Hans van der Slikke, MD, PhD

  “We are at ESHRE 2003 in Madrid,  Spain and we have here Dr. Basil Tarlatzis from Greece and Dr. Bart  Fauser from Holland and they talk this afternoon about the new  guidelines for PCO and PCOS.  Welcome gentlemen! Could you give a little  summary, in a few words, of the main diagnostic criteria and  nomenclature you talked about?” 
 
 

  “Now the three criteria that will appear in the new guidelines are the clinical picture of abnormal ovarian function: 
 
 1) oligoamenorrhoea
 2) any form of hyperandrogenemia, either clinical, being hirsutism, acne  or endocrine which means the hormonal diagnosis of high androgen  levels, and 
 3) the ultrasound picture of polycystic ovaries. 
 
 Those three are the major criteria but it’s important to realise that in  order to make the diagnosis it doesn’t need to fulfil all three  criteria but only two out of three.  That makes it into a heterogeneous,  so if you have polycystic ovaries and hyperandrogenemia you don’t need  to have cycle abnormalities for the diagnosis.  Or if you have cycle  abnormalities and polycystic ovaries you don’t need hyperandrogenemia  for the diagnosis. 
 
 So I think that’s a real advancement in terms of way you are thinking  because as gynaecologists usually we are not used to that kind of  thinking although in other specialties that’s pretty common.  Indeed I  think it’s the ultimate: it’s a syndrome.  We know that not a single  symptom or sign is mandatory for the diagnosis and that’s usually still  how our mind works.  We want to see it in black and white.  It should be  there or it shouldn’t but here sometimes it can be but it doesn’t have  to.”
 
 

  “This is important because it’s  not a disease of importance for gynaecologists only but it is a serious  disease for long-life diabetes, cardiovascular disease maybe?”
 
 

  “Yes!  Right!  Therefore they may  visit a cardiologist, they may visit an endocrinologist, a medical  endocrinologist, paediatrician if they are relatively early with their  complaints, a dermatologist because of hirsutism, so they have very  different phenotypes.  And depending on age, indeed they may go on with  obesity problems, and signs of early diabetes. 
 
 The key issue and the problem is, and the major controversy has been,  the ultrasound.  That started in the UK.  All the first papers were from  the United Kingdom, and they were widely accepted I think in major  parts of the world, except North America and that still is the case.   It’s still clear, and what we’ve done now is try to unify in order to  make something workable for everyone.  Clearly now too we got criticised  this afternoon because some people were saying, “Yes but ultrasound  should be mandatory. I would never diagnose a PCOS without the  ultrasound picture.”   And two weeks ago in the US there were quite some  complaints, people there were saying, “We don’t need ultrasound at  all.”  So it’s interesting.  Now you see we all have our own perceptions  and world and cultural things and if we can really get it to work, get  it on paper supported by all the participants and then get it published I  do believe it’s a clear step forward.”
 
 

  “Dr Tarlazis?  How many Americans participated in this workshop?”
 
 

  “Approximately 10, almost half of  the participants, and they were the leading figures working in the  field.  Of course we had very intense discussions because, as Professor  Fauser said, the problem is that   they have focused mainly on the  menstrual ovulatory irregularities and the high androgens, but we know  that, as I said, the phenotype PCOS is variable, so you may have high  androgens without menstrual irregularities but on an ultrasound,  polycystic ovaries. 
 
 And then, if this woman gains a few kilograms or pounds, she becomes  irregular in her menses.  Hence, the syndrome is there, but you may see  it at a different phase in her life.  Therefore, we tried to be as  inclusive as possible, namely to include all possible phenotypic  disorders in order to be able to understand what is happening with the  disease and move forward to its aetiology. Obviously, that was the  difficulty.  When such a thing is being proposed, as Professor Fauser  said, you face opposition from both sides. I mean, those who have been  used to use ultrasound only, they say, “Why do you need all these  androgen measurements and stuff?”  If on the other hand, you speak with  the American colleagues who have been used to use only the blood  measurements and very elaborate endocrine tests, they say, “Why do you  need the ultrasound?”  The fact that the complaints come from both sides  means that we are on the right track. 
 
 The second thing that we tried to do, and which will hopefully appear on  the paper, was to set criteria, because indeed both the measurement of  the androgens but also the ultrasonographic evaluation of the ovaries,  have pitfalls.  Thus, in the paper we will put some guidelines again on  how we should determine ultrasonographically that an ovary is polycystic  and the same we will try to do for the androgen determinations”.
 
 

  “Actually there was a clear consensus there which I think already is a step forwards.”
 
 

  “Indeed, and ultrasonography, ovarian volume should be the feature because  it is simple and  the  current equipment, can automatically calculate ovarian volume, if you  properly measure the three dimensions.  Thus, we can have a more  objective   measurement.  And for the androgens we will also have some  guidelines on which tests to use and what are their limitations.”
 
 

“It’s going to help it and I think  it’s going to stimulate certain developments and it’s certainly going to  put more emphasis on certain androgen assays which will be developed  further as being the most reliable marker.”
 
