Speaker 1: Hi.
Speaker 2: My name's Dominique, and a few years ago I went
Speaker 2: through IBF. I had been married for a while. My
Speaker 2: partner has testicular cancer, so we figured that even though
Speaker 2: we'd been trying for a long time, it might have
Speaker 2: been that previous illness and resulting surgery that was getting
Speaker 2: in the way. Now, we actually ended up splitting up
Speaker 2: for other reasons. But after I had kind of set
Speaker 2: myself up on my own, I just figured, you know,
Speaker 2: mid thirties, I wanted to get on with it. So
Speaker 2: I consulted with my GP and started the process of IBF.
Speaker 2: There were a lot of hormone injections and other things,
Speaker 2: pelvic scans, ultrasounds, oral medications, and everything went pretty well
Speaker 2: for the first little while, but then it started to
Speaker 2: become a little bit more of a roller coaster. So
Speaker 2: my first egg collection day, I had a scan. I
Speaker 2: said I had thirteen really nice follicles. That was what
Speaker 2: the obgian said. I went into surgery. When I woke up,
Speaker 2: they told me all of the follicles had been empty.
Speaker 2: Now I didn't know that this was a thing, but
Speaker 2: there is a syndrome called empty follicle syndrome, where you
Speaker 2: have a lot of fodicles, but they don't actually have
Speaker 2: any eggs in them. I was really devastated. I had
Speaker 2: to go another round with different medications, different dosages, and
Speaker 2: I went in for my next surgery, egg collection surgery,
Speaker 2: with eleven follicles ready to go, and they were able
Speaker 2: to obtain three eggs from those. One of those is
Speaker 2: a dud. Two of them successfully fertilized. Out of those two,
Speaker 2: the first transfer didn't stick, and by this point I
Speaker 2: was actually getting pretty broke. I sold stuffed my motorcycle
Speaker 2: and things to cover these expenses, and I had the
Speaker 2: final transfer about a month later. And now I have
Speaker 2: a four year old. People ask me if I'm going
Speaker 2: to have another one. I don't have any more embryos.
Speaker 2: Follicles are probably not actually making many eggs, and this
Speaker 2: is actually probably the biggest reason why I wasn't able
Speaker 2: to get pregnant beforehand, and I just didn't even know.
Speaker 2: I also found out I had a retroverted uterus throughout
Speaker 2: the process, which was another surprise. So there's a lot
Speaker 2: of things that can come up during IVF that you
Speaker 2: don't necessarily expect, and it can happen just about any stage.
Speaker 3: Yeah, I don't think.
Speaker 2: That people ask if I'm going to have a second
Speaker 2: one if they know my journey. Everybody's IVF journey is
Speaker 2: really really different, but they're all roller coasters. I think
Speaker 2: they all have ups and downs, so that those are
Speaker 2: big or small.
Speaker 4: As a gestational carrier, my view on IVF wide and
Speaker 4: broadly throughout that process. So just a quick comparison for
Speaker 4: my own child, I went off birth control in that
Speaker 4: first month I got pregnant with her, and it was
Speaker 4: very quick to conceive, and and that was it, you know,
Speaker 4: I didn't have to think about it. I didn't have
Speaker 4: to do anything. And so fast forward to when my
Speaker 4: daughter was twelve and I decided to work with a
Speaker 4: a sergucy agency to become a gestational carrier for our family.
Speaker 4: I didn't fully realize that process. I just wanted to help,
Speaker 4: mainly a member of the LGBTQ become a family because
Speaker 4: I knew that that's a struggle for a lot of
Speaker 4: gay men to have children, and so I wanted to
Speaker 4: do that. That was my choice I made, and so
Speaker 4: when I went into that process, I guess I didn't
Speaker 4: think about, like the full what all has to happen?
Speaker 2: Right?
Speaker 4: My husband and I we decided to have a baby, Boom,
Speaker 4: we had a baby. Whereas, especially from the gestational carrier standpoint,
Speaker 4: I had to go through a psychological exam. My husband
Speaker 4: and I had to go through counseling, and we had
Speaker 4: to be like checkboxed that we were okay to do this,
Speaker 4: which I am one percent understand why. But I didn't
Speaker 4: have to do that to have my own child, right,
Speaker 4: And then I had to be made They had to
Speaker 4: make sure I was like compatible with the family that
Speaker 4: I worked with, and so it was such a different experience.
Speaker 4: But then when you get into having to have your uterus,
Speaker 4: your ovaries, your fallopian trips, everything examined very thoroughly to
Speaker 4: make sure they're all functional. I didn't know mine were
Speaker 4: functional prior to that. I mean, I remember the doctor
Speaker 4: giving me the compliment that I had like very nice
Speaker 4: eggs and I could have donated them that kind of comment,
Speaker 4: and I had no clue about that kind of thing
Speaker 4: prior to this experience. And like talking to people who
Speaker 4: I now know who have struggled with IVF, because I
Speaker 4: think my gestational carrier experience has caused people in my
Speaker 4: life to come and talk to me about their own
Speaker 4: struggles with it has really made me empathetic and really
Speaker 4: made me realize how hard it is, because like I
Speaker 4: went through this for somebody else, but it's I can't
Speaker 4: imagine just like going through that. I had to go
Speaker 4: through two cycles because I had one miscarriage and then
Speaker 4: I was pregnant and I carried that baby to term.
Speaker 4: But to go through that month after month after month,
Speaker 4: like the psychological toll it must take on a person,
Speaker 4: and I just like, like I was on hormone suppressants
Speaker 4: and then I was on estrogen and progesterone and I
Speaker 4: had to do shots, which I hate, needles. I can't
Speaker 4: imagine having to do. I think if it had been
Speaker 4: me in a situation at my own child, I might
Speaker 4: have gone down a different path because it's a lot
Speaker 4: to put on a person, and it's so like they're
Speaker 4: so brave for doing it.
Speaker 3: Thank you again so much to the providers of all
Speaker 3: of these first hand accounts. It really is, it's just
Speaker 3: thank you. I don't have the words.
Speaker 1: Yes, seriously, thank you so much. It's yeah, we can't
Speaker 1: thank you enough.
Speaker 4: Hi.
Speaker 1: I'm Aaron Welsh and I'm Erin Allman Updyke.
Speaker 3: And this is this podcast will Kill You.
Speaker 1: Welcome to part two of our three part series on
Speaker 1: infertility and IVF.
Speaker 3: YEP. Part two this is where So if you didn't
Speaker 3: tune in to our first episode in this series, then
Speaker 3: in that episode we talked a lot about infertility, basically
Speaker 3: concepts of infertility, how you can define it, how it
Speaker 3: has changed throughout time, different perceptions of infertility, and then
Speaker 3: what happens if you go in for fertility testing, What
Speaker 3: are the type of tests, what are they going to
Speaker 3: be looking for? How can we categorize infertility in the
Speaker 3: broadest and most non broadway possibles, Like non broadway that's
Speaker 3: a very confusing thing to say, and like broad and
Speaker 3: narrow definitions. How about that? Really just like the full
Speaker 3: gamut of things. And then in today's episode we are
Speaker 3: going to be talking about IVF, and so of course
Speaker 3: infertility is just one of the things that IVF is
Speaker 3: used for often as a treatment, but it's not the
Speaker 3: only thing. And so really we're just going to approach
Speaker 3: this from like, hey, how did it get developed, how
Speaker 3: does it work? What does a typical cycle of IVF entail?
Speaker 3: And so on.
Speaker 1: If you haven't listened to our first part, you don't
Speaker 1: have to to get through this episode, but you should.
Speaker 3: It's a really great episode. Yeah.
Speaker 1: And if you're looking for context and you're really like,
Speaker 1: where's the context, it's there. It's in that episode.
Speaker 3: It is, it is. And also in that first episode
Speaker 3: is where we shared the quarantine y for We sure
Speaker 3: did three parter, which was a work of art. It's
Speaker 3: such a great name, and so if you want to
Speaker 3: know the recipe for that, check our socials, or tune
Speaker 3: into that first episode, or check our website, which is
Speaker 3: also where you can find all kinds of stuff. Aaron
Speaker 3: take us here, so.
Speaker 1: You can find the sources from all of our episodes.
Speaker 1: You can find a link to our Goodreads list. You
Speaker 1: can find Bloodmobile, who does our music. You can find
Speaker 1: our bookshop dot org affiliate account. You can find our
Speaker 1: incredible merch Do you have a head? Can you get
Speaker 1: your hands on it? It's so good. You can find
Speaker 1: transcripts from all of our episodes, which are apparently also
Speaker 1: now available on Apple Podcasts. That's so exciting. There's a
Speaker 1: lot there. This podcast will kill you dot com check
Speaker 1: it out.
Speaker 3: Check it out. Should we just start again?
Speaker 1: I really feel like we should because I'm super excited
Speaker 1: to learn about the history of how IVF was developed.
Speaker 1: Because I know nothing, Aaron.
Speaker 3: I mean, I know a little bit more than nothing,
Speaker 3: So let me tell you yourself. Credit we'll see. Right
Speaker 3: after this break, I will get into it.
Speaker 5: We were a little older than I would say many
Speaker 5: people are when they decide they want to start trying
Speaker 5: for a baby, and I had done one of those
Speaker 5: at home fertility tests a couple years prior and found
Speaker 5: out that my ovarian reserves were lower than.
