SART Fertility Experts - What is IVF?

In this episode, we discuss the ins-and-outs of in vitro fertilization (IVF). Dr. Elizabeth Ginsburg, Professor of Obstetrics and Gynecology at Harvard Medical School, discusses why patients may need IVF and the IVF process. She also mentions lifestyle intervention and issues regarding cost. For those considering IVF, or just want to have a better understanding of the process, this is a great place to start.

The information and opinions expressed in this podcast do not necessarily reflect those of ASRM and SART. These podcasts are provided as a source of general information and are not a substitute for consultation with a physician. Welcome to SART Fertility Experts, a podcast that brings you discussions on important topics for people trying to build a family.

Our experts are members of SART, the Society for Assisted Reproductive Technology, an organization dedicated to ensuring you receive quality fertility care. Hello, my name is Brooke Rossi and I'm a practicing reproductive endocrinologist and infertility specialist in Columbus, Ohio. We will be doing the SART podcast today on in vitro fertilization.

We have Dr. Elizabeth Ginsburg, who is a practicing reproductive endocrinologist and infertility specialist, as well as the Medical Director of Assisted Reproductive Technologies at Brigham and Women's Hospital in Boston, Massachusetts. She is a professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School. She is an expert in infertility and in vitro fertilization with almost 30 years of experience in this field.

She is a very busy clinician and a great contributor to research in IVF. The SART podcast series is grateful to have Dr. Ginsburg joining us today to discuss in vitro fertilization. So maybe we could just start by talking about what IVF is.

Can you explain that to our listeners? Of course. So in vitro fertilization, we are actually fertilizing eggs outside a woman's body. In order to do this, an egg has to be taken out of the ovaries, and this is done with a transvaginal ultrasound, generally with some intravenous anesthesia.

Meanwhile, sperm are obtained and processed so that the non-moving sperm are taken out of the sample, and then sperm are either incubated with the eggs that we obtain, or in cases of poor sperm counts or poor sperm parameters, a single sperm can be injected into each of the eggs that has fully matured. Okay. So sometimes patients get a little bit confused about the difference between IUI or insemination, intrauterine insemination, and IVF.

Can you just remind our listeners the difference between the two of those? Sure. And intrauterine inseminations, or IUI, sperm are processed. Again, the non-moving sperm are taken out of the sperm sample, and the resulting moving sperm are placed in a very thin catheter, and this is passed through a woman's cervix, and the sperm deposited up into the top of the uterus.

So this bypasses any obstruction to sperm, such as hostile cervical mucus, women who have had a history of surgery on the cervix that may impair sperm transport. This is also used in couples where there is unexplained infertility to just improve sperm delivery so that sperm are closer to where the eggs end up in the fallopian tubes. But in IUI treatment, the eggs and sperm are fertilizing inside a woman's body.

Great. One of the things I think that patients are concerned about through the IVF process is the work they have to do in terms of taking shots. The reason why IVF increases pregnancy rates is partly because we have more than one egg to work with.

So one of the major advances in in vitro fertilization was the ability to get a woman's ovaries to produce multiple eggs at a time, and this does take about two weeks of injected medication treatment. The medications that we use contain FSH hormone, and this is the hormone that stimulates eggs to mature in the ovaries. And women take injections typically one to even up to four times a day for about a week and a half, sometimes two weeks.

These injections are given at home under the skin, so it doesn't require finding a vein, doesn't require an intramuscular shot. This is medication that's easy to self-administer or to have a partner administer. But it also does require monitoring.

So most women are in for four to five days of testing because it's important to know how many eggs are developing. Because an egg is a single microscopic cell, the monitoring involves transvaginal ultrasounds so that we can visualize the small fluid collections or follicles that grow around the maturing eggs. We're also measuring blood estrogen levels and progesterone levels, so we get a sense for the hormonal function of the follicles because that also reflects how the eggs are maturing.

Great. So the whole process takes probably several weeks to grow the eggs, and then they have the egg retrieval, and then after the transfer of the embryos it takes about, you know, one to two weeks to find out if it was successful. Correct.

So it's about a month between when a woman starts taking her injections and when she ultimately comes in for a pregnancy test. It's about a month. Great.

