Efficacy of non invasive diagnostic procedures in evaluation of maternal autoimmune thyreoiditis effect on the fetus

Kod fetusa majki sa autoimunim obolenjem štitaste žlezde povećava se rizik za razvoj hipo ili hipertireoze ploda, zbog prolaska antitiroidnih antitela i tireosupresivnih lekova kroz posteljicu. Cilj studije: Primarni ciljevi studije su: korelacija antitiroidnih antitela majke i fetusa sa ultrazvučno procenjenom veličinom štitaste žlezde fetusa i sa slobodnim tiroksinom fetusa (fT4); procena karakteristika ultrazvuka štitaste žlezde fetusa kao dijagnostičkog testa za otkrivanje izmenjenih vrednosti fT4 fetusa kod majki sa autoimunom bolešću štitatse žlezde. Sekundarni ciljevi su ispitivanje povezanosti fT4 fetusa majki sa autoimunimobolenjem štitaste žlezde, sa ultrazvučnim biometrijskim parametrima, terapijskom dozom leka koji uzima majka zbog obolenja štitaste žlezde i sa hormonima štitaste žlezde majke. Pacijenti i metod: Ispitivanje je sprovedeno prospektivnim praćenjem 51 trudnice sa autoimunim obolenjem štitaste žlezde, 20 u grupi obolelih od hipertereoze i 31 u grupi obolelih od hipotireoze. Kontrolnu grupu je činilo 20 zdravih trudnica. Hormoni štitaste žlezde i antitiroidna antitela majke i ploda odreñivani su iz uzoraka krvi dobijenih venepunkcijom kod majke i kordocentezom kod ploda, izmeñu 26-e i 30-e nedelje gestacije: fT4, tireostimulišući hormon (TSH), koncentracija antitiroidnih antitela (antitireoperoksidazna-anti TPO i antitela na receptor za tireostimulišući hormon- TRAK). Istovremeno je urañena ultrazvučna procena veličine štitaste žlezde, rasta i morfologije ploda. Podaci su obrañeni statistički, uz pomoć softverskog paketa SPSS 15.0. Rezultati: U grupi žena obolelih od hipertireoze 40% fetusa imalo je povećane fT4 u krvi. U grupi žena obolelih od hipotireoze, povećane vrednosti fT4 imalo je 48.4%, a snižene vrednosti fT4 je imalo 3.2% fetusa. Antitiroidna antitela majke i antitiroidna antitela ploda bila su u jasnoj, pozitivnoj korelaciji. Anti TPO majke i ploda korelirala su statistički visoko značajno sa standardizovanim vrednostima fT4 ploda (Spearman-ov koeficijent korelacije: majka: 0,396, p=0,004 i plod: 0,466, p=0,001). Prosečne koncentracije anti TPO i majke i ploda značajno su se razlikovala kod fetusa sa normalnim i izmenjenim obimom štitaste žlezde (kod normalnog obima štitaste žlezde ploda/ kod povećanog obima/ kod smanjenog obima: anti TPO kod majke su: 119 ± 247 vs 377 ± 506 vs 376± 422; Kruskal- Wallis: 10,726, p= 0.005, a kod ploda su: anti TPO 43,98 ± 63,99 vs 140,48 ± 136,99 vs 85,49 ± 88,42; ANOVA, F= 5,567, p<0,05). Kada su anti TPO majke u opsegu referentnih vrednosti, 100% fetusa je imalo normalan obim štitaste žlezde i svi su imali normalne vrednosti fT4...Maternal autoimmune thyroid disease increases the incidence of foetal hypo and hyperthyreosis due to antithyroid antibodies and thyroid suppressive drugs passage through the placenta. Aim of the study: Primary aims: Correlation between antithyroid antibodies level in mothers and foetal serum with ultrasound estimation of foetal thyroid size and free thyroxin (fT4) in foetal blood; ultrasound morphology of foetal thyroid as diagnostic tool in estimation of foetal fT4 values. Secondary aims: to investigate correlation between foetal fT4 with ultrasonographic foetal biometry, therapeutical drug dosage used to treat maternal thyroid disease, and maternal thyroid status. Patients and methods: The study was conducted as a prospective follow up of 51 pregnants with autoimmune thyroid disease, 20 patients hyperthyroid, and 31 hypothyroid. Control group was consisted of 20 healthy pregnancies. Thyroid hormones and anti thyroid antibodies values were measured from blood sampled from mothers and from umbilical cord in foetuses, between 26-30 weeks of gestation. These included: fT4, TSH, antithyriod antibodies (anti thyreoperoxidase At-TPO, TSH receptor antibody-TRAK). At the same ultrasound estimation of foetal thyroid volume, foetal growth and morphology were assessed. The data were statistically analyzed using SPSS 15.0. Results: 40 % of foetuses in hyperthyreotic pregnancies were found with increased fT4 in cord blood. 48,4% foetuses from hypothireotic pregnancies were found to have increased fT4, and 3,2% were found to have decreased fT4 in cord blood. Maternal and foetal antithyroid antibodies were in obvious positive correlation. Maternal and foetal anti TPO correlated highly significant with standardized values of foetal fT4 (Spearman correlation coefficient: mother 0,396, p=0,004, foetus 0,466, p=0,001). Mean concentration of anti TPO in mother and foetus significantly differed in foetuses with normal and impaired foetal thyroid size (normal foetal thyroid size/increased foetal thyroid size/decreased foetal thyroid size: maternal anti TPO: 119 ± 247 vs 377 ± 506 vs 376± 422; Kruskal- Wallis: 10,726, p=0.005, foetal anti TPO: anti TPO 43,98 ± 63,99 vs 140,48 ± 136,99 vs 85,49 ± 88,42; ANOVA, F= 5,567, p<0,05). In maternal anti TPO within normal range, all foetuses were found with normal thyroid size and normal fT4..

