Egg Freezing & Endometriosis - Tomer Singer, MD

Good afternoon. First, I would like to thank, uh, Dr. Kin and the organizing committee. I think this is maybe year 10 that I'm giving a talk in your foundation, which is, uh, amazing. And you know, I've listened to the last lecture and I think that, um, you know, education is really key. Uh, and one of the titled, uh, that was mentioned is Vice Chair of Education. And I trained under Dr. Seckin for four years and then went for fellowship at the Cornell for reproductive endocrinology and infertility. And the reproductive part is where the endometriosis really, uh, is key because you need to first focus on the organs of the patients. And later on comes to infertility. And a lot of fellowships now unfortunately, are focusing on IVF and egg freezing and forget that there is a patient that there's, uh, other issues and there are other E that you need to address.

And, uh, that was just a comment in relation to the last lecture. So I'm gonna be talking today about egg freezing and, uh, fertility preservation in patient who are, uh, diagnosed with suffering with the endometriosis. We'll talk about the age impact on fertility. We all know as, um, the former speaker was mentioning and, and some others, that the A count and the A quality goes down with age, but also significantly goes down with endometriosis. We know that in the twenties it's pretty stable, but then late twenties, early thirties, we know that there's a significant decline. When I started doing that, and I think that most women in the late thirties were considering egg freezing, we now see patients in their mid twenties and early twenties who have the knowledge of the pelvic pain and endometriosis already seeking care. And I think that if I have to focus on one thing today is education, education, education.

And if you know that you may have endometriosis and you have pelvic pain, it's much better to do fertility preservation when you're in your twenties or early thirties rather than delayed until you find Mr. Wright or Mr. Mabe and actually have to jump on it. So that's one key that is really important and I've learned along the years because you can do one egg freezing cycle instead of five or six egg freezing later on when you're in your early forties. In the mid thirties we know that the decline in egg quality and a quantity starts to really accelerate and it reaches about 1% when you're 45 and the rate of miscarriages goes up exponentially at that age. This slide shows you how the egg count and egg quality goes down in the thirties into the forties, and how the blue line shows that their rate of miscarriages goes up exponentially too. This slide shows that when we look at women who underwent, uh, a miscarriage unfortunately, or had an amniocentesis in their uh, second trimester, the rate of chromosomally abnormal go up and unfortunately endometriosis accelerate that process. So if we see a one in 350 risk of down center 35 when a patient has endometriosis with the bilateral endometriosis, we see that that rate goes up even at the earlier age.

This light shows all the factors that could affect fertility. And I, I want to focus on endometriosis today. You know, age is obviously key factors, smoking healthy lifestyle, BMI undergoing ovarian surgeries as a we've mentioned today in the conference. Uh, but endometriosis in it of itself without any treatment is just deteriorating the egg quality. And we need to be educating our general obgyn, our primary care physician to address those things. What is egg freezing? So we know that egg freezing has been around for about 30 years now since the beginning of eighties. And it's been very challenging to freeze eggs, much more challenging than freezing embryos cause it's a one cell, that 90% of it is fluid. And in the past we thought that if we're gonna slowly freeze the eggs, it's gonna survive in a better form or a better way. And we learned that that wasn't the case.

We learned that there are crystals that are being formed and the eggs don't really survive. And what happened about 10 or 12 years ago, we learned from studies coming from mainly Italy in Spain that if you actually fast freeze and you take those eggs and you dump them into liquid nitrogen within minutes, they actually survive in 90% of the cases. So we need to thank the Vatican and other states or countries in Europe that did not allow to fertilize too many eggs. And instead of discarding those eggs, we did research on those eggs. And also patient with cancer, which there's a lot of resemblance with the oncological patient and endometriosis patient that have essentially a set, uh, time that they can re retrieve eggs, freeze them and use them in the future. We have patients that are coming with a pending surgery two or three weeks down the line and the best you can do is try to harvest as many eggs as you can before they start the endometriosis journey.

