Knocked Up Podcast - IVF, STEP BY STEP
In this episode, we walk through the IVF process from your first consultation right through to that all important pregnancy test.
Starting IVF can feel overwhelming, but understanding each stage can make the experience far less daunting. In this episode, we walk through the IVF process from your first consultation right through to that all important pregnancy test.
Dr Raelia Lew breaks down what really happens at every step, why certain tests and treatments are needed, and how the team at Women’s Health Melbourne and Melbourne IVF work together to give patients the highest possible chance of success.
From investigations, stimulation and egg collection to embryo development, transfer and early pregnancy monitoring, this episode is designed to be your roadmap.
If you are beginning IVF, considering treatment, or simply want to understand how it all works, this conversation offers clarity, reassurance and expert insight from a CREI specialist who has supported thousands of patients through their fertility journey.
TRANSCRIPT
JORDI MORRISON: Okay. Hello and welcome to Knocked Up, the podcast about fertility and women's health. You are joined as always by me, Jordi Morrison, and Dr. Raelia Lew, CREI Fertility Specialist. Welcome, Raelia.
DR. RAELIA LEW: Hi, Jordi, great to be here.
JORDI MORRISON: Thanks, Raelia. Today we are talking through the IVF process in some detail. You often say, as do many of our guests, that it takes a village to create an IVF baby. I thought it'd be great if we went through all of the steps involved to sort of explain how this team, the village, are involved and how long it can take really from your first appointment.
DR. RAELIA LEW: Absolutely. Happy to do that. So the first step is meeting with your fertility specialist.
JORDI MORRISON: Yeah.
DR. RAELIA LEW: When you meet with a fertility specialist, it can be in a range of different contexts. I think nobody wakes up and thinks, yay, I'm going to do IVF today. I think when patients come and see a fertility doctor because they've been struggling to get pregnant or they have another reason for IVF, an example might be... that they have discovered they have a genetic condition that they want to screen embryos for so they don't have a baby with a terrible problem, or in some circumstances it's even more traumatic, they might have a cancer diagnosis or a serious reason why they can't have a baby now for medical concerns and it's to talk about fertility preservation for the future. Often when patients come and see a fertility doctor, they carry a burden of stress. And in order to see a fertility doctor, there is a backstory there. So in the first visit with your fertility specialist, you will have already hopefully seen your GP and they will write a referral letter. That's very important because your GP knows you, hopefully, or have a... GP who looks after you, and they present in their referral letter a summary of your journey to date and requesting of your fertility specialist for their help and giving a bit of context to us about your past medical history, any medications you might be taking and a little bit about the reasons for the referral. They'll also usually give us a summary if they have information that's relevant, things like recent investigations they might have done with you, blood tests, ultrasounds, sperm tests, that kind of thing. And also importantly, your GP referral is your way to access Medicare benefits, both towards the cost of your specialist appointment, but also to any subsequent treatments that might be necessary.
JORDI MORRISON: So when the patient comes to you for their first appointment, they're already a little bit prepped, aren't they, by their GP usually?
DR. RAELIA LEW: Sometimes yes and sometimes no. So it's my job in the first appointment to really do two things. One is to form a relationship with the patient and form a bond of therapeutic trust, which is essential moving forward. So I want to, when patients are sitting in front of me, make sure they feel heard, make sure they feel comfortable and make sure that they are allied in whatever we do moving forward so that we can move forward with effective investigations and treatments for them. Also, I need to find out about them. If you're trying to get pregnant in a relationship, it is so important that you both engage and attend this appointment together because it is never something that we can move forward with alone as a single person when you are trying to get pregnant with another person without their presence, engagement and involvement. about discovering what all the elements at play are and that's learning about you and your partner in a lot of depth and detail, making sure we don't miss anything. So I like to appreciate what investigations your GP might have done already and also fill in the gaps of any other investigations that may not have been done already that I think are relevant to understanding the full picture of your delay to pregnancy. And I use all of that information to effectively counsel you about your personal prognosis for success with or without fertility treatment, to try and have a hypothesis of what might be the barriers for you and your partner and then to strategize as to what might be the best way forward, the most effective treatments that you can undertake. And also to gauge where you are at and what treatment pathways might be acceptable to you. And one thing I also ask patients when they come to see me are, what are your goals in planning not just a pregnancy but a family? Because for many couples who start their family at a later point in their reproductive life, sometimes the way to help them achieve the goal of the number of children that they would ultimately like to have is to have that candid discussion. Where are you at right now? Where will you be at when you're planning your next pregnancy? Should we be successful this time? Do we need a strategy to help you have a larger family over time and would we incorporate that into our primary strategy to help you have this baby? So these are conversations that are started at a first consultation with a CREI fertility specialist. Sometimes we don't have the full picture at that consultation and we need to organise investigations in order to personalise advice and have a fuller picture. So sometimes at that consultation, I'll ask you to do certain things and undertake certain tests or imaging investigations. Potentially, sometimes it might also involve things like surgical fixes for certain problems or surgical explorative investigations. An example might be if I'm suspicious on history or on preliminary imaging that someone might have a condition like blocked fallopian tubes or endometriosis, or if there might be a uterine problem like adhesions or polyps or fibroids that need to be treated so you can get pregnant. These conversations start at your first consultation and sometimes a follow-up appointment is required in order to move forward.
