Welcome everyone. My name is Vance Broach and I'm a gynecologic oncologist at Memorial Sloan Kettering Cancer Center in the United States. I'd like to welcome you to today's Surgical Film Festival. This is our third festival for 2020. We're thrilled with yet again another full house today with attendees from 80 countries around the world. I want to mention a few housekeeping notes relevant to the Zoom platform of this festival. For optimal viewing of our presentations today, please adjust the Zoom settings to full screen mode in the top right corner of your screen and adjust your view settings to fit to window. Second, the quality and clarity of the video presentations are linked directly to the speed of your internet connection. High speed and wired connections are best for viewing these videos. If the quality of your video stream is poor during our presentations today for any reason, the webinar will also be available to view on the IGCS website and the IGCS educational portal and that'll be uploaded in a timely manner. We have an incredible panel from around the world who'll be sharing their expertise on fertility sparing techniques for pelvic cancers. Immediately following the films, there will be time for discussion and we encourage you to submit questions through the Q&A feature at the bottom of your screen and we'll do our best to address as many questions as possible and time allows. I'd like to give a very big thank you to Rathusilani who will be helping field questions as well. Finally, I'd like to give an enormous thanks to all the IGCS staff who've made this possible. As you can imagine, there's a lot of behind the scenes things that happened to make this move move so smoothly and we're incredibly grateful for all of their help. Now it's my honor to introduce today's speakers. Joining us are Professor Alejandro Sotorini, who's the Associate Professor of Gynecology and the Chairman of Gynecologic Oncology, also the Director of the Fellowship at the University of Buenos Aires in Argentina. Also joining us is Ratan Ribeiro, who's a Surgical Oncologist in the Department of Surgical Oncology at the Eraso-Geitner Hospital in Brazil. Dr. Sushmita Gordhandas, who's a fellow on the Gynecology Service and the Department of Surgery at Memorial Sloan Kettering Cancer Center and finally Dr. Paula Brady, who's the Director of the Oncofertility Program and Assistant Professor of Obstetrics and Gynecology at the Columbia University Fertility Center in the United States. And now, without further delay, we'll begin our session today with Professor Sotorini setting the stage and discussing fertility-sparing radical trachelectomy for cervical cancer. Professor Sotorini? Okay, this is our technique we designed some years ago and we call it now the C1 radical hysterectomy and I will tell you why. And this is the surgical anatomy at first. We must have a very good training in surgical anatomy first. You can see we spurred the uterine arteries and the hypogastric nerve. That's the reason why we call it C1 ART. And as you can see, all the complexity of the uterine basal and this kind of web and the uterine blood supply provided by the uterine arteries for the uterus much more than the ovarian web. And this is the radicality we can obtain and why we decide to spur the uterine arteries. Because we will have a very good supply, a blood flow supply to the endometrium for the case of a fertility-sparing, but also if we spurring the uterine arteries and the blood flow to the uterus in the case of a recurrence, we will have all the blood supply for performing the treatment, the oncological treatment as a chemoradiation. And why we spurred the nerves also? Because spurring the autonomic plexus, the hypogastric plexus following the Michael Hegel's principles of the total mesometrectomy will avoid all the autonomic complication of the bladder and of the rectum and to the sexual function. This is an open surgery. We designed the protocol many years ago in 2003. And the first surgery was in 2004. And we present this video for first time in Bangkok in 2008. First of all, we perform a complete surgical station, dissecting all the pelvic structures, as you can see, all the fossils and the spaces. Then we perform a complete pelvic lymphadenectomy and frozen section of the lymph nodes in order to continue or not the operation. As you can see here, the lymph nodes. And now we completely dissect the uterine artery, as you can see here. Yes, all the whole uterine artery, since it begins at the hypogastric artery. Then we perform the same thing on the other side. Here you can see all the structures, the whole uterine artery here, and here the urethra. And here you have the nerves going to the bladder with the urethra. We dissect it from the anterior parametrium. Then in the posterior space, we dissect the hypogastric nerve, as you can see here. We have the urethra here, the uterine artery, the hypogastric artery, the vesicle artery, and the other, the external iliac artery and vein. As you can see, in the posterior space, we can dissect every pelvic structure after the lymphadenectomy. Here we can see the hypogastric artery, the vesicle one, and here all the uterine artery. And here we can see how we can spur perfectly the hypogastric nerve. We recheck always all the structures. Here you can see the nerve. Yes, here is the nerve. And we perform the surgery through peritoneal foramens for performing all the dissections and spurring all the blood vessels. Here we clamp the posterior parametrium, the utero-sacral parametrium. Here you can see how we spur the nerves in the pararectal space. We can see the urethra and the peritoneal foramen. Then we dissect the posterior parametrium, the utero-sacral ligament. And we can see all the structures. Here the rectum, the parietal space, the rectovaginal space. And we check the radicality and the other structures before for continuing the surgery. It's here you can see the uterus. For continuing the surgery. It's here we clamp the lateral part of the parametrium or mesometrium. You can see the good radicality we can obtain with this spurring all the pelvic structures. You can see very well the radicality we can obtain. Then we open the vaginal cuff. And after that we are going to transect the cervical stump. Okay, we rechecked the arteries before this, and we proceed to dissect the cervical stand. Here, we have the right barometrium in the clamp, pressing the clamp, and then you will see the radicality we obtain with this technique. Here, you can see the left barometrium. After that, we proceed to the frozen section, and with the frozen section of the upper side of this cervical stand, of the remnant cervical stand. Here, we can see how the uterus is preserved, the whole uterine arteries, as you can see here, the round ligaments, and here is the rectum, as you can see. Then, we suture the vagina to the remnant of the upper side of the cervical stand and the isthmus, and then we proceed to the posterior part. As you can see, we close the foramens and the posterior space. And here, you can see the surgical specimen with the radicality we obtain. And I would like to show to you a few slides about to support this presentation, and as you can see, when you are planning to perform this kind of less radical surgery you must always remember the prognosis factors, the classical prognosis factors, the probability of having, or the possibility of lymph node metastasis, of course, the figure staging, this