And the same goes with patient who are diagnosed with breast cancer or other cancer. They're embarking on chemotherapy that's gonna have a definite impact on their fertility. And we have very short period of time. What we're doing is essentially retrieving eggs through the vagina going into the ovaries after about 10 to 12 days of stimulation as I'm gonna show you and freezing those eggs for a later time. On the left you can see that that's what we've been doing since 1980s until 2010. And what we learned in 2010 is that we do vitrification. We'll have 90 to 95% survival of those eggs, which has really revolutionized the way we think about reproductive medicine. This is the initial workup and we've mentioned it in a couple of the, the speakers before. So the patient comes into their OB gyn or the reproductive endocrinologist and essentially gets an ultrasound and gets a blood test.

The first blood test here is called fsh. That's an egg quality blood test. The tricky part of this blood test is that it has to be done with the patient's menses. It cannot be done when a patient is on birth pills. And it's very tricky to do it when a patient has an I U D because you don't quite know where she's in her cycle. FSH has been around since the seventies and you want that level to be as low as possible. It's a hormone that's being secreted by the brain, by the pituitary. And it tells me how hard the work the brain works to convince the ovaries to produce healthy eggs. And normal range is less than 10. A lot of patient with endometriosis is will have a FSH of 12, 15, 20. And then we know that there is a problem with the A quality.

So that's the first step AM H which can be done at any given time of the cycle. So whenever a patient goes for a pap sear, she can definitely ask her OBGYN to run. It is an A quantity test and normal range depends on the age of the patient, but normal range is above two usually. And we thought that in the past if anyone has an a h, we should essentially scare them Like the, you know, the person who was here before me mentioned a H of 0.1 or 0.2 freaked out a lot of patient and instead of taking ownership of that and starting to to work around how we can work with the AM h that's slow, patients started essentially not doing anything about it and OB gyn stopped doing it because they did not want those annoying phone calls of explaining the patient that you may be menopausal or perimenopausal.

So I think it actually is very important to educate the OB gy, how to counsel patient even with a low A H because what's important is even low a H has a very good outcome in most patient. The second thing that we do is an ultrasound. And the ultrasound looks at four things. We count falcos. So you can go to your OB gy, have a transvaginal ultrasound and literally look at those Fs, each one of those pockets contained one egg. So just by a glance I can tell that this patient has a normal ovarian reserve. If I take a patient who's 50, I will barely see one or two follicles at most. So that's an intra follicle count. This second thing, especially in patients with endometriosis, this we want to make sure that the patient does not have endometriosis or ovarian cyst. And that's usually how patients are being diagnosed with endometriosis before they go for surgery.

The third component is the ovarian volume. We know that the normal ovarian volume is about two and a half centimeter by two. So if you multiply it's about nine or HCCs. And if we see that that volume is small, we know that we don't have a lot of eggs to work with. And lastly, when you're considering egg freezing or ivf, you wanna make sure that there is a good access to the ovaries. This is the patient that is undergoing now egg freezing. I just pulled those slides this morning, you see in March seven. And you can see the, she has bilateral endometriosis. You can see that here on the right ovaries. She has a big endometrioma right there. There's a blood vessel, the bowel is right there. There are a few falcos and this is where the retrieval is gonna be happening. For on the left over, you see again a large cyst in Endometrioma and couple of fco.

If the patient goes for surgery before an egg retrieval, before egg freezing, by default we're gonna resect this endometrioma and potentially could harm healthy eggs. That's why most endometriosis surgeon, when they have a patient with low variant reserve or bilateral endometriosis will refer them to a fertility specialist to at least discuss fertility preservation prior. Cause if you come out of the surgery with a very small portion of right or left over, it's gonna be more challenging to conceive whether spontaneously or with in vitro. This is a normal menstrual cycle, usually 28 to 35 days. There is a secretion of FSH from the brain as I mentioned, and that recruits one dominant follicle releases an egg if there's a sperm around, there's a chance of creation of an embryo and achieving a pregnancy. What we do in an egg freezing cycle, we block that FSH and give injections for about 10 to 12 days to try and recruit several eggs instead of just one egg.

