Sunday, November 17, 2013

Taking the sensible approach to treat infertility

This post was prompted by two things:  another blogger's accounting of her painful response to lupron during a FET, and yet another multiples pregnancy that may just end in the unthinkable

All in all,  I am struck by how often  doctors just follow a set protocol without being thoughtful about the situation, the patient's problem, the patient's comfort, and the long-term safety of both the mother and the child. If the doctors can't think about all these things, then the patient should, because ultimately, they are the ones facing it all. 

There are many roads to infertility. All we can do is identify the problem and treat it intelligently. When I say treat it intelligently, I mean choose a path that minimizes the number of injections you have to take, the hormonal overload you face, the number of FETs you have to do, and importantly, choose a path that allows single embryo transfers so you do not have to face the higher risks associated with a twin/triplet/quad pregnancy.

Here are some practical examples:
  • If you have a high-ish antral follicle count and a normal-ish cycle, choose the antagonist protocol over the long agonist protocol: The antagonist protocol is infinitely more "natural" than the agonist. Overall, most studies fail to show any benefit of one over the other.  The antagonist protocol is infinitely kinder to patients: you have to take a far fewer number of injections (Doctors, yes, this DOES matter). You can skip lupron. You have a reduced risk of OHSS. Knowing all this though, many doctors prefer the long protocol to the short protocol simply because it has been around longer.
  • If you can identify a relative date of ovulation, even with +/-3 days of variation, choose to do a natural FET over a medicated FET. That way, you don't have to start your pregnancy already having been on lupron followed by estrogen followed by progesterone injections, you simply start with Beta-HCG (RMA-NJ has a trial on this) followed by progesterone, and transfer 3 or 5 days after ovulation. Many doctors are now going with a natural FET now. Incidentally, this study found better results with a natural cycle as opposed to a medicated cycle. This does not surprise me, because mother nature is the best architect, and giving somebody three hormones to mimic the complex natural process should logically be the less efficient approach. I don't know why REs prefer a medicated FET.  One fertility center basically said that some doctors like the medicated cycle better because it is less of a hassle with respect to scheduling. Needless to say, I don't respect doctors who would pick medicated FETs for solely this reason. 
  • If you end up with a large number of embryos, then do your best to pick the best one in the bunch from the getgo, so you do not have to do 5-10 transfers to find your two good ones.  There are two things you can do for this: let your embryos grow till day 5 (most of which arrest are shown to be chromosomally abnormal) and test the rest. This part is up to your doctor. The embryoscope has some utility in this weeding out process to allow you to transfer your best embryo first. But it is not a conclusive/fool proof test by any means.  To really know which of your embryos is okay, you need to find a doctor who has the technology to offer a trophectoderm biopsy with CGH microarray testing. Note that a Day 3 biopsy and FISH testing are useless. Day 3 biopsies are bad for two reasons: Most embryos are actually chromosomally abnormal at day 3, and if you test at this point, you may throw out a good embryo (the doctor at RMA-NJ told me that a lot of the embryos that they had discarded as "abnormal" through day 3 testing/FISH turned out to be normal when tested at day 5 with CGH microarray: they had been "rescued"). The second reason is that the biopsy itself can damage the embryo, given that you are pulling out 1 cell out of 8. 
  • Avoid transferring multiple embryos: To do this, you have to let the embryo grow in the lab till day 5. This is where the patients may balk: if a low number of eggs are obtained, then most patients are reluctant to even grow their embryos to blasts. They don't want to see their embryos arrest in the lab, and somehow feel that if it goes into them, it may have a better chance. Here is the problem with that idea: right now there is little to no evidence to show that the womb poses any advantage over the petri dish. If you transfer all 3 of your day 3 embryos or two blasts at one go, you may win the battle but lose the war. I've lost count of the number of people on the blogsphere I've seen this happen to.  I've seen some people pull through through the skin of their teeth, after being on bedrest for months, and enduring unbelievable stress. Compared to that, a failed IVF cycle is a walk in the park.  If you can...grow your embryos to blasts, biopsy them on day 5, find out which one is chromosmally normal, and transfer that (pregnancy rate: 66.4%). Failing that, transfer one blast at a time without biopsying (pregnancy rate: 47.9%). 
The first two things I've talked about here, picking a more natural IVF, choosing strategies that minimize the number of injections you have to take (it is really easy), and picking a  natural FET is doable for many, and most people would have no issues with these things if they fit the necessary patient profile.

