[Natural cycle for frozen-thawed embryo transfer: Spontaneous ovulation or triggering by HCG]. / Transferts d'embryons congelés en cycle naturel : ovulation spontanée ou déclenchement par hCG ?

OBJECTIVE: To compare frozen-thawed embryo transfer (FET) outcomes in natural cycles according to ovulation induction: spontaneous versus recombinant human chorionic gonadotrophin (r-hCG) triggering. METHODS: This retrospective study included all patients monitored for natural cycle FET during one year. When serial monitoring were performed until spontaneous LH rise, patients were included in group A (n=38) whereas those receiving r-hCG for ovulation triggering formed group B (n=43). All embryos had been cryopreserved by a vitrification method following a previous IVF cycle. No luteal phase support had been given. We compared outcomes between the 2 groups. RESULTS: After checking groups comparability, we didn't find significant difference for the implantation rate, clinical pregnancy rate and live birth (31% vs 45%, 32% vs 51% et 21% vs 32%, respectively for group A and B). The number of monitoring was significantly lower in group B (1,9±0,8 versus 2,5±1, P=0,006). DISCUSSION: Although no consensus has been yet established, natural cycle seems indicated for normo-ovulating patients but the question of ovulation induction is still debated. In our study, triggering ovulation by r-hCG, respecting strict criteria, seems provide good results while reducing both protocol's constraints and cost.

[In vitro fertilization and smoking: use of urinary cotinine and expired air carbon monoxide measurements]. / Fécondation in vitro et tabac: intérêt de la cotininurie et de l'analyseur de monoxyde de carbone expiré.

OBJECTIVE: To study the correlation between expired air carbon (EACO) and urinary cotinine, and to determine the impact of tobacco smoking on in vitro fertilization (IVF) results. PATIENTS AND METHODS: We studied prospectively 221 patients in our ART center from October 2002 to October 2004: 51 active smokers, 85 passive smokers, and 85 non-smokers. Patients were classified into active, passive smokers, or non-smokers, based on a questionnaire. We measured urinary cotinine and EACO on the embryo transfer day and we recorded the IVF parameters. RESULTS: Two hundred and twenty-one patients were included. We observed a 17.2% reduction of estradiolemy (P=0.05), a 1.5% reduction of pregnancies (NS), a 7.8% reduction of infants born alive (NS), a 28.5% reduction of twin pregnancies (P=0.06), as well as a 10% increase of miscarriages (NS) in the active smokers in comparison with non-smokers (the same trends were observed between active and passive smokers). EACO and urinary cotinine were well correlated. There was a negative correlation between estradiolemy and urinary cotinine (R=-0.15, P=0.02). DISCUSSION AND CONCLUSION: Tobacco smoking intensity may be dilatory on IVF results. There is a high correlation between EACO and urinary cotinine. Other larger studies would probably obtain results more statistically significant.

Use of a low-molecular weight heparin (enoxaparin) or of a phenformin-like substance (moroxydine chloride) in primary early recurrent aborters with an impaired fibrinolytic capacity.

An impaired fibrinolytic capacity, defined as an insufficient venous occlusion-induced shortening of the plasma euglobulin clot lysis time, is a common feature in women suffering from primary early recurrent unexplained miscarriages. We investigated the therapeutic effect of a low-molecular-weight heparin and of a phenformin-like substance. In a prospective, randomized trial, 30 consecutive patients initially received either enoxaparin, 20 mg per day during one month, or moroxydine chloride, 1200 mg per day during one month. In case of fibrinolytic status normalization, they were treated during 6 months by the beneficial treatment which was planned to be continued during eventual pregnancies. Patients with hypofibrinolysis persistence received the alternative treatment during another month and a new evaluation was performed. No treatment was given when a persistent abnormal response to the venous occlusion test was evidenced. In case of positive response, the treatment was continued during 6 months. The primary study end-points consisted of any of the following: effect of the treatments on the fibrinolytic response; number of patients becoming pregnant during the 6 months following the last venous occlusion test; number of full-term pregnancies. Concerning the effects on the fibrinolytic system, 20 out of 29 women responded to the first or second-line enoxaparin treatment whereas only 1 woman out of 19 responded to moroxydine chloride (p = 0.00002). Concerning the effects on fertility, responders to LMWH were more likely to initiate a new pregnancy than non-responders (16/20 vs 2/10, p = 0.002). In patients conceiving, LMWH responders were more likely to obtain live births than nonresponders (13/16 vs. 0/2, p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Case-control study of the frequency of thrombophilic disorders in couples with late foetal loss and no thrombotic antecedent--the Nîmes Obstetricians and Haematologists Study5 (NOHA5).

