Knocked Up Podcast - Embryo transfer types
Which one is right for you?
Embryo Transfer Types
Turns out there's more than one embryo transfer type, so what is an embryo transfer, what are the different types and which one is going to be right for you.
Hosted by Dr Raelia Lew and Jordi Morrison
Dr Raelia Lew is a RANZCOG Board Certified CREI Fertility specialist, Gynaecologist and the Director of Women’s Health Melbourne.
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Have a question about women's health? Is there a specific topic you'd like us to cover? Email podcast@womenshealthmelbourne.com.au. We keep all requests anonymous.
TRANSCRIPT
Women's Health Melbourne is an innovative, holistic fertility and women's health practice. We are world leaders in IVF and egg freezing and provide our patients with every opportunity to achieve their goals. Our handpicked expert team provides the ultimate care experience for our patients. Reach us at womenshealthmelbourne.com.au and follow us at women's health melbourne and @doctorraelialew. Hello, and welcome back to Knocked Up, the podcast about fertility and women's health.
Jordi Morrison: You are joined as always by me, Jordi Morrison, and Doctor Raelia Lew, CREI fertility specialist. Welcome, Raelia.
Dr Raelia Lew: Hi, Jordi. How are you doing?
Jordi Morrison: I'm great. Thanks. Thanks for another episode. This one's a good one. It's something that is real bread and butter to me, things that I do every single day, cut with my hat on as a reproductive endocrinologist and fertility specialist and IVF doctor. It's an episode about embryo transfers. It turns out there are many different types or several different types.
Dr Raelia Lew: Yeah. I guess we can start off with what is an embryo transfer because not everyone would necessarily know exactly what that is.
Jordi Morrison: In IVF, there are two elements of treatment, but basically what we're trying to do in IVF is make a baby. And the earliest stage of fetal life is called an embryo. The first stage of IVF is a stimulated cycle where we give medications to ask women's ovaries to reduce multiple eggs. We extract those eggs, extract those eggs, we fertilise them with sperm, and the result we hope are some embryos. And we usually culture embryos in the laboratory for either transfer or for freezing. And over the years, our practice has changed quite a lot as IVF doctors in the way that we transfer embryos. It used to be when I started studying to be an IVF doctor, the majority of embryo transfers were happening actually on day two or three after fertilisation when embryos were somewhere between two cells and and eight cells. These days, we tend to do the majority of embryo transfers once the embryo reaches the stage of blastocyst, which is about day five to seven of development, we we tend to do the transfer only on day five in a stimulated IVF cycle if we do a transfer in a stimulated IVF cycle. That's one of the types we'll talk about today. But an embryo transfer involves placing an embryo into the uterus to try and create a pregnancy. And we do that for most people with them awake coming into the clinic. We ask you to have a full bladder for an embryo transfer because we often do an ultrasound to guide the embryo transfer. I personally always do an ultrasound to guide the embryo transfer because we wanna place the embryo perfectly. Perfectionists like myself wish the embryo to be about a centimetre from the fundus of the uterus, the top of the uterus, in the thickest area of the uterine lining. And we place a tiny little guiding tube through the cervix, and then the embryo is loaded in an even tiny little tube that goes through the outer tube, and that's called an embryo transfer catheter. And the embryo is placed in the womb in a little well of fluid, often with a little bit of what we call embryo glue, which is hyaluronic acid to help the embryo stick, and then it is down to the embryo to make a baby.
Dr Raelia Lew: What's really important for that embryo to be able to make a baby are two things. One is its intrinsic potential. It has to have the right DNA. It has to have metabolic competence. It has to perform complex developmental tasks without making a mistake. But the other thing that could make or break an embryo's chance of making a baby is the environment of implantation. So where we've put this embryo has to be receptive. It has to be inviting. And if the environment of the uterus is in any way hostile, that makes life a lot more difficult for the embryo to successfully implant.
Jordi Morrison: And so there are different types of embryo transfer cycles. Why are there different types?
