Thal major chances in second pregnancy

My wife and I are both Thal minor and we've had a very stressful MTP when we found out that the foetus had both our mutations, thal major.

Now, we don't know the way forward? Is it advisable to try again? Is it likely to be again in the same situation? There is so much anxiety, we really don't know what to do. Please advise.

Hi Pal,

I'm really sorry to hear this. it is going to be difficult, but i hope both of you can leave the past behind and look ahead.

there are options available and this forum has lots of people who can help with answers. one option available is IVF+PGD. depending on where you live, hopefully there would be a center near-by where you can ask about IVF+PGD. From what I've researched, these options in US are costly though ($20,000). But in other parts of the world, these might be less expensive. Where do you live ?

the probability of this happening again if you tried remains the same - 25%.

there are many senior members in this group, i'm sure there will be more responses to your questions.

take care.

In each natural pregnancy you would have a statistical 25% chance of having another major, as Sumit has told you. My observation is that you cannot rely on the odds. I've known of several families with 3 thal majors and this represented 75-100% of the total pregnancies. I can never suggest taking the chance and hoping, although many people do just that.
Also as Sumit has told you, PGD/IVF can be used to choose a thal free embryo, but the cost can be an issue. If your government provides health care or you have private insurance, then this becomes an easier option (and governments and insurance companies should be made aware that in the long run that this is actually a much more inexpensive option than lifelong treatment for thal majors).

In theory IVF/PGD seems like a great option, however from my personal experience there is a huge financial and emotional cost involved with such a procedure and its not an exact science. My fertility specialist gave me between a 30% chance of successful implantation after a healthy embryo was determined. In the three IVF/PGD cycles I went through, I only had 3 viable embryos (although not high quality embryos - 2 in the first cycle, 1 in the second and none in the third). None of them implanted successfully and I was extremely upset with each failed pregnancy. Luckily IVF is heavily subsidised here in Australia as it cost approx. $5000.00 AUS out of pocket medical expenses for each cycle. Still quite a significant amount for such little return and such small odds. I would have been even more disappointed if I paid $20,000 out of pocket like some countries.

As far as Thal major chances - I had 1 healthy pregnancy (Thal minor), then the next two pregnancies were unsuccessful (Thal Major). Although there is a one chance in four the pregnancy will be healthy, the odds seem much greater to me. Most people I know have had more Thal Major pregnancies than healthy ones. I feel your pain and anxiety and it is an extremely difficult journey where extremely painful and difficult decisions need to be made. All I can say is there is hope as I am proof that a healthy pregnancy is possible and let me tell you the joy my little girl gives me is worth every bit of pain and suffering one has to endure. Hang in there, be strong, don't dwell on the past and look forward to the future each time you try. Try not to give up, eventually things will work out - its like a lottery - the more you try the greater the chance your number will come up. I wish you all the very best of luck.

A key to success with IVF/PGD is realizing that the percentages are low even for every natural pregnancy. Only 20-25% of naturally formed embryos make it to full term. Keeping this perspective right from the start helps one accept the failures and to keep going until success is found. I know a thal major in Australia who went through this. Even though she experienced several failures, she refused to let herself be discouraged and kept trying until she successfully got pregnant. There is no doubt that in the end, it was all worth it, as you have expressed in your own post. When a couple chooses this route of IVF/PGD, they must be strong and prepare themselves for multiple disappointments, because this is the reality of it.

Your observation about the odds is of having a major should be noted by everyone. I know a man whose first 4 kids fit the odds perfectly. One major, two minors and one non-carrier. Yet, with the huge amount of thals I have known, this is the only time I have seen the odds break down to fit the theory. I know of at least 3 families with 3 thal majors. Odds need to be ignored in this.

Andy, what you have stated about IVF/PGD is very true. There came a time where we had to stop as the stress involved was having a negative effect on our relationship and marriage. Even if money was no object we couldn't have gone through another cycle - It took its toll on me emotionally and physically. My hair started falling out, my body was swollen and I developed a thyroid condition which would cause miscarriage if I tried to get pregnant again. This too eventuated with my last natural pregnancy about a year ago so I gave up the fight altogether. I really wish the IVF worked when I first tried it before trying naturally - it would have saved me a great deal stress and emotional pain. I try not to think about it too much, it upsets me greatly. I try to focus on the positive aspects of my life, that is my one beautiful girl, my highly rewarding teaching job and my passion for sport and recreation.