The third thing is a comfortable place to be in: If you have 12 day-3 embryos, you can easily make the decision to grow them further, and most people do. The testing is up to your doctor anyway. On the day of transfer, you have to make the harder decision of transferring one or two. Remember, a day 5 blast has about a 50% chance of implanting.

The fourth choice is the hardest. What if you get only 3 fertilized eggs? Making the decision to wait and grow those in the lab for 5 days, knowing that all of them may arrest at day 3 or 4,  and facing the reality of going home empty handed from your IVF is the hardest decision to make.  But therein is the gamble. You could transfer all three embryos on day 3, be ecstatic when you have a positive pregnancy test, and 20 odd weeks later, lose two or three babies. It has happened so many times, and I'm writing this post because I am very, very tired of seeing it happen. Everybody thinks that this could not possibly happen to them, or they choose not to think of it at all when going for embryo transfer, but really, they should. Not all doctors have a single embryo transfer policy, and they should. Because gambling with lives like this is not acceptable.

Despite my preaching, and my knowing all this, I gambled too. I wanted to transfer only one blastocyst at a time, but my doctor froze my embryos in pairs even after I specified that I wanted an elective single embryo transfer. I could have done a single embryo transfer and frozen the second embryo. I did not, because I was too afraid that freezing twice many be damaging. I green-lighted the transfer of two embryos to one surrogate, and prayed only one would implant, and I got lucky. My OB-GYN, who regularly sees surrogates, told me that she considered all surrogates high-risk. My mouth fell open then, and I asked, "Even the ones carrying singletons?" She said yes. They are apparently high risk for many reasons, not all of which that I bought completely.  As we move into the second half of pregnancy, I am terrified of pre-term birth. And that is with a singleton. If there were twins now, my stress levels would be much higher, and my fears would be perfectly valid. 

Take home message? Think long term, not short term. So hard to do, I know, but so prudent.


  1. I always respect how much thought you put into the science of infertility and your understanding of it.

  2. I just hope you whiz past 24weeks in a bullet train. Too much sadness around....i am praying for ur baby and wish you all the best.

  3. Thanks for sharing all this info. I work in Ob/Gyn and for my first IVF cycle I was planning to do a freeze-all, PGD testing, and a single transfer with one euplolid embryo. Unfortunately, on day 3, I only had three decent looking embryos (of the five that fertilised) and went along with my RE's recommendation to transfer two. It was such a painful decision, as I have labile blood pressure issues, so twins increases my pre-eclampsia risk, but having seen so many complications relating to twins in my professional experience, it felt so professionally irresponsible to transfer two. Yet with all that we had invested to get to that point, I felt that I couldn't hold out for day 5 and risk having nothing to transfer. In the end, we did have two that became blastocysts. I almost feel that if my beta is negative, I can have a sigh of relief and move on to working with my fro-yos, one at a time.

  4. Wow...I can't believe your RE pushed you to transfer 2 when he was aware (I'm assuming) of your BP issues. We all do this though...we don't want to deal with immediate failure so we toss the dice and hope we get lucky. REs I think hate seeing "failed IVFs"...that really should not influence their decision making, but I'm sure it does.

    We all need to stop thinking in the short term, and thinking long term. But it is human nature to grab what we can today, and think of tomorrow, tomorrow. That can be very dangerous here though, because because if stuff does not work out 20-ish weeks into the pregnancy, the results can be shattering.

    I'm hoping you get pregnant with only one of them, or failing that, neither implants.

