Recurrent miscarriage

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THURSDAY,

FC4.11.08 OVARIAN RESPONSE DURING USE OF HORMONE AGONIST PROTOCOLS

E. S. Isianovska (11, S. Adamoska-Klisaroska (2), S. Isjanovski (l), (1) GYN. Clinic “Ultra Medica”, Ilindenska 97, Skopje, Macedonia, 91000, (2) Medical center Prilep, Prilep, Macedonia. Objectives: The aim of the study was to investigate the effect of ovarian responses with two groups of women age 38-43 years, which had been treated with two kinds of stimulative protocols with the use of GnRH agonist: long protocol & Improved boost protocol. Study methods: Thirty women were included in this ovarian response study. Group A: consists of 15 women between 38-43 year, all treated with long protocol. The administration of GnRHa started at day 1 to day 14 from the cycle in daily doses of 0,6 ml Suprefact SC. In the next 9 days 300 1.~. Methrodine were used per day + Suprefact in 0,6 ml. dose. Group B: Consists of 15 women between 39 and 42 years, treated by improved boost protocol. The administration of GnRHa (Suprefact), started at day 2 of the cycle, in doses of 0,9 ml SC. per day. From day 5started with 300 1.~. of Methrodine in the next 9 days + 0,9 ml Suprefact continuously. Hormonal analysis: Serum LH, E2 and P4 were measured during the both protocols continuously. The growth of the follicles was observed by Ultrasound equipment. Results: Group A: At the critical day, just before administrating the HCG, 2 or less follicles bigger or equal to 18 mm were detected at 86.5 % of woman, and 300. 500 pg/l of serum E2 levels were measured. Group B: At the critical day, just before administrating the HCG, more than 2 follicles, bigger or equal to 17 mm were detected at 93.5 % of the women. E2 levels were 500-1400 pgil. Conclusion: At the more mature women group, the usage of GnRHa with modificated boost protocol of ovarian stimulation gives much better results. However, the danger of early luteinization of the follicles is still present as result of inadequate desenzibilisation of ovaries. That danger was avoided by adequate administration of the long protocol, which, however, gave a poor ovarian response in our case.

FC4.12 RECURRENT

MISCARRIAGE

FC4.12.01 RECURRENT MISCARRIAGE AN ASPIRIN A DAY? R. M. Backos, L. Reagan, Imperial College School of Medicine at

St Mary’s, Norfolk Place, London, United Kingdom, W2 1NY. Introduction: Pregnancy is a hypercoaguable state. Recent evidence suggests that (a) some women with recurrent miscarriage (RM) are in a pro-thrombotic state outside of pregnancy and (b) some cases of RM are due to an exaggerated haemostatic response during early pregnancy. Low dose aspirin (acetylsalicylic acid; 75mg daily) is frequently prescribed on an empirical basis to women with unexplained RM. The purpose of this cohort study was to determine the efficacy of this intervention in improving the subsequent live birth rate amongst these women. Subjects and Methods: The prospective pregnancy outcome of 1055 women with a history of either (a) 3 or more consecutive first trimester miscarriages (n=805) or (b) at least 1 second trimester miscarriage (n=250) was studied. All women had persistently negative tests for antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) and a normal peripheral blood karyotype as did their partners. Results: Amongst women with recurrent first trimester miscarriage, the subsequent live birth rate was similar amongst those who took low dose aspirin from the time of a positive pregnancy test (2511367; 68%) compared with those who those who did not take aspirin (2781438; 64%: p=O.14). There was no significant difference in either the ages or the number of previous miscarriages between the two groups of women. In contrast, amongst women with a previous second trimester miscarriage the subsequent live birth rate was significantly higher amongst women who took aspirin (1221189; 657)D compared with those who did not take aspirin (30161; 49%: p=O.O3;OR 1.88; 95%CI 1.04. 3.37). Again, women in the two groups were of similar age and had a similar number of previous miscarriages. Amongst pregnancies that resulted in a live birth, there was no significant difference in either the median gestational

SEPTEMBER

age at delivery {aspirin: median 36.4 weeks (24.1 40.4); no aspirin: 36.2 (24.6 39.6): p=O.50} or in birth weight {aspirin: median 3.14 kg (0.55 4.4); no aspirin 3.22 (0.86 -4.2: p=O.42)} between the two groups of women. Discussion: Low dose aspirin, which irreversibly inhibits platelet thromboxane synthesis, significantly improves the subsequent live birth rate amongst women with unexplained second trimester miscarriage. This finding supports the hypothesis that this condition has an underlying pro-thrombotic aetiology. Whilst there is no benefit from low dose aspirin amongst women with unexplained recurrent first trimester miscarriage, a heterogeneous group, it is possible that aspirin may be of benefit to a sub group with a proven thrombophilic abnormality

