Posts Tagged ‘IVF – In Vitro Fertilisation’

2-day, 3-day or blast transfer?

Friday, September 25th, 2009

When you do IVF, it is possible to transfer your embryos

  • on Day 2 after egg collection (usually 4-cell embryos),
  • on Day 3 after egg collection (usually 8-cell embryos) or
  • on Day 5 (after the embryos have reached blastocyst stage).

If you have only a small number of embryos and plan to transfer them all, the usual procedure is to put them all back on Day 2 because the uterus is the best possible place for them. However, if you’re doing assisted hatching, you usually need to keep them out for one more day and transfer on Day 3.

If you have a large number of embryos, and particularly if several of them are high grade, you will usually be encouraged to take them all to blast because that turns your ‘longlist’ dilemma (which to choose, which to choose …) into a ‘shortlist’ of embryos that are more likely to be viable.

As any specialist will tell you, odds of a pregnancy with a blastocyst transfer are higher than the odds with a Day 2 or Day 3 embryo transfer. This is an undisputed fact.

Some specialists will also tell you the extreme version of this (which is not actually proven, and is IMHO quite questionable), i.e. that if your embryo doesn’t make it to blast it wouldn’t have been a viable pregnancy anyway.

At virtually all NZ clinics (from what I have heard), the default is to make any leftover embryos go to blastocyst stage before they are frozen. The kicker is that many (and sometimes all) embryos don’t make it as far as blastocyst, i.e. they die in the petrie dish some time between Day 3 and Day 5.

Why does my clinic want us to take our embryos (or leftovers) to blastocyst stage?

The main reasons for these policies (as I understand it) are:

1. For women and couples with a large number of embryos, it is often difficult to tell which are the ‘winners’ that should be put back to give the best odds. By taking them all to blast, only some will make it, and in the ones that do, quality differences will hopefully be more obvious, thereby making the choice easier.

2. There are loads and loads of frozen embies that will never be used and no-one knows what to do with them. Ethical dilemma, and a logistical storage dilemma. Getting people to take their fresh embies to blast, and/or making any leftovers go to blast, cuts those numbers down.

3. More frozen embies means more TERs, which means greater expense for the govt (if you are publicly funded) or greater expense for couples (if you go private) – and more stressful 2wws with lower chances of a BFP each time (compared to a blast transfer). If those embies aren’t going to make it, they think you are better off finding out during the 2ww of your fresh cycle than prolonging the agony and expense. [Personally, I think this is a trade-off each couple needs to consider for themselves; having all frosties tank while you’re in the 2ww makes a VERY stressful time even worse.]

4. They don’t want to give people the “false hope” of thinking that their spares in the freezer are potential children because most of them are not. Quite apart from the points made in #3, above, if you’re an older mum, the months you spend doing TERs that end in BFN are months you are getting older before trying another fresh cycle. [I know some women overseas who cycle and freeze several times before transferring ANY for this reason; if they do get pg on the fresh cycle they will be too old and very low odds by the time they try for a sibling, so they bank several embies up front in the hopes that they might get 2-3 kids out of the lot. I have a friend who banked about a dozen embies at age 43-44, got pg on her last fresh cycle at 44, now is 46 and looking to do TERs, thankfully using embies made at age 43-44, not the near-zero-odds ones she’d produce now (if any).]

5. If you’re transferring blasts it’s easier to talk couples into transferring just one (because of the higher odds) and this reduces the number of twin births, which reduces the burden on the taxpayer, health system, the pregnant mum (twin pgs are sooooo not fun, trust me!), and the parents (possibility of losing one or both is higher, health problems are higher in twins than singletons, the first few months in particular are really really gruelling).

So, what are the main arguments against making your fresh embryos or leftovers going to blast?