general consideration as age, and the strictly follow-up is the most important thing. Apologies, Dr. Sotorini, for interrupting. We just can't see your slides. I'm gonna go ahead and share them for you, okay? Okay, okay, okay. Okay. It does, okay, okay. Remember this, you must always remember, have in mind the possibility of nodal metastasis. Please continue. The other one, the figure staging, as I told you before, general consideration as age. We never know when a woman, or which way women will, we can say it's young. We have no age now. In the past, we say, okay, up to 35 years old, but with these results, we really, we are not sure to tell when is young a woman. And remember, they will be for selected patients, because very less than the 46% are presented in stage one. So it will be always for selected patients. The next, please. And these are the women candidates for a fertility sparing, A1A, A1-2, and 1B1 less than two centimeter. But what support this idea? Because less radical treatments, and the consequences of it is the fertility sparing, have the same rate of recurrences than compared with radical ones. The next, please. We perform the staging under the FIGO staging system. We add the MRI in order to see the tumor volume. And we add the hystereoscopy in order to evaluate the magnitude of the endocervical involvement, especially in patients who will receive new adjuvant chemotherapy. We performed the hystereoscopy previously to the chemo and after the chemo. These are the possibilities to a less radical treatment. Remember, this kind of stages, and especially in 1B1 patients, now the 1B2 patients with more than two centimeters and less than four centimeters, the possibility of performing new adjuvant chemotherapy followed by less radical surgeries. The next. And after new adjuvant chemo, what can we do? We can perform a radical trachelectomy colonization plus lymphadenectomy, simple vaginal trachelectomy plus lymphadenectomy. The next. What kind of trachelectomy we can do? The vaginal approach or abdominal one. Next, the vaginal is a shouter adaptation or a shouter-like surgery. The advantage of this surgery is that it is absolutely extraperitoneal. And for the lymph node, you can perform the lymphadenectomy. Extraperitoneal for the, an extraperitoneal approach to the next. What about the ART? We can perform the, without sparing the uterine arteries as the original technique of Laszlo Ungar that he described in 2002 at the NGO, or our technique sparing the uterine arteries and the autonomic plexus. And we rename it as C1-ART. The approach could be laparotomic, through laparoscopic approach or robotic. The next one. This is the classical ART. It's like a radical hysterectomy sparing the uterus. The next one. This is the principles that I told you before that support our surgery. The next. This is the scheme of our, the radicality we can obtain. The next one, please. This is some slides of our technique. As you can see, again, the radicality we can obtain. Lateral, posterior. And what about our results? You can see that we are very, very young patients. It was a feasible technique. We can, we must abort only one case because of a positive lymph node in the anterior parametrium. We obtained four pregnancies, the most important. All of them with using neoadjuvant chemotherapy before the radical trachelectomy. We have two recurrences and two deaths in the first two patients we perform. And this is a summary of our experience. In 2008, we present this technique at Bangkok, at the IGCS meeting. Then the first cases in 2010, using the first cases of neoadjuvant chemotherapy before the ART. Then at the HEO, our pregnancies after performing neoadjuvant chemo followed the ART. The next one, please. This is the summary of all our experience with this technique. The next, please. This is the whole experience of our group with using neoadjuvant chemo follow the ART. And we can see the feasibility of the technique and the very good results in obstetric results and most important in the oncological ones. And this is our last presentation about this technique using this kind of technique, demonstrating that it was oncologically safe with the same radicality that the C1 radical tracheotomy at the same survival rates. The next. The next, please. This is the radicality we obtained and we compare the radicality of the C1 ART versus the next one with the C1 radical hysterectomy. And we found no difference in radicality with both techniques. The next, please. And this is the reason why we continue thinking that for fertility sparing, the radical tracheotomy must be continued being the standard for this kind of surgeries of this radical treatment because of the 8% of parametrial metastasis that we can be found. The next, please. Performing a routinary ultrastation. And this is the case we must abort the surgery because of the lymph node at the right anterior parametrium. And this was very interesting because it was after neoadjuvant chemo with a complete central pathological response. So we must taking this thing into account. The next, please. So we can demonstrate that like radical surgeries are feasible and absolutely oncologically safe. The next one, you must remember always to tailor the treatment for each patient. All the patients are not the same. And I want to thanks to my mentors and Professor Sardia and DiPaola who introduced the neoadjuvant chemo and the chemotherapy to the primary treatment of cervical cancer to Daniel Darshan because he was a great surgeon. He described the vaginal radical tracheotomy and with a great courage performing it in 1997. And with Zaldo Ungar and our group, Professor Cuno and Alex Aragona at the time of his fellowship. And of course, I want to end the presentation with the other slide presenting and give my gratitude to all of my fellows and my partnerships at the oncologic hospital. Thank you all for inviting me to share this experience with you. Thank you. Well, thank you so much for a wonderful presentation. So informative and a great video. We can't thank you enough. And we have a few minutes for questions and we'll just, we'll start. If we don't get to your questions, we'll try to answer them through the chat or we may have some time for questions at the end. The first question was about the use of surclage at the time of- No, we don't use any kind of surclage and all the patients become pregnant, became pregnant spontaneously, they, after neoadjuvant chemo. The other patient that did not become pregnant, they didn't try to become pregnant. So it is very interesting because the patients with pregnancies after neoadjuvant chemo were mothers as teenagers at 15 years old. And they were very young women with invasive cervical cancers. Imagine after neoadjuvant chemo, they were tumors more than two centimeters and less than four. So they are, for very young people, they had really bad tumors, really bulky tumors. So one of them became pregnant twice. So it's very interesting. And all of them are alive without any kind of recurrence. And during the cesarean section, we re-stage the patients and we found anything and they have not any signs of choroambionitis and something like that, that is described for as a complication and for the miscarriages described for any kind of less radical treatment or fertility sparing procedures, especially with the vaginal ones. Okay. I think there is just one moment for a comment from the audience that we're getting. And I believe this is