Bruno Lunenfeld, MD

                *requires       RealPlayer - 

:  "Today on February 10, 2001 it is my  pleasure to interview Professor Bruno       Lunenfeld, the starter of the GnRH Analogue Conferences the sixth  of which we are holding at the present time in Geneva.  I would like to  ask him when these meetings started, what is the intention of the  meetings, and what is the future?  Let us start with the historical  part, please."
       
       

:   "As you know very well, this is the 6th GnRH meeting.  We started some  fifteen years ago, and in the beginning we were investigating the  possibility of the uses of GnRH agonists.  We were then investigating  the possibility of the use of GnRH agonists in precocious puberty; this  was indication number one at that time.  We were then already thinking  of the possibility of using GnRH in four different situations; in the  situation where we would like to intervene or to modulate diseases that  are dependent on sex steroids, which could be, endometriosis, uterine  fibroids, and you can name many more.  The second indication was to stop  sex steroid production if it is too early or too modulated like in  precocious puberty or in order to prevent an untimely LH peak as we saw  often in ART protocols.  The third situation was to look at situations  where there are hormone dependent cancers and whether we could intervene  by these situations.  We already knew by that time that castration was  one of the main treatment modalities for prostatic cancer and,  therefore, we thought we could use GnRH agonists for this kind of  purpose.  The fourth situation, which we're still debating today, is can  we use GnRH agonists or analogues in the modulation of cancer specific  areas not directly via the steroid patterns.  Now this all became clear  of course because we already knew at that time that GnRH agonists were  the first and only medication which could do exactly the same that a  surgically hormone specific type of vasectomy could do or what a  castration,       orchiectomy, or a male castration could perform.  We could do this  reversibly with GnRH analogues; this was the beginning and the  rationale of having these GnRH meetings.  The meeting was opened at that  time by Andrew       Schally, the discoverer of GnRH who also received the Nobel Prize  for this purpose."
       
       

:  "Let  us go now to the two different sides - agonists and antagonists.  At  this meeting we have for the first time clinical data on interaction of  antagonists so please differentiate the two, and how do you foresee the  future interaction of these two lines?"
       
       

:   "The main problem of the GnRH analogues was the flare up effect, and  because of the mechanism of action of GnRH analogues, you know that the  first situation is a flare up of the hormones (LH and FSH) and then  there is a desensitization.  This flare up effect, of course, can be  detrimental or has a negative effect in hormone dependent diseases like  prostate cancer.  It can have a negative effect in the uterine fibroid  situation, and it can have negative effects in many other situations.   Therefore, the moment we had antagonists, which worked by competitive  binding, we get a direct inhibition of the gonadotrophins and do not  have this flare up effect. This is with of course a major advantage.   The big problem with the antagonists was that the first generations had  histamine release and we needed a lot of work and many, many years of  work until antagonists could be used clinically without side effects."
       
       

:  "At the present time, which other fields are antagonists already used?"
       
       

:   "In the beginning I forgot to stress one of the most important uses of  GnRH agonists namely in assisted reproductive procedures.  As you know  and have heard in this meeting, 80% or maybe even 90% of assisted  reproductive cycles are used together today with GnRH agonists.  In this  area, the antagonists are playing a very important part as you have  heard in this meeting because they can reduce the time of treatment and  they reduce the number of ampoules of       gonadotrophins. This makes treatment more acceptable by patients.   It's a more friendly treatment for the patient and permits a more  flexible therapy than with the  use of  GnRH agonists.
       
       

:  "So in the area of reproductive medicine it's already an accepted concept.  How is it in the area of urology?"
       
       

:   "The main problem was that the GnRH antagonists available today, as you  have heard here, were mainly short acting antagonists. Only very  recently has a long acting GnRH antagonists been discovered.  It is now  in Phase II and Phase III clinical trials and it will be on the market  very soon, and this is Abarelix which has a very, very long action and,  of course, can be used then in diseases which need very long  suppressions of sex steroids like prostate cancer, uterine fibroids, and  endometriosis."
       