Speaker 3: Average for my age.
Speaker 5: So when my husband and I started trying to get pregnant,
Speaker 5: I figured it would take a couple months and we'd
Speaker 5: nail it eventually. I was also very fortunate that at
Speaker 5: the time I was working at a company that offered
Speaker 5: significant fertility treatment benefits. So after six months and no pregnancy,
Speaker 5: I was able to schedule an appointment with our preferred
Speaker 5: fertility clinic, where they ordered a barrage of tests for
Speaker 5: me and my husband. We found out at that time
Speaker 5: that not only are my ovarian reserves low, but that
Speaker 5: my husband's sperm count and sperm motility are really low
Speaker 5: as well. Essentially, doctors gave us a one percent chance
Speaker 5: of conceiving naturally. The first IVF.
Speaker 1: Round we did.
Speaker 5: The doctors put me on the catalac of treatment. They
Speaker 5: gave me a strict schedule of a high dose of drugs,
Speaker 5: trying as hard as they could to get my ovaries
Speaker 5: to produce enough mature eggs for retrieval, fertilization, and implantation. Unfortunately,
Speaker 5: even with all that medication, my ovaries produced only three
Speaker 5: eggs for retrieval, and only two of them were mature
Speaker 5: enough to be fertilized, and only one of those embryos
Speaker 5: made it to day three after fertilization, So they scheduled
Speaker 5: my embryo implantation that day to give the fertilized egg
Speaker 5: the best shot at growing and attaching in my uterus,
Speaker 5: since we had no backup eggs or embryos that could
Speaker 5: be frozen. That embryo resulted in a chemical pregnancy where
Speaker 5: it had attached. I got a positive early pregnancy test,
Speaker 5: and then it was lost. We tried another round of
Speaker 5: IVF a couple months later, this time with far less medication,
Speaker 5: since the doctors figured I'd only produce three eggs regardless,
Speaker 5: and this time my ovaries produced only one egg, resulting
Speaker 5: in a canceled retrieval and a failed IVF cycle. My
Speaker 5: husband and I decided to stop IVF at that time
Speaker 5: and are now determining if we want to go any
Speaker 5: other routes to grow our family. The whole time, I
Speaker 5: knew our chances were maybe slim, but going through the
Speaker 5: process ourselves and seeing the actual stats, percentages, and chances
Speaker 5: to get pregnant, keep a pregnancy, and then deliver a
Speaker 5: baby were wild. In a world that told me how
Speaker 5: easy it was to get pregnant, turns out it is
Speaker 5: actually pretty difficult for some people.
Speaker 6: Hi, I'm Adrian. One thing that needs more discourse is
Speaker 6: the complex miasma of emotions IVF creates. For example, I
Speaker 6: felt torn about sending this in because so many people
Speaker 6: struggle with IVF, and my husband and I were incredibly lucky.
Speaker 6: We had six genetically normal embryos and went two for
Speaker 6: two with successful transfers. It's a miracle. But I don't
Speaker 6: feel comfortable talking to other people who did IVF because
Speaker 6: so many times their experience was so much harder than
Speaker 6: mine that I feel I should just shut up. But
Speaker 6: at the same time, I can't talk to anyone who
Speaker 6: conceived naturally because they do not understand the stress and
Speaker 6: darkness that comes with IVF, the pain of watching everyone
Speaker 6: around you get pregnant, the oppressive anxiety of will it
Speaker 6: work this time, the constant needles doctors, meds, and having
Speaker 6: to juggle work at the same time. I'm a wildly
Speaker 6: successful example of IVF, and it was still one of
Speaker 6: the most difficult times in my life, not to mention
Speaker 6: the special hell it is trying to get pregnant by committee.
Speaker 6: I had a transfer canceled and postponed indefinitely because of
Speaker 6: a hurricane, and I had to go to a different clinic.
Speaker 6: This meant months went by, more paperwork, and I had
Speaker 6: to do all the medical tests again. That's not something
Speaker 6: people who conceive naturally have to give a second thought about.
Speaker 6: In short, IVF sucks, and it's a miracle that I'm
Speaker 6: thankful for every day.
Speaker 3: In Part one of this series, I explored infertility throughout history,
Speaker 3: how people wrote about it, who wrote about it, what
Speaker 3: explanations did people come up with? And I ended up
Speaker 3: just like summarizing the entire twentieth century by saying, like,
Speaker 3: as our scientific and medical understanding of infertility and fertility grew,
Speaker 3: infertility began to be increasingly seen as a thing for
Speaker 3: science to overcome first with surgeries, hormonal regulation, especially as
Speaker 3: our understanding of undercnology grew in the early twentieth century,
Speaker 3: artificial insemination, and ultimately leading to IVF and the first
Speaker 3: IVF babies born in nineteen seventy eight. Today, I want
Speaker 3: to get into that journey to IVF by talking about
Speaker 3: how this technology was developed, the foundational research that made
Speaker 3: it possible, and what happened when this pie in the
Speaker 3: sky idea became reality. Framing it that way makes it
Speaker 3: kind of sound like developing IVF to treat infertility was
Speaker 3: the goal all along, all roads lead to IVF, but
Speaker 3: that really wasn't the case, huh. Much of this research
Speaker 3: came out of a desire to understand how human reproduction worked,
Speaker 3: including IVF and the applications, including using IVF for reasons
Speaker 3: other than infertility, which is a big part of IVF.
Speaker 3: These applications kind of arose later on. It's just something
Speaker 3: I want to put out there because I feel like
Speaker 3: we tend to think of IVF as like and this
Speaker 3: has been the end goal and this is the thing
Speaker 3: that IVF is used for, and that is really an oversimplification.
Speaker 1: It's leaving a lot of the story out interesting.
Speaker 3: Yeah, So, because we're doing this episode out of our
Speaker 3: usual order, I don't get to benefit from having the
Speaker 3: biology of IVF already so thoroughly explained by you Erin,
Speaker 3: and so I know that we'll get there later on
Speaker 3: in the episode. But for the purposes of the history
Speaker 3: section today, I'm going to lay out the steps of
Speaker 3: IVF in the most basic way that I could think of.
Speaker 3: At the core of it, IVF in vitro fertilization in vitro,
Speaker 3: meaning in glass outside of the organism. It consists of
Speaker 3: four basic steps. Number one, retrieving an egg or multiple eggs.
Speaker 3: Number two fertilizing that egg with sperm. Number three culturing
Speaker 3: the fertilized egg for a while until it turns into
Speaker 3: a cluster of cells called a blasticist. And number four
Speaker 3: transferring the blasticist or blastocysts into a uterus where it
Speaker 3: will hopefully implant and develop into an embryo, a fetus,
Speaker 3: and then ultimately a baby.
Speaker 1: Yeah, one hundred percent. We'll get into so much more
Speaker 1: detail later on, but that's a good basic.
Speaker 3: So these are the basic steps that scientists and clinicians
Speaker 3: had to figure out in order to get to nineteen
Speaker 3: seventy eight, which makes it sound like a whole lot
Speaker 3: of blurt than it actually is, because like it is
Speaker 3: so complex. I also feel like it sounds so harsh.
Speaker 3: I know it does, but it's like, here are these
Speaker 3: four basic steps. Just figure this out. Just you know,
Speaker 3: retrieve an egg. Just how do you do that? Fertilize
Speaker 3: the egg with sperm? That took a lot culturing, you know,
Speaker 3: like all of these things took a long time to
Speaker 3: figure out. And it was really decades, decades of work,
Speaker 3: of trial and error, of collaboration between scientists and physicians,
Speaker 3: and of really courageous participation by so many volunteers and
Speaker 3: patients to get all of these kinks worked out in
Speaker 3: this process, which like also they're not fully worked out.
Speaker 3: But even still, even in nineteen seventy eight, or especially
Speaker 3: in nineteen seventy eight, there was no certainty that this
Speaker 3: would become a standard treatment and an industry, or this
Speaker 3: industry that it has grown into. And it also took
Speaker 3: a detailed and thorough under standing of human reproduction, not
Speaker 3: just the role of major organs like the uterus or ovaries,
Speaker 3: but also at the cellular level, at the hormonal level,
Speaker 3: at the genetic level, and how these things work together
Speaker 3: to lead to the development of embryos into fetuses into infants.
Speaker 3: It's incredible, it's really cool. By the middle of the
Speaker 3: nineteenth century, studies in anatomy and physiology started to shed
Speaker 3: light on how the reproductive system worked, but this was
Speaker 3: mostly at the organ level, with things visible to the
Speaker 3: naked eye. Scientists had known about eggs and sperm since
Speaker 3: the sixteen seventies, but it took another one hundred and
Speaker 3: fifty years for people to understand how the two work together.
Speaker 3: Was the sperm just food for the egg? Was the
Speaker 3: egg passive?
Speaker 1: That was actually thought at one point, which is kind
Speaker 1: of fascinating. Yeah, much much much like a little pac man.
Speaker 3: Yes, yes, was the egg passive fertile soil in which
Speaker 3: the seed is planted. The nineteenth century clarified things, in
Speaker 3: part with Gregor Mendel and others showing that parents contribute
Speaker 3: equal heritable material to offspring. Wow.
Speaker 1: I don't think that I ever thought about people knowing
Speaker 1: that eggs and sperm exist before they knew about DNA
Speaker 1: and like chromosomes, and oh wow, that is so interesting.
