Posts Tagged ‘egg quality’

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:

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.

Our IVF/IUI/TI cycle just failed … What should we be asking at the review?

Thursday, September 24th, 2009

After all the waiting to GET on the waiting list and then all the waiting ON the waiting list, finally you got to try the “big guns.” You’ve somehow overcome your fear of needles, vaginal scans and then (for IVF) the dreaded egg collection procedure; you’ve survived the harrowing 2ww … and it’s a BFN. Or a chemical pregnancy. Or a pregnancy and then a miscarriage.

After all that anxiety, fear, hope and expectation, a failed cycle is just devastating. You’re booked for a review appointment with your specialist – but what should you be asking about now?

The most important question, of course, is WHY your cycle failed. There could be many possible explanations, some of which are just guesses and some of which are backed by concrete evidence or could be investigated further.

You don’t want to go through the expense and stress of another IVF cycle and only afterwards find out there was something else you should have addressed first. Here’s a quick list of other things you should be sure to have checked out if you haven’t already:

  • Male Factors. A full semen analysis is necessary – not just counts/motility/morphology but also tests for antisperm antibodies and SCSA (tests for DNA fragmentation).
  • Polyps and Fibroids. Uterine polyps and fibroids, even if they’re small, can influence the menstrual cycle and can interfere with implantation. They can typically be seen via ultrasound and can be removed through a relatively simple surgical procedure.
  • Thyroid Issues. Thyroid issues can impact fertility and need to be ruled out as a contributing factor. A thorough thyroid test needs to include TSH, free T3/T4 and anti-thyroid antibodies.
  • Ureaplasma. Ureaplasma is an infection for which you should be tested. “Ureaplasma may cause the formation of sperm antibodies and an inflammation of the uterine lining, either of which may interfere with implantation of the embryo” (Source)
  • Factor V Leiden. Testing for Factor V Leiden is also important. “Factor V Leiden is a relatively common hereditary blood coagualtion disorder and can lead to stillbirth or unexplained recurrent miscarriage” (Source)
  • Hysterosalpingogram (HSG). An HSG is a test to determine whether the fallopian tubes are open. Even if you’re doing IVF this is important because you could have a hydrosalpinx, which is a blocked tube that leaks toxic fluid into the uterus and can affect implantation. (More info)
  • Recurrent miscarriage/recurrent implantation failure testing panel. In New Zealand, the usual procedure is to run a set of blood tests (on the female partner) such as:
    • Coagulation screen
    • Thrombophilia screen
    • Autoantibody screen incl.
    • antithyroid antibodies,
    • anti-gliaden antibodies
    • Factor V Leiden
    • Karotype
    • MTHFR mutation
    • Anticardiolipin antibodies
    • Lupus anticoagulant
    • … and a karotype for the man

Follow this link for a very comprehensive list of possible causes of recurrent miscarriage that can be investigated systematically if you need to do some more serious digging.

  • Endometriosis. If you have period pain that requires more than a couple of Panadol (or any other of the possible symptoms of endometriosis), ask for a laparoscopy to investigate. Endometriosis is quite common and often missed or misdiagnosed, e.g. because women think their period pain is normal. For more information, check out Endometriosis New Zealand’s excellent website.

OK, nice laundry list, but what should I be asking my doctor?

Before your review appointment, if you did IVF, call the embryologist who worked with you during your cycle and ask him or her what they thought about the quality and maturity of your eggs, the fertilisation rates and the quality and development of your embryos. If you can, it’s best to do this soon after (or, the day you go in for) embryo transfer so that it’s fresh in the embryologist’s mind. Pump them for any information you can get.

When you see your doctor, start with an open-ended question about what he or she thought went well in your cycle and what didn’t. Summarise what the embryologist told you as well and ask the doctor to comment.

Your next question should be around the various other possible causes of cycle failure listed in the bullet points above. How many of these have we eliminated as a possible cause, how did we do so, and which of them should we investigate before leaping into another cycle? Make sure you study these beforehand and think whether you recognise any relevant symptoms.

You may find yourself in a situation where the doctor pronounces you have an egg quality problem. Now, this is a difficult one because, from a Western medicine perspective it’s seen as untreatable and just the hand you’ve been dealt. Further, this is really little more than an “eyeball” assessment, assuming you haven’t done a PGD (preimplantation genetic diagnosis) IVF cycle where the embryos are actually tested for chromosome abnormalities. Visual egg and embryo quality is correlated with chromosomal normality/abnormality and pregnancy rates, but it isn’t a direct assessment of these things. You can definitely have great looking eggs/embryos that are abnormal. And there are a few instances where very scrappy, sad-looking eggs and embryos turn into perfectly normal babies, but unfortunately not very often.

If you do get the “bad eggs” speech, there are a couple of questions you should raise. One is whether you can try a different protocol that might be better suited to your delicate eggs. For example, some specialists argue (and have evidence) that higher doses of stims can “fry” some women’s eggs, so that a lower dose may be more gentle and damage them less. [I personally had a dramatic improvement in embryo quality when I dropped my dose from 450IU to 150IU, and I know others who have experienced the same.]

The other thing to insist is that “bad eggs” isn’t just assumed to be the ONLY cause of your failure. Even if it’s true and you are looking at moving forward with donor eggs, you need to be sure you don’t have uterine or autoimmune issues or endometriosis (etc) that could jeopardise the success of that cycle.

Most fertility specialists in New Zealand don’t really buy into the idea of alternative medicines, but if you’ve been given the “bad eggs” or “old eggs” speech, I’d strongly recommend reading the following piece by Dr. Randine Lewis about the Chinese medicine perspectives on “poor egg quality” and whether there’s anything you can do to address it.

This website/blog also has several posts on acupuncture and Chinese medicine – see the menu at left to find items on that topic.