Dr Raelia Lew: Our practice has really evolved quite a lot in IVF. When IVF was first invented in humans, which was only in the very late seventies and early eighties, we had lots of missing pieces of the puzzle, and we still do have lots of missing pieces of the puzzle. But over the last few decades, we've been putting pieces of the puzzle together, the last four decades of IVF that things have been evolving. So the oldest IVF baby in the world is one year older than myself. Well, I guess we have to say mid forties now, don't we? In her early to mid forties. In terms of lab development in that time frame, the first scientists who made IVF embryos, they didn't know how to freeze them. They didn't know how to freeze them, and they couldn't survive freezing. And they didn't know how to culture them either. So culture techniques have just been so phenomenally advanced in the last forty years of IVF. We have amazing incubators now. We have cultured media that you can buy perfect media off as an off the shelf product. Labs used to mix their own media that they used to grow embryos in, and we've learned a lot about what embryos need to thrive and survive outside the body. But in the early days, embryos used to be put back pretty much straight away as quickly as possible. And because the embryos were at risk of being lost, if they weren't transferred because we couldn't effectively freeze them, IVF doctors used to put multiple embryos back at the time. We knew that not every embryo would make a baby. That's the case now to this day, but that's why IVF got a rep for twins and triplets and quads and whatnot that we have been struggling to correct for many decades. It used to be always that an embryo was replaced in a stimulated cycle for that reason. A stimulated cycle refers to the cycle that we give medications to the woman to collect her eggs. Just historically has been an expectation that an embryo transfer would happen most of the time in a stimulated cycle. What we've learned over the past decades where we've got really good at freezing embryos and really good at culturing embryos out in the lab is that there are really great disadvantages to transferring an embryo in a stimulated cycle for a lot of people, and that for many women, actually, the best thing is not to have a transfer in a stimulated cycle at all. There are certain risks in IVF that we combat when we ask a woman's ovary to make lots and lots of eggs in one month, and one of them is called ovarian hyperstimulation syndrome. It's actually quite a serious problem. It used to be even more of a problem in the past because as IVF technology has evolved, we've actually, luckily, and my generation are very spoiled and privileged to have access to really safe drugs to treat our patients. But back in the day, those weren't on the table. And so the old fashioned drugs and certainly an HCG trigger, which is used to be the only type of trigger we had in IVF, is a major, major risk factor for hyperstimulation syndrome. A woman can get really sick with DASH. We've covered it extensively in another episode. That's one, one risk of a fresh transfer in a stimulated cycle. But another risk is we're putting out precious embryo, our most beautiful chance of making a healthy child into this really zipped up, hormonally overcooked, hostile environment because the woman's had hormone levels that are ten, twenty times what they should be in an ideal implantation environment. The pendulum has kind of swung and a lot of us believe as fertility specialists, that for some women, the best thing to do is actually to freeze the embryo and separate the cycle out into an embryo making enterprise and then idealise the environment for implantation in another cycle. Stimulated cycle, embryo transfer has really a lot of cons, and there are good reasons not to do it for a lot of people.
Jordi Morrison: So if we're not doing it in a stimulated cycle, what are our other options? What are some other cons of transferring an embryo in a stimulated cycle?
Dr Raelia Lew: In a stimulated cycle, we know that the pattern of progesterone rise is really weird compared to a different cycle type. Firstly, the progesterone rise is premature, and then it goes to a really artificially high level after an IVF trigger. And then progesterone production plummets and the corpus luteum, which is the follicle that makes progesterone after an egg has been either released or collected, it becomes deficient in the context of the stimulated IVF cycle. This always happens to every single person. And for that reason, if we don't give a lot of progesterone as a drug, an embryo will always fail in that context. One disadvantage of a stimulated cycle embryo transfer is we have to use a lot of artificial progesterone. In the context of coming down off the stim hormones that can make someone really, really labile, moody, bloated, uncomfortable, and upset. So it kind of adds to the hormonal trauma of IVF. And another disadvantage I feel of a stim cycle transfer is that it's kind of out of the frying pan into the fire for the patient because there's a lot of uncertainty that reveals itself during the embryo culture process of IVF, and that follows on from some uncertainty in the phase where they're getting ready to collect eggs. When a woman's in simulation, she's having scans. She doesn't know how many eggs are going to be collected. The follicles generally give us an idea, but it's not exact. She finds out how many eggs have been collected on the day of her egg collection, but then it's always the way that only 50 to 70% of the eggs will fertilise and only about 50% of those fertilised early embryos will make it to be a day five embryo. So there's a lot of uncertainty and with it, a lot of anxiety, which I find that when patients separate out the embryo transfer to another month, you know, it's a lot easier for them emotionally because they know they've got an embryo to transfer and they're not stressed in the laid up.
Jordi Morrison: Okay. So moving on to frozen embryo transfer, what are our options here?