Speaker 3: Right, because it's like, how are these things put together? Oh?
Speaker 1: That is so incredibly fascinating to think about Aaron.
Speaker 3: It's amazing. But even still, the nitty gritty of mammalian
Speaker 3: reproduction was largely a mystery, since fertilization and implantation and
Speaker 3: development all happened internally out of sight like you couldn't,
Speaker 3: whereas like a lot of the other chasearch was done
Speaker 3: with like reptiles for instance. Yeah, researchers like Walter Heap
Speaker 3: and Albert Broshet didn't let that stop them though. In
Speaker 3: eighteen ninety one, Heap transferred rabbit embryos from one rabbit
Speaker 3: to another, and that rabbit became pregnant and delivered baby
Speaker 3: rabbits or kids. As I learned that they're called. How cute.
Speaker 3: It's very cute, very cute. Cool, but not in vitro fertilization.
Speaker 3: A few decades later, in nineteen thirteen, Albert Broschet was
Speaker 3: the first to successfully culture mammalian blasticists before implantation. Also cool,
Speaker 3: still not in vitro fertilization. Things were moving steadily but slowly.
Speaker 3: In the first few decades of the twentieth century, the
Speaker 3: field of reproductive biology seemed to attract more interest from
Speaker 3: science fiction enthusiasts than it did from biologists. The public
Speaker 3: seemed particularly interested in the idea of ectogenesis, so fertilization
Speaker 3: and gestation, completely outside the box.
Speaker 1: Brave New World.
Speaker 3: Exactly, I was, That's my next line. In nineteen thirty two,
Speaker 3: Aldus Huxley published Brave New World. And this book opens
Speaker 3: with a description of the Central London Hatchery and Conditioning Center,
Speaker 3: which is basically a baby factory, complete with artificial wounds.
Speaker 3: And I know, like, I'm how many times have you
Speaker 3: seen Brave New World mentioned in papers about IVF? Yeah,
Speaker 3: every single one?
Speaker 1: Right, you can't, well, not everyone that I read, but
Speaker 1: I could see it.
Speaker 3: Yes, it is. It is persistent. And Aldus Huxley probably
Speaker 3: got this idea from conversations with his brother Julian, who
Speaker 3: was a scientist, and Gregory Pinkis, who was an endocrinologist
Speaker 3: that helped to create the first oral contraceptive pill and
Speaker 3: also did a lot of work of really important work
Speaker 3: on IVF and rabbits. I'll talk a little bit more
Speaker 3: about him. Yeah. The popularity of Brave New World reflected
Speaker 3: this growing sense of disillusionment with technology. People no longer
Speaker 3: believed as they had at the turn of the century
Speaker 3: that technology would solve all of life's woes. War and
Speaker 3: economic downturn had tipped the scales from assisted reproductive technologies
Speaker 3: being perceived as part of a utopian future to these
Speaker 3: technologies being a sign of our ultimate downfall. And maybe
Speaker 3: that's dramatic, but maybe not, because consider what happened to
Speaker 3: Gregory pinkis so. Pincus was appointed assistant professor of biology
Speaker 3: at Harvard in nineteen thirty one, where he did research
Speaker 3: on in vitro fertilization in rabbits and studied the hormonal
Speaker 3: changes that lead to one mature egg being released each month.
Speaker 3: In nineteen thirty six, his work and his claim that
Speaker 3: he and colleague ev Nsman were the first to successfully
Speaker 3: demonstrate IVF and rabbits. That claim was later challenged by
Speaker 3: people who couldn't replicate it. I'm not sure it's yeah.
Speaker 3: There's a lot of claims and a lot of skepticism
Speaker 3: throughout this whole history, but this his work. Pinkus's work
Speaker 3: drew the attention of the popular press, mostly falling somewhere
Speaker 3: between speculative and negative reaction Wise, some journalists imagined a
Speaker 3: world where human children would be brought into the world
Speaker 3: by a host mother not related by blood to the child,
Speaker 3: eventually leading down the slippery slope of eugenics, where quote
Speaker 3: advocates of race betterment might urge such procedures for men
Speaker 3: and women of special aptitudes, physical, mental, or spiritual end quote.
Speaker 3: Others warned, what would happen to the men if this
Speaker 3: science were applied to humans? Quote? In the resulting world,
Speaker 3: man's value would shrink. It is conceivable that the process
Speaker 3: would not even produce males. The mythical land of the
Speaker 3: Amazons would then come to life, a world where women
Speaker 3: would be self sufficient. Man's value precisely zero. End quote.
Speaker 3: That is so telling, Aaron, Wow, isn't it?
Speaker 1: That is so telling? Wow? IVF will create the world
Speaker 1: of the Amazons.
Speaker 3: Where women are self sufficient and so men's value is zero.
Speaker 1: It's I mean again, there's so many layers here, so.
Speaker 3: Many layers, so many And Pinkus himself wasn't interested in
Speaker 3: these broader implications of the research that he was conducting.
Speaker 3: He just wanted to do his experiments and like learn more.
Speaker 3: But that didn't matter. The negative press was enough to
Speaker 3: get him denied tenure at Harvard and let go Wow,
Speaker 3: and that wasn't the end for IVF or for Gregory Pinkus,
Speaker 3: who would go on to help create the birth control pill,
Speaker 3: along with the next name in our IVF story, John Rock,
Speaker 3: a gynecologist at the Free Hospital for Women Boston and
Speaker 3: Harvard Medical School. Rock had come across the rabbit IVF
Speaker 3: paper by Pinkus and became fascinated so much so that
Speaker 3: he decided to work on IVF. He teamed up with
Speaker 3: Miriam Menken, who had been a research assistant working on
Speaker 3: hormones with Pinkus at Harvard before he was kicked out,
Speaker 3: And I just I kind of love that, and also
Speaker 3: her story is really interesting and like, definitely at least
Speaker 3: go to her Wikipedia page and check it out. But
Speaker 3: the third member of their team was pathologist Arthur Hertig,
Speaker 3: and together these three performed groundbreaking research in reproductive biology
Speaker 3: in three big areas. The first area was capturing the
Speaker 3: timing of ovulation, which would prove to be super helpful
Speaker 3: in IVF later on for egg retrieval, but also for
Speaker 3: artificial insemination, which began to be more popular around this time.
Speaker 3: And the second area was in describing the early stages
Speaker 3: of human embryonic development, which they did at a time
Speaker 3: when really no one knew how anything worked before even
Speaker 3: the development of the ultrasound wow, which is wild. And
Speaker 3: the third was in the fertilization of human eggs outside
Speaker 3: of the body, and so to do this they enlisted
Speaker 3: the help of women who were set to undergo hysterectomies,
Speaker 3: and they performed the surgeries just before the volunteers ovulated
Speaker 3: so that they could extract as many eggs as possible,
Speaker 3: And after getting the donated tissue, Menken would run like
Speaker 3: literally run up and down flights of stairs over to
Speaker 3: the lab where she would begin trying to fertilize these
Speaker 3: eggs outside of the body in vitro. But after years
Speaker 3: and over one hundred and thirty eggs exposed to sperm
Speaker 3: out of the eight hundred they collected, nothing seemed to work.
Speaker 3: And then one day in nineteen forty four, exhausted from
Speaker 3: staying up late with her baby, Menkin only washed the
Speaker 3: sperm once as opposed to the usual three times, and
Speaker 3: later she returned to see that the egg had divided
Speaker 3: into two cells, and they repeated this a couple more
Speaker 3: times with the revised protocol with fewer washes, and took pictures,
Speaker 3: and I feel obligated to include this, like this is
Speaker 3: a well actually that I'm going to throw in here.
Speaker 3: There does seem to be some debate on whether that
Speaker 3: actually represented fertilization, since people later realized that freshly ejaculated
Speaker 3: sperm actually needs to spend a period of time in
Speaker 3: the genital tract before they're ready for fertilization, in a
Speaker 3: process called capacitation. I don't know, I'm not really clear
Speaker 3: on this, but some people have been like, Okay, maybe
Speaker 3: the egg just divided without being fertilized, which also has
Speaker 3: been known to happen or seen to happen. But yeah, okay,
Speaker 3: I don't know. That's like my little pedantic well, actually.
Speaker 1: All have them, Yeah we do, we do.
Speaker 3: But in any case, this was huge news all over
Speaker 3: the news outlets, just like global headlines. Rock immediately saw
Speaker 3: the potential application of IVF for treatment of infertility, and
Speaker 3: as did all of these news outlets, and he and
Speaker 3: Menken received dozens of letters from women all over hopeful
Speaker 3: that they could use this new technology to help them
Speaker 3: have children. Rock personally replied to many of these letters
Speaker 3: with like cautious optimism and was like, maybe someday we're
Speaker 3: not quite there yet, But he also took the time
Speaker 3: to explain the science and I just appreciate that I
Speaker 3: don't know. And by and large, the public response to
Speaker 3: this announcement seemed positive. The war had just ended, and
Speaker 3: this is also like primarily US specific, but like the
Speaker 3: war had just ended, the economy was booming, pro natalism
Speaker 3: was in full force, and IVF was going to solve
Speaker 3: the problem of involuntary childlessness. Over the next couple of decades,
Speaker 3: things were kind of quiet on the human side of IVF,
Speaker 3: but some researchers were exploring the technique and other animals,
Speaker 3: and in nineteen fifty nine, doctor Min Chua Chang successfully
Speaker 3: used IVF in a rabbit to produce kits nineteen fifty
Speaker 3: nine nineteen fifty nine. The enthusiasm for IVF in humans
Speaker 3: began to die down by the end of the nineteen sixties,
Speaker 3: in part due to a lack of progress, in part
Speaker 3: due to rejection of technology sort of across the board,
Speaker 3: and in part due to a decline in pro natalism.
