Selected Podcast
40 years of success in the IVF lab at RSC
For 40 years RSC has been a pioneer in the fertility space. As we look back we remember where we started and where we are today.
Featuring:
Kristen Ivani, PhD, HCLD
Dr. Kristen Ivani has served as the laboratory director at Reproductive Science Center of the San Francisco Bay Area since 1989. She is a board-certified high-complexity clinical laboratory director in the disciplines of embryology and andrology and an inspector for the College of American Pathologists Reproductive Laboratory Accreditation Program. Dr. Ivani is also a member of the American Society for Reproductive Medicine, the International Embryo Transfer Society, the American Association of Bioanalysts and several scientific honor societies. Her areas of interest include embryo cryopreservation, in vitro fertilization, gamete micromanipulation, patient education, and preimplantation genetic diagnosis (PGD). Transcription:
Maggie McKay (Host): As a couple, planning a family should be a joyful journey. But when fertility issues arise, making it difficult to conceive, it can be stressful to say the least. Our guest today is Dr. Kristen Ivani, who is a retired IVF lab director with more than 30 years of success in the IVF Lab at the Reproductive Science Center of the San Francisco Bay Area.
Host: This is Fertile Edge, a podcast from the Reproductive Science Center of the San Francisco Bay Area. I'm Maggie McKay. Thank you so much for being here, doctor. It's so exciting to talk to you about this because I don't know that much about it, and I'm interested to learn more about embryologists, what you do. So, thank you for making the time to be here. To start, what is an embryologist and what do you do?
Dr Kristen Ivani: Well, thank you so much for having me, Maggie. It's a real pleasure to be here. An embryologist is a scientist usually with a background in the biological life or animal sciences who's responsible for taking care of the sperm and eggs from the time they are received in the laboratory until they are embryos ready for implantation in the uterus. The embryology team is also responsible for maintaining laboratory equipment, the lab environment, the cryo storage inventory, and performing all of the technical procedures that go into helping patients complete their families.
Host: And how did you get into this field more than 30 years ago?
Dr Kristen Ivani: Well, my background, like most early embryologists, is in animal science, specifically in animal reproduction. And as many of us moved into the clinical IVF arena after graduate school, we were able to apply some of the animal research tools to human embryology.
Host: What was the embryology lab like at that time?
Dr Kristen Ivani: It seems like forever ago. But many of our early IVF programs were located in hospitals and the embryology labs were often carved out of existing space, sometimes even in closets. We didn't know nearly as much about air handling systems and the importance of air quality for growing embryos as we do today. And often, we had no control over the air quality coming into our early labs. IVF cycles were quite simple compared to today's IVF cycle. There were a few stimulation protocols and clinics often made their own culture media tools and even supplies.
A patient had an egg retrieval. We mixed the sperm and eggs together in a dish or a test tube by what we call conventional insemination and left them alone in the lab over night. The next morning or day one, we checked for evidence of fertilization and separated the normally fertilized zygotes or one-cell embryos from the abnormally fertilized and unfertilized eggs. The following day, which is day two, we usually did a fresh transfer at the two to four-cell stage, froze the rest of the embryos, and the cycle was done. We are actually happy to see 30% pregnancy rates in those days. And as amazing as that was, we were still frustrated that we were not able to help more patients have their families.
Host: How has the embryology field changed in the past 30 years? What new treatments became available and how did they influence patient care?
Dr Kristen Ivani: Wow, there have been so many advances, Maggie. We first moved from day two onto day three, transfers and freezing, which allowed an additional day of embryo selection before transfer time. Soon after that came a procedure known as assisted hatching, in which we made a small opening in the zona pellucida, which is the protective coating around the embryo. That procedure was initially thought to improve implantation rates. But over time, the results were debatable. The optimization of embryo culture media has enabled us to grow embryos out to the blastocyst stage now, which allows for better synchrony with the uterus for fresh as well as frozen embryo transfers. This important step led to the development of elective single embryo transfer, also known as eSET. At RSC, almost 100% of transfers are done with just one embryo. This step drastically reduced the number of twin and triplet pregnancies, making pregnancy and delivery safer for both the mother and the baby.
