Friday, July 29, 2011

What happens to patients who do IVF before doing their homework !

I received this email from a patient.

I have edited it , but reading it still makes me cringe !

My case details :

- I am 32
- My husband has slightly low motility (around 30% -including slow and rapid linears- during the best of times). However, doctors have always told us that since he has a decent sperm count, the motility is not something to worry.
- We have been trying for a child for 4.5 years. We have tried on 7 clomid cycle and 1 letroz cycle. None of them were monitored. But i did check on OPKs. I always ovulated on the minimum dose of clomid.
- I used to get my periods regularly (35 day cycle). But my cycle became irregular after we started to try for a baby. However, I still got my periods every 35-45 days

IVF Details:

- I had my IVF done through NHS. However, it was a self-funded cycle
- I only got to meet a doctor twice during my cycle. Once during a scan (when they wanted to run back and watch the royal wedding) and once during the egg retrieval. I saw different doctors both the time and I could not relate to either of them because they were both busy, hassled and just wanted to get the job done.
- They never performed any bloods on me.
- They did not try to control my period and just took the payment and did not even speak to us after that, inspite of us making several attempts to speak to them.
- We waited for 2 months for my period- after making the payment. I finally got desperate and took the oral progesterone supplements that I got from India, to bring my periods on.
- I don't have the details of the exact medication used, as all the papers related to the IVF was retained by NHS (as is the rule here).
- The medication given to me were self-injectibles, that my husband had to inject.
- all my scans were very promising, with a decent number of follicles developing and with a healthy trilaminar endometrium.
- During egg retrieval, they retrieved 15 eggs.
- However, only 5 were mature and only 3 fertilized. All the other eggs were immature.
- 1 fertilized naturally and 2 fertilized 'supposedly' slowly.
- the naturally fertilized ovum was a good 4 cell on day 2
- 1 of the 2 late comers was also a good 4 cell on day 2
- the only other embryo was a 2 cell on day 2.
- No images were taken and the center 'supposedly' did not grade the embryos. All that the embryologist said was 'they look fair enough'
- They did a day 2, 2 embryo transfer of the 4 cell embryos (they said that there was no point in waiting longer, as there weren't any embryos to choose from).
- After the ET, they just gave me a vaginal progesterone supplement and sent us home. They never saw us again. I got to speak to some nurses twice during the 1 ww (it wasn't even a 2ww), when I called them crying because I had started bleeding exactly 1 week after ET.

This story is not unique - and it's something I have come across before as well. This is a very smart, well-informed woman. Sadly, she only did her homework after her cycle failed, by which time the damage had already been done ! If only she'd asked for some Information Therapy before starting her IVF cycle, she would have been able to save herself a lot of needless distress !
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Thursday, July 28, 2011

Clueless doctors - and clueless patients !

I just received an email from a very upset patient.

" Dear Doctor,

Can you please help me make sense of my report ? I was asked to give my semen sample for culture and sensitivity. On the report I received just now, the only statement was - " sterile semen culture'.Nothing else ! What does this mean ? Does this mean I am sterile and cannot get my wife pregnant ? How do I treat this ?"

This would be comic, if it weren't so tragic !

A sterile semen culture is a good report, and means that no bacteria were grown from the semen after culturing it in the lab for 48 hours. This means the semen is free of infection.

However, the poor man mis-interpreted this report as meaning that he was sterile !

I wish doctors were a little more thoughtful when designing reports. The least they could do was provide a short explanation of what the result means !

Wednesday, July 27, 2011

IVF, science and pseudoscience

Medicine is not an exact science. It’s not possible for us to predict what the outcome of an IVF cycle is. While we are very good at making embryos in the lab, once we transfer the embryos into the uterus we still cannot predict which embryo will become a baby & which one won’t. When an IVF cycle fails , especially after the transfer of Grade A embryos, the first question the patient is going to ask is - Why did the cycle fail? When this happens , a lot of doctors become very defensive because they feel the patient is blaming them for the failure. This is why they are reluctant to tell the truth , which is - We really don’t know because we don’t have the technology to be able to answer this question. This is the honest scientific answer ! After all, human reproduction is an inefficient enterprise, whether it’s in the lab or in the bedroom !

A lot of doctors will provide pseudoscientific explanations in order to keep the patient happy. Partly they do it in order to protect themselves ; and partly they do it because this is what patients expect. Patients don’t want to be told that doctors are human and that there are lots of things they don’t know. Patients want answers because they feel doctors are experts to know everything about what’s happening. This is why doctors will then spend a lot of money doing expensive tests such as immune testing, endometrial function tests, and tests for tuberculosis by doing PCR on an endometrial biopsy in order to keep their patients happy.

While some of these tests may be useful in a research setting , the honest truth is they are not very useful in a clinical setting , because we still don’t know how to interpret these tests for the individual patient. Then why do doctors make patients do these expensive tests ? For one, doctors are pleased , because they’ve done some additional tests and found some additional information ( even though it may be clinically useless). Patients are happier too , because they feel the doctors are getting to the root of the problem and after getting the computerized result of an expensive test, he finally knows what’s happening, so he can fix it for the next attempt ! Unfortunately, most of these tests don’t provide any useful results , and they actually can be harmful to the patient.