Speaker 3: But that happens to be when significant progress on the
Speaker 3: technique began to be made in nineteen seventy three and
Speaker 3: nineteen seventy five, researchers reported the first IVF pregnancies, although
Speaker 3: they only lasted a few days, and the first IVF
Speaker 3: babies were just around the corner. Robert Edwards, Patrick Steptoe,
Speaker 3: and Jean Purdy formed a powerful IVF team in England
Speaker 3: that had spent a good deal of the nineteen seventies
Speaker 3: working on this technique, leading to a chemical pregnancy in
Speaker 3: nineteen seventy five that turned out to be ek topic.
Speaker 3: But this heartbreaking result did show them that they were
Speaker 3: on the right path, and a few years and a
Speaker 3: few tweaks to the protocol later, and they tried out
Speaker 3: their new method on a few people at their clinic.
Speaker 3: Nine months later, on July twenty fifth, nineteen seventy eight,
Speaker 3: the second person they tried this out on, Leslie Brown,
Speaker 3: gave birth to Louise Brown, the world's first IVF baby.
Speaker 1: That is very cool.
Speaker 3: It's amazing. Yeah yeah, And Louise's birth was like a
Speaker 3: total media circus. Oh I bet, I mean Leslie had
Speaker 3: to constantly move houses and hospitals. There was a bomb
Speaker 3: scare to the hospital to try to get a picture
Speaker 3: of her. People would dress up as window cleaners to
Speaker 3: try to like, find out which room she was in
Speaker 3: and get a picture for the papers.
Speaker 1: Oh my god.
Speaker 3: And the cesarean was filmed to show that Leslie had
Speaker 3: no phallopian tubes in anticipation of people doubting that it
Speaker 3: was actually like IVF Wow. Wow.
Speaker 1: Also, did they do a cesarean just because of that?
Speaker 3: That might be more detail, but I don't know.
Speaker 1: That's fascinating.
Speaker 3: I don't know. Yeah, amazing though.
Speaker 1: Wow.
Speaker 3: And in twenty ten, Robert Edwards was awarded a Nobel
Speaker 3: Prize for his work. Steptoe and Purdy had both died
Speaker 3: and it's not awarded posthumously. Only ten weeks after Louise
Speaker 3: Brown was born, Kanyupriya Agarwal was born in India. The
Speaker 3: second test two baby quote unquote, as they began to
Speaker 3: be called, led by a team consisting of Subas Mukerjee,
Speaker 3: Sunit Mukerjee, and Saraj Kanti Badachara. Whereas Steptoe, Edwards and
Speaker 3: Purdy relied on natural cycles of ovulation, the team in
Speaker 3: India used drugs to induce ovulation and then froze the
Speaker 3: embryo before implanting it.
Speaker 1: Wow.
Speaker 3: I think it is so interesting to see these different
Speaker 3: methodologies and how like which clinic uses what and I
Speaker 3: don't know. I guess you'll talk about sort of what
Speaker 3: what are the different pros and cons? But many different
Speaker 3: ways to get a result? I think, yeah, yeah, so
Speaker 3: you don't. You don't always see this birth mentioned in
Speaker 3: histories of IVF, because almost immediately after it was met
Speaker 3: with skepticism it was described as a fluke, as experimental
Speaker 3: and likely to be a standalone And this might have been.
Speaker 3: This reaction might have been because the Indian team allegedly
Speaker 3: carried out the work somewhat secretively and without formal approval,
Speaker 3: but it wasn't a fluke or fraudulent. That didn't matter though,
Speaker 3: to the institutions where Subas Mukerjee, who was the team
Speaker 3: leader worked. Mukerjee was sent to an ophthalmology institute where
Speaker 3: he couldn't do He couldn't do any work, but it
Speaker 3: was just as a way to be like, we're preventing
Speaker 3: you from doing any of the work that you actually
Speaker 3: want to do. He was forbidden to present his IVF
Speaker 3: research or participate in conferences, and in July of nineteen
Speaker 3: eighty one, he took his own life.
Speaker 1: Oh my god, yeah, not.
Speaker 3: Awful, awful, awful. The nineteen seventy eight birth of Kanye
Speaker 3: Pria Agarwal was really only recognized in nineteen ninety seven,
Speaker 3: I read, and it's so it's still sort of making
Speaker 3: its way into these global histories of IVF. After these
Speaker 3: two nineteen seventy eight births, several more followed. The first
Speaker 3: Australian IVF birth was in nineteen eighty and the next year,
Speaker 3: nineteen eighty one, the first American IVF baby was born.
Speaker 3: But even with these births, IVF was by no means
Speaker 3: a sure thing technologically speaking, financially speaking, and in terms
Speaker 3: of regulation. The news of these first IVF babies was
Speaker 3: met with a lot of feelings, some very pro, some
Speaker 3: very anti, but rarely indifferent. The potential that IVF held
Speaker 3: good bad other was and is tremendous. And we'll get
Speaker 3: into some of these things next week. But I want
Speaker 3: to wrap up today's history section with a brief look
Speaker 3: at when IVF came to the US and how that
Speaker 3: set a precedent for IVF becoming a mostly private pay
Speaker 3: for services institution, a market driven enterprise for better or worse.
Speaker 3: After the birth of Louise Brown and the other early
Speaker 3: IVF babies. The US realized that IVF might be here
Speaker 3: to stay, so they began to call for congressional hearings
Speaker 3: to discuss the implications of IVF and policies for how
Speaker 3: treatment and research should be regulated. Should IVF research or
Speaker 3: research involving embryos be allowed to receive federal funds? That
Speaker 3: question has been debated for years, and there is currently
Speaker 3: a ban on federal funding for research involving embryos in
Speaker 3: the US, but for quite a long period of time
Speaker 3: it was anticipated that it would be allowed. To verify,
Speaker 3: the research is still allowed to be conducted, it's just
Speaker 3: that it can't be federally funded. The funding has to
Speaker 3: come from other sources, just throwing that out there. In
Speaker 3: the late nineteen seventies, when it was looking like federal
Speaker 3: funds would be approved, two researchers, slash clinicians and married
Speaker 3: couple Georgiana Seeger Jones and Howard Jones, left Johns Hopkins
Speaker 3: University for Eastern Virginia Medical School where they could pursue
Speaker 3: IVF research. Their story is actually really cute and it
Speaker 3: goes back like really far and there are like cute
Speaker 3: letters during the war. Anyway, Georgiana was a pioneering, highly
Speaker 3: accomplished reproductive endocrinologist and her husband, Howard, trained as a
Speaker 3: general surgeon and then specialized in gynecology so that he
Speaker 3: could work closely with his wife, and for years they
Speaker 3: worked together, sharing a lab, an office, even a desk,
Speaker 3: and Robert Edwards from the England IVF team actually trained
Speaker 3: with them for a while. But not being willing to
Speaker 3: wait for federal funding for IVF to be approved, they
Speaker 3: would still have been waiting, they decided that this technique
Speaker 3: was enough in demand that they could seek private funds
Speaker 3: and charge for services. In nineteen eighty one, the first
Speaker 3: IVF baby in the US was born from their clinic.
Speaker 3: Each couple had to meet the following criteria youth under
Speaker 3: thirty five, good health, bad fallopian tubes, a husband, and
Speaker 3: the unspoken one was that you had to have money.
Speaker 3: Each couple had to shell out around four thousand dollars
Speaker 3: in nineteen eighty dollars or fifteen thousand dollars in today's dollars,
Speaker 3: but the cost didn't keep people from flocking to the clinic.
Speaker 3: Other IVF programs in the US followed shortly, first primarily
Speaker 3: at medical schools, then in community hospitals, in partnership with
Speaker 3: private infertility practices, and finally in independent centers. Despite urging
Speaker 3: from the American Fertility Society to come up with federal
Speaker 3: guidelines and oversight for these clinics, progress was slow. The
Speaker 3: most they could do, like the Society was establish a subgroup,
Speaker 3: the Society for Assisted Reproductive Technology, and required clinics to
Speaker 3: follow particular standards if they wanted to be SAAR Team members.
Speaker 3: But there was no way to enforce these guidelines, and
Speaker 3: the number of clinics grew steadily, in part because of
Speaker 3: the appeal of no strict regulation, or really no regulation.
