetric and perinatal outcomes in IVF versus ICSI-conceived pregnancies at a tertiary care center – a pilot study. Reproductive Biology and Endocrinology 2013, 11:84

9 Things You Should Know About the EmbryoScope

The EmbryoScope seems to be the latest ‘big thing’ in the fertility clinics and is being offered by more and more clinics to more and more women. Although it seems there are definitely benefits to using the EmbryoScope it may not be useful to everyone. Here are 9 things you need to know before deciding with your doctors whether or not to use the EmbryoScope:

It is a new type of incubator

Essentially, EmbryoScope is the trade name for a type of incubator that uses time-lapse photography to continuously monitor the embryo as it grows in the laboratory.

In traditional IVF, the sperm and egg are mixed together in a dish, hopefully the magic happens and the sperm fertilises the egg, or, if you are doing ICSI, the embryologist will inject the egg with the sperm, again, hopefully the magic happens and the eggs fertilise. The fertilised eggs, now embryos, are in their ‘dish’, surrounded by a ‘culture’ which is a substance that supports the growth of the embryos. The embryos are then placed in an incubator. The incubator enables the embryos to be locked away in an environment controlled for temperature, humidity, pH and gases (such as carbon dioxide, oxygen and nitrogen). About once a day the incubator is opened to monitor fertilisation rates, embryo morphology – that is what they look like, monitoring how many cells are there, if the cells dividing appropriately, if there is fragmentation and if the nuclei are behaving appropriately, just to name a few of the markers that are monitored. Each time the incubator is opened the highly controlled environment the embryo is in is disturbed. Therefore, it makes sense that the least amount of times the incubator can be opened the better.

By monitoring embryos in this way, the only information that technicians have on what has happened over the past 24 hours is what you can see at that very point in time. It provides a ‘snapshot’ so to speak. Cells can divide at different rates, can reverse the number of cells they have and nuclei can come and go over a 24 hour period. These events can be easily missed if only checking on the embryos once a day. All these events are also known to have significant impact on implantation rates and ongoing success of an embryo, therefore if extra information can be provided on early cell development it will be easier to choose the best embryos capable of ‘going the distance’.

What the EmbryoScope does is allows many photos (amount of photos per hour can be chosen by your laboratory) to be continuously taken of the embryos without them needing to be taken out of the incubator and disturbed. This ensures that the environment they are contained in is kept constant at its optimal settings. It also enables much more information to be collected on how your embyros have behaved over the last 24 hours and in theory the embryo that has shown the most favourable development and seems to be the best can be chosen.

2. Your embryos are kept at the ideal conditions for more time

The people that make the EmbryoScope, Virtolife report that the EmbryoScope incubator can hold up to 72 embryos – that is six clients can store up to twelve embryos at a time. This makes the EmbryoScope much smaller than a standard incubator. Because of this the environment inside the incubator is able to return to the ideal pH, temperature and gas levels at a much quicker rate when it has been disturbed. This is important because although the embryos do not need to be taken out to monitor them, the doors of the incubator do still need to be opened from time to time to place new dishes in or change culture media and the quicker the embryos can be returned to that ideal environment the less they are disturbed leaving them to grow into happy and healthy day 3 or 5 embryos!

3. Early evidence says that it can increase your chances of an ongoing pregnancy.

OK, so this is perhaps the thing that we want to know the most. One recent study (1) compared the ongoing pregnancy rates for women with embryos that were grown in a standard incubator against the pregnancy rates for women who had embryos grown in the EmbryoScope. What they found was that for women with embryos incubated in the EmbryoScope, there was a higher rate of ongoing pregnancy (54% for women with embryos grown in the Embryoscope versus 45% for women who used a traditional incubator) for each transfer. They were also shown to have lower early pregnancy losses and higher implantation rates, though interestingly the pregnancy rate was not statistically different. What this possibly indicates is that although there may be no statistical difference in getting that initial BFP by using the EmbryoScope and the information that is collected on your embryos early development, it allows for healthier embryos to be selected that are capable of going the distance and that are less likely to be abnormal which typically results in early miscarriage.

