What if you could prevent passing on a genetic condition like familial Alzheimer’s disease to your child? In this episode of Youngtimers Ask the Experts, Lindsay Hohsfield speaks with Dr. Sinem Karipcin to learn about one option: in vitro fertilization with pre-implantation genetic testing (IVF with PGT).

Dr. Karipcin breaks down the science, process, and emotional journey behind this advanced reproductive technology, explaining:

How IVF with PGT works, from ovarian stimulation to embryo transfer
What “non-disclosure” testing means for those who don’t want to know their genetic status
The costs, timelines, and success rates families can expect
Differences between various PGT methods

At Youngtimers, we respect all reproductive options, whether that be natural pregnancy and conception, adoption, deciding not to have children, or pursuing assisted reproductive technology. Whether you’re considering IVF, weighing other reproductive options, or simply looking to learn, this episode provides a compassionate and informative guide to empower your family planning decisions.

Dr. Sinem Karipcin is a fertility specialist at Columbia University Fertility Center and Assistant Professor of Obstetrics and Gynecology at Columbia University. As Director of the Pre-Pregnancy Genetics Program, she focuses on reducing the risk of genetically heritable diseases and specializes in pre-implantation genetic testing.

This conversation reflects the unique perspectives and experiences shared with us on January 26, 2021. Insights from experts like Dr. Karipcin help us navigate the unique challenges we face as members of this community.

This transcript has been edited for clarity and readability. For the full interview, watch the video.

LINDSAY: Dr. Karipcin, thank you so much for joining us.

KARIPCIN: Thank you so much, Lindsay, for having me. It's an honor to speak to Youngtimers and thank you for the invitation.

LINDSAY: I think we should start by saying that at Youngtimers, we aim to educate the familial Alzheimer's disease community, so they can make the most informed decisions about their future and care. Our goal is to inform.

Dr. Sinem Karipcin is now Director of Pre-Pregnancy Genetics Program at Columbia University Irving Medical Center.
Learn more about Dr. Karipcin.

KARIPCIN: I'm glad you specified that, because for the Pre-Pregnancy Genetics Program, our goal is to reach autosomal carriers of genetic diseases, and inform them about their reproductive possibilities. The reproductive possibilities are not only limited to pre-implantation genetic testing. It's just one of the options.

We have genetic counselors from Colombia that work with us, so patients may learn not only about their option for PGT, but also other options: no testing, no children, adoption, donor egg, donor sperm. All of these are possible.

LINDSAY: Yes, and genetic counseling is so important to this discussion. Can you talk at a high level about what's involved with IVF with PGT?

KARIPCIN: Great question. This is what I talk with my patients [about] every day.

As of 2021, the process for IVF with PGT looks like this.

Extended culture: We will be bringing embryos to the one week culture stage (a blastocyst)
Embryo biopsy (sometimes): Testing for the chromosome numbers and/or analyzing for family-specific mutations which can be indicative of some genetic conditions.
Vitrification (sometimes): Flash freezing of the embryos or eggs
Long term storage (sometimes): They don't have a shelf life. They could be stored five years, 10 years, 15 years.
Single embryo transfer: IVF has historically been known to result in multiples (twins, triplets) but that is no longer the case. With PGT, it is the guideline to transfer just one embryo at a time.

LINDSAY: OK. I've seen many different abbreviations for this. There's preimplantation genetic diagnosis, which is PGD. There's preimplantation genetic testing, PGT. Then there's pre-implantation genetic testing (monogenic), or PGT-M. Are these the same thing?

KARIPCIN: It's all under the PGT umbrella now. WHO [World Health Organization] released nomenclature 2017.

Under PGT, there are subclassifications.

PGT-A (previously called PGS, or pre-implantation genetic screening). The A stands for aneuploidy, which means looking for chromosome numbers. What's a known condition that we are looking for chromosome numbers? Down syndrome.
PGT-M stands for monogenic. That’s what we are talking about today, because we are looking for a single gene condition. it doesn't mean only one gene; you could be checking for five or six mutations. And it could be more conditions, but you're looking for things that are inherited because of a change in one variant in a single gene.

As we are doing the PGT-M, actually, we are looking at the chromosome numbers from the same biopsy. All the patients who are doing PGT-M, we encourage doing PGT-A. At Columbia University, very likely when they come to us, we are going to do these cases with PGT-A, because the same biopsy could go for the analysis of chromosome numbers as well.
PGT-SR is to look for structural (chromosomal) rearrangements. Let's say if somebody had a balanced translocation that does not affect their health, but it could impact their offspring. That's looked at with PGT-SR. The audience here probably would not be interested in hearing about that.
PGT-HLA. The HLA stands for Human Leukocyte Antigen. is when we are looking for a tissue match. For example, a child’s sibling has sickle cell disease, and we are looking for a bone marrow or stem cell transplant.

[For familial Alzheimer's disease], we're interested in the first two types, PGT-A and PGT-M.

PGD stands for pre-implantation genetic diagnosis, and it now includes PGT-M as well as translocations, and chromosome exchanges.

LINDSAY: Thanks for clarifying that. With PGT-M, is there anything that has to happen before the IVF process starts?

KARIPCIN: Yes. Before the IVF process starts, there is a setup called parental allele characterization. This is the direct mutation analysis. It's just like checking for the presenilin mutation. Looking for the surrounding markers, that's going to be telling you what's close to here.

It's like you want to go to an address. For example, our office is at 5 Columbus Circle. I could tell you there is a Starbucks downstairs from us, and there is a Nordstrom on the other side of us. This is just telling you what's in the neighborhood. You find the address.

This is the same for PGT-M. The direct mutation analysis and the markers that are family specific to, for sure, know we are accurately identifying the mutation. And the diagnostic techniques that are performed, these actually are society's best practice guidelines to do with linkage analysis and it should be always performed.

But with the diagnostic techniques that we are using right now, just by even giving the address –by just saying presenilin mutation–a majority of the lab techniques will be able to give us more than 98 percent accuracy, but still it's important to follow the guidelines and to do family specific setup.

Majority of the labs will be amplifying this DNA. The concern is during that amplification, the genetic information drops, and the area that you're interested is failing to amplify.

Again, this risk is getting low and low as diagnostic techniques are improving, but we want to also look at the surrounding markers. We don't want to be only one time sure, we want to be several times sure- at least three times sure, sometimes six times sure- that it's really detecting the mutation of interest, and that's the purpose of going through IVF for many couples.

The setup would be asking for some family members. Sometimes it could be a report of having a family member and a genetic testing report for non-disclosure testing that could be sufficient. It could be really depending on the technique that we are using.

In the case that there are no family members available, it could be possible to do the setup after the IVF is done, but this is the more traditional setup, including the family members testing.

And this takes about 5 to 8 weeks from the submission of all the required DNA, which feels like forever sometimes. This is at the moment what technology is, but we could be speaking about this two years later and it could be that green light process could be even shorter.

LINDSAY: OK. So after the family specific setup, what happens?

Now, it’s the IVF process. How does the IVF process happen? Once we get the green light from the lab, we’re ready for ovarian stimulation.

In a natural cycle, the process of IVF is the same since 1982, not much has changed.

Follicles are the houses of the eggs. They each have one egg in them, as well as some cells that help support the growth of the egg.

In a natural cycle, there is a single dominant follicle and the rest of the follicles, they die off. In an IVF cycle, instead of that one follicle there are multiple dominant follicles, right? We are trying to grow multiple eggs at the same time.

The way that we do that is by giving injections of the gonadotropins, the follicle stimulating hormone, and LH hormone.These are naturally occurring hormones that our body makes, and we tell our patients how much they should be taking and our patients administer every day. Then it's 10 to 14 days of ovarian stimulation as followed by the egg retrieval. The time of the egg retrieval will be decided based on how the follicles do when they grow, the estrogen levels.

Initially, the patients will be coming every 3 to 4 days and close to the egg retrieval, they could be coming every day.

On the egg retrieval day, we are under sterile technique. The patient is receiving IV sedation, and we are collecting the follicular fluid and we are passing it to our embryologist.

We zoom into a follicle and we aspirate the egg from it. There are no incisions involved. The needle is teeny tiny. It goes through the vaginal wall, and we are aspirating the follicular fluid.

Then, the sperm is going to be injected inside the egg, and the cells around the egg will be cleaned. The reason for that is, we don't want the data from the cells surrounding the egg, and we don't want the data from a bunch of sperm that's trying to fertilize the egg. We only want the information from the embryo that forms. Intracytoplasmic Sperm Injection (ICSI) will be performed with every egg retrieval case.

About 30 to 50 percent of the embryos will make it to this one week stage. This is blastocyst. It contains inner cell mass, which is the embryo that makes the baby, and in the trophoblast, which makes the placenta.

The biopsy comes from trophectoderm. We are biopsying that. We're taking 5 to 10 cells.

This is a very high technology, of course, in order to do all of these. Even though it's done and more than 50 percent of the cycles in the United States, we need optimal ovarian stimulation, optimal embryology conditions, and experienced embryologists. We need to use the diagnostic methods that are appropriate for the condition that's tested. And all of these are very important.

We're going to be freezing all the embryos in our biopsy. It's going to be the flash freezing, the vitrification technique.

Following that, we're going to move with the single embryo, transferred when the patient is ready.

If you look at the overview of the full process, the traditional method is about 5 to 8 weeks for the setup. After the DNA and required reports and everything that the PGT lab needs is submitted, then it's going to be about three weeks of ovarian stimulation and embryo biopsy. Following that, it's about 3 to 4 weeks for analysis at the PGT lab, and that's a lab only analyzing the embryos. They are supposed to do linkage analysis and direct mutation analysis, because these are the guidelines. This is what's really required. Then we are going to know which embryos are suitable for transfer.

LINDSAY: Can you tell us more about the steps and timeline involved with IVF?

KARIPCIN: Absolutely. The IVF process, it's about a 10 to 14 day process for ovarian stimulation.

It typically starts with the woman having her period. It doesn't necessarily start with a period, but what we do is, we give naturally occurring hormones, follicle stimulating hormone, and LH hormone from outside, to grow multiple follicles at the same time.

During the IVF process, the woman will be administering herself the shots of follicle stimulating hormone and LH hormone. These shots will be under the skin every day.

She'll come for ultrasound monitoring. Those are pelvic ultrasounds and initially, those ultrasounds will be every three days, then every two days close to the retrieval, it could be every day. This is going to be finalized with the egg retrieval. After that, she is done, and everything takes place in the IVF lab [for a while].

In the IVF lab, we put the eggs that are collected together with the sperm, injecting the sperm inside the egg which is called ICSI. Then we are going to culture the embryos for a week in the IVF lab, until they form a blastocyst, which has the inner cell mass that makes the baby, and the placenta, which is called trophectoderm at this stage.

More than 50 percent of the IVF cycles in the United States include genetic testing of the embryos. That's taking five to eight cells from the culture, and sending that analysis. The genetic testing lab may look at chromosome numbers, and for a small proportion of those cases, they’re also looking for a certain condition [such as a mutation that causes familial Alzheimer’s disease.]

This is overall the IVF process in a nutshell.

IVF is not always like this. It's not always embryo biopsy. it's not always culturing to day seven; it could be sometimes day three cultures, fresh transfers, but that's the most common type of IVF that we do.

LINDSAY: Once you have the embryo, what is the next step?

KARIPCIN: Actually, there is more to expect before the embryo [is ready for implantation].

When we are looking for a couple who are carriers of a condition, for example, if they know they are at risk for familial Alzheimer's disease, we can test the embryos for that. But that requires a setup before the IVF cycle starts.

That setup is a family-specific mutation analysis. And the PGT lab gets ready before the IVF cycle starts, to test for that family specific mutation.

Before we start IVF, we are waiting for the PGT lab to give us a green light.

Then you're going to say, Dr. K, what is that family specific mutation setup for? And I'm going to tell you the purpose of that.

If someone wants to know their own genetic status, they do a blood test or a saliva test, right? In that test, there are thousands of cells; no shortage of cells.

But the blastocyst we are biopsying in PGT has only about 100 cells. We biopsying five to eight cells from what makes 100 plus cells.

The DNA is limited, and in order to get the information that we want from that small sample, we need to look not only at the gene of interest, but also the surrounding markers. If the mutation is at the Presenilin, we are looking at the family specific markers for that individual around Presenilin.

LINDSAY: What's a general timeline for a couple to think about, when preparing for this process? How long is it from when a woman starts fertility medication until she’s four weeks pregnant?

KARIPCIN: It's about two months, if they want to transfer as soon as possible.Two to three months, because after the embryos are formed, depending on the PGT lab, we could be getting the results in about three to four weeks.

And if they're transferring with the period after, we could look into two to three months to get into that four weeks pregnancy point.

But from the moment they walk in, it's going to be maybe 5 to 8 weeks for the setup.

LINDSAY: Once you have the eggs and the sperm, how is it that you combine them, in the lab? What does fertilization look like in a petri dish?

KARIPCIN: The eggs are isolated from that tube, and then a couple of hours later, the cells around them are cleaned.

That is followed by the injection of the sperm inside the egg. Basically, embryologists will wash the sperm, and then they will put the sperm into a solution that will make them swim a little slower, so they can catch them. Then, the one that looks good and swims good will be selected and injected inside the egg.

The next day, the embryologist will go in on your microscope and see how many of the eggs fertilized.

This is the fertilization process.

LINDSAY: How does normal inheritance work? Going from an egg and a sperm, how do those genetic components work together to then make the genetic components of an embryo?

If a woman has an autosomal dominant mutation, how is it that she has a 50 percent chance of passing a gene onto her children?

KARIPCIN: We inherit one allele from each parent to our offspring.

LINDSAY: What is an allele?

KARIPCIN: There is a copy of a gene. Each gene is represented with two copies, and there is a copy that's inherited from our mom, and another copy that's inherited from our dad. Once we are inheriting that to our offspring or our embryos, we are going to pass on one, not both. And in this case, there is going to be a 50 percent that woman will have a risk of passing on that mutation to her embryos.

The 50 percent comes from that, because we inherit one. Because the embryos are supposed to have one copy of each, because they're going to get one copy from our partner. Her male partner is going to be also contributing the other 50 percent to that embryo's makeup.

[Editor’s note: Because familial Alzheimer’s mutations are dominant, inheriting the mutation means a very high likelihood of developing the disease.]

LINDSAY: When you think about a woman who carries the mutation, would you say that 50 percent of her eggs probably have the gene that carries the mutation. And the other 50 percent don't have that gene that causes the mutation?

KARIPCIN: Statistically, yes. It's not always the statistics, it's not always what it turns out. The same for men. It's overall for a dominant condition is going to be expected to be 50 percent.

LINDSAY: OK. You talked about when the genetic testing is done and that you're growing the embryo to a certain point that then you can take 5 to 8 cells for genetic testing. Can you talk about what happens to those cells and how is testing done? And why is it important that we test embryos instead of eggs or sperm?

KARIPCIN: Great question. What happens is, typically, those cells are put in a tube. They have barcodes and they have identifiers.

Cell samples, biopsy samples, come from each embryo. They'll be labeled to the matching embryo. They're kept in frigid conditions until they're shipped to the PGT lab.

Once they're shipped, they're lysed, meaning to get the genetic material out. Then after that, it's going to be depending on the lab that is sent to. It could be an amplification, or it could be direct analysis of the cell sample after the lysis. It's going to be the laboratory methods to identify the mutation and the surrounding markers from that embryo.

LINDSAY: Why can't we just test eggs and sperm before we create an embryo to see if they have a mutation?

KARIPCIN: The sperm, you wouldn't be able to test for it, because it will kill the sperm. Once we take the DNA content of the sperm out, it will kill that sperm. It's no longer going to be able to be used. Sperm testing is not possible before using it.

A lot of my patients ask that question, too. I don't think it's going to be possible for many years, because you just have to use that sperm, right? Also testing a bunch of sperm doesn't tell us anything about that individual sperm's outcome.

Sperm can't be tested before use.

An egg can be tested before use, it's called polar body biopsy.

Here when you're looking at the egg.

Once it's retrieved, it's going to have a polar body and some cells surrounding it. This is the results of the first cell division of first meiosis of the egg, called a polar body.

It's possible to biopsy that polar body, but biopsying it is technically challenging.

The egg is still going through cell division. As you're biopsying it, you could damage the cell division process. There's a spindle here and you could damage the egg.

In the trophectoderm biopsy, when we grow the embryos to 'one week' stage and many cells, it has that inner cell mass and the trophectoderm. This is the most resilient stage. The blast stage is the best stage to biopsy the embryo. It's still going to be representative to the egg.

Because for monogenic conditions, polar body biopsy is going to be representative, but it's not going to be as representative for the PGT-A part [chromosome count.]

Overall for aneuploidy, we get better information when it's biopsied at the one week stage, and also the embryo is more resilient, and we are going to have better outcomes if we test at the 'one week' embryo stage.

For people who are thinking that they might be carriers, but they don't have a partner, and they are not ready to move forward with embryo freezing, egg freezing is an option for them, because they could use those eggs to fertilize with their future partner.

LINDSAY: That's such a good point. Especially for women who are not yet ready to make a decision about family planning yet.

KARIPCIN: Certainly.

LINDSAY: I s there any risk to the embryo by performing genetic testing or by freezing it? Do we harm the embryo at all during that process?

KARIPCIN: Great question, and there was a study done and it was published in our journal, Fertility Sterility. Basically they biopsied the embryos as they took embryos, and then the study showed the trophectoderm biopsy, the stage that we are talking about did not have any impact on the embryo.

What they did–to get into the details of the study–they took couples who had two embryos suitable for transfer. The first group was 'day three' embryos, and the second group was 'one week' embryos and blastocyst. They biopsied one blastocyst. They didn't biopsy the other.

Then they biopsied one 'day three' embryo. They did not biopsy the other 'day three' embryo and they transferred both of the embryos. Then they follow the pregnancy and they did DNA fingerprinting during pregnancy of the woman, detecting the DNA from the embryo and then once the baby is born, they did buccal swabs, cheek swabs, to follow which one created the pregnancy.

The 'day three' embryos, they had a 40 percent reduction and pregnancy rate, when there was a biopsied embryo.

The 'day five' embryos, the blast stage embryos, did not have any change in creating pregnancy, whether the embryo was biopsied or not. That study on its own was already a challenging study to perform because of all the research approvals. Lindsay, you will know the IRB approvals and everything.

It's the best study out there to look [at]. The same group looked at their retrospective data. They compared their biopsied embryos to non-biopsied embryos, all comers, all age groups, and they did not see any change in implantation rates, too.

Overall, I would say it's the survival of the fittest in a way that if a woman is young and she has good egg embryo quality then those embryos will have a less impact. If you're older and you have poorer quality embryos or few embryos, those embryos may not be doing well with embryology procedures, which comes back to: all of these are actually better at a younger age. After the age of 35, there is going to be an increase in chromosomal abnormality.

The [drop in] egg quality doesn't happen all of a sudden after the age of 35. It happens gradually, but the sooner we do this, the better. If a 43-year-old woman is trying to do PGT-M, she's got less embryos to work with, just because embryos will be eliminated due to chromosomal abnormality.

To summarize your question, no known impact. The data is from really good studies, but unfortunately those good studies are not too many because of the limited nature of assessment.

One thing that I would add is that the embryo in this early stage of development is able to renew itself really quickly. If it's biopsied, a couple of hours later, you can't tell it's biopsied because all those cells already make up for it, and it renews itself quickly. In medical terms, we call it pluripotent. That's an advantage.

LINDSAY: It sounds like if you just take a few cells out of maybe a 'day five' embryo, there's really very little harm to the embryo and you can't even really detect that cells were taken from that embryo versus if you take it from a sperm or an egg, you're more likely to cause harm to those cells.

KARIPCIN: Exactly.

LINDSAY: I've heard some couples talk about how they're waiting for a probe to get generated, that you need to have a person's blood drawn or you need to have a family member's genetic testing report in order to generate a probe. Can you talk about what that process looks like and what a couple can expect during that time?

KARIPCIN: It all depends on the case.

If we already know our status, it's easy. That's disclosure testing. Yes, there is a family specific setup, but I could even tell you, if you can't find any family member, we could test your embryos that are sibling embryos, and they could serve as siblings, and they could be serving as a setup. The setup and the probe preparation could be even after the IVF cycle.

If you're doing disclosure, traditionally, the labs will ask to look for family members, but we could find a way with beautiful, accurate diagnostic accuracy to do a setup after the IVF is done. That's not a problem.

The non-disclosure cases, if you don't want to know your own status: Now, the family members will be needed. Most labs will ask you to have a report, or at least a family member, and that may not always be an effective family member. It's going to be based on the PGT lab's decision. So our patients will be meeting with the genetic counselor of the PGT lab, in addition to our genetic counselor.

We want to get our genetic counselors involved, and the PGT lab's genetic counselor is always going to be involved, and they're going to say, "These are the reports that I need, and these are the family members that we need. Who can we work with?" That discussion will be with the PGT lab and the couple.

But overall, typically, when there is a non-disclosure case, at least an unaffected family member (preferably an affected family member, but at least an unaffected family member) will be asked, and every lab is going to be different on what they're asking and what their comfort level is.

And also it could certainly be different for each mutation.

LINDSAY: If a person is interested in having a baby without the mutation, but can they do the procedure?

KARIPCIN: These are such great questions, Lindsay. It's certainly something that I discuss every day. A person who's interested in doing IVF PGT-M for neurodegenerative disease has the option to get themselves tested.

And this is going to be disclosure testing. That's one option we discussed.

The other option (PGT without learning your own genetic status) is called non-disclosure testing. But when we are talking about the non-disclosure testing, it gets even more complex. There is direct and indirect non-disclosure testing.

Direct non-disclosure testing involves direct mutation analysis [looking for a specific genetic mutation in the embryo. The PGT lab knows whether any embryo inherited the genetic mutation, meaning they know the parent’s genetic status.] But they typically blind their genetic counselors and sometimes also the embryology team.

[With direct non-disclosure testing,] I encourage my patients to not know egg numbers [until the end of the IVF cycle]. That means no follicle numbers, no embryo numbers, no numbers at all.

When they have ultrasounds, we turn the ultrasound away from them. And it's something we discussed in the beginning.

I do have patients eventually that ask me, "What's my number? I want to know." But I specifically tell them, if you're going to ask for a number, only ask me, because the team is instructed not to share numbers. The majority of my patients will say, "Doctor, I understand what you're saying. Nobody give me numbers, please." But here and there, I have some patients that will say, "Actually tell me my numbers, I want to know."

Even with that though it's impossible for me to know. I'm not blinded to all of these numbers. I get to see all of these numbers, even though I don't share unless asked. Once I get the report, I only see the embryos that are suitable for transfer. I wouldn't be able to tell if that embryo is eliminated because it had a Down syndrome or a chromosomal abnormality, or if that embryo is eliminated because it was really a carrier of this condition.

[With direct non-disclose testing], you'll get to work with more eggs and more embryos, because you're directly testing each and every embryo.

Indirect non-disclosure testing is based on family members DNA. It certainly requires family members, for sure.

Let's say, a woman has the early onset Alzheimer's risk, and her father was at risk of passing on the condition, right? Everything that comes from the father would be eliminated, and any surrounding marker that comes from the father will be eliminated. Anything that comes from her mother (the grandmother of the embryos) will be included.It's going to eliminate more embryos.

Choosing between types: Most patients choose direct non-disclosure because they're going to work with more embryos. But not all the labs will do direct non-disclosure. They could do the indirect method more. Overall in my practice, I see more direct non-disclosure from my patients compared to indirect, because our patients want to get more numbers from their embryos.

Risk of disclosure: There is always a risk of accidental disclosure. It's always a risk. Somebody in the recovery room could be speaking up louder than you could think of, or somebody may not look at the chart and give the patient the numbers. This accidental disclosure of a number is a possibility, but even when that can happen, it really doesn't tell somebody what their status is.

Honestly, thinking of all of my patients who did direct non-disclosure, it doesn't come to my mind. Sometimes when I see somebody having many embryos and they are a lot of embryos that are looking good, I just want to say, "Oh, this is great. Maybe they are not a carrier of this condition," but it's impossible for me to say that. Actually, I'm not even authorized to give them that information because I don't want to give them false reassurance. I can't tell either. Nobody could tell. We are blinded at each stage for the part that belongs to us.

When I speak with the genetic counselors from the lab, they don't even know how many embryo biopsies that we sent to them. They just know what the report comes, and the majority of the communications are just limited to the doctor who's in charge.

I hope I could break down this complex part to [make it] a little bit easier, but if a patient is interested in coming to us, we're certainly going to discuss those two of the possibilities, including the PGT lab; [they’re] going to discuss all the possibilities too.

Just know that you don't have to know your status. In some cases, you may not need the family members that you were thinking that you needed. It's just every case is different. Always give yourself a chance of having a consultation and exploration.

LINDSAY: That's such an important point. A fertility consultation will really help answer some of those questions.

Let's say we have embryos that have tested normal. When do you begin the process of putting that embryo into the female and what does that cycle look like?

KARIPCIN: That's the easiest part! Now everybody can relax and give their brain a break.

If they're having regular periods, I will put the embryo inside the uterus one week after ovulation.

It's just with a catheter, teeny tiny catheter. You don't even feel it. It's just like having a pap smear. It's just really simple. If they're not getting regular periods, we could give them medications, estrogen and progesterone, a hormone to prepare the uterus and it's about three weeks after their period starts they could have the embryo transferred.

It's always single embryo transfer because the chromosomally tested embryo our guidelines are to transfer one embryo at a time.

LINDSAY: What are the typical success rates of IVF to end up with a live birth of a healthy baby?

KARIPCIN: Once we have a chromosomally balanced embryo, it's about a 60 percent chance that embryo will create a pregnancy and a live birth. If we are talking about a woman in her early 30s, if she has good ovarian reserve, we could end up with several embryos.

And if it's somebody that is late 30s or early 40s and could take a couple of cycles to reach that point. But it really depends on that person's ovarian reserve.

Sometimes we start a PGT-M cycle, thinking that person does not have any issues getting pregnant and is just doing this process for PGT-M purposes, and we find some fertility issues along the way.

My experience is if somebody is younger age, we could end up sometimes four or five embryos from one cycle. Sometimes there are outliers. My last non-disclosure report (that I shared with her), it was 10 embryos from one cycle that she had suitable for transfer. That's an outlier. That's a lot of embryos. Not everyone will have that response. She was 29, turning 30. The younger that we think of it, the younger we start to process, the better ovarian reserve we'll have and the better quality our embryos will be. It's going to be a better outcome.

LINDSAY: How many cycles–egg retrievals and implants–can a couple expect to undergo to get pregnant? Is there an optimal number of embryos that they should have, if they want to have a certain number of children in the future?

KARIPCIN: The first depends on the person.

The second question, I do have an answer. If they want two children, I would say four embryos because 60 percent implantation rates. It's just always good to have a backup. But again, it all depends on the ovarian reserve and age. There's an attrition at each step.

It's anticipated that once the eggs are fertilized, only 30 to 50 percent will make it to the last stage. The rest of the embryos will be arrested, and for human reproduction, that's always the case. We see that happening in the human body, just reflecting as no pregnancy that month.

This is, we are a selective species. The embryos that divide abnormally, they're not going to be going through further stages. Not every egg that is collected will become an embryo.

Let's say we got 12 eggs, 10 were mature, 9 fertilized, maybe 3 of them will make it to the blast stage. And we are looking for a condition that affects 50 percent of the embryos. It's possible that a person could have just one embryo suitable for transfer at the end of all that.

LINDSAY: If you can't disclose how many embryos were, let's say, normal, is there a way for a couple to let their fertility specialist know, "We want to have this many kids. Can you have us undergo the amount of required cycles needed to get this many embryos?”

KARIPCIN: That's a great question. The non-disclosure part ends at the time of the report's release. For me, once they do the cycle, the final outcome, I give the results. I'll give the results of the embryos that are suitable for transfer, and if they want to know the sex, I tell them the sex. I tell them about the grading of their embryos.

At the end of the cycle, they know that part, because that's important for their family planning.

If the first cycle did not reach their goal of that number, they could do the second cycle in that case. It's going to be at the end of each cycle, they're going to know the numbers. Numbers of embryos suitable for transfer, just to clarify.

LINDSAY: What is the typical cost of a single IVF cycle and the added cost of genetic testing, specifically PGT-M?

KARIPCIN: Absolutely. It's about $16,000 for the embryology procedures, if it's self pay. In New York State, we have IVF coverage. Three cycles of IVF will be covered typically in the state of New York. Most of my patients that part is covered.

My insurance, thankfully, and I hope more and more people have it covered.

The set up at the PGT lab will have some specific rates for non-disclosure cases. Testing for PGT-M could take anywhere between $4,000 to $5,000. Sometimes it's closer to $3,000; it just depends. But for non-disclosure cases, just expect somewhere between $4,000 to $5,000 for the PGT analysis.

And that's independent from us, that's only the lab. The medications could cost somewhere between $4,000 and $10,000.

Altogether, the average cost of an IVF PGT-M cycle is about $25,000. The younger we start, the cost is going to be lower, because it's going to be less cycles and also, it's going to be less medication.

LINDSAY: You mentioned that some health insurance does cover these costs. And of course, that's probably dependent on whether your state mandates that IVF is covered, but are there ways couples can reduce the costs?

KARIPCIN: Especially when there's an infertility diagnosis involved, they're more likely to cover the state mandate.

The challenge here is when there is a non-disclosure case, you don't want to submit your PGT analysis to the insurance. Everything could go to insurance as an IVF cycle. And sometimes there's hidden infertility. Sometimes there's male factor when you're looking at it. Finding insurance coverage may not be problematic most of the time for the IVF and the medications.

The PGT lab part–anybody who's doing non-disclosure testing should anticipate paying that part out of pocket, if they're not willing to share this with insurance.

Another way to decrease the cost is actually really there should be grants for this. And I really It's really heartbreaking for me.These technologies are out there, and there are people who really want to use it, but it's not accessible to everyone. These are expensive technologies, really expensive technologies. Organizations for carriers of certain conditions should consider this, to support their members to want to pursue this technology.

LINDSAY: What about people who live in rural areas? Do most hospitals and clinics have this technology? Do they need to then go to a specialist? How would they go about finding a specialist that can do this?

KARIPCIN: I would not do this technology anywhere, because it's really important where you go. The embryology lab should be good. The ovarian stimulation should be good. And the lab should be the right lab. All of these are really important decisions.

This is not a technology for everywhere, unfortunately. Everywhere could say, “Yes, we could do it.” But many sensitive steps are involved.

Certainly it should be somewhere that has experience. Looking for places that would have more experience is going to be important.

LINDSAY: Yes. Is there a right time or age to pursue IVF with PGT-M?

KARIPCIN: The sooner they know that they want to do IVF PGT-M for this, do it, because you don't have to transfer your embryos. My patient that I shared the reports, she just had her Mirena IUD placed after the egg retrieval cycle.

It's just really, you don't have to transfer the embryos. It's important to do it sooner than later. I don't want to give an age cutoff, because we only look at the future. If anybody watching is above that age cutoff, it will discourage them, and they could be doing great. I sometimes see 42-year-olds who have much more than anticipated number of embryos, too, but they're outliers.

The sooner, the better.

LINDSAY: Are there physical and emotional burdens that come with IVF and genetic testing that individuals and couples should know about and prepare themselves for before pursuing this procedure?

KARIPCIN: It is emotionally challenging, especially for people who did not have trouble getting pregnant. I see a lot of PGT-M patients because of the Pre-Pregnancy Genetics Program. I have patients, for example, who come from natural pregnancies, and they had to terminate the pregnancy because they found that they are passing on a certain genetic condition.

It's just really heartbreaking sometimes. If there's not an embryo suitable for transplant, or if there's a pregnancy loss, it's just really emotionally challenging. If the results are good, it’s a happy process.

Overall, the cases that I have observed have had good outcomes. Sometimes, once in a while, I have patients with lower ovarian reserve that have to do a couple of cycles.

I had a patient, for example, who had premature ovarian insufficiency and the husband was at risk for neurodegenerative disease. She had to do a couple of those cycles. Every time it's just one to two eggs, one to two eggs. They all made embryos, but now she's pregnant. It was every time and there was just a low number of eggs. We were holding our breath: Will they fertilize? Will they make it to blast? Will they?

She wanted to know all the numbers and actually knowing her numbers, nobody could tell what status is because the numbers are low, but it's an emotional challenge for sure.

About IVF pregnancies versus natural pregnancies: once we transfer one embryo at a time, their outcomes are comparable to natural pregnancies. That's what the data shows.

Overall, it's important to do single embryo transfer. Based on historic data, the obstetricians will do a cardiac echo on the baby, but overall majority of the IVF pregnancies will be healthy children. It's overall a safe process with more than 40 years of data behind it and the embryo biopsy and the freezing of the embryos.

There are a lot of data accumulating from that too. There is a slightly higher risk of hypertension of pregnancy, preeclampsia, when there are frozen embryo transfers, and especially with the medicated transfer technique, the preeclampsia risk is increased. Overall it's a slight statistical increase.

Majority of the babies as a result of IVF are healthy, perfect.

LINDSAY: For anyone thinking about this, we do have members of our community who have gone through it, and would be more than happy to connect with you. It can feel isolating. Support makes it that much easier.

Are there any physical risks to IVF that women should be aware of before they begin?

KARIPCIN: The risks of this are bleeding and infection, which is extremely rare. Bleeding and infection that would require hospitalization, transfusion or IV antibiotics is less than 1 in 10,000.

There is also risk of ovarian hyperstimulation. Hyperstimulation is when a woman is responding too much. Their ovaries are very enlarged with electrolytes shifts. It's called the ovarian hyperstimulation syndrome. With the current techniques that we are using, the risk of ovarian hyperstimulation is actually getting lower and lower; the risk of severe hyperstimulation is about 1%. Freezing the embryos takes care of it, and in the case of PGT-M, the embryos will always be frozen [for testing].

Also when the ovaries get big, they could twist, which is called ovarian torsion. Our patients are careful, but if somebody is not careful, and if they're doing burpees, as they're going through the IVF process, the ovaries could twist. These are the things to know overall.

LINDSAY: OK. Are there any limitations people should be aware of?

KARIPCIN: Yes. People who do this are going to test their embryos, and it's very obvious, but you're only testing the embryos for THAT condition.

When we are testing for the presenilin mutation, it's going to be exactly that mutation that you are inheriting, or you have the risk of inheriting, from your parents that we’re testing for. If there is a new mutation in the presenilin 1 gene, it's not going to be showing up on this testing.

Chances of that happening are going to be extremely rare, but if there is a new mutation in another gene, it's not going to show up. It's still only testing for that specific mutation the person is at risk of inheriting.

LINDSAY: Thank you for clarifying that. And thank you, Dr. Karipcin, for joining us and giving your time and expertise to this topic. The potential and the power of stopping this disease after one generation is important to think about.

KARIPCIN: It's my pleasure.