Speaker 3: The introduction of the vaginal ultrasound probe made things easier
Speaker 3: for IVF, which required only local anesthesia and meant a
Speaker 3: surgeon and operating room were no longer required, and this
Speaker 3: marked the end of many relationships between private IVF clinics
Speaker 3: and academic medical centers in the US, and it enabled
Speaker 3: even more growth, which led to, among other things, improvements
Speaker 3: in technique and application for IVF, so people not just
Speaker 3: with tubal factor infertility, but also endometriosis, unexplained infertility, male
Speaker 3: factor infertility, genetic conditions, same sex couples, single parents, and
Speaker 3: so much more. Age restrictions began to be raised. Intracytoplasmic
Speaker 3: sperm injection was introduced at ICSI, as was egg and
Speaker 3: embryo freezing, and many clinics began to incorporate donor eggs
Speaker 3: and embryos and gestational and traditional surrogacy. IVF was bringing
Speaker 3: more and more people the children they had always wanted,
Speaker 3: and as the number of clinics grew globally, as technological
Speaker 3: advancements were made, more questions were being asked about the
Speaker 3: financials of IVF, about access, about ethics, about transparency from clinics,
Speaker 3: about what the future could hold. That's what we'll be
Speaker 3: getting into next week. But for now, Aarin, I'll hand
Speaker 3: it over to you to tell us all about how
Speaker 3: IVF works.
Speaker 1: Excellent. I can't wait to kind of go over what
Speaker 1: it looks like today just after this break. Hi.
Speaker 7: My name is Yohanna, and in February of twenty twenty three,
Speaker 7: I give birth to our daughter, who was conceived with
Speaker 7: intrauterine insemination using donor sperm. When my partner and I
Speaker 7: first talked about getting pregnant, we had to do a
Speaker 7: lot of googling, a lot of reading and a lot
Speaker 7: of talking to our fertility specialists to figure out what
Speaker 7: our options are for a same sex couple and how
Speaker 7: the logistics of it all work, the ins and out
Speaker 7: of getting the sperm, genetic testing, and the different ways
Speaker 7: of getting the sperms inside of my uterus. So we
Speaker 7: wound up going with intrauterine insemination, which is really just
Speaker 7: inserting the sperm through the cervix with a long needle
Speaker 7: directly into the uterus. The chances of pregnancy are slightly
Speaker 7: higher than with just intercourse, but not super high, so
Speaker 7: that's usually the first step, and then if that doesn't
Speaker 7: work after a few cycles, the next step would be
Speaker 7: using medication to boost fertility, and then after that is
Speaker 7: IVF and mutual fertilization. So we did all of the
Speaker 7: prep stuff. We did genetic testing, we bought sperm off
Speaker 7: a sperm bank, and we also did genetic counseling, which
Speaker 7: is required because they just want to kind of gauge
Speaker 7: how you would deal with having a donor conceived child,
Speaker 7: how you would talk about that with friends and family,
Speaker 7: and of course, most importantly, how you would talk about
Speaker 7: that with your child. So, after all of that prep
Speaker 7: work was done. I'd been charting my cycles and tracking
Speaker 7: my ovulation, and then once it was regular, I alerted
Speaker 7: the fertility clinic when I was ovulating, and we got
Speaker 7: the sperm transported from the storage facility to the fertility clinic,
Speaker 7: and I went in for my first insemination. The first
Speaker 7: one didn't take, so we did a second one the
Speaker 7: next cycle, and that one did take and I became pregnant.
Speaker 7: So the first few weeks they monitored my pregnancy at
Speaker 7: the fertility clinic. They did a couple of tests to confirm,
Speaker 7: they did the first ultrasound there, and then I was
Speaker 7: released into regular prenatal care with my regular obgyn, and
Speaker 7: I wound up having a great pregnancy and giving birth
Speaker 7: to an amazing baby. Our daughter is fifteen months now,
Speaker 7: and she is absolutely the best. And I am so
Speaker 7: glad and so grateful for all of the support that
Speaker 7: we had and for the fact that we have that
Speaker 7: option and that that was something that we were able
Speaker 7: to do to have our baby, and to live in
Speaker 7: a state where most people are supportive and understanding and
Speaker 7: where we didn't have to fight very hard to make
Speaker 7: this a reality for us. It's been a really amazing
Speaker 7: experience and I'm really proud to be part of the
Speaker 7: of the IUI community of having used as system reproductive
Speaker 7: technology and having had the chance to have that in
Speaker 7: my life to help bring our child.
Speaker 8: My name is Lilian and I'm an IVF long holer.
Speaker 8: My husband and I started trying to conceive in twenty seventeen,
Speaker 8: soon after I turned thirty two. After two miscarriages. We
Speaker 8: began IVF treatment in twenty eighteen after I was diagnosed
Speaker 8: with diminished ovarian reserve. We've done eleven IVF retrieval cycles
Speaker 8: to pay embryos, four retrievals in twenty nineteen, three in
Speaker 8: twenty twenty and four in twenty twenty two, and two
Speaker 8: frozen embryo transfers, one in twenty nineteen and one in
Speaker 8: twenty twenty three. We've experienced a total of seven pregnancy
Speaker 8: losses through unassisted spontaneous conceptions and frozen embryo transfers, including
Speaker 8: the seventeen week fetal demise of our daughter conceived through
Speaker 8: IVF tank in March twenty twenty, and have had no
Speaker 8: live births throughout the years of IVF treatments and multiple surgeries.
Speaker 8: I was diagnosed with endometriosis suspected adnomiosis, gestational trophiblastic disease,
Speaker 8: autoimmune disease that attacks my reproductive organs and pregnancies, and
Speaker 8: Asherman syndrome following multiple miscarriages. We've completed IVF with three
Speaker 8: different clinics, two conventional clinics and one specialty clinic that
Speaker 8: uses mini IVF, both in and out of state, worked
Speaker 8: with a reproductive immunologist out of state, and consulted with
Speaker 8: almost a dozen reproductive endocrinologists specializing in recurrent pregnancy loss
Speaker 8: and endometriosis across the country. However, despite pursuing every evidence
Speaker 8: based treatment and if you not so evidence based, my
Speaker 8: body is unable to sustain a pregnancy to term and
Speaker 8: live birth, even with the perceived quote guarantee of IVF
Speaker 8: resulting in a live baby. A critical factor in our
Speaker 8: pursuit of IVF was having insurance coverage, which made a
Speaker 8: huge difference in our treatment options because we weren't limited
Speaker 8: to what we could afford at the time. Since most
Speaker 8: of our IVF was covered by insurance, we didn't deplete
Speaker 8: our savings then, which allows us to now pursue gestational surrogacy.
Speaker 8: Following the suggestions of our physicians and the limits my
Speaker 8: husband and I agreed we'd reached, which we called our
Speaker 8: heartbreak tolerance. We are grateful for the opportunity to try
Speaker 8: to have a biological child through IVF with gestational surrogacy,
Speaker 8: and we grieve everything we've been through. There aren't many
Speaker 8: stories from long haulers who've suffered multiple miscarriages like myself,
Speaker 8: for whom IVF doesn't end with the live baby, because
Speaker 8: our stories are sad, but we do exist.
Speaker 1: So you walked us through aarin four main steps of IVF,
Speaker 1: or at least four main things that had to be
Speaker 1: figured out to be able to do IVF. So I'm
Speaker 1: going to break it down into five just to make
Speaker 1: it a little bit more extra. Honestly, some of the
Speaker 1: sources that I read broke it up into like nine steps,
Speaker 1: and I'm like, that's not wrong. It's just like, let's
Speaker 1: chill with the detail.
Speaker 3: Okay. I mean, it's all a balance, right, It's.
Speaker 1: All we're going to conflate some Okay, Well, let's keep going,
Speaker 1: shall we. This is going to be kind of the
Speaker 1: main person of art in general. Art in general, and
Speaker 1: again I mentioned this in the last episode, but art
Speaker 1: is anything where eggs and embryos are being handled outside
Speaker 1: of the human bod, so this includes IVF. It includes
Speaker 1: IVF with ICSI or that interra cytoplasmic experm injection. It
Speaker 1: also even includes things like egg and embryo freezing, even
Speaker 1: without the in vitro fertilization part of it, and again
Speaker 1: those other less common procedures that people don't do as
Speaker 1: much anymore today. So how do the steps of this work?
Speaker 1: Because the steps for all of these different procedures start
Speaker 1: out in many cases the same, and I caveat this
Speaker 1: as of course, each cycle of IVF is going to
Speaker 1: be very individualized. So these are just like broad overview steps.
Speaker 1: But step one, and this is the step erin that
Speaker 1: didn't happen in your cycle, I guess in your description.
Speaker 1: And that's because it doesn't didn't always happen, though it
Speaker 1: pretty much always happens today. But step one is to
Speaker 1: overstimulate your ovaries to produce a whole ton of eggs. Right,
Speaker 1: So typically we produce and ovulate only one egg per
Speaker 1: menstrual cycle. Sometimes two and multiple eggs do start to
Speaker 1: develop during each menstrual cycle, but typically only one kind
Speaker 1: of comes all the way to the point of being ovulated.