Exogenous luteinizing hormone for assisted reproduction techniques in poor response patients

Background/Aim. Two gonadotrophins, two cell theory refers to necessity of both gonadotrophin activities for theca and granulose cells steroidogenesis of dominant follicle. The aim of this study was to determine the influence of recombinant LH in women qualified as poor responders in the first assisted reproduction procedure (IVF), on fertility results, expressed as percentage of clinical pregnancies. Method. The study included 12 women, 35 years and older who were their own controls. The next trial of IVF was with the same dose of recombinant FSH and GnRH agonist, and with the same, long protocol. Recombinant LH was added in the dose of 75 IU from the 2nd to 7th day of the cycle, and 150 IU from the 8th day of the cycle to the aspiration of oocytes. Results. Within the two different protocols: there was no significant difference between LH concentration in 8th and 12th day of cycle; there was no significant difference between E2 concentration on day 2nd and day 8th; there was a significant difference between E2 concentrations on day 12th; endometrial thickness was not significantly different on the day of aspiration, neither was the number of follicles and embryos. In the two patients, clinical pregnancy was detected (pregnancy rate 17%), and they delivered in term. So, a statistically significant difference between the two protocols was in the rate of clinical pregnancies. Conclusion. The patients with low response to a long protocol in IVF procedures had significantly better results according to the clinical pregnancy rate when the recombinant LH was added to recombinant FSH in the stimulation protocol