JORDI MORRISON: So these, I guess, pathologies that you've described, would you find that most of your patients don't know they have them, the polyps, the endometriosis, before they see you for the first time? Or will some people know?
DR. RAELIA LEW: Quite often. Yeah, well, look, it's a mix. What I like patients to consider is that fertility is often multifactorial. So it's not always one problem that's stopping someone from getting pregnant. Often it is a combination, multiple issues, and those issues can range from minor and modifiable to major and non-modifiable. So an example of major and non-modifiable is advanced age, we can't turn back time, and an example of minor and modifiable might be, say for example, a submucous fibroid in the uterus that we can remove and that might help a patient to then conceive naturally or with assistance. So it's about discovery. Also modifiable can be male factor concerns and they're often unappreciated, so I feel women often consider just subliminally and subconsciously fertility to be a female problem, and both women and men can be shocked when we find male factor problems, so looking into that in great depth is also important. And I think the factors of age — we touched on this on an episode we recently released on perimenopause and fertility — but age is a really big problem for people trying to get pregnant. And we're all trying to get pregnant later in life than is ideal these days when we look at society trends. And it's a factor for both men and women, male fertility doesn't burn out but it does decline with ageing as does female fertility, and recognising that and strategising to try and make the best of the situation is part of what we do.
JORDI MORRISON: And it sounds like your patients can turn up to this appointment with a referral from the GP and you'll start everything from scratch, but is there anything a patient can do to prepare for this first appointment?
DR. RAELIA LEW: Yeah, definitely. So there are some pretty standard tests that we do for almost everybody who's trying to have a baby and doing those tests with your GP before you arrive and bringing those test results with you might reduce the time it takes me to figure out what's going on. So those are tests like a pelvic ultrasound. I might still... patients in certain circumstances to go on and do a more sophisticated pelvic ultrasound potentially with fallopian tubal patency testing if I'm worried that blocked or partially blocked fallopian tubes might be part of their presenting concern. From a female perspective there is a routine panel of blood tests that we do for everyone who's trying to get pregnant and that's recognised and ratified by both RANSCOG, the Royal Australian and New Zealand College of Obstetricians and Gynecologists, as well as RACGP, which is the general practice equivalent college. And so getting those done is important. And that's also to check for pre-pregnancy health promotion, giving us the opportunity to make sure patients have immunity to things like rubella and chickenpox. For fertility, we like to know your karyotype and your partner's karyotype. That is the map of what your chromosomes look like because having an abnormal karyotype is a silent fertility problem that if you don't do the test, you could never be aware of. And it's not that uncommon in an infertility population. So we like to know that your karyotype is normal. We feel a sense of obligation and responsibility to have at least a discussion with you about reproductive genetic screening and carrier screening for recessive conditions. And your GP may have already had that conversation with you and offered you the opportunity to undertake preconception genetic screening. The current status quo is the government in Australia funds through Medicare screening for three common conditions, cystic fibrosis, spinal muscular atrophy and fragile X. Many couples these days choose to undertake further testing because we can screen for literally over a thousand conditions. That while each being relatively uncommon, together represent a lot of the burden of childhood illness that we see in our hospitals and our society. So people can choose to screen for those things at... out-of-pocket costs to the patient, but having the conversation and letting the patient know that these things exist is part of our duty of care as doctors in modern reproduction. And of course from the male side of things we also like to do a semen analysis. One of the ways we can help couples conceive involves assisted reproductive treatment, so when we're doing bloods for a male, we often do screen for some viruses like hepatitis and HIV because we do need to know a person's status when we are using sperm and biological materials in a laboratory context, and we screen females for these factors as well. So there's an STI screen as part of the initial workup. We like to know that your cervical screening test is up to date as a woman and if we find preliminary problems, for a male that the sperm test has been abnormal, we may follow up with other investigations, a physical examination or a ultrasound of the scrotum and testes. And we may also follow up with a hormone profile for the male and we always do a hormone profile for the female. So all of those investigations can be done with your GP. There's also some baseline health investigations that we like to know about. What's your kidney function, liver function, full blood count, blood group, what's going on with your thyroid, what's going on with your iron status and vitamin D, your nutritional status. So all of these things are interesting to us and we check them. There'll also be some other investigations that might come to mind for a fertility doctor based on your background, ethnicity and history. So for example, if you're from a place where thalassemia is endemic, we might check you for that. So that's usually Mediterranean background and particularly if those initial investigations were showing a low hemoglobin on your full blood count. So there are things that we will personalise to you as well and we may screen for things like celiac disease if we find a family or personal history of symptoms. So there are targeted investigations as well as those basic ones that we do for everyone that we might choose to do for you as an individual based on your circumstances. Another investigation that I haven't talked about is the AMH test for a woman. This is something we always do for anyone we're thinking about in terms of assisted reproduction. AMH has a more limited impact on natural conception, for someone who has a regular cycle the AMH test even if it's low doesn't mean that the person is going to be infertile. So the AMH test is a nuanced test, it's looking at your egg reserve and the number of follicles you have in your ovary that make AMH, so it's a indirect reference to how big your ovary is, how many eggs you have. And as a consequence of that, how well you're likely to respond in assisted reproduction. So that's also a test we do. And timing your pelvic ultrasound at the beginning of a menstrual cycle also allows us to do what's called an antral follicle count. So that's another measure of egg reserve. So some patients come and they've done all of these tests and that's really... because you can really at a first consultation get right into it and have a good analysis of where they're at. Other patients have come and they've done none of these tests and that's okay, we can do them and we'll likely follow up results at a second appointment before moving forward with treatment advice.
JORDI MORRISON: Are there any key medical or lifestyle preparations people can undertake before IVF begins? Is this discussed in any of your appointments before starting treatment?
DR. RAELIA LEW: Look, hopefully in an ideal world, hopefully you've seen your GP and they've had a chat to you about planning a pregnancy because all of the things that are a good idea before starting assisted reproduction are a good idea in general for anyone trying to have a baby. So things like taking a folic acid supplement, optimizing your diet and lifestyle, optimizing weight. Some patients who are seriously overweight might actually pause their plan for pregnancy to do things like medical-assisted weight loss to improve their fertility and also health during pregnancy and reduce risk of things like gestational diabetes, optimising any underlying medical conditions that you may have, including optimising the safety of any required medications when it comes to planning a pregnancy. So that might be, for example, changing your blood pressure medication, or if you're diabetic,... making sure that your sugar control is optimised. If you have epilepsy, moving on to a safer medication that is less likely to cause birth defects, those kind of adjustments can be made specifically and individually for patients with their GP. And just looking at general health measures, reducing toxins, reducing things like alcohol to either, well usually when we're trying to conceive, we say complete abstinence. And reducing things like coffee to having one espresso a day, and just things like looking at our diet and making sure we've got all the nutrients that we need to succeed in a healthy pregnancy.
JORDI MORRISON: In Victoria, there's compulsory counselling before you can begin IVF or RT. Where does that fit into the pre-treatment stage?
DR. RAELIA LEW: Tree and Zika counselling is more for a patient who's already on a committed pathway to IVF. So let's pretend that you've had all of your fertility work up, that we've diagnosed the underlying factors and we've decided that IVF is the right way forward for you. From there, what we do is we organise some preliminary pretreatment education. So in that appointment that we've made that decision, I would have taken all of the different factors involved in your presentation, be it male factor infertility, be it endometriosis, be it age-related infertility. We will have come to a working hypothesis as to why you're not getting pregnant. And then what we will do is we will make an IVF treatment plan. So I design a plan that looks at how we're likely to stimulate the ovary, what medications we're going to utilize and in what sequence and in what dose and I'll chart that plan up for you. An IVF cycle where we're trying to get a patient pregnant will start with a menstrual period. So our approach is really to get you ready so that you can start and then you activate the cycle once you've done all of the pre-treatment preparation by calling with the period and you can get started with a period. If the plan is to try to get you pregnant with a fresh embryo transfer that's what we do, and if the plan is to try and get you pregnant with a frozen embryo transfer that's also what we do. So the counselling has to be done and completed before you are able to call with day one in your period to start the cycle of the plan that we make together. So what will be organised for you in our unit is usually attendance at a counselling session and we're able to deliver... the mandatory information usually in a group context in a webinar setting so it's not overly arduous, it can often be done after hours so it's not overly burdensome on work and things like that, but in Victoria we do need to ensure that the legally prescribed matters, as they're called, are covered and this is all outlined in the Assisted Reproductive Treatment Act. And we also have the facility to arrange individualised counseling for patients if they need it, for supportive counselling. That's a little bit different to the prescribed counselling. So the prescribed counselling talks more about, what does it mean to have embryos in the freezer? What does it mean to have a descent between a couple if they split up? What would happen to the embryos? How long can the embryos be stored? What if we want to extend that storage? What do we have to do? What happens if a tragedy occurs? What if one of the partners passes away while treatment's underway? Would the other partner be allowed by that partner to use their eggs, sperm or embryos? So all of these things are covered in this mandatory counselling. So it's not really psychological support counselling per se. It's more about... counselling of some of the complexities and legalities in regards to IVF, and really an educative session, and supportive counselling can also be accommodated and offered through most IVF units just to help couples cope with the complexities and emotional support needs during IVF.
JORDI MORRISON: And then once I go, I guess these hurdles have been overcome, treatment begins and we are... the purpose of this podcast, assuming treatment is IVF. Of course, there are a multitude of possibilities when it comes to ART. But when IVF begins, is there a set day that it starts?
DR. RAELIA LEW: It depends. So if an IVF cycle has the goal of creating a pregnancy in that month, then the cycle has to start with a menstrual period. And usually a patient is given the mantra call on day one, day one being the first day of the menstrual cycle, and we don't actually start medications until at the earliest day two or three, but we ask you to call on day one and that is so... we can get you organized in the next couple of days, knowing your plan, having some nursing support to run through your plan. You will have had a nurse education session before your cycle starts outlining exactly what to do and giving you all the support channels that you can activate should you need. But the call on day one and the chat with the nurse on day one from our team will make sure that you know exactly what to do on what day of your cycle, make sure that your medication is arranged for you to collect. And also make sure you have a written plan so you know exactly what to do on what day. And to schedule the first monitoring appointment where you'll come and see us for an ultrasound assessment and potentially a blood test. So that'll all be organised for you and diarised when you call with day one. In some other cycles, so for example an embryo freezing cycle. And you may be doing an embryo... freezing cycle in IVF for a variety of reasons. You might be doing it because you've got a very high egg count and we're worried about hyperstimulation syndrome, which is a side effect of IVF medications in vulnerable people who have a very high egg count. So if you have a high AMH then usually what we do in IVF to keep you safe is split the cycle into two halves, we do an egg collection and embryo freeze and then we do a transfer in a frozen cycle in a natural cycle, and that reduces your risk to almost zero of having serious hyperstimulation. So that might be one reason to do an embryo freeze. Another reason to do an embryo freeze may be because of uterine receptivity. Some patients, particularly with a higher egg count, also have lower uterine receptivity in a stimulated cycle and a frozen embryo transfer is thought to have superior success rates. So sometimes we do that for those reasons. You might be banking embryos as part of your big picture long-term family. So you might be in your late 30s wanting to have two children and banking embryos while you're young enough to make healthy embryos, knowing that when you return a few years later to IVF, your personal prognosis for making healthy embryos will be seriously lower. And you may be freezing embryos because you're wanting to genetically test your embryos, either for chromosome error in the context of aging, or potentially because there's a genetic condition that you know you or your partner may carry and we wish to screen out so your children are not affected by that condition. So there are many reasons where we might do a freeze-first approach. With a freeze first philosophy, you actually can do a planned IVF start. You don't have to start the cycle with a menstrual period. And the reason for that is we're not doing an embryo transfer. So in summary, when we do an embryo transfer, the uterus and the ovary must be aligned and synced so that they're getting the right hormone signals both to the ovary and the uterus, not just to make eggs grow, but also so that the uterus becomes receptive to an embryo implanting at the appropriate time. However, if we're doing a freeze-first cycle for any reason, we don't really care what's going on in the uterus and we can start that cycle at actually any time point. And that's very powerful for people who have life needs that they can't have an egg collection at a particular time. So someone who might have work commitments or travel commitments or they need to take leave at a certain time because that's when someone can help care for them during their period of time where they might have an egg retrieval. So everybody's got... own needs and schedule and with a freeze first cycle we can tailor our approach to your schedule, whereas with an embryo transfer cycle we need to start with a period because that's when the uterus and the ovary will be aligned by the time we get to a transfer. We can still schedule a cycle for a patient who has issues in their life when they want to do a fresh embryo transfer, but in order to do that, we do it with the oral contraceptive pill. So we kind of move where the day one happens using the pill rather than doing a random or planned start cycle for that patient. So we make things work for us. We have many tricks up our sleeve to make IVF achievable for any patient in any circumstance.
JORDI MORRISON: Everyone's always a bit obsessed about the medications that are used in ART, probably because it's the first time we often are injecting ourselves. The first medications that we might begin, what are these and are injections involved?
DR. RAELIA LEW: One of the ways that we, in modern IVF, injections are almost always involved. There are certain cycle types where we can minimise the number of injections significantly, but there's always at least a couple of injections in IVF. There are lots of different types of IVF... medications and lots of subtypes within each variant. But according to the patient's plan, there'll be in an IVF cycle where we're going to do an embryo transfer, the certain elements that are common. So one will be a medication to stimulate the ovary, some form of follicle stimulating hormone. And we may also have the addition of luteinizing hormone in that phase. There'll also be... kind of medication to stop ovulation happening prematurely and there are different approaches to that depending on whether we're doing a fresh embryo transfer or not, depending on whether there's a risk of hyperstimulating or not. There are different medications that are able to do this, both oral tablets or injectable medications or even sometimes we use a nasal spray medication for this purpose and it will really depend on the cycle strategy. The thematic point is there'll be a medicine to stop you ovulating. There'll be an IVF medication called a trigger, which is a once off medicine that comes later in the cycle. We can come back to talking about the trigger in a little bit of time. And then after the trigger, there's the luteal phase. And if we are doing an embryo transfer in a stimulated cycle context, we... that there are always problems with progesterone production in an IVF cycle where we're doing a fresh transfer and we need to give extra progesterone in the luteal phase. So in summary, those are the types of medicine that we would use in IVF.
JORDI MORRISON: And what should patients expect in terms of side effects at the very beginning of their treatment?
DR. RAELIA LEW: Every IVF patient will have some side effects of medication. How those side effects affect patients will be to some degree subjective. So some people are more sensitive to side effects than others. And also it may be in relation to the dose of medication that's used for that patient, the type of medication that's used for that patient, and also their ovarian response actually, because a lot of the side effects that patients feel from IVF treatment are actually not directly related to the medicines per se. They're more related to the way the ovary responds to those medicines. In other words, the hormones that you make are some of the things that cause the side effects rather than the hormones that you take. So the main side effects that people experience in IVF in the first instance may be related to mood, because hormones can affect the way we feel. That can make you feel a little agitated and anxious and emotionally vulnerable. At the end of a cycle, you can feel sad. What were we up to?
JORDI MORRISON: Side effects, but I'm not sure exactly where you were up to.
DR. RAELIA LEW: Okay, I'm just, I've lost the script.
JORDI MORRISON: Oh, it doesn't matter. So side effects, I talked about bloating. Did I talk about bloating?
DR. RAELIA LEW: No, I think I talked about emotions.
JORDI MORRISON: Yes, you talked about emotions, not bloating.
DR. RAELIA LEW: Okay, another side effect that is always felt is a bit of abdominal bloating and that is because the ovaries are getting larger and the hormones that we make in a cycle, and also at the end of the cycle the hormones that we take like progesterone, can make us bloated. And they can make us feel a bit sluggish in the bowel. They can cause constipation. And sometimes I ask my patients if they're showing signs on ultrasound of the bowel getting a little bit full, to make sure that they're drinking a lot of water during a cycle to help them avoid constipation. And also occasionally... ask patients to take something like a little laxative to help things along at that stage of the cycle. So those are the main side effects. Mood side effects are profound in IVF and I reflect that in a natural menstrual cycle, when we release one egg and we have the hormone fluctuations resultant of that, we can feel moody around the time of our period or just before, we can feel heightened emotion. If you get a period at the end of an IVF cycle and it means you're not pregnant after everything you've just been through, that happens in the context of the hormones having been radically elevated and taken a big dive. So IVF, it's often called an emotional rollercoaster. And that's how it feels for patients when an embryo transfer doesn't work. It feels devastating because they were very hopeful that they were going to become pregnant in that cycle. That is also in the context of significant hormonal side effects. So it can be very difficult. I often find, interestingly, as an aside, that when I treat patients with very similar medications,... as I do in IVF, but their goal is egg freezing, they don't have as profound an emotional reaction to the same hormones. So I think that illustrates that the hormones make you vulnerable, but other things also make you vulnerable. Like, for example, an expectation of pregnancy that doesn't happen. I would also say at this point to patients that just because someone doesn't get pregnant with their first embryo transfer doesn't mean game over. And most patients who have a baby have had a few embryo transfers before they succeed. So sometimes it's about a different embryo that does the right thing rather than a different situation. And quite often in IVF we have... a cumulative pregnancy rate when we make more than one embryo from the same IVF cycle, and at least half of the patients that we treat in our unit we see getting pregnant with one of the embryos they make in an IVF cycle. So they might not get pregnant with their first embryo but many will ultimately succeed, and of those who don't succeed in the first cycle, many who require more than one stimulation will ultimately succeed as well. IVF success is not really realistically thought of as the success of one embryo transfer. While every baby does come from one embryo, not every embryo makes a baby, but patients who are ultimately successful, many do experience that that does take more than one treatment.
JORDI MORRISON: You mentioned ovarian stimulation, which is, I suppose, the phase we're in right now when we're talking through the treatment. Why is this needed?
DR. RAELIA LEW: Overcome infertility is to allow multiple eggs to be achieved, matured and collected in a cycle where naturally without medications only one egg would ripen. So the medication is to allow you to up the chance of you getting pregnant, remembering that when patients need IVF we're not treating healthy fertile people, we're treating patients who may otherwise be quite healthy but we're treating patients who have profound infertility for one reason or another. That may be primary infertility where they've never had a baby, or it may be secondary infertility where they've had a baby before, but since they had that baby, their fertility has significantly changed. And that may be that they're much older and their egg quality is poorer. Or it may be that they have other things going on as well that weren't there before. Male factors can happen where they weren't there before as well. And combinations of factors can get worse with confounding factors like age. So it's a group of patients who are not getting pregnant by themselves month after month of trying. And so the chance per egg is not that high. So what can we do? Well, we can try and fix the things we can fix. And where there are things that we can't fix, we can stack the odds of success in the favor of the patient by having more eggs in play. So really the point of the medications is to get eggs to the laboratory that are mature so that they can meet with sperm and have a chance. And more eggs equals more chance.
JORDI MORRISON: And in the phase where our eggs are maturing, there are often daily injections. How do these work to recruit as many eggs as possible?