FC4.12.02 PRE PREGNANCY THROMBOPHILIC ABNORMALITIES ARE ASSOCIATED WITH SUBSEQUENT MISCARRIAGE L. Renan cl), R. Rai (l), E. Tuddenham (2), M. Backos (l), (1) Imperial College School of Medicine at St Mary’s, Norfol Place, London, United Kingdom, W2 lNY, (2) MRC Haemostasis Unit, Hammersmith Hospital, London, United Kingdom. Introduction: The haemostatic pathways play a crucial role in implantation, trophoblast invasion and placentation. Pregnancy itself is a hypercoaguable state and recent evidence suggests that recurrent miscarriage (RM) and later pregnancy complications are in some cases due to an exaggerated haemostatic response. Thromboelastography is a sensitive and reproducible means of assessing whole blood haemostasis. We have previously reported that 30% of non-pregnant women with a history of RM have an increased clot strength (MA), as assessed by thromboelastography, compared with parous controls. The MA correlates significantly with both platelet reactivity and aggregation responses to collagen and adenosine diphosphate. Subjects & Methods: The prospective outcome of untreated pregnancies amongst 32 women (median age 33 years; range 19-42) with RM (median 4; range 3-12) who had pre-pregnancy thromboelastography performed was studied. All women had persistently negative tests for antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) and a normal peripheral blood karyotype as did their partners. No woman received pharmacological treatment during pregnancy, apart from folic acid as prophylactic against neural tube defects. Results: The pre-pregnancy MA was significantly higher {median 69mm (56 73)) amongst the 10 women who miscarried compared with the 22 women who had a live birth {(median 63mm (54 73; p = 0.02)). There was no significant difference in either the ages or the number of previous miscarriages between the two groups of women. Furthermore, serial thromboelastographic assessments during early pregnancy demonstrate that an increase in the MA precedes pregnancy loss in some cases. In all pregnancies that resulted in a live birth, there was no significant change in the MA between 5 and 12 weeks gestation. Discussion: A sub-group of women with RM are in a thrombophilic state outside of pregnancy which predisposes them to future pregnancy loss. This hypercoagulability is in some cases amplified by the known haemostatic changes that occur during pregnancy and lead to subsequent pregnancy loss. Serial thromboelastography during pregnancy allows the detection of the development of a hypercoaguable state prior to pregnancy loss which may be amenable to correction with thromboprophylaxis. Whether this is the case is under investigation in a randomised placebo controlled study.

FC4.12.03 RECURRENT MISCARRIAGE ; WHEN TO INVESTIGATE M.Formosa. M.Brincat, St Luke’s Hospital, University, Gwardamangia,

Malta, MSD07. Objectives: Following an audit of an ongoing Miscarriage Clinic the question of whether it is justified to allow patients to suffer three miscarriages before investigation was put. Methods & Materials: Because of the increasing awareness of the problem of recurrent miscarriage a dedicated miscarriage clinic was setup in the Department of Obstetrics & Gynaecology , St Luke‘s Hospital, Medical School, Malta. The clinic is a referral service for patients with at least two miscarriages. The aims of the clinic are to investigate these patients with a view to making a diagnosis and advising on appropriate

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THURSDAY,

SEPTEMBER

7

treatment. The couple are also provided with information, counselling and support which is an integral part of the management of this problem. A review of the clinical notes of one hundred and twenty patients who were assessed at the clinic were reviewed. Patients are investigated according to a standard protocol. The causes of recurrent miscarriage that were encountered were: anatomical, endocrine (including PCOS), immunological, genetic, unexplained and chronic maternal illness. The patients concerned were divided almost equally into those who had had two and those who had had three miscarriages. The causes of the miscarriages and the eventual outcome of the two groups were compared. Results: 120 cases from the clinic were suitable for this study. The greater majority of patients were nulliparous and had two miscarriages (64), while 56 had had at least three miscarriages. The age range of the patients was 19-44 years with a mean age of 31 years at referral. The percentage of 1st trimester miscarriages was 86.6% while 13.4% represented the 2nd trimester miscarriages. No differences were encountered in the assessment of the two groups of patients. Patients with either two or three miscarriages did not differ significantly in either the type of pathology encountered or the eventual outcome. Conclusion: Recurrent miscarriage is a very distressing condition for the patient and one associated with much frustration for the investigating physician. The condition is a homogenous one and different causes can account for successive miscarriages in the same patient. Recurrent miscarriage is classically defined as three successive miscarriages. It is our contention that this is not justified and patients should be investigated after two successive miscarriages. This will reduce much unnecessary anxiety on the part of the patient and possibly also unjustified fetal loss.