So we're tricking the brain to think that the body's already recruited an egg and we take over. Essentially that process takes about 10 to 12 days. Once we complete those 12 days, we go for an egg retrieval and the egg retrieval is done transvaginally. So there's no scar, A abdomen, we go with a transvaginal probe. There's a small needle that goes on top. And as you can see here, that needle goes through the vagina into the ovary. You can guide yourself with an ultrasound, drain the fluid, and then get a tube with eggs in it. The process takes about 12 days and the patient will see her reproductive endocrinologist for about 4, 5, 6 visits usually in the morning. During that visit, they'll have a transvaginal ultrasound and we'll check hormone levels. We check estrogen, we check lh, we'll check progesterone. And every day the patient, uh, when the patient comes, she'll get a phone call from the fertility nurse telling her what she should do that evening.

And those injection takes about 12 days, takes about five minutes every evening between eight and 9:00 PM After about 12 days, we give the final trigger shot. The trigger shot is usually Lupron in patient with endometriosis. The same Lupron that we give with patient to suppress their ovulation when they have severe pelvic pain. But it's a much, much lower dose. It does not suppress them for a month or three months as uh, Lupron depo would, but it's essentially causes maturation of the eggs. And the good news is that we have so many medication now that we can lower the estrogen level throughout the stimulation such let Letrozole and Lupron that all the symptoms of bloating, discomfort, pain are much, much better tolerated. The egg retrieval itself takes about 15, 20 minutes. We've had five retrievals between 8:00 AM and 11 this morning. So every patient gets a slot for about 30 minutes, just like colonoscopy.

You come in, you get IV propofol, the procedure is done in an OR and then we get the fluid out and we take the, uh, fluid under the microscope and we search for the eggs. This is a, a picture of a mature egg. We can see there is a polar body there that allows that egg later on to fertilize with sperm when the patient is using donor sperm or partner or husband sperm. Without that polar body we know that the eggs essentially is immature. So we cannot just take a patient who comes to see me take it to the OR and just yank eggs out because those are not gonna fertilize. They have to go through this whole maturation phase and 12 days of stimulation. The twilight sedation is basically propofol, uh, as some of you may have heard. And you do have to have someone, uh, take you back home and the same day you know how many eggs you got patient with low AMH will get less eggs.

Patient with high MH will get more eggs and the keys that you want to get to a certain amount of eggs before you're completed. The fertility preservation journey, and that's really one of the most important question that every reproductive endocrinologist should be able to answer When a patient is uh, assessed. This is a good, uh, slide that shows you the egg freezing timeline. You can see that the patient comes in with her period. She gets that ultrasound andro follicle count, fsh a h all in one session. She goes in a short course of birth control, which helps with endometriosis, suppresses recruitment of a follicle, and then the stimulation commences. You have about 10, 12 days of stimulation and then you do the trigger shot and the egg retrieval and the doctors may use letrozole progesterone, i u d can be in placed. You don't have to remove an I U D or focusing on the ovaries here.

You may use a patch or lepro or or different medication that can suppress or control ovulation later on. The eggs are frozen in liquid nitrogen. And essentially we have patient that have frozen eggs over 18 years ago and took babies home. So essentially it's indefinite. I usually tell the patient you can use it all the way to H 51. At that point you'll have to donate it to research or to a sister or who knows, maybe to your daughter the associated risk. So this is obviously an elective procedure when a patient is just single and freezing eggs. I'm a big believer that endometriosis should be looked at just like any other disease. And you should be covered by insurance. It should be completely under any healthcare insurance. And we are fighting, and I can't tell you this week I had four peer-to-peer consultation with different insurance companies explaining them how detrimental this disease to the patient besides the fact that it has an impact on the uterus and the Fallon tube and the ovaries patient don't have as much sexes patient without endometriosis.

So checking ovulation is really just to kind of like pinpoint it to the day that they have to have sex, not because they're dying to have sex that day and they're still healing from a surgery that they had a month or two or three before. So all those conversation and at the end of the day you get to a medical directors, a dermatologist sitting in Iowa and trying to explain in reproductions not, doesn't always go well. But I think that we're definitely, uh, dreading the needle and every session, every year, I, I'm happy to tell that more insurance companies are considering it. And when you look at your insurance policy, it will say egg freezing is coverage for medical indication, which is a code code word for cancer. I want to include endometriosis. That code ward. That's really what we should focus on.

