K Nouza’s research while affiliated with Ústav pro péči o matku a dítě and other places

Objective: To summarize recent knowledge concerning mechanisms which influence the implantation of embryo. Design: Literature-based overview. Setting: Institute for the Care of Mother and Child, Prague. SUBJECT OF THE STUDY: Factors influencing implantation of embryo in the uterus elicit increased interest due to study of unexplained failures of embryotransfer following the successful in vitro fertilization. Our article points to recent information about physiology and pathology of mechanisms controlling implantation, namely the factors of immunity (antibodies, cells, cytokines and other mediators) whose exact regulation on the feto-maternal interface is a crucial precondition of successful implantation. Also the genetics of early embryo, as well as the possibilities of modern endoscopic techniques offer new insight onto mechanisms of implantation. Recommendations for diagnostics and treatment of implantation failure are given in the end of the article.

Pregnancy represents the most important exception from immunological laws, where the mother's organism not only tolerate, but even provides many-sided support to semiallogeneic blastocyst, embryo and fetus. The remarkable tolerance is guaranteed by complex immunoregulatory mechanisms on the part of mother, trophoblast and fetus. Their failures belong to the most frequent causes of fetal losses. The key step to successful pregnancy is the implantation - nidation - of the fertilized egg. Its mechanisms are lately intensively studied with the goal to determine the nature of concrete implantation failures, responsible not only for recurrent abortions, but also for significant portion of sterilities and unsuccessful embryotransfers. Gradually we register new diagnostic methods of pregnancy failures and an increase of efficacious prevention and treatment.

To provide an overview of the results obtained from the more than ten-year systematic monitoring of the contribution of immunopathological mechanisms to the ethiopathogenesis of fertility disorders in men. A summarising retrospective study. Mother and Child Care Institute, Prague. The data source is a selected group of a total of 3,800 couples, who were examined in the Immunobiological Department (ID) of the Mother and Child Care Institute (MCCI) in Prague- -Podolí for fertility disorders in the past. From among the laboratory quantities, the following ones were systematically monitored: a) sperm parameters; b) cell-mediated immunity against spermatozoa; c) the presence of anti-spermatozoa auto-antibodies attached to spermatozoa; d) in a part of the clinical group, the serum concentrations of FSH, testosterone, SHBG and the free androgen index (FAI) were monitored. After selection was made according to defined criteria, the group comprised of a total of 1,680 men, of whom 49.4% were normozoospermic and 50.6% suffered from some form of seminal pathology. Increased cell-mediated immunity against spermatozoa was identified in 10.2% of fertile men, in 18.5% of normozoospermic men and in 66.3% of azoospermic men. In asthenozoospermic and teratozoospermic men, the increased cell-mediated immunity against spermatozoa was identified in 48.3% and 53.1% of them, respectively. The auto-antibodies attached to spermatozoa were identified in 3 out of every 42 fertile men (7%), while in asthenozoospermic men, it was a total of 21% (IgA antibodies) and 22% (IgG antibodies). As concerns the concentration of free androgens (FAI) in the serum, there was no difference among the individual subgroups of men. In oligoasthenozoospermic men, FSH was significantly higher on the average in comparison with normospermic men. The significantly higher incidence of increased cell-mediated immunity against spermatozoa in men with a pathological spermiogram in comparison with the control group (fertile men and normozoospermic men) indicates that cell-mediated immunity participates in the pathogenesis of seminal pathologies.