And what are some of the main medical indications or reasons why a couple may be considering IVF or may have their doctor tell them that IVF may be the right treatment for them? So from a standpoint of fertility treatments, I would say the absolute contraindications to try other treatments would be extremely poor sperm function, meaning sperm that move very poorly or very low sperm counts, women with occluded fallopian tubes, and I think you could also argue that women in their very advanced reproductive years who may not have much time to undergo fertility treatments just because of the aging of their eggs, those women may be best served also by what we call fast tracking to IVF. And then do you want to just mention a little bit about other groups of patients because there are a lot of other groups of patients that do IVF also. Sure.

For example, male couples who want to have children will often use an egg donor, so hire a woman to or ask a friend or relative to be an egg donor. That woman's eggs are extracted from her ovaries, fertilized with one of the male partner's sperm, and then the pregnancy can be occasional surrogate. So that's not uncommon in our country and many other countries around the world.

Also, single-sex female couples may opt to share the experience of pregnancy by one undergoing IVF, so having her eggs extracted and having the partner or wife be the one to carry the pregnancy and deliver the baby. And then there's also, you know, other general groups of patients like patients with endometriosis, polycystic ovary syndrome, and what do you, what percentage do you think of patients with unexplained infertility end up doing in vitro fertilization? Is that a big part of patients who do IVF, maybe 25% of the general IVF group or? So, so patients also, so, so other, other, other indications may be endometriosis, unexplained, same-sex women, couples, or with men. But a lot of patients, you know, will be doing IVF for many different reasons.

Correct. And, and really regardless of what the underlying fertility factor is, IVF does have the highest pregnancy rate and live birth rate per treatment month. And that's great.

That's what, that was what I was going to ask you about next. How well does it work? IVF works extremely well. Data in terms of live birth rate per stimulation start are available on the SART website, also the CDC website.

And I think it's very important for patients to understand what's involved when you look at outcome data. When a couple or a single person is deciding to do in vitro fertilization, you're deciding how much time, effort, and potentially financial resources to put into it. So it's very important to look at your age, your fertility factor, and get a sense from your physician and also online published data about what the likelihood is that you'll take home a baby after one cycle of stimulated treatment.

And this live birth rate per cycle will report primarily based on a woman's age and also based on her ovarian reserve. Ovarian reserve mean are markers that predict how a woman will respond to fertility medications. So when women have low ovarian reserve, this predicts to us that we will not get that many eggs from a stimulated IVF cycle.

And if we don't have very many eggs, this will result in a lower number of embryos and so fewer chances of pregnancy for one stimulated cycle. And how would a patient know their ovarian reserve? Would that have been something that would be checked by their doctor at some point? Yes, certainly reproductive endocrinologists will all check it. Also as general OBGYN physicians become more experienced with fertility evaluation, this can also be checked in a generalist office.

But blood markers such as antimullarian hormone or AMH are important markers to check. This hormone is made by the cells around the eggs in the ovaries. So predict very well how many eggs are a woman is likely to be able to produce during an IVF treatment.

Another test that can be done is an ultrasound called an antral follicle count. And this is a transvaginal ultrasound where we count the number of follicles in the unstimulated ovaries that are between 2 and 10 millimeters wide. And we do a count that counts up the number of follicles in both ovaries combined.

And that again gives us a sense for how a woman is likely to respond to fertility medications. So great. So we talked a little bit about how age is a major factor in determining success, somebody's ovarian reserve.

Are there any other factors that influence how well a patient may do with IVF for her chance of having a baby? Well, there are other factors that we don't know of yet. Unfortunately, unexplained infertility diagnosis for many couples because there isn't a test for it. It basically means all the tests we have came back negative.

And there are occasional couples where we find some severe problem when they undergo IVF such as eggs that don't fertilize or eggs that fertilize but don't divide well. And so there are certain things that we still can't bypass with standard IVF treatment. However, when we find out at times that the problem is egg quality, which can result in poor embryo quality, this can be bypassed by the use of donor eggs, for example.

Is there any other, like does their diagnosis of infertility impact their chance of getting pregnant with IVF? Or are there any other what we call kind of modifiable factors such as obesity, smoking, what they're eating? People always want to know what they can do to help increase their chances with IVF. Those are very important points. Yes, there are modifiable factors.

We know that women who smoke cigarettes have substantially lower likelihoods of live birth with IVF. The same thing with obesity. For example, women who are obese, this means that their body mass index, their height weight ratio is greater than 30.

These women have a 30% lower chance of pregnancy than someone with their exact same diagnosis and age, but who is of a normal weight. So weight loss, if possible, is a very important factor. Smoking cessation, also very important.

We do not have a lot of data on diet, quite frankly. This is a common thing patients ask us. But there have not been identified any particular diets that can help someone's fertility specifically.

The other factor I just would like to say is that it's always tricky to juggle the impact of age against factors such as weight loss. This is something we also struggle with when we're counseling our patients in that, is it better to be younger with a higher body mass or a normal body mass but at an older age where we would expect the egg number and quality to be lower? These are not easy questions for couples and individuals to decide on. Right.

So I think because this is sometimes a balancing act, it's always good for patients to meet with someone and help that provider help talk with the patient about what is the right treatment plan for them and to not be nervous or scared away by the thought of doing IVF or thinking they can't do it or they're not a candidate because they very well may be if they can sit down with a provider and talk about their options. Exactly. And I think for some women, depending on what the clinical situation is, taking a year or a year and a half off to lose weight or to modify other health factors may be really beneficial to their fertility.

And for example, who may have very low ovarian reserve may not be able to afford to take that much time off before starting with IVF. Great. We hope you're finding this episode of SART Fertility Experts helpful.

Remember, for more information on this and related topics, visit www.sart.org and click on the tab labeled Patients. And now back to SART Fertility Experts. Some of our listeners may have questions about the safety of IVF.

They may want to know what could be the safety issues for them or any potential safety issues for their children that may be born from IVF. Can you talk a little bit about that? We know that women with infertility are at higher risk of certain cancers, but the studies have shown that undergoing IVF doesn't change these risks. So for example, women who have their first baby when they're over 30 years old are at higher risk of breast cancer.

And this is true whether women have infertility or don't. But we do know that the fact of having infertility does increase the risk of certain ovarian cancers and breast cancer, but that IVF treatment doesn't change that risk. What about the children born from IVF? Are there any problems that they may have down the road or any birth defects, learning issues, anything? So if you look at babies born to couples with infertility, whether they get pregnant through IVF or whether they get pregnant on their own or through other fertility therapies, they do have slightly lower birth weights, and they are born at a slightly lower gestational age.

However, it doesn't appear that IVF is the main factor here, but rather the underlying infertility itself. There is some data, however, suggesting that when cytoplasmic sperm injection is done, that this may actually increase the risk of chromosomal and birth defects. It has not been shown to increase a specific abnormality, but it does appear that from a population standpoint, the incidence of certain abnormalities may be higher than when IVF is performed without ICSI.

And so ICSI is that procedure that some of our patients may have heard about, which is a procedure where they put the sperm into the egg, which is used for patients with severe male factor infertility. So that may have an association with other birth defects beyond the regular IVF population. Correct.

Okay, great. You know, our patients often come to us and have done a little bit of Internet research before coming to the office, and they often have questions about frozen embryos. Some of them will ask us, you know, is it better to have a frozen embryo transfer or a fresh? Can you just discuss that briefly? This is a controversial topic right now, actually.

There were a couple of studies recently done that did not support the contention that frozen embryos have higher pregnancy rates than fresh embryos. We had thought that because in a stimulated IVF cycle, estrogen levels are very high, much higher than in a cycle where a woman's conceiving naturally, that the pregnancy rates might be better if the estrogen levels were in a more physiologic range. But in fact, the randomized trial showed equivalent pregnancy rates whether fresh or frozen embryos are used.

There is some evidence that when babies are born from frozen embryos, they actually have higher birth weights. And this may be a result of placentas that grow more exuberantly. The reason for this so far is unknown.

Great. Okay. One of the questions that some of our listeners may be considering or thinking about would be egg freezing.

So we hear a lot in the news right now about women freezing eggs as they're getting older or maybe even for cancer patients. But can you just discuss briefly women who may be considering egg freezing because of their age and maybe they don't have a partner and are thinking about having kids in the future? I think it's a reasonable thing to consider because egg freezing for this reason has not been going on for very long. We do not have a lot of data about what percentage of women will actually use those eggs and really a large amount of data about what percentage of women who freeze their own eggs for future use are going to have babies.

So a lot of the data we have is extrapolated from egg banks. Egg banks are places where women may donate eggs to another couple and a couple may go there and choose to use specific eggs. So there are two different ways of obtaining donor eggs.