Speaker 1: But for IVF to have a real chance at being successful,
Speaker 1: you have to boost this number in large part because
Speaker 1: there is attrition at every step in this cycle. So
Speaker 1: that process of overstimulation involves often a lot of needles,
Speaker 1: but definitely a lot of hormones. This is one of
Speaker 1: the first places where there's going to be a huge
Speaker 1: variety of variation in what the specifics of each algorithm
Speaker 1: are going to be, Like the specific drugs that are
Speaker 1: going to be used is going to be very person
Speaker 1: and patient and doctor specific. So I'm not going to
Speaker 1: get into all of that, but all of these are
Speaker 1: doing the same basic thing, all of these various hormones,
Speaker 1: and there's a number of different options that you can
Speaker 1: use trick your body into readying for ovulation a whole
Speaker 1: bunch of eggs at once, and this process often starts
Speaker 1: the month before in order to get your body ready
Speaker 1: to next month start this process of inducing a whole
Speaker 1: bunch of eggs to be ready for ovulation. That whole
Speaker 1: process often takes about two weeks, but again it starts before,
Speaker 1: like the month before, so we're talking already like a
Speaker 1: multiple week process. And then we get to step two
Speaker 1: and that is taking the eggs out. Yeah, so egg
Speaker 1: removal usually starts with yet another hormone injection the day
Speaker 1: or so before the egg removal process, and that's to
Speaker 1: help the eggs mature at the correct rate to be
Speaker 1: ready for aspiration. And the aspiration process takes place in
Speaker 1: usually a doctor's office or at a hospital under ultrasound guidance,
Speaker 1: which you mentioned aaron, where they take an ultrasound and
Speaker 1: a very long needle, hopefully under mild ivy sedation, though
Speaker 1: not always, and they use that to not always, it
Speaker 1: is standard practice to do ivy sedation, but I think
Speaker 1: in some cases, either for patient preference or for a
Speaker 1: number of reasons, they might not, and they might use
Speaker 1: like a regional anesthesia or something like that. Okay, yeah,
Speaker 1: but they use this really long needle to through the
Speaker 1: back of the vaginal wall aspirate out as many of
Speaker 1: those ripe and ready eggs as possible. While this is
Speaker 1: happening Step three, potentially your sperm donor or your partner
Speaker 1: is leaving their sperm sample or it is being defrosted
Speaker 1: from the freezer. These sperm have to then be washed
Speaker 1: and checked to pick the healthiest sperm. To pick the
Speaker 1: ones most likely to be able to fertilize the egg,
Speaker 1: and then comes the in vitro part step four. The
Speaker 1: eggs and the sperm unite, and this process can go
Speaker 1: one of two ways. So traditional IVF throws all of
Speaker 1: the sperm in with all of the eggs, and the
Speaker 1: sperm are going to fertilize the eggs in a similar
Speaker 1: way that they would in the reproductive tract. Or there's
Speaker 1: ICSI interra cydoplasmic sperm injection, which is fascinating and exactly
Speaker 1: what it sounds like. It's injecting using a very very
Speaker 1: very tiny needle, one single sperm directly into the egg.
Speaker 1: And then that fertilized egg is grown in culture for
Speaker 1: between three and five days until it reaches either the
Speaker 1: cleavage stage or the blasticist stage. And the final step,
Speaker 1: step five, is that this blasticist is transferred back into
Speaker 1: the uterus via a long catheter tube that goes up
Speaker 1: through the cerfax towards the top of the uterus and
Speaker 1: is deposited there either one or a number of blasticists.
Speaker 1: Most people then still need to keep taking some form
Speaker 1: of hormone, either injections or oral medications for the first
Speaker 1: few days or weeks of that potential pregnancy to try
Speaker 1: and get it to stick. This is especially true in
Speaker 1: US using frozen embryo cycles because you haven't just ovulated,
Speaker 1: and so you have no corpus lutium of which to speak,
Speaker 1: which is the hormone producing part of your ovary. That's
Speaker 1: IVF in like a very small nutshell, And shout out
Speaker 1: to pen Medicine's Patient facing website because I thought that
Speaker 1: was the most comprehensive but detailed breakdown of IVF that
Speaker 1: I found on a patient facing website.
Speaker 3: I have a couple questions if I met me, Okay,
Speaker 3: picking the sperm, what differentiates one sperm from another? Like
Speaker 3: you said, pick the good sperm or whatever you said,
Speaker 3: the highest quality.
Speaker 1: So that's a good question. It's mostly based on morphology,
Speaker 1: and so it's looking at the sperm under very high
Speaker 1: powered microscopes. And there are other techniques, like more advanced
Speaker 1: techniques that people might be piloting or that can be
Speaker 1: used in some cases, but in general, it's looking at
Speaker 1: the morphology of the sperm and that's how you make
Speaker 1: your decision, okay, on which sperm to pick?
Speaker 3: Okay, all right, so let's timeline this. So you you
Speaker 3: go in for fertility testing, you decide IVF is the
Speaker 3: next step. IVF either with or without ICSI you get
Speaker 3: seen by someone, hopefully not like six months later, although.
Speaker 1: I probably months later, but anyways, huh.
Speaker 3: Anyways, you you get seen by someone who starts this process,
Speaker 3: you start taking hormones how you know. So you mentioned
Speaker 3: that it's like a few weeks of hormones for stimulation
Speaker 3: and then egg retrieval and then like what is the time,
Speaker 3: like what is a typical cycle time?
Speaker 1: Yeah, a lot of times it's cited that that a
Speaker 1: typical cycle length of IVF is about six weeks. Okay,
Speaker 1: but like you just mentioned, that doesn't account for all
Speaker 1: of the other time. But that is typically about the
Speaker 1: length of one typical cycle. And again it might vary
Speaker 1: depending on what protocol you're using. There's like longer protocols
Speaker 1: and there's shorter protocols, because it all depends on what
Speaker 1: the side effects and things that you're trying to manage
Speaker 1: really are. How many blasticists, how many blastoicists at what stage?
Speaker 3: Okay, good question. The transfer, Yeah, that is a loaded question.
Speaker 1: So historically multiple blastoists were transferred almost always with IVF,
Speaker 1: and that's because I mentioned that there is attrition at
Speaker 1: every stage of the IVF process, and there really is.
Speaker 1: In fact, about ten percent of IVF cycles are stopped
Speaker 1: before you even get to egg retrieval, and then you'll
Speaker 1: get you know, X number of eggs. Some percent of
Speaker 1: those eggs won't be fertilized for one reason or another,
Speaker 1: and then some percentage of those fertilized eggs won't make
Speaker 1: it all the way to the blasticis stage, especially, and
Speaker 1: some of those blasticists won't manage to implant or therefore
Speaker 1: won't cause a pregnancy, so to kind of help counteract that,
Speaker 1: especially historically kind of actually before we got to blasticis
Speaker 1: stage culture, because it used to be more common that
Speaker 1: IVF happened at day three, which is when you're still
Speaker 1: in what's called the cleavage stage, then multiple blasticism would
Speaker 1: be transferred during that IVF process. Today, what's called single
Speaker 1: embryo transfer is actually a lot more common, and in
Speaker 1: some places it's like the recommended, if not required, thing
Speaker 1: to do. And that's because the risk of multiple pregnancies
Speaker 1: is significantly higher than the risk of a singleton pregnancy,
Speaker 1: that is, twin or triplet pregnancies are significantly higher risk
Speaker 1: than a singleton pregnancy. So in some cases, single embryo
Speaker 1: transfer has become the kind of norm in most places,
Speaker 1: But it all just depends on the situation. Because you
Speaker 1: can also imagine, especially in maybe an older couple who
Speaker 1: only has either a certain amount of money left to
Speaker 1: be able to do more transfers because each transfer costs money,
Speaker 1: or who only has a certain amount of time or
Speaker 1: a certain number of embryos that are left, then they
Speaker 1: might opt for a multiple embryo transfer. So there's kind
Speaker 1: of a lot. There's a lot that goes into that
Speaker 1: decision of how many embryos to transfer. The lowest risk
Speaker 1: in terms of like birth risk and risk of the
Speaker 1: pregnancy is going to be a single embryo transfer, but
Speaker 1: with multiple embryos you might have a greater chance at
Speaker 1: a live birth. Okay, I also just want to this
Speaker 1: is a little bit pedantic, but.
Speaker 3: I'm around It's okay. Yeah.
Speaker 1: IVF terminology pretty much universally refers to this process as
Speaker 1: embryo transfer, and that's fine. That has become the kind
Speaker 1: of norm. It's not accurate though, and I do feel like,
Speaker 1: especially as politicians start making decisions about what they think
Speaker 1: constitutes a person and who does not constitute a person.
Speaker 1: It's kind of important to point out that in this process,
Speaker 1: what we are talking about is a clump of cells
Speaker 1: that has been growing for five to six days. In
Speaker 1: culture media, this particular stage of development is it's fast.
Speaker 1: It's one cell layer thick that forms about a ball
Speaker 1: that has a fluid filled portion, and then one section
Speaker 1: of it that's about three to four cell layers thick.
Speaker 1: So in total we're talking about two hundred or so cells,
Speaker 1: and this little part of the blastocyst that's three to
Speaker 1: four cell layers thick. That is what will become an
Speaker 1: embryo upon implantation in the uterus. There's number of steps
Speaker 1: that have to happen. Usually around days nine to ten
Speaker 1: is when it is then becoming an embryo, which will
Speaker 1: then eventually develop into a fetus and then eventually a baby.
Speaker 1: And so I do think that these terms are kind
Speaker 1: of important because they help us conceptualize what we're really
Speaker 1: talking aboutte So I just want to point that out,
Speaker 1: but I'll probably say embryo transfer because that's what literally
Speaker 1: all the literature says.
Speaker 3: It's what all the literature says, but I think I
Speaker 3: was surprised, and I'm going to talk about this a
Speaker 3: little bit next episode, but not very much, but that globally,
Speaker 3: the definition of embryo varies quite a bit.
Speaker 1: That's interesting.