gonna be from Giuseppe Del Poir. Are you able to share your comment, sir? I think I made that a positive no doesn't abort a trachelectomy. You could apply, I heard Michael Herkel's work referenced and you could treat it that way. Or adjuvant chemotherapy is certainly not proven inferior to adjuvant RT. So under certain circumstances, I think it's very rare if you apply all possible imaging techniques, MR, PET preoperatively, that you're gonna have a surprise finding. But if you do, you should be prepared to employ either of those two options to preserve fertility. Okay. Okay, it's a possibility, but everything is changing every day. It was a protocol that began at 2004 and all the patients were treated by the same team with the same technique performing all the same to evaluate or to have the best evaluation at the end of all the patients at the result of the protocol. All right. Well, thank you so much again for a really excellent talk and discussion and a beautiful video. In the interest of time, we're gonna go ahead and move on to Dr. Ribeiro, who is a surgical oncologist in Brazil and who's gonna be demonstrating a video of a uterine transposition. Dr. Ribeiro, thank you so much for being with us. Thank you, Vince. So thank you to the IGCS for the invitation. I'm so pleased to talk to you about the uterine transposition, which is this new, exciting technique and I hope you enjoy it. So can I change the slides? Let's see if it works. Okay. Not working. Vince, can I share my screen and then you just play the video? Okay. So those are my disclosures. Okay. So the idea is today to try to share with you how to identify possible candidates for uterine transposition, describe the technique and discuss some pros and cons of this new technique. So just to make sure we are all on the same page, pelvic radiation causes infertility even in low doses and it's also dependent on the age of the patient when they do, on the patients when they do radiation. So at birth, they need more radiation but as they get older, lower doses of radiation are capable of causing ovarian failure and just, and not just ovarian failure, but also myometrial fibrosis, endometrial fibrosis. And actually there are just two cases reported in the literature of women who got pregnant after pelvic radiation. And one of them, it was a very low doses, usually much half of the dose that we usually do for anal canal cancer, so. So what's uterine transposition? So the whole idea is instead of performing radiation with the uterus in the pelvis for patients with pelvic malignancy is to remove the uterus from the, to the upper abdomen, perform the same treatment, same radiation and then after radiation, just putting the uterus back to the pelvis. So this idea came from two very well-known techniques. One is the radical trachelectomy. So we know that ovarian vessels can provide good blood supply, not just for the uterus, but for tubes and ovaries. And also we know from ovarian transposition that mobilization of the ovaries to the upper abdomen can preserve their function. And patients can have not just hormonal function, but also oocytes and reproductive function. So we reported the first case in 2017. And one year after that, Glauco Baiocchi from Sao Paulo reported the first case of uterine transposition for a patient with cervical cancer. So this was a big change because we were not thinking about using it for gyne tumors. Those are the countries who have, who already reported cases of uterine transposition, not published all the cases, but have reported some cases. So this is the video about the updated technique, which was presented in the last year's Congress of American Society of Fertility. So uterine transposition is divided in two parts. So first of all, doing the transposition to the upper abdomen. Then after radiation, the second part, which is putting back the uterus with ovaries and tubes, of course, back to the pelvis. So re-implanting the uterus. So how do we start the first procedure? Usually we use the same setting for laparoscopic approach as we use for any pelvic disease. We call it French positioning. And we use also a uterine manipulator, but just a Egger manipulator, so nothing. Actually, I think we moved. Vince, can you go back for the video? Okay. Thank you. Yeah, that's it. So how does the procedure start? It's pretty much like a hysterectomy, a simple hysterectomy. So we start doing the section of the round ligaments. You can see this is a rectal cancer. It's infiltrating the uterus sacral ligament, and we just remove on the surgery for the rectal cancer. So this is how the procedure starts. Looks pretty much as a simple hyst, but different from a simple hyst, we do a very large dissection of the ovarian vessels. But at this point, you can see, like, sectioning the posterior part of the insertion of the uterus sacral ligaments, and now ligating the uterine vessels. So you have to ligate the uterine vessels, like in a radical trachelectomy, but closer to the uterus. Not too close, because if you cut it too close from the cervix, usually you have a ischemia of the cervix. So you have to, it's more like a type A radical hysterectomy or something like that. One other detail is, now we close the vagina in two planes, because those patients usually, they start radiation in 10 days, sometimes 15 days. So you don't wanna have a cuff dehyscent. So now we do two planes. On the first case, we had a dehyscent, so now we always use two plane suture. You can use wherever you want, barbed suture or whatever. The important thing is it has to be well done, let's say something like that, because patients start radiation in a couple of weeks. So that's how the pelvic look like. And now we are moving to the heteroperitoneal dissection, which is very important, because you have to mobilize the uterus. So now we are looking from the pelvis to the upper abdomen, and then we dissect from lateral to medial, the left column. And after dissecting the left column, we start the dissection of the gonadal vessels. And we go all the way very close to the renal vein, so we can have full mobilization of those vessels. The same thing on the right side, you can see the appendix and the mobilization of the right column. And then this is the mobilization of the right gonadal vessels. You can notice that we don't dissect direct on the vessels, we try to get a little bit away from them to avoid like burnings or thrombosis or anything like that. At the minimum, you have to dissect it at the level of the umbilicus. Once you have done it, you can mobilize the uterus as high as the diaphragm. So actually you could put the uterus inside the thorax if you want, if you have a very good dissection. One thing that we are doing now, we also suture the ovaries to the anterior abdominal wall. And you can see this is very close to the costal margin. And now we also place clips. So it's very easy to identify where the ovaries are. And usually the dose of radiation is less than one grade. So it's a very low dose. Also very important to attach the eyepiece to the pelvic side wall to avoid hernias. And I know some surgeons they don't wanna do it, but I highly recommend to do it because also the gonadal vessels, they suffer some retraction. So if you don't do this arch in the abdominal wall, they retract and sometimes it's a little bit hard to put the uterus back to the pelvis. Then we suture the cervix to the umbilical fascia. And you see, there is not a prolapse. You cannot