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Intrauterine system
THURSDAY,
SEPTEMBER
7
Progestogens remain the drugs of choice. We are of the opinion that the problems are two: the first is the type of progesterones used and the second is the protocol of administering the drug. Dydrogesterone a new progesterone we thought was capable of fulfilling the criteria demanded from a drug in the treatment of DUB. We also modified the protocol starting from the drug from llth day of the cycle for 15 days instead of from the lSh day as reported for the other drugs. With the Assumption that oestrogen are intercepted early and the drug will not affect ovulation. We have so far had a study published from our encouraging results on a cohort of 30 patients and after the publication we have recruited a further 50 patients. Our entire group of 80 patients have given us extremely heartening results. Further to this a multicentric trial caried out all over India has recruited 400 patients where the results of our initial study have been reproduced.
EN4.02.03 INTRAUTERINE SYSTEM E-M Rutanen, R. Hurskainen, Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland The intrauterine system that releases levonorgestrel20 g/24 h into the uterine cavity for a time period of 5 years was originally developed for contraception. Many studies have been published during the past decade, describing the system as one of the most effective treatments in reducing the amount of menstrual blood loss in women suffering from menorrhagia. High dose of levonorgestrel in the uterus has strong suppressive effect on the endometrium. Endometrial epithelium becomes atrophic and the underlying stroma is decidualized. This change is constant during the use of the system but reversible in one month after its removal. The concentration of levonorgestrel is high in the endometrium but very low in the circulation, and ovarian function remains almost unaffected. There are several mechanisms that may account for the reduction in menstrual blood loss. The morphological changes in the endometrium are followed by changes in endometrial function. It has been shown that production of many local factors that are involved in the regulation of endometrial proliferation, shedding, remodeling and haemostasis, may undergo changes under continuous progestin stimulation. These changes are likely to favor the reduction of endometrial bleeding. The most common side effects of levonorgestrel intrauterine system are spotting and mild irregular bleeding, which are mostly reported during the first months of treatment. However, levonorgestrel intrauterine system is an alternative to surgical treatment of menorrhagia and especially in women who still want to become pregnant and have an increased risk of iron deficiency anemia. It is also suitable during premenopausal years, since only estrogen needs to be added when climacteric symptoms appear, and if the woman wants to start hormone replacement therapy.
EN4.02.04 VARIATIONS IN SURGICAL TREATMENT J. Emory University School of Medicine, Woodruff Memorial Research Building, Dept. of Gynecology and Obstetrics, Georgia, United States Over 250,000 hysterectomies are performed for dysfunctional uterine bleeding each year in the United States. Some surgeons have suggested that endometrial ablation is now a realistic alternative to hysterectomy. The goal of most ablation techiniques is to remove or destroy the endometrium creating an Asherman like scar. This session will critically assess and compare the techniques of endometrial ablation. Current indications and current contraindications will be presented. Moreover, the complications and percentage of women requiring additional treatment will be reviewed. The goals of this presentation is to bring into focus a realistic appraisal of the role of endometrial ablation in gynecology.
15
FM4.05 RECURRENT
EARLY PREGNANCY
LOSS
FM4.05.01 GENETIC CAUSES ARE RESPONSIBLE FOR MOST FIRST TRIMESTER PREGNANCY LOSSES Joe Leinh Simuson, Baylor College of Medicine, Department of Obstetrics & Gynecology, Houston, Texas, United States Pregnancy loss occurs very commonly, both pre-clinically and clinically. At least 25.50% of embryos die before implantation; another 30% of implanted embryos are lost. The likelihood of losing a clinically evident pregnancy is lo-12%, two-thirds occurring before 8 weeks. Despite a host of potential explanations (endocrine, anatomic, infectious, psychologic, autoimmune, alloimmune), genetic factors are accepted as the most important cause for both sporadic as well as recurrent abortion. Using fluorescent in situ hybridization (FISH) with chromosomespecific probes, 25.50% of morphologically normal and 75% of morphologically abnormal preimplantation genetic embryos are chromosomally abnormal. At least 60.70% of first trimester clinical abortuses are cytogenetically abnormal. The frequency is the same in recurrent as well as sporadic abortuses. Aneuploidy may also be recurrent in successive clinical and successive preimplantation pregnancies, indicating heritable factors. Distinct from cytogenetic causes are single gene mutations and polygenic factors, both more common genetic explanations for anomalies in liveborns than are cytogenetic causes. Non-genetic factors doubtless are occasionally causative for first trimester losses and could also be relatively more important in recurrent losses; however, overall the attributable risk due to non-genetic factors is low in both recurrent as well as sporadic first trimester abortions.