4. The culture that the embryos are in in the EmbryoScope is different (and some say better).

The culture system your embryos are grown in are different when using the EmbryoScope then what is used in the traditional incubators. One study (2) looked at if more fertilised eggs would grow to blastocyst when using the EmbyroScope as opposed to just a normal incubator. What they found was more embryos grew to blastocyst stage in the EmbryoScope then in the normal incubator. Remember the EmbryoScope is mostly being used as a monitoring system to pick out good embryos – and it can’t magically turn a bad embryo good – it just hopefully helps laboratory staff pick the best one to transfer. Therefore the fact that the study found more blastocysts were produced is kind of interesting, because up until now the EmbryoScope wasn’t expected to change the development of the embryos. The scientists who conducted this experiment thought of a couple of reasons for this result. One was that, as we have already discussed, the environment in the EmbryoScope was able to return to those ideal conditions much faster than a traditional incubator and the other reason was that culture system and EmbryoScope slides were different and possibly better at supporting growth to blastocyst then traditional incubator culture and equipment.

5. Its still only experimental.

Although there does seem to be some promising data coming out supporting the EmbryoScope it is still a new technology. A recent metaanalysis published in the ‘The Journal of Assisted Reproduction and Genetics’ (3) warns that despite the initial optimism, the data is insufficient to warrant the extra cost to prospective parents. In fact they were only able to find four studies that investigated using time lapse monitoring of embryos and the impact of using this method for selection on ongoing pregnancy rates. Needless to say, as always it seems in fertility research, more studies would be beneficial. Saying that though, all technologies and advances are new at some stage, so as long as your doctor isn’t concerned that there could be any disadvantages and if your clinic is one of the ones that provides the use of EmbryoScope free of charge, then surely there are not costs to trying?

6. It can cost more money.

If your clinic is not one of those clinics offering it to you free of charge, the extra costs on top of your normal IVF or ICSI charges can be significant. In Australia the extra costs to you can be between $0 to $800… a wide variation! Because there is no Medicare number for this you are also unable to claim any out of pocket expenses. In the UK I have seen quoted surcharges of between £400 –£600. The EmbryoScope, from what I have seen, doesn’t seem to be as widely advertised in America (please correct me if I am wrong!) but when it is used, the cost of it seems to be included into the cost of the IVF cycle and isn’t charged as an extra. Clearly, this is one of those things that needs to be discussed with your clinic.

7. May not be helpful to you if you are a ‘poor responder’.

You may already have the gist, but the idea of the EmbryoScope is to help laboratory staff chose the best embryo out of your batch for you to transfer. Ladies who traditionally don’t have success with IVF cycles generally don’t produce many viable embryos. (This is a big generalisation though!) Therefore if you don’t have many embryos the need to use the EmbryoScope to pick the best one isn’t necessary because you may only have one or two available anyway. In this case it doesn’t really matter what your embryo looked like at every stage because chances are you are going to transfer it regardless. Saying that though, even if you don’t have many embryos and its not going to help your treating team chose the best embryo it still might be helpful to them from a diagnostic point of view. That is they can see exactly where and when the embryo does (or doesn’t!) stop developing normally which might be helpful in planning future treatments.

8. May not be helpful if your clinic grows embryos to Day 5 as routine.

EmbryoScope is mostly used to pick the best embryo up to day 3. For clinics that routinely grow their embryos to blastocyst stage the EmbryoScope may not be considered as important. Though as discussed above, with studies showing that an embryos early development, development that is best seen in the EmbryoScope, having a positive impact on ongoing pregnancy rates, this seems to be a bit of a short sighted reason. Simply getting to blastocyst stage, in whatever shape or form, isn’t necessarily enough to go the distance. It would still be good to know what happened in those early days to chose the best one for transfer.

9. Its going to become more and more useful.

As the EmbryoScope is used more and more, laboratory staff and our doctors are going to be able to learn and collect much more data on embryo development than ever before. This will hopefully let them learn new things about how an embryo develops in the very early stages and its impact on implantation, ongoing pregnancy and the chances of the take home baby we always talk about. One journal article (4) suggests that by watching the appearance of the embryo very closely embryologists can watch out for distinct milestones and markers in the embryo development. By using this information they will then hopefully be able to develop more of a ‘predictive model’ for the embryos success. What they hopefully aim to do is identify by day 2 or 3 which embryos are those destined to become your take home baby by examining how it looks and behaves. By identifying the embryos at this much earlier stage this means that they don’t have to grow to blastocyst in an artificial environment – a situation which is sometimes associated with problems of its own.