       

:  "In  the gynecological area the antagonists have also been discussed at this  meeting in uterine fibroids and endometriosis.  How many of these  products are available that are not given daily?"
       
       

:   "For the time being the only antagonists which is a long acting  antagonist is a product which is not yet on the market which is       Abarelix."
       
       

:  "Cetrorelix has a 3 mg compound from the Serono Company which is used in  reproductive medicine.  Has it also been used in clinical trials for  myomas and endometriosis?"
       
       

:   "Very limited trials in this respect, and very limited material with a  very nice potential I am not aware of large scale clinical trials.
       
       

:  "Professor Lunenfeld, my last question  goes to the field of cancer.  Cancer is still a threatening disease, how  is the future action of antagonists and agonists in the field of  cancer?"
       
       

:  "I  think we've had a very nice symposium here on this respect.  Professor  Bartsch has given some very nice data, and I believe OBGYN.net already  interviewed him.  I think, again, the antagonists don't have the flare  up effect and they probably do much more than just decrease testosterone  on prostatic cancer.  I think they have a nice and big future in  prostatic cancer but it's only at the next Congress in two years that  we'll be able to tell."
       
       

:  "May I  finally allude to some personal aspects?  Your birthday is going to be  on Sunday and already OBGYN.net would like to congratulate you for all  your achievements in our field and wishes you a very happy birthday."
       
       

Articles

OBGYN.net Conference CoverageFrom the 6th GnRH Analogue ConferenceGeneva, Switzerland February 2001

The History of the GnRH Analogue Conferences

click             here for RealAudio/Video version

       "I'm here with Dr. Tulandi from McGill University in Montreal, and       we're going to talk about endometrial ablation versus hysterectomy."
             
             

       "The treatment of abnormal uterine bleeding could be medical       treatment or surgical treatment. Most people who elect to have a surgical       treatment do so because they want a long-lasting cure, but people who want       endometrial ablation do so because they want to avoid major surgery. In       selection of endometrial ablation, it is important to tell the patient       that this is not to eliminate the bleeding but to decrease the bleeding -       so patient selection is very important."
             
             

       "What other factors point towards successful surgery?"
             
             

       "Number one is patient selection. Number two is the surgeon's       expertise, if you're using a hysteroscopic technique."
             
             

       "There are a lot of new techniques that are out there; we hear about       microwave, cryoprobe ablations, balloon techniques, resection techniques,       or hysteroscopic vaporization techniques. What are your thoughts and       what's your take on this plethora of techniques? What should someone do to       figure out which technique is best?"
             
             

       "Again, it depends on the surgeon's familiarity with the technique.       If they know how to do a good hysteroscopic procedure, there's nothing       wrong with that. The technique is more difficult; it depends on the       expertise of the surgeon. The norm hysteroscopic technique is certainly       easier. There are many techniques, as you mentioned; one of them is       microwave endometrial ablation. There is a good randomized study conducted       by David Park in Aberdeen, showing the technique is as good and your       results are as good as resection. This is a good randomized study."
             
             

       "In failures, the patients who come back afterwards who are not happy       with the results, are they frequently candidates for another ablation       technique, or do they often go on to hysterectomy, or is medical treatment       considered again prior to another surgery?"
             
             

       "In general, they don't want to go back to medical treatment. Usually       our patients have been treated medically, and that's why they chose       surgical treatment. Now it depends, again, on the patients. Most of them       will go through a hysterectomy, some of them will say, "okay, why       don't you redo it" - and we have done two, three patients       successfully."
             
             

       "Have you seen any patients who've had pregnancies after this, and       have they been successful? How have you managed that, or are patients       generally too old?"
             
             

       "Luckily, I have never had any patient who got pregnant. But again,       it is important that we tell the patients before an endometrial ablation       you should not get pregnant."
             
             

       "Is adenomyosis a contraindication in your practice? Do you treat       those patients differently or advise them differently when approaching       ablation?"
             
             

       "At the moment, no, it's not contraindicated in my practice. I have       to admit that the failure rate is higher for women with adenomyosis. The       problem is we don't know which comes first - adenomyosis or the       endometrial ablation."
             