actually see the cervix unless you open the umbilical. So don't worry, the patients will not see this, will not see it. But during post-op, you can examine it. And I'm gonna show you how important this is. Two days after surgery, we always do a Doppler ultrasound of the gonadal vessels. And usually two weeks after that, we do an MRI. So you can see the uterus attached to the umbilicus at this point. And this is like how menses are. Don't worry, patients, they don't get upset because of it. So actually they are quite happy because they know it's working. So for this second procedure, we start with the adizolizis. And this is how the trochospectomy looks like. And usually the uterus is quite attached to the abdominal wall, but nothing that you cannot just, maybe in 10 or 15 minutes, you can just release all the adhesions that's usually not that hard. Obviously, you have to be very meticulous with the hemostasis, because you don't wanna go back and have lots of adhesions. And then now you can see, we are taking out the cervix from the umbilicus, and then we start the new 10-millimeter support to go to the pelvis. And now you start placing the uterus back to its position. When you are going to do it along with a retosigmoidectomy for rectal cancer, this is the moment we do a retosigmoidectomy. And it's exactly the same how we do in a patient who had not a uterine transposition. There is no change at all. And it's quite easy. And don't worry if you have a colorectal surgeon working with you, you can tell him, don't worry because it's gonna be pretty much the same. It's not more difficult. And sometimes it's even easier because the left colon, it's already dissected. So this is another point. So you can see here how it works performing the retosigmoidectomy, quite straightforward. It's the same technique, no change. And you can see this is a patient with a very low anastomosis. And actually the problems the patients have is more related to the retosigmoidectomy than to the uterine transposition. This is just the test of the anastomosis. And then we grasp the uterus, put it back in the pelvis. And basically we just reconstruct all ligaments and everything. So you just remove the fibrotic tissue, suture the cervix to the vagina. Usually with some prolapse, so to get back to its normal position, let's say. We use absorbable sutures. It's the Vicryl or whatever you want to use. And then we use proline to suture the ligaments, the uterine ligaments. We suture all of them because we don't wanna have an internal hernia. And we want it to look exactly like a normal patient. And actually that's how it goes. And usually if you take a look now, it's pretty much like a normal patient. This is six months after surgery when we went back to remove the ilostomy. And this is the cervix six weeks after surgery. It's raining. So this is tropical country. Let me check. Next one. So you can use robotics for a uterine transposition also. We have published one case, but we use the SI platform and it was not that good because you have to change docking and stuff like that. And I believe the XI is the best one to do a uterine transposition. So we started with a feasibility trial in 2017, and we finished it in 2020. And this year we finished collecting data from those patients. And the indications were mainly non-gynecologic cancer, like rectal cancer, canal, anal, pelvic sarcomas and other tumors. And the objective was mainly safety and uterine preservation. Obviously, if you want to evaluate other factors, you need more patients. And our secondary endpoints were like regular menses, normal hormonal function, quality of life and surgical complications. The results, we expect to publish them in the beginning of next year. And then we have just, by June, we started the second phase of our studies, which is this fertility and oncological safety of the procedure. And we have expanded the indications for some vulvar, vaginal and some selected cervical cases. And I think the most interesting part is obviously the cervical cancer patients, because you have to consider that you cannot just leave the uterus if you do not have a safe margin at the cervix. So we are indicating mostly for patients with very small cervical tumors and micrometastasis at the pelvis and patients with a very good margin. The tumor cannot be close to the uterus. And also the patients have to understand that they may have a higher recurrence rate. So we are working on that. So, and actually the first case of robotic surgery we have published was a patient with a post-trachelectomy with one tumor, 1A1 with a lymphovascular invasion and a micrometastasis. And it was quite similar to a regular uterine transposition, just we leave the residual cervix, let's say some of that, and we remove some margin of the vagina. And it looks pretty much like a trachelectomy where you just have to put the uterus in the upper abdomen. And now the same thing works for vaginal cancer. We have a patient with vaginal cancer. The only difference is we keep the cervix in the vagina. And we just like, we do like a trachelectomy and because we want to irradiate the cervix of those patients too. And after radiation, we have re-inserted the residual cervix into the vagina. How we are so far. So 14 patients with a median follow-up of 22 months after actually a little bit more now. One of the important things is no patient had delay on their treatment. 11 patients have regular menses and normal hormonal function. So it seems it's working well so far. We have a girl with a nine years old girl from Colombia. She has normal hormonal function, but no menses so far. And we have the case of uterine necrosis in one patient died from cancer before placing the uterus back to the pelvis. So she had a carcinomatosis during new adjuvant treatment. So this is the patient with the uterine necrosis and you can see a perfusion is quite bad. But this patient had a different vascularization of the cervix. And you can see half of the uterus is perfused after the uterine transposition on the MRI. And this is one of the reasons why I think it's so important to attach the cervix to the umbilical. So we could just see it was not good. The perfusion was bad. And actually we were able to preserve her right ovary because the perfusion of the right side was okay. And then we removed the uterus and the left ovary and the patient it's doing well so far, but lost her uterus. Well, probably the best way to go is with ICG. I think that's a great option for evaluating perfusion. This is a video from the last IGCS, Irish video. So I'm very happy to see other people making it evolve. So pregnancy rate so far, just one patient tried to get pregnant, which is, she's 42 years old. So in and now she's preparing for IVF, but she did not manage to get pregnant spontaneously. That's it. Major complications, uterine necrosis. And we had a uterine obstruction. It's the same patient who now is trying to get pregnant, but the intestinal obstruction was because of the retrosigmoidectomy. But anyways, it was related. And most of all, the most common complication is certainly is stenosis of the cervix. And around 30% of the patients or have some atrophy of the cervix and stenosis. So you have to be aware of this. So in conclusion, we believe uterine disposition is a feasible procedure. It's not standard of care. I don't recommend to do outside clinical trials. We understand that this procedure, it's research is not something that you should