Archive for April, 2010

Conflicting expert opinions – how do I know who’s right?

Saturday, April 10th, 2010

So, you finally plucked up the courage to go for a second opinion (see also When and how should I seek a second opinion?) and guess what – now you have two or more well-qualified and plausible experts with compelling arguments telling you to do the exact opposite. Maybe one cites empirical research and another doesn’t; maybe they all cite different research. Maybe one sides with the ‘mainstream’ while the others are mavericks – who’s more credible? Who should you trust?

Here’s a classic example encountered by women in their late 30s and 40s with elevated FSH or low AMH (which means they have diminished ovarian reserve – very few eggs left, on the fast track to early menopause). [This example may not relate to your case specifically, but the reflections about how to deal with it are definitely generalisable.]

Specialist A: Once your Day 2/3 FSH is over [insert cut-off; some say 10, some say 12, some say 15, some say 20] the odds of pregnancy through IVF are so incredibly low that IVF is a waste of time altogether, so we would actually not treat you unless you plan to use donor eggs. Just move on already!

Specialist B: Your FSH is elevated, which means you will be a poor responder to stims (Gonal F, etc) and your odds will be lower than other patients your age. It’s like your ovaries are old and going deaf, so we have to give you a very high dose of stims (i.e. ‘shout’ at your ovaries) to get them to wake up and produce any eggs at all. So, I would recommend we put you on maximum dose stims and see what happens. If that doesn’t work we will try mega mega doses.

Specialist C: Your FSH is elevated, you will be a poor responder, but actually, large doses of stims for women like you will often cause your ovaries to shut down and not respond at all. If they do respond, the dose is so high that you will end up with fried eggs that are unlikely to result in a live birth anyway. No, your ovaries are like an old squeaky violin that has to be coaxed gently into life so that it sings the sweetest tune  it possibly can. I recommend a very low-stim IVF, IUI or TI (timed intercourse) cycle with either very low stims right from the start, or just starting with no stims and letting your own [already elevated] FSH drive follicle growth before adding a ‘tiny boost’ to help things on their way.

Yes, intelligent people do hold different views. The field is still growing and not everything is cut-and-dried (and  actually, never will be). They all have theory and evidence to back their explanations …

Specialist A will cite a ton of empirical research showing the inverse correlation between FSH levels and IVF response (number of eggs produced) and success rates. No argument with that.

Specialist B will cite studies showing that the higher the dose, the more eggs patients produce, and the more eggs you retrieve the higher the success rates. It’s a numbers game.

Specialist C will say ah yes, but what those studies don’t show (but mine do) is that, although you get more eggs from higher stims, in older women and those with high FSH, those eggs are of lower quality, less likely to fertilise, and most importantly, less likely to result in live births.

They are all speaking the truth based on what they have seen and read; they all have evidence and experience to back their claims. So, how do we weigh up conflicting arguments and figure out what makes the most sense for us?

First, let’s talk about the big studies (either randomised experimental trials or retrospective studies) showing that Protocol X works (or, helps) better than protocol Y. These are very important to understand, but what YOU need to consider is not “does it help” on AVERAGE across a large study of all sorts of different women; the real question to have in mind when you read (or, discuss with your dr) such research is WHOM does it help (what age, dx, individual characteristics), and under what conditions? And, will it help ME with my unique constellation of age, treatment history, diagnosis and other characteristics?

There are some aspects of fertility treatment that are so nuanced, unpredictable and idiosyncratic that the reality is NO-ONE is ever going to get “the” answer through large study research. Once you’re past the relatively well-established big picture stuff and trying to individualise protocols based on what you see and what you’ve seen in the past, it’s less about big picture science and hypothesis testing and more about human judgement and pattern recognition.

When we’re in this territory, fertility treatment is less a “science” and more of an “art” or a “craft”. You’re having to trust pattern recognition, judgement, intuition and instincts because the research just isn’t there to the level of detail you’d need to be able to make a call. Also, many of the cutting-edge treatments have no more than a plausible theory and a few success cases; the research needed to fully test them is still in progress or may be years away or may never be done because they help such a small segment of the ttc population – but they may still help (see also New and “untested” treatments). Just about all of my ttc journey was in that murky domain -  I was too specific a mix of age, diagnosis and treatment history for enough large studies to have been conducted to clearly indicate what would work in my case. There were no easy answers – there wasn’t a clear right or wrong because the research out there could only predict what would happen across a large group (that included many women NOT like me), not what would happen in MY case (or cases very similar to mine).

