Howard Carp, MD

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       "I'm sitting now with Dr. Dan Farine, who's the Director of Fetal       Maternal Medicine at Mount Sinai Hospital in Toronto, Canada. He was the       chairman of the session on twin pregnancy this morning. Dr. Farine?"
       
       

 "Thank       you, Howard. It was actually a very pleasant session. The controversy was       not that much in terms of arguing between the speakers about their       approaches, it was more comprehensive in the sense that we had a few       speakers that touched on different aspects of twinning. The first talk was       actually quite provocative. It was given by Lewis Keith, who was the head       of the Institution for Twin Studies in Chicago. Lewis presented his own       personal experience with him and his twin brother that were labeled as       monozygotic and dizygotic in four different ways over the years. What he       brought up was the issue of zygosity from a different prospective, and the       fact that the genetics of twinning could be different after conception so       twins may be quite similar, but not perfectly similar, and there could be       some delayed variability which is introduced after conception. This led us       to into the discussion on how to diagnose monozygosity using new DNA       technology. It was pretty clear that, number one, there is no gross       standard and, number two, the more testing you're going to use, the more       you're going to find twins that are not exactly identical."
       
       

 "I       found this very interesting because what you were saying is, rather than       assuming that monozygotic twins were exactly the same genetically,       psychologically, etc., as we assumed before, he was now talking about a       new classification of monozygotic twins who were discordant for various       other features."
       
       

       "Absolutely, and those features could be specifically genetic,       diseases, or other conditions, so this is a new concept that kind of takes       us from the dichotomy of monozygotic--dizygotic."
       
       

       "And I understand there was also a lot of discussion on the ways to       diagnose twins early on in pregnancy rather than diagnosing monozygotic       and dizygotic twins at the time of delivery. That comes up with early       ultrasound, about the ultrasonic signs of monozygosity, isn't that       right?"
       
       

 "This       was discussed by Israel Meizner, and what he did was actually lump       together the data about ultrasound scanning and zygosity, which is       actually crucial for the management of the pregnancy. He did a very nice       summary of the early ultrasound data and the late ultrasound data leading       obstetricians to the best diagnosis of zygosity. He also touched on other       issues, like monoamniotic twins and conjoined twins, but the major issue       was actually trying to determine zygosity using ultrasound scanning. What       came out very, very clearly was that you need to scan those patients more       than once, and preferably somewhere before the eighth week mark, then       after the eighth week mark and at the second trimester, to get the optimal       ultrasound data which allows you to determine zygosity."
       
       

       "Yes. Could you also comment on the multiple pregnancy work and the       iatrogenic causes of multiple pregnancy? There was some discussions on       IVF, I understand - how many eggs were replaced in the uterus and, of       course, did this influence the multiple pregnancy rate."
       
       

 "This       actually came up several different times. It came up in the presentation       of Lewis Keith. It came up again in the presentation of Issac Blickstein       that actually made this as one of the determinants of how to deliver       twins, and the fact that many of these patients are infertile. He used       different technologies to get pregnant, and this modifies their perception       and the obstetrician's perception. This culminated in a very heated       discussion at the very end in terms of how many embryos should actually be       implanted back into the uterus and whether it would be re-suited to two or       to three. It was actually quite interesting to see Nick Fisk and Chervenak       disagreeing, very politely but very firmly, and then hear the input from       everybody else around the table and in the audience. It was also       interesting to see the difference between people with reproductive       endocrinology backgrounds. Dr. Insler discussed it in terms of the       perspective of the endocrinologist infertility specialist, and he       confronted those with the views of the maternal fetal medicine people on       the panel that felt that having triplets carries major risks. Lewis Keith       discussed the psycho-social issues, and he quoted the data from France       that showed that many of the families of triplets are devastated by major       social effects within the three years from the time of delivery. So it's       not only just a pure medical issue, but also it also has psychological       aspects."
       
       

       "Was the place of reduction of triplets down to twin pregnancies       discussed?"
       
       

 "I       think that in a way we tried not to discuss it too extensively since there       was another session devoted to that, but it certainly came up. I think       that the most interesting way it came up was Nick's provocative statement       that what you should do is either put back two eggs or put twenty back in       and then have a reduction. So the issue of reduction also became quite       extensive and served as a function of the next ethical issue in terms of       how to approach each reduction from ethical perspectives, and he gave a       very elegant overview of that issue."
       