             

       "What about insurance companies - do you see them mandating this? In       our country, they quite often will mandate an ablation technique before       moving on to hysterectomy, even when the ablation technique may not be the       appropriate choice for that patient."
             
             

       "In Canada, we have social medicine. We're lucky that it's dictated       to us on what to do, so everything is based on medical decision or       indication."
             
             

       "Do you see new alternatives to management and dysfunctional bleeding       coming up in the near future?"
             
             

       "Like everything else, I think more and more medical treatment is       being instituted. We have been using a lot of Cyklokapron in the past two       or three years trying to decrease the amount of surgery but most of them       still come back for another procedure."
             
             

       "What sort of pre-treatment do you use before the ablation, and do       you feel that that plays a role in the success of the operation?"
             
             

       "I think most people will use GnRH analogue. Some people use danazol       or birth control pills. My favorite is GnRH analogue, but five weeks       before a procedure. Some other people will use suction curettage before       endometrial ablation, especially microwave - apparently the results are       the same."
             
             

 "I       have a colleague in St. Petersburg, Russia, who reported on 250 cases, and       that's the technique they used. They did not have the analogue available,       and they found that the suction was adequate preparation. We've used GnRH       analogues in our practice, mostly, and have been very pleased with the       results of that."
             
             

       "One thing which is important and interesting is that Dr. McCausland       from California has just published a paper - he called it "Partial       Endometrial Ablation," and he leaves the posterior wall intact. He       did not ablate the posterior wall. The purpose is so the patient can still       bleed. Again, he will tell the patient this is not to eliminate the       bleeding but to decrease the amount of bleeding. So basically, he wants to       prevent intrauterine adhesions."
             
             

       "Do you advise these patients any differently in the subsequent use       of hormone replacement therapy and menopause?"
             
             

       "I will still use estrogen and progesterone. I think it's important       to use progesterone."
             
             

       "Have you seen any malignancies in patients who've been treated with       estrogen alone after ablation?"
             
             

       "So far I have been lucky - I've never seen these patients, but we       are very careful. We do an endometrial biopsy in all patients before       endometrial ablation. If there is hyperplasia, especially in typical       cells, then we don't do it. So you might as well have resected."
             
             

       "Thank you so much. I appreciate it"
             
             

OBGYN.net Conference CoverageFrom First Congress on Controversies in Obstetrics, Gynecology & Infertility Prague CZECH REPUBLIC - October, 1999

Endometrial Ablation vs. Hysterectomy

       "We're here at the first Congress on Controversies in Obstetrics and       Gynecology in Prague. I'm here with Professor William Ledger from       Sheffield, U.K., and I'm wondering if you would tell us about your project       here at the meeting."
       
       

       "What we're running here is a interactive session, trying to       determine variations in practice or treatment of endometriosis around the       world. One of things which is quite obvious to those of us that work in       the area is variation in practice. In a meeting of colleagues from the       U.S., for example, the way they manage patients with endometriosis seems       quite different from the way we think we should be doing it in the U.K. So       we've got a panel of experts from the U.S. and the U.K. who are going to       work through a model using an actual patient history. We'll stop at       various points in her history and determine how we would manage the case       on the two sides of the Atlantic. We then are able to interact with the       audience who come from many countries around the world, and they'll be       able to vote on how they would have managed the case at these different       points in her history. I think, overall, it will be fascinating to see       whether there are big differences in practice around the world and trying       to reach some sort of a consensus as how to manage these problems."
       
       

 "I       think there are so many factors that might affect the decision making. In       the U.S. we find that the disease may, because of the symptoms, present to       a family practice, to a urologist or a gastrointestinal specialist, or       maybe to a physician who is working in a HMO where there's insurance       coverage for one way where the patient primarily has to pay. Are those       issues and wide variations seen in the U.K., as well, in similar fashion       as the U.S.?"
       