I am aware of your statistics on pregnancy - the fertility specialist said the exact same thing. But how do explain the fact that I fell pregnant first time for each natural pregnancy yet I couldn't fall pregnant with IVF. For some reason the more FSH they gave me the less eggs I would produce. I was on the highest dose on the last cycle and only produced 1 low quality egg that didn't get past day 3. The specialist couldn't give me a reason, he just said IVF just isn't for me and that my body does not respond well to the medication. He was the one who finally said I should not continue with another cycle.

By the way - I noticed you are in the Maldives. We went there for our honeymoon -  the island of emboodhu finolhu from memory. It was a wonderful, peaceful and serene place. I often wish I could go back to get away from it all. An island paradise with such beautiful crystal blue, calm, warm waters. Heaven on earth! The snorkelling was amazing. I must go back one day!

Hi Karen,

It does seem really odd that your normal fertility has been fine, but it dropped when on FSH. This would seem to rule out any problem with the pituitary. I assume your normal fertility was tested in advance. Was this level normal? Also, if you were taking folic acid while undergoing IVF, what dose did you take daily? And were you supplementing with iron at the time?

My heart is in the Maldives, but I live in upstate New York. I have a special bond with the Maldivian thals, and if not for their warm acceptance of me when I first joined the thal group at Lisa's request, I doubt I would have become very involved with thalassemia. I also had the honor of being a guest there for International Thalassemia Day in 2006, for four days of events and counseling. I hope to return some day, but life has not yet allowed for it.

Hi Andy

My fertility was not tested in advance as I had a natural pregnancies before during and after IVF. I was taking the recommended level of folate (5mg I think) and I was not taking iron supplements as I never have issues with my iron levels. It's just one of those things. Works for some, not for others. The only way I could justify in my head was that there was some sort of negative feedback process happening i.e. I was producing normal levels of hormones and when they put more into me, the body would respond negatively to below normal levels to balance things out? Who knows! That ship has sailed now. I am too tired and emotionally drained to go there again. My counsellor said I will know when its time to stop. There will come a time when enough is enough and gladly I can say that time has come.

Your observation about the odds is of having a major should be noted by everyone. I know a man whose first 4 kids fit the odds perfectly. One major, two minors and one non-carrier. Yet, with the huge amount of thals I have known, this is the only time I have seen the odds break down to fit the theory. I know of at least 3 families with 3 thal majors. Odds need to be ignored in this.

I agree with your observation, Andy - I have also seen families at my centre with multiple Thal Major kids. It seems like the probability chart is mathematically correct, but there is a biological/genetic factor not being considered.

My own (half-baked) thesis is that sperm cells carrying the thal gene may be more mobile and stronger (ironic, eh?) than the ones not carrying the thal gene - after all, the thal gene came about due to a positive evolutionary response to Malaria.

That would imply that whether a baby is thal major or not would depend, probability wise, more on the mother - ie, a 50-50 chance. Let us assume, for sake of convenience, that thal gene carrying sperms are twice as fast as non thal gene carrying sperms. Then the probability on the father side is 66.7% (2/3) that a thal gene would fertilise the egg, instead of the 50% we have been assuming.

Then, thal major probability becomes 0.335 ie 33.5% and not 25%

What if the thal gene carrying sperms are thrice as fast? The probability goes up to 37.5%

It would be good to see some research work in this space. After all, we do know that all sperm cells are not created equal.


Cheers
 

Poirot, that is a very interesting hypothesis. In addition to live births of thal majors seemingly being higher than the odds, I would have to say that the number of pregnancies terminated also seems to be evidence of a rate higher than 25%. I don't know if this has ever been analyzed, but for parents who have had multiple major pregnancies, the odds certainly seem to be high.

As far as natural selection theories go, Poirot's observations seem to make a lot of sense and are quite interesting. From my experience of waiting for CVS results - I don't look at percentages as they seem to be incorrect. I believe I was mislead by my genetic counsellor and was given false hope. She kept telling me that there are three chances in four I will have a healthy baby. When that did eventuate with my first pregnancy, I was even more convinced that my chances of having a healthy baby were a lot higher than having a Thal. major baby. As you know from previous posts, the next two were Thal. Major. I would have much rather been told that I was very lucky the first time and I should be happy with one healthy child and not try again. Hindsight is a wonderful thing and who knows if I would have followed that advice, but if I did, I could have saved myself much heart ache and grief.

When deciding on a natural pregnancy I think the best way to look at it is to not consider probabilities at all. One must go into a pregnancy expecting one of two things. The baby will either have Thal. major or not have Thal. major, just like it will either be male or female. It's 50-50 in my eyes. More research in these statistics and probabilities is highly justifiable.