Posts Tagged ‘treatments’

What are the main IVF options for poor responders?

Tuesday, June 1st, 2010

In an earlier post I covered what a high FSH/low AMH reading means, what else to ask for in the way of diagnostic investigation, and the basics about whether this is a ‘no hope’ diagnosis or not.

I’ll talk in this post about the main IVF protocol options for women with high FSH/low AMH/DOR and poor responders, but will be back sometime soon with a post about other lower-cost options for those not willing or able to do [more] IVF.

IVF Protocol Options

OK, first let’s talk about protocols. As I mentioned in the post about the main about IVF protocols used in New Zealand, there are basically three possible protocols that are used for poor responders, and 1. The “long protocol” is NOT one of them. The main options for poor responders are:

2. The microdose flare – usual starting protocol for high FSHers and women over 40. It’s less likely to oversuppress poor responders than the long protocol.

Usually but not always starts with a course of BCPs (birth control pills) for about three weeks, then you stop for a couple of days, then start your microdose course of Buserelin (this gives your ovaries a kickstart or ‘flare’), then a day or two later you start your stims (Gonal F injections). As with the long protocol, you stim for about 10 days with scans and blood tests every 2-3 days. When your follies are ready, you are instructed to take a trigger injection and turn up for egg collection about 36 hours later.

3. The antagonist protocol another option for high FSHers, poor responders and older women. Often the first choice protocol for these women, but in NZ it’s typically tried only after the flare protocol has given a weak response because the drugs are cheaper for the flare.

Usually starts with a mild pre-cycle suppression course of estradiol valerate (E2V) from CD21 or 7dpo the previous cycle (you can ttc on your own the previous cycle; this won’t affect a pregnancy); when AF (your period) arrives this is counted as Day 1 and you may be asked to go in for a baseline scan to check that you have no cysts, your antral follicles are ready to go and no big dominant follicles; on CD2 you start stimming, having bloods and scans every 2-3 days. When your lead follicle reaches 14mm, you start Cetrotide (the antagonist that stops you ovulating too soon). When your follies are ready, you are instructed to take a trigger injection and turn up for egg collection about 36 hours later.

4. The Modified Colorado protocol (a.k.a. The “Wellington”)

“As an adjunct to standard IVF or TER for patients with recurrent implantation failure who have had no problems identified following a recurrent implantation failure screen. The Wellington is a treatment that in theory will improve the lining of the uterus to aid implantation of the embryo.”

Stim Options

OK, having discussed with your specialist which protocol to try first – and don’t forget to ask what he/she would try next if the first one works very poorly! – the next question to discuss is what to use to stimulate your ovaries. The usual default is to start with straight Gonal F; if that doesn’t work well, you might raise the possibility of adding something else as well. The options are:

  1. Straight Gonal F (or Puregon) – this is pure FSH
  2. Combination of Gonal F (or Puregon) and Luveris (pure LH)
  3. Combination of clomiphene (Clomid) and Gonal F or Puregon

Dose Options

There are two diametrically opposed schools of thought among specialists when it comes to how to treat poor responders. They are basically:

1. SHOUTING: High FSH means your ovaries do not respond well to IVF stim drugs. It’s like having ovaries that are hard of hearing when it comes to stim drugs’ message, so the best strategy is to shout at them very loudly (i.e. give you a high dose of stims). This might just get you an extra egg or two. IVF is a numbers game, so more eggs improve your odds.

2. Coaxing: Women with high FSH often have eggs that are more fragile, especially if they are ‘older’ as well. High doses of stims simply ‘fry’ those eggs. If you have high FSH/low AMH, you are going to be a poor responder, so it’s a waste of time going after quantity; the best strategy is to go for quality. You can’t actually improve egg quality per se, but you can avoid damaging eggs with high doses of stims by using very low stim protocols. ‘Low stim’ usually means 75-150IU/day. [I’ll write more sometime about the details of some interesting low-stim protocols used overseas.]

