New Developments in Fertility - Janelle Luk, MD FACOG

Big one. The big one

About that. Oh, above. Thank you. <laugh>. Oh yeah. Dis Scotia. None. I'm, um, I'm the medical director and the founder, uh, co-founder of Generation X fertility, but no other companies. Um, so this very standard graph of courses of infertility. Um, and I think Lydia also mentioned this, which is about the, an explained infertility. So I don't know if the diagram is a little bit fuzzy. I'm gonna read, uh, some of the numbers. So for couples who come in for infertility, um, about 35% of them have male problems. Uh, 35% of them have tubal and pelvic pathology issues, which including endometriosis. Um, and then for an explained fertility is around 10%. Um, and then ation dysfunction, um, aging or, um, anything with the ovaries not able to olay. So that is about 15%. Um, I get very, um, excited and also <laugh> with the patients and a little bit vulnerable telling when the patient come to your office and asking for explanation why she's not getting pregnant, then I say, Hey, you belong to unexplained infertility.

That is a very humble experience because she's coming here for you to explain something. You tell her this is unexplained fertility. It's really ironic sometimes, but that category, that's what Lydia was trying to say. Ha may have patient with endometriosis. And this become very tricky. How do you diagnose that? How do you put the patient day in the category of unexplained fertility, but to the pelvic and tubal pathology? Um, so this is something we, we will talk about as a patient, come to me with infertility and what are the things and thinking that I have. Um, so 30 to 50% of patient with infertility of endometriosis and 10% of patient in the world has endometriosis. So it is a disease that is a, um, it does affect patients. Um, I did a great Instagram live, I think with Dr. Haas. And, um, and we had lots of questions.

And they, the poor patients are so savvy. I didn't know they're from endo fund, from my patient. They were asking all this questions before even the Instagram li uh, uh, started. They asked this IVF the only option for women of endometriosis. I have two chocolate cys in my ovaries. Should I do surgery with excision, cost diminished ovarian reserve? Why would I have endometriosis if I don't have symptoms? Does endometriosis removal help with IVF outcome? What are tests for endometriosis and how come there are different approaches for endometriosis? So we are going to try to cover all these questions in my LA lecture. And then I saw your beautiful agenda, uh, from Tame Ashkin, uh, whole weekend of the symposium. Some of them has been answered already, I know from other lectures. So I'm going to just go through some very simple and the thinking that I go through with my patients as they come to me with, um, some of these questions.

So what to do and how to treat. Um, so this is a little bit different from, uh, some patients just coming in for pelvic pain. You have to understand these people. Uh, these patients are really trying to just get pregnant, have a baby when they come to my office. So pain is secondary to them. And usually they don't mention about their pain, they just say, Dr. Lou, give me a baby. Get me pregnant. Um, so surgery is not on the top of their mind. They just want to have a baby. They just wanna get pregnant. Um, the idea is that we as doctors, we always go to the chief complaint. We start always from there, then we go like, I have leg pain. And you go, why do you have a leg pain? I have stomach pain. Then you go to stomach pain. So you always go through why patient come to your office.

A majority patient go to a refer, a refer two center is, um, have want to have a baby. Um, and so for fa, so I always look at what is the presenting symptoms, because that would differentiate suddenly how I think about this patient. Um, and presenting symptoms is, so chief complaint is, I wanna get pregnant. Then I ask, what is your presenting symptoms like? Do you have other presenting symptoms? I was like, what, what else do you have except that you want to get pregnant? How are your cycles? Uh, do you have pain during period? So those are the things that elicited. Um, the diagnostic tool usually is physical exam, ultrasound, mi, laparoscopy, which went through by some of the doctors from yesterday, how to diagnose endometriosis. But endometriosis can be silent. Endometriosis can be, you can still have endometriosis with a great physical exam with no ultrasound of any endometriotic cyst.

Uh, MRI doesn't show any highlighted lesions. You can still have endometriosis. So any non-invasive accepted laparoscopy, which is a surgical intervention, any non-invasive tools, doesn't mean if this is all negative, doesn't mean you don't have endometriosis. So that this where my professor, when I was at Yale Medical School, they always say, Janelle, we have lots of fancy tests and ultrasound and everything out there, but at the end, the best thing a doctor can do for a patient is history, history, history. Um, taking a great history is so, so, so important. Um, and quite honestly, I see a patient in my room. We take a history. It usually take about, usually diagnosis is about 70 to 80% of the time. I'm very accurate with my diagnosis, just taking a history. I can do ultrasound, I can do other evaluation to confirm, but taking a great history, asking and be open about endometriosis and learning about it is so important to a patient and empower them.

Um, because some patients, they are so absorbed of having a baby or the fertility, they may say, oh, Dr. Luke, I've been having pain for 20 years. This is great. I just take two Tylenol. It was great. Um, they may have lost, um, because they're sucking it up. They like, they don't want this to be intervened with their career or their life. They may not see as a symptom. So I have to elicit, I have to bring it out from them because they, it is not easy sometimes because patient's priority was not because of, um, pain. That's why they come to you. So taking a great history becomes so important. Um, why I am start to go into medical treatment. And I know, um, uh, the lecture before me, they went through a lot of like, um, uh, loss of this great and medical treatment.

And, and so endometriosis treatment for when you're trying to seek a baby's very limited because all medical treatment is anti fertility. You cannot get pregnant on this medical treatment. So you cannot say, oh, let's take some birth control pill, then you will be great <laugh> to get pregnant. No, you can't because of birth control pill. Oh, take some Lupron. No, you can't, you cannot get pregnant if you're not cycling. So medical treatment is not a choice for endometriosis, um, when patient is seeking for fertility. So then this remained in surgery. So after I elicit a question to a patient, this is where the trick comes in. Um, hey, so and so you have in pain. I was like, you may or may not have endometriosis, and most majority of patients will be like, oh, really? I said, how do you diagnose it Dr. Luke? How do you confirm that?

I said, I cannot confirm that. However, um, we are on the way. The gold standard of endometriosis diagnosis is usually the oscopy, which is a surgery. And majority for my patients, do not like to go to surgery as the first, um, as the first intervention. And this becomes really tricky for us as infertility doctors, because pain is not that bad. They just wanted baby. And you are telling them you need to do a surgery in the, in the operating room to diagnose an endometriosis. Sometimes they're hesitant. So now how do you educate these patients? And what do you tell them? Now? Um, I know Dr. Sha in the, uh, kin in the audience, we say, well, Dr. Little surgery can help fertility. That is why we do surgery. Absolutely. And this is some of the things that we are and, and, and, and forced to do.

But then that's why in the couple of slides in the, at the end of the lecture, I also talk about some of the non-invasive testing as also how to take care of some patient who is unwilling to do surgery. Um, so how the surgery able to improve fertility. Actually, many studies has discover for stage one and stage two, I know Dr. Shahan also talk about yesterday at the lecture. Um, surgery improved tremendously in the fertility for patients of endometriosis and IVF may not be the first, um, treatment they go to. They go to surgery first because it can decrease the inflammation environment in the belly, improve quality of the eggs, increase treatment of, uh, the improvement of the movement of the Celia, um, and resection of the scar tissue. Um, it decreases any oxidative stress. Um, so it has to multiple organs. Um, so it is not a bad thing.

Um, at, I had a patient with, um, severe, uh, endometriosis. She did not have the, um, financial means to do ivf. So I sent her to, um, her surgeon who say endometriosis specialist. And they, her tube was basically twisted around the ovary. And I want to show you this diagram is to show you that how the gamut migrate to the uterus. So when the patient getting resection or scar tissue, that can also help, uh, with the, um, movement of the, um, in the into, from the ovary to the UUs. So, um, they, it freeze her ovary, freeze her tube, and she got pregnant after three months of, um, time intercourse and after surgery. Um, second thing we do for treatment of mild, uh, for, excuse me, for endometriosis, uh, is ivf. So, uh, there were also papers coming out. And I know when you have a hammer, everything is a nail.

