Liselotte Mettler, MD

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:  "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

:   "This morning, Professor Mettler, you showed us a beautiful picture of  an         endorecto-sonography and it showed that we're not very  experienced in this type of gynecology.  It was one of your questions,  and I think these exams are really helpful to detect, as you call it,  the peritumoral infiltration of the rectal wall.  Sometimes it's a  fibrotic invasion by the fibrosis and in some case it's not necessary to  remove the rectum, as you mentioned this morning."
             
             

:  "Yes,  endorecto-sonography is a technique that rectal surgeons are applying a  lot.  It shows exactly if the mucosa is infiltrated or not or if it's a  perirectal lesion but for the patient this mostly fibrotic invasion is a  typical example of a new disease that you are now calling         RAD.  It is one that we have to attack either surgically or by  hormonal treatment.  Of the different techniques that are available  diagnostically of the retroperitoneal space including the ureteric area,  which techniques do you think are the most suitable ones and which ones  are you applying?"
             
             

: “In fact, in case of a big  nodule, I will systematically ask for a barium enema and intravenous  pyelography.  A CT scan  can be helpful to see the lateral extension but  don’t forget that the first tool for diagnosis is the pelvic, vaginal,  and rectal examinations.  I’m not sure that we have to examine the  patient during menstruation, if we look very well in this space and we  explore the rectovaginal septum with the fingers, if a nodule is present  we will surely feel it.”
             
             

:  "Now my last question to  you is what do you think about treating these patients not surgically?   We both agree that it is the method of choice for a young patient.  In  little advanced aged patients with severe pain that want to avoid the  surgery, would you give them a trial with an endocrine approach?"
             
             

:  "As you said, in young  patients that are less than thirty-five years of age and in the majority  of the patients who experience this type of pathology, I would  recommend laparoscopic excision, not the very aggressive one with rectal  excision, I prefer a debulking surgery.  I would take care of the  lateral extension because already in my series so far five patients have  experienced the loss of a kidney because it was completely silent.   They had pain in the pelvis, severe dysmenorrhea, and dyspareunia but  never pain in the back.  Nevertheless, they lost a kidney so I should  recommend surgery but should I also agree that in some instances in  older patients or patients with recurrent disease who have symptomatic  impression of pelvic pain of deep dyspareunia, I should have endocrine  therapy, as you mentioned, long term therapy with GnRH agonists and  progestogens combined.  Nevertheless, we have to know that these  progestogen receptors even if present are probably inactive so that we  don't reduce it by endocrine therapy.  We don't reduce the size of the  nodule but we stop the symptoms and it depends on what the best benefits  are for the patient."
             
             

:  "You mentioned that you  mainly use laparoscopic surgery for these lesions.  If it's a nodule of 3  cm in extension and going into the rectal wall, it may not be possible  to avoid a rectal resection.  Do you then do this by laparoscopy or in  combination or how do you do this surgery?"
             
             

:  "When we decide to do a  resection of a part of the rectum it's because a complete invasion  includes the rectal mucosa; if there is no rectal mucosa involvement, we  don't do a resection of the rectum even if the tubal wall shows signs  of         perivisceritis.  If there is invasion of the rectum, we will  perform a laparotomy but I agree with you, like in your video, probably  with the collaboration of the rectal surgeon we can in the future do the  resection on this part of the rectum by laparoscopy also."
             
             

:  "Jacques, thank you for  the nice interview.  OBGYN.net has a good future and we're happy to have  interviewed Professor Donnez today."
             
             

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

Aplastic Nodules: Surgical Interventions - Practical Approaches

This interview is also       available in 

       it is my pleasure to interview today in Orlando at the end of the year       2000, Professor H. J. Lindermann, from Hamburg, Germany.        I am Professor Lisolette Mettler from Kiel, Germany.  We are from neighboring cities, and it’s my very big       pleasure to talk with a pioneer of hysteroscopy.        Professor Lindermann, what is hysteroscopy?”              

:        “What is hysteroscopy?  Hysteroscopy       is looking into the uterine cavity.  Before       it was not possible to get information on what is going on in this cavity       but now we have the possibility to see what is going on.”              

:        “When did you start to look into the uterine cavity with this       hysteroscopy?”              

:        “It was long time ago, about thirty years after a very       interesting Congress of sterility and infertility patients in Yugoslavia.        This time it was very peaceful and wonderful.  We started with the idea to bring in a practical technique to       look into the uterine cavity and to see what could be inside the uterus       and the cause for the infertility.”              

:        “How did you look inside?  Did       you use some medium to expand the cavity or how could you see an otherwise       collapsed part of the uterus?”              

:        “Good question, normally the uterine cavity is only a flat slit       and it’s not possible to take a look into it because the distance was 3       inches of an endoscope through the uterine wall.        It’s not possible so you would need dilation of the uterine       cavity to see the uterus wall.  We       started with physiologic solution, water solutions, and later we used       water fluids with physiologic fluids.        Today, I would make a spring from 1970 to…”              

:        “A jump, you’re jumping from 1970 to 2000.”              

:        “Yes, to 2000.”              

:        “What are we using nowadays to explore the uterine cavity?”              

:        “I think it is a wonderful method and a very simple technique to       take a look into the uterine cavity for information, in other words, to       make a good diagnosis.  You       can recognize a very early carcinoma and it’s very important to treat a       case very early.”              