Which of these makes more sense for you? Well, the body of research is building but still hasn’t yielded a definitive answer. My own observations over several years (talking to high FSH women and watching who achieved success and who didn’t, plus reading the empirical research) have been that the only high FSH successes on high stim IVF seem to be women under the age of 40. The vast majority of high FSH IVF successes over age 40 seem to be low stim (with a few exceptions). Younger women with high FSH can also do well on low stims. This isn’t scientific research; just my own observations based on a lot of cases I have known about internationally.

Having said that, the New Zealand definition of ‘max stims’ (usually 300IU) is actually more like ‘medium stims’ internationally. In the States, ‘high stim’ generally means 600IU or more, and there are (believe it or not) some total egg-frying protocols that crank it all the way up to 900IU.

My own hunch is that if you are under 40 OR if you have a reasonably decent antral follicle count, consider giving 300IU (or 450IU) a shot. But if that doesn’t get you decent numbers or,  if embryo quality looks poor, consider a switch to low stim for your next try.

If you’re self-pay, there’s a cost advantage to low stims as well.

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.

When and how should I seek a second opinion?

Thursday, October 15th, 2009

Suppose you had a friend who was grappling with a cancer diagnosis and kept wondering whether his/her specialist had really considered all the possible treatment angles that might work. Suppose he or she had been receiving some treatment but there hadn’t really been any sign of progress. What would you advise? Probably a second opinion, right?

For some unknown reason, fertility patients seem to struggle with this notion that it’s somehow disloyal to seek a second opinion. Yes, it is awkward. But actually, it’s just good common sense if there’s any little voice inside your head saying “maybe there’s a better way …”  I know several women/couples who have switched specialist within the same clinic and have really agonised over how they are going to “break up with” their initial specialist. But the reality is this happens all the time, and people need to find the fit that’s right for them. My local clinic (FAA) actually makes that transition incredibly smooth and most of the drs are perfectly happy when it happens. [Actually, some may be relieved about getting rid of a “difficult” patient! ;)]

Even if you’re not actually switching specialists, it’s perfectly reasonable to seek out a second opinion if you want to. If you’re publicly funded you may have to pay for the second opinion consult, but that’s money well spent if it’ll give you peace of mind and/or some good ideas that can get you closer to building the family you want.

Remember, just as in any other profession, each individual specialist has certain diagnoses and treatments that they have a particular interest in and more experience in treating. Some gravitate toward the more straightforward cases (early 30s, no tubes, standard protocol, easy success); some specialise in particular issues (endometriosis, PCOS, thyroid problems); some are really passionate about taking on the really challenging cases (women over 40, poor responders, egg quality problems). It’s a good idea to ask around about who’s had success with cases like yours. And that’s a good place to start for a second opinion. Just think, women/couples in the States fly 5 hours from coast to coast seeking a second opinion; we are incredibly lucky that even the other end of the country isn’t that far away! And if travel is really a problem, you can often book a phone consult.

Over the years, one thing I’ve noticed is that the truly professional specialists I’ve spoken to have NO problem at all with my seeking a second opinion. They support my being proactive and are very happy to listen to any ideas I glean from those other consultations. They don’t let egos get in the way of my treatment. While working with my own specialist, I got a copy of all my notes and did a phone consult with a specialist in the States who’s considered the #1 go to guy for women with my particular diagnosis. My specialist in NZ was like nooooo problem – and was very open to the ideas I came back with. We did, of course, have a healthy debate about which of the ideas seemed to make the most sense in my case, but the main thing was that we had that discussion and we made some good decisions together about what to try next.

How do you know you should seek a second opinion?

Well, everyone’s different. For some people, it’s when they’ve just had a failed cycle, they can’t afford to do more than about one more, but the specialist is suggesting just going with the same again. For others, they’ve tried discussing other ideas with their specialist but feel like these aren’t being taken seriously or at least the reasons for not trying these things aren’t being adequately explained. For me, it was feeling like we’d already discussed and tried all the ideas we could think of together, so I needed a fresh perspective, a new source of ideas. Whatever the situation, if there’s a little voice in your head wondering whether you and your specialist have adequately explored all the possibilities, that’s a sign you might want a second opinion. It could just end up confirming what your current specialist is telling you, in which case that’s also useful because it eliminates doubts that you’re doing the right things.