Whether or not you chose to use the EmbryoScope is up to you in consultation with your doctor. By discussing things through with your doctor taking into account your own individual circumstances can you make the best informed decision.

References

1. Rubio I., Galan A., Larreategui Z., Ayerdi F., Bellver J., Herrero J. & Meseguer M. 2014. Clinical validation of embryo culture and selection by morphokinetic analysis: a randomized, controlled trial of the EmbryoScope. Fertility & Sterility. 102(5):1287-1294.e5.

2. Speksnijder, C. van de Werken, S.M. de Jong, A.J.A.M. Dons, J.S.E. Laven, E.B. Baart & Erasmus MC . 2011 Abstract: Improved embryo development in a time-lapse incubator system evaluated by randomized comparison of surplus embryo development to the blastocyst stage. Abstracts of the 27th Annual Meeting of ESHRE, Stockholm, Sweden, 3 July – 6 July, 2011 (doi: 10.1093/humrep/26.s1.26)

3. Racowsky, C., Kovacs, P. & Martins, W. 2015. A critical appraisal of time-lapse imaging for embryo selection: where are we and where do we need to go? Journal of Assisted Reproductive Genetics. 32: 1025 – 103

4. Milewski, R., Kuć, P., Kuczyńska, A., & Stankiewicz, B., Łukaszuk, K. & Kuczyński, W. 2015 A predictive model for blastocyst formation based on morphokinetic parameters in time-lapse monitoring of embryo development. Journal of Assisted Reproductive Genetics. 32:571–579

Acupuncture and IVF: Does it help?

***For a 2018 update click here…

Acupuncture. Its one of those things that you feel you should do when having fertility treatments, but you’re not really sure why, when in the cycle you should have it or if it does actually work. I took the time to sift through all the research to see if it is actually worth our while. By the way, this is a long post packed full of evidence and information. If you are limited for time skip towards the end for a quick summary.

I remember my trip to an acupuncturist. And yes, I use the word ‘trip’, as in singular. Having decided to try and leave no stone unturned in the pursuit of a BFP I duly attended the acupuncturist which was attached to a nearby nutritionist (using the theory that if she was attached to other holistic type health people then surely I was on to a winner!). Despite looking up her qualifications, experience and interests (there was ‘women’s fertility’ listed with about 10 other ‘specialty’ areas) I was disappointed about her lack of insight into the fertility world and I definitely got the sense that she considered me to be ‘jumping on the bandwagon’ by pursuing IVF. Sitting down to discuss the treatment I told her my diagnosis, which included PCOS and she didn’t seem to think that there was a problem with the fact that ovulation was few and very far between, along with all the hormonal difficulties women with PCOS can have, and said that pregnancy was just a matter of time. When I asked about the mechanisms behind acupuncture I was told it was just about improving blood flow to the uterus and pointed at a diagram on the wall that was meant to be the explanation. I perhaps wasn’t the best acupuncturist patient and was a little anxious about the whole thing and the sensation of the needles going in was not a pleasurable one (for me anyway). But I think relaxing and discussing problems with a patient is as much part of the therapy as the therapy itself. Well, kind of. But I think the real kicker came when I was left to ‘relax’ for 20 minutes, which incidentally turned into 50 minutes, without music but with the soundtrack of the man next door discussing his bowel habits with the nutritionist! Anyway, convinced that she had forgotten about me and shouting out to attract her attention, she eventually came back and I eventually left– it was all quite bizarre. You hear a lot that the main benefit to acupuncture is taking the time to relax and distress and that’s the main way that it helps you, if that is the case it certainly didn’t help me. For those that are wondering it was a BFN that cycle by the way.

But that’s just me. I know a lot of people who have had acupuncture and rave about it. A lot of people find it relaxing and its stress relieving properties, like I said, seems to be one of its main perceived benefits in fertility treatments. Along with its ability to ‘improve bloodflow’ that is.

So how does acupuncture work?

In its most basic form, acupuncture involves inserting a number of needles into the body at certain points, or acupoints, along meridians in the body. There are around 400 acupoints running along 20 meridians – 12 primary ones which are generally associated with internal organs, and 8 extradordinary ones. Accupuncuretoday goes on to describe that ‘qi’ flows along the meridians. Qi is described as kind of like an energy or a vibration that carries the effects of the acupuncture from one acupoint to another. When the qi flows the body is able to work properly. There are certain acupoints that must be stimulated on various meridians to treat different ailments. For example, the acupoints for treating fertility will be different to those for treating back pain. For a full list of acupoints, have a look here.