use on a regular basis. So fortunately so far, no patients have significant delay on the treatment. So this is good too. But you still, you have to understand that there are complications and the rate of complications is not so low. But as we learn more with the technique, the last patients, we did not have complication, but still a very small experience. And pregnancy rate and oncological outcomes need further investigation. So we need to go ahead with those trials. So thank you so much for this opportunity and I hope you enjoy it. Thank you. Thank you so much for an absolutely spectacular video and discussion that was really impressive and wonderful. We have a few questions from the audience and I'd encourage the audience members, please send in your questions. We're very happy to answer them. Well, first question we had was about the use of a nomental flap. Is that something that you've considered and what would be the potential benefit of doing that, do you think? Well, it depends on the idea of the nomental flap. The idea is something like taking the uterus from like the rectum or something like that. That's what I believe the question is about, right? Yeah. Yeah, so the point is those is like two grays, five grays are enough to cause ovarian failure. So even if you put the omentum, probably the ovaries will not get far enough to avoid ovarian failure. And that's what happens for instance, with a canal canal cancer, because those patients also, it's not the center of the field, the ovaries are quite high. They are around 10 centimeters from the main target, but those patients still get lost their ovarian function. And there's a paper about gluteal sarcomas and thigh sarcomas and some patients also get infertility because of the distance. So you have to get really high, really far from the site of the tumor to make sure the ovaries are not getting too much radiation. So I think omentum flap, probably it's not gonna be enough. Okay. And another question, you talked a little bit about the placement of the cervix at the umbilicus to be able to, both so that the patients can menstruate, but also to be able to evaluate the perfusion of the cervix. We've gotten questions about, potentially using either continuous OCPs or GnRH agonists to cease menstruation during the time where the uterus is transposed. Have you, is that something you've considered as something you'd try or? Yeah, yeah. We did in a few cases and actually for patients after radical trachelectomy, we have four patients now. We use, we block their menses and, but still some of them, they have some bleeding. And, but we don't, do not use agonists because those patients, the problem is they already are on chemo. They are young. And then you're causing menopause to those patients. This is, they lose lots and the quality of life gets so much worse. And we usually, I do not recommend that. We just try to use their regular and conception that they use in like without a pause. And if it works, that's fine. But we had one patient who had like a hematoma on the cervix and because of, we did not place on the umbilicus and there was like a destruction, a partial destruction of the cervix because of this hematoma that looked like endometrioma. It was not actually on the final pathology, which was just a hematoma at the cervix, like something like that. So I still recommend, we tried not to do it. And then we just realized maybe we should keep doing it. And actually I know most of people, they are very impressed about it. And they think, wow, the patients will not like or something like that. And actually the patients really don't care. They really, and they really don't care. I'm not sure if we're talking about him. Sorry. I'm sorry, I think there's just some background noise. And the other thing is, just final question about the, does the size of a patient's panus and their umbilicus, is that, might end up putting the umbilicus in the radiation field. Is that something that has been a problem in the past and kind of in addition to that, has there ever been an infection at the cervical umbilical side? Okay, yeah, that's a good question. So one of the, one thing, one more thing is those patients, they still have mucus from the cervix, right? Even when you suppress menses, they have mucus. So that's interesting because they have to use some, some, I don't know, gauze or something like that because they always have some mucus, which are regular, it's normal thing from the cervix, right? So placing the uterus at the cervix, the cervix of the umbilicus also helps with that. So, and we did not have any infection so far at the umbilical side, but we had three patients who had fever after the procedure. We are not sure exactly why, they just have like fever and we treated like with metronidazole and some cephalosporin and they just get better. So this is a good point. Maybe we are causing some infection and we just don't know exactly how it's working, but they get much better in a couple of days, let's say something like that. So, and this is one of the interesting things about the uterine transposition is that those patients that have normal sexual function after surgery because they have lubrification of the vagina because they have normal cervix. So this is one interesting thing. It's because their quality of life and their lubrification is much better than the other patients we see after chemoradiation or radiation of the vagina and cervix in-situ. Gotcha. Well, thank you so much again for such a spectacular presentation and discussion. We're gonna go ahead and move on to our next presenter who is Dr. Sushmita Gordhandas, who's a fellow on the gynecology service at Memorial Sun Kettering in New York. And she's gonna be discussing ovarian transposition. All right, thank you. I'm just gonna open my slides. Okay, so good evening. My name is Sushmita Gordhandas, and as Dr. Broach said, I'm a fellow at Memorial Sun Kettering, and I'm pleased to be presenting on ovarian transposition. Just some background on transposition. It is a surgical relocation of the ovaries away from the planned radiation field prior to radiation therapy. The goal is to preserve ovarian function for fertility and hormone production. In terms of the lethal dose for the human oocyte, the median lethal dose is actually less than two grays, and the sterilizing dose, as we've mentioned before, is age-dependent. At age 20, it's about 17 gray, and at age 30, 14. And the average treatment dose in cervical cancer is 80, and rectal cancer is 45 gray, so well above that sterilizing dose. And so in which types of cancers do we do this procedure? I'll be talking mainly about lateral transposition, which is in cervical and colorectal cancers. And this image on the right, you'll see the red area indicates the dose distribution of about 40 grays in cervical cancer radiation, and the green is about 10 gray. And then there is a thing called medial transposition that they typically do for lymphomas with anterior field radiation. In those cases, the ovary is attached to the utero-sacral ligaments, and then the uterus acts as a shield for the ovaries. In terms of ovarian survival after radiation, a 2018 retrospective case control study looked at 27 patients who had ovarian transposition prior to EBRT, and ovarian survival was measured based on lab values, which were FSH and estradiol, symptoms of menopause, or the use of HRT. They found that ovarian survival was age-dependent, so in the cases who had