Posts Tagged ‘protocols’

What seems to work best for which poor responders and women over 40?

Thursday, June 3rd, 2010

This is one of those areas where we’d hope the empirical literature would be able to tell us what works for whom and under what conditions. But unfortunately poor responders and women over 40 – and particularly poor responders over 40 – are a relatively small group and rather neglected in the research (JMHO). So, what can we draw on instead?

This isn’t particularly scientific, but if you look at some of the research that’s been conducted over the years and combine this with informal sources such as the Over 40 High FSH Board‘s Timeline post (click here or search for “timeline” to find the latest) and also the high FSH google stats page, and also based on what I observed (IVF successes and failures) over many years on those high FSH boards, here’s what I concluded:

  1. There didn’t seem to be any pattern about whether the flare protocol, the antagonist protocol, or Mini IVF worked best – it’s basically a crap shoot. You just have to try them and see.
  2. The high stim success cases (live births) were generally women under 40 with a lot of antral follicles. The few over 40 exceptions tended to have higher AFCs (>5).
  3. The VAST majority of over 40 IVF success cases were low stim. [Lots of natural conceptions too, but of course there are many more people ttc naturally than with IVF, so it’s hard to infer whether, say, low stim IVF is more or less effective per cycle than ttc naturally – High FSH specialist Dr. Jerome Check thinks IVF gives high FSHers 2.5 times better odds for that cycle cf ttc naturally in your late 30s and early 40s.]
  4. Often on high stims you can get more follicles and sometimes more eggs retrieved, but the number of embryos generally seemed to be the same from either high or low stim (I’m excluding natural and boost protocols from low stim here). In other words, on high stims you often get more empty follies and/or lower fert rates.
  5. Those of us over 40 gals who’ve tried both high and low stim have quite often seen a difference in eyeballable embryo quality – just one example, but check out my high and low stim embie pics and see for yourself

So … based on what I’ve seen, my conclusions for poor responders/high FSHers/low AMHers were:

  • Under 40 and with OK AFC –> give medium-high stims a try first (say, 450-600IU)
  • Over 40 but a pretty decent AFC (say, consistently >5) OR under 40 with a low AFC –> try medium stims first (225-375IU)
  • Over 40 with a low AFC and FSH not through the roof –> try low stim (75-150IU)
  • Really excessively high FSH or a system that goes wacky with drugs –> go natural (BD or IVF) or try a ‘boost’ cycle (start natural, add tiny 75IU boost IF needed based on monitoring)

Not very scientific, but FWIW, that’s what I concluded in the end (after starting medium/high stim at age 40 and eventually listening to my wise board buddies and Jerome Check – and trying low stim).

Please note that this post is directed at couples and women who do NOT at this point want to consider donor eggs, but want to try and get a handle on what might be the best approach to try with their own eggs.

Other posts of potential interest:

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.

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:

What are the main IVF protocols used in NZ?

Wednesday, September 23rd, 2009

Why is this important?

First, it’s good to know roughly what’s out there, and that there is more than one option, so that you can get your specialist to explain why this one and why not that.

Second – if you don’t do well on one protocol you may do fine on another.

Some women will need a few tries to find their “Goldilocks” (just right) protocol, but because most of us have only limited finances and stamina, it’s important to make sure you’re satisfied the first one is a good choice for you.

Basically there are three main protocols used by NZ clinics (plus a few variations, which I’ll try to add later):

1. The ‘long’ protocol (default for young women and those with normal FSH; not generally used on high FSHers unless they are quite young, and seldom on anyone over 40 because it can easily oversuppress those with diminished ovarian reserve).

Buserelin for about 10 days to downregulate (put you into temporary menopause), then the Buserelin dose is lowered and you start stims (Gonal F injections), 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.

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.

There’s another called the Colorado protocol, which is a variation on the antagonist. I don’t have all the details on this and how it’s done in New Zealand, but if someone would like to email me or post it as a comment, that would be a big help!

If you are a poor responder, have high FSH, low AMH, a low antral follicle count, or have been told you have diminished ovarian reserve (DOR), follow this link to check out protocols used for poor responders.