When you’re in instinct and judgement and pattern-recognition territory, the only things you can do are arm yourself with as much knowledge as you can muster, listen to the instincts and judgement of the people who have had more experience with cases specifically like your own, and listen to your own instincts and debate these back and forth with your specialist(s). It’s a crap-shoot, but some people have a knack for this stuff …

Or, the simple version for the example above (please just insert your own dilemma and the answer is likely the same): high stims work for some people; low stims work better for others. Which are you? Well, you won’t know until you try because the studies have been done on a huge range of women, only a fraction of whom are like you in various ways – and none of them are exactly like you. So, research like crazy to try and figure out what seems promising for women and couples most like you, and when it’s still not clear how to choose among various plausible options on your shortlist, go with your gut.

See also: New and “untested” treatments for some thoughts about which new-fangled ideas to consider seriously.

How do we know when to move on?

Friday, April 9th, 2010

“Moving on” can mean a lot of different things:

  • stopping IUI or IVF and switching to ttc naturally and/or with alternative medicine
  • opting for donor egg IVF (or donor sperm IUI or IVF) instead of trying more with your own eggs (or sperm)
  • trying with donor embryos (these are frozen embryos left over from other couples’ IVF cycles who have had success and have finished building their families)
  • pursuing adoption (domestic or international) or foster parenting
  • deciding to live child-free or (in the case of secondary infertility) with just the one(s) you have

But how do we know when it’s time to move on to the next option? And, when should we (and when should we NOT) be making those choices?

It might help if I share a bit of my story from the very lowest points of my ttc journey.

I think one of the worst parts of my whole ttc journey was right when we found out that our miracle natural conception after 2 years ttc#2 was in fact, at 7 weeks, a blighted ovum. At that point I was almost 42, where they say your fertility falls off a cliff, and I really felt like this pregnancy was my last chance slipping through my fingers. I had six failed IVFs under my belt, 2 cancelled for poor response, 4 that had gone to egg collection, a total of 9 embies transferred, no leftover frosties, 4-5 other natural conceptions that were chem pgs (mostly) and now this 7-week miscarriage.

Every BFN and especially every loss was a major low point for me. Not only did life/reality totally suck; estrogen levels at the end of a failed cycle or failed pregnancy are in freefall and that makes anyone feel really really crappy. So, the one thing I learned is NO negative decision making while climbing out of the vortex. But once out …

It’s a very personal decision about how much more of this you can take. The costs are high on every level (physical, emotional, financial), and you lose major chunks of your life clawing through this stuff. Your career suffers, relationships with friends and family suffer, and if you have one or more children already there’s this awful feeling that you are losing precious time with them while you are consumed with cycles and blood tests and scans and peesticks and phantom pregnancy symptoms and researching next options. And infecting them with the sadness and depression that comes with a long struggle with infertility.

As one of my NZ board buddies pointed out, it is really important to sit down with your partner regularly through the ttc process (and with a good counsellor, if you choose) and ask yourselves some very difficult questions such as:

  • What does my partner want, what do I want, how do we resolve things if there are different goals? (this can change at different stages of the process)
  • What’s the impact of this treatment (or yet another treatment) on our relationship? How do we stay strong together as a couple?
  • What’s the impact on our lives if we don’t have children after [insert number of] IVF/treatments? What’s the vision for our future without children?
  • [and I’d add one for the secondary IFers] What’s the impact of this treatment (or yet another treatment) on any child(ren) we have? What is the cost to their quality of life of having their parents going through this gruelling process? How well are we ensuring they get the love and nurturing they need while we try for a sibling? How long/often can we keep trying before the negative impact on our child(ren) makes it no longer worth it?

The financial drain is very stressful on top of everything else. It was hard to take on much work while having to avoid travel during only partially predictable cycle dates, so income can be down anyway. We were lucky to get some help from family and the bank manager, but everyone has a limit to how far they can stretch before they are really in trouble. My philosophy was that I could make money after menopause but not eggs – and that any resulting child would cost far more over a lifetime than a few IVFs. I needed to get to 50 with no more regrets, whichever way it went. So we kept on, making the decision after each cycle – at least a couple of weeks after the BFN or the D&C (no sooner).

