Posts Tagged ‘blastocyst’

IVF – the hurdles

Friday, October 2nd, 2009

So you’ve read the IVF manual and are all ready to start a cycle. What are some of the “wish I’d known that” snippets that veteran IVFers can share with you to help fill the knowledge gaps about what to expect? Well, one that comes up a lot is having a clear understanding of the not-so-straightforward hurdles involved in an IVF cycle. Here’s a typical comment from an IVFer …

When you start this journey you read the “ivf manual” and all sounds so easy – take some drugs, grow some eggs, have them collected, fertilised and put back in and voila! a baby. Ha!! They don’t tell you about the things that go wrong. Or the things that don’t work the way they should.

So, what are the main hurdles you face in an IVF cycle?

  1. Downregulation or precycle suppression might take longer – some gals do their downregulation blood tests after several days on Buserelin and find they need to keep downregulating for several more days before starting stims. If you’re on no precycle suppression or something very mild, you may find that you have a dominant follicle or a cyst at the beginning of your cycle and it may not be a good idea to proceed with stims.
  2. Assuming you get out of the starting blocks, your first hurdle is whether your ovaries will respond to the stims. This is assessed with blood tests (for estrogen, or E2) and an ultrasound. If you grow too few follicles or your E2 is too low or the follies don’t grow fast enough or your E2 doesn’t rise enough, the clinic is likely to cancel your cycle for poor response. The good news is that you may do better on another protocol – see an earlier post on IVF protocols for more information …
  3. Some women have the exact opposite problem to poor response – they overrespond. They grow too many follicles and their estrogen shoots dangerously high. In this case the clinic will either drop your dose of stims or stop stims altogether (this is called ‘coasting’). The blood tests continue, and if your E2 drops to a safe level they will let you trigger and go ahead with your egg collection; if the levels stay too high for too long, you may be cancelled for your own safety because you are at high risk of OHSS (ovarian hyperstimulation syndrome). Even if you make it to egg collection, you may be told it’ll be a freeze-all cycle – research shows that women at risk of OHSS are at higher risk if they do a fresh transfer and get pregnant.
  4. You make it as far as egg collection (a.k.a. ‘retrieval’) and have 10 follicles. That’ll be 10 eggs, right? Unfortunately not. Not all follicles yield an egg, and some women have major problems at this hurdle, getting only eggs from only 50% of their follicles, or sometimes fewer. [See Empty Follicle Syndrome] Others have a 100% strike rate just about every time. So, it’s just the luck of the draw. In any case, you shouldn’t expect to get an egg from any follicle that was smaller than about 15-16mm at trigger, and you shouldn’t expect all your mature (large) follicles to yield eggs.
  5. Yay, we got six eggs!! That’ll be six embryos, right? If you’re lucky, yes, but there are more hurdles here too. First, it’s possible not all of your eggs were mature. Only the mature ones can potentially fertilise. And not all of them do. Some couples get 100% fertilisation just about every time, and others get a very low %. Some also get abnormal fertilisation, such as when two sperm enter one egg. ICSI can improve fertilisation rates if there are sperm issues or if the eggs have hard ‘zona’ (eggshells).
  6. The day after egg collection, the embryologist will usually call you to let you know how many of your eggs were mature and how many have fertilised normally. From there, you are in a waiting game to find out how many of those embryos will make it to Day 3, and how well they divide. Some may ‘arrest’ (stop growing) along the way, some will divide more slowly (or quickly) than is optimal. The best possible result is to have 4-cell embryos on Day 2 and 8-cell embryos on Day 3. The survival rate from fertilisation to Day 3 is not usually too bad.
  7. If you’re taking your fresh or leftover embryos from Day 3 to blastocyst stage, there is a VERY high die-off rate at this point. Before deciding to do this, I strongly recommend you read the post on this issue (2-day, 3-day or blast transfer?), discuss it with your doctor, nurse and embryologist, and make your wishes crystal clear.
  8. Once the embryos are transferred back to the uterus, you are in the dreaded 2ww (2-week wait). Arrrghh! Enjoy the first week because you are going to drive yourself insane in the second week obsessing about every twinge. 🙂

Well, those are the main hurdles for an IVF cycle. The bad news is that if you DO get a BFP there’s a whole other set of even more hair-raising hurdles to clear! But we’ll save that for another post …

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!