And here’s another link in case you want to know more about the various IVF, IUI and TI (timed intercourse) cycle medications and what they do.

Questions to ask a prospective specialist

Tuesday, September 22nd, 2009

Before committing to working with a particular specialist, it’s a good idea to ask them a few questions to get a feel for their approach to treating patients like you.

All too often I have talked with women/couples who have gone through their first consult with a specialist and simply assumed that whatever treatment plan they are prescribed is somehow the “right answer,” that there’s nothing to question or compare. In reality, specialists do vary quite substantially in how they approach the treatment of couples with a particular diagnosis – even specialists working in the same clinic. You need to use your first consultation to get a sense of whether the specialist’s approach makes sense and feels right for you.

The following questions might help get the conversation started:

  1. What kinds of protocols do you use for couples of our age and with our diagnosis; which would you try first and why, and what would you suggest next if we didn’t do well on that?
  2. What successes have you had with cases like ours in recent years? Please describe a couple of recent cases you can recall.
  3. What is the most innovative or non-standard protocol you have used with a couple of a similar age and diagnosis to us? [You want to get a sense of whether they use a one-size-fits-all approach or whether they are prepared to think outside the box.]
  4. What is the minimum number of follicles you require in order to proceed with egg collection? Is there a minimum E2 (estrogen level) too? To what extent will we be consulted about whether to proceed with egg collection if numbers of follicles or E2 levels are lower than the norm? [You don’t want a dr/clinic that just makes unilateral decisions and dishes out instructions without discussion.]
  5. Under what other conditions would you cancel a cycle on us?
  6. What would you see as the main risks/difficult hurdles for a couple like us as we go through an IVF cycle?
  7. How many [IVF, IUI] cycles would you let us try if we (a) have been cancelled for various reasons (e.g. poor response) and/or (b) still haven’t attained a pregnancy after several tries?
  8. What other clinics or specialists in New Zealand do you know of who have experience with cases like ours? Is there anyone else you would suggest we speak with before deciding where to cycle?
  9. What is the cost of a cycle? Will we be eligible for public funding? If so, when? How long is the waiting list once we become eligible? Is there anything we can do to speed up our eligibility or waiting time, such as further diagnostic testing?
  10. Who does the ultrasound monitoring at this clinic? Who does the egg collection and embryo transfer procedures? Will I get my own specialist for these procedures? What if my egg collection or embryo transfer days fall on the weekends?
  11. If we have questions or problems (including when the clinic is closed), who will we call? [The reason to ask this is that at some clinics, you will never get to speak to a dr on the phone. The questions are often fielded by nurses (or answerphones!!) who will sometimes – but not always – ask the dr. But at some clinics, you are given your specialist’s cell phone number in case something urgent comes up after hours or when you can’t get through to a nurse who can answer your question promptly.]
  12. Do you believe that immune issues play a role in IVF success, and do you test for them in advance? If not, when would you test for such things? After how many failed cycles? How do you treat immune issues if and when they are diagnosed?
  13. [For high FSH/low AMH/poor responder gals …] Are you open to high, medium and low stim protocols for cases like ours, or will you insist that we do (say) medium stims every cycle?
  14. [Also for high FSH/low AMH/poor responder gals …] Is there a maximum FSH cutoff in order to be able to start a cycle? If so, how high is it, and can I take suppression beforehand to bring FSH down below the cutoff?

Before going into your first consultation, it is well worth learning as much as you can about the basics of IVF and the main protocols. The first consult always rushes past in a blur, but it helps a lot if you have just a little knowledge to get you started and a good list of questions to make sure you find out what you need to know.

If you’re nervous about the first consult, consider taking a support person with you, e.g. someone who’s been through the process before, or someone who knows a bit about it.

If you’d like some time to process the consult and think about the answers, and/or speak with another specialist to allow a comparison, don’t fee pressured to commit on the spot to starting a cycle. Tell the specialist you’d like a few days to chew it all over and will contact them or their nurse to let them know what you decide.