Меtformin-associated maternal and neonatal outcomes in women with gestational diabetes - a retrospective cohort study.

OBJECTIVES: To assess the maternal and neonatal outcomes in women with GDM treated with metformin, medical nutrition therapy (MNT) or insulin. MATERIAL AND METHODS: The current retrospective cohort study includes data from 233 women diagnosed with GDM who gave birth between January 2017 and January 2019 at an obstetrics and gynecology hospital in Sofia, Bulgaria. Patients were assigned to three groups, according to the treatment approach - metformin group (n = 70), insulin group (n = 40), and MNT group (n = 123). Values of fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) have been evaluated at diagnosis of GDM and the third trimester of pregnancy. A comparative analysis of pregnancy outcomes and short-term neonatal characteristics in the investigated groups has been performed. RESULTS: Women indicated for pharmacological treatment (metformin or insulin) had significantly higher BMI (p < 0.01), FPG (p < 0.001), and HbA1c levels (p < 0.001) at baseline. However, during pregnancy, patients treated with metformin showed a significantly lower BMI (p < 0.01), FPG (p < 0.01), and HbA1c (p < 0.01). Neonates born to metformin-treated mothers had lower birth weight compared to those born to women in the MNT and insulin groups (metformin vs MNT, p < 0.001; metformin vs insulin, p = 0.03). The lowest incidence of newborns with macrosomia and neonatal hypoglycemia has been observed in the metformin cohort. Not a single newborn with an Apgar score under 7 has been identified in the metformin group. CONCLUSIONS: According to the current analysis, women with GDM treated with metformin demonstrated better maternal and neonatal outcomes. No short-term complications in newborns have been associated with metformin use during pregnancy.

Economic Burden of Cervical Cancer in Bulgaria.

Bulgaria is among the European Union (EU) countries with the highest burden of cervical cancers and life expectancy below the EU average. The majority of cervical cancer cases (more than 95%) are caused by the human papillomavirus (HPV). The aim of this retrospective, cost of illness study is to identify direct healthcare costs of cervical cancer in Bulgaria from the payer perspective and to calculate indirect costs and the associated years of life lost. Costs data were sourced from the National Health Insurance Fund from January 2018 to December 2020. Years of life lost were calculated based on the country and gender-specific life expectancy. Indirect costs due to productivity loss were calculated using the human capital approach. The total treatment costs for 3540 patients with cervical cancer are EUR 5,743,657 (2018), EUR 6,377,508 (2019), and EUR 6,751,182 (2020). The costs associated with drug acquisition and administration accounted for the majority (63%) of total healthcare costs followed by hospital management costs (14%). An estimated total of 20,446 years of life were lost due to cervical cancer for the period 2018-2020. The costs of productivity losses are estimated at EUR 7,578,014. Our study showed that the economic burden of cervical cancer in Bulgaria is substantial. Focus on cervical cancer prevention via vaccination against the human papillomavirus, timely screening, early diagnosis, and higher vaccine coverage rates could reduce its economic burden in Bulgaria.

Benefits of using a microencapsulated vitamin D delivery system in women with polycystic ovary syndrome.

OBJECTIVE: To compare and assess the efficacy of two vitamin D delivery systems (oil-based and microencapsulated) on 25-hydroxy-vitamin D (25(OH)D) levels, body mass index (BMI) and insulin resistance (IR) in women with established polycystic ovary syndrome (PCOS) and vitamin D deficiency. MATERIALS AND METHODS: A monocentric, retrospective study was conducted, using the data of 70 female patients, who visited the endocrinology department of the "