BACKGROUND: Women with familial thrombophilia have an increased risk of still birth. We postulated that the presence of asymptomatic risk factors for venous thrombosis might be a risk factor for late foetal loss. METHODS: We performed a case-control study on the prevalence of heritable thrombophilic defects, of antiphospholipid-related markers and of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with at least one episode of late unexplained foetal loss and in control women with successful pregnancies. Partners of cases and controls were also studied. Written conclusions of the pathological examination of the placentas, when available, were also reviewed. RESULTS: We found at least one positive biological risk factor for venous thrombosis in 21.1% of the patients and in 3.9% of the controls (p < 10(-4)). In women, the crude odds ratio for still birth associated with any positive biological risk factor for venous thrombosis was 5.5, 95% confidence interval (95%CI) [3.4-9.0]. No difference was found between partners of cases and controls (5.2% and 4.7%). Using conditional logistic regression analysis, 4 adjusted risk factors for still birth remained: protein S deficiency, positive anti beta2 glycoprotein I IgG antibodies, positive anticardiolipin IgG antibodies and the factor V Leiden mutation. The C677T mutation in the MTHFR gene was not an individual risk factor but an homozygous genotype was strongly associated with the former 4 risk factors (16.8% of patients vs. 0.9% of controls). In women with such associations, still births always occurred in absence of folic acid supplementation during pregnancy. Available conclusions of pathological analysis of placentas were found to have a very high proportion of "maternal vascular disease of the placenta" in patients with at least one positive risk marker for thromboembolism, specially in case of association with the C677T MTHFR homozygous genotype, compared to patients with negative markers (p <10(-4)). CONCLUSIONS: Late foetal loss, through placenta thrombosis, may sometimes be the consequence of a maternal multifactorial prothrombotic state associating traditional heritable or acquired thrombosis risk factors to conditions predisposing to an acute mild hyperhomocysteinaemia (coexistence of a genetic predisposition with late pregnancy-related increased folate needs).

Respective evaluation of the prevalence of haemostasis abnormalities in unexplained primary early recurrent miscarriages. The Nimes Obstetricians and Haematologists (NOHA) Study.

The prevalence of haemostasis abnormalities was evaluated in 500 consecutive women with unexplained primary recurrent miscarriages. Two matched reference groups with no antecedent of miscarriage were studied: 100 healthy mothers and 50 childless women. In the prospective part of the study, we found 9.4% of the patients (95% C.I.: 6.8-12%) with an isolated factor XII deficiency, 7.4% of the patients (5.0-9.8%) with primary antiphopholipid antibodies, 47% of the patients (42.6-51.4%) with an insufficient response to the venous occlusion test and an isolated hypofibrinolysis was found in 42.6% (38.2-47%) of the patients (reference groups: respectively 0/150, 3/150, 2/150, p < 10(-3)). Willebrand disease, fibrinogen, deficiency, antithrombin, protein C or protein S deficiencies were not more frequent in recurrent aborters than in members of the reference groups. In the retrospective part of the study, cases of plasma resistance to activated protein C were not abnormally frequent. Patients had higher Willebrand factor antigen (vWF), tissue-type plasminogen activator antigen (t-PA), plasminogen activator inhibitor activity (PAI) and D-dimers (D-Di) than the reference women. Values of vWF, t-PA, PAI and D-Di were altogether correlated but were not related to C-reactive protein concentrations. Among patients, those with an antiphospholipid syndrome and those with an insufficient response to the venous occlusion test had higher vWF, t-PA, PAI and D-Di values than the patients with none of the haemostasis-related abnormalities. Thus, factor XII deficiency and hypofibrinolysis (mainly high PAI) are the most frequent haemostasis-related abnormalities found in unexplained primary recurrent aborters. In patients with antiphospholipid antibodies or hypofibrinolysis, there is a non-inflammatory ongoing chronic elevation of markers of endothelial stimulation associated with coagulation activation. This should allow to define subgroups of patients for future therapeutic trials.

Antiphospholipid and antiprotein syndromes in non-thrombotic, non-autoimmune women with unexplained recurrent primary early foetal loss. The Nîmes Obstetricians and Haematologists Study--NOHA.

Various antiphospholipid and/or antiprotein antibodies have been suspected to be associated with recurrent early foetal loss in absence of any habitual aetiology. We conducted a hospital-based case control study on women with no antecedent of thromboembolic or autoimmune disease. We studied 3 groups of 518 women: patients with unexplained primary recurrent early foetal loss, patients with explained episodes and mothers with no previous obstetrical accident. Matching the 3 groups was carried out on the basis of age, number or pregnancies and time elapsed since the end of the last pregnancy. Significant biological markers were then prospectively tested. The various antibodies were shown to be dependent on parity and on the presence of previous foetal loss: cut-off values were thus calculated using data obtained from the group of explained accidents, and adjusted for parity. Only anti-phosphatidylethanolamine IgM [odds ratio: 6.0, 95% confidence interval (2.3-15.7), p = 0.0003], anti-beta2-glycoprotein I IgG [4.4, (1.6-11.7), p = 0.0035] anti-annexin V IgG antibodies [3.2 (1.2-8.1), p = 0.015] and lupus anticoagulant [3.0, (1.3-6.8), p = 0.009], were found to be independent retrospective risk factors for unexplained early foetal loss. These four markers were subsequently found to be, during the following pregnancy, associated with a significant risk of foetal loss despite a low-dose aspirin treatment. In non-thrombotic, non-auto-immune women with unexplained primary recurrent early foetal loss, subgroups of patients with positive anti-phosphatidylethanolamine IgM antibodies, or positive anti-beta2-glycoprotein-I IgG antibodies, or positive anti-annexin V IgG antibodies or lupus anticoagulant must be particularised. This should allow therapeutic trials to be carried in well-defined patients.