 

  “It is extremely important to be as  precise as possible, because trying to diagnose such a variable syndrome  with tests that are not objective and accurate, you can imagine, ends  up in chaos.”
 
 

  “Not only for treatment but also for science and for evidence based medicine.”
 
 

Associate Professor Basil C Tarlatzis, MD, PhD:

  “And for advances in the field because  you can, obviously you can build a house with bricks and stones but if  the foundation is not good then it’s not going to work after all.  And  that’s the fear obviously that people are doing so many different things  and later on you have to start from scratch again.  So now we try to  work on the foundation to make that more solid.  From there on we can  build again.”
 
 

  “It’s very good.  I congratulate you both on the results of these beautiful consensus.”
 
 

  “It’s going to be published both in  Fertility and Sterility and Human Reproduction at the same time.”
 
 

 “Hopefully by the end of the  year.”
 
 

  “This will be great. Thank you both very much.”

Articles

OBGYN.net Conference Coveragefrom the 19th Annual Meeting of ESHRE - Madrid, Spain

PCOS: What is the Diagnostic Criteria?

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          "It's the third of July in 2001, and we're in Lausanne at the  ESHRE Conference.  Next to me is Professor Hans Evers from Maastricht  and he will be the next president of ESHRE.  Good morning,       Hans."
       
       

  "Good morning."         
       
       

         "You were so kind to give us a little overview of the highlights  of this 17th ESHRE Conference.  What do you think are the most  impressive presentations you saw?"
       
       

 "I'm a  clinician so you have to allow me some leeway but I visited  predominantly clinical sessions and I was impressed by many papers on  external effects on reproduction.  We have always thought that some  factors might influence, for example, sperm quality, oocyte quality, and  fertilization but now it's getting more and more obvious and clear that  amongst those factors are really household items like smoking and being  overweight.  The overweight issue has especially been found out quite  nicely at this meeting.  There is such a strong correlation between  overweight and effects in natural reproduction and also in IVF that the  best way to advise a woman who is overweight is to lose weight.  It's  much better, much more efficient, and much more cost effective than any  of the new reproductive medicine treatments.  I was impressed by the  results there. 
       
       The same holds for smoking; we have always thought that smoking is  not good for you and we know of several diseases related to smoking but  fertility also is effected in such a heavy way that fertilization  results in IVF may be halved in people who smoke….  That's surprising  even to me and so I was surprised to see it, and I can say positively  surprised because it's good that we ban smoking.  I hope that in this  way by losing weight and by stopping smoking that patients can  contribute so much to their treatment that either the treatment is no  longer necessary or at least they have the emotional feeling that they  have contributed in a major way to the success which they do of       course."

"It seems you're talking now about women but yesterday  one of the keynote lecturers, Professor Skakkebaek from Denmark, talked  about the environmental influence on male sperm."
       
       

  "Yes,  that's another aspect which is becoming more and more exciting, it's an  aspect that we have always neglected a little bit because you could  always argue that studies from the 1950's and from the 2000's are not  comparable because the methods of investigating sperm were different  then and now.  What Skakkebaek showed is that in long-term studies in  the same laboratory with the same technicians and without much variation  among the technicians you see a decline in sperm quality.  He could  also relate it to other problems in the male genital tract; he could  show abnormalities of the testes, the penis, and problems in early use  related to the urogenital track in little boys that at an adult age were  reflected in low sperm counts and infertility in males as well.  They  have a quite clear hypothesis that the substitutes that we take in our  daily food and environmental factors that come to us via air- and water  pollution are the main causes of this decrease so they are continuing  these studies but it's obvious.  That was what the impression of the  public was in the audience that they are on the right track and that we  should really fear for a decrease in reproductive capacities both in men  and in women."
       
       

   "After Skakkebaek there was another lecture which made it clear that  influences on the embryo are already very important for later life."
       
       

  "Yes,  that was by Professor Barker from Southhampton.  It's a theory that has  been around for quite some time already and the problem with the Barker  theory is that people are shooting more and more holes in it.  In the  beginning it sounded very fascinating that women who got small children  and when the children grew up they had more cardiovascular problems.   It's getting more and more clear that it is not that simple.  There has  been a follow-up study of the women giving birth to these children and  these women have a seven-fold increase in hypertension and cardiac  problems.  So it may even be that there is a genetic component and that  is correlated with the result and it's not being small as a baby which  determines your later life problems but there is a gene in the family  which makes on one hand the mother becoming pre-eclamptic and giving  birth to small babies and on the other hand is inherited by the baby to  give it problems.  So it's not quite clear for me that this hypothesis  is still valid but people are working on it and it is an interesting  hypothesis but it may be of less significance in the near future."
       
       

   "This afternoon the results of the consortium on IVF in Europe will be  published again after the first draft, one could say, in Bologna last  year.  Can you tell us something about this consortium?"