DR. RAELIA LEW: It's more about the fact that the drugs we give... have a half-life or amount of time in your system of a certain amount of time and a lot of the drugs in IVF have a daily half-life. So what that means is that's right, they wear off, so it's not so much that you have to give them every day for any other reason. And in fact there are some drugs that have a longer half-life that we sometimes use that can last up to a week. So the dosing of the medication is about how long the drug's active in your system. And the medication we give is called follicle stimulating hormone. So it needs to activate that receptor and that's what causes follicles to stimulate and mature.
JORDI MORRISON: And what factors would affect how someone responds to the drugs?
DR. RAELIA LEW: Factors can be how many follicles they have. So I always say to patients, you can't stimulate a follicle that isn't there. You have to work with what you've got. So if you've got a low egg count, no drug regimen is going to give you a high egg count. So there are some patients who have to get there eventually over multiple cycles to get the same number of eggs that someone else might get in one cycle. It's not fair, but it's their body and that's what we have to work with. And they want to have their own baby with their own egg, not someone else's egg potentially. So we have to work with their ovary and we have to get the best result that they can, a personal best. And sometimes patients say to me, what can you do to get me more eggs? And sometimes I have to say, you're doing the best that... you can and nothing's going to make you do better because that's what you can do. There are other patients who might have a complex concern where we think based on their pre-treatment investigations that they should be able to make more eggs and they're just not. And that's called a poor responder in IVF, and it's not because of an obvious diminished ovarian reserve, it might be due to something like a receptor mutation so that the medication and the hormone in the body doesn't necessarily stimulate their receptors effectively because of the shape of their receptor being different. So there are other reasons that someone can be a poor responder and that's unpredictable, and again sometimes in those circumstances it can be very frustrating, but we need to then, in that type of patient, we need to make sure that we have tried all the different medicines that we can to see which one's going to fit their receptor best and get the best post receptor response.
JORDI MORRISON: Okay. Okay. So this phase where we are administering this medication and our follicles are being stimulated and they're growing, how long does this phase usually last?
DR. RAELIA LEW: Usually for most people, it will last between 10 and 16 days, usually somewhere in the middle.
JORDI MORRISON: And during this phase, are there blood tests and ultrasounds performed to check in on how you're reacting?
DR. RAELIA LEW: Blood tests are done at some units and ultrasounds are used more commonly at other units. So there's different ways to check how you're going. And there are places for both. Your doctor will design your model protocol. In my practice, I try and minimize blood tests only because they're unpleasant for patients and painful to undertake. There will be times where I ask my patient to have a blood test, but I try and keep it to a minimal. So what I like to do is bring patients in for an ultrasound scan. What I'm interested to see is how their lining of their womb is progressing and how the ovarian follicles are looking physically. And I can tell a lot about the hormones by those two observations. And that helps me decide what to do next.
JORDI MORRISON: And then how do you decide when to trigger the ovulation and schedule the egg collection?
DR. RAELIA LEW: This will depend on how the follicles are looking physically. I want to know that the patient is getting... a good response that's going to give them the best result that they can from their egg collection. So I look at the cohort of follicles on both ovaries holistically. Some will be larger, some will be smaller, some will be somewhere in between. And I'll make a decision on the day for the egg retrieval that's a best fit for most follicles to get them their best outcome. And that may be a different day in different cycles in the same patient, even if they're using a repeat regimen with the exact same medication. I always say we're mammals, not machines. And there's cycle to cycle variation in every cycle in every person. So it's really important to individualize the timing of egg retrieval. And for that reason, I often in my practice work with trusted colleagues so that I can choose the day of an egg retrieval that will best fit the patient's biology. So that if I can't be there on that particular day, that the egg collection will still happen on the day that's most likely to get that patient pregnant, either in the current cycle or by making the most embryos possible for the future. So we individualize care and it's very important to do the egg retrieval at the ideal time.
JORDI MORRISON: And what does the egg collection procedure involve?
DR. RAELIA LEW: This is actually an interesting time to talk about it because I was having a chat just a few days back with some of my nursing colleagues about this. I think the egg retrieval procedure can be very scary for patients, sometimes because they don't really understand what is involved. But actually, it's very safe. It's very simple. It's an ultrasound procedure. I think the fear comes from, this is often the first time a patient of this age would have had a procedure. Yeah, potentially, and also maybe the first time that they have an anesthetic. But the anesthetic that we give for egg collection is very simple and short. It is not a general anesthetic. So people sometimes don't understand the difference between what is a general anesthetic and what is a twilight or anesthetic or a conscious sedation. And a general anesthetic is what you have for a major operation and when you have a general anesthetic the anaesthetist paralyzes your muscles and takes over your breathing and really controls every system of the body while you're completely unconscious. That's not what we do for... egg retrieval. Retrievals can be done under local anaesthetic if the patient wants. In our practice, we tend to use something called twilight anaesthesia or conscious sedation, and that's basically giving the patient something to make them sleepy and drowsy. They're breathing for themselves the whole time. It's generally less than 20 minutes. What it does is it makes them feel like they don't know what's going on, they don't have any pain and they don't have any memory of the procedure, but actually they are breathing for themselves the whole time and not actually under general anaesthetic. And we do this for patient comfort because the egg collection procedure, while relatively minor, can be quite confronting a weight because it's transvaginal. So we use the ultrasound probe, much like when you have... pelvic scan pre-treatment to have a check out of your anatomy, but we put pressure and so it's really pushing firmly with that probe, and we minimize the amount of effectively your tissue between the probe and the ovary, and we put a really fine needle which is the same gauge needle that you might have for a blood test, and we use that needle to gently probe the ovary and aspirate, so under suction it's under a suction tube system, the fluid in the follicles that you see on scan. And we drain the follicles off one ovary and then we drain the other. So if your anatomy is normal, if your follicle count is normal, the procedure should take less than 20 minutes. You wake up in recovery, it feels like nothing's happened. And you might be a bit sore. The ovaries can be a bit tender. Generally, the anaesthetist has given you pain relief while you were sleeping. So you're not too sore, hopefully, when you wake up. Just a little achy and you can feel a little spacey. But generally, you go home that day and most patients are fine. Some patients feel more uncomfortable than others. I always say the bigger the ovary, the more uncomfortable you might feel. So if you've had a really big response to IVF, you might feel more uncomfortable. And patients who have endometriosis can sometimes feel more uncomfortable as well. So that's the egg collection in a nutshell.