       

       "Yes, I understand from there that you went on to the more       straightforward obstetric issues about twin-to-twin transfusion syndrome,       and how you should, in fact, deliver twins in the labor ward. Do you have       some comments on that?"
       
       

 "I       think Nick has given an excellent overview of the issue of the       twin-to-twin transfusion, and it was very provocative. I think that the       first point that he made was the fact that we have seven different therapy       modalities indicated, and none of them are perfect. He then looked at our       ability to diagnose the twin-to-twin transfusion as well, and he compared       his own data and other centers' data in terms of laser versus amnio-reduction,       and what would be the right indication to intervene. I think he gave a       very well balanced overview of the issues. We are still pretty far away       from where we should be, and the maternal fetal medicine community is       trying to overcome some of those hurdles by having conjoint efforts as       multi-center studies looking at specific modalities of therapy like       fenestration of the membranes."
       
       

       "Thank you very much, Dr. Farine."
       
       

Articles

OBGYN.net Conference CoverageFrom First Congress on Controversies in Obstetrics, Gynecology & Infertility Prague CZECH REPUBLIC - October, 1999

Twins and Multiple Births

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       "I'm here with Dr. Louis Keith, who is the Professor of Obstetrics       and Gynecology at Northwestern University in Chicago, and the Director for       the Center for the Study of Multiple Births, also in Chicago. Dr. Keith       presented this morning, but I understand that he is also a 'professional'       twin who has described some of the problems that come up with twins. Dr.       Keith, could you give us a summary of some of the things that you were       speaking about this morning concerning twins and, particularly,       monozygotic twins?"
       
       

       "First let me clarify, if I may, the issue of being a 'professional       twin.' By this I mean that my brother and I speak frequently to the       public, the media, and the medical profession in general on behalf of       twins. In my case, I speak as an obstetrician and president of the Center       for the Study of Multiple Births. My brother and I both view the picture       on a broad canvas; we see many of the problems, as well as the joys. I'm       not aware of too many of my obstetric colleagues who are twins, or if they       are, who might address these issues in public-that's what I meant.
       
       Now, in terms of the issues that were addressed this morning, it was a       rather basic discussion that pointed out some of the medical problems that       accompany multifetal pregnancy reduction and deal with iatrogenic multiple       pregnancy. In this regard, the birth of the seven sextuplets in Iowa was       cited as an example, whether the public found this a joyous event or not.       In one way or the other, the public pays for this and for the cost of       other iatrogenic multiples. This is the point that I stressed-that the       public is paying for this epidemic of multiples."
       
       
       

       "One of the points that came up this morning was iatrogenic multiple       births that result from assisted reproductive technology. There is a very       real question being addresses as to how many embryos should be replaced,       whether reduction should be performed, or whether fewer embryos should be       replaced in the first place. Do you have any views on this, Dr.       Keith?"
       
       

 "l       think you summarized it very, very eloquently. This is a world-wide       debate, and this debate is becoming more and more acrimonious, if I may       use that term, as people begin to look at costs in terms of dollars,       pounds, Deutsch marks, French francs, Swiss francs, or in terms of the use       of the resources of entire nurseries that are often given over to the care       of iatrogenic multiples. Now, resource drain should be factored into the       equation whether one is for or against the production of iatrogenic       multiples and whether one is for or against the use of reductive       techniques. You can't very well discuss these two major issues without       bringing society into the discussion, noting that society is concerned       with the cost. From the point of view of the family, all too often there's       an enormous cost in terms of disruption of what is considered normal       family life to give three or four young babies the care that they need in       the first year. We know from the Iowa experience that this often requires       a tag team of helpers."
       
       

       "You also spoke this morning about a different concept regarding       monozygous twins, about the differences between monozygous and dizygous,       and how sometimes it will be very, very difficult to reach a diagnosis       about zygosity. Could you elaborate on this, please?"
       