But HOW does it work for FERTILITY?

In an overview of the use of acupuncture in gynecology, Napadow et al stated that in her view, recent basic and clinical research has demonstrated that acupuncture regulates uterine and ovarian blood flow, and that the effect is most likely mediated as a reflex response via the ovarian sympathetic nerves, and that the response is controlled via the supraspinal pathways

So it seems as if my acupuncturist was correct in that acupuncture assists with blood flow. AND there seems to be some sort of medical explanation for it. Because of the increased blood flow to the uterus, it also produces a healthier uterine lining and helps with implantation (1)

Besides in just assisting with blood flow, there are a number of other ways in which it can possible help IVF and pregnancy outcomes:

Acupuncture is well utilised for the management of pain. This is due to an increase in a type of endorphin when acupuncture is performed. When endorphin is altered it has a knock on effect of affecting hypothalamic function which is responsible for gonadotropin-releasing hormone which in turn impacts Follicle Stimulating Hormone and Luteinising Hormone and the overall functioning of the menstrual cycle (1). As we know these are all very important hormones in the IVF process (and the ones that are monitored closely when you go for regular bloods) so regulating these with help from acupuncture, should impact positively.
Acupuncture can encourage the production of naturally occurring opioids which are generally pain killers but is part of a chain of events that can also manage stress(1). Which brings us back to that chestnut of ‘relaxing’. Obviously if you are in my situation and find the acupuncture stressful, whether that be due to the process itself, the financial costs or the time it takes, then these benefits are probably not going to be felt and acupuncture may not be your thing.
Another study found that if acupuncture is done in the follicular phase, that is before egg collection, then it may affect the stem cell factor in the follicular fluid that surrounds the eggs causing better quality eggs and hence a better quality embryo (Chen et al as cited in 3)
And finally, acupuncture may also assist in hormonal balance during the implantation stage, again regulating hormones in this way and helping the embryo to implant (3).

So… Does It Work?

There have been quite a number of studies done on acupuncture trying to determine its use and benefit. It seems that each study seems to say a different thing. This is event the case for meta-anaylsis studies (where a researcher looks at all the relevant experiments that have been completed and combines it into one big summary so to speak). One article will state that acupuncture is helpful in increasing pregnancy rates whilst another will say that it does not increase live birth rates.

The most recent Cochrane Review stated that there was no significant difference of acupuncture on fertility treatments. This was regardless of whether acupuncture was done around the day of egg retrieval or around the day of embryo transfer (4).

Interestingly though the Cochrane Review evaluated acupuncture against different types of controls. That is, they compared the effectiveness of acupuncture against having no acupuncture and also examined studies where the effectiveness of acupuncture was compared against sham acupuncture. Sham acupuncture is where needles are used that retract back into themselves after hitting the skin and hence doesn’t penetrate the skin like a normal acupuncture needle – though the feeling is still the same and women receiving this treatment would have definitely have thought they were having acupuncture done. What they found was that when having acupuncture was compared against this sham acupuncture there was no significant differences in the live birth rate; however, when acupuncture was compared against having no treatment at all there was a significant difference in the live birth rate! This perhaps suggests that it is not the actual acupuncture and its effect on qi and manipulation of acupoints but that perhaps some placebo effect is having effect and the act of participating in the treatment is more beneficial then the actual treatment itself.

Saying all that though, there was another study done that looked at when in their cycle women had acupuncture done and if this had any impact on pregnancy. They looked at women who had it done during follicle phase (when eggs are still developing before pick up), on the day of egg pickup, before and/or after embryo transfer and during implantation stage. What they found was that there was ‘no statistically significant difference in … treatment (that was) performed only around the time of embryo transfer, follicle phase or implantation phase’ (3). They did indicate though ‘that acupuncture increased pregnancy rates when performed at follicle phase and 25 min before and after embryo transfer or 30 min after embryo transfer and after the implantation phase in the IVF process’ (3)What this seems to be saying is that acupuncture does seem to have a roll but just going at egg pick up or transfer isn’t going to be enough. It needs to be done consistently throughout the follicular phase, that is when you are being stimulated and taking medications, AS WELL AS before and after embryo transfer and even perhaps during implantation phase.