       

       "I think there's some nice data that's showing that the delay in       diagnosis of endometriosis is one of the major problems. It's as you say -       they don't present to physicians in different disciplines who don't       understand gynecology. They often are not aware of the importance of       pelvic exam and the findings that they should be looking for and who,       therefore, delay the diagnosis with inappropriate treatment. The mean time       to diagnosis endometriosis is something like seven or eight years which I       think is way too long."
       
       

       "Yes, that still appears to be a factor, though an inordinate delay       in women who present with systems to a gynecologist."
       
       

       "I hope that's changing, and I hope that meetings like this are going       to move that process further along. One of the big debates now is whether       we should be laparoscoping when there's pelvic pain or whether we should       offer them treatment with a GnRH analogue as a first line diagnosis, as       well as treatment. Because if they respond to an analogue, it may be that       we've made the diagnosis of endometriosis without having to perform a       surgical procedure."
       
       

       "Are you doing that presently in your practice?"
       
       

       "In my practice - no, it seems rather too radical for the rather       conservative part of England I now work in. But again, speaking to       colleagues in the U.S., this is what they're piloting at the moment. It       needs to be researched. Depending on all of this is there's so little       research evidence out there that most of us practice according to our gut       feeling and our medical training rather than in an evidence based way. And       this is really where the focus has to be made in endometriosis, we need       more proper randomized studies to tell us the answers to these       questions."
       
       

       "It's hard when you're looking at pregnancy as an end point. It's an       easy objective measure but when you're talking about symptom control, it's       a lot harder because the symptoms don't always correlate with the extent       of visible or apparent disease. So obtaining objective evidence may be       hard when it talks about controlling the patient's sense of wellness       during the latter half of the cycle."
       
       

       "But do you not agree that these problems can be solved, and the way       to solve them is to adopt a true multidisciplinary approach in the       management of endometriosis? I think for too long gynecologists have       maintained possession of this disease in terms of its management. I think       many people have been reluctant to involve nutritionists, pain experts,       and psychologists in the light of a really meaningful way in the       management of the patient. If we were to do that, they have good methods       of measuring pain score, feeling of wellness as you say, scales of       depression, anxiety and the like which we do in a somewhat amateurish way.       We do the best we can but this is not our training."
       
       

       "There are tools such as EuroQoL and SF36 that may be very valuable       if it were encouraged to include these in the in-studies to measure       effectiveness. You mentioned the controversy surrounding initial use of       the GnRH analogue in the patient as far as part of your diagnostic       evaluation. I think in our country, predominantly birth control pills or       non-steroidals, may be the initial approach. What time frame do you think       a trial would be appropriate before saying that a patient had failed the       trial, perhaps, before moving on and other findings on physical exam such       as cul-de-sac nodularity, that might take you to surgery right in the       beginning?"
       
       

       "I think, you're looking at a spectrum of disease. At the one end of       that spectrum is the woman in her middle thirties with severe dysmenorrhea,       dyspareunia, cyclical symptoms, finding an irregularity on the uterus       sacral ligaments on pelvic exam, who most certainly has endometriosis and       almost does not need to be laparoscoped for diagnostic purposes. Now you       might wish to offer a surgical solution to that problem but do actually       have much doubt in our minds about the pathology. You then look at the       other end of the spectrum as someone who is perhaps a lot younger, who has       severe problem with pelvic pain but not in a particular non-cyclical way,       without significant findings on pelvic exam, perhaps with superficial       problems with dyspareunia rather than deep. That is much more the       diagnostic change. Traditionally, one would offer laparoscopy in that case       even in someone who's maybe only twenty-two or twenty-three years of age.       That's not bad management in any way but the idea that I find quite       attractive is exposing the GnRH analogue, say for three months only, and       suppress the ovarian function. If the cause of the pain is related to an       ovarian endocrine drive, that drive is interrupted, and the pain is       treated properly - then we have an answer."
       
       

       "So with that answer, would that then suggest continued suppression       with add-back ad infinitum or do you then use that to indicate that the       patient ought to be treated surgically?
       
