Endometriosis and Infertility

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Dr. Mark Perloe: "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?"

Professor Bruno Lunenfeld: "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."


Dr. Mark Perloe: "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?"

Professor Bruno Lunenfeld: "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."

Dr. Mark Perloe: "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?"

Professor Bruno Lunenfeld: "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."

Dr. Mark Perloe: "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?"

Professor Bruno Lunenfeld: "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."

Dr. Mark Perloe: "Thank you."

Professor Bruno Lunenfeld: "Thank you."