   "Yes, I've seen the results, the consortium is composed of members  from all membership countries of ESHRE in so far as those countries have  representative figures.  What they do is they collect the figures on a  national basis and then add them up on a European basis.  What you see  is that this consortium, which gathers two times a year to coordinate  the efforts and to present the data shows very clearly, as opposed to  the United States, in Europe there is a clear tendency towards the  replacement of fewer embryos.  We have been extremely annoyed in the  first report by the high number of multiple pregnancies, which is a  disaster, as opposed to the United States where the tendency is to put  back more and more embryos to increase the success rates and to give the  patients what they pay for.  Fortunately in Europe we are much more  modest and we realize that multiple pregnancy is not what we're suppose  to have; our women don't have a uterus that can support a twin easily.   What you see is that in the Northern countries of Europe one has gone  back from three to two to even single embryo replacements as an average  and in the south of Europe it still is a little bit lagging behind  but  they are now gradually going back from three to two.  The result is that  although the pregnancy figures remain almost the same compared to the  first report, the multiple pregnancy figures are finally declining  although they are still quite high in some countries of Europe.  It's a  little bit of a problem to see that in some countries the overall  results can only be good at the cost of a 40% multiple pregnancy rate,  whereas, for example, in Finland they have excellent results with less  than 10% multiple pregnancies and that's due to the good selection of  embryos and the elective single embryo transfer."
       
       

  "So this will be presented by Professor Nygren?"
       
       

  "Any other highlights we can expect today or tomorrow?"
       
       

  "Of  course, there are many highlights on the basic science fields.  The  cloning issue is all over this meeting and the replacement of older eggs  and rejuvenating the older eggs.  Of course, that's an effort that  everyone is interested in especially because we know that there is a  certain group of women who have aging of the eggs in a rather fast way  so in their thirties they already have eggs that are very difficult to  fertilize.  If you can improve the quality of those eggs without  effecting their genetic component, that would be a big issue.  The  problem there is that it can be misused and that's one of my main goals  during my presidency.  I am so strongly opposed to misuse of  reproductive techniques by all kind of crooks that are around us and  that use these techniques to raise hopes in infertile couples that are  not justified.  What I hope to achieve in these two years is that we get  a decent group of fertility experts in Europe that use these techniques  and that can prove that they are worthwhile of the trust of the public  but we should get rid of all these people trying to clone human beings  or to make pregnancies in sixty-two year old women only for the money."
       
       

  "I think this is a very good message to end this interview.  Thank you very much, Hans."
       
       

OBGYN.net Conference CoverageFrom the ESHRE 2001 Conference - Lausanne, Switzerland

Presentations at ESHRE

          "Good morning, it's July 3, 2001 and we're at ESHRE in Lausanne.   Next to me is Jorgen Persson who is the Product Manager of Ferring.   Good morning, Jorgen."
       
       

  "I  want to talk with you about ESHRE as it is now and especially about the  symposium that Ferring had.  Can you tell us what the headlines of this  symposium were?"
       
       

  "Yes, the  headlines from the symposium were that we wanted to show the role of LH  and the importance to include LH into treatment of       any ovulation induction, IVF, and ART.  We had some new data  coming up from a recent largest study comparing highly purified HMG  Menopur® and Gonal-F®."
       
       

  "Is this the German study?"
       
       

  "This is a  multinational study so there was some sent to us from Germany as well  the Netherlands, the UK, Israel, and some other markets as well."
       
       

  "How many cycles were there?"
       
       

  "There were 727 cycles so it's the largest study so far."
       
       

  "What are the results of this study?"
       
       

  "The results showed that Menopur® is at least as effective as Gonal-F® in the treatment of IVF and ICSI patients."
       
       

  "What about side effects?"
       
       

  "The side  effects are comparable so you get the same treatment, and you could see a  trend in the study but this should be published further on in  journals."
       
       

  "We  can refer to the interview that we also have with the presenter of this  study.  Were there other papers that you presented in your symposium?"
       
       

  "Yes, we had a  very nice presentation from Dr. Lucas Klentzeris from the UK.  He  showed his results with Doppler examination of the women in the  development of their oocytes or follicles, I should say, and that was  interesting results."
       
       

  "This was the Doppler flow.  Why did you put this in your Ferring symposium?"
       
       

  "I think it  is innovation; it's a new technology that we started to use.  Lots of  physicians were very interested to see the results and the experience       he has  from this kind of examination.  He also showed very nice  data of the difference in patients in the blood flow in the ovarium if  they were treated with either highly purified HMG or if they were  treated with recombinant FSH."
       
       

  "Indeed, he had beautiful pictures and slides with nice colors.  Were there any others special topics within your symposium?"
       
       

  "Then we  introduced at the symposium a nice presentation from Zeleznik where he  showed us the two-cell theory and the importance of LH in the  treatment."
       
       

  "I  think this was a very interesting paper as well.  So indeed, this was a  very interesting symposium you presented.  Thank you very much, and I  must congratulate you on your symposium."
       
       

Hans van der Slikke, MD, PhD

Articles

PCOS: What is the Diagnostic Criteria?

PCOS: What is the Diagnostic Criteria?

Presentations at ESHRE

Ferring Symposium