FM4.05.02 THROMBOPHILIA: AN EXAGGERATED PROTHROMBOTIC RESPONSE TO PREGNANCY UNDERLIES MANY CASES OF RECURRENT PREGNANCY LOSS Leslev Renan, ICSM at St. Mary’s, London UK 1) 2)
Pregnancy is an hypercoagulable state Microthrombi identified in the placental vasculature of women with recurrent miscarriage. 3) Prospective studies demonstrate an increased prevalence of antiphospholipid (aPL) antibodies amongst women with recurrent miscarriage and a high rate of early fetal loss. 4) Pregnancy outcome in women with aPL is significantly improved when thromboprophylaxis is prescribed during pregnancy. 5) Retrospective studies of women attending haemostasis clinics suggest that thrombophilias are a risk factor for miscarriage and stillbirth 6) Placental histology demonstrates widespread thrombosis and infarction in some women who carry the factor V Leiden gene mutation 7) Prospective pregnancy outcome studies in women with inherited and acquired thrombophilic defects are urgently needed 8) Conventional haemostasis tests fail to identify all women with thrombophilic defects. Future research should include global markers of haemostatic function such as thromboelastography 9) Protocols need to be established to 1) avoid diagnostic pitfalls when screening 10) for thrombophilic defects and 2) determine the basis for future prospective therapeutic studies Suggested references : Backos M, Rai R, Chilcott I, Cohen H, Regan L (1999) Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid syndrome treated with low dose aspirin and heparin. Br .I Obstet Gynaecol; 106, 102 -107 Brenner B, Mandel H, Lanir N et al (1997). Activated protein C resistance can be associated with recurrent fetal loss. Br .I Haematol97, 551 -554. Cumming AM, Tait RC, Fildes S et al (1995) Development of resistance to activated protein C during pregnancy. Br .I Haematol90: 725. Dizon-Townson D, Meline L, Nelson L, Namer M, Ward K. (1997) Fetal carriers of the factor V Leiden mutation are prone to miscarriage and placental infarction. Am J Obstet Gynecol; 177: 402 405. Grandone E., Margaglione D., Cola&o D., and D’Addedda M. (1997) Factor V Leiden is associated with repeated and recurrent unexplained fetal loss. Thrombosis Haemostasis 77, 822 - 4.
SEPTEMBER
7
Progestogens remain the drugs of choice. We are of the opinion that the problems are two: the first is the type of progesterones used and the second is the protocol of administering the drug. Dydrogesterone a new progesterone we thought was capable of fulfilling the criteria demanded from a drug in the treatment of DUB. We also modified the protocol starting from the drug from llth day of the cycle for 15 days instead of from the lSh day as reported for the other drugs. With the Assumption that oestrogen are intercepted early and the drug will not affect ovulation. We have so far had a study published from our encouraging results on a cohort of 30 patients and after the publication we have recruited a further 50 patients. Our entire group of 80 patients have given us extremely heartening results. Further to this a multicentric trial caried out all over India has recruited 400 patients where the results of our initial study have been reproduced.
EN4.02.03 INTRAUTERINE SYSTEM E-M Rutanen, R. Hurskainen, Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland The intrauterine system that releases levonorgestrel20 g/24 h into the uterine cavity for a time period of 5 years was originally developed for contraception. Many studies have been published during the past decade, describing the system as one of the most effective treatments in reducing the amount of menstrual blood loss in women suffering from menorrhagia. High dose of levonorgestrel in the uterus has strong suppressive effect on the endometrium. Endometrial epithelium becomes atrophic and the underlying stroma is decidualized. This change is constant during the use of the system but reversible in one month after its removal. The concentration of levonorgestrel is high in the endometrium but very low in the circulation, and ovarian function remains almost unaffected. There are several mechanisms that may account for the reduction in menstrual blood loss. The morphological changes in the endometrium are followed by changes in endometrial function. It has been shown that production of many local factors that are involved in the regulation of endometrial proliferation, shedding, remodeling and haemostasis, may undergo changes under continuous progestin stimulation. These changes are likely to favor the reduction of endometrial bleeding. The most common side effects of levonorgestrel intrauterine system are spotting and mild irregular bleeding, which are mostly reported during the first months of treatment. However, levonorgestrel intrauterine system is an alternative to surgical treatment of menorrhagia and especially in women who still want to become pregnant and have an increased risk of iron deficiency anemia. It is also suitable during premenopausal years, since only estrogen needs to be added when climacteric symptoms appear, and if the woman wants to start hormone replacement therapy.