       

       "This is the interest in the case we're presenting today because I       think this physician is managing a chronic and incurable disease. Firstly,       you have to negotiate with that individual how she wants her management to       be run. She needs to have the biggest say in whether surgery is used,       whether drugs are used, and what combination for how long. Secondly, try       to do as conservative as possible, these women almost invariably want to       maintain their options regarding fertility. If they present at the age of       twenty-four, more than likely they're planning children later in their       lives, and we need to look very hard to avoid any unnecessary damage to       ovarian function from the fertility perspective. So you mix and match, if       we have a diagnosis, as you say, birth control pills in some women will       work well for a certain length of time. Often the pain will break through       later so then we move on up the ladder of treatment medically or if she       prefers it, the laparoscopic approach with diathermy to the lesions.       Monitoring these days with ultrasound and MRI perhaps is much better than       it used to be so we can look for disease progression physically but in       terms of treating the symptoms, I think a conservative approach is the one       that one would adopt."
       
       

       "The patient with recurrent disease, that's a different story because       you don't have to go in. While the initial surgery may have been performed       by a less skilled individual, often there's not documentation or adequate       documentation regarding the treatment steps that occurred surgically the       first time around. So you're faced with deciding there again the same       issue - do we do another surgery or do we consider a GnRH analogue? Is       your thinking different there?"
       
       

       "I think so, the evidence is clear that surgery done in specialty       centers by people who have a true interest in this disease and who operate       on it frequently has better outcome. I think that is beyond doubt now.       Someone who comes having had treatment elsewhere in a small district unit       that does general obstetrics and gynecology, I think probably one would       want to re-laparoscope. Our own practice now, and very interestingly also       in talking to colleagues from the U.S. from consensus, they routinely       video procedures and offer the videos to the patient. That's very       different because if she can come with objective evidence with what was       done in the previous procedure, we don't need to repeat it. But if that       wasn't done, and again, this is the exception rather than the rule, I       think nowadays to allow patients to see their own procedure, I think this       is a fantastic offer to make to someone - to let them see their disease.       If they don't have evidence, then I think it's appropriate to re-laparoscope       first as a diagnostic procedure and then move on to analogue treatment       unless there is major progression surgically."
       
       

       "Unfortunately in the U.S., insurance companies are advising       physicians against doing that. But as a physician who sees patients       referred in for either infertility or persistent pain, I'm hindered in my       ability to make the diagnosis or to make a determine whether surgery may       be appropriate when I lack that visual evidence."
       
       

       "We're trying a mini-laparoscope at the moment, and there's quite       little data out there again with this sort of device, a 3-mm fiberoptic       device which can be used without a general anesthetic, cutting the costs       and the time involved tremendously. I don't think there's much scope for       it as a surgical tool for operative laparoscopy, but in this kind of       circumstance where one's trying to reach a diagnosis to inspect the pelvis       and look for disease progression, maybe there's a part for that, and it       would keep costs down."
       
       

       "Larry Demco has shown some very interesting work suggesting that the       pain is often not where we see the lesion. Have you had a similar       experience in terms of finding that you would treat the patient       differently based on the findings with conscious pain mapping?"
       
       

       "I think it's quite scary actually, that we have been burning lesions       of endometriosis for many years now in the belief that we're treating       pain. And as you say, the evidence clearly is that the site of the pain is       often not where the visible lesion is. How you get around that, I'm not       sure because trying to undertake surgical treatment on a conscious       patient, I think, is going beyond what most women will accept. Therefore,       are we going to do conscious pain mapping, then anesthetize a patient in a       general anesthetic sense and try to operate on the areas that we thought       the pain originated from? That argument, I don't think, has been resolved       yet to be honest."
       
       

       "We have done this in a hand full of patients, and it's been of       limited use in that about half the patients are unable to tolerate the       procedure and everything hurts. In those that you find the source of pain,       it's usually confirming where you thought the pain might be. Another       controversy that comes up is the issue of what sort of energy source do       you use - and whether endometriosis should be excised or vaporized. What       are your thoughts on that?"
       