[The use of sulprostone (Nalador) in the evacuation of uterine contents. Apropos of 32 cases at the Department of Gynecology, University Hospital Center, Nîmes, over 2 years (a retrospective study)]. / Utilisation du sulprostone (Nalador) dans l'évacuation du contenu utérin. A propos de 32 observations du Service de Gynécologie CHU Nîmes sur deux années (étude rétrospective).

We have studied the use of sulprostone in evacuating uterine contents in 32 patients, the majority of whom were in the second trimester of their pregnancies. There are three ways to administer the drug (continuous intravenous, intermittent intravenous, and intramuscular); the best results were obtained when the drug was administered continuously intravenously. It was well tolerated, the use of Nalbuphine reducing pain. There were few side effects. The use of this product is discussed in connection with a few of the cases as well as the possible alternative treatments in difficult cases.

[Post-radiation coronary diseases. Presentation of 7 cases and review of the literature]. / Les coronaropathies post-radiques. Présentation de 7 cas et revue de la littérature.

Coronary lesions are one of the complications of mediastinal radiotherapy; they are more uncommon, at least in their clinical expression, than the involvement of the pericardium, but they are interesting by their gravity and occurrence in young patients (35 years old, in an average). We are reporting 7 cases in addition to the 53 already recorded in the literature. The neoplasm which led to the radiation treatment is, in 85 p. cent of the cases Hodgkin's disease and in 10 per cent of the cases a breast cancer. The time of occurrence of the clinical signs is of 5 years, in an average. The revealing symptom is an initial necrosis or an angor, most often unstable (45 p. cent of the cases, for each of them), more exceptionnally it is a sudden death or a pericarditis. The coronary risk factors have been determined in 37 patients; 45 p. cent had none. In half of the cases, the coronary involvement is monotruncular and frequently proximal (the anterior interventricular trunk is affected twice as often as the right coronary); in the other half, there is an equal distribution between bi-troncular and tri-truncular involvement. There are various pathological lesions: typical with isolated fibrosis of the intima and aventitia, pure atherosclerotic lesions or association of the two. The prognosis of these coronary lesions is severe (43 p. cent of deaths), but the patients who underwent revascularization procedures (by-pass or more seldom transluminal angioplasty) have in 80 p. cent of the cases a favorable evolution.(ABSTRACT TRUNCATED AT 250 WORDS)

[Congenital cervical agenesis: pregnancy after transmyometrial embryo transfer]. / Agénésie cervicale congénitale: grossesse obtenue après transfert intra-myométrial d'embryon.

Cervical agenesis is a rare congenital pathology linked to an anomaly of development of the Mullerian system. We described a case report about a 22-year old woman, consulting for infertility, who had a complete cervical agenesis. The first evaluation suggested a 46 XX karyotype and a normal ovarian reserve. The surgical examination confirmed the absence of cervix with impossibility of catheterization. She became pregnant thanks to an in vitro fertilization (IVF) with transmyometrial embryo transfer. Caesarean was decided at 36 weeks of gestation (WG) due to spontaneous uterine contractions. An injection of medroxyprogesterone was made after the placenta delivery in order to warning the partum hemorrhage. The ultrasound examination, realized 15 days after caesarean, underlined a good uterine involution. The surgery by cervico-vaginal anastomosis can be offered to patients because it offers chances of spontaneous pregnancies. But this surgery exposes women to a risk of failure, and of severe complications such as pain or infection, and might end in a hysterectomy. By choosing the transmyometrial transfer by vaginal way, the patient was exposed to the risk of spontaneous miscarriage. It was raising the problem of the uterine evacuation. This delivery after 34 WG is encouraging for the infertility by cervical agenesis.

[Apheresis for Byler syndrome in pregnancy: tolerance and effectiveness]. / Aphérèse pendant la grossesse dans un syndrome de Byler: tolérance et efficacité.

We report the first known case of a successful pregnancy in a 22-year-old white woman suffering from hepatic Byler's syndrome, a familial fibrogenic cholestasis observed in children and usually leading to death during adolescence or to liver transplantation. A first pregnancy was unsuccessful with intrauterine death. Medical surveillance of the second pregnancy was reinforced due to major cholestasis and itching sensation. Plasmapheresis was employed weekly from the 19th week of gestation. Within 2 weeks of treatment onset, plasma alkaline phosphatase levels returned to normal; pruritus completely disappeared after the second session. Delivery was decided at 33 weeks gestation with uterine section. The female baby weighed 2,090 g and outcome was excellent. This is the first reported case of Byler's syndrome with successful pregnancy. We underline the efficacy and safety of apheresis in this very particular disease.