EN4.02.04 VARIATIONS IN SURGICAL TREATMENT J. Emory University School of Medicine, Woodruff Memorial Research Building, Dept. of Gynecology and Obstetrics, Georgia, United States Over 250,000 hysterectomies are performed for dysfunctional uterine bleeding each year in the United States. Some surgeons have suggested that endometrial ablation is now a realistic alternative to hysterectomy. The goal of most ablation techiniques is to remove or destroy the endometrium creating an Asherman like scar. This session will critically assess and compare the techniques of endometrial ablation. Current indications and current contraindications will be presented. Moreover, the complications and percentage of women requiring additional treatment will be reviewed. The goals of this presentation is to bring into focus a realistic appraisal of the role of endometrial ablation in gynecology.
15
FM4.05 RECURRENT
EARLY PREGNANCY
LOSS
FM4.05.01 GENETIC CAUSES ARE RESPONSIBLE FOR MOST FIRST TRIMESTER PREGNANCY LOSSES Joe Leinh Simuson, Baylor College of Medicine, Department of Obstetrics & Gynecology, Houston, Texas, United States Pregnancy loss occurs very commonly, both pre-clinically and clinically. At least 25.50% of embryos die before implantation; another 30% of implanted embryos are lost. The likelihood of losing a clinically evident pregnancy is lo-12%, two-thirds occurring before 8 weeks. Despite a host of potential explanations (endocrine, anatomic, infectious, psychologic, autoimmune, alloimmune), genetic factors are accepted as the most important cause for both sporadic as well as recurrent abortion. Using fluorescent in situ hybridization (FISH) with chromosomespecific probes, 25.50% of morphologically normal and 75% of morphologically abnormal preimplantation genetic embryos are chromosomally abnormal. At least 60.70% of first trimester clinical abortuses are cytogenetically abnormal. The frequency is the same in recurrent as well as sporadic abortuses. Aneuploidy may also be recurrent in successive clinical and successive preimplantation pregnancies, indicating heritable factors. Distinct from cytogenetic causes are single gene mutations and polygenic factors, both more common genetic explanations for anomalies in liveborns than are cytogenetic causes. Non-genetic factors doubtless are occasionally causative for first trimester losses and could also be relatively more important in recurrent losses; however, overall the attributable risk due to non-genetic factors is low in both recurrent as well as sporadic first trimester abortions.
FM4.05.02 THROMBOPHILIA: AN EXAGGERATED PROTHROMBOTIC RESPONSE TO PREGNANCY UNDERLIES MANY CASES OF RECURRENT PREGNANCY LOSS Leslev Renan, ICSM at St. Mary’s, London UK 1) 2)
Pregnancy is an hypercoagulable state Microthrombi identified in the placental vasculature of women with recurrent miscarriage. 3) Prospective studies demonstrate an increased prevalence of antiphospholipid (aPL) antibodies amongst women with recurrent miscarriage and a high rate of early fetal loss. 4) Pregnancy outcome in women with aPL is significantly improved when thromboprophylaxis is prescribed during pregnancy. 5) Retrospective studies of women attending haemostasis clinics suggest that thrombophilias are a risk factor for miscarriage and stillbirth 6) Placental histology demonstrates widespread thrombosis and infarction in some women who carry the factor V Leiden gene mutation 7) Prospective pregnancy outcome studies in women with inherited and acquired thrombophilic defects are urgently needed 8) Conventional haemostasis tests fail to identify all women with thrombophilic defects. Future research should include global markers of haemostatic function such as thromboelastography 9) Protocols need to be established to 1) avoid diagnostic pitfalls when screening 10) for thrombophilic defects and 2) determine the basis for future prospective therapeutic studies Suggested references : Backos M, Rai R, Chilcott I, Cohen H, Regan L (1999) Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid syndrome treated with low dose aspirin and heparin. Br .I Obstet Gynaecol; 106, 102 -107 Brenner B, Mandel H, Lanir N et al (1997). Activated protein C resistance can be associated with recurrent fetal loss. Br .I Haematol97, 551 -554. Cumming AM, Tait RC, Fildes S et al (1995) Development of resistance to activated protein C during pregnancy. Br .I Haematol90: 725. Dizon-Townson D, Meline L, Nelson L, Namer M, Ward K. (1997) Fetal carriers of the factor V Leiden mutation are prone to miscarriage and placental infarction. Am J Obstet Gynecol; 177: 402 405. Grandone E., Margaglione D., Cola&o D., and D’Addedda M. (1997) Factor V Leiden is associated with repeated and recurrent unexplained fetal loss. Thrombosis Haemostasis 77, 822 - 4.