The risks are very minimal, uh, especially because there is usually diminished ovarian reserve. Ovarian hyper stimulation is not something we see quite often in, uh, endometriosis patient. That's something that we see with P C O S. With patients that have 20 or 30 folles, that's a different condition. Ovarian torsion very rare as well. It usually happens when a patient has a lot of eggs. And as the ovary heals, if the patient is very, um, using, doing a lot of high impact physical activity. So as long as she follows the instruction from the nurse, that's very unlikely. Plus with endometriosis, there's a lot of adhesion and scars and paradoxically that protects from torsion because the over is tucked in. Uh, the procedure related complication, just like any other procedure, d nnc, uh, pap smear, uh, coposcopy biopsies, bleeding and infection, which are very rare. One in 500 to one in a thousand medication side effect is probably the most common, uh, issue.

Bloating, pelvic pain, most of our patients starts with endometriosis is pain. And that can bring bad memories from prev, you know, prior surgery or prior cyst. So that's really key. You want to see a reproductive endocrinologist that knows how to manage that post-op, not just to go for the two weeks of stimulation. Do the egg retrieval that everyone can tell can do. Post-op is where most of our endometriosis patients are dreading. That's why they don't go for egg free. Cause they're really afraid that after that there's gonna be a long-lasting pain or cyst that's gonna be developing or something that's gonna be making things worse for them after the retrieval. So that's really key to discuss with your patient, with your team before you go for retrieval. Ovarian cyst and known endometriosis are obviously can make things a little bit more complicated. As I showed you in the picture before, sometimes we have to go to an endometrioma to get a patient six or seven eggs, which will be her future child potentially.

So we need to make sure that you communicate with anesthesiologists if you need to give certain amount of antibiotics or adding an antibiotics or pa bringing the patient more frequently. Post-op because you did, you did go to the retrieval. Uh, true endometrioma. So that's another, a unique component when the endometriosis patient is freezing eggs. And the good news is that there is no increased risk of cancer impact on future fertility. If a patient did not use her eggs, the patient essentially just salvaged some of the eggs that otherwise would've died. This is a good study that looked at how many eggs we need to take a baby home. And you can see that in blue it's age 30 to 34. 35 to 37 is uh, in yellow, 38 to 40 is in red and 41 to 42. So again, when I started the reproductive endocrinology department here at Lenox Seal in 2012, most of the patient I saw were 41 42 year olds single who just wanted to freeze their eggs and wait for the right partner.

We now see a significant shift in, in 2012 we saw one or two a month. We see now three or four a day. So egg freezing has really shifted to a younger age and many more are aware and the price went down and I'm hoping it'll be completely free in the future. Results are based on the number of eggs. So if you take a 30 year old, if she had 10 eggs, her chances of taking a baby home, it's about 50%. If you get 20 eggs, her chances of taking a baby home is 80% and 30 eggs will get us through about 92%. The older the patient is, the less likely those eggs will yield a viable pregnancy and the patient most likely will need to go through more stimulation to get to that number. So how many eggs to freeze? That's a big question.

So usually a good rule of thumb when you're in your thirties is half of your age in eggs is a good number to land on. But it's definitely an age dependent. The younger the patient, a better day quality. You can see here that based on that study, 15 to 20 mature eggs and women younger than 37 will give you a very good chance. Close to 80%. A patient who's a little bit older and is doing it when they're 38 to 40 will need about 25 to 30 eggs. And women who are forties and 41 will need many more eggs and usually will discuss at that point also maybe freezing embryos. Women 40 years of age with normal ovarian reserve, an average of 13 eggs can be retrieved. I mean this, this week we've had 25 retrieval. One got two eggs, another one got 66 eggs.

So it ranges just like any other, you know, medical condition. It depends of what they age. What's the thero follicle count the age of the patient are now? Well, she stimulated to the medication that we've given them upon returning the eggs or can be taught in batches. I always joke with my single women that if we got 30 eggs, it's enough for three husbands, that's enough for a lifetime. We can batch 10, 10, 10. Uh, and essentially we now in New York can do a gestational carrier, which is amazing. That's another big revolution because as of two years ago, we can actually take those eggs, fertilize it with a partner or a donor sperm and transfer the embryo to a gestational carrier. When just two years ago I used to go to Connecticut or Pennsylvania to do the transfers, you know, because it was illegal in New York. So now everything can be accomplished here in New York State and there is more and more coverage by, uh, some of the, uh, insurance provider for a transfer into a gestational carrier, which is a big revolution as well.

