Genetic Testing & Fertility: What You Need to Know Before Trying To Conceive w/ Dr. Lucky Sekhon
Today, I’m delighted to be speaking to Dr. Lucky Sekhon, or as many of her patients call her, Dr. Lucky. She is a reproductive endocrinologist and infertility specialist at Reproductive Medicine Associates of New York, a large New York City based IVF center. She also has a great website, TheLuckyEgg.com, which is chock full of great information. She was born and raised in Toronto, Canada and moved to NYC to complete her OB/GYN residency training. She’s here to talk to us about Genetic Testing & Fertility: What You Should Know Before Trying to Conceive.
Dr. Aimee: Welcome to the show, Dr. Lucky. Tell us about your practice.
Dr. Lucky Sekhon: I’m based out of New York City. I live in Brooklyn, but I practice at RMA of New York, which is a large IVF center in the middle of Manhattan. We have six different locations. I’m based downtown in SoHo and in Midtown East.
Dr. Aimee: Why did you choose reproductive medicine as your focus in medical school?
Dr. Lucky Sekhon: I always knew that I wanted to go into women’s health. I don’t really know exactly why. I think it’s because I grew up in a female dominated household, I have sisters and my mom is a strong influence in my life, so I feel like women’s health has always been very top of mind.
Then specifically within OBGYN I was really drawn to the field of REI or infertility and fertility medicine because it’s amazing. IVF was invented not that long ago. I just feel like it’s such a fast-paced growing field and the cutting-edge research really spoke to me. I am still active in research, it’s a passion of mine. I just love that the things we’re debating and looking into and investigating today are becoming part of the standard of care a year or two from now. That to me is exciting.
Dr. Aimee: I agree. It is very exciting. IVF has touched you personally as well. How did you guys grow your family?
My husband and I froze embryos right after we had our first. Right after I finished breastfeeding that was the first thing I did. It was important to me because I didn’t want to feel rushed to have another when I wasn’t ready. Now, being 38, I am so glad that I have those frozen embryos. I just had my daughter Gemma last year during the pandemic. That wasn’t really my plan, but it all worked out, and she’s healthy and beautiful.
It really speaks to me when I see my patients, a lot of them are in the same age group and the same phase of life. Secondary infertility is a very real thing. Even if you start out in your mid-30s and it works out that you’re able to get pregnant with your first, just because of the amount of time it takes to be ready for that second child, if that’s something that you want for yourself, because of the challenges of biology and time, it can be more difficult. I just didn’t want my biology to be the determining factor.
Dr. Aimee: I always say it’s always nice to have embryos on ice. I want to talk more about genetic testing today. I feel like when I say genetic testing people really don’t know what that means. Let’s get into it, what people really need to know before trying to conceive. What are some of the basic things that people should know about genetics?
Dr. Lucky Sekhon: I totally agree with you, I feel like when people hear about genetic testing they shut down. It either seems complicated and boring or it sounds scary. But it’s really simple, and that’s what I’m hoping we can break down for everyone today.
There are different types of genetic testing. When we say genetic testing, it’s a very general umbrella term and we might be talking about very different things.
To start out with the first category of tests are ones that you can do preconception or when you’re already pregnant. I refer to it as a risk assessment tool where we can draw blood on yourself and, if you have a partner, your partner, or on sperm donors or egg donors, and we can determine what mutations they carry (if any).
That’s another word that scares people, mutation. What I explain to everyone is that it’s very common to carry a mutation. A lot of the genes that we have we’re supposed to have two copies, and it’s not uncommon to carry one mutated copy of a gene. For the most part, for a lot of disorders, it doesn’t really matter, if you have one functioning copy. We just want to know what mutations you carry. As a human being, it’s normal to have a mutation. We want to make sure that you don’t match up, that you don’t carry the same mutation.
Around 2% to 4% of the couples that I see are what we call joint carriers, meaning they both happen to carry the same type of mutation. In those rare cases, you have a 1 in 4 chance of having a child with two copies of the mutated gene, and that means that you have the actual disease that gene mutation corresponds to. Examples are things like cystic fibrosis, a serious lung condition, congenital deafness, but the list goes on.
We were just talking about this earlier. One of the biggest panels out there that a lot of us use has just included 500 different types of conditions and the associated mutations. It’s not trying to diagnose anything in you. This isn’t something that insurance companies can use against you to say that you’re at increased risk of developing a disease later or anything like that. Those are the typical worries that I hear about. It’s a risk assessment tool to see if there’s any chance that you and your partner could contribute two mutated copies and have a child potentially that could have any of these conditions on the panel.
Some of the conditions don’t really work like that, and that’s a little bit more complex. Conditions where a woman can carry one of these mutations on one of the X chromosomes, so if she has a son and they inherit that one X chromosome and the Y from the dad, the condition could manifest in that case.
Before you get this blood test drawn, you’ll be counseled and given a list of what conditions are covered on the panel. When you get the results back, you’ll get a call from a genetics counselor, and they’ll explain what all of that means. The main thing is just ruling out that you don’t carry the same thing.
Now, if you do carry the same thing, that is useful information because you could say, “Now I know there’s a 25% chance that I’m going to have a child with _____ disease.” What can you do with that information? You can do nothing and say, “I’m just going to go into the pregnancy with eyes wide open and know that this is something that I could test for,” as early as 11 to 12 weeks, or later in the pregnancy, “and then make a decision if we find that the pregnancy is affected of whether or not I want to continue the pregnancy or not.”
You could say, “I want to be proactive and not find myself in that situation where I could be pregnant for the entire first trimester and worried and wondering if this baby is affected,” so you could preemptively do IVF, create embryos, and then genetically test the embryos in a very targeted fashion to figure out which embryos carry the condition, which embryos have two copies of the mutation and have the actual disease, and which embryos don’t have any copies of the mutation. That’s called preimplantation genetic testing. There are lots of different types of testing that can be done on embryos, but that’s one focused test that you can only do if you know what you’re looking for. That’s why we do this carrier screening on prospective parents.
Dr. Aimee: I love what you called it, you called it joint carriers. Is that what you said?
Dr. Lucky Sekhon: Yes.
Dr. Aimee: I think that’s a lot better than saying you’re genetically incompatible.
Dr. Lucky Sekhon: Right. Exactly.
Dr. Aimee: Joint carriers just sound like you’re in it together and you’re going to get through it together.
When it comes to eggs, what is happening over time from a genetic standpoint?
Dr. Lucky Sekhon: We talked about preimplantation genetic testing. I’m sure many of the people tuning in today have heard that term, PGT. It’s most often not used to test embryos for a targeted gene mutation. I would say the most common use of PGT is to count the number of chromosomes in each embryo. That is a very common problem, that you can have an embryo form from sperm and egg that doesn’t have 46 packages of DNA or chromosomes.
If you don’t have 46 chromosomes in an embryo, one of three things is going to happen. Either it’s going to stop growing before it can even get to the wall of the uterus and implant, and you just don’t get pregnant that month. If the egg that you ovulated was abnormal and turned into an embryo that didn’t have the right amount of DNA, it might just stop growing and not actually turn into a pregnancy. It could also implant and then stop growing, and that’s the number one cause of a miscarriage.
Then there are very few types of typos or errors, I call them, that are compatible with life. An example is Down Syndrome. You could have three copies of chromosome 21 and that can result in a live birth of an individual that has significant medical problems as a result.
Those are the three different things that can happen. Why is it so common to have embryos that don’t have 46 chromosomes? A lot of it comes down to the egg in your original question.
What’s happening to the eggs? We’re born with all the eggs we’re ever going to have, and we can’t fix our eggs or repair them over time like a lot of the other types of cells in our body. We start to accumulate errors in the eggs, and there’s an increased tendency for us to lose chromosomes or gain extra chromosomes in our eggs. As the egg is growing and dividing, it goes through different stages of development. As you age, it becomes more common to release an egg that doesn’t have the 23 chromosomes it’s supposed to contribute to that 46-chromosome embryo.
No one is immune. This is what I always tell my patients. No one makes perfect embryos. When you were in your 20s, what we see when we look at PGT results from women going through IVF in 20s is that about 20–25% of those embryos coming from a woman in hers 20s to early 30s are going to be genetically abnormal, either they’re missing chromosomes, or they have extra chromosomes. At 35, we start to see rates of 30–35% of embryos having the wrong number of chromosomes. At 37 and 38, that’s when we start to see a real uptick, you start to approach rates of about 40–50% of embryos being affected and not having 46 chromosomes. At 40, it’s like 60–70%. At 42 and 43, we start to approach 80% and more.
That is why there’s a link between female age and infertility, female age and miscarriage. It comes down to this fundamental fact of the embryo just not having the right amount of DNA to grow and persist as a healthy pregnancy. That’s what’s happening with age.
The good news is you can use this technology, PGT, where you’re basically capitalizing on the fact that an embryo has 100 to 200 cells by the time it gets to day five of development after fertilization, a lot of the time they separate out into two cell types if it’s growing at a normal pace or if it’s a fast developing embryo, and you can remove some of those placental cells, the cells that will someday become the placenta, and send them off for genetic testing and count the number of chromosomes. You can tell if it’s going to be a female or male embryo, and you can also look for a mutation in a targeted fashion.
Dr. Aimee: You brought up Down Syndrome. I’m sure you get this as well, patients leave your practice, they’ve done the genetic testing of the embryo, the PGTA, and then they email you, “Did we screen for Down Syndrome?” Can you talk a little bit about what is Down Syndrome, what is Turner Syndrome, and how is that related to the chromosome?
Dr. Lucky Sekhon: Down Syndrome is when you have three copies of chromosome 21. There are 23 different types of chromosomes, there’s the sex chromosomes and then you go from 1 to 22 in numbers. If you have three copies of chromosome 21, for whatever reason the genes that are on those chromosomes, having that imbalance doesn’t prohibit the embryo from implanting and turning into a pregnancy, and you can actually get to a live birth. But individuals with Down Syndrome have a shortened lifespan. A lot of them have cardiac malformations and a host of other medical problems, and it’s this lifelong thing that you deal with.
You can screen for this in early pregnancy. I don’t want patients to think that the only way to prevent this is doing IVF and genetically testing embryos. This is something that can be screened in the first trimester with blood work, ultrasound markers which can be done at the end of the first trimester. Then you can do a chorionic villus sampling (CVS) at the end of the first trimester or an amniocentesis during the second trimester. These are invasive, but are associated with a low rate of complications, and they can give you definitive information about the genetics of the pregnancy. So, you always have the option to do this testing to understand more about the health of a pregnancy.
Turner Syndrome is where you’re missing an X chromosome. Similarly, it can cause a host of problems affecting kidneys, intellectual function and ability, height, all sorts of body systems are affected across the board.
Dr. Aimee: If a patient says to you, “We don’t have Down Syndrome in our family. Why would we need to check for this?” how would you respond to that?
Dr. Lucky Sekhon: It goes back to what I said at the beginning. There are so many different things that you can test when you think about genetics. The things that run in your family refers to those gene mutations and the things that we can pass on, but these chromosomal count errors can happen to anyone, it has nothing to do with the genetics of your family. It has more to do with age.
Dr. Aimee: What are the three big categories of genetic testing that you do as a fertility doctor?
Dr. Lucky Sekhon: Carrier screening on patients, individuals, or couples. This can be done prior to getting pregnant. A lot of times, people will get pregnant on their own and just go to their OBGYN and get this testing done to determine if they should be doing any more detailed testing on the pregnancy later down the line.
Preimplantation genetic testing, which is testing on embryos. This involves biopsying an embryo, removing some of its cells, and sending it off for analysis. Most places are freezing the embryo to wait for the turnaround time for the results.
The third category is something that has come up yet. It doesn’t really impact most individuals. This is called a karyotype. This is a test where blood is drawn, and the cells are fixed on a slide and looked at under a microscope so that someone can actually analyze the structure of those 46 chromosomes. By doing that, you can learn a lot. You can learn whether all 46 chromosomes are present.
If there is any structural rearrangement, believe it or not, you can have a breakage in the chromosome where for some reason a piece of one chromosome got translocated to the end of another chromosome, and you can be a completely healthy individual because you have all your genes, you have the right amount of DNA, it’s just rearranged. What happens if you join your DNA with a partner or an individual, there’s going to be a higher than expected rate of abnormal embryos that have imbalances in the proper amount of DNA they’re supposed to have.
Inversions are when there’s a section of a chromosome that’s flipped. Again, a similar situation. You have all the right number of genes and DNA that you’re supposed to have as a human being, but when your DNA joins with that of another individual there’s going to be a higher than expected rate of errors.
This is something that is first line testing done in couples or individuals who have recurrent miscarriages because sometimes recurrent miscarriages can happen because of chromosomally abnormal embryos that resulted from one of these structural rearrangements. We were talking about this earlier, that we often as reproductive endocrinologists will think to do this testing on patients who don’t do as well with their IVF cycle as we expected them to.
An example is, let’s say, a 31-year-old who has 10 fertilized eggs to start with and nothing grows to the blastocyst stage, and you’re thinking, “Why would there be such a sharp drop off?” The number one cause of why embryos stop growing in the lab is that they were genetically abnormal, that’s one of the common causes. You may do a karyotype on that individual and their partner to see if either of them have any of these issues that could explain why none of the embryos made it.
Anytime I have a patient who has really diminished ovarian reserve at a young age, I might do a karyotype on them. This is where things get more complicated. Sometimes not all your cells have an abnormal number of chromosomes, but some of them may. They might be missing that X chromosome and you could be a Turner’s mosaic. Mosaic means some of the cells are normal, some of them are missing that X chromosome. Those patients are known to be at risk of premature ovarian insufficiency or early menopause.
Dr. Aimee: Thank you for breaking down the three types of genetic testing patients should know about as fertility patients. Is there anything else patients should know about when it comes to genetic testing during this phase in their life when they’re working with a doctor like us?
Dr. Lucky Sekhon: Yes. I think the most high-yield thing to talk about is preimplantation genetic testing. I think a lot of times patients receive great counseling from their doctor but it’s hard to retain all of the information. I feel like IVF patients have to learn so much, it’s such a steep learning curve. Either you may not get all of the nitty-gritty details because it’s too overwhelming and your doctor is not necessarily going to want to go through each part of it until it becomes relevant, or you hear about it and it’s just hard to retain. So, I want to go through it today.
What should you expect going into a cycle where you intend to genetically test the embryos for the purpose of determining whether the embryo has 46 chromosomes or not?
The first thing to know is that you’re not necessarily going to get a black and white answer. There are many different types of answers you can get. The easiest answer, the one that we hope for the most, is that the embryo is euploid, which means it has 46 chromosomes. From that, if you want to know the sex, we can either blind you to that information if you don’t want to know, or we can tell you if it’s female or male. The answer we don’t want to get is that the embryo is aneuploid or has the wrong number of chromosomes. Most people would not transfer that, because either it’s not going to implant or it’s going to result in a miscarriage or an individual with medical problems, so you wouldn’t knowingly transfer that.
Then there are these in between situations. There is where you get inclusive or indeterminant results, and I think it’s important to know that’s a possibility that can happen. It doesn’t necessarily mean anything about your embryo. It really is just a technical factor, because to get this testing done the DNA has to be extracted from the cells and amplified. It’s amazing, we’re taking very few cells from the embryo, it might be as limited as four or five cells. Sometimes things go wrong when you’re trying to extra little itty-bitty amounts of DNA from that small number of cells, so you just might not get a call with confidence of whether this embryo is normal or not.
You have options. You could say, “Okay. I’m just going to use the embryo,” or just have it on the back burner and use it maybe last because you don’t have information about it. Or you might choose to re-biopsy it. We can thaw the embryo, re-biopsy it, re-freeze it. We don’t have a lot of data on what that does in terms of the effect it may have on the implantation rate of that embryo, but it’s reasonable to assume it’s not a wonderful thing to expose it to an extra freeze and thaw and an extra biopsy, so it’s not something that I love to do. But if a patient is at a high risk of having an abnormal embryo, it might be the right call. That’s an individualized decision and conversation you should have about whether to re-biopsy the embryo.
The other situation that can arise, and this is a major hot topic in our field, and it has been for the last couple of years, is when you get a mosaic embryo. Mosaic, just like pretty tiles on a wall or table, it’s a pattern where you can have some normal cells mixed in with abnormal cells. That four to nine cell sample that was sent out for testing, there were some abnormal cells that were detected in there, but it’s this in between result because there are some normal cells.
That’s a very gray area. It’s important to know that we don’t know everything there is to know about mosaic embryos. They do have reproductive potential and they can be transferred, and it just depends on the situation. There have been live births from mosaic embryos. There have also been conditions that pediatricians will talk about that we know can be traced back to the karyotype for that child with that development disorder or disability is mosaic. So, there are risks that you take on when you transfer a mosaic.
If you were considering transferring a mosaic, you would have to talk to your doctor. Every clinic has its own policy. There are some clinics that may say, “We don’t transfer mosaics at all. We’re very risk averse. We don’t want to be involved in anything that might result in an unhealthy child and we don’t know enough about this.” Then there are clinics that are much more liberal. Then there’s the in between. Where I work currently, our policy is that we will transfer a mosaic embryo if it’s the only embryo you have. If you have a healthy embryo, we would prefer that you use that first.
I think it’s important to address what the policy is before you go into a cycle, because you never want to be in a situation if you find yourself with only a mosaic embryo of not being able to transfer it if that’s something that you might want to do. I think it’s important to talk to a genetics counselor because there might be some literature and some information about that particular type of mosaicism, depending on what chromosome is involved. They can also tell you things like the level, how many abnormal cells versus normal cells percentage wise, and what the risk could be as a result of that.
So, it’s a complicated thing and it’s just important to know that it exists. Don’t expect to have this just binary yes or no, normal, or abnormal result.
Dr. Aimee: That’s super helpful. I wish everyone could listen to this who is doing PGTA so they can understand what information you might get. I think knowing that it could be inconclusive, knowing you could get a mosaic embryo and what it could mean for you in the future is extremely important, because you don’t want to find out later that your center won’t transfer mosaic or won’t even tell you if an embryo is mosaic or not. I think that can be really tough on people to find out that potentially that information wasn’t given to them when they might have made a different decision and not have discarded a mosaic embryo and it was called abnormal. Thank you for that.
Lucky, thank you so much for being on today. It was so awesome talking to you about genetic testing. Thank you for joining us today. I really appreciate your time. I can’t wait to have you back on.
You can find Dr. Lucky Sekhon at RMA of New York in New York City,on Instagram @ Lucky.Sekhon, or on her personal website TheLuckyEgg.com.
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Originally published at https://www.draimee.org.