:        “So would you suggest then to use a saline solution or a high       molecular fluid solution for a biopsy of such a lesion or would you prefer       the CO2 hysteroscopy in these cases?”              

:        “We now change back to the beginning of the diagnostic       hysteroscopy in the time before we used CO2, which is carbon dioxide.        Now we have with the industry apparatus makers’ agreements with       our ideas to construct apparatuses with a safe outflow of the CO2 gas into       the human body so that we no longer have any problems or complications       with this method.  With       surgical procedures if you do it with the hysteroscopy, the CO2 gas is not       the right medium, I would say a fluid medium is much, much better.        Why – we have bleeding in the uterine cavity if we work inside       it, we make injuries of the endometrium, and then the blood comes out and       bleeding prevents your vision, it’s over then.        If you have a fluid, then the blood is going with the fluid out       from the uterine cavity and you have a clear view.”              

:        “I know that besides the operative hysteroscopy that we use       nowadays for septum resection, myoma resection, and polyp resection you       have been very interested in the field of sterilization.        Do you see that a hysteroscopic technique can help for a definite       sterilization in mankind?”              

:        “I hope so in the future, we have tried for thirty years with the       help of the WHO and until now in every country where the gynecologist was       interested to make a practicable method for sterilization, it doesn’t       work.”              

:        “At this Conference, I’ve seen a presentation by a company that       showed a device that they put into the tube.        It then provokes and closes up the tissue and histologically       they’ve proven that the tubes are blocked.        They call this device the STOP device, and it is placed by       hysteroscopy.  Do you think       that this can work?”              

:        “Why not, when I hear this I would immediately go after our       interview and look for that.  I’m       very interested in it because I was the first man in the world who started       with this idea to make a closing of the fallopian tubes in the area of the       uterine wall.”              

:        “It’s a big pleasure to have Professor Lindermann who has       attended all of the twenty-nine meetings of the AAGL I would think since       it began, and he’s really one of our world       famous pioneers.  Thank you       for talking to 

:        “Nice to meet you, Lisolette.”

OBGYN.net Conference CoverageFrom American Association of Gynecological LaparoscopistsOrlando, Florida, November 2000

Hysteroscopy

Click             here for Audio/Video Version

   Good morning, Dr. Amar Sawhney, I am Professor Liselotte Mettler from the Department of Obstetrics Gynecology,  University of Kiel, and we have met before.  I know that you are the  President of Confluent Surgical, welcome. We would like to talk at the present time  about adhesions, which is a very big problem for women.  Adhesions  results after any surgery, any infection, and it brings many patients to  us as gynecologists for a second surgery and we, so far, do not have  any good products to prevent new adhesions.  So what is your product  that the company is at the present time supporting and doing trials  around the world, I understand.  What is the product?
 
 

 Professor  Mettler, it is a pleasure to meet you and see you again.  My company,  the company I am the President of Confluent Surgical, is based out of Boston, Massachusetts, specifically  in Waltham, Massachusetts.  We’re a small company, we’re working on some  innovative products and technologies, especially designed for the  problem of adhesion prevention and our products are currently going  toward laparoscopic prevention of adhesions for which there is no  product currently approved in the United States.  Our product, SprayGel,  which consists of two liquid components that can be sprayed by a device  that goes through keyhole surgery, so it can be used laparoscopically.
 
 

 While here at this meeting of the American Association of Gynecological Laparoscopists, I see the doctors running to your booth.
 
 

 Yes, it is an  exciting development for them because they have not had this tool before  and they are looking forward to participating in the US in trials and  in Europe and Australia, where the product is actually commercially  available now and it’s been used in many countries, such as in Germany,  in Italy and a few other countries in Europe it has been used and in  Australia and New Zealand, also.  In the United States currently, it is  undergoing multi-centre clinical testing.  We have finished one series  of clinical testing with Dr Alan Johns and now we have some additional  clinical trials which are underway at some medical centers across the  United States and more information on Confluent Spray Gel can be found on our website, at 

  I  personally have used the gel for now probably 200 patients, and I’m very happy with it.  I think it’s one of the newer products  which has a future.  We have to wait and see.  It will be very  successful because of the studies we’ve done, but we are optimistic and I  do hope that you have a good future with this product and we can help  many women for this product adhesions, which is a great problem and  there is no cure for the present time.
 
 

 I hope so.  We  are actually getting a lot of requests from patients who need this  product and some of them actually are going to Europe to get treated,  unfortunately right now because the product is not approved in the  United States.  Women who are suffering from problems of adhesions,  caused either due to previous surgery or due to endometriosis and  resulting in pelvic pain are unfortunately are coming to us seeking use  of the product.  Unfortunately right now, it is under only clinical  trials in the US and only available in, of course, the clinical study;  but in Europe, Australia and New Zealand, it is commercially available  and we hope to do that shortly in the United States, too.
 
 

  Thank you for your kind interview.  Appreciate your help.

OBGYN.net Conference CoverageFrom the 31st Annual Meeting of the American Association of Gynecological Laparoscopists (AAGL)

Liselotte Mettler, MD

Articles

The History of the GnRH Analogue Conferences

Aplastic Nodules: Surgical Interventions - Practical Approaches

Hysteroscopy

A Solution to the Problem of Adhesions