One is by hiring, essentially hiring a woman to go through the IVF process for you, obtaining her eggs and then having them fertilized and then you would be using the embryos for yourself or for your partner. The other way to obtain donor eggs is purchasing them from an egg bank. Kind of like a sperm bank.

It's like a sperm bank but women have previously been hired to go through the IVF, the ovarian stimulation process, have eggs extracted, have the fully mature eggs frozen and then ship to an egg bank. So women or couples can look online and purchase eggs directly from an egg bank. There are now data coming out from SART showing that the likelihood of live birth from an embryo from a donated egg that has previously been frozen is in fact somewhat lower than if that egg were fertilized in a fresh state and subsequently resulted in a frozen embryo.

So at this point it does look as though the likelihood of having a baby with a frozen egg is probably lower than if that egg were fertilized in a fresh state. With that said, if you're not in a position to have a child now and you are concerned about ovarian aging and reduction in your ovarian reserve, it's perfectly reasonable to consider going through a cycle of ovarian stimulation to have your eggs frozen for future use. Right, because as we've discussed, one of the major factors with success with IVF is the age of the woman who at the time she creates the egg or donates the egg, so it'd be very important to people to consider that now if they were going to use them in the future.

Yes, and I think in the same line, when an egg is frozen it has the chromosomal complement of an egg of any woman at that age. So for example, if a woman freezes eggs when she's 36 and is not ready to have those eggs fertilized until she's 42, the likelihood of having a baby with a chromosome abnormality is the same as a woman who is 36, not a woman who is 42. So the eggs really are truly frozen in time from the standpoint of their ability to generate a healthy pregnancy.

So I often tell patients that they have the chance of having a baby that they would when they were younger and also the risk of miscarriage that they would when they were younger as well. Correct, because miscarriage rates increase as women age along with the reduction in the egg quality. Dr. Ginsburg, you're in Massachusetts where a lot of your patients do have coverage for IVF, but most patients around the country do not.

Can you discuss a little bit about the cost of IVF and why it ends up being so costly for patients? It is very frustrating, and even in Massachusetts only about 36 percent of our patients actually do have coverage because of employment and the way the laws are written. With that said, IVF is an incredibly labor-intensive, time-consuming process not only for the patient or the couple but also for the center. So the many ultrasounds that are done, the blood drawing, processing of blood, reporting of results, the operating room time to extract the eggs, anesthesia time to make sure a woman is comfortable during her egg retrieval, and then the very large and experienced embryology staff that's working with those eggs, sperm, and embryos, as well as just the infrastructure to keep 24 hours a day, 365 days a year makes the costs extremely high.

The price of IVF, though, does vary around the country really based on the cost of the infrastructure and how much it costs to run a lab and pay the staff. The other major costs are the medications as well. They can be very costly, upwards of maybe even $5,000 or so for the medications, and that's dependent on, you know, how much each patient needs, but it is a barrier.

And patients should know, though, that because, as Dr. Ginsburg is saying, some patients do have insurance coverage, it's definitely useful to check with their insurance company to see if they have any coverage for IVF, the medications, the ultrasounds. Some patients will also have infertility testing coverage, which may help with some of the overall costs also. And have you had any patients do any other things to help, you know, I heard there are grants out there sometimes, sometimes family members will help.

Are there any other things? Yes, absolutely. And I think the other resource for patients is Resolve. So Resolve is a national infertility support network, and they are very good at helping patients and giving patients resources that they can bring to their own HR departments to see if there can be expanded coverage for fertility treatment.

There are also companies developing that are specifically geared towards loans to pay for IVF treatment at a reasonable rate. But unfortunately, the costs for some couples really preclude them proceeding with IVF, which is heartbreaking, and the reason why we are so actively working to advocate for our patients to get it covered across the country. I agree with you.

And I do find, though, that sometimes patients are very scared of the cost of IVF and actually think it's more expensive than it is. And so, again, I would never want a patient to be out there thinking, oh, we need to do IVF, but we just can't, so we don't even want to go in and talk with that doctor about it. Because a lot of times if they can just come in and meet with you, first of all, maybe they do have any other options besides IVF.