This is a good slide that tells us the chances of a second child and a third child. That's the largest study that I'm aware of that looked at women who froze eggs and essentially wanted to have second child or were crazy enough to have three kids. Uh, you can see that if a patient is 30 to 34 and started with 20 eggs, the chance of one baby is about 80% with the same 20 eggs and you're gonna have some leftover eggs or embryos, 50% chance for a second baby and 20% for third baby. So those women who wanted three kids, that's where the data comes in. You can see that the likelihood of achieving a second and third child at age 41, 42 when you're starting the journey is very low. This is an important topic to cover because the patient says, okay, so now I have 20 eggs, what does it mean really?

So what we see is with a new technology is that for each 10 eggs that we have, only two embryos make it to the finish line. There's a lot of attri, we usually blame the husband for that. But to be frank, it's usually the egg. 10 eggs will, will t 90% will survive. That 90% was about 5% when we used the old technique of slow freeze, just to, to give you a reference of what we've been doing in the eighties and nineties and 2000. And then out of those nine eggs, 75 will percent will fertilize from a single 80. They tell them on the second date they want to sim sim analysis, make sure that it's worth going for a third date cuz you brought a lot of eggs to that relationship, but don't do it on the first date. That's too scary. And then we check the sperm and if it's a normal semen analysis, you'll get about six or seven embryos out of it.

Two will make it to the finish line and implantation rate, which means they have a normal embryo and a freezer and I transferred it into the uterus and the patient took a baby home is about 50%. In endometriosis, it can be at time 30% because endometriosis goes hand in hand sometimes with adenomyosis and with some inflammation and sometimes fibroids that you've heard. So the better the uterus, the better implantation rate, the the more challenging uterus, you'll need more eggs to compensate for that. Lastly, there's obviously the financial consideration, which I think is the rate limiting step for every patient who's considering that. It's not a cheap process. Usually the process of just coming to talk to a fertility specialist during amh, during FSA discovered by insurance, you can see here that egg freezing cycle can range from 5,000 to 12,000 in most places in New York it may be arranging around seven to 9,000.

Monitoring appointment included. All the blood tests and ultrasound during those two weeks in the post-op monitoring appointment begins with the start of the medication and then the egg retrieval is included, the medications sometimes are included and we fight for a patient to try and get that covered. I think that another journey for us or another avenue for research is how can we justify doing those injection and getting them covered by insurance even if a patient doesn't have egg-free in coverage or doesn't have a partner, which I feel, uh, is a significant amount of the, the expense there. Storage fee is about 60 to $90 a month. And then thank God New York is a, New York is a mandate state now. So as of January, 2021, every patient who has insurance in New York state who works for a company that has more than a hundred employees should have three IVF coverage. What that means, if she froze eggs, they will cover the creation of the embers and getting her pregnant with those eggs. That's it. Thank you so much for listening and I'm happy to take any questions.

Thank you so much for this. Um, I think this is a, a very important topic, obviously, um, you know, for all of us with endometriosis. Um, just a quick question for you actually, two questions. One, um, I've heard a lot about, um, endometriosis patients staying on if they're on birth control, staying on birth control at times to do egg retrieval and all of that. I just wanted to see what your thoughts are on that.

So I'm a big, big believer that birth control pills should be used freely in endometrial patient and I think they're much better tolerated than, uh, Lupron, uh, in most patient. Uh, and as well as i u d progesterone, uh, product with, uh, Miano Sky and others birth control pills prevent a patient from ovulating every month. And as we know, pain during the menstrual cycle could be debilitating around the time of the menstrual period and also around the ovulation. It actually has a term, it's called middle schmidtz. So it took a German doctor to find <laugh> a name of a painful period, but the birth control prevents ovulation and prevents a recruitment of a follicle. And usually what happens after 14 days, you release an egg, that egg by default becomes a cyst, a corpus luum cyst. And if there's no pregnancy, that cyst usually goes away two or three weeks later.