For me, the decision about whether to move on was all about whether I thought we were out of plausible ideas and just spinning on some hamster wheel. But even after 6 IVFs I still felt like we had ideas to try that we hadn’t tried before. Thankfully we had a specialist who would work with us to try anything plausible. And go figure, after no success in 2 years age 40 to 42+ (and high FSH to boot), IVF#7 at age 42.3 gave us not just one baby but fraternal twins.

Unfortunately, though, success isn’t going to be the outcome for everyone who persists. I knew I had to be at peace with eventual failure. I wanted to look back after menopause and know that we had tried everything that we could, and that we did it without sacrificing our relationship with the one we were already so lucky to have (and who we were told would never happen either).

Early on in the process, after my first IVF at age 40 was unceremoniously cancelled for ZERO response, my first thought was “Oh well, that protocol (microdose flare) didn’t work; now there’s really only one other for me to try (antagonist). If that’s a zero response too, then that’s that for IVF. Simple.” If that had happened, the choice would have been very clear to me – ditch the IVF and try naturally with acupuncture, herbs and supplements (we’d 99% decided against the other family building options already; my tubes were fine and we had only mild MFI). In some ways that scenario felt like a relief because it was unambiguous and the treatment less taxing on many levels. But on IVF#2 I did actually GET a response, though not a great one. From then it was a case of hunting for the Goldilocks (just right) protocol, and giving up on IVF once it was clear we’d exhausted all the plausible ideas (or our emotional capacity for going through the process).

It’s a very personal decision for each person or couple about when to move on and which options you would consider. My advice (and I know a lot of people would advise the exact opposite) would be to NOT decide in advance how many cycles you’ll do or whether a particular cycle is definitely your last shot at anything – it puts a LOT of stress on the so-called “last” cycle.

Another very good read on this topic is Janey’s post on the Fertility NZ blog. Janey’s been through the IVF mill and is reaching the end of the journey, but unfortunately without a baby in her arms. Here are some snippets from her very real reflections …

We are all at such individual, personal stages in our journey with creating our own families. This could be trying IVF for the first time, or the sixth because you’re a “poor responder” – how dare they label us that – or having had a miscarriage, or having realised that it’s time to accept our shape of ‘family’ might include dogs, step children, and a trips to India. I’m at the later end of the spectrum. It’s immense.

I no longer want to hear about people getting pregnant, or want to support another friend through IVF. It’s too heartbreaking. The lovely people at Fertility NZ have compassionately identified this, and are saying, “That’s okay”. How nice to feel valid, in a journey that is anything but valid or fair.

=> Read Janey’s whole post and the 30+ comments from women in the same boat.

As another board buddy said, “Getting on the infertility treadmill is easy – its when to hop off that is the problem.” So true.

We did IVF but had heaps of empty follicles – help!

Monday, April 5th, 2010

Some of us do IVF, go for those scans and see hardly any follicles after all those injections. Others are relieved to see a healthy crop developing as they go through their cycles. Unfortunately, the number of follicles (or “follies”) doesn’t necessarily equate to the number of eggs collected. And for some women, a huge proportion of the follies are ’empty’. This is sooo frustrating after seeing all those follies on the screen and usually having a fantastic E2 (estrogen level) to match.

There is such a thing as “empty follicle syndrome”, but unfortunately it’s still not all that well understood, and there are various theories …