FC4.12.04 PREDICTIVE VALUE OF 3 DIMENSIONAL VOLUMETRY OF GESTATIONAL AND YOLK SAC FOR PREGNANCY OUTCOME IN TIE FIRST TRIMESTER A.Babinszki(l), T. Nyari(2), T. Mukheriee(3), A.B. Copperman(3) (1) Dept. of OB/GYN (2) Dept. of Medic. Inform. University of Szeged, Ilungay; Div. of Reproduction Endocrinology. (3) Dept. of OB/GYN and Reproduction Sciences, the Mount Sinai School of Medicine, New York, USA. Objectives: We proposed that first trimester volume calculations of the gestational sac (GS) and yolk sac (YS) using transvaginal3 dimensional ultrasound technique might have predictive value for adverse reproductive outcome. Study Methods: 49 consecutive patients (treated for infertility) with singleton pregnancies were included in this prospective study. 94 examinations were performed in pregnancies with normal, and 14 with abnormal outcome. GS and YS volumes as well as CRL were plotted against gestational age (GA) (25-65 days post ovulation) to create nomograms for normal outcome. Measurements of abnormal pregnancies were compared with these nomograms. Specificity, sensitivity, positive and negative predictive values were also calculated. Results: Regression analysis revealed a power correlation between GS volumes and GA and a logarithmic relationship between YS volumes and GA. CRL showed logarithmic correlation with GA as well. Both GS volumetry and CRL measurements proved to have statistically significant predictive value for adverse outcome (p
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FC4.12.05 THE PATTERN OF RECURRENT PREGNANCY LOSS IN KUWAIT F.M.E. Dieiomaoh (l), M. Al-Azemi (2), .I. Jirous (2), A. Bandar (2), P. Egbase (2), N. Al-Sweih (3), S. Al-Othman (2) (1) Dept. OBIGYN, Faculty of Medicine, Kuwait University, Kuwait. (2) Dept. OBIGYN, Maternity Hospital, Kuwait. (3) Dept. Microbiology, Faculty of Medicine, Kuwait University, Kuwait. Objectives: The aim of this study was to identify the etiological factors and the pattern of recurrent pregnancy loss in Kuwait. Study Methods: 90 patients attending the special recurrent spontaneous abortion clinic were studied prospectively. A comprehensive history of all previous abortions and pregnancies, past medical and gynecological events were established. A physical examination was undertaken. Extensive investigations including immunological and endocrinological tests, Karyotype and radiological studies and transvaginal ultrasonography and Doppler studies were undertaken. Pregnancies which occurred during the study were monitored carefully. Statistical analysis was by xz and Fisher’s exact two-tailed test. Results: 60% of the patients were Kuwaitis. The mean age of the patients was 30.46 f 6.04 years. The patients were subdivided into the groups of secondary (57%) and primary (43%) recurrent abortions. 85% of all previous abortions occurred in the first trimester. The main etiological factors were uterine anomaly 2.2%, chromosome anomaly 2.2%, PC0 13.3%, antiphospholipid syndrome 38.9% and unexplained in 33%. Although the incidence of cesarean section was significantly higher in primary recurrent abortion cases (P
FC4.12.06 EPIDEMIOLOGY OF SPONTANEOUS RECURRENT ABORTION M.Y. El-Zibdeh, Dept. OB/GYN & Infertility, Islamic Hospital, Amman, Jordan. Recurrent abortion is defined as a loss of three or more consecutive pregnancies. The incidence and the prevalence of this problem depend on the gestational age accepted as lower limit for the fetal viability. Data from various studies indicated that after two miscarriages, the risk of third miscarriage is about 30%. The possible etiological causes of recurrent pregnancy loss (PRL) are numerous and many of them are controversial. Objectives: The aim of this study was to identify the etiologic causes of RPL as seen in patients attending our hospital. Study Methods: 142 women with RPL were included in this study. The clinical, laboratory sonagraphic and radiological assessment were reviewed to identify the possible causes. Results: Hormonal abnormalities were found in 35 patients (25%), anatomical abnormalities were seen in 14 patients (lo%), immunological abnormalities in 18 patients (12.6%), maternal infections in 8 patients (5.6%). In 44 patients (31%) no causes were identified. Conclusion: Evaluation of women with RPL should be comprehensive and treatment should be curtailed accordingly.

FC4.12.07 LOW LEVELS OF ENDOMETRIAL DECAY ACCELERATING FACTOR (CD55) MAY BE AN INDICATOR OF SPONTANEOUS ABORTION M.Martens (11, AKaul(2), D,Brown (2), RKaul(2), (1) Hennepin County Medical Center, 701 Park Avenue, Minneapolis, United States, 55415.1829, (2) Minneapolis Medical Research Foundation, Minneapolis, Minnesota, U.S.A. Objective: Immunologically a fetus is a semiallogenic graft and for a successful pregnancy, it needs to be protected from the autologous complement cascade. Decay accelerating factor (DAF; CD55) is a complement regulatory protein that inhibits complement activation and thus protects the autologous tissues from the cytotoxic effects of complement. To investigate the possible role of DAF during pregnancy, we investigated its expression in the endometrium of pregnant women.