And when yeah, when you have, yes, that's right, <laugh>, I was just like the nail. Um, so I mean, IVF doctor, so the first thing patients come in is, and I told you the majority of them do not want to go to surgery. They just want a baby. So they would ask me, Dr. Luke, can you have me, um, do a ivf I really just retrieve eggs, make an embryo. Um, I have patient even have chocolate cyst inside the mri c the endometriosis. I told them, you have endometriosis. Um, they say, no, no surgery, Dr. Luke. So we did my ivf where we do ol and this some of the things I feel passionate about my ivf. Um, what we do is that we give a pill, which is the aromatase inhibitor, um, which decreases the estrogen exposure for the patient. Uh, then we stimulate them with low dose of, um, injections of FS and hope to get good number, um, of x.

Some of this patient, when they do have endometriosis or has surgery in the past, some of them may have diminished ovarian reserve. And so the a quantity is not a lot already. By using this kind of protocol, I do have to adjust the FSH dosage in really individualize from day to day to try to maximize the ovarian potential. Um, and so we give electrosol in conjunction with the shots. Uh, the way he is very general presented. Sometimes I do give shots in the middle means I don't stimulate them at the beginning. I usually do electrosol first, then stimulate. It really depends on how the ovary is waking up, uh, during the cycle. Um, so one of the questions I didn't address in here, that's why I brought that to Sly, is, um, what if the patient have chocolate SISs, um, with the, in the ovaries?

One of my friend who gave me this picture, um, with the chocolate CYS and the endometriosis, uh, my colleague Dr. Farrell. And so, um, what do you do with that, with that surgery? Um, and, uh, sorry, let me go. Yeah, so what to do with the chocolate cyst. And so one of the thing I was just showing, showing you the picture, um, if you do have chocolate cys, the idea is what's the size and has it bothering to the patient. And for me, when patient of one or two millimeter, two centimeter, um, chocolate cyst, sometimes they do not want to remove the chocolate cyst because it's small. It's not bothering them. Um, when it is bigger than or bothering the patient. Like pain is a bigger driver for surgery for me to tell patients, especially when patient again is not seeking for surgery. They're just here for free a baby, um, for two centimeter cyst or small assist.

Why IVF doctors are like, oh, don't do the surgery if you doesn't need to because the ovaries wrapping around the cyst. I don't know in the previous picture that I was just showing you. Um, and when that happens, um, when you're trying to cut the cyst, um, it can sometimes damage the ovarian epithelium. Um, and as a result diminish ovarian reserve, have I have seen them after multiple surgeries or multiple chocolate CS resection, it does diminish the ovarian reserve. So that's why, uh, we don't usually promote when the smally or is not bothering patient to remove the surgery, uh, to remove, to do surgery first. Um, so then the next talk is, which is very controversial, which I mentioned with Dr. Haas, um, in our Instagram life is what is it possible to diagnose and treat endometriosis without surgery? Um, so I am a very old school.

I know, I, I I don't know. I I am I've been practicing now 12 years. Uh, so fif 15 years ago when I was 17 years ago when in medical school I was, uh, never learned non-invasive testing. Gold standard is always, always laparoscopy. Uh, two, three years ago, a new test came out, um, called uh, Reva, uh, where involved with biopsying, the UUs means they take a little sample of the UUs, um, and then they try to find a marker called BCL six. I was with, uh, Dr. Hugh Taylor at Yale Medical School. I was one of those medical students who collect this tissue in the operating room for all patients with endometriosis or no endometriosis. Sign up for the study and we will be checking, we'll bring the tissue from the surgery. I remember suite, uh, back to the Yale research lab. And then we just trying to find a marker to see if there's any marker we can check for endometriosis.

So this was the marker and the couple of them, so this got famous, which is called BCL six, um, positive patients in the recept study. So then my patient, obviously the study went very public. Uh, patients start to ask me, because now they say, Dr. Luke, my Amin implant check, do you now need to do surgery to see if I have endometriosis? They have no pain. This are now is ironic. This are no pain patients. And I told you endometriosis can be silent. Now they come to me with a presentation with embryo, not implanting. So that is tricky because now there's not in pain, don't immediately to do anything, but it's because of embryo, not implanting. They're asking me, do I need, does she need surgery? And it becomes very interesting is because, um, last 10 years, I don't know, some of you who are in the IVF world may also know we start to screen embryos to know if the embryo are genetically normal or not.

So in the past 10, maybe 12 years before the last decade, we usually cannot test embryo. So when the embryo went into the UUs, I put it back into UUs and it's not implanted. Our stock is a very easy job. We just say, oh, don't worry, it was just a bad embryo. So the implant, so let's do more ivf, we need to get better embryo. So then it will get in and stick. Then this pg t a testing came out, which is a genetic screening of the embryos, which supposedly is that to screen if there's a down syndrome or anything genetically wrong with the embryo. And if it is normal, it should stick. That is the theory. So then the test came very famous. I remember when I first came practice the first year, everyone I'm like, yes, do the screen. Who doesn't want to predict a boy?

Girl, normal. Uh, you tell them it's high success rate when you screen the embryo. So I did all that. Then after you do, after a couple of cycles, then you start to have patience. Didn't have a, have a great normal embryo but didn't stick. Now the patient come back to your office and say, Dr. Luke, you, you made me this embryo and it didn't stick. So what is wrong with me? So then this very smart, the researchers in the last 10 years, and we discovered, wait, endometriosis, right, can cause us, maybe can cause us bad implantation, but no one really wants surgery. Again, this patients do not usually have pain, they just want to get a baby. So now, um, they came in and say, Dr. Luke, I saw this test. So this test developed in the last five years and I got this on my desk and, and they say, Dr.

Luke, I want to dova. I said, wow, okay, let's do that. And if you do a biopsy, you will know if I have endometriosis or not. And I was so hesitant to do it because I told you I learned the away the gold standard is laparoscopy. Now you're asking me to do some new test three years ago, do some biopsy and some market goes up and now I'm saying, you know what? The market went up. So you need to go for surgery. Now it's first one's a big deal telling a patient go for surgery, who is have no pain and no, no, not never asked me for surgery and just coming in to ask me to implant an embryo. So it was become a very difficult choice for me, um, in some way. So I, I waited a little bit, so I I I was more skeptical, kind a doctor.

Um, so one year later, however more study came out by five big institutions and say, wait, we found a treatment. The treatment is if you give the patient Lupron for three months, it will improve success rate by 15 to 20% or surgery that will improve 10%. So suddenly I have this di this kind of, um, feedback from the, from, from the, from social media, from the study. Then this test becomes more valid to me because now I can give patient the choice of either doing surgery or Lupron. It's still a big thing. Lupron is a hormone medication, which you've described by the previous speaker. It shut downs a woman menstrual cycle. One more time. This patient's here tried to cycle and have a baby and have sex. Now you're shutting down biological clock for three months and say, wait, get some treatment and we will give you Bain an embryo. So this test just came in last two to three years and becomes a still many places of redoing some of the research and data. I know, um, Colombia, Zev Williams is my, uh, friend and also IVF director there. And um, they are doing studies and looking at endometriosis and really one-to-one correlation. Still try to, um, kind of, um, discover the more, the validity of this test. But, um, but that is right now the only test I know where we will do something or not do something from a non-invasive way from endometriosis.

Okay, I'm pretty good,

Right?

So we'll take, oh yes, I think there's some questions. DRAs. Yes.

Thank you for your presentation, Amanda here. So, um, I have done two laparoscopics, 1, 2, 5 rounds of IVF and then five transfers, two miscarriages, three that didn't stick. But I have genetically tested embryos that are normal. And so what would you recommend as kind of a next step? Could, would it be the, and I've done the era A and some others, but

Hmm, I know, I know. I'm, um, thank you for sharing your story. I know it's hard. The process is so, so growing and hard. Um, so

As some of you may know, I know endometriosis, the ETI ideology of it, um, have lots of causes and, um, and thank you Amanda for sharing this story. Um, the, there's lots of inflammation in the, uh, possible. So endometriosis, one of the theories that the Simpson three back in 1926, which is retrograde menstruation, um, and one of the theories that if there's, um, uh, there's some dysregulation of immune system in the belly that can cause us high inflammation. Um, so when patients are having this discussion with me, this is a day-to-day discussion, um, uh, that I have with my patients. So I just want you to know, uh, generations next, when is first started, uh, of, of course we don't have the big institution's name around the city. So many of our patients is when they failed and they come to our office and we had to think outside the box to treat patients.