JORDI MORRISON: So what happens to the eggs after collection?
DR. RAELIA LEW: So the eggs are collected on the day of the egg collection. And so what happens is as the follicular fluid is aspirated out of each follicle, it's passed down a line into a tube. And the embryologist is sitting right there at the other end of a window in the operating theatre, looking under the microscope at each one of those tubes as they come through to find and identify the eggs. So it's a team effort. So the doctor and the nurse are in the operating theatre. The embryologist is sitting in the laboratory. And as each follicle is drained, that sample is passed straight to the embryologist and they look for the egg in that sample. And then they collect up all the eggs that are retrieved and they're placed into culture media and into an incubator. And they're kept there until the following morning when they will be inseminated with sperm. So there are two ways to inseminate eggs. One is conventional IVF which is where you put the sperm and the eggs in a dish and you let them find each other, which is a little bit like natural conception. And the other is ICSI or intracytoplasmic sperm injection, which is where a single sperm is selected and it's injected directly into an egg. So there are different reasons why we would choose one or the other and that would be a discussion that you would have with your IVF doctor and your laboratory team.
JORDI MORRISON: And the sperm collection, when does that happen in this whole process?
DR. RAELIA LEW: Usually the sperm is collected on the day of the egg collection. So the partner will come in on the day and produce a sperm sample. That sperm sample is then processed in the laboratory and prepared for fertilisation. Sometimes the sperm is previously frozen. So that might be the case where the male partner can't be there on the day or there might have been a reason to freeze the sperm ahead of time. There are also situations where sperm can't be produced by the partner. And in those cases, there might be surgical options for sperm retrieval where we go directly into the epididymis or the testicle to obtain sperm. And that would happen usually as a planned procedure before the egg collection.
JORDI MORRISON: And then when do you find out how many eggs have fertilised?
DR. RAELIA LEW: You find out the next day. So on day one of the IVF process, the egg collection happens. On day two, you get a fertilisation report. And you find out how many of your mature eggs, eggs that were mature enough to fertilise, have fertilised normally. So normal fertilisation is when you see two pronuclei, which is one from the egg and one from the sperm, and that indicates that normal fertilisation has happened. Some eggs will fertilise abnormally and those won't be suitable to use. Some eggs won't fertilise at all, and that's usually because the egg wasn't mature enough. So you go from the total number of eggs collected to a smaller number of mature eggs, to a smaller number of normally fertilised eggs, and those normally fertilised eggs are now called zygotes and they're placed back in the incubator.
JORDI MORRISON: And then what happens from there?
DR. RAELIA LEW: So from there they keep developing. So we observe them over the next few days as they develop from what we call a day two or day three embryo, which is a cleaving embryo — so it's just cells dividing — through to a blastocyst, which is what happens on day five or day six. And a blastocyst is a more developed embryo. It's got two cell types. It's got cells that are destined to become the placenta and cells that are destined to become the baby. And a blastocyst has the highest chance of making a pregnancy. So our goal is to get embryos to blastocyst stage. Not all will make it. Some embryos will stop developing early, and that's just natural attrition and it reflects the fact that not all embryos have the potential to become a baby. So by selecting at blastocyst, we're selecting the embryos that had the most developmental competence of the group.
JORDI MORRISON: And that's also when genetic testing of the embryos can happen, isn't it?
DR. RAELIA LEW: Exactly right. So on day five or day six, if we are going to do PGT, we take a small biopsy, a few cells, from the trophectoderm, which is the outer layer of the blastocyst that's destined to become the placenta. And we send those cells off to a genetic laboratory for analysis. And the results come back within a week or two, and we then know which embryos are chromosomally normal and which are not. And those that are normal are the ones that we would prioritise for transfer.
JORDI MORRISON: And at what point would you freeze the embryos?