Speaker 3: So I believe it is Spain that the an embryo,
Speaker 3: it's only an embryo if it is implanted in the uterus,
Speaker 3: like the uterus is an essential part of that terminology,
Speaker 3: whereas I think that's not necessarily the case in a
Speaker 3: lot of other places, or at least like in casual usage.
Speaker 1: Yeah right, Yeah, it's kind of that difference in casual
Speaker 1: uses versus like strict scientific usage. But I just feel
Speaker 1: like it's important to point out. So, yeah, So that's
Speaker 1: like the main process of IVF, and I think you
Speaker 1: can lay it out and make it sound like, well,
Speaker 1: it's not that big of a deal. It's a huge deal.
Speaker 3: It's a huge deal. It's a huge process.
Speaker 1: It's a long process, and there are so many steps
Speaker 1: in which it can go poorly, and there are some
Speaker 1: really important risks that I think that we have to
Speaker 1: talk about with IVF, not just with IVF the process,
Speaker 1: but also with an IVF pregnancy. So there are risks
Speaker 1: associated with the surgical procedures involved in IVF, like the
Speaker 1: aspiration and potentially the embryo transfer as well. These risks
Speaker 1: are the kinds of risks associated with any surgical procedure,
Speaker 1: things like bleeding or infection or injury. These risks exist,
Speaker 1: they tend to be very small. The other major risk
Speaker 1: of IVF as a process is something called ovarian hyperstimulation
Speaker 1: syndrome or OHSS. This the risk I see cited usually
Speaker 1: as between one and five percent, but it really can vary.
Speaker 1: But this is a life threatening complication of that. In
Speaker 1: process of stimulating the ovaries to make a whole bunch
Speaker 1: of eggs all at once.
Speaker 3: What happens, What happens?
Speaker 1: Yeah, yeah, So symptom wise, what happens is significant abdominal bloating,
Speaker 1: ovarian enlargement acieties, which means fluid in the abdomen, and
Speaker 1: all of these things can result in significant electrolyte imbalances
Speaker 1: that can then also lead to decrease to urine output,
Speaker 1: kidney failure, and hypercoagulability respiratory distress. This can be very
Speaker 1: severe and life threatening. We don't fully understand the exact
Speaker 1: causes and mechanisms of this, but it's thought that it's
Speaker 1: a result of the ovary responding to this like supra
Speaker 1: physiologic doses of hormones signaling ovulation, that what it results
Speaker 1: in is really large scale vasodilation, so all of your
Speaker 1: blood vessels dilating, and that causes this increased capillary permeability.
Speaker 1: So basically all your vessels like get really wide and
Speaker 1: then permeable, so that fluid can shift from inside of
Speaker 1: your blood vessels to the outside of your blood vessels.
Speaker 1: And these fluid shifts are things that happen during pregnancy,
Speaker 1: but in a much different and slower fashion, And so
Speaker 1: this is something that's happening at a very fast and
Speaker 1: like super physiologic rate.
Speaker 3: Did this happen before IVF or before like you know,
Speaker 3: stimulating with hormones.
Speaker 1: So it's something that is specific to the process of
Speaker 1: ovarian stimulation, so it can happen in other ways, but
Speaker 1: it's totally like an iatrogenic like a we do this
Speaker 1: piece someone by stimulating the over east.
Speaker 3: Yeah, it's a twentieth century and beyond condition. Okay, okay, okay, interesting.
Speaker 1: One hundred percent. It can be prevented, and in some
Speaker 1: cases you can some tests can kind of try and
Speaker 1: help predict who might be at higher risk for ovarian
Speaker 1: hyperstimulation by looking at like things like ovarian reserve and
Speaker 1: seeing if someone is likely to be a really good
Speaker 1: responder versus a poor responder. So you can try and
Speaker 1: like predict that and then pick a protocol that puts
Speaker 1: you at lower risk of hypersimulation syndrome.
Speaker 3: And so what happens if you develop this, like how
Speaker 3: do you manage it?
Speaker 1: Often people have to be hospitalized, especially if it's severe,
Speaker 1: to be really closely monitored, have their fluid balance like
Speaker 1: checked and regulated and things like that. But it kind
Speaker 1: of just depends on the severity. Almost always what it
Speaker 1: means is it could mean like a cessation of the protocol,
Speaker 1: so like having to stop the IVF at the point
Speaker 1: that you're at. But almost always what it does mean
Speaker 1: is that if you were planning on a fresh embryo transfer,
Speaker 1: So we talked about that whole process of IVF, kind
Speaker 1: of assuming that at the end of it you take
Speaker 1: those embryos and put them directly into the uterus. But
Speaker 1: the other option is to freeze them. And so if
Speaker 1: someone develops ovarian hyperstimulation, then almost certainly they're going to
Speaker 1: have to have those embryos frozen because they have to
Speaker 1: have that condition managed before you can go on to
Speaker 1: then complete the steps of IVF.
Speaker 3: Okay, is it too early to ask about like rates
Speaker 3: of all of this or like breakdown of rates or
Speaker 3: and you know, like it's just I don't even know
Speaker 3: how to begin to ask these questions.
Speaker 1: It's such a good question, and it's funny because I
Speaker 1: have I kind of put a lot of that initially
Speaker 1: in our next episode, but I would be happy to
Speaker 1: talk about it at this episode as well too. But
Speaker 1: first I want to talk about the risks of IVF pregnancies.
Speaker 3: Yes, that's right.
Speaker 1: Sorry, because I think that this is something that isn't
Speaker 1: widely known, is that there are risks inherent to a
Speaker 1: pregnancy that's conceived with ART or IVF, and we don't
Speaker 1: fully understand the mechanisms behind this risk and some of
Speaker 1: these are still a little bit controversial. So out the
Speaker 1: outset pregnancy, and we're going to do a whole series
Speaker 1: on pregnancy. Don't worry. Pregnancy is a very risky state
Speaker 1: of being. It is physiologically incredibly demanding. It's associated with
Speaker 1: significant morbidity and mortality. It is not a riskless condition.
Speaker 1: But what's interesting is that it seems that IVF pregnancies
Speaker 1: are also a bit riskier than spontaneous conception pregnancies as well. Specifically,
Speaker 1: we see in some studies an up to fifty percent
Speaker 1: increased risk of hypertensive disorders including pre eclampsia, and an
Speaker 1: up to fifty percent increase risk of gestational diabetes, and
Speaker 1: these risks seem to differ between frozen embryo transfers compared
Speaker 1: to fresh embryo transfers. Again, we don't fully understand the
Speaker 1: mechanisms behind this, and it might have something to do
Speaker 1: with whether or not there is like a corpus lutium
Speaker 1: like I mentioned that's in the ovary, but we don't
Speaker 1: really know. There also seems to be an increased risk
Speaker 1: of abnormal placentation, and that's especially true in fresh embryo cycles.
Speaker 1: So that means that the placenta is either implanting in
Speaker 1: a place that's a little bit more risky in the uterus,
Speaker 1: like overlying the cervix or something like that, or in
Speaker 1: some cases invading a little bit too far into the
Speaker 1: uterus than is typical. And those kinds of abnormal placentations
Speaker 1: can put somebody at higher risk of hemorrhage during delivery
Speaker 1: or after delivery. And then there also seems to be
Speaker 1: an increased risk of severe outcomes like stroke or blood
Speaker 1: clots or ICU admission kind of in the postpartum period,
Speaker 1: which seem to be higher in iv F or ART
Speaker 1: pregnancies compared to spontaneous conception. And that does include after
Speaker 1: controlling for things like maternal age or comorbidities that might
Speaker 1: affect those risks.
Speaker 3: And is it the same for like gestational carriers versus.
Speaker 1: No, that's a very good question. I didn't see data
Speaker 1: on that specifically, but I would think so because all
Speaker 1: of the data just looks at IVF in general. But
Speaker 1: it's a really good that's a really good question. Just
Speaker 1: I don't know that we have enough data on that
Speaker 1: specific subset of IVF.
Speaker 3: Okay, I have. I have a few more questions about this, Okay,
Speaker 3: thank god to me. So what is I'm not asking
Speaker 3: for like specific numbers on all this, but like higher
Speaker 3: risk is relative? Like what is the degree? Is it
Speaker 3: substantially twice? You know?
Speaker 1: Like, yeah, it's a good nu it's a good question.
Speaker 1: I didn't see numbers for the like especially the later
Speaker 1: like maternal outcomes. I didn't find exact numbers on those.
Speaker 1: They just say slightly increased risk. For hypertensive disorders and
Speaker 1: gestational diabetes, we see like an up to fifty percent
Speaker 1: risk in some of the meta analyzes that I looked at,
Speaker 1: but a lot of the others they just say, like
Speaker 1: a slightly increased risk. I don't have a good number
Speaker 1: on it, okay, which is disappointing.
Speaker 3: One of the things that I'm wondering about is IVF
Speaker 3: pregnancies I would assume are more closely monitored throughout every
Speaker 3: step of the way. Does that mean that the likelihood
Speaker 3: of capturing some of these things is much higher? And
Speaker 3: so is that accounting possibly for some of these differences
Speaker 3: and risk.