       

       "Yes. That, of course, was my assigned topic. I spoke about the fact       that it's too simplistic to continue to say that a pair of twins is merely       monozygotic, meaning derived from one fertilized ovum, or a dizygotic       derived from two fertilized ova. This approach does not take into account       the possibility that there will be some differences, although minor, and       something as simple as the placement of a mole or as simple as the       presence or absence of a derelict hair that's coming out of the right       eyebrow. My brother has the same derelict hair coming out of his left       eyebrow. Thus, one might say we're not just the same, but that we're       mirror-image twins, in that regard. But there are other pairs of twins       where one will have cancer and the other won't, or where one has a       paralytic disease and the other doesn't. In the last couple of years, many       researchers have been trying to explain this phenomenon, and this is what       I threw out in this morning's discussion."
       
       

Twins

Twins Video

OBGYN.net Conference CoverageFIGO 2000 INTERNATIONAL FEDERATION of GYNECOLOGY & OBSTETRICS: Washington DC, USA

Recurrent Pregnancy Loss

       "I'm here with Dr. Genazzani and Dr. Carp. Can you tell us about your       practice and where you're in practice?"
       
       

       "Yes, I am a Professor of Gynecology and Obstetrics in the University       of Pisa in Italy."
       
       

       "Yes, I'm senior lecturer in Obstetrics and Gynecology and Embryology       and Teratology at the University of Tel Aviv in Israel."
       
       

       "Thank you. Dr. Genazzani, you spoke earlier on menopause, and I hear       that you have a conference coming up. Can you tell us a bit about the       conference?"
       
       

       "Yes, we will organize for the 8th World Congress of Gynecological       Endocrinology in Florence in December of 2000. This is a conference, which       came after our previous venues in Buenos Aries, Barcelona, and others. We       expect to have more than 2,000 people and all the areas of gynecological       endocrinology will be analyzed starting from the embryonic function to the       counsel of the other function to the placenta in pregnancy and then also       we will move on to the effect of hormones on cancer tissues and how to       manage the postmenopausal woman, how to take care of the pelvic floor       disorders and as you can see a series of items will be covered."
       
       

       "Professor Genazzani, I was very interested to hear your lecture       which you gave just a little while ago in the conference in which you were       speaking about hormone replacement therapy after menopause. I think one of       the things you mentioned was what are the indications. Is hormonal       replacement therapy indicated for all patients, is it a preventative       measure, is it just for some patients, and is it treatment for       symptoms?"
       
       

       "I think that it's difficult to give a general answer. Certainly the       hormone replacement therapy after menopause is treatment for symptoms but       it's also very efficient therapy to prevent diseases later on then for       it's positive effect on cardiovascular levels, for the prevention of       osteoporosis, for the measure effect on the brain. I think it's       conceivable for a woman without symptoms to start the therapy to prevent       possible diseases later on. Mostly women are coming in from the symptoms,       and their symptoms are not only the hot flashes or insomnia but are also       other symptoms of the changes in the hormonal age that affect the female       population. They don't accept having to watch their weight and the changes       in the quality of their skin, and the quality of the mucosa. I think       better attention from the general practitioner or the specialist should be       on how the female body acts in regard to hormone deprivation right after       menopause. This is considerable now, and I think a woman can start therapy       and the therapy can be changed throughout the years because as long as       she's under therapy, her body is changing so she will need different       amounts of hormones at different times. There are also other therapies       that can be done after the first year after menopause. They are considered       to not only treat a woman for the preventative effect on the womb and on       the cardiovascular but also to prevent some possible problems that she has       by the fact that she has taken the estrogen therapy for ten years."
       
       

       "We've had a lot of new estrogen replacement therapies and routes of       administrations and protocols that have come in front of us. I think it's       a bit confusing for physicians to understand both the safety and the       efficacy of each of these various methods in relieving these symptoms.       What are your comments on that?"
       
       

       "I agree completely with you but you know human beings are so       different from one to another. So it's considerable, you don't have the       same therapy for everybody. It would be impossible to treat all women with       the same therapy. Some of them need other therapies, some need smaller       doses, some higher doses, some may prefer the patches of administration or       they prefer to have them by administration by any kind of gel or any other       therapy. I think gynecologists now can provide general practitioners and       the other specialists a variety of therapies because they are facing a       variety of individuals. Not only do we now have hormonal replacement       therapy with estrogen and progesterone but also it's conceivable now that       after ten years of hormone replacement therapy, the woman can start with       selective estrogen receptor modulators or other kinds of therapy when       she's no longer symptomatic, and when she wants again to prevent the       possible risk acquired and linked to the estrogen administration for a       long time and also to prevent the bone deterioration and cardiovascular       irregularities. I think we are facing forewarnings of the scientists to       women to try not only to prolong their lives but to reduce the period of       validity they have in the last five years of their life when the       osteoporosis, the cardiovascular changes, and all the problems that a       woman has, that can give absolute deterioration of the quality of       life"
       
