Tuesday, February 08, 2011

I have failed five IVF cycles , Dr Malpani - what do I do next ?


My patient was at her wit's end and was sobbing her heart out. I have done 5 IVF cycles all over the world, Dr Malpani - and they've all failed. What do I do next ?

This is always a complex question - and there's no easy answer. You need to be analytical and logical, so we know what to do next. The trick is not to waste time looking for problems, but rather to focus on solutions which will allow us to bypass the problems !

We need to ask ourselves - what have we learned from these failures ? What can we do differently the next time ? What can we change to increase the chances of success ?


If you do need to change something, remember that there are only 5 things we can change in any IVF treatment

1. The IVF treatment protocol
2. The clinic
3. The sperm
4. The eggs
5. The uterus

Let's think through this process logically , so we can prepare a plan of action for the next cycle.
This is a very useful framework, which helps you to analyse the failure; learn from it; and then move on !

First, I need to emphasise that sometimes there's really no need to change anything at all. Not every IVF cycle is going to result in a baby, even it it's text book perfect. Sometimes, all you need is to be patient - and a little bit of luck !

But what if 3 cycles have failed ? Then what ? Let's look at what we can change, step by step.

1. The IVF Treatment protocol. While the IVF treatment protocol is pretty standard, every woman's body is different, and every patient responds differently to IVF medication ! Each cycle teaches us how your body responds to superovulation - and a lot of the art of IVF and the skill of a good IVF doctor consists of superovulating you with just the right dose of medications, to get you to produce an optimal number of high quality eggs. While most young patients with normal ovarian reserve grow well in response to a standard protocol, patients with poor ovarian reserve and those with PCOD need a lot of extra attention and closer monitoring. We may need to use additional alternative medicine supplements such as DHEA for these patients; while others may need higher doses of HMG. Some of this is trial and error - and you must keep careful records and learn from each cycle , until we can customise the perfect protocol for you !

2. The clinic. If you find your doctor is very rigid and is not willing to make any changes inspite of repeated failures, then it's a good idea to get a second opinion, to confirm you are on the right track. Getting a fresh brain to look at the problem can be very helpful and can offer new insights ! While the basics of IVF are the same all over the world, there is a great deal of difference in the quality of the services IVF clinics provide - and it's a good idea to keep an open mind and explore alternatives if you feel your present clinic is stuck in a rut; or refuses to do anything different. This is especially true if your doctor batches patients; does IVF on a part-time basis; refuses to share medical information with you; or does not provide you with photos of your embryos ! A word of warning here - doctor shopping is not usually a smart thing to do - and if you have a competent doctor with whom you have a good relationship, then it's best to preserve this, and ask him to offer additional options to you, rather than to establish a new relationship with a new doctor. However, when you do go from one IVF clinic to another, you are quite likely to get VIP care, because IVF doctors are quite competitive, and it's often a matter of pride for them to get a patient pregnant when the earlier IVF doctor has failed to do so !

3. The sperm. If you have failed fertilisation in an IVF cycle, then you need to do ICSI in your next cycle. This will ensure fertilisation and is a simple and effective solution ! Using ICSI allows us to work with practically any man's sperm, no matter how low the count or poor the motility and morphology . I do not believe DNA fragmentation affects success rates if ICSI is being used if the embryologist is competent ; and I believe that if we have poor quality embryos after ICSI even in men with severe oligoasthenospermia, the problem is usually because of the egg or the lab, and not because of the sperm. ( I know that many clinics will blame the poor sperm quality when they get poor quality embryos after ICSI. This is rubbish - it's usually just a poor quality lab which is to blame ! However, men with a low sperm count have low self-esteem - and they are quite willing to accept this flawed conclusion - and use donor sperm for the next cycle ! ) . It's possible that in a very very few men who have persistently poor embryos after ICSI, it could be the poor quality sperm which are responsible. The only way to prove this is by split crossover testing ( fertilising the wife's eggs with donor sperm; and fertilising donor eggs with the husband's sperm, and then comparing the embryo quality ), but as you can imagine, this can be very hard to do in real life !