transposition prior to radiation, the patients who were 25 to 30 years old, 88% had ovarian survival, and that decreased to 63% in 31 to 35-year-old, and 43% in 36 to 40-year-olds. In the control, or those patients who did not have transposition prior to radiation, survival of the ovary was actually 0%. Another study in 2000 looked at 107 patients who had transposition during surgical treatment for cervical cancer, and ovarian function after RT was assessed by post-op ultrasound and measurement of FSH and estradiol levels. They found that ovarian survival was dependent on the type of radiation, so in vaginal brachytherapy alone, 90% had ovarian survival, and then if they had EBRT with brachy, then it was 60%. In terms of risks, there is a risk of ovarian metastasis. That risk is higher in cervical adenocarcinoma compared to squamous cell, and then there are the surgical risks, such as bleeding or damage to surrounding structures. In this case, we would think of the bowel, ovarian vessels, and the ureters, and there is the risk that we fail to preserve fertility or ovarian function. So it's very important for the surgeon to collaborate with medical oncology, radiation oncology, and especially a fertility specialist. We feel it's imperative for a patient to meet with a fertility specialist prior to undergoing the procedure to understand their reproductive potential following treatment. Furthermore, it's important to understand that if they are interested in fertility, if they're not interested in fertility and were just interested in transposition for preservation of hormonal function, that hormonal replacement therapy is often an option for these patients. In terms of efficacy, the data is very limited. There are mostly case reports and case series. There are a few systematic reviews, but the data is very heterogeneous, and so there are no meta-analysis. Overall, we think it's very important for us to remember that there are options for women for fertility preservation in the setting of pelvic radiation, and it's a very personal decision for each individual patient. In terms of our future research, our group at MSK, specifically myself and Dr. Long, are planning to do a survey of gynecologic oncologists to better understand the practice patterns associated with ovarian transposition, looking at things like the barriers, surgical approach, and perceived risks and benefits. Overall, we hope to gain an insight to better guide our patients in the future, and so be on the lookout for that, and we would very much appreciate everyone's input. All right, so I think the next part will be the video. Dr. Birch, will you be sharing that video? Can you see the video now? One moment. Sorry, one second. I'm not seeing it. I'm not sure why. Do you mind if I just go ahead and share it? I'm having a hard time seeing. No problem. Go ahead. All right. One second. All right. Is everyone seeing that? Yes, we can see that. Okay, great. All right. So this video highlights a case of a 31-year-old with a history of T3 rectal cancer, and she also has a history of two prior cesarean deliveries. She was counseled regarding her options for fertility preservation as well as hormone production, and she elected to undergo ovarian transposition with opportunistic self-injection. So in this case, the procedure began by readying the pelvis for transposition. On the right, the appendix was physiologically adherent to the right pelvic sidewall, and this was dissected free. The patient elected to undergo opportunistic self-injection, and this was completed bilaterally. So now we'll be turning our attention to the left ovary. The retroperitoneum was entered, and the utero ovarian ligament is ligated and divided. So the patient was able to perform the transposition, and this was completed bilaterally. And the process of skeletonizing the ovarian vessels is now brought cranially. Both the lateral and medial attachments are dissected with careful attention to the ureter during this dissection. So right here you'll see the ureter. The proposed location of the transposed ovary is scouted. Ideally, this would be above the iliac crest at L5-S1 level, as this ensures the highest likelihood of being out of the radiation field. The IP ligament is further skeletonized in order to allow sufficient length to reach the desired location. Again, this is done both medially and laterally in order to provide sufficient length. And during this dissection, care is taken not to injure the ovarian vessels. So, once sufficient length has been determined, a window is made in the peritoneum. In this case, the ovary will be tunneled in the peritoneum to reduce the likelihood of internal herniation. Ensuring that the ovarian vessels have not been twisted, the ovary is then brought through this tunnel to the location of the transposition. Then the ovary is secured to the peritoneum with a delayed absorbable suture in this case. We will suture it to the peritoneum at three locations to reduce the likelihood of torsion. Some people do use permanent suture in this situation as well. And then lastly, the radio-opaque clips are placed around the ovary to allow for identification of the ovarian location by the radiation oncologist. The clip is typically placed at the most caudal portion of the ovarian parenchyma. And then the procedure is repeated on the contralateral side and concluded. So that's the end of my portion of the presentation. Thank you all for your attention. I think we'll go directly to Dr. Brady's presentation before questions. Great. Thank you so much for an excellent video and presentation. That was really spectacular. As you said, Dr. Brady, I think given the similarity in the topic, we'll go ahead and get you started. It's such a pleasure to introduce you. Dr. Brady is the Director of Oncofertility at Columbia's fertility program in New York. Dr. Brady, thank you. Dr. Brady, I think we're just having a little bit of a difficulty hearing you. Is that better? Yes, it is. Thank you. Okay, great. Thank you to Dr. Broach and the IGCS for having me tonight. It's my pleasure to talk about fertility preservation in the gynecologic oncology population. These are my disclosures. Tonight I want to discuss or to review fertility preservation options. Primarily oocyte and embryo cryopreservation. I'll say a few words about ovarian tissue cryopreservation, and then we'll review fertility preservation procedures in the context of gynecologic cancers. Things to consider when referring patients for fertility preservation is their age and in the context of reproductive aging, which I'll talk about a little bit later. Their overall health, the type of cancer and planned treatment, and importantly, the available time before cancer treatment, so what fertility preservation can we squeeze in in that time? Cancer prognosis is not necessarily part of the decision-making. The ASCO suggests not excluding patients from referral based on their cancer prognosis. Overall, the options are oocyte cryopreservation, egg freezing, embryo cryopreservation, which requires a sperm source, and ovarian tissue cryopreservation, which requires laparoscopy for the removal and freezing of tissue. I just wanted to say a few words about ovarian reserve. You'll see that term in our notes and a lot about AMH. Just to catch everybody up to speed on that. AMH stands for anti-mullerian hormone. It's in the TGF beta family. It's produced by early ovarian follicles. The higher, the better. It does not