So, um, thank you for sharing. Um, so it, yes, so ectopics, uh, just listening to your history, um, that I know there's lots of inflammation already in the belly. Um, and I, there are two things and then there's also the embryo screening normal. So I'm going to discuss two things. One is the environment, two embryos, um, the environment, so the environment, I know, um, yeah, surgeries, uh, we talk about exploratory laparoscopy. Um, it's so funny, I don't know how, uh, Dr. Shek does it, but I used to learn from some of the endosurgery. They, they sometimes wash the belly from the inflammation. They would just kind of flush the belly. Um, and <laugh> get the fluid out. I know <inaudible> like, hmm. Uh, so there's the inflammation kind of a treatment of the belly Lupron. There's another treatment that's can think about like how to shut down the ASINs, the feeding of the endometriosis.

Um, the second thing is about embryos. This is really, really hard for me to tell my patients because I do also have normal embryo fail for implantation, um, or miscarriage, repeated miscarriage, two or three and the fourth stock stock. So for stories like this and also patients I've seen have multiple means they do gc they do many things and still have a miscarriage. So then I want to remind of us what they screen to normal embryo means is screen normal embryo or it means is that it is a 46 chromosome and sometimes it cannot screen trip ploy, by the way. So it has a, if there's a repeated set, it doesn't it, the, the the machine miss it. Okay, so just be mindful error rate is due 3%, but I'm not trying to say all your embryos are in the 3%. I'm trying to say is that the other things, this genetics are not being screened for, um, that such as, uh, placental cells implantation to affect the derm.

How healthy are this cells? Um, so as my career is growing and watching the failure of norm screened normal embryo not being sick or having issues like this, um, I do reinvestigate the environment with the patient, uh, with Dr. Shukin, with all the endometriosis experts. Um, I reinvestigate the belly. Um, I, yes, we do sometimes have to transfer sometimes em two embryos in because that means not all the embryo, even though they're screen normal, have good placenta cells. So let's say I, my patients have five normal embryos already, FA too. I may have to the third transfer not to went through the tr the emotional trauma is horrible for these patients and to just put two in so they don't have to go two more separate transfers to get to the right one. Um, so some, those are my, some of my suggestions. Oh yes,

Very

Ignorant question, but oh, okay. I feel very ignorant for asking this question. But um, for ivf, how many browns of IVF is recommended? Do most people just have one? Um, is very expensive to do. And then how many eggs? Like when do you know it's, you need to do another I guess. I don't know if it's the term as chronic. No,

Don't worry about it. That's a great

Question. I've can concentrate on other things. <laugh>, yes,

No, no, no, that's a great question. So thank you. Um, average patients, um, have about, um, let's say a patient. So this is all depends on age. Uh, I go back to the age factor. So in a patients with the, uh, in the thirties, they usually can get over maybe five five. The range can be huge. So yes, there are low, low normal number of eggs, but like, let's say five to 15 eggs, um, usually will get like three to four or two, three to six em blasts. Uh, means the end stage of the embryo and then screen wise, half of them will be normal for a patient who is between 30 35 and then it's like 10% decrease as the age goes on. So for patient who are under the age of 35, if they have a good quantity of eggs and they making good number of embryos, they usually need one ivf, they don't need more.

Now I told you our generation X was started when there are loss of giants around me and how can then walk out patients come in. I don't usually get 10 50 eggs. We usually get two to three eggs, <laugh> 1, 2, 3 or four. Um, so this are usually patient with diminished ovarian reserve. I'm passionate about endometriosis, but I'm very, very passionate about a diminish of and reserve. Um, so this patient only have one or two eggs. Some of them are older, some of them younger, but what we do is that we keep on retrieving the eggs. Now the younger you are, even though you get two eggs, please don't cry. Usually you have one good embryo, so it doesn't matter. There's only two eggs. So quantity, never justify fertility potential. Um, is the h h HH and how long you have been trying to get pregnant? Um, so one, two, or three. So for those patients, some of them we do need repetitive, um, uh, retrieval to bank enough for embryos because usually, uh, they want to get pregnant breastfeeding three years later. They want to make sure because now the, the ovary is more decreased in their, in terms of their reserve. So then, um, they will need to use the ember that they banked, uh, three years ago and put be their second baby. So that is when people would do multiple IVF cycles.

Any other

Questions? Oh, this question.

Hi Dr. Luke, how are you?

Hi.