       

       "You mentioned in your lecture some of the problems a patient       complains about, some patients might have bleeding during the time or       after a course of hormonal replacement. Do you think women are getting       enough supportive therapy when the side effects come up but they will       still continue with treatment, particularly you mentioned the SERM,       sometimes the symptoms such as hot flashes may come back. Is there still       enough support in your opinion?"
       
       

       "I think we have to personalize the therapy. Concerning the bleeding,       we have to change the therapy to correct the regular bleeding, such as       menstrual bleeding, or in any case to correct the irregular bleeding.       These are the things that women don't accept. Concerning the SERMs, for       that reason I sustain that some are useful later on after menopause but       not at the moment of the menopause because they activate in some subjects       the hot flashes, and the hot flashes are symptoms. I think we have the       experience from many studies that even though the woman start again, after       a few months the hot flashes will disappear, The entity is absolutely not       putting out some of the therapy for the patient, this was our experience.       But certainly I believe that the woman has to ask the doctor when she's       under therapy to personalize the therapy and she needs measure       control."
       
       

       "Many of the women that we see either have had thrombotic events in       the past or as part of their screening for recurrent pregnancy loss or       pregnancy complications. People have looked at various clotting factors       such as Factor X Leiden and the like and have said that if these clotting       factors are abnormal or there's been a past history, then estrogen is       contraindicated. The only one hormone replacement that I'm aware of now       that is not contraindicated is tibolone in that environment. Have you had       experience with this or how do you redress the needs of that patient       population?"
       
       

       "Yes, we also have an analogue of PSA tibolone for many years. First       of all, the women who have real clotting problems, it's not so big and       certainly estrogen that also serves to activate their clotting system. For       that reason, they remain a risk factor, and tibolone doesn't seem to       effect the clotting system in the same way even though tibolone also has       estrogenic effects. I think it's very important that doctors make some       kind of screening, mostly on an annual or periodic basis. We don't need to       at each exam but certainly as a screening exam. But when on an screening       basis you can be aware that it can be a possible risk, then I agree that       you can measure those parameters which can indicate easy activation of the       clotting system. In such a case, you have to try to correct it, and don't       use therapies while there's an estrogenic effect on the vessels. Even with       this genic effect on the vessels, they are very positive in another area       because they are positive from the endothelial sense. They can give a       better endothelial function, and they can show antiagonist sporadic effect       on the arterial wall. Then I think you have to balance this impossible       situation."
       
       

 "I       think in the states it will be hard to do those studies but I'd like to       see in the low risk group maybe coming in with low estrogen and baby       aspirin or some effective factor but I don't think those studies are going       to happen in the states."
       
       

       "There's a chance only one of the major concerns of estrogen       replacement therapy of course, is the effect on the breast and sometimes       also on the endometrium where there also may be a constant genetic effect.       What is current thinking on the effect of the breast?"
       
       

       "The effect on the breast, first of all, they have never shown from       the estrogen any cardio-genetic effects on the breast. They have shown the       promoting effect, this is what we believe more now, that we can activate       the replication of the cells and then this can have some negative impact.       But you know the figures are in 1,000 women followed for twenty years and       who are not treated with estrogen - they have thirty-five with new breast       cancer. If they are treated for five years, you move this forty-five to       forty-seven, and for ten years you move this thirty-five to fifty-two.       These are the figures, the figures also sustain that the mortality in       these same groups are more or less the same, indicating that the quality       of the tumors that they had, this seven in omission, are of a more curable       kind. I think in another size and a series of studies that show that       having a baby prior has shown that the positive effect of vascular levels       are so deep, but if we make a mean of the pull and counts, the pull still       remains more than the count. A record should be kept of any anomalies,       it's very important for the woman to share any personal history regarding       breast cancer in her family history to make an adequate screening       protocol. I think at least now we can believe that our hormonal therapy       can be given for ten years and probably can be a full load by certain       therapy just to counteract the effect on the breast. This I think should       be a good general strategy but as I was sustaining, this is on the breast.       Concerning the endometrium, on the endometrium you know If we give a       progesterone together with estrogen it has been shown that they have a       reduction of naturally expected cancer or smaller - more or less 50%. It's       the same from colon cancer, and speaking about cancers, I think that the       dollars are in favor of the therapy. It may be adequate screening if we       follow the woman, if we do mammograms as they have to be done, and then if       you maintain a close connection between the patient and the doctor."
       
