Local lymphocytic and epithelial activation in a case of autoimmune oophoritis.

OBJECTIVE: To further define the immunological tissular modifications in premature ovarian failure (POF). METHOD: The patient was followed up for premature ovarian failure and mild endometriosis associated with serum antiovarian antibodies. A laparoscopic ovarian biopsy was decided on to analyze the tissue and support the onset of immunosuppressive therapy. Immunohistochemistry was performed using monoclonal antibodies directed against T cell membrane markers, as well as activation molecules, to define the composition of the cellular infiltrate and the consequences on ovarian tissue. RESULT(S): A dense infiltration of activated T lymphocytes was observed in close contact with follicular epithelium expressing HLA-DR and CD40. CONCLUSION(S): This observation supports the role of cellular immunity in ovarian autoimmunity with features very similar to those reported in murine models and other human autoimmune endocrine pathologies.

Outcome for children infected with congenital toxoplasmosis in the first trimester and with normal ultrasound findings: a study of 36 cases.

OBJECTIVE: We wished to investigate the prognosis of children infected with Toxoplasma gondii during the first trimester of pregnancy and whose ultrasound findings were entirely normal, in order to find out whether congenital toxoplasmosis did or did not justify termination of pregnancy if there was no fetal abnormality on ultrasound. STUDY DESIGN: A prospective and retrospective study was carried out by 12 French centers who enrolled 36 children infected with T. gondii during the first trimester of pregnancy and whose ultrasound examinations showed no anomaly. The outcome of these children after the age of 12 months (mean 50 months, range 12-144 months) was analyzed. RESULTS: Of the 36 infected children, 28 (78%) presented subclinical toxoplasmosis. Only specific IgG antibodies persisted after 1 year. The principal manifestation in 7 children (19%) was chorioretinitis without major vision loss. Their intellectual development was entirely normal. One child (3%) developed severe congenital toxoplasmosis. CONCLUSION: Since 97% of children infected with toxoplasmosis during the first trimester of pregnancy are asymptomatic or only slightly affected, we believe that in such circumstances termination of pregnancy is not indicated. However, appropriate treatment is essential and prenatal ultrasound examinations should be free of any anomaly.

Corticosteroids in patients with antiovarian antibodies undergoing in vitro fertilization: a prospective pilot study.

OBJECTIVE: Antiovarian autoantibodies (AOA) have been associated with reproductive failure, especially in in vitro fertilization (IVF) patients. Thus, the success rate of IVF might be improved by the use of corticosteroids. However, therapeutic trials with these drugs have yielded conflicting results, particularly because of heterogeneous inclusion criteria. Among women with previous IVF failure, we selected those who presented with a positive serum AOA assay, and analysed the efficacy of corticosteroids in improving the IVF outcome in these patients. METHODS: One hundred patients with serum AOA detected by ELISA and at least two previously failed IVF attempts were selected. These patients underwent a further IVF cycle with 0.5 mg/kg prednisolone, started on the first day of the treatment cycle. In patients who became pregnant, corticosteroids were administered until the end of the first trimester of pregnancy and then progressively discontinued. AOA were assessed before and after oocyte retrieval. Clinical data of the corticosteroid-treated cycle were compared with data from the preceding IVF cycle for each patient. RESULTS: No adverse effects resulting from corticosteroids were observed. Post oocyte retrieval antiovarian IgG were significantly lower in corticosteroid-treated attempts when compared with the preceding cycles. Twenty-six pregnancies resulted in the birth of 30 healthy children. The pregnancy rate, implantation rate, and live birth rate were 38.8%, 17.8%, and 26.5% respectively in prednisolone-treated cycles. CONCLUSION: This study confirms the usefulness of corticosteroids in improving the success rate in a subset of patients with previous IVF failure and significant serum AOA levels.

The influence of cigarette smoking on human sperm quality and DNA fragmentation.

The aim of the present study was to evaluate consequences of cigarette smoking on male gametes. In this prospective study, sperm parameters such as sperm density, motility, viability and normal morphology were measured according to the WHO criteria. In addition to these standard parameters, we analysed the degree of DNA fragmentation in spermatozoa using the TUNEL-assay with flow cytometry detection in 57 non-smokers and 51 smokers seeking for infertility counselling. The smoking intoxication was assessed by questionnaire and measured with the CO-Tester. We show that smokers' spermatozoa have a significantly higher DNA fragmentation than non-smokers (32% versus 25.9%, p<0.01). In contrast there is no significant difference in conventional parameters between smokers and non-smokers. The degree of sperm DNA fragmentation is not significantly correlated with any of the conventional parameters. These findings suggest that cigarette smoking may have deleterious effects on sperm nuclear quality and that sperm DNA fragmentation can therefore be considered as an independent parameter with diagnostic, prognostic, and strategic value in the treatment of infertility.

Transdisciplinary training in reproductive health through online multidisciplinary problem-solving: a proof of concept.