4. The eggs. When you remember that the egg is a thousand times bigger than the sperm; and that the energy for cell division during embryo cleavage comes from the mitochondria in the egg's cytoplasm, it's hardly surprising that the vast majority of time embryos fail to implant is because of "egg problems". The problem is that it's very hard to make this diagnosis, as eggs are just spherical blobs, and we simply do not have the technology to assess egg quality or egg function. However, if there is a problem with embryo quality in a good IVF lab, 9 times out of 10 the problem is because of the eggs. While it's sometimes possible to correct this problem in the next cycle by using various measures to optimise egg quality ( such as DHEA or a more aggressive superovulation procotol), most of the time the most effective solution is to use donor eggs. This option has a very high success rate - but it can be quite hard for some women to accept - especially those who are young and have a good ovarian response, with a normal AMH level and a normal antral follicle count. It can be hard for them to come to terms with the possibility that their eggs may be flawed - and the idea of using foreign genetic material can be unpalatable to many women ( and their partners).

5. The uterus. Surrogacy has become very popular recently because of the disproportionate amount of media attention it attracts, and many women feel that the best medical solution for them after many failed IVF cycles is surrogacy. After all, the fact that the embryos are not implanting means the uterus must be " defective" , so doesn't it make sense to use a fertile woman's uterus as an incubator for 9 months ? However, the truth is that surrogacy is an expensive and complex treatment option, which is best reserved for women without a uterus. Research shows that the reason for failed implantation is much more likely to be genetically abnormal embryos ( because of poor quality eggs), rather than a uterine problem. However, because it's very profitable to offer surrogacy , many IVF doctors are keen to push their patients towards this option . For a woman who has failed 5 IVF cycles and is fed up and frustrated, surrogacy does seem to be a very attractive option - no hassles with the dreaded 2 week wait - someone else can do all the hard work ! However, the success rate for surrogacy for these women is very poor, because it's not their uterus which was the problem ; which means that using another woman's normal uterus is not going to help at all !

I remind patients who have failed IVF to remember the Serenity Prayer -
God grant me the serenity to accept the things I cannot change;
the courage to change the things I can;
and the wisdom to know the difference. Outcomes are always uncertain, but if you take well-informed decisions on a logical basis, you will have peace of mind you did your best !


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4 comments:

  1. Excellent post. I just have a comment to make about the final bit, about surrogacy being reserved for women lacking a uterus. There is another class of women to be considered here, and these are those who keep suffering from recurrent pregnancy loss sometimes in the first (risk factors like Anti-thyroid antibodies or anti-phopsholipid antibodies for example), but also in the second trimester and 3rd trimesters.

    Why these losses happen is the billion dollar question, but after you move past a certain point, you can conclude with some certainty that it is no longer an embryo issue, but a complex problem with the woman's physiology that hinders pregnancy.

    I know somebody who recently lost her 3 day old baby- This woman was diagnosed with PCOS after many long years, finally conceived with metformin (stopped after the first trimester. One of the many issues when the baby was delivered- there was grade 2 premature aging of the placenta. The risk factors for this include smoking (obviously not in play here) and diabetes. You have to wonder if PCOS had something to do with it, but how do you ever know for sure?

    ReplyDelete
  2. Anonymous2:41 AM

    Hello Dr-
    Me and my wife have failed 2 IVF cycles and 1 IUI.
    I have problem of Retrograde Ejaculation. The root cause has been told to us by a specialist in Urology at Batra Hospital is my single kidney. For iUI the sperms were collected from urine.
    The IVF cycle is very very tough for us to carry out due to the high costs involved. Do you think doing repetitive IUI would help as it is feasible for us to spend 10K each month rather than investing 200K in each IVF cycle and moreover the expectation and pain involved in a failed iVF are exponentially higher than the one from
    iUI!
    Also, will a kidney transplant help us in correcting the retrograde issue?
    Kindly advise!

    ReplyDelete
  3. Men with retrograde ejaculation often have poor sperm quality. If it is poor, then an IUI will not help, sorry

    Don't do the wrong treatment just because the right treatment is expensive !

    No, you do NOT need a kidney transplant

    Dr Malpani

    ReplyDelete
  4. Hello dr I have 3 failed ivf(1. self, 2. donor egg, 3. donor embryo). My age 35 and husband 37. My dr says its implanting issue. Is der solution for this issue? Wat say abt embryo glue, assisted hatching?. Other than thisissue I dont have any other problem. All my reports are clean. Did reproductive molecular immunology test, where nk cell is negative, tnf alpha positive, adhesion molecule alpha beta integrins negative. Did tnf alpha blood test to know the levels and it is 5.2 within the range. This whole immunology test was performed before 3 ivf.
    Pls let me know the solution for implantation failuer.

    ReplyDelete

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