       

       "Working in the U.K. National Health Service, we invariably are       offered the cheapest. So although I appreciate the science that's gone       into trying to decide on these questions of how best to do the surgery, in       practice we get electrodiathermy with monopolar and bipolar, again,       depending on the nature of the disease we're approaching. My practice is       now going along with what I think is a European group management of       endometrioma is to drain an endometrioma, cauterize it's base looking for       the site of active disease but no longer trying to strip away the       pseudo-capsule. Again, from the point of view of preserving fertility, it       seems that that capsule contains follicles which would be lost if we       surgically remove them reducing that woman's chances of pregnancy."
       
       

 "I       think it's important if one is going to use an electrical energy source on       the inside, that a bipolar or laser will be less damaging than using a       monopolar energy source which will have more tissue penetration and more       likely to take out an ovary. I'm sure we've all seen patients who end up       amenorrhea secondary to ovarian failure after aggressive or too aggressive       surgery."
       
       

       "That's absolutely right, and again, there are big issues of consent       here that you have to be very careful to explain to the patient - what it       is we're trying to achieve and what the potential dangers are. You know       you see someone without endometriosis and you try your best to remove all       visible deposits, and yet at the same time try not to damage an ovary.       That is very difficult."
       
       

       "It certainly is, and I think the management of large endometrioma is       certainly one of the challenges we face. It's certainly a challenge we       face in managing our IVF patients too. What are your thoughts about the       management of endometriosis? It seems that overall, having endometriosis       or not - doesn't effect the outcome of IVF. Do you see the endometrioma as       a special case though?"
       
       

       "Yes, there was an interesting presentation yesterday saying exactly       that, that patients with endometriosis seem to do just as well as any       other group of patients having IVF. I'm still doubtful I have to say. I       think it's clear that mild, moderate disease probably does not impact an       IVF outcome. I just think from the basic view of how does the ovary       function in IVF if both ovaries are occupied by large cysts which will       have an effect on blood flow, and which probably will contain substances       which can be toxic to this development. It is almost impossible to believe       that those cysts will not have a negative impact on the IVF outcome. The       studies that have been done have not included many women with severe       disease in the IVF context because thankfully it is less common in the       milder form of the disease. So I think probably there's still some work to       be done there. As to treatment, I think the evidence would suggest that if       a lesion is over five centimeters in size, it should be dealt with before       the IVF cycle is started. Secondarily, if a smaller cyst is there, one       should make every effort to avoid it. There's always a temptation with a       needle in the pelvis and a cyst full of fluid to put the needle into the       cyst and drain it. And again, those presented here and elsewhere, the risk       of infection in that drained cyst because of the multiple needle punctured       IVF is not small and can cause great damage."
       
       

       "Absolutely, that's certainly our finding. One of the other things       that has been interesting is that there has been some authors who have       suggested that antiphospholipids are a problem in patients who are faced       with endometriosis. I think that data has really been gone over and would       lead one to think that it's not a factor in IVF. What is your belief, do       you think that data's conclusive?"
       
       

       "No data's ever conclusive, but I think that it is much more solid       now than it was a year or two ago. But again, evidence presented yesterday       of increased rates of miscarriage in women treated with IVF after       endometriosis are quite striking in a very small series, and suggest that       maybe there's more work to be done looking at links between having       positive endometriosis in the pelvis and pregnancy outcome. The data is       there. All our IVF units monitor their patients through pregnancy       meticulously. I just wonder if there's a need for a real analysis of big       data bases looking for links between endometriosis and miscarriage."
       
       

       "One of the problems with this is that you get the diagnosis, you       have the surgery, and the physician generally would have treated the       disease at the time of that surgery. The diagnosis is made - so whether       there's significant disease present at the time, and it's the       endometriosis that's causing the problem or the underlying premise that       brings about endometriosis that would interfere - I think is an       answer."
       
       

       "It's a fascinating question, and maybe you could use it as an       argument to explore the hypothesis that it is a defect in endometrium       itself which is leading to endometriosis, and secondarily, is causing       problems with implantation and pregnancy failure. For as you say - there's       no signs there, there's nothing more than an idea that would be       interesting to explore."
       
