Metabolic and hereditary factors of reproductive health-Labour II

1. Screening tests for chromosomopathies and pregnancy complications. Free beta HCG nd PAPP-A values between 11. and 14. week of gestation in pregnant women with trisomy 21, trisomy 18 or sex chromosomes abberations are different from the values in pregnant women with normal fetuses. The values of these markers can also be different in women where fetal karyotype is normal but complications in pregnancy occur. Screening tests for Slovenia will be validated. Analysis of false positive results, predictive values and appropriateness according to the population characteristics will be performed. 2. Influence of chemical and biochemical factors on reproductive health. Those toxic, subtoxic and biological effects of mercury, connected to lipid peroxidation and oxidative DNA damage will be studied as well as some biological markers. Cumulation of mercury in epiphysis, anterior hypophysis, thyroid gland and testes can potentially influence function of the glands. We will evaluate the effects of mercury retrospectively; in the city of Idrija after 500 years of mercury mine functioning the pollution and exposition are high. 3. The incidence and forms of thyroid dysfunction in reproductive period. We will try to evaluate if the iodine intake in pregnancy in Slovenia is adequate, as this has influences on the fetus and the incidence of thyroid diseases later in life. We want to ascertain the incidence of thyroid diseases in pregnancy and puerperium and etiology of these diseases for our population. 4. Hereditary factors of menstrual irregularities. In patients with menstrual irregularities we will continue with analysing some of the genetical factors (DNA ploidy of granulosa-thecca cells, mutaitions in the GALT gene, variations in the CYP11a gene). 5. Preterm delivery is the most frequent complication in pregnancy, adding most to perinatal morbidity and mortality. With additional analyses of signals of electrohysterograms we will try to improve predictive value for preterm delivery and institute a system with simple and repeatable recording of signals. Psychological stress and labor and delivery as the central life event will be studied. 6. Primary infection with Toxoplasma gondii in pregnancy. Study of congenital toxoplasmosis detection with DNA analysis of amniotic fluid with PCR analysis will be performed.

The programme “Metabolic and Innate Factors of Reproductive Health, Labour II” is based on the need to broaden knowledge and improve the performance in the field of reproductive health with the implementation of basic scientific and clinically applicable research work. In the 5-­year period and based on the set objectives in the 4 work packages the research group has published 87 publications in journals cited by the SCI/SCE with impact factors (IF) ranging from 0.067 to 10.603. There are 19 articles, which have been published in journals ranked A' or A''. The members of the research group were doctoral mentors to 10 candidates, master’s thesis mentors to 10 candidates and involved in 3 specialist’s projects. They were also doctoral co­-mentors to 5 candidates and master’s thesis co­-mentors to 3 candidates. Four Prešeren’s student research projects have also been completed. The results were presented in many international meetings as invited lectures, oral presentations and posters. The researchers participate in various international projects; they are editors of international journals and co-organizers of international meetings. The results have raised many new questions that enable us to actively pursue new objectives to work towards in the coming years.

Achieved objectives in all 4 work packages have resulted in new knowledge which has already proven to be successful in direct clinical practice and that we have been incorporating into clinical guidelines and clinical pathways. 1 – There are 6­7% of premature labours in Slovenia; however, they contribute to 60% of perinatal mortality and morbidity, which places us in the group of European countries with an averagely high incidence of premature labour. An agreement is in place between the 14 maternity hospitals in Slovenia that a pregnant woman in danger of labour before the 32nd week of gestation is sent to one of the tertiary­ level hospitals in Ljubljana (University Medical Centre Ljubljana) or Maribor (University Medical Centre Maribor). With the development and application of methods to more reliably predict preterm labour we wish to reduce costs, avoid unnecessary side effects of treatment with tocolytics and therapy for foetal maturation with corticosteroids and an unnecessary relocation to a tertiary­ level hospital, thus reducing the risk of neonatal mortality and morbidity. A fact important for Slovenia is that we have properly translated neuropsychological tests into Slovenian language which have already been used in the clinical follow­up of former neonates with perinatal hypoxia and its lifelong effects on the quality of life. 2 – We will improve the quality of perinatal care in Slovenia by analyzing the data from the National Perinatal Information System (NPIS) and incorporate them into the renewed clinical guidelines. 3 – We observed serum levels of cadmium, lead and mercury in the Slovenian population of women living in urban environment that are comparable to those of countries in the Central and Northern Europe. However, the concentrations mentioned above are lower compared to those in Asia. 4 – The results of genetic research in the field of disorders of ovarian function play an important role in everyday clinical practice and present a possibility of direct integration of new diagnostic methods in the treatment of patients. By indentifying polymorphic alleles of genes involved in the metabolism of estrogens we would specify the group of women with an increased risk for breast cancer due to the additional estrogens exposure when on hormone replacement therapy (HRT).