The Role of FSH and Isoforms in Oocyte Maturation

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Dr. Hans van der Slikke: “It’s the 3rd of July in 2001, and we are here at the 17th ESHRE Conference in Lausanne. Next to me is Dr. Clans Yding Andersen; he’s a researcher at the University of Copenhagen. Good afternoon.”

Professor Clans Andersen: “Good afternoon.”

Dr. Hans van der Slikke: “I want to talk with you about your presentation from yesterday, and I want to have more of an explanation because it was a very difficult topic. You talked about the role of FSH and especially the different isoforms in the role in oocyte maturation. Could you explain first these several isoforms?”

Professor Clans Andersen: “Yes, FSH, as you may know, is a hormone which affects the ovary and can make follicles grow and mature oocytes but it turns out that FSH, when it’s released from the pituitary, can exist in several different forms. It’s not the backbone of the molecule that’s altered, that’s similar for all the different FSH isoforms but there is some sugar residue sitting on it and they can change. They can actually affect the function of the molecule so it relates to the sugar residues which is attached to the molecule.”

Dr. Hans van der Slikke: “And this means they all have a different action?”

Professor Clans Andersen: “It actually may mean that they interact with the FSH receptor on the follicles in a different way which we thought but just don’t quite know at the present time how this interaction with the different FSH isoforms actually occurs quite precisely. There may be different ways that FSH interacts with its receptor; it may give some responses in some situations and other responses in other situations.”

Dr. Hans van der Slikke: “That’s what you presented; you have a model to test these several ways of action?”

Professor Clans Andersen: “Yes, we have tried to use oocyte-cumulus complexes, the complex which the oocyte - the egg - is sitting in when it’s released from the follicle. We tried to use that as a model to study the effect of the different FSH isoforms and this actually may turn out to be quite a good model to study this in because the cells which surround the egg and which support the egg only have FSH receptors, they do not have LH receptors. They’re only affected by FSH and, furthermore, when the oocytes - the egg - is taken out from the ovary it’s in the cycle when there is a lot less acidic isoforms in circulation. So it may well be that the responses we obtained from this specific model is actually reflecting quite well what happens in the body.”

Dr. Hans van der Slikke: “Could you explain what the clinical implication of this research could be?”

Professor Clans Andersen: “If we understand in more detail what the different FSH isoforms are actually doing and we can apply that in a clinical situation then we may actually be able to obtain eggs which upon fertilization in vitro or for that matter in vivo have a higher developmental competence and are more likely to generate embryos which will implant and can result in a child.”

Dr. Hans van der Slikke: “Can there also be a difference in the recombinant FSH and the purified FSH in terms of the isoforms?”

Professor Clans Andersen: “There is the recombinant FSH preparation, they have almost a similar FSH iso-hormone profile but compared to the urinary derived gonadotrophins they have a slightly more acidic isoform distribution and, therefore, you may actually expect a higher biological in vivo activity from the recombinant gonadotrophins.”

Dr. Hans van der Slikke: “Which doesn’t appear in clinical practice.”

Professor Clans Andersen: “It’s a matter of how well the different gonadotrophin preparations will affect oocyte maturation the way that their stimulation protocols are done today because you use a large bolus of HGG to induce ovulation. In the final stages of oocyte maturation, actually, there may be a beneficial role for FSH. This is not used in the current day protocols but if you include FSH and have a signal which induces ovulation and final oocyte maturation, which resemble the mechanism that nature uses, you may actually be able to obtain oocytes that have a better competence.”

Dr. Hans van der Slikke: “I see but could this research also mean that you find a certain isoform of FSH that’s more active than the recombinant FSH of nowadays that will be a little change towards another isoform?”

Professor Clans Andersen: “Yes, I think maybe you could imagine that in the future you would use different FSH isoforms in different parts of the cycle. Maybe you would start off by using more acidic isoforms and then as ovulation approaches you would change to less acidic isoforms. If you could also use the less acidic isoforms in connection with a mid-cycle surge of gonadotrophins then I imagine that you could actually obtain eggs which were more competent and had a better maturation.”

Dr. Hans van der Slikke: “Thank you very much, Dr. Andersen.”

Dr. Andersen's presentation is available for reading.