       

       "Many physicians in our country see the patient with endometriosis       and believe that that's an indication to move on to in-vitro       fertilization. They don't feel that that's an appropriate patient for       ovulation induction and insemination. What do you think about that?"
       
       

       "Again, I think you must look at the severity of the disease. There       are people with severe endometriosis who've had multiple pelvic surgeries       who are unlikely to conceive with something as simple as superovulation       IUI. On the other hand, in my practice the cost of superovulation IUI is       so much less than IVF, and the human cost of doing IUI is also low. It's       an easy treatment for most women to undergo without all the rigors of the       IVF process. But I think the data would suggest that in mild or minimal       disease, superovulation IUI has a clear place to pay. In your country, the       dollar cost of IVF is even greater than in mine, and I'm sure there must       be many couples who cannot afford that cost perhaps for more than one       occasion. If you look at key success rates with IUI, maybe on a cost       benefit analysis, three or four attempts at IUI would actually perform one       cycle of IVF."
       
       

       "And still for less costs than the IVF."
       
       

       "And still for less costs, yes. Many centers do IVF, they're only       there for IVF, and other things are seen as old fashion or less effective.       They are less effective on a cycle-per-cycle basis but they still make       plenty of babies. But I think a good fertility center should have a range       of treatments at their disposal, then again, reach a decision as an       individual basis with the couple concerned."
       
       

       "There's been data presented that pre-treatment with GnRH analogue is       more important even in the patient who's undergoing IVF with endometriosis       and that perhaps, even a three months pretreatment period improves the       results."
       
       

       "Yes, but there's evidence on both sides of that, isn't there. Again,       a good study is waiting to be done. Sam Marcus and Rob Edward several       years ago now produced a paper showing that long term suppression of       patients with severe endometriosis had a dramatic effect on IVF outcome.       More recently there have been small landmark studies better designed than       Markus and Edwards that seem to contradict that conclusion. There are some       nice pilot pros in long term suppression which might give some theoretical       basis to a benefit. It's not easy for them to be suppressed for many       months at a time, I think you must be careful not to offer these       treatments without some reasonably good scientific basis that's going to       help. So again, I would encourage those out there that can put studies       together to maybe think about running a proper multi-center study of one       month versus three or four month suppression. It needs to be done but it       needs to be done with big numbers."
       
       

       "Yes, it does. That would be exciting to see those results."
       
       

       "I'm sure we'd both want to participate."
       
       

       "I'm excited, we have a new program starting in Atlanta, and       hopefully, we'll have the numbers to participate in those kinds of trials.       Thank you so much Professor. It's been a pleasure talking to you."
       
       

OBGYN.net Conference CoverageFrom First Congress on Controversies in Obstetrics, Gynecology & Infertility  Prague CZECH REPUBLIC - October, 1999

Treatments of Endometriosis Around the World

click             here for audio/video version

  "I       am here with Dr. Lunenfeld, and I remember the wonderful discussion and       breakfast we had back in Geneva. I am so excited that you let me know that       we will have an opportunity to meet in Geneva again. Can you tell us a       little bit about the conference that is going to be coming up in       Geneva?"
       
       

  "Dr.       Perloe, I am glad you enjoyed the meeting in Geneva and I am happy to       inform you that the 6th International Congress on GnRH Analogues in Cancer       and Human Reproduction will again take place in Geneva on February 8-11,       2001. It will be a very interesting meeting because at that time we hope       to be able to arrive at a consensus on the role of GnRH analogues in the       treatment options of endometriosis and in the management of uterine       fibroids. The use of cyclic 'add-back,' as well as adjunctive therapy in       patients treated with GnRH analogues for extended periods, will be       discussed. I am sure there will be long and heated debates on the use of       agonists via antagonists. We will learn the advantages and disadvantages       of agonists and antagonists, and I hope it will become clear when agonists       should be used and when to use antagonists.
       