  5. I absolutely agree that doctors need to tailor the treatment to the patient. While I understand your inclination to go to the more "natural" protocol, I think there are benefits, in some patients, for choosing the more medicated route. By the time the patient gets to IVF there has generally been a failure in the natural process and controlling it with medication can help. (Also the testing isn't fool-proof plus its expensive, unless someone has had multiple losses, I personally, wouldn't recommend it as heavily as you do unless the patient was at a clinic that does the testing often and the patient can afford the added expense).
    I did the long agonist protocal which I am not certain was the best possible one for me (only 10 of my 17 eggs were mature and only 5 survived to day 3).
    But, I did do a day 3 medicated FET of untested embryos, based on my experience (and that of my RE) after a long conversation with my RE, we collectively decided that was the best plan for me. I honestly didn't expect it to work based on the poor quality of the embryos (which may have been crappy eggs, or may have been a crappy protocol)- however the medicated FET appears to have worked (I'm currently 11 weeks with a singleton) so, I can't complain about that.

  6. That is awesome news, congrats!!

    Yes, the natural process fails in some, but definately not all the patients who go for IVF. That is why I stipulated that
    My point was that if you don't test, or take a chance and transfer a single blast/day 3 embryo, you end up doing transfers of multiples. From that point on, what happens is solely luck. If you get pregnant with a singleton, great. If you get pregnant with multiples, you can run into all sorts of hell, or you could be lucky.

    When you rely on luck, and you lose, you lose in a way that will shake you to your foundations. Bfns and failed cycles are nothing in the face of a loss at 20 weeks, and I beleive taking such a chance is foolhardy. Having said that, I've taken it too, and like you I got lucky. But I still think what I did was stupid, and if I ever have to transfer more embryos, I'll not do it again.

  7. Rebecca (Which Way to Baby)November 19, 2013 at 11:22 AM

    First of all, thank you for this post. We have been debating between transferring 1 or 2 (transfer is on Thursday), and this post helped remind me what is most important, so we're going to contact the clinic to let them know we're switching to transferring a single embryo. I'm not judging others, because if some of our circumstances were different (namely, if I was 10 years younger, in better shape, with lower blood pressure), we would most likely be transferring two.
    One thing that struck me about your post is the comment you made that you took the gamble as well. I'm not criticizing you, because I believe everyone needs to make the decision that is best for them. But based on what I have read in your blog for the past couple of years, you're clearly very well educated (better than most patients, I think) about reproductive issues and the risks involved. From what you've said in previous posts, finances also seem to be somewhat less of a concern (not saying that they don't matter at all) for you than the average patient, and you also have surrogacy resources that are another thing that is perhaps a little bit easier for you to tap into than others. So given all of that, and you chose to transfer two, it makes me wonder what it would take to get people to choose to transfer one instead of two. That's not a dig in any way - it's a sincere question that I'm interested in hearing your thoughts about. What would it have taken to make you choose to transfer to two surrogates or refreeze one instead of transfer both of them? What do you think it would take to get others who have perhaps fewer resources (particularly financial) to transfer one instead of two?

  8. What it would take for people to transfer one instead of two or three would be to fast forward to the late second trimester, when they were actually dealing with the reality and the risks associated with that period. Nobody ever thinks that far ahead though: We are all about thinking what will happen 20 days later at that point...all we can actually think about then is that BFN or that failed IVF cycle, we don't factor in long term risks at all, and that is classic human nature.

    You are right...I knew all the risks, and but I had thought about them in abstract. After my RE had boxed me into a corner by freezing in pairs, one of the options (refreezing one) was something I did not want to pursue because I was afraid it might damage the implantation potential. The other option, hiring two surrogates, was definitely doable. Had both transfers actually worked, the cost would have been painful but affordable, and would have taken more time. I took the easy way out, and In retrospect, I totally criticize/chastise myself for not doing it, because it was not the sensible thing to do.

    But, as I said in the start, all I could focus on then was short term gratification: the BFP and how quickly I could get it. I also had the "not believing in my embryos" issue...I honestly thought none of them would implant, or very few of them would, in the discriminatory uterus (I'm assuming my surrogates had them, based on their lack of loss). And the evidence suggests that overall, there WAS an issue, because out of five transferred blasts, which have a 50% chance of implanting, only one did. But still, that is a gamble. You could have only 2 good embryos out of 10, and if your luck is really bad, those two would be frozen together.