reflect egg quality, just quantity. But it's a useful marker because there's very little variability across a cycle or between cycles, and it predicts response to ovarian stimulation medications. It naturally decreases over time with age, and a low level is on average less than 0.9, which predicts a more modest egg yield in IVF. Ovarian reserve is negatively affected by pelvic surgery, chemotherapy, and radiation, as the prior speakers have all addressed so well. All of these treatments also affect ovarian response to stimulation, and that includes pelvic surgery that doesn't touch the ovaries. Any pelvic surgery has been shown to negatively affect AMH and response to stimulation. AMH may recover to a limited extent after some of these treatments, and the ideal is to fertility preserve before any oncology treatment. Specifically about chemotherapy and ovarian reserve, it causes follicular apoptosis, so loss of the egg-growing units in the ovary that we call the follicle, and oxidative stress. Alkylating agents are particularly damaging. The sterilizing dose is lower as women are older. Chemotherapy affects oocyte count, but not quality. Any function or reserve they have after chemo should be commensurate with their age. There's some research into mTOR inhibitors that they may protect ovarian reserve during chemotherapy, but it's still very much in the research realm. The other presenters have discussed this, the impact of radiation on fertility. It damages both the uterus and the ovaries. Pregnancy rates are cut in half after 5-10 gray, to the uterus, and by 80 percent after greater than 10 gray. Uterine radiation causes myometrial fibrosis, which is associated with poor B-cap outcomes like miscarriage and preterm birth, and damages the endometrial stem cells. Women may no longer menstruate and that they may not be able to grow an endometrial lining to support implantation of an embryo. The sterilizing dose is lower as women are older. Just a few words about ovarian stimulation overall. It's done with subcutaneous gonadotropin injections, primarily FSH and sometimes with some LH, that conventionally starts on the second or third day of the menstrual cycle, but we can also start randomly, meaning at any point because new waves of follicles are stimulated all the time. We do that in patients who have limited time before cancer treatment. We can start wherever they are in their cycle. We can use letrozole during a stimulation if a woman has estrogen receptor positive cancer, so endometrial or breast. We can continue Mirena IUDs or oral progestins, specifically for endometrial cancers if necessary. We trigger or promote final egg maturation before retrieval with HCG or Lupron. I bolded the HCG just to remind us that patients may show up for chemo or cancer surgery with a positive HCG due to the exogenous HCG that we give them, which can last up to 10-14 days. Just a few words about egg retrieval. On average, it's done 11-14 days after cycle start. Patients are usually done within two weeks. Low risk, low risks of bleeding, infection, no eggs retrieved or torsion. It's a quick procedure done under propofol in their home in one to two hours. Specific to gynecologic oncology, the retrieval is done by transvaginal needle puncture into the ovary. If there is a vaginal or cervical cancer, ovarian cancer, you are potentially puncturing that in order to get to the eggs, which I'll talk more about. There is the option of transabdominal egg retrieval. This is done when the ovaries are not accessible transvaginally and the vast, vast majority of our cases are transvaginally, but this is an option. When patients have had oophoropexy or they have very large fibroids displacing the ovaries. We've sometimes done transabdominal retrievals to avoid transvaginal puncture to prevent tumor spread, so a vaginal or cervical cancers, things like that. Certain considerations specific to fertility preservation in ovarian cancer. There is a concern about spreading tumor if there's a malignant mass on the ovary that's punctured with a retrieval needle. It's also very hard to monitor the ovaries accurately for recurrence for about a month or two after retrieval because the ovaries are full of these complex cysts, multiple corpus luteums. They have some hemoperitoneum and the sides related to the stimulation. Specific to cervical cancer, there's a question of whether to fertility preserve before or after surgery. Any pelvic surgery affects AMH and ovarian response, so ideally before. But then that leaves open the question of tumor spread with transvaginal, which is sometimes transcervical puncture. Patients with prior oophoropexy will require transabdominal egg retrieval. Depending on the treatment plan, patients may require gestational carrier. Uterine cancer, same thing. Should we fertility preserve before or after treatment for the cancer? As a reproductive endocrinologist, I prefer before because hysterectomy does affect AMH and ovarian response. But we have to take into consideration, of course, the urgency of the surgery. Sometimes it is better to do the surgery first and fertility preserve after. We can use aromatase inhibitors and we can continue progestins during the cycle as needed, if the cancer is still in place. Depending on the treatment plan, these patients may require gestational carrier in the future. This is a common question. When is it too late to refer patients for fertility preservation? Consults are reasonable up to age 44, but prognosis is generally poor at more advanced ages, so like over age 40, 41, 42, and beyond. That's due to the age-related reduction in egg quantity and quality. With rising age, there's a rising risk of having to cancel a cycle because there's no response, not getting any eggs, not having any viable eggs, related to age-related quality changes. Just to give you a sense, this is from our national organization showing just broadly IVF success rates by age. This is not an ecology population, but it gives you a sense like how quickly success rates fall when we get into the 40s. Again, due to quantity and quality changes related to age. Just a quick word about using frozen eggs or embryos after cancer. When these patients come back to see us, we send them for MFM consultation. That can include talking about OB complications of pelvic radiation, any cardiopulmonary assessment like if they got atriomycin or gliomycin. We also deal with gestational surrogacy, so meaning a woman's eggs or embryos carried by another individual. In the US, we have to check certain labs mandated by the FDA when the eggs and embryos are originally frozen. Then patients have to work with lawyers to come up with the agreements with the gestational carriers that in the US are state-specific and internationally laws, of course, vary widely. It's also very expensive in the US, it's over $100,000. Finally, we have the option of doing pre-implantation genetic diagnosis of embryos, not of eggs, but of embryos for patients who are known to carry hereditary cancer syndrome. I've done it for BRCA, Lynch, P10. That is an option as well to prevent transmission of those genes to their children. Quick word on ovarian tissue banking. Basically, we do laparoscopy to remove strips of ovary and freeze it for future use. It's good in that they don't need stimulation, minimal delay in treatment, we don't need a partner or sperm, and it's the only option for prepubertal girls. But it does require surgery to remove the tissue, and the