But with endometriosis, because of the anatomy that has changed, whether because of the actual disease or the surgery that was proceeding, that cyst can linger a longer time and can cause issues. So birt to pills when a patient is not trying to conceive and has known endometriosis has been shown to help with preservation of the egg count and prevention of torsion prevention of ovarian cyst. So yes, we do use be control pills quite, uh, frequently and sometimes even continuously for three months or six months. There's no reason to have a period every month from the health perspective. Right. And one of the big theories of how endometriosis, uh, started is retrograde menstruation. So if the patient has a very thin endometrial lining and less periods per year and less menstrual period, it could slow down the deterioration of the disease besides preserving some of those follicles.

Thank you. And just one quick other question. Um, you touched on the, the point that a lot of patients that you see that have endometriosis have, um, you know, concerns about after going through everything for, you know, egg freezing, um, their symptoms afterwards and how they're going to feel. Um, just curious on, you know, I don't know, maybe the percentage of patients and how, can you explain a little bit more about some of the treatment

Afterwards? Post, post-op? Yes. Yes. Okay. So the, the good news is that if you go to a reproductive endocrinologist and most of the centers here in New York know how to manage patient with endometriosis, eh, essentially most patients will have some discomfort a day or two after the retrieval, even if they don't have endometriosis. It's definitely more pronounced in patient with endometriosis A because they're more aware and all the nerve endings are already hypersensitive. So in those patients we will give post-op medication preventively rather than waiting for the patient to have pain similar to C-section. In the past we used to kinda like be ugh, you know, only if you really need to. Now we give it in a regimen we know every six hours you can take Tylenol, you can take Motrin. There's no reason why the patient should suffer, especially once the anesthesia is getting out of your system.

So if you have a retrieval on the Friday and Saturday is 24 hours later, that's when I'm expecting the patient to have most of the, uh, tenderness. So at that point we'll start a regimen of post-op pain, usually with nonsteroidal antiinflammatory Advil or Motrin and Tylenol, nothing, uh, more than that. And usually within two to three days the pain, uh, resolves the pain, the pain goes completely, uh, back to normal, usually with the patient's next period when the cyst are shrinking completely. And that's when we usually give two weeks of birth control pills. So if the patient started on April 1st, the journey of egg freezing and say by tax day she had a retrieval by, uh, May 1st you got her next period two weeks after the period, she'll go on a pill for two weeks and then by mid-May the overs are back to normal and should not have any residual effect. Thank you so much.

One more

Thing. Yeah,

Congratulations. Ask me if you can just explain real quick, can you do the egg retrieval the same time as surgery?

You spoke on it already, the eggs have to be matured mm-hmm. <affirmative>, but can you just explain one more time to patients why it is we don't do egg retrieval the same day as their endosurgery?

Yeah, I mean, intuitively it would make sense to go under anesthesia one time, right? You stimulate the ovaries, I do my egg retrieval here in the hospital, and then Dr. Sk, you know, Dr. Scher, Dr. Goldstein will do the surgery. The issue with that is two things. One is the ovaries stimulated. So instead of being two or three centimeters, now it's six or seven or eight centimeter, that's one two in the hospital, you don't have the embryology lab, which is where the eggs are being frozen. And when you stimulate an ovary, the planes are different. So if the surgeon needs to remove an endometrioma by default, there's gonna be more bleeding from the follicle surrounding that. So you want to come down those ovaries after the stimulation, wait two weeks and then go for surgery. So usually if the patient has stage four, stage three endometriosis and we know we may end up with losing the Fallon tube and one ovary, we will see them before, at least for consultation and strategize. Sometimes you have to do the surgery first for us to have access to the ovaries. Sometimes you'll have the retrieval before the surgery. That's is where the key communication between your endometriosis surgeon and the reproductive endocrinology. You don't want to go to a surgeon at, you know, a Cleveland Clinic and a du egg retrieval at U C S F. You want a team that's there from start to finish.

Thank you so much guys. Enjoy evening.