Um, I was just wondering if there are women who are in their early twenties and they've been diagnosed with endometriosis twenties, do you recommend these women with endometriosis to freeze their egg early? Um, and during that time when you, when these women are are, are going to freeze their eggs early, the process to actually give them different types of hormones to freeze these eggs, would it make endometriosis worse? It's just understanding the irony of this.

Uh, i I was going to address this. This is such a great question. You guys are so smart. Oh my god, these are tough questions also. So, um, I was just talking to the patient and uh, patient's father. So usually when patient come in the young twenties, they come with their parents <laugh>, they just finished college, they're in pain, they have endometriosis. They come to ask me the exact question, the way you worded it and say, Dr. Luke, I'm scared. I want babies. I'm in pain, I have endometriosis. And uh, this is a very knowledgeable, um, uh, college, uh, student. And she was asking me an also talking to her dad with her by her side, I want to freeze my eggs. And then the daddy asked me those questions, is it worth it? Is it very expensive? Why am I doing this now for my daughter?

And, and I was like, okay, so here we go. So, um, so first of all, um, why is this patient no stress? Endometriosis is usually <inaudible> so young coming to BSS pain. And as a, as a woman, we should never live this way. Pain is not normal. We should not say it's normal. We, oh, it's okay. Pain's okay, it's okay. I sweep, I wash the dishes and I go home. I'm kidding. I tell that to my husband. But women should have their own empowerment and no, and it's not okay. Certain things is just not okay and we should not live that way. So, um, I I usually, um, just kind of, uh, think about it this way. Use this absolutely right. Every time you stimulate for I freezing, you can invoke endometriosis. So this patient also thought about this and the logic was this. Um, she also had diminished event reserve.

That's how she came to my office and she has pain. She knew and she read about endometriosis and she actually went to see endometriosis surgeon before seeing me. So the discussion went out like this, if you have, um, we actually went ahead and did two eight retrievals to get her eggs because she's young knowing that endometriosis is flare. So I talked to endometriosis surgeon knowing that, um, I did give that ol, uh, protocol, which is turning down her estrogen and kind of the same. So two, uh, one don't hits two birds. One is to stimulate her ovaries and one way is also to st uh, suppress the estrogen. So we stimulate her with ol with fsh, um, and also to cut down the cost of IVF because ol has a, uh, is much cheaper than fsh uh, medication. And we did the, we do encourage her to do that.

And she wanted it, she wanted egg freezing. And she said Dr. Luke and told daddy next to her, I'm not gonna have a baby at 2 35. Like she was very determined. She knows her path, she knows her career. She's a photographer, she's gonna travel. She's not, she's at, but I love to want to have a kid and as a result I want to do my egg freezing. So, um, we did the two A freezing and now she's going through surgery and we got pretty good. Her am h was slow. So this funny am h is one of the marker looking at ovarian reserve. Um, and that's really prompted her coming in. But when you are young, um, sometimes the image does not reflect totally the number, um, of X that you have with stimulation, I can get more. Um, so each really beats fertility in many ways or even fertility preservation.

So the younger you come, uh, it is a amazing story. Now just want to reverse back when I will say don't do egg freezing. So I usually challenge my patients with egg freezing because I want them to be empowered. It's a very expensive, you put your body through a lot. So I usually challenge them because I don't want regrets to do egg freezing. So I know today's not egg freezing talk, so I'm just going to say why one, in what situation, I will tell her not to do egg freezing. If she's planning, let's say I'm planning of a baby in one year or planning to go, then you don't need to because she's young, she's gonna get pregnant if she's going to, you know, have develop her, you know, um, have a family in one, two years. So some of the times I usually ask Why are you doing egg freezing? What is thinking? Um, then I would then would say yes, because she does not need, she can also do a surgery and have a family. She doesn't. But the reason why she was egg freezing was because she was knowing determinate that she's not having a child in her twenties, um, and she's going to have her career and so forth. So that's why egg freezing was in her agenda. Just want people to know.

Great. You have

I, uh, yes, yes. I have to coach my, uh, daughter's basketball team. I used to play basketball in Hong Kong, so, uh, I have to coach your basketball team fucking Scarsdale. So I have to go. So sorry. Thank you. Thank you. Thank you.