DR. RAELIA LEW: So embryos are frozen at blastocyst stage. So once they reach blastocyst on day five or day six, if we are not doing a fresh transfer that day, we will freeze them. And we use a process called vitrification which is a rapid freeze process and it's very effective at preserving the embryo. The survival rate of embryos through vitrification is very high, over 95% of embryos will survive the freeze and thaw process. So it's a very reliable method of preservation.
JORDI MORRISON: So at this stage we have embryos, possibly frozen, possibly fresh. What happens with regard to the transfer?
DR. RAELIA LEW: So the embryo transfer is, I think, the part of IVF that probably patients are most excited about because it feels like the closest they are to being pregnant. And it is a very simple procedure. It doesn't require any anaesthetic. In our practice, we ask patients to have a full bladder, and the reason for that is that a full bladder pushes the uterus into a better angle for the catheter that we use to transfer the embryo to navigate the cervix easily. And it also acts as an acoustic window on the ultrasound. So we do the transfer under ultrasound guidance. The embryologist loads the embryo into a very fine catheter, a transfer catheter. The doctor then passes that catheter through the cervix and into the uterus under ultrasound guidance and deposits the embryo at the optimal position in the uterine cavity. And the whole procedure is usually over in a few minutes. Some transfers are more straightforward than others. And that's really about the anatomy of the cervix. The cervix can sometimes have a curve or a bend that makes it a little bit more technically challenging to navigate. And that's one of the reasons why sometimes we do a dummy run called a mock transfer or a trial transfer to check the anatomy of the cervix ahead of time.
JORDI MORRISON: And then after the transfer, what do we do? What happens?
DR. RAELIA LEW: So after the transfer, you go home and you rest. And the next couple of weeks are what patients refer to as the two-week wait. And it is one of the most difficult periods in IVF. I've had patients tell me it's actually more stressful than the stimulation and the egg collection. And I completely understand that. Because you're sitting at home waiting and hoping and wondering. And every twinge and every sensation, you're wondering, is this implantation? Is this something happening? Or is this nothing? And it can be very difficult. And I always say to patients during the two-week wait, try to live your life as normally as possible. You don't need to be on bed rest. Bed rest doesn't improve IVF success rates. In fact, some studies suggest it might be worse. So live your life normally. Keep doing gentle exercise. Look after yourself. Eat well. Try to manage your stress. And we will let you know what to do at the end of the two-week wait.
JORDI MORRISON: And at the end of the two-week wait, what happens?
DR. RAELIA LEW: So at the end of the two-week wait, you do a pregnancy test. And we ask our patients to do a blood pregnancy test rather than a urine pregnancy test, because the blood test gives us a quantitative result. So it gives us a number, the beta HCG level, and that tells us not just whether you're pregnant but how pregnant you are. And a level that is appropriately high for the day past transfer gives us more confidence that it's a good pregnancy than a level that is a little bit low. And of course it can also come back negative. And that is, as I said, one of the most devastating moments in IVF.
JORDI MORRISON: And if it comes back positive, what then?
DR. RAELIA LEW: If it comes back positive, we usually ask patients to repeat the blood test in two days to make sure the level is doubling appropriately. Because in a healthy ongoing pregnancy, the beta HCG level should roughly double every 48 hours in the early stages. And then once we have two positive rising blood tests, we organise an ultrasound scan, usually at around six to seven weeks gestation, which is about three to four weeks after the transfer. And that scan is to confirm that there is a pregnancy sac in the uterus, that it's in the right place, that we can see a heartbeat. And that scan, when it goes well, is one of the most joyous moments in fertility treatment. And that's when we can really celebrate with our patients and then refer them on to their obstetrician for ongoing pregnancy care.
JORDI MORRISON: And what if the pregnancy test comes back negative?
DR. RAELIA LEW: If it comes back negative, then we debrief with the patient. We talk about what happened in that cycle, what we know, what we don't know. We talk about what we might do differently next time. We talk about what embryos remain if there are any frozen embryos left. And we make a plan. And really the message is, this is not the end of the road. This is one step in the journey. And we keep going. And I think one of the most important things I can do as a fertility specialist at that point is to help my patient find a way to keep going, because IVF is hard, it's expensive, it's emotionally draining. And sometimes patients need to take a break and that's okay. And sometimes they're ready to go straight back into it. And we just meet people where they are.
JORDI MORRISON: Raelia, this has been such an incredible and comprehensive overview of the IVF process. I feel like I've learned so much and I've been alongside many patients through this process. Thank you for going through it so thoroughly.
DR. RAELIA LEW: Look, it's my pleasure. I love talking about this. And I think it's so important that people understand what they're in for so that they can prepare themselves emotionally and logistically and physically. And the more informed our patients are, the better they cope and the better they do. So thank you for the opportunity.
JORDI MORRISON: Thank you, Raelia. To support Knocked Up, leave us a review or recommend to a friend. Join us on Instagram @knockeduppodcast and join Raelia at @drraelialew. And email us your questions to podcast at womenshealthmelbourne.com.au.
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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