And, you know, maybe you could talk with them or the provider could talk with them about exactly how much it costs and sort of, you know, different ideas for how to make it something that they could consider. So I definitely think it's important for patients to go in and try to seek a provider to talk with them about that. I think that's a really critical point.

And the other thing is sometimes couples think they need IVF and they actually don't. So I think having a consult is really important and virtually all health care insurances will cover a consultation with a reproductive endocrinologist as well as the most of the testing. And the final thing I just wanted to discuss, which, again, a lot of patients may have heard about either from their friends or family members doing IVF, is a lot of patients will come in and ask about testing embryos.

They'll say, oh, my friend did IVF and she had all her embryos tested. So that's PGT. And can you briefly just touch on that so our listeners have an idea about what that is? So there are different categories of preimplantation genetic testing.

And just to give a little bit of a sort of back story, in order to test an embryo, that embryo has to be able to grow in culture for five to six days. The embryo then has about 100 cells in it. Five to six cells are removed from the outer layer of that embryo, the layer that ultimately becomes the placenta, and that embryo is frozen.

Once those cells are obtained, it can be tested for chromosomes. The normal number of chromosomes is 46. So men have 46 chromosomes, including an X and a Y chromosome, and women have 46 chromosomes, including two X chromosomes.

So embryos can actually have these cells removed and they can be tested for their chromosome complement. This is called preimplantation genetic testing for aneuploidy or chromosome abnormalities. The problem is that when we're testing only for an embryo, that doesn't necessarily definitively represent the chromosomes that the baby component of that embryo will develop into.

So I do think we are a little bit in a quandary right now with preimplantation genetic testing. If an embryo is tested and is found to be chromosomally normal, that one embryo has more than a 60% chance of ending up as a baby. If an embryo is tested and some of the cells are found to be abnormal, or only parts of some of the cells are found to have sections of abnormal chromosomes, those embryos may actually still be able to support growth of a normal pregnancy.

At this point, when an embryo is considered abnormal, we are still trying to determine what percentage of those abnormal embryos have any chance of resulting in a normal baby. There are no randomized studies currently showing that testing an embryo for chromosome abnormalities will increase your likelihood of pregnancy. And again, this testing doesn't make an embryo better.

It doesn't make it able to create a pregnancy or a baby. It just gives us more information about the embryo. But again, the caveat is that we do know that babies have been born who are completely healthy from embryos where the testing did not indicate that the embryo was completely normal.

So I think we are still in a learning curve with this technology. Right. So it doesn't actually change the embryos a patient has, but it may narrow down which are the ones that are more likely to help them have a baby.

Correct. To select the one that's most likely to result in a normal baby. Right.

And it sounds like there's still a lot of studies that need to be done to know exactly who are the best patients that may benefit from that treatment the most at this point. Correct. And that technology is generally never covered by insurance.

So it is an added cost to the patient. So I think when it's cost effective is also not known. Correct.

The other type of pre-implantation genetic testing that can be used is if an individual or a couple knows that they're a carrier of a genetic disorder. So for example, if two people know that they're both carriers of cystic fibrosis, they have a 25% chance of having a baby with this serious disease and they may elect to have embryos tested so that they do not have a baby with cystic fibrosis. And there are many other genes that cause disease or predispose to high risks of cancer that can be tested for so that couples or individuals can avoid having a baby with a particular condition.

And sometimes patients will say, well, I want to have my embryo tested to make sure that it's healthy. And I think it's important to let patients know, you know, you have to know what specific disease you're looking for. Like you mentioned cystic fibrosis, it could be sickle cell disease, it could be spinal muscular atrophy, but we have to be looking for a specific disease or for chromosome number, not just quote making sure that the baby is healthy.

Correct. And there are many abnormalities that babies or individuals can have that are not testable. So for example, we do not have a test for autism at this point.

Congenital heart disease or birth defects do not have genetic tests or chromosome tests that will predict them. Great. Well, it sounds like we'll be looking forward to having more studies done in that area of IVF soon.

Well, thank you so much, Dr. Ginsburg, for meeting with us today to talk about in vitro fertilization. Again, we really appreciate your contribution to the SART podcast series. Thank you.

It was a pleasure. Thank you for listening to SART Fertility Experts, your resource for information on IVF. If you found this podcast useful, please like us on your favorite social media platform and tell your friends about us.

For more family building resources, visit www.sart.org slash patient dash information or www.reproductivefacts.org.