This is because when the results are abnormal , the doctor is then obliged to try and so something in order to “ fix “ the problem. All this over testing leads to over treatment - none of which actually helps to improve outcomes ! This is where the difference between science and pseudoscience comes in. Honest doctors will tell the patient that we have now reached the limit of our technology. We don’t have very good answers because it’s hard to track the fate of a microscopic ball of cells once it’s transferred into the uterus. There are certain tests which are useful on a research basis and not a clinical basis ; and if the patient still wants these tests done, we can do them but we are not certain whether the results of these tests will help us to improve the outcome. Most patients are intelligent and understanding. They know that doctors are not God , and if the doctor takes the time to explain things to them properly and don’t insult their intelligence by talking down to them, they will accept the limitations of medical science , and will be happy to continue with their next IVF cycle. However when doctors don’t take the time and trouble to counsel their patients , they get fed up and frustrated , causing a lot of unhappiness both for patients and doctors .

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Tuesday, July 26, 2011

Eggs are not follicles !

Many infertile women are very confused about the difference between follicles and eggs
Just because they ovulate, they feel they much be producing good eggs every month.

However this is not always true ! Women can have anovulatory cycles - and even ovulatory cycles may be the result of poor quality eggs !

What about those women who are happy that their ultrasound scans for follicle tracking/ ovulation monitoring shows that they grow follicles every month ?

While I agree this is reassuring, it does not mean that the egg quality is fine - especially in an older woman

Remember that the follicle is only the black bubble which the sonographer can track during your scan. Normally, a good follicle ( one which grows at 2 mm per day and ruptures on Day 14 at the time of ovulation) does contain a good egg ( especially if the cervical mucus is good and the endometrial stripe is thick and trilaminar at this time - but this is not always true !

Eggs are microscopic structures , and can only be seen under the stereozoom microscope in the IVF lab when the doctor does an egg retrieval and sends the follicular fluid to the embryologist for scanning

Remember, that :
Not all follicles will contain eggs
Not all the eggs will be mature
Not all the mature eggs will fertilise

There's many a slip twixt the cup and the lip - and this is especially true for older women, whose ovarian reserve declines as they age.

Sadly, they ( and their gynecologists as well !) are often lulled into a false sense of security as a result of the ultrasound scanning. However , if you remember the fact that eggs are not follicles, you'll not fall into this common trap !
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Monday, July 25, 2011

Is it the egg ? or the sperm ?

Whenever an IVF cycle fails, the commonest question patients ask is - was there a problem with the eggs ? or with the sperm ?

Logically, one would expect the answer to be 50-50 - after all, both are gametes which contribute the 50% of the DNA to the embryo.

In fact, this is one of the reason there are so many tests for testing sperm "quality" - ranging from the zona free hamster egg penetration assay ( which is now obsolete) to the newer sperm DNA fragmentation tests ( which are very fashionable and popular right now, but will also soon get relegated to the dustbin).

However, these tests are useless in clinical practise.

Why do I say so ?

Let's consider a couple who does ICSI treatment for a low sperm count, and gets poor quality embryos . They are disheartened and upset, so they get a second opinion from another "expert"

This doctor does additional tests to show how much of an expert he is, and how much better he is than the original doctor ( who did not have the sense to do these advanced tests, because he is not as well-informed ! ) These tests are understandably very expensive and esoteric ( after all, they are not done frequently, because they are not very useful, which is why the lab charges more to do them !)

In many of these men, the lab will find the sperm has high DNA fragmentation. The expert says - Aha ! this is the reason for your poor quality embryos, which the earlier doctor missed !

This is highly logical and makes sense to the patient - after all, if the sperm have fragmented DNA, it's quite logical to expect them to make fragmented poor quality embryos !

The husband starts to beat up on himself; and the doctor congrats himself on making the right diagnosis and pinpointing the " problem". He then suggests that they need to use IMSI to solve the problem- even though the success rates with IMSI are lower than with ICSI !

However , in reality these new sperm function tests are often very unreliable , because they have not yet been adequately researched . They have not been standardised - and lots of fertile men have sperm with high DNA fragmentation levels ( and are blissfully unaware of this "defect" in their sperm because they have enough sense not to go to a doctor !)

New is not always better ! In reality, poor sperm do not contribute to poor quality embryos !

Just look at the image of the sperms and the egg above . The sperms are tiny, which means the sperm which fertilises the eggs has very little role to play in embryo cleavage after fertilisation has occurred ! The reason for fragmented embryos is usually an egg cytoplasm problem, because the mitochondria in the egg cannot prove enough energy to drive cell division.

What about the high DNA fragmentation report ? As I said, many fertile men have high DNA fragmentation rates - this does not correlate well with even in vivo fertility at all !

In theory ( or in a mouse lab), the right way to determine if the reason for the poor quality embryos lies with the egg or with the sperm could be performed by doing cross-testing. The wife's eggs could be fertilised with donor sperm; and donor eggs could be fertilised with the husband's sperm. The embryos could then be grown in the same incubator, to see which ones divide well, and which ones start to fragment.

However, it's extremely difficult to do this in real life, which is why we tell patients that if we have poor quality embryos after ICSI, 9 times out of 10 the problem ( based on years of experience) , the problem is with the egg and not the sperm !
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