The big issue here is, of course, could a potentially viable embryo die in the lab when it would have lived in utero? It’s unlikely but possible, in my view. Here’s why:

1. The number of embies that don’t make it to blast seems to me to be far higher than you’d expect for the age of the woman. Just an observation. This not only raises suspicions for me that viable embies are being lost this way, but in all those cases where there are none left to freeze (so many recently, it’s heartbreaking), it also massively increases the stress when you are in the 2ww and find out that EVERYTHING now hinges on your fresh cycle. Even if the day 3ers aren’t viable, some couples would rather have the psychological comfort of knowing there was another non-zero chance if they get a BFN.

2. There are some absolutely clear cases where people have had babies from embies that any self-respecting embryologist would stake their career on their not making it to blast. Case in point a board buddy of mine who put back four including two 5-cells that were so fragmented they looked like dollops of oatmeal, in her words. The embryologists gave them NO hope of surviving, so she just thought what the heck, put them all back. She’d had 5 failed IVF cycles already and was 35. She got pg with quads including one set of identical twins, so one of those oatmeal dollops turned into a baby (or two!). They are now 6yo, BTW.

3. The research apparently shows that blast pregnancies are more often boys, yet this is not the case with IVF pgs from 3-day transfers. This strikes me as extremely compelling evidence that SOME genetically normal girl embryos for some reason don’t make it in the lab but DO make it in utero.

It’s not an exact science of certainties; it’s a mix of probabilities and possibilities. Each couple is going to weigh these considerations quite differently. A lot depends on the woman’s age, how many cycles and TERs you can do without going broke or insane, how many kids you want eventually (and how you feel about ‘surplus’ embryos once you’ve achieved your quota), how stressful the various scenarios are to YOU, how many eggs you get each time, etc etc. Also, the aforementioned downtime (with the woman getting older) while you try multiple low-odds TERs instead of moving onto another fresh cycle.

The major issue I have with this is that IMHO (and based on reports from women all over the country I have spoken to) clinics in New Zealand consistently fail to consult adequately with patients, particularly on whether leftover embryos are taken to blast. The vast majority of patients are left with the impression that they had no choice in the matter. Frequently, ALL leftover embryos die before making it to blast, and patients are upset and dismayed to find out that they COULD have asked for their leftover embryos to be frozen on Day 3 instead. Here’s a typical comment from an IVF patient:

I had no idea we had the opportunity to freeze embies at day 3. This has NEVER been offered to us. From what we understand they are to be frozen day 5. We unfortunately have never had any to freeze as we’ve waited to day 5 for them to get to blast. I didn’t even know it was possible? I wonder why [my clinic] have never mentioned this?

This situation is especially upsetting if you are on your last IVF cycle and can’t ttc any other way (e.g. because of no tubes or MFI/sperm issues). When you’re standing in those shoes, it can just feel like the clinic has done everything it can to get you off their books (or onto another fresh cycle and more $$ in their coffers). I’m not saying that’s the motivation behind what clinics do; I’m just saying that can be what it feels like for patients who haven’t been offered the opportunity to give genuine informed consent on an important aspect of their treatment.

So, how should we tackle this and make sure we get what we want?

  • Think through these issues ahead of time and discuss them as a couple – there are trade-offs for either choice and there’s no single right answer
  • It may also be useful to ask the clinic lab/embryologists for some concrete data on what % of embryos make it to blast for women your age
  • Discuss the issue with your doctor and state clearly what you want
  • Write on your IVF consent form exactly what you want – make sure the nurse is clear on this too
  • Confirm this with the embryologist when you meet with them (e.g. at egg collection)
  • Confirm this AGAIN with your embryologist when you go in for embryo transfer
  • If you get any resistance from the embryologist, call in your doctor and refer them both to your consent form – INSIST on what you want. It’s your right!

Do more IVFs give you higher chances of success?

Friday, September 25th, 2009

“I’m wondering is it true what they say that the more cycles of IVf you do the higher your chances of getting a BFP? Depending on quality and # of embies put back of course.”

There are basically three schools of thought on this, as I understand it:

1. It’s a numbers game. If 15% of your embies are viable (the % varies according to age; this is the ballpark for women aged about 39/40) you’ll need to put back half a dozen or so before you have a 50/50 chance of becoming pregnant. Although the odds per cycle don’t increase, the cumulative odds based on having done several cycles do increase, if that makes sense.