       

       "Dr. Carp, I'm interested and have been following your work in the       literature about evaluation of the immune system in patients with       recurrent pregnancy losses. What is the status of immune testing now? How       do you answer critics who say that there really isn't a place for this       because if you do nothing, 65% of the people are going to do quite well if       they've had three losses?"
       
       

       "I'm pleased that you mentioned that 65% of the people do well,       because the opposite side of the equation is 35% do not do well. But there       are people that actually seem to second that, now the first 35% will not       do well, that means they will come back again with a fourth pregnancy       loss, if you take as your basis three pregnancy losses. Those who come       with four pregnancy loses, 60% do not do well. That means that you're       talking about 20% or so of your patients who will come back after three       pregnancy losses with a further two losses. I think that our       responsibility as physicians is not to look at the 60% who do well but to       look at the 35% who do not do well or the 20% who come back with the       further two losses. That's why even though we treat patients with three or       more pregnancy losses, we try to limit our research to patients with five       or more losses because I think what tends to happen is that patients are       told 60% do well, therefore, go away and become pregnant again. On that       basis, when a patient comes to you with five or ten miscarriages, you may       be denying her investigation and treatment on the basis that the patients       with three loses do well. I really don't think that's fair to the       patient."
       
       

       "What happens to the patient who comes in with two losses and says,       "I've heard about this immune stuff, I don't want to lose       again."
       
       

       "You do have a very difficult clinical question because there are       patients who will look up sites on the Internet such as this one and       others, and they will come to you today and say, "I have heard about       immunization, I have heard about immunoglobulin, I have heard about other       methods of treatment. I want to be treated, I don't want another       loss." I think with these patients you have to explain to them that       the patient with two losses, 80% do well but we do not really have an       accurate enough diagnostic test to see who is the patient who will do well       and who will not do well. The patient has to realize that even if we       investigate the pregnancy loss, and we find a cause of pregnancy loss, it       will not necessarily be the cause of pregnancy loss, and that often       treatment of the moment is empiric. Immunotherapy is empirical treatment,       resection of the septum whether done hysteroscopically or in another way       is empirical, and immunoglobulin is empirical. Recent work on reduction of       LH levels has been empirical because patients with two pregnancy losses,       for example, most pregnancy losses will be due to chromosomal arrangements       in the fetus. I think it is still accurate, we can ask Professor Genazzani       as well, what is current practice in Italy but I think it's still       reasonable to say that in 90% of the world or 90% of the patients with       pregnancy losses where there is two, three, five, or ten losses, that       conceptus when it is lost is not karyotyped. We cannot even give the       patient an accurate diagnosis against that basis. We are being asked to       summarize treatment, to prove the treatment is effective, and that is       almost impossible."
       
       

       "So one of the things your suggesting when that second loss comes       along is to try to get the chromosomes to a consultant who may see the       patient after two or three losses for evaluation?"
       
       

 "I       say that most definitely, yes, because if you find the patient who has       lost an embryo which is chromosome 16 trisomy, x monosomy, you know that       he's elected to be chanced chromosome agents. You can then say to the       patient, "Your chance next time around is very, very good." You       can even give them figures depending on whether this is two losses or       three losses and discuss with them whether they want to spend the time for       other investigations or not. If however, you find that a patient is losing       normal embryos, then you have to investigate the other factors. Then I       think there's a place with immune investigation and other investigations       and probably treatment which is then much more directed at the cause of       pregnancy loss rather than the empirical fetus."
       
       

       "Do losses tend to cluster around the same indication so that if you       have patients who've had three or four losses, and you know that one or       two of them are chromosomal, is it in all likelihood that the others were       chromosomal or that future loses will be chromosomal? If per chance you       had someone with three losses, and you knew they were all chromosomal,       would your evaluation be different?"
       