Dr Raelia Lew: So there are four different ways of doing a frozen embryo transfer. The first way is a natural cycle transfer with no intervention whatsoever. So with a natural cycle transfer, we are actually relying on the woman's own body and her own hormones to dictate when the embryo goes back, and we're not giving any drugs. A completely natural cycle transfer is best for a woman who has a regular menstrual cycle. It's pretty tricky if she doesn't. And what we do is we bring her in just before we think she's going to ovulate, and we start doing daily blood tests to figure out when she naturally ovulates to the best of our ability as exactly as possible. And then once we know when the right day to put the embryo in the womb is, we take the embryo out of the freezer and put the embryo back inside the uterus and let nature take its course. A variety on this theme is called an augmented natural cycle. I actually favour an augmented natural cycle over a completely natural cycle for a couple of different reasons. Mainly patient convenience, just to be able to plan our days and plan our lives and not subject the patient to so many blood tests. With an augmented natural cycle, when the woman comes in and has a ultrasound and we see that there's a follicle ready to go, she hasn't yet ovulated, and she's got a lovely lining, and, really, the scene is set. But we're just waiting for that hormonal surge to happen, and we're not quite sure if it'll be today or tomorrow. What we sometimes do is give a trigger, and that is a one off injection that makes sure that the cascade of ovulation happens at a time that we predict it's going to happen, and we use that trigger at a time when the embryo transfer is going to be. So that allows me as a doctor to plan my day, but it also allows the patient to have notice that she can plan her day and plan when she needs to be available for embryo transfer with a lot more certainty. And it allows us to get the timing right because when we do blood tests to estimate when the ovulation surge is happening, it's it's a guesstimate. Whereas when we give a trigger, we know exactly when we gave that trigger. So it's just more precise. The other thing that I often do in an augmented natural cycle is give a little bit of progesterone support. The analogy I use for patients when I talk about the corpus luteum, the corpus luteum is the progesterone making factory factory from which the egg is released in the cycle that we're talking about, is that if you make orange juice from oranges, not every orange is as juicy as every other orange. Not every corpus luteum is as good at making progesterone as every other corpus luteum. And we're putting back a really nice embryo. We just wanna make sure that the environment is as good as it can be, better than nature intended. And so we give a little bit of extra progesterone just as a belt and braces approach to make sure that the body's got enough because progesterone is an aptly named hormone. It's the pro pregnancy hormone, and it helps a pregnancy to stick. So making sure the levels are adequate is really important.
Dr Raelia Lew: The augmented natural cycle is one of my favourite cycle types in IVF for frozen embryo transfer. I always think the body is very clever. As doctors, we're trying to understand, emulate, and manipulate body processes. But, you know, every every year of my practice, I learn new things, so there's always things that we don't know yet, and I think the body, the natural cycle should be honoured, and it's a beautiful way to transfer embryos. One of the downsides to a natural cycle is that embryo transfer can happen seven days a week. Sometimes we try and schedule a natural cycle by giving a tiny little bit of additional augmentation. Sometimes we use what's called a GnRH antagonist for a couple of days in the cycle just so that we can time your embryo transfer at a time where your scientist and doctor can can do it. But, it's mainly leaving it to nature still and minimal intervention in terms of medications to the cycle. The other type of cycle where we try and achieve the same thing that just needs a little bit of medication is when someone doesn't have a regular natural cycle. So it's like, hey. I'd love to have a natural cycle transfer, but where's my natural cycle? I've got PCOS. I don't ovulate regularly, so I might be waiting three months for an ovulation, and that's not very fun. So an ovulation induction cycle can also be used to prepare an ovulation and a uterine lining for an embryo transfer. This can use medications ranging from letrozole to clomiphene to FSH itself, follicle stimulating hormone. The goal of medications are to achieve an ovulation, and from there, it's augmented natural cycle. But that's to help someone who doesn't regularly ovulate have the benefits of a natural cycle transfer. One thing to say is that natural cycle transfers and ovulation induction cycle transfers involve the release of an egg. And for some patients, it's not common, but for some patients who have sex around the time that they release that egg, they could theoretically get pregnant from the egg they release. If they don't get pregnant from the embryo or if they get pregnant from both, then they might be having twins. So that's a little bonus of a of a natural and an an ovulation induction cycle. And if having twins would horrify you or if we don't want you to get pregnant naturally because we're testing the embryo for something genetic you carry or something like that. We tell you not to have sex in those cycle types. But otherwise I mean, my personal approach for my patients is if if they're suffering long standing infertility, often the chance of putting an embryo back and making a baby is something like one in three. I don't tell them not to have sex in a natural cycle or an ovulation induction cycle. If they wanna roll the dice, then I support them in that.