Speaker 1: It's an interesting question. I don't I don't expect so, okay,
Speaker 1: because these are things that you're going to probably catch
Speaker 1: at delivery. If not, you know, maybe you hopefully you
Speaker 1: would catch it sooner in the cases of things like
Speaker 1: yer intensive disorders or gestational diabetes. But yeah, it's an
Speaker 1: interesting question. They definitely are monitor a lot more closely,
Speaker 1: but I don't know that that would necessarily result in
Speaker 1: an increased like a perceived increased risk that isn't a
Speaker 1: real risk. I guess if that makes sense, Okay, And
Speaker 1: we talked already about the risk of multiple pregnancies as
Speaker 1: a risk because of multiple blastocyst transfer. But what I
Speaker 1: also learned is that the rate of monozygotic twins, that is,
Speaker 1: like identical twins, is also significantly higher in IVF pregnancies.
Speaker 1: And I do have numbers on this, okay. The baseline
Speaker 1: rate in spontaneous conception pregnancies of identical twins is like
Speaker 1: zero point four percent. It's super low. It's between two
Speaker 1: and three percent in IVF. Wow. And we don't know
Speaker 1: what the mechanism is. The thought is maybe because in
Speaker 1: an identical twin pregnancy, what has to happen is that
Speaker 1: during the development the blasticist. Usually I always thought of
Speaker 1: it as the zygote. I don't think I even realized
Speaker 1: it could happen like post blasticis stage. But the blasticist
Speaker 1: or the zygote prior to that divides into two separate
Speaker 1: blasticists or two separate zygotes, rather than implanting two genetically
Speaker 1: different blasticists. And that's how you end up with identical twins.
Speaker 1: So we don't know what the mechanism of this is
Speaker 1: the thought is maybe it's related to the culture media
Speaker 1: that's used. Maybe it's related to the timing of the transfer. Again,
Speaker 1: absolute risks still very low, but significantly higher than the
Speaker 1: population level, which I think is so interesting.
Speaker 3: That's fascinating. Yeah, that's fascinating.
Speaker 1: And so you asked earlier aarin like, what's the what
Speaker 1: are some rates here? What are some numbers here? I
Speaker 1: don't have numbers on like the percent of attrition at
Speaker 1: every stage in this because that is going to vary
Speaker 1: so much person to person. There's not like a generalizability
Speaker 1: on like what's the chance that if you have X
Speaker 1: number of eggs or x number of embryos that you're
Speaker 1: going to be able to have a live birth. I
Speaker 1: don't have those numbers. It's going to vary a lot
Speaker 1: person to person. But there's obviously a huge question of
Speaker 1: like what's the overall success rate, Like if you go
Speaker 1: through this whole IVF process, what are the chances that
Speaker 1: you are going to have a baby at the end
Speaker 1: of it? Right, we don't have numbers on that either,
Speaker 1: And it is in part because it's going to vary
Speaker 1: so much person to person, but it's also in part
Speaker 1: because it's going to vary so much location to location.
Speaker 1: And there's some really interesting papers that I read that
Speaker 1: are looking at, like how do we even define what
Speaker 1: a success rate actually is? Are we talking about, like
Speaker 1: what is the live birth rate per cycle? And usually
Speaker 1: when we say per cycle, we're meaning like one embryo
Speaker 1: transfer or do we mean per retrieval where you might
Speaker 1: have to do multiple embryo transfers after that one retrieval?
Speaker 1: And also, are we talking about the success rate of
Speaker 1: like first berths or if people then are going through
Speaker 1: IVF to try and have a second child. Are we
Speaker 1: looking at total births? Are we combining fresh and frozen
Speaker 1: cycles or are we separating those two out there's so
Speaker 1: much nuance it's almost it's almost impossible. And that being said,
Speaker 1: people cite rates like most websites, most papers say like
Speaker 1: up to four twenty percent of cycles of IVF will
Speaker 1: result in a live birth, and that's a huge generalization,
Speaker 1: and if you look at global numbers, it's actually also
Speaker 1: a real overestimation because just we'll talk more about global
Speaker 1: numbers next episode. But what it has been reported to
Speaker 1: the institution, this large international institution that tries to monitor
Speaker 1: IVF globally in twenty twenty one, they reported about three
Speaker 1: million cycles of IVF and about seven hundred and fifty
Speaker 1: thousand babies A little bit more, okay, so that Aaron
Speaker 1: math is about twenty five percent as a success rate
Speaker 1: per cycle. The CDC has a very interesting calculator where
Speaker 1: you can input your individual data and it'll estimate your
Speaker 1: probability of a live birth, and you can break it
Speaker 1: down by like one two or more retrievals and one
Speaker 1: two or more transfers, which I think is really interesting
Speaker 1: and paints some more realistic picture, though it is still
Speaker 1: going to vary like place to place.
Speaker 3: That's fascinating because that is exactly what I was thinking.
Speaker 3: There should be something like that out there, because it's
Speaker 3: like there are so many variables that can affect all
Speaker 3: of this, and you could put in all of that,
Speaker 3: all of your your own data, and still like will
Speaker 3: that number be accurate high or like you know, it's yeah, yeah.
Speaker 1: It's it's interesting. We'll put a link to it. People
Speaker 1: can check it out. It's still just an estimate, but yeah,
Speaker 1: So that really is IVF in a nutshell, and.
Speaker 3: It's a pretty big nut It's a very large nut
Speaker 3: with a very large shell.
Speaker 1: And what I do want to just kind of say
Speaker 1: as we wrap up this episode, before we get into
Speaker 1: like the changes in technology and the industry that has
Speaker 1: been born of IVF, what I just want to take
Speaker 1: a moment to acknowledge is that I tried, but I
Speaker 1: still don't think that this medical description does a really
Speaker 1: good job of encompassing what it is like to go
Speaker 1: through this whole process, especially when you want a baby
Speaker 1: very badly. And so because of that, I really just
Speaker 1: want to say thank you again so much to everyone
Speaker 1: who took the time to write in and share your
Speaker 1: story and record yourselves and share it with us and
Speaker 1: with everyone that is listening, because one of the things
Speaker 1: that I hear over and over again is just how
Speaker 1: hard this experience is, regardless of what the outcome is,
Speaker 1: for so many people. And so I just want to
Speaker 1: say again, thank you so much for sharing your stories.
Speaker 1: And we'll get to talk a lot more about what
Speaker 1: IVF looks like on a larger scale and a less
Speaker 1: personal scale next episode.
Speaker 3: Yeah, well, said Aaron, I agree, I agree entirely. Like
Speaker 3: the I think one of the things that has been
Speaker 3: so incredible, like we keep saying thank you, thank you,
Speaker 3: thank you, But just also I think for us to
Speaker 3: hear the range of experiences, the range of ways that
Speaker 3: this can feel, is really powerful and really important to
Speaker 3: remember that it's not just one thing. It's like, there
Speaker 3: are commonalities and maybe that is reassuring or helps, you know,
Speaker 3: with sense of belonging or you know, not feeling so isolated.
Speaker 3: But then there are things where it's like, maybe that's
Speaker 3: not that way, and so it's like, I think that's
Speaker 3: That's what I just keep circling back to, is how
Speaker 3: important it is to understand that there's it's not just
Speaker 3: one thing, it's not just one feeling, it's not just
Speaker 3: one experience, and it's many, many, many, many different things.
Speaker 1: Yeah.
Speaker 3: Yeah, sources sources on that, Yeah, I have two main
Speaker 3: ones that I have several, but I have two main
Speaker 3: ones that I read for this. One is a book
Speaker 3: called The Pursuit of Parenthood by Margaret marsh and Wanda Ronner,
Speaker 3: and the other is a book by Sarah Ferber, Nikola
Speaker 3: Marx and Vera Mackey called IVF and Assisted Reproduction, a
Speaker 3: Global History.
Speaker 1: Like I mentioned in the last episode, a lot of
Speaker 1: my sources ended up overlapping for these episodes, but a
Speaker 1: few that were particularly helpful for this episode was that
Speaker 1: textbook that I used in last episode, which was the
Speaker 1: Johns Hopkins Manual of Gynecology and Obstetrics. There's a few
Speaker 1: chapters in there for details on the risks of IVF pregnancies.
Speaker 1: There was a paper in BMC Pregnancy and Childbirth from
Speaker 1: twenty twenty one untitled Assistive Reproductive Technology and Hypertensive Disorders
Speaker 1: of Pregnancy Systematic Review and meta Analysis, and a few
Speaker 1: other papers as well. We will post the sources from
Speaker 1: this episode and all of our episodes on our website,
Speaker 1: this podcast will Kill You dot com under the episodes tap.
Speaker 3: Thank you to Blowmobile for providing the music for this
Speaker 3: episode and all of our episodes.
Speaker 1: Thank you to Leanna Scuialacci and Tom Briy Fogel for
Speaker 1: the incredible audio mixing.
Speaker 3: Thank you too, exactly right, and thank.
Speaker 1: You to you listeners. We hope that this is a
Speaker 1: fun episode. We hope you've got enough in you for
Speaker 1: one more episode, because we've got it coming to you.
Speaker 3: We've got it coming yeah next week, I believe, so
Speaker 3: you know, stay tuned. Yeah, and a big thank you,
Speaker 3: as always to our fantastic patrons you know, thank you,
Speaker 3: thank you, thank you. Your support means everything so much.
Speaker 1: Thank you.
Speaker 3: Until next time, wash your hands.
Speaker 1: You filled the animals.
Speaker 3: Um um.
Speaker 4: Um um um um