The Importance of GnRH-Analogues in Infertility

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Dr. Hugo Verhoeven: "My name is Hugo Verhoeven, I'm from the Center for Reproductive Medicine in Dusseldorf, Germany, and I'm on the Editorial Board of the OBGYN.net. I'm reporting today from the 6th International Symposium on GnRH Analogues in Cancer and Human Reproduction in Geneva, Switzerland and it is an exceptional honor for me to talk with Professor Victor Gomel who is the Chairman of the Department of Obstetrics and Gynecology in Vancouver, Canada..."

Professor Victor Gomel: "Was the Chairman."

Dr. Hugo Verhoeven: "Or was the Chairman in Vancouver, Canada, British Columbia. Victor, we've known each for twenty years, and I think I can say that without your help I wouldn't be here. I would maybe be a small gynecologist somewhere in the countryside in Belgium."

Professor Victor Gomel: "You are being very humble, a talented man like you would never remain in the shadows, I know that."

Dr. Hugo Verhoeven: "I want to take this occasion to thank you for that."

Professor Victor Gomel: "Thank you very much."

Dr. Hugo Verhoeven: "Victor, I think you are absolutely the right person to overview this meeting. You were a guru in the field of infertility surgery since the beginning. Every new treatment possibility for different diseases like endometriosis, myoma, adhesions was co-invented by you. You followed also the medical treatment of diseases leading to infertility very close. The inauguration of the GnRH-Agonists some ten years ago was very important. Now we have the antagonists. So, what fascinated you years ago at the moment of the introduction of the first analogues, and what is fascinating you now, some few years after the introduction of the antagonists?"

Professor Victor Gomel: "If we take the antagonists first, the beauty of the antagonists is the immediacy of their effect and the ability to play on surge in a very short period of time without the, if you like, lack of immediacy of agonists. On the other hand, the agonists have been surprisingly useful. You who do an awful lot of IVF are aware of this; we also do a lot of IVF, for that matter. Vancouver was the first department in Canada to achieve an in vitro baby first and that baby was born in 1983 so it goes back a long way but agonists have had a tremendous effect on surgical problems as well. For example, certainly in endometriosis one can see the difference in a patient who has very active and very inflammatory endometriosis. Usually in such patients surgical treatment is delayed and analogues are used to cool down the disease and see what really needs to be removed. This is the kind of inflammatory endometriosis where you can see the peritoneum being just like algae growing very red and so on."

Dr. Hugo Verhoeven: "So the gold standard for the treatment of extensive endometriosis is still a combined therapy of an agonist and surgery."

Professor Victor Gomel: "Followed by surgery if it is inflammatory endometriosis. You can have extensive endometriosis that is largely scarred, in that particular case, I wouldn't use analogues first. The other area of interest for analogues for me is in myomas; a lot of the myoma patients come to you with very severe anemia, secondary to abnormal bleeding as a cause of myomas. You can restore those patients' hemoglobin in a very short period of time by giving them analogues and also have the benefit of reduction in the size of their myomas whether you're going to do a myomectomy or a hysterectomy. Frequently, you can turn a case of hysterectomy by reduction in size into a reasonably easy vaginal hysterectomy so that the patient doesn't even have to have a laparoscopy assisted hysterectomy so you can turn it into a vaginal hysterectomy."

Dr. Hugo Verhoeven: "Are you really convinced that agonists are of any benefit in myomas?"

Professor Victor Gomel: "Benefit, no, it depends on what you call benefit. I don't like to operate on a patient who has 8 grams of hemoglobin for elective surgery, and a patient who has been bleeding chronically and who has a hemoglobin of 8 grams is not an acute situation. By giving her agonists, you restore her hemoglobin to 12 or 13 grams and you can operate very comfortably and diminish that patient's chance of having a secondary infection. I think that is a very important benefit. I am not suggesting the big benefit to be reduction in the size of myomas when you are going to do a myomectomy because you may have some dissection problems with some of the patients."

Dr. Hugo Verhoeven: "We've talked now about endometriosis, myomas, and agonists - let's switch now to the antagonists. The first antagonist on the market was Cetrorelix, then came Ganirelix, and now here at this meeting we are talking quite a lot on depots especially in urology with molecules like Abarelix. What are your expectations, what are the potential benefits, clinically speaking, of the antagonists? What is going to be the benefit for the patients?"

Professor Victor Gomel: "I think that in IVF we are going to have substantial benefits. Instead of giving the patient a longer period of medications as we do with agonists we will be able to reduce that period of time and use the antagonists for a short period to just inhibit the surge. There are sufficient data published on that so I look forward to further studies with other analogues. Now with regards to the depot preparations, whether these are going to have a benefit over the agonists, I don't know, we have to wait and see. What do you think about that?"

Dr. Hugo Verhoeven: "I am not sure neither. Nobody likes the flare up effect of agonists. What's wrong with the flare up? In in vitro fertilization this is not a problem, do you expect some negative effects of the flare up in myomas or in endometriosis?"

Professor Victor Gomel: "You're talking about the flare up effect of agonists - we have lived with the effect of the agonist, the desirable effect of ovarian blockage, if you like, is delayed, that's really your only problem. This is why I do not know whether or not the depot preparations of antagonists will provide us with a greater benefit - that has to be seen."

Dr. Hugo Verhoeven: "Don't you think an ideal tool would be an antagonist that works longer then cetrorelix, let us say 5 to 8 days, but shorter then the real depots like abarelix. With a single shot you could prevent premature ovulation for a longer period of time ..." 

Professor Victor Gomel: "Yes, that I can see."

Dr. Hugo Verhoeven: "The final thing is : I'm always thinking about the future, do you expects some spectacular new antagonists or even agonists ?"

Professor Victor Gomel: "What I would really like is drugs that will directly treat endometriosis and myomas and not indirectly by ovarian suppression. We will come to find medications that will directly inhibit the growth of endometriotic tissue and directly inhibit the myomatous tissues, then you are treating patients histologically so I'm looking forward to that not only for endometriosis and myomas but especially for cancer."

Dr. Hugo Verhoeven: "That was a very important point, and I would like to finish the interview with saying thank you, Victor. It's a pleasure like always, and have a good stay in Geneva."

Professor Victor Gomel: "Thank you."