Archive for the ‘Advanced Maternal Age’ Category

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.

What is assisted hatching?

Saturday, May 1st, 2010

Assisted hatching is an optional extra procedure used in IVF where a small hole is made in the shell (or ‘zona’) of a Day 3 embryo. This is supposed to help (in some cases) the embryo ‘hatch’ out of its shell and transform itself into a blastocyst (usually on Day 5).

Probably the best site to get a clear understanding of assisted hatching is the one from the Advanced Fertility Center of Chicago, which shows in great detail how the hatching process works, including a pic of an embryo actually in the process of hatching to become a fully hatched blastocyst. Cool!

In New Zealand assisted hatching is not part of the default IVF protocol, so you would need to ask your specialist about it.

My understanding is that public funding won’t cover assisted hatching (I could be wrong about this – please chime in if you know of criteria for eligibility). But, if you were doing a publicly funded cycle and your specialist agreed it might be a good idea, you could presumably pay for it out of pocket (it’s a few hundred dollars).

If you are a self-pay patient, obviously the choice is with you and your specialist, so ask. However (and someone please update me if this is no longer the case), if you have the OK to transfer more than 2 embies, apparently the clinics are not allowed to do AH on more than two. I can’t fathom the reasoning on that (especially for women over 42), but there you go … Minor trivia, but worth knowing in advance (if you’re like me, you hate surprises cropping up during the cycle).

Just to give a broader perspective, in the States, where patients are either paid for by insurance or out of pocket, assisted hatching (AH) seems to be used more widely. The Advanced Fertility Center of Chicago says they do it on all embryos, but they also offer the following useful list of criteria:

Who should be treated with assisted hatching?

The most commonly used indications for assisted hatching with an in vitro fertilization case are:

  • Age factor – Couples having IVF with the female partner’s age over 37
  • Egg quantity and quality factor – Couples in which the female’s day 3 follicle stimulating hormone (FSH) level is elevated
  • Embryo quality factor – Couples having IVF with poor quality embryos (excessive fragmentation or slow rates of cell division)
  • Zona factor – Couples having IVF with embryos that have a thick outer shell (zona pellucida)
  • Previous failures – Couples having IVF that have had one or more previous IVF cycles that failed

In our IVF clinic, we use assisted hatching on just about all cases – because we think it increases the pregnancy and delivery rates.

For the original page, see http://www.advancedfertility.com/hatching.htm

I’m pretty sure that assisted hatching can be used whether you are doing a 3-day or a 5-day transfer, but generally not for 2-day transfers (the embryologists say the embryo is usually too small then and there’s a risk it could break up if the zona is punctured). With a 3-day transfer, they will do this immediately before they put your embies back. With  a blast (5-day) transfer they would presumably do the AH on day 3 before putting the embryos back for their last two days of development. Anyway, these are just a few things to discuss with your specialist.

As for risks, my understanding there is a very very small increased likelihood of conjoined twins if assisted hatching is used. My own specialist told me that, although this was statistically true, the reality was that the increased chances are so miniscule that they don’t really have practical significance.

Who should be treated with assisted hatching?

The most commonly used indications for assisted hatching with an in vitro fertilization case are:

  • Age factor – Couples having IVF with the female partner’s age over 37
  • Egg quantity and quality factor – Couples in which the female’s day 3 follicle stimulating hormone (FSH) level is elevated
  • Embryo quality factor – Couples having IVF with poor quality embryos (excessive fragmentation or slow rates of cell division)
  • Zona factor – Couples having IVF with embryos that have a thick outer shell (zona pellucida)
  • Previous failures – Couples having IVF that have had one or more previous IVF cycles that failed

In our IVF clinic, we use assisted hatching on just about all cases – because we think it increases the pregnancy and delivery rates.

The Biological Clock: Cool interactive tool from Fertility Associates

Monday, March 29th, 2010

Wondering how much time you have left to dilly-dally before seeking treatment? Fertility Associates has just put out a very cool, interactive ‘Biological Clock’ to show you the odds of getting pregnant naturally vs. IVF at your age and beyond, and how long you should wait before seeking treatment depending on your age and how long you’ve been trying.