Poor ovarian response to stimulation for in vitro fertilization

The term “poor respond (POR) patients” is used for the group of women who respond badly to usual doses of gonadotropins in in vitro fertilization (IVF) treatments; the consequence is low pregnancy rate. A consensus was reached on the minimal criteria needed to define POR. At least two of the following three features must be present: 1. advanced maternal age (40 years or more) 2. previous POR (3 or less oocytes with a conventional stimulation protocol) 3. abnormal ovarian reserve (AMH 0.5-1.1 ng/ml or AFC 5-7). The aim is to find better therapeutic options for these patients. Increased levels of day 3 follicle stimulating hormone (FSH) and estradiol (E2), as well as decreased levels of anti-Mьllerian hormone (AMH) and antral follicle count (AFC), can be used to assess ovarian reserve, as indirect predictive tests. A larger number of well designed, large scale, randomized, controlled trials are needed to assess the efficacy of different management strategies for poor responders: flare up gonadotropin releasing hormone (GnRH) agonist protocols, modified long GnRH agonist mini-dose protocols, luteal initiation GnRH agonist stop protocol, pretreatment with estradiol - GnRH antagonist in luteal phase, natural cycle aspiration or natural cycle aspiration GnRH antagonist controlled, adjuvant therapy with growth hormone or dehydroepiandrosterone (DHEA). The results of up to now used protocols are unsatisfactory and stimulation of the ovulation in poor responders remains a challenge, especially when bearing in mind that in the majority of cases the patients will be menopausal in relatively short period of time

The Comparative Effects of Myo-Inositol and Metformin Therapy on the Clinical and Biochemical Parameters of Women of Normal Weight Suffering from Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is a multisystem reproductive–metabolic disorder and the most common endocrine cause of infertility. The objective of our study was to determine the influence of myo-inositol (MI) on insulin resistance (IR), menstrual cycle regularity, and hyperandrogenism in women suffering from PCOS with normal BMI and diagnosed IR. Methods: We performed a prospective randomized controlled trial (RCT) that included 60 participants with PCOS who had IR and a normal BMI. Two groups were formed. A group of thirty patients received MI, and thirty patients in the control group received metformin (MET). Results: A statistically significant reduction in the area under the curve (AUC) of insulin values during the oral glucose tolerance test (OGTT) was recorded in both examined groups after the applied therapy with MI and MET. The regularity of the menstrual cycle in both groups was improved in >90% of patients. A statistically significant decrease in androgenic hormones (testosterone, SHBG, free androgen index—FAI, androstenedione) was recorded in both groups and did not differ between the groups. Conclusions: Both MI and MET can be considered very effective in the regulation of IR, menstrual cycle irregularities, and hyperandrogenism in women with PCOS

Prevalence, Risk Factors, and Pathophysiology of Nonalcoholic Fatty Liver Disease (NAFLD) in Women with Polycystic Ovary Syndrome (PCOS)

Background: Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine disorders in women&rsquo;s reproductive period of life. The presence of nonalcoholic fatty liver disease NAFLD, one of the leading causes of chronic liver disease in the Western world, is increased in women with PCOS. This review aims to present current knowledge in epidemiology, pathophysiology, diagnostics, and treatment of NAFLD in PCOS with an emphasis on the molecular basis of development of NAFLD in PCOS women. Methods: Authors investigated the available data on PCOS and NAFLD by a MEDLINE and Pub Med search during the years 1990&ndash;2021 using a combination of keywords such as &ldquo;PCOS&rdquo;, &ldquo;NAFLD&rdquo;, &ldquo;steatohepatitis&rdquo;, &ldquo;insulin resistance&rdquo;, &ldquo;hyperandrogenaemia&rdquo;, &ldquo;inflammation&rdquo;, &ldquo;adipose tissue&rdquo;, and &ldquo;obesity&rdquo;. Peer-reviewed articles regarding NAFLD and PCOS were included in this manuscript. Additional articles were identified from the references of relevant papers. Results: PCOS and NAFLD are multifactorial diseases, The development of NAFLD in PCOS women is linked to insulin resistance, hyperandrogenemia, obesity, adipose tissue dysfunction, and inflammation. There is the possible role of the gut microbiome, mitochondrial dysfunction, and endocannabinoid system in the maintenance of NAFLD in PCOS women. Conclusions: There is a need for further investigation about the mechanism of the development of NAFLD in PCOS women. New data about the molecular basis of development of NAFLD in PCOS integrated with epidemiological and clinical information could influence the evolution of new diagnostic and therapeutic approaches of NAFLD in PCOS