Dr Raelia Lew: The final type of embryo transfer cycle is called an artificial or HRT cycle. This is a cycle favoured in certain circumstances. It's a cycle with a lot less uncertainty of timing. We can pretty much schedule when the embryo transfer will happen in an artificial cycle. There are lots of pros and cons to this cycle type compared to a natural cycle. Compared to a natural cycle, there's a lot more medications, and the medications need to continue for a lot longer. In an artificial cycle, we need to support the pregnancy for the first trimester. So the medications we use, while they're often not injections, have to continue until twelve weeks of pregnancy. An artificial cycle can help someone get pregnant if they're menopausal. So if you've had premature ovarian failure or if you're trying to have a baby after the age that you have stopped ovulating and and stopped having a regular cycle, then we can do this type of cycle to help you get pregnant. What it does is give oestrogen and then subsequently progesterone, and those are the two main hormones to prepare a lining of the uterus and then to make it receptive, to help you then have an embryo transfer five days later. It is the preferred cycle type for long distance travel. So often when someone's living rurally or we can't monitor and get same day blood tests back, or if they're travelling internationally, because some people do travel internationally for embryo transfer for various reasons. This is the regimen of choice because we have much more control. It's also the regimen of choice for many people using frozen eggs to conceive because we can time the day we're gonna take the eggs out of the freezer, when we need the sperm, and how your uterus is going really well for the first embryo transfer using a frozen egg. I often use an artificial cycle in that context for the precision that it offers. The other thing that it's really good for is if we're coordinating a donor and a recipient. So if there's an egg donor and an egg recipient and we're trying to get the egg recipient pregnant in the same cycle that an egg donor does in egg collection, we can really sync their cycles using the pill before we get started and then use an artificial cycle to make sure that the timing of when the recipient's uterus is ready is the timing of when an embryo is is at the right stage of development to be transferred. So that, again, the precision timing of this cycle type is advantageous. And another scenario where this precision timing is advantageous is if the male partner is having a testicular sperm retrieval in an open operation, and we're using frozen eggs in that context because we can time the cycle by the calendar to the day after the sperm is retrieved for the eggs to be taken out of the freezer and the transfer to happen subsequently. So we've got a lot of control. Some people prefer artificial cycles because they have control. Some people who don't ovulate prefer artificial cycles because they find ovulation induction tedious. There are some reasons why artificial cycles are not always the perfect way. We know the risk of blood pressure for some people in preeclampsia is slightly higher in an artificial cycle compared to a natural cycle. We know that most people who have an artificial cycle don't have those problems, but the risk of it happening is a little bit higher. And that's because when you ovulate and release an egg, the corpus luteum, yes, makes oestrogen and subsequently progesterone, but it also makes lots of other vasoactive peptides that can help make a healthy placenta. And so we're replacing the main ingredients when we do an artificial cycle, but there are some ingredients of the cycle that we don't replace. We can kind of compensate for that with the use of aspirin. But in terms of choosing a cycle type, some people who might have a family history of preeclampsia or personal history of preeclampsia, we might choose a different cycle type rather than artificial in that situation.
Jordi Morrison: How do you know which type of infra transfer to do?
Dr Raelia Lew: Usually, I actually discuss the pros and cons of different types with my patients and their scenario and also their preference will come into it. I would say the majority of my patients do an augmented natural cycle because there are lots of advantages of that cycle type, but equally, I do quite a lot of artificial or hormonally supported cycle types for the reasons we discussed. And sometimes it's just patient preference. They just prefer one way versus the other, which is fine. It it's really important to say that when you take out of the mix the fact that when you ovulate, you could get pregnant from the natural ovulation, the chance of pregnancy in each of these cycle types is is very, very similar to the point where there's absolutely no clinical difference. So no cycle type is better than any other cycle type, and it really comes down to clinical relevance and patient preference.
Jordi Morrison: Thank you so much, Raelia. Really interesting. Who knew? There were so many types of embryo transfer.
Dr Raelia Lew: I think one really important thing about how I practice IVF and about IVF in general is that nothing is a cookie cutter experience and every treatment should be individualised to the need of each individual patient. There's lots of ways of solving the same problem. And in choosing our solution, we have to take individual patient factors into account.
Jordi Morrison: To support Knocked Up, leave us a review or recommend to a friend. Join us on Instagram at @knockeduppodcast and join Raelia at @doctorraelialew, and email us your questions to podcast@womenshealthmelbourne.com.au.