Of course, the odds vary a lot depending on your specific diagnosis. If you have blocked tubes or serious male factor infertility, then there’s no point trying naturally at all. If you’ve got high FSH, low AMH or diminished ovarian reserve (DOR), step on the gas sooner rather than later!

My own experience is that if there’s a little voice inside your head wondering if you need some help to get pregnant, listen to that voice sooner rather than later! Don’t let precious time tick by; don’t put up with a laissez-faire attitude from your GP or OB; if you need to, find a few $$ and book yourself a private consultation with a fertility clinic. It doesn’t rule you out for public funding if you do need it.

What is DHEA?

Friday, November 27th, 2009

DHEA (Dehydroepiandrosterone) is a naturally occurring hormone in our bodies which depletes as we get older. Here’s some info quoted from a UK site (<– click the link for more detailed info):

Description: DHEA, also known as “the mother hormone”, is produced by the adrenal glands and is the most dominant hormone in the body. The body converts DHEA into whatever hormone it needs (i.e. estrogen, testosterone, progesterone, and coriconsterone) In both sexes, blood levels of DHEA peak at 20. Thereafter, the levels steadily decline throughout aging, more dramatically with child bearing and with menopause. By eighty years old, the body only has 5% of the DHEA levels it had at 20! Many age-related conditions appear associated with lower than average levels of DHEA.

OK, so what’s all this got to do with infertility?

Dr Norbert Gleicher and colleagues at the Center for Human Reproduction in the States stumbled across the idea when a poor responder over 40 patient of theirs started having better and better responses to IVF – she had been secretly taking DHEA. Since then they (and others) have conducted some randomised trials and have seen some promising results in poor responders.

Here is a CBS News video of Dr. Gleicher, that older patient of his and a couple of other doctors talking about DHEA.

Want more info? Here are a few useful links to some of the research (you can find more through Google Scholar):

OK, sounds like a miracle cure – should I take it?

It does sound amazing, but the reality is that it doesn’t help all poor responders. In fact, the poor responders I have spoken to over the years have seldom had such obvious beneficial effects. Also, it does have some downsides for some people. Here are the ones I’ve become aware of:

  • Anyone who has higher than normal androgen or DHEA-S levels should definitely NOT take it because it can exacerbate these issues. Be especially cautious if you have PCOS or PCO, or any facial hair issues. Make sure you get DHEA-S and androgen levels measured first by your doctor and discuss the idea with him/her thoroughly to decide together whether it’s right for you. You have to do this anyway because it is only available on prescription in New Zealand. And even then, you can expect it to cost about $75/month.
  • If you’re under 40 then your DHEA levels may already be normal, so you wouldn’t benefit from it. It’s really only useful for those whose levels are seriously depleted.
  • Anyone who has a history or risk of ovarian cancer should not take it.
  • Some women have experienced hair loss and wacky cycles after taking DHEA.
  • Some women get too high levels of testosterone after taking it, and can end up with facial hair and deeper voices.
  • It can cause sleeplessness, especially if you launch straight into a high dose. If your doctor does agree and prescribes it, ask to start on a lowish dose (like, 25mg), take this in the morning (not the evening), and let yourself get used to it for a week or two before increasing the dose.
  • If you are taking Dexamethasone during your stim cycle to enhance response or help with implantation, the general advice is to stop DHEA before you start Dex because they apparently work in opposite ways.

So, are there any upsides? I took it myself for a couple of years, and had some upsides (also reported by others). The flipside of the sleeplessness thing is that it can make you feel like you have more energy. I also found it seemed to increase my metabolic rate, so I lost a couple of kilos while on it. But did it help my response to IVF? Well, not obviously, but it certainly didn’t hurt.

To sum up, the jury’s still out on this one. Do your research, talk to your doctor, get your DHEA-S levels tested first before agreeing to try it. Dr. Gleicher says that he sees many spontaneous natural pgs among women taking it while waiting to start IVF, so don’t wait until you start cycling. Many say it takes about 4 months before the effects really kick in. If you notice any adverse effects, talk to your dr straight away about whether you should stop it or reduce the dose. Make sure your DHEA-S and androgen levels are retested regularly to make sure they aren’t going too high.

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!