       

       "My evaluation would be different, my advice would be slightly       different. It would depend on what sort of chromosome losses. The chance       for an assembly arrangement such as chromosomal 16 trisomy, which is the       most common, when we find in our series such as x monosomy, these do not       have high recurrence risks and an open chance is very good. You do       occasionally pick up a translocation, and when you pick up a translocation       then there may be a chance of that coming from one of the parents. You can       check the parents to see whether they have the same translocation, which       they have passed on. In most cases there is a very high recurrence risk,       and you can explain that recurrence risk to the patient. After that, you       may decide to investigate patients of those. The patient who loses the       chromosomally abnormal fetus may also have a septum present, similarly a       patient with septum may also lose chromosomally abnormal embryos. One does       not exclude the other and the fact that you have found one cause of loss       does not mean that you have found the cause, this is problem that we're       facing today. However, I do feel that much of the literature does depend       on finding one cause of loss, they don't find other causes of losses. I       think it also depends very much on the clinical presentation. If I give       you an example, we had one patient who had two pregnancy losses at twelve       weeks. She had septum within the uterus, she was advised of the       contraindication, she lost the third pregnancy also at twelve weeks. We       resected her septum, and she lost the third pregnancy at eight weeks. Now       this obviously sounds like a failure with treatment. Now if I give you       some more details about this patient and say that these three previous       losses were losses of live embryos at twelve weeks there was a fetal heart       present, the uterus started to contract, she started to bleed, and she       aborted a live embryo. The fourth pregnancy loss was ablated over at eight       weeks, now that sounds different because it doesn't sound quite so much as       it is a failure of treatment. If I now present the patient with even more       detail and say all pregnancy losses due to chromosome 16 trisomy, and that       the fifth and sixth pregnancies were induced labor each time at forty-two       weeks, you realize that the resection of the septum was not a failure of       treatment. It was in fact, a successful treatment and unfortunately these       things are not taken into account. As Professor Genazzani said about       hormone replacement therapy, patients are individuals, and if we stay with       this definition of assessing all patients with three or more losses,       that's one homogeneous basket we're never going to make any sense on this       subject."
       
       

       "One invariance being evaluated is again the clotting factors that       prothrombin gene mutations and Factor X Leiden in this area. Do you see       patients in Italy being screened for clotting factors as part of that       evaluation?"
       
       

       "Only if they have very special reasons to do this, and it's not yet       in the general practice also in the measures that we have to start in some       kind of screening problem but we also need to be concerned about pregnancy       loss. This is one area where we're defectors. It has to be taken into       consideration and we need to try to personalize all the screening project       and the screening problem. So it's not only bad for the patient but also       for the doctor who follows the patient when you have seen three to six       losses. Then you have to exam the embryo and there may be some genetic       defects in some and not in others and some others there might not be any       presence of the embryo. At the end of the study, you cannot know what kind       of therapy, if any therapy or what kind of approach you have to do. You       only have to hope that God will help us and that she can have live       children."
       
       

       "With thrombotic pregnancy loss, whether it's due to either       antiphospholipid antibodies or simply by a cyst or due to genetic       predispositions which is Factor X Leiden and prothrombin malformation and       so on. I think that first of all, clinically we have to define a certain       type of pregnancy loss. Now with antiphospholipid antibody syndrome, the       preponderance of second and third trimester losses is much higher than it       is in unselected patients in common pregnancy loss. Patients who receive       it, the current pregnancy loss, 90% were in the first trimester and about       10% in the second and third trimesters. Patients with antiphospholipid       syndrome, they're not 30-40% in the second and third trimesters so it may       be that in traumatic pregnancy loss, we have a normal embryo or fetus but       then due to the clotting, we get ischemia and the effects of retardation       and fetal death. Now certainly if you look at Preston's paper summarizing       the EPCOT study on thrombophilias, they did say that the chance of a       stillbirth - and they define stillbirth as being a fetal loss of about       twenty-eight weeks - is also much higher than the chance of what they call       the scavenge, which in their definition is a loss below twenty-eight       weeks. So I think there is a clinical picture starting to become clear,       when this becomes clearer and more accepted, I think we'll have a much       better indication as to who may need treatment for thrombotic pregnancy       loss."
       
       

       "Do you believe that placental evaluation is an important tool either       in determining patients who may be at risk for an immune basis or a       thrombotic basis for their loss?"
       