goal is to put the tissue back into the pelvis in the future. Women will need repeated surgeries and it's not a great option for GYN oncology because of the concern of reintroducing cancer cells when the tissue is replaced. It's really not something that I use or recommend for GYN oncology patients. In conclusion, this was a review of egg and embryo freezing. It requires about two weeks before starting cancer treatment. We can do transvaginal or transabdominal egg retrievals, and we work with the GYN oncologist to decide if this can or should be done pre or post surgery. Ovarian tissue cryo, it's an option broadly, but it's not a great one for GYN oncology patients. Finally, all cancer patients should be informed of the risk to their fertility posed by treatment and fertility options available. Fertility preservation does have some risks. It can delay cancer therapy. It's costly and invasive. For GYN cancers, we risk spreading the cancer with vaginal, cervical, or ovarian punctures. Next, I have a short video that was put together by my former co-fellow who's now attending at Brigham and Women's Hospital. I think Dr. Broach has the video. Our group has previously described the transabdominal approach to follicular aspiration for oocyte retrieval. Published in 2011 in Fertility and Sterility, our approach has been replicated at other centers. This video provides a step-by-step description of our published technique in the context of a case presentation of a patient with cervical cancer, who previously underwent ovarian transposition to the upper abdomen. In this video, we present the case of a 35-year-old woman, G1P1, with newly diagnosed cervical cancer who desired fertility preservation prior to chemoradiation for her stage 1B1 cervical cancer. To avoid the risk of seeding the parametrium and ovaries on transvaginal approach, the patient underwent laparoscopic transposition of her ovaries to the upper abdomen 10 days prior to her retrieval. The patient underwent controlled ovarian stimulation with gonadotropins and her oocyte retrieval was scheduled for 36 hours after her trigger injection. One hour prior to the retrieval, she was given our standard antibiotic prophylaxis protocol for oocyte retrieval, a single dose of second-generation cephalosporins. If transvaginal aspiration is not possible for one or both ovaries, as in our patient's case, transabdominal aspiration is performed. The patient is placed in the dorsal supine position with an empty bladder. General anesthesia with intravenous propofol is administered. A chlorhexidine solution is used for skin preparation, which is then carefully washed off the abdomen. The patient is then draped in a standard sterile fashion. A sterile needle guide is attached to a sterilely draped abdominal ultrasound probe. Pictured here is the curved 5-9 MHz probe. The ultrasound operator then places the ultrasound probe on the abdomen in a location to best visualize the ovary. Under ultrasound guidance, a standard 17-gauge retrieval needle is inserted through the skin using the needle guide. Due to decreased elasticity of the abdominal skin, each ovary typically requires multiple punctures to complete the retrieval. After the procedure is complete, puncture sites are covered with sterile bandages. Please note that the port sites from this patient's recent laparoscopic surgery should not be confused with the retrieval puncture sites. This patient had a total of 12 oocytes retrieved, seven of which were mature, six fertilized, and all six 2PN embryos were cryopreserved. Given the pelvic radiation this patient will undergo, her future pregnancies will utilize a gestational carrier. This is the first video tutorial for the transabdominal approach to follicular aspiration for oocyte retrieval. This procedure is safe, effective, and reproducible. Patients whose ovaries are not accessible transvaginally should be offered transabdominal egg retrieval rather than being subjected to the added cost and challenges of egg donation. Thank you so much for a really spectacular presentation and a wonderful video. We have a few questions relevant to this topic that I'll start with. The first was going back to the first presentation that we had about the use of surgical clips. How about using surgical clips altogether rather than using sutures plus clips to denote the location of the ovaries? What would be your thoughts about that? I think most of the literature shows using suture, and I'm not sure if anyone has published about using the clips alone. I think the suture sometimes people can feel a little bit more comfortable that the ovary is well-connected to the sidewall, so it's not going to twist. If one clip comes off or something like that, you might be nervous about possible torsion. But it's very possible that you could use clips, I just haven't seen it before. Great. Then another question, just in terms of position of the ovaries following transposition, if you could just clarify, I know you mentioned in your presentation the optimal location for different cancer types, but how high do you want to get the ovaries and how do you identify that when you're in the operating room? We work very closely with the radiation oncologist so we can determine the ideal location for transposition since it really depends on what their treatment plan is. But in general, we aim to go as high as we can, but around L5-S1 is typically where we try to go. One question I had for Dr. Brandy is, when you're trying to decide, and particularly in these patients where time is somewhat of the essence, choosing different medications for ovarian stimulation, how do you go about that with the patients and are there different medications that you'd use in different circumstances depending on cancer type? It's a good question. For the most part, we use FSH in pretty much all patients with or without some LH. For some patients, there's the rare case of maybe a patient with specific types of ovarian malignancies like some types of stromal tumors, I might not use the LH portion to try to avoid stimulating it, but that's theoretical at best. We really use the standard medications, but we can add the aromatase inhibitor if we're worried about estrogen, we can continue the progestins. In general, I try to use high doses of our stimulatory meds because this is often their one chance before fertility compromising treatment. Well, I think we've gotten to the end of our scheduled time. I just wanted to thank all of our speakers today for their time and their expertise and their insight. We really had spectacular presentations across the board and I'm so grateful for their participation. We're looking to continue our surgical education and we'll post information regarding the next session on the IGCS website soon. If people have specific topics that they'd be interested in and having a surgical film session on, please feel free to reach out to us either through the chat now or through e-mail. With that, I'd just like to thank again our speakers and to all of you for attending, and we wish you all continued health and safety. Take care.

fertility preservation

gynecologic cancers

ovarian function

oocyte cryopreservation

embryo cryopreservation

ovarian tissue cryopreservation

collaboration between gynecologic oncologists

fertility specialists

chemotherapy impact on ovarian function

radiation impact on ovarian function

risks of fertility preservation procedures

benefits of fertility preservation procedures