2. Although the cumulative odds increase, the odds per cycle actually decrease with each failure because now you’re not just someone aged 39 ttc via IVF, you’re someone aged 39 with four failed cycles under her belt ttc with IVF – odds are lower for a 39-year-old with 4 failures than for someone who hasn’t tried at all. Does that make sense?

3. Although 1 and 2 above are true in theory, you may actually be increasing your odds in subsequent cycles BUT ONLY if you are using what is learned from each failure to make improvements to the protocol (and any other fertility-related treatments or interventions) to find your “Goldilocks” (just right) formula.

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.

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.

Can acupuncture help?

Wednesday, September 23rd, 2009

There’s a very interesting difference between Western and Chinese medicine on how fertility is viewed. Western doctors tend to focus on the cycle in which your eggs are produced (e.g. the cycle in which you do IVF), whereas Chinese medicine takes a much more long-term view.

To help understand the difference in thinking, here’s a quick (and hopefully not too inaccurate) summary of where eggs come from.

The process starts about a year before you actually ovulate, when a bunch of ‘primordial follicles’ are recruited within the ovary. These are developed very very slowly over the course of several months.

At about three months before ovulation, these primordial follicles start a different phase in their development and are now known as ‘antral follicles’. At the very start of any given cycle, an ultrasound will show several small antral follicles that are ready to go. In fact, this antral follicle count (AFC) is a good rough indicator of your ovarian reserve – check out this guide to how AFC helps predict a patient’s response to IVF stims.

During a natural cycle, just one or two of these antral follicles are recruited and will mature, leading to ovulation of an egg or sometimes two. The remaining antral follicles just fizzle out and undergo ‘atresia’ (basically, they bow out of the race). Here’s a link to a really excellent animation showing what happens in an ovulation induction (e.g. Clomiphene) cycle, which is not that different to what happens in a natural cycle (in a natural cycle you usually only ovulate one egg).

During an IVF cycle, the goal is to try and get more of those antral follicles to mature and fewer of them to undergo atresia.

So, how do the Western and Chinese perspectives on this process differ?

Your Western specialist tends to focus on a particular treatment cycle (i.e. that one month), which is the journey from antral follicles to ovulated eggs, fertilisation and beyond.

A Chinese medicine doctor, in contrast, takes a much more long-term view of the process. The intent is to create the optimal and best balanced environment for the development of your primordial follicles and then their further development once they become antral follicles, and then finally (the last and very short conclusion of the journey), the recruitment of antral follicles to produce an egg, get it fertilised, etc.

This is why the Western view is that there’s nothing you can do to influence egg quality – you are dealt the hand you’ve got; you just have to harvest as many eggs as possible, play the numbers game and hope that one of them is good.

The Chinese medicine perspective is that, although age and heredity are huge determinants of egg quality, eggs and their chromosomes can also be damaged during their development if they are subjected to toxins or have to grow in a sub-optimal environment. So, if you maximise the quality of the ‘soil’ in which they develop, then you will be able to get the best possible eggs that the woman can produce at her age.

This is why acupuncturists (and naturopaths, for that matter, who subscribe to a similar view) will tell you that you should do acupuncture for at least three months before expecting to see real benefits. Here they are talking about optimising the development of your antral follicles prior to a particular cycle. And if you do acupuncture for a year, you are not only helping this part of follicle development, but also the development of the primordial follicles as well.

Is there any actual research that shows acupuncture works?

Yes!! OK, acupuncture is hard to evaluate because treatment is very individualised (you can’t just standardise and expect the same treatment to work on different people). Also, it’s highly dependent on the competence of the practitioner. But there have been some very good studies done that show the benefits of acupuncture on fertility. Dr. Vitalis in Auckland has posted a really excellent summary of the effectiveness research on acupuncture – check it out.

I hope all this makes sense! Please post comments or questions below if not, or if you have something to contribute. Thanks!

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.