       

       "I can only say - what kind of placental evaluation? Maybe Dr. Carp       can give us a better, more precise results on what kind of placenta       screening and evaluation you would like to suggest to the standard       patient."
       
       

       "First of all, if we're talking about first trimester losses - there       is no placental evaluation. We're really in the hands of nature as to see       what comes out after that but you do have to access maybe not the       placental factors or the projected factors. Once we come to the second and       third trimester, unfortunately antiphospholipid antibodies have not proven       that good an indication of what goes on. So if you check 80% coagulum by       clotting factors whether it's either the activated PTT or Russell's viper       venom time, none of them has proven to be a good indication of what's       going on in with the pregnancy. Anticardiolipin antibody is notorious for       its intralaboratory/interlaboratory variation, you cannot trust antibody's       levels. Therefore, you can only trust placental assessment, and it's usual       to send for assessment, non-stressed cardiotopography, fetal growth on       ultrasound, flow studies, and they'll give you an indication that the       pregnancy is doing well or whether you may need to intervene and stand on       a sentry basis."
       
       

       "Dr. Genazzani, thank you."
       
       

       "I'm sorry, I thank you but I have to leave."
       
       

       "Dr. Carp, thank you so much."
       
       

Discussing Hormone Replacement Therapy

       "My name is Howard Carp and I'm from the University of Tel Aviv. I'm       sitting this evening with Bruno Lunenfeld, a noted professor at Bar-Ilan       University just outside of Tel Aviv, Togas Tulandi, who's Professor of       Obstetrics and Gynecology at McGill University in Montreal, and Alan       DeCherney, Professor of Obstetrics and Gynecology at the University of       California, Los Angeles. They've been discussing some of the sessions,       which have gone on here today. Professors Tulandi and DeCherney, I       understand that you were speaking about some of the controversies       surrounding ectopic pregnancy. Could you please tell us some of the       controversies which came up for discussion and the things which were       discussed at the meeting?"
       
       

       "We talked about which surgical approach was better, salpingoscopy or       salpingectomy, and I think that we concluded that salpingoscopy in most       incidences in a first ectopic pregnancy was better. We also discussed       whether a laparotomy or a laparoscopic approach was better, and we came up       with the conclusion that a laparoscopic approach was preferable if the       patient was stable. And last, we talked about chemotherapy and the       discussion there centered around whether a local injection or a systemic       injection was preferable. It seems that since they both have the same       outcome, the systemic treatment is better because it doesn't really       require any skill, and it doesn't have to be injected into the ectopic. So       we came up in the end with a continuum-the best way to treat a patient       fulfilling criteria of small size was first methotrexate, then a       laparoscopic approach, and last a laparotomy."
       
       

       "Do you feel that the surgical management was adequately discussed in       this session?"
       
       

       "Yes I do. Actually, the last three sessions today did cover surgical       aspects, but basically they were the sessions only looking at real       surgical aspects. So I think that if this was to cover the whole field,       perhaps a shortage was not enough coverage of some of the surgical       controversies. But perhaps that will be covered in another meeting."
       
       

       "Now Professor Tulandi, I know that you've also been discussing       surgical aspects this afternoon, but also surgical aspects of a different       nature-hysterectomy and the alternatives to hysterectomy. Could you tell       us a little about what was discussed this afternoon, please?"
       
       

       "Yes. We discussed the treatment of abnormal uterine bleeding, by       hysterectomy or other methods, and we came up with the conclusion that an       alternative to hysterectomy such as endometrial ablation has a place in       the treatment of abnormal uterine bleeding. Those talking about subtotal       or total hysterectomy were also represented, and I think we agree that       there is a place for subtotal hysterectomy, as well for benign       gynecological conditions."
       
       

"When       you were speaking about endometrial ablation, were you only speaking about       the hysteroscopic forms of ablation under direct vision, or also possibly       some of the catheter techniques, such as using heat to ablate, and so       on?"
       
       

"We       talked about both hysteroscopic techniques and non-hysteroscopic       techniques. The non-hysteroscopic techniques are microwave, balloon,       thermal balloon, and VestaBlate, which is with electrodes. It seems like       the results are often similar."
       
       

       "Were there any conclusions reached as to which may be an optimal       method of ablation, or does that still remain controversial?"
       
       

       "The hysteroscopic technique certainly works very well. It has high       efficacy, and several endometrial studies have shown that the newer       methods are as effective."
       
       

       "Thank you. Professor Lunenfeld, I understand that you touched on a       very important subject this afternoon when you talked about a cancer risk       in patients who have had ovulation inducing agents. Could you please       elaborate on the points which were discussed?"
       
       

       "You probably remember that after the Witmore paper in 1992, there       was a big problem and people were afraid that using drugs may increase       their risk of ovarian cancer. This was increased even further by the       Austin paper, which showed that patients who receive more than twelve       treatment cycles with clomiphene citrate had an accelerated risk of       ovarian cancer. We are now able to look at other studies, concentrated and       modulated by Professor Mundon, in which we collected some 130,000 women in       Israel with a mean age of patients of 52. We demonstrated very, very       clearly that there is no increased risk of ovarian cancer. Furthermore, we       were able to obtain the data from the California study, which is around       65,000 patients from 15 IVF centers and 40 physicians, and their study is       only preliminary for the time being, also. But the data on ovarian cancer       is already there. They observed no increased risk of ovarian cancer when       the patients were treated or were not treated. I think this is an       important result, although the author said at the end of the study that he       still would like to wait another ten years to see the patients after the       age of sixty. I think we can be quite comfortable today. I think this       data, at least for me, is sufficient reason not to be afraid anymore of       the relation in using drugs. We did not discuss assisted productive       techniques because the time interval between ART and ovarian cancer is too       short, for the time being. Although we were told that in approximately       three to four weeks a paper will appear in the Lancet in which the       Australians will claim there is an increased risk of breast cancer about       one year after treatment, and after ten years this risk equalizes to the       non-treated patients. So today we believe-and Dr. Carson agrees with me       fully-that this first increase after one year that comes after ART, or       after stopping contraception, may just be a group of patients who had       already harbored a tumor and where the treatment actually stimulated this       harboring tumor and brought this tumor about. Of course, when we look       after ten years, we'll disseminate this out. This is what we believe is       probably the reason, and I'd like to ask Alan if this sounds reasonable to       you?"
       
       

       "Yes. Reasonable, I agree with that. It's very much like endometrial       cancer, where the high estrogen levels are exaggerated, but it's already       present."
       
       

       "Professor Lunenfeld, this is taking the whole group of ovulation       inducing agents as a whole. Was there any difference between various sub       groups, possibly women who had had urinary menotropins, possible       menotropins based on FSH alone, or the most classical ones which also       included LH in the preparation? Was there any difference seen or was that       not looked at?"
       
       

       "Don't forget this was a study where the patients are now 52 years       old. This was a study that was performed between 1961 and 1984, where       there was no other preparation other than the old H&G preparations. We       do not have any data yet on the newer preparations."
       
       

       "Thank you. I understand that another subject which you spoke about       was the so-called andropause, or partial androgen deficiency. Could you       elaborate on some of the points that came up in that discussion       please?"
       
       

       "Yes, I think we all agreed today that in men there is a gradual       decline of the Leydig cell function and adrenal cell function related to       dehydroepiandrosterone, not cortisol. There is a decrease in cortisol       hormone, there is an increase in melatonin, and there is a decrease in       IGF-1. That means that today, with the prolonged life span of men, they       will live about one-third of their lives in partial endocrine deficiency.       Now, if we have endocrine deficiency which is expressed by clinical signs       and proven by laboratory tests, then I believe only in these cases should       we start using replacement therapy. It has been shown quite well today       that testosterone is probably not a risk factor for cardiovascular       disease. I believe the our study team demonstrated quite elegantly that       you can reduce cardiovascular risk because you reduce visceral effect, and       that it seems quite likely that testosterone does not induce prostatic       cancer, but it may stimulate existing prostatic cancer. Therefore, the       guidelines of today suggest that, before initiating testosterone therapy,       we should have a digital examination and a PSA (prostatic specific       antigen), and if there's anything suspicious, a transrectal       ultrasonography. And we should repeat this three months after the       testosterone therapy because this could create a very early diagnosis of       cancer, should the PSA go up within three months. So I think guidelines       are being developed. We are in the very, very beginning-we are where we       were with HRT about thirty years ago."
       
       

       "Professors Lunenfeld, Tulandi, and DeCherney, thank you very       much."