  1. The most common explanation given by the specialists is that egg maturity and quality are related to how easy they are to get out. Those that are flushed out are lower quality than those that came out easily. ‘Empty’ follicles may not actually be empty; they may just contain very poor quality eggs. OK, there’s obviously a heavy element of truth to this (i.e. it’s a known fact about eggs in general), but the big question, of course, is whether (and how much) it applies in YOUR case. It probably does, to some extent, in just about all cases of empty follicle syndrome. But that’s actually a “There’s nothing we can do about it” diagnosis, and not much use unless you are looking for  a reason to switch to donor eggs or give up altogether. So, the following are some other plausible theories that may or may not apply, but many of which CAN be addressed.
  2. One theory is that you got a dud trigger shot. It’s rare, but it can happen. And it’s unlikely to happen again. But if you want to be absolutely sure, some women use a double trigger shot the next time. This is when you inject not one but TWO vials of Ovidrel (the usual trigger used in NZ), one after the other. Very important: The vials should come from two different batches (check the batch numbers on the packet before signing them out and taking them home – you can’t return injectable drugs for exchange or refund). I’ve not seen any mention that this could have any adverse effect on the egg quality – it’ll cost you some $$ for one more vial of trigger (but this is cheaper than one more IVF cycle and a lot cheaper than the baby once he/she arrives!), but apart from that, it’s a “won’t hurt, might help” measure as far as I can tell. But ask your dr.
  3. Another theory floated a lot is that you may have ovulated just before retrieval, but not so long before that they would have seen collapsed follies. The remedy for this, if true (and it’s very hard to tell) is to schedule your egg collection just a bit earlier – say, 34 to 35 hours after trigger, instead of the usual 36. Reasons to hesitate about doing this might be if several of the eggs that were retrieved were immature – collecting early could exacerbate this problem.
  4. A rather delicate theory to probably NOT raise with your specialist is that the person doing the retrieval wasn’t very skilled. Yes, well, obviously a possibility, but hard to tell as a patient, and there’s no way you’ll get an admission about this one!! If you’ve had several cycles with ’empty’ follies, was it the same person doing the procedure each time?
  5. OK, time to start thinking outside the very simple boxes outlined above. One possibility is that the protocol disagrees with you – gets you follies but most of them are ‘decoys’. Now, you won’t get far on this one if you are under one of NZ’s one-size-fits-all specialists. Obviously, there are some cases where a change in protocol might be risky (e.g. greater risk of overstimulation, OHSS), but personally, I couldn’t bear to go into a new cycle on the exact same protocol as a failed one, so ask lots of questions about alternatives – and see also the post: What are the main IVF protocols used in NZ? The other protocol-related thing to ask about is what stims are being used. In NZ, just about everyone gets put on straight FSH (Gonal F or Puregon), but some specialists will add some LH (e.g. Luveris) into the mix. This seems to help some women with egg quantity or quality or both; others seem to do better on straight FSH.
  6. Some fertility specialists say that if your eggs are overcooked, i.e. if you stim too long before triggering and the egg over-ripens, then the resulting egg will stick to the follicle lining and not come out easily. The same is said about eggs that are ‘undercooked’ (i.e. if you triggered too early and the egg is not yet mature). Although there is some empirical research on the best time to trigger based on follicle size, it’s become quite clear to me (after listening to others’ experiences) that one size does not fit all, and some women need to trigger earlier than the norm, some a bit later.
  7. The other possibility is that maybe your ovaries are of the “less is more” variety, so that if you halve your dose you may get fewer follies but the eggs in them are likely to be (a) really there and (b) better quality. I haven’t seen a lot of research on the latter, but I have talked to a low-stim specialist about this in some depth, and also to several women who swear they get far fewer empty follies when they are on a much lower dose. [And, I suppose my experience was similar numbers but better embryo quality, so I’m a fan of the low-dose option in general.] Internationally there is a fast-growing interest in the reproductive endocrinology (fertility specialists) community about low-stim and natural approaches to IVF.One of the more interesting recent innovations in IVF is in vitro maturation (IVM), where the eggs are removed from the follicles while immature and then matured in the lab. This is nil to near-nil stims technology. Last I heard – in a Nov 2007 National Radio interview with Dr. Simon Kelly (Fertility Associates Auckland) it hadn’t been approved by the ethics people, but it may be by now, or that  may be coming soon. If it sounds interesting, get yourself a consultation with Simon – he did a post-doc fellowship at McGill in Montreal, where IVM was pioneered.

OK, there’s a big laundry list of possibilities here. My own experience grappling with infertility has taught me to push back quite hard if only the “we can’t do anything about it – you just have bad eggs” explanation is being offered. OK, the bad eggs thing may be true (and in my case it certainly was, since I was IVFing over 40 and with high FSH!), but that doesn’t mean there aren’t some other treatable explanations that are also in play. There are quite a few non-drastic options here to tinker with the protocol, and IMHO they are well worth discussing seriously with your dr. If he or she is reluctant, make sure you ask whether your specialist thinks this is likely to be risky or harmful in some way, or whether they think it’s relatively harmless but just unlikely to be effective. If it’s the latter, and if your instincts are telling you it makes sense, then ask to try it.