If you think you might want to get a second opinion on your case, here’s what to do:

  1. Get a copy of your notes from the clinic so you know exactly what protocols you have tried already, any testing that’s been done, how you responded to treatment (including E2 levels, follicle sizes, the embryologist’s ratings of embryo quality, etc).
  2. If you can, make a 1-2-page bullet point summary of your history and any testing. This makes it a LOT easier for the new dr to get up to speed quickly on where you are at.
  3. Ask around (e.g. on the Everybody BB’s Infertility forum) to find out which drs at which clinics have had success with your particular diagnosis and history.
  4. Call that dr’s clinic and speak with his/her receptionist; ask for an in-person or phone appointment; ask where and how to send your summary/notes/file.
  5. You don’t have to formally tell your current specialist that you’re seeking a second opinion, but you’ll probably end up informing his/her nurse or receptionist when you request a copy of your file/notes. It’s a courtesy to mention it, but if it’s causing you anxiety then don’t force yourself to. The specialist will understand.
  6. If you are doing a consultation with someone who works at another clinic from your ‘home’ clinic and if you like what they are suggesting as a new plan, discuss with them whether it would be feasible/advisable to (a) ask your current specialist to follow a new protocol; (b) cycle at your local clinic but with the new specialist either calling the shots or providing advice to your own specialist; (c) travelling and doing the whole cycle at the new clinic; or (d) doing egg collection and transfer at the new clinic, but monitoring (ultrasound and bloodwork) locally. All of these options have been done around the country at one time or another.
  7. Don’t worry too much about having to persuade your current specialist to try something new – quite often the specialists will just get in touch with each other and work out how best to work together. Ask your ‘second opinion’ specialist what he/she thinks is the best way to handle this. The politics and the details of this shouldn’t be your problem – you are going through enough stress already!
  8. Don’t worry too much about the ‘disloyalty’ issue either. You have the right to expect specialists (and any healthcare provider, for that matter) to be professional about second opinions and NOT to make you feel guilty about seeking one out. If you find someone is not being particularly professional about it, that tells you more about them than it does about how you handled it. Your priority is to get a baby/family out of this, and their priority should be to help you achieve that dream. The specialists won’t be a part of your life forever, but your babies will!

New and “untested” treatments

Wednesday, September 23rd, 2009

Here’s a topic that comes up for discussion quite a lot.

“My dr won’t let me try X – why not?”

“My doctor talked about the ethics of infertility treatment and how some clinics will try (and charge for) all sorts of unproven treatment where often there was no medical reason for a particular patient to require that unproven treatment.”

The unproven treatment issue is a really interesting one because most medical professionals consider “proven” to mean something supported by multiple randomised controlled trials. The problem is that cutting-edge ideas are new and haven’t had the chance to be sufficiently trialled (or, in some cases, don’t lend themselves to such randomised designs for ethical and/or practical reasons).

So, should all the new ideas be ignored until they are considered “proven”?

Well, here’s how I tackled this dilemma with our doctor. If I’d already tried the standard options and if there was another idea that (a) wasn’t too off the wall, (b) had at least a plausible basis in theory, (c) had some small-scale evidence that it might help and (d) there was no logical reason to think it would hurt, then we’d discuss it and he’d often agree to let us give it a shot.

Of course, there were quite a few things I argued pretty hard on and he just wouldn’t do it because he didn’t think there was sound enough reason. He always explained why and didn’t treat me like an idiot – very important; I think every patient has the right to expect this.

Moral of the story:

  • Do educate yourself about the various options and ideas that might help someone like you
  • Do ask your doctor about them – and take copies of any research papers you can find
  • Do insist your dr explains their rationale for not trying them – or for tweaking them before trying them
  • If, after you listen to the rationale, it still seems to you that your doctor is being overly conservative in not trying something that seems to make sense to you, do seek out a second opinion

When you’ve only got a few shots at something so life-changingly important as conceiving a child, you owe it to yourself to make sure you don’t get to the end of the struggle with regrets and what-ifs. Leave no stone unturned!

See also: