Tomer Singer, MD - Why Some Eggs Belong in the Freezer
Patient Awareness Day 2019: HEALTHY MIND & HAPPY PELVIS
Living Your Best Life With Endo
March 10, 2019 (8am - 5pm)
Einhorn Auditorium, Lenox Hill Hospital, New York City
https://www.endofound.org/patientday/2019
Thank you so much, Carly. I would like thank Dr. Seckin for inviting me to the 10th anniversary of this amazing, amazing foundation. In the fertility world, we always say that about 15 to 20% of women with infertility has something unexplained infertility. The fact of the matter is that a lot of those patients have endometriosis and just people are not aware enough and they just go it unexplained. I'll touch upon a few topics today. The objective of the talk is just to go over what egg freezing is, to describe the process a little bit, the risk and benefit, and then to discuss what's the ideal number of frozen eggs for a patient with endometriosis. What is an egg? An egg is the largest cell in the human body.
It contains the patient's DNA and without it, we cannot create an embryo. It is visible to the naked eye and not that I'm an expert, but the size of it is about diameter of a hair follicle. Women are born with a finite number of eggs. When they are born in the sixth floor in labor and delivery, they have about roughly two million eggs. In uterus, they have six to seven million eggs, so there's a big decline from 21 gestation to the birth and then when they get their first period, it's estimated to be about 300, maybe 400,000 eggs. From that age, let's the [inaudible 00:01:39] is about age 11, that's when they get their first period all the way through age 51, which is the average age of menopause in the United States.
You have about 40 years when women ovulate. Every month, there's about 750 eggs that are competing to be the one that's going to be released and only one gets released. Over those 40 years about roughly 400 eggs are being released. The whole purpose of egg freezing is to try and get those eggs at early stage when the genetic material is still healthy rather than wait to age 40, 45 when most of them are going to be abnormal. This slide here shows the impact of age in the egg quality and the chance of getting pregnant. You can see that there's a steep decline beyond age 37, 38 and the decline starts really in the early 20s. When everyone is trying to avoid having kids in college, that's when the best time to get pregnant.
When they're ready to have a family, there's already a significant decline. If you look at this graph, the first baby can be achieved in the early, mid 30s. But if someone wants two or three kids, this will push her well into her early 40s, which will be very, very challenging. When you look at this graph, you see that the main issue and what the main reason why women don't get pregnant so easily in their early 40s or late 30s is because of the egg abnormalities. You can see that at age 30, 23% of the eggs are abnormal and when the patient is 35, about 35% are abnormal and there is a significant decline in egg quality. At age 40, 58% are abnormal and up to 84% will be abnormal when a patient is 45 years of age.
This shows how a DNA will tell us if an egg is normal or abnormal. To the left, you'll see normal genetics with 23 sets of chromosomes and to the right you see there is an extra chromosome, which suggest that this embryo has a trisomy 10, which is an embryo that will end up in a miscarriage. The same goes with down syndrome, which is trisomy 21 and other syndromes that we are all heard and are aware. This shows both the decrease in egg quality and the increase in miscarriage rate with relation to age. You can see the graph showing the spontaneous abortion. At age 40, every patient who gets pregnant, about 50% chance that this pregnancy will result unfortunately in a miscarriage.
When a patient is 45 and got pregnant, up to 85 to 90% of those pregnancies will result in miscarriage. This another way of showing what we already know from just looking and observing women who are pregnant. This is data that's taken from IVF patient who underwent something called preimplantation genetic screening, which is essentially taking a small biopsy of what becomes the future placenta and analyzing the embryo before putting it back into the uterus. When a patient is young, younger than 35 years of age, about 48% or 50% will be normal and 50% will be abnormal. When patient is over age of 42, you can see that only nine to 11% will be found to be normal, meaning 90% of embryos that are being created via IVF, women who are older than 42 will unfortunately be chromosomally abnormal, which means that that patient, like I'll already suggested, will potentially have to go through several IVF cycles.
This is a funny slide that shows the ratio between single women and single men. The single ladies, California is the place to be. All the single men should come here to New York. This is the process of egg freezing, what the idea of egg freezing essentially is. Egg freezing is aimed to remove the eggs from the body and save it in a freezer while the body undergoes all the changes that comes with age. We remove the eggs from the woman's ovaries and freeze them so they can be used in the future when she's ready to establish a family. We basically have several indication. The main indication for egg freezing in the past decade has been the medical condition. It started with cancer in the '80s and '90s in studies that were performed mainly in Spain and in Italy.
Then in the past decade, endometriosis became a very, very important part of why we freeze eggs. Then, there's obviously the social reason. A woman who's single, a woman who's planning on focusing on her career, school, and so forth, and patient that just want to preserve her fertility without compromising that chances that she'll have a miscarriage at a later age. You choose the time when it's right to freeze your eggs. You see your daughter. You decide to freeze it at age 30, 35. You need to have several assessment before that and we'll touch upon it in a few slides. What does endometriosis do to the eggs? As you can see in the slide, endometriosis affects every pelvic organ, the uterus, the ovaries, the Fallopian tubes.
The ovaries are the organ that contains the eggs. These are some pictures from surgical slides that show that ovaries are completely obliterated. There's a lot of adhesions. There's no good blood supply to the ovaries. There are cysts, endometriomas, and those have a direct effect. This is one of them, the grading system. There are several out there that show that when you have a stage four endometriosis usually the ovary is completely obliterated, completely stuck to the side wall. It's even difficult for us to get eggs at that point. Usually when you have a stage one, stage two endometriosis, it's much easier. It's not uncommon for me to send Dr. Seckin or Dr. Goldstein to have surgery just so I can get eggs if a patient wants to freeze their eggs.
This is an important slide. Not a lot of people know, but there is a marker there that's called AMH. Anti-Mullerian hormone is a marker that's been around since the, I would say, 2005 to 2007. It's a simple blood test that you can ask your doctor to send and it will tell you what's the ovarian reserve at a given time. You don't have to go at a specific time in your cycle. You can be on birth control pill. You can have a [inaudible 00:07:35] IUD and you just have a simple blood test and about two weeks later you'll get a result. If the AMH is low, that means you have low amount of eggs. If it's normal, then that means you have some time. Endometriosis patients have much lower AMH as has been shown by the literature. Egg freezing got a lot of publicity as you know and the process is basically takes about two to three weeks.
You meet with your fertility doctor, you have a consultation, you do a quick HMP medical history, a physical exam, you do the blood test including the AMH, and then you discuss with your nurses the injections, the stimulatory medication, and the hormone testing results. After that, you start the stimulation. You have a graph down at the bottom that shows you that it takes about two to three weeks. Most endometriosis patients will benefit from being on birth control pills for short period of time and use a medication called letrozole, which reduces the estrogen level. Takes about 10 to 12 days of self injected medication, usually in the evening, and then you get a trigger shot and 35 hours later, you do an egg retrieval.
This is a picture that shows the actual procedure. You get propofol. There's not intubation. There's some [contresedation 00:08:40]. The same propofol that we give for colonoscopy or endoscopy and about 15 to 20 minutes later, the eggs are out. The patients spend about an hour in recovery room and goes home. After the egg retrieval, embryologist is looking for the eggs. They count them, they clean them, and then they give us the report. Those eggs can be frozen all the way to age 50. What are some of the risks? The risks are bleeding, infection, hyperstimulation, injury to surrounding organs, and in some scenarios no eggs are retrieved. Those are very, very rare conditions.
I can tell you we do 10 to 15 retrievals a week. I've never had a situation with no eggs retrieved because you have some markers that tell you what to expect. The eggs are frozen in liquid nitrogen for years and then when the patient is ready to get pregnant, she brings her partner or uses a donor's sperm, we warm the eggs, we inject the sperm, and three to five days later, we transfer the embryo back into the uterus. These are eggs on the left hand side all the way to the right, which shows the day five embryo blastocyst and you can decided either to transfer that embryo or you can do a biopsy again, find out if the embryo chromosomally normal, if it's a female, a male, down syndrome, and then make a decision.
This is the embryo transfer. There's not anesthesia involved with that. About two weeks later, the patient finds out if she's pregnant. What are the chances of having a baby with frozen eggs? It's very challenging to assess. There's no guarantee with undergoing egg freezing and therefore we try to guide our patient. We quote about two to 3% of live birth per egg. If you have 30 eggs, multiply that by two to three, you'll get about 50 to 60% chance of having a baby. It also depends as I showed you on the age that you freeze the eggs. The younger you are, the better the chances. The egg freezing is a relatively new technology, it's no longer experimental as of 2012. All the guidelines from the American College of OBGYN, American Society of Reproductive Medicine promote egg freezing in patients, especially in patients who have endometriosis or cancer.
Initially, it was used mainly with patients with cancer, but then we extrapolated and we use it now mainly for social reasons for other medical conditions. This is a good slide that shows you how many eggs are retrieved and what is the chance of conceiving. This is for patients who are younger than 35 years of age. If you get five eggs and you're young, you get 15%. If you get 15 eggs and you're young, you get 85% chance. You can assume that the numbers are much lower for women who are freezing their eggs in their 40s. There's no real ideal age to freeze, but the younger the better. It's been shown that age 34 is the most effective age. That means you're most likely going to use eggs either for baby number one, two, or three, and that the age 35 to 37 is the most cost effective and the most common age.
At that point, as I mentioned, 50% of the embryos derived from those eggs are going to be chromosomally abnormal, so we need to take that into account. We've seen a trend in the last two to three years that special people that are aware of endometriosis or have frozen eggs for that reason freeze their eggs in their 20s to get a better outcome. There's a lot of cost involved in egg freezing. I think that's the main hurdle. You can see the list of things that the patient will have to pay for and unfortunately, and this is the take home message here, that we should push for egg freezing coverage for all patients with endometriosis. Endometriosis is just like dealing with cancer, just like dealing with any other medical condition.
The insurance companies are not covering it because they think it's just for social reason. Just because the patient is not ready. We know that the eggs are being deteriorated by the year and this is something that we should push for. In summary, egg freezing is a powerful tool that allows women to freeze their biological clocks by storing to use in a later time. It's very important to educate our patients about the chance of conceiving with those frozen eggs. The younger the patient, the better. It's not only a true insurance policy because we need to discuss with them also the option of getting pregnant at a younger age when they're not completely ready.
Whether to freeze eggs or whether to choose to do it in an earlier age is a very personal decision, so you need to discuss it with your doctor. The main thing is discuss it. Go to your doctor, have an AMH test, speak to your endometriosis surgeon, and just be aware of the options. Thank you so much.