OBJECTIVE: The problem of iatrogenic multiple pregnancies has been addressed through an online multidisciplinary discussion forum with the primary aim of developing a transdisciplinary research and training tool. STUDY DESIGN: The pedagogical approach was divided in three phases, unidisciplinary, multidisciplinary and multi/transdisciplinary. Evaluation of the level of transdisciplinarity reached by each of the students was based on their capacity to translate disciplinary knowledge, to establish a frank dialogue, to cross disciplinary barriers, to detach from their initial opinion, and to develop curiosity for others' perspectives and concerns. RESULTS: Translation of disciplinary knowledge and frank dialogue were easily performed by all. Most students showed curiosity towards the others' point of view and started to be preoccupied with the concerns of other students. CONCLUSION: Online discussion forum is a particularly well-adapted tool for transdisciplinary research and training.

Management of delayed-interval delivery in multiple gestations.

OBJECTIVE: Proving that delayed delivery is possible, debating its modality, suggesting a guideline for its managing. METHOD: Six cases of delayed delivery were treated at the Maternity Hospital of Nancy, between 1979 and 2001, and the results were compared to a literature review of 148 found thanks to Medline database. RESULTS: Delayed delivery reduces the risk of neonatal mortality and morbidity. The delivery interval is 2-93 (median 7) days in our experience and 2-153 (median 31) days in the literature. After the first expulsion, cerclage was used in 60% of the cases, prophylactic tocolysis and antibiotics in 79% and 71%, respectively. CONCLUSION: There is no consensus for its management but it must be performed with precise conditions to restrict both maternal and fetal risks. Our study is supporting an interventionist attitude with cerclage, prophylactic tocolysis and antibiotics.

Gonadal antibodies interfering with female reproduction.

While the involvement of anti-ovarian antibodies (AOAs) is highly likely, yet still controversial, in patients with patent premature ovarian failure (POF), it is even more difficult--for several reasons--to ascertain the clinical significance of these antibodies in patients without obvious ovarian failure. First, AOAs form a heterogeneous group of antibodies recognizing several different antigenic targets such as granulosa and thecal cells, zona pellucida, oocyte cytoplasm, corpus luteum, as well as gonadotrophins and their receptors. Second, the detection of AOAs in various clinical situations does not readily imply a causal relationship between these antibodies and impaired ovarian function. Third, diagnostic tools for detecting AOAs and their molecular targets have to be improved to yield more reliable data and allow a better comprehension of the pathophysiology of AOAs. Preliminary results with immunosuppressive therapy in selected AOA patients have been encouraging, but randomized trials have to be performed.

Iron therapy in iron deficiency anemia in pregnancy: intravenous route versus oral route.

OBJECTIVE: The aim of this study was to compare intravenous iron sucrose versus oral iron sulfate in anemia at 6 months of pregnancy. STUDY DESIGN: A random, prospective, open study with individual benefit was performed involving 50 patients with hemoglobin levels between 8 and 10 g/dL and a ferritin value of <50 microg/L. In the intravenous group (IV group), the iron dose was calculated from the following formula: Weight before pregnancy (kg) x (120 g/L - Actual hemoglobin [g/L]) x 0.24 + 500 mg. The oral group (PO group) received 240 mg of iron sulfate per day for 4 weeks. Treatment efficacy was assessed by measurement of hemoglobin and reticulocytes on days 8, 15, 21, and 30 and at delivery and of ferritin on day 30 and at delivery. The baby's birth weight and iron stores were noted. Results were expressed as median +/- interquartile range. Mann-Whitney and Wilcoxon tests were used for the analysis, with P <.05 considered significant. RESULTS: An increase in hemoglobin was observed, rising from 9.6 +/- 0.79 g/dL to 11.11 +/- 1.3 g/dL on day 30 in the IV group and from 9.7 +/- 0.5 g/dL to 11 +/- 1.25 g/dL on day 30 in the PO group (not significant). On day 30 (P <.0001) and at delivery (P =.01) ferritin was higher in the IV group. A mean higher birth weight of 250 g was noted in the IV group (not significant). CONCLUSION: Iron sucrose appears to be a treatment without serious side effects indicated in correction of pregnancy anemia or iron stores depletion.

Hyperhomocysteinemia is related to a decreased blood level of vitamin B12 in the second and third trimester of normal pregnancy.

Hyperhomocysteinemia has been associated with several pregnancy complications. We have investigated the variation of plasma total homocysteine (tHcys) during the 2 last trimesters of normal pregnancy and related it to blood vitamin B12 and folate and to the excretion of the degraded intrinsic factor receptor (IFCR) in urine, in a follow-up study of 15 cases. A significant rise in tHcys was observed between the beginning of the second trimester and the third trimester with respective values (median) 6.1, 5.8 and 6.7 micromol/l (p = 0.038). The tHcys/albumin ratio also increased significantly, while no correlation was found between albumin and folate blood concentration. In contrast, a significant decrease in vitamin B12 was observed (279, 225 and 199 pmol/l, between the 4th and 6th, and the 6th and 9th month, respectively (p = 0.017-0.002)). A significant negative correlation was found between tHcys between the 4th and 9th month of pregnancy and the ratio of vitamin B12 between the 4th and 9th month of pregnancy (r = 0.55, p = 0.037). The urine excretion of IFCR was increased and was not related to vitamin B12 and tHcys. In conclusion, we have observed a rise in tHcys between the beginning of the second trimester and the third trimester of pregnancy which was related to the decreased blood level of vitamin B12. Subclinical deficiency of vitamin B12 should be further investigated in pregnant women who remain on inadequate diet.