At exactly what times in these phases isn’t exactly known. Some studies had women having acupuncture at day 1 or 7 or 9 …or more! It varies a lot and seems to be at the whim of whoever designed the experiment. Perphas if you think that acupuncture might be worth trying, and you have the time and the money to give it ago, that should be something that you can discuss with your experienced acupuncturist.

You haven’t really given me an answer here…

No, to reply to my own comment, I haven’t. Although from what I have read, most articles seem to support the theory that acupuncture is not of any significant assistance in fertility treatments there is none the less still wide ranging views.

There are a number of reason why there is so much disparity:

Having acupuncture can come in many different forms. As we have noted, some women go for just a ‘one off’, some may go for the duration of their cycle, some just before egg pickup and some just before and/ or after embryo transfer. There are many different timeframes as to which you can receive acupuncture and to date studies seem to be evaluating the effectiveness of acupuncture (in no consistent format) to no acupuncture, rather than evaluating the effectiveness of the different formats…This makes it more difficult to compare apples with apples, so to speak.
It seems that the skill of the practitioner can and does, impact on success of the acupuncture. When these studies have been completed there are some instances of inadequately trained practitioners performing the acupuncture. If it is not an experienced and knowledgeable practitioner inserting those needles it may as well be as useful as having sham acupuncture (though as we previously noted this has been found to be just as useful! Confusing much?!)
The location of the acupuncturist and the effort it takes to attend such appointments also needs to be taken into account. There was one trial in which acupuncture was found to lower the rate of pregnancy. One theory for the reason for this result was that the study required patients to drive to an acupuncturist before and after embryo transfer rather than have acupuncture ‘on site’ where the transfer was being completed. It is thought that driving to this extra appoinment timed just before and just after the transfer, added stress in an already stressful day and this extra stress helped explain this difference (2). Don’t get scared off though, this (from what I have read) is the only study to have had this ‘negative’ result, it should also be noted that the group NOT receiving acupuncture had a freakishly high success rate – nearly double of what it should be. This in turn would make anything in comparison look bad.
None of the studies seem to break down what the medical conditions are of the women receiving the treatment and the reason they are receiving IVF. That is a woman who is having IVF due to male factor infertility will likely to have different hormone levels then a women with severe PCOS and hence the impact of acupuncture may be different. If further research was completed it may, or may not, help to identify, or rule out, which groups of women are likely to benefit from acupuncture.

So in summary…

Evidence is varied whether or not acupuncture in fertility works and as in many of the topics surrounding fertility more research is needed. Some say it does and some say it doesn’t have any impact on pregnancy rates and increasing the chances of you getting your ‘take home baby’. If you do happen to have the time and the money there does not appear to be any harm done so is perhaps worth a try – even if it is just to get some ‘stress relief’ or benefit from a placebo effect.

If you do decide to that acupuncture is for you, remember that some of the evidence suggests that there is only benefit if done throughout the cycle and not just as a one off, tick the box kind of activity. Unfortunately, there is no set regime for these what days to get acupuncture and you would need to find a reputable acupuncturist specialising in fertility to help you form a treatment plan. Put the effort into finding an acupuncturist who understands the unique challenges that fertility patients face, the various medical conditions that cause fertility and is willing to take the time to tailor your treatment for you.

References

1. Cochrane, S., Smith, C., Possamai-Inesedy, A. & Bensoussan, A. 2014. Acupuncture and women’s health: an overview of the role of acupuncture and its clinical management in women’s reproductive health. International Journal of Women’s Health 6: 313 – 325

2. Stener-Victorin, E. & Manheimer, E. 2011. Commentary on the Cochrane Review of acupuncture and assisted conception. Explore (NY). 2011 ; 7(2): 120–123. doi:10.1016/j.explore.2010.12.01

3. Shen, C., Wu, M., Shu, D., Zhao X. & Gao, Y. 2015. The Role of Acupuncture in in vitro Fertilization: A Systematic Review and Meta-Analysis. Gynaelogical and Obstetetric Investigation 79:1–12 DOI: 10.1159/000362231

4. Cheong YC, Dix S, Hung Yu Ng E, Ledger WL & Farquhar C.2013. Acupuncture and assisted reproductive technology (Review). The Cochrane Library, (http://www.thecochranelibrary.com) issue 7