       Furthermore I hope we will also come to a consensus on what the three most       important challenges for ART procedures are: to increase pregnancy rates,       decrease high-order multiple pregnancies, and avoid and manage       hyperstimulation. Also, concerning cancer and particularly prostate       cancer, new information will be made available in Geneva.
       
       The above are only a few topics to demonstrate to you why I think the next       meeting in Geneva in 2001 will be extremely interesting and will have a       very strong impact on our medical practices. Now, on to your question       concerning today's management of endometriosis with antagonists... For the       time being, there are no long-acting antagonists on the market. Since the       medical treatment of choice for hormone-dependent endometriotic lesions is       the administration of long-acting depot preparations of GnRH analogues,       long-acting GnRH agonists will remain the only therapeutic option.       Long-acting GnRH antagonists should become available for clinical use in       about three or four years, but for now, there is no question that the       long-acting GnRH agonists are the first line of treatment of any       hormone-dependent endometriotic lesion.
       
       As to your question concerning uterine fibroids, I think there is a       consensus - or at least I believe there will be after Geneva, 2000 - that       the primary treatment of most uterine fibroids will be with GnRH analogues       prior to surgery. I am sure most of my colleagues even today agree that,       following GnRH analogue treatment, there is a definite decrease in fibroid       size and decrease in blood loss. In many instances it will allow surgery       through the vaginal route. As I said previously, for the time being there       are no long-acting antagonists on the market and long-acting GnRH agonists       will remain the only therapeutic option."
       
       
       

  "It       appears that the initial protocols in the initial results from Dr.       Felderbaum's study suggest that while you are using less FSH, you may       shorten the number of days by using an antagonist and lower the risk of       hyperstimulation. I'm not yet convinced that the pregnancy rates will be       better. Is that enough to get us to switch from a analogue to an       antagonist?"
       
       

  "You       are perfectly right. I agree that both Felderbaum (multiple-dose protocol)       and Olivienne (single-dose protocol) have clearly demonstrated that GnRH       antagonists such as cetrorelix and ganirelix prevent premature LH surges,       are safe and effective, and reduce treatment time and the amount of       gonadotropins necessary for successful ovarian stimulation. Fertilization       rates obtained are comparable to those obtained with GnRH agonists       protocols. If GnRH antagonists will be replaced in the future, all GnRH       protocols remain an open question. We have insufficient data, for example,       on the use of GnRH antagonists in PCOD patients."
       
       

  "Markus       and Edwards have suggested in their early work that a three-month trial or       three months pretreatment with analogue may improve the outcome in IVF.       What are your thoughts on that, and is there more data available now that       clarifies that picture?"
       
       

  "In       my opinion, this is true only for PCOD patients and this is probably one       of the reasons that you get similar effects if you pre-treat for one or       two months with some of the oral contraceptives. I know we will get some       more good data in Geneva in February of 2001."
       
       

  "I       think one of the things that's exciting to me in the PCOS patient is the       difference in vascular flow patterns. There's increased stromal flow,       there's decreased follicular flow, there's increased VEGF, there's       diminished blood flow in the endometrium, and these may all be factors.       Many people are utilizing metformin for ovulation induction, and we've had       in our program a number of successes in deliveries. Some people are even       suggesting that we continue using metformin to lower insulin levels and       maintain it during the pregnancy, suggesting that the diminished blood       flow or the destruction in blood flow associated with hyperinsulinemia may       be a factor in miscarriage. Do we need to look at that in the IVF patient,       and do you believe that insulin may play a role? Are you aware of any       other studies that are working on that role right now?"
       
       

  "Thank       you for enlightening me. I have heard about some of these studies, but I       have no personal experience. But the results make sense - they're logical.       We know, for instance, from a study done by Dr. Steve Frank in London that       when we reduce weight in some of the obese patients, insulin levels go       down and pregnancy rates are improved. We are planning a symposium on this       subject in Geneva during the GnRH meeting. I hope it will       materialize."
       
       

Bruno Lunenfeld, MD

Articles

The History of the GnRH Analogue Conferences

Endometrial Ablation vs. Hysterectomy

Treatments of Endometriosis Around the World

Endometriosis and Infertility