To test the hypothesis of relationship between sperm pathology and elevated humoral and/or cell-mediated antisperm autoimmunity in male partners from infertile couples. Analytic study. Department of Immunobiology, Institute for the Care of Mother and Child, Prague. Sperm samples were evaluated according to WHO rules. Sperm-bound antisperm autoantibodies (ASA) were determined by SpermMar Test (FertiPro N. V., Sint-Martens-Latem, Belgium). For evaluation of cell-mediated antisperm autoimmunity (CMAA) the authors used their own modification of migration-inhibition test (Dimitrov et al., J. Immunol. Methods 154: 147, 1992). The pool of men was divided into groups according to the result of sperm examination: normozoospermia (740 men), asthenozoospermia (244), teratozoospermia (191), oligoasthenozoospermia levis (61), oligoasthenozoospermia gravis (29), oligoteratozoospermia (82), and azoospermia (54). Subgroup of fertile men (32) consisted of normozoospermic men--fathers of child younger than 3 years. Percentage of sperm-bound ASA-positive samples was significantly higher in asthenozoospermia in comparison with normozoospermia in both IgA (20.8% versus 10.6%) and IgG classes (13.8% vs 6.8%). Positivity of CMAA was significantly more frequent in group of asthenozoospermic (52%) than in normozoospermic (28.5%) and fertile (12.5%) men. Antisperm autoimmunity, namely its cell-mediated form, appears to play a significant role in impairment of spermiogenesis. Sperm-bound autoantibodies were found more frequently in asthenozoospermia, but also in some men with normozoospermia they may impair fertility.

Objective: The objective of the investigation was to follow up the course of pregnancy in 32 women with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS) and to evaluate selected clinical and laboratory parameters. Method: Clinical status, total SLE activity according to the SLEDAI score, treatment during pregnancy and selected haematological, biochemical and immunological parameters were investigated. The patients were examined before conception, at the onset of pregnancy and then after each trimester of pregnancy, and immediately after delivery. Results: Eighteen of the patients suffered from SLE, five had SLE with secondary APS and nine patients had primary APS. The majority of patients with SLE was treated with a small dose of corticosteroids, patients with APS took small doses of anopyrin as antiaggregation thexapy. The total SLE activity was in the great majority of patients low, as apparent also from the low values of the SLEDAI score. Organ manifestation of SLE was present in two patients. All women with primary APS and 21 women with SLE had a pregnancy without complications and in term gave birth to a healthy child. These patients had at the onset and in the course of pregnancy a low clinical and laboratory activity of the disease and had no significant organ manifestations of SLE. Two women developed a serious life threatening exacerbation of the disease with severe manifestations of lupus nephritis with acute risk of survival of the foetuses. Both these patients had to be treated during pregnancy by combined immunosuppressive treatment, and premature delivery had to be induced. One of the neonates died on the fourth day, the second one survives and is doing well. Conclusion: Pregnancy took a normal course without complications and without exacerbation of the disease in all patients with primary APS and in 21 patients with SLE (without or with secondary APS), who had at the time of conception a low activity of the disease. In two patients with SLE who had also a low activity of the disease before conception exacerbation of SLE occurred during pregnancy with serious organ manifestation. Pregnancy was very complicated in these women, both had premature dehvens and one of the neonates died because of immaturity. Increased activity of SLE and the presence of organ manifestations during pregnancy were in the investigated group important predictors of the development of SLE as well as of the whole course of pregnancy.

The authors dealt with the urgent problem under what conditions it is possible to achieve in a woman with systemic lupus erythematosus (SLE) or another collagenosis, or secondary antiphospholipid syndrome (APS) a favourable outcome of pregnancy and the delivery of a healthy infant. The investigation comprised 23 women incl. 20 with SLE, two with the mixed form of a diffuse connective tissue disease (MCTD) and one with Sjögren's syndrome of the primary type. From the total number of 20 pregnancies six were consulted in advance with a doctor (group I-s-called planned pregnancies) and all terminated by a successful delivery. Of 11 pregnancies which were not consulted with a doctor in advance (group II-so-called unplanned pregnancies) 9 were terminated in term, however, only 5 with a successful delivery (55.5%), two women are still pregnant. Exacerbation of the basic disease during pregnancy was recorded only once and did not lead to discontinuation of the pregnancy. The authors provide evidence that desired pregnancy of informed women suffering from SLE or another collagenosis when assisted by a specialized medical team can lead to a successful delivery of an infant.