An ultrarapid freezing method known as vitrification was developed, which resulted in better embryo survival rates and embryo quality after freezing when compared to the slower, older freezing method we used to use. Blastocyst embryo survival at RSC is close to 99%. But one of the most important advances in the embryology lab is known as ICSI or intracytoplasmic sperm injection. This technique was developed in Brussels and the first ICSI baby was born in 1992. This technique involves using a very fine microneedle to actually inject a single sperm cell into the egg cytoplasm. This was initially developed to help men with poor sperm quality, meaning poor sperm count or the number of sperm present; poor sperm motility, how they are or are not swimming; or poor sperm morphology, which is the shape of the sperm. And some men, unfortunately, may have more than one of these issues. ICSI is also used for men who do not ejaculate sperm either because of very low sperm production or because of some blockage that prevents the sperm from being ejaculated. This procedure enabled men to become parents using their own sperm. And previous to this, donor sperm was likely their only option. All of these developments played a role in the introduction of new technologies that are commonly used in the IVF lab today.
Host: Dr. Ivani, what are some of the newer technologies? And have these technologies improved workflow and efficiency, as well as improved a patient's chances of taking home a baby?
Dr Kristen Ivani: Well, Maggie, it took us a while, but extending the vitrification process from embryos to eggs or oocytes opened many new opportunities for patients to create their families. Oocytes can be frozen now for fertility preservation in the case of a patient wishing to start her family later, but wanting to freeze her eggs while she's young. Oocyte freezing has been used extensively for fertility preservation for patients beginning any medical treatment that may affect their egg quality. And oocyte freezing absolutely revolutionized oocyte donation treatment. Eggs can be frozen and shipped all over the world through an increasing number of egg banks. This eliminated the need to synchronize the donors and the recipient cycles. It allowed for much more extensive donor selection. It resulted in often fewer embryos left over after the patient's family was complete. And the process now provides success rates that are comparable to using fresh donors.
Pre-implantation genetic testing or PGT has been discussed in several RSC podcasts. And it's a tool that we use to improve the implantation success of the embryo to be transferred. This involves growing the embryos to the blastocyte stage, either day five, day six, or even day seven, and biopsying five to seven cells from the trophectoderm, which is the part of the embryo that becomes the placenta. After biopsy, the embryo is assigned a number and is frozen individually. The small piece of trophectoderm tissue is sent to the genetics lab for analysis. And the genetics lab then sends a report back to the clinic that lets us know which embryos are chromosomally or genetically normal for transfer. PGT has been shown to be most helpful for patients over 37 years of age, as well as patients with a known genetic condition such as Tay-Sachs or cystic fibrosis.
Host: That is so amazing that they can be flown all over the world. I've never ever heard that. I did not know that. And what do you see emerging in the field of embryology?
Dr Kristen Ivani: Well, we're on the cusp of great change again, Maggie. The field of embryology is evolving even more with the goals always being improved outcomes for patients and shorter time to pregnancy while at the same time maintaining safety and efficiency.
Currently, research is being done to automate certain procedures in the lab, such as ICSI or vitrification. This would help with repeatability and consistency. A process known as electronic witnessing is being used to minimize the risk of identification errors in the laboratory. Methods of non-invasive PGT where the embryo is not actually biopsied, but rather the culture medium surrounding the embryo is sampled for DNA markers, is currently being investigated as well. And artificial intelligence or AI plus machine learning are being used in embryology research to analyze millions of data points in minutes or even seconds to identify embryo development patterns that are associated with positive outcomes to select the best sperm for ICSI based on motility and morphology, and even to identify genetic characteristics that will improve implantation. AI is also being combined with our electronic medical record or EMR, which will enable us to evaluate laboratory data in real time and react to any deviations much more quickly.
Host: I've heard that they spin, is that the embryos or the sperm or what, so you could choose a son or a daughter, female or male, do they still do that?
Dr Kristen Ivani: It's not commonly done anymore, Maggie. That was a procedure that was performed many years ago where we were putting the sperm sample on a gradient that separated the X-bearing from the Y-bearing sperm. There's also a procedure known as flow cytometry that was being used to separate X and Y-bearing sperm. Those aren't used so much in clinical practice anymore, especially now since many patients are moving toward PGT where they're able to actually select the sex of the embryo with virtually a hundred percent confidence.
Host: Wow, that sounds so science fiction, doesn't it? I mean, just think of when you started 30 years ago, did you ever think that these things would be possible?
Dr Kristen Ivani: No, I remember so many times thinking, "What happens when we have eggs collected and the male partner was unable to produce a sperm sample?" We had to discard the eggs or hopefully if he could do it the next day, we could use that sperm and now we're able to freeze the eggs and it's taken so much pressure off the partners, both partners actually. And I would say that's probably been one of the most helpful things for patients in the last 30 years, egg freezing for sure.
Host: And when someone has leftover embryos, so to speak, do they ever donate them?
Dr Kristen Ivani: Yes, patients do have the opportunity to donate their embryo. They can donate their embryos to another patient. They also have the opportunity to donate their embryos to research. And finally, they have the opportunity to release their embryos to the IVF lab. It can be used for training purposes and quality control purposes that will help the next generation of embryologists and patients.
Host: That's amazing. We've heard a lot of advancements in the field. What do you see as the biggest challenges facing embryology today?
Dr Kristen Ivani: Well, this is an easy question to answer, unfortunately. As fertility treatments and access to care increase, the biggest challenge we face in the embryology lab today is finding and training enough embryologists and lab leaders to carry out all of this exciting work. You might think that all of this automation and AI may render embryologists unnecessary. And while some of these new technologies are currently in use, widespread of others may still be a long way off in the future. But remember, we used to think that about egg freezing and PGT years ago, right? And they're everyday lab procedures today.
Fortunately, there are a number of embryology training schools around the world today that are helping to train the embryologists of the future. Many IVF programs offer financial support to their existing staff to obtain advanced degrees and specialized training. And as a group, we embryologists are also attempting to reach out to undergraduate programs to raise awareness on what an awesome field this is to go into. Our emerging embryology leaders can look forward to advances that we can only dream about today.
Host: I think it would be really exciting to do that for a living and maybe just students don't know about it or hadn't considered it.
Dr Kristen Ivani: I think you're absolutely right about that. And that is a responsibility that we are taking on now to bring new people into the field because they're just not aware of it as a career. And when I started, most people were animal scientists and we were doing all these techniques in the lab every day, but there weren't very many human IVF labs to go into. Now, we have so many lab opportunities and not enough people.
Host: Wow. Isn't that amazing? Wow. Well, I hope that changes quickly, Dr. Ivani, anything else you'd like to share in closing?
Dr Kristen Ivani: Well, I have to say, Maggie, this has been an exciting, challenging, and fun journey to lead RSC's IVF Lab for over 30 years. It was a journey that was both an honor and very humbling at the same time. And I wanted to share to close a quote from Dr. George Corner, who is an American physician, an embryologist and a pioneer of the contraceptive pill. In addition, he played a key role in the discovery of progesterone. I came across this quote while writing my PhD dissertation. And 30 years later, Dr. Corner still sums it up for me with this thought: "The fertilization of an egg by a sperm cell is one of the greatest wonders of nature, an event in which magnificently small fragments of life are driven by cosmic forces toward their appointed end, the growth of a living being. As a spectacle, it can be compared only with an eclipse of the sun or the eruption of a volcano. It is in fact the most common and nearest of nature's cataclysms, and yet it is very seldom observed because it occurs in a realm most people never see. And in the embryology lab, we get to see that every single day." And what could be better than that, Maggie?
Host: This has been so fascinating and encouraging for couples facing fertility issues. Thank you so much for sharing your knowledge and being here today, Dr. Ivani.
Dr Kristen Ivani: Thank you, Maggie. It was great to be here and we look forward to the future of embryology.
Host: Again, that's Dr. Kristen Ivani. To find out more or to make an appointment, go to rscbayarea.com/treatments/ivf/lab. If you found this podcast helpful, please share it on your social channels and check out the full podcast library for topics of interest to you. This is Fertile Edge, a podcast from the Reproductive Science Center of the San Francisco Bay Area. I'm Maggie McKay. Thanks for listening.
Maggie McKay (Host): As a couple, planning a family should be a joyful journey. But when fertility issues arise, making it difficult to conceive, it can be stressful to say the least. Our guest today is Dr. Kristen Ivani, who is a retired IVF lab director with more than 30 years of success in the IVF Lab at the Reproductive Science Center of the San Francisco Bay Area.
Host: This is Fertile Edge, a podcast from the Reproductive Science Center of the San Francisco Bay Area. I'm Maggie McKay. Thank you so much for being here, doctor. It's so exciting to talk to you about this because I don't know that much about it, and I'm interested to learn more about embryologists, what you do. So, thank you for making the time to be here. To start, what is an embryologist and what do you do?
Dr Kristen Ivani: Well, thank you so much for having me, Maggie. It's a real pleasure to be here. An embryologist is a scientist usually with a background in the biological life or animal sciences who's responsible for taking care of the sperm and eggs from the time they are received in the laboratory until they are embryos ready for implantation in the uterus. The embryology team is also responsible for maintaining laboratory equipment, the lab environment, the cryo storage inventory, and performing all of the technical procedures that go into helping patients complete their families.
Host: And how did you get into this field more than 30 years ago?
Dr Kristen Ivani: Well, my background, like most early embryologists, is in animal science, specifically in animal reproduction. And as many of us moved into the clinical IVF arena after graduate school, we were able to apply some of the animal research tools to human embryology.
Host: What was the embryology lab like at that time?
Dr Kristen Ivani: It seems like forever ago. But many of our early IVF programs were located in hospitals and the embryology labs were often carved out of existing space, sometimes even in closets. We didn't know nearly as much about air handling systems and the importance of air quality for growing embryos as we do today. And often, we had no control over the air quality coming into our early labs. IVF cycles were quite simple compared to today's IVF cycle. There were a few stimulation protocols and clinics often made their own culture media tools and even supplies.
A patient had an egg retrieval. We mixed the sperm and eggs together in a dish or a test tube by what we call conventional insemination and left them alone in the lab over night. The next morning or day one, we checked for evidence of fertilization and separated the normally fertilized zygotes or one-cell embryos from the abnormally fertilized and unfertilized eggs. The following day, which is day two, we usually did a fresh transfer at the two to four-cell stage, froze the rest of the embryos, and the cycle was done. We are actually happy to see 30% pregnancy rates in those days. And as amazing as that was, we were still frustrated that we were not able to help more patients have their families.
Host: How has the embryology field changed in the past 30 years? What new treatments became available and how did they influence patient care?
Dr Kristen Ivani: Wow, there have been so many advances, Maggie. We first moved from day two onto day three, transfers and freezing, which allowed an additional day of embryo selection before transfer time. Soon after that came a procedure known as assisted hatching, in which we made a small opening in the zona pellucida, which is the protective coating around the embryo. That procedure was initially thought to improve implantation rates. But over time, the results were debatable. The optimization of embryo culture media has enabled us to grow embryos out to the blastocyst stage now, which allows for better synchrony with the uterus for fresh as well as frozen embryo transfers. This important step led to the development of elective single embryo transfer, also known as eSET. At RSC, almost 100% of transfers are done with just one embryo. This step drastically reduced the number of twin and triplet pregnancies, making pregnancy and delivery safer for both the mother and the baby.
An ultrarapid freezing method known as vitrification was developed, which resulted in better embryo survival rates and embryo quality after freezing when compared to the slower, older freezing method we used to use. Blastocyst embryo survival at RSC is close to 99%. But one of the most important advances in the embryology lab is known as ICSI or intracytoplasmic sperm injection. This technique was developed in Brussels and the first ICSI baby was born in 1992. This technique involves using a very fine microneedle to actually inject a single sperm cell into the egg cytoplasm. This was initially developed to help men with poor sperm quality, meaning poor sperm count or the number of sperm present; poor sperm motility, how they are or are not swimming; or poor sperm morphology, which is the shape of the sperm. And some men, unfortunately, may have more than one of these issues. ICSI is also used for men who do not ejaculate sperm either because of very low sperm production or because of some blockage that prevents the sperm from being ejaculated. This procedure enabled men to become parents using their own sperm. And previous to this, donor sperm was likely their only option. All of these developments played a role in the introduction of new technologies that are commonly used in the IVF lab today.
Host: Dr. Ivani, what are some of the newer technologies? And have these technologies improved workflow and efficiency, as well as improved a patient's chances of taking home a baby?
Dr Kristen Ivani: Well, Maggie, it took us a while, but extending the vitrification process from embryos to eggs or oocytes opened many new opportunities for patients to create their families. Oocytes can be frozen now for fertility preservation in the case of a patient wishing to start her family later, but wanting to freeze her eggs while she's young. Oocyte freezing has been used extensively for fertility preservation for patients beginning any medical treatment that may affect their egg quality. And oocyte freezing absolutely revolutionized oocyte donation treatment. Eggs can be frozen and shipped all over the world through an increasing number of egg banks. This eliminated the need to synchronize the donors and the recipient cycles. It allowed for much more extensive donor selection. It resulted in often fewer embryos left over after the patient's family was complete. And the process now provides success rates that are comparable to using fresh donors.
Pre-implantation genetic testing or PGT has been discussed in several RSC podcasts. And it's a tool that we use to improve the implantation success of the embryo to be transferred. This involves growing the embryos to the blastocyte stage, either day five, day six, or even day seven, and biopsying five to seven cells from the trophectoderm, which is the part of the embryo that becomes the placenta. After biopsy, the embryo is assigned a number and is frozen individually. The small piece of trophectoderm tissue is sent to the genetics lab for analysis. And the genetics lab then sends a report back to the clinic that lets us know which embryos are chromosomally or genetically normal for transfer. PGT has been shown to be most helpful for patients over 37 years of age, as well as patients with a known genetic condition such as Tay-Sachs or cystic fibrosis.
Host: That is so amazing that they can be flown all over the world. I've never ever heard that. I did not know that. And what do you see emerging in the field of embryology?
Dr Kristen Ivani: Well, we're on the cusp of great change again, Maggie. The field of embryology is evolving even more with the goals always being improved outcomes for patients and shorter time to pregnancy while at the same time maintaining safety and efficiency.
Currently, research is being done to automate certain procedures in the lab, such as ICSI or vitrification. This would help with repeatability and consistency. A process known as electronic witnessing is being used to minimize the risk of identification errors in the laboratory. Methods of non-invasive PGT where the embryo is not actually biopsied, but rather the culture medium surrounding the embryo is sampled for DNA markers, is currently being investigated as well. And artificial intelligence or AI plus machine learning are being used in embryology research to analyze millions of data points in minutes or even seconds to identify embryo development patterns that are associated with positive outcomes to select the best sperm for ICSI based on motility and morphology, and even to identify genetic characteristics that will improve implantation. AI is also being combined with our electronic medical record or EMR, which will enable us to evaluate laboratory data in real time and react to any deviations much more quickly.
Host: I've heard that they spin, is that the embryos or the sperm or what, so you could choose a son or a daughter, female or male, do they still do that?
Dr Kristen Ivani: It's not commonly done anymore, Maggie. That was a procedure that was performed many years ago where we were putting the sperm sample on a gradient that separated the X-bearing from the Y-bearing sperm. There's also a procedure known as flow cytometry that was being used to separate X and Y-bearing sperm. Those aren't used so much in clinical practice anymore, especially now since many patients are moving toward PGT where they're able to actually select the sex of the embryo with virtually a hundred percent confidence.
Host: Wow, that sounds so science fiction, doesn't it? I mean, just think of when you started 30 years ago, did you ever think that these things would be possible?
Dr Kristen Ivani: No, I remember so many times thinking, "What happens when we have eggs collected and the male partner was unable to produce a sperm sample?" We had to discard the eggs or hopefully if he could do it the next day, we could use that sperm and now we're able to freeze the eggs and it's taken so much pressure off the partners, both partners actually. And I would say that's probably been one of the most helpful things for patients in the last 30 years, egg freezing for sure.
Host: And when someone has leftover embryos, so to speak, do they ever donate them?
Dr Kristen Ivani: Yes, patients do have the opportunity to donate their embryo. They can donate their embryos to another patient. They also have the opportunity to donate their embryos to research. And finally, they have the opportunity to release their embryos to the IVF lab. It can be used for training purposes and quality control purposes that will help the next generation of embryologists and patients.
Host: That's amazing. We've heard a lot of advancements in the field. What do you see as the biggest challenges facing embryology today?
Dr Kristen Ivani: Well, this is an easy question to answer, unfortunately. As fertility treatments and access to care increase, the biggest challenge we face in the embryology lab today is finding and training enough embryologists and lab leaders to carry out all of this exciting work. You might think that all of this automation and AI may render embryologists unnecessary. And while some of these new technologies are currently in use, widespread of others may still be a long way off in the future. But remember, we used to think that about egg freezing and PGT years ago, right? And they're everyday lab procedures today.
Fortunately, there are a number of embryology training schools around the world today that are helping to train the embryologists of the future. Many IVF programs offer financial support to their existing staff to obtain advanced degrees and specialized training. And as a group, we embryologists are also attempting to reach out to undergraduate programs to raise awareness on what an awesome field this is to go into. Our emerging embryology leaders can look forward to advances that we can only dream about today.
Host: I think it would be really exciting to do that for a living and maybe just students don't know about it or hadn't considered it.
Dr Kristen Ivani: I think you're absolutely right about that. And that is a responsibility that we are taking on now to bring new people into the field because they're just not aware of it as a career. And when I started, most people were animal scientists and we were doing all these techniques in the lab every day, but there weren't very many human IVF labs to go into. Now, we have so many lab opportunities and not enough people.
Host: Wow. Isn't that amazing? Wow. Well, I hope that changes quickly, Dr. Ivani, anything else you'd like to share in closing?
Dr Kristen Ivani: Well, I have to say, Maggie, this has been an exciting, challenging, and fun journey to lead RSC's IVF Lab for over 30 years. It was a journey that was both an honor and very humbling at the same time. And I wanted to share to close a quote from Dr. George Corner, who is an American physician, an embryologist and a pioneer of the contraceptive pill. In addition, he played a key role in the discovery of progesterone. I came across this quote while writing my PhD dissertation. And 30 years later, Dr. Corner still sums it up for me with this thought: "The fertilization of an egg by a sperm cell is one of the greatest wonders of nature, an event in which magnificently small fragments of life are driven by cosmic forces toward their appointed end, the growth of a living being. As a spectacle, it can be compared only with an eclipse of the sun or the eruption of a volcano. It is in fact the most common and nearest of nature's cataclysms, and yet it is very seldom observed because it occurs in a realm most people never see. And in the embryology lab, we get to see that every single day." And what could be better than that, Maggie?
Host: This has been so fascinating and encouraging for couples facing fertility issues. Thank you so much for sharing your knowledge and being here today, Dr. Ivani.
Dr Kristen Ivani: Thank you, Maggie. It was great to be here and we look forward to the future of embryology.
Host: Again, that's Dr. Kristen Ivani. To find out more or to make an appointment, go to rscbayarea.com/treatments/ivf/lab. If you found this podcast helpful, please share it on your social channels and check out the full podcast library for topics of interest to you. This is Fertile Edge, a podcast from the Reproductive Science Center of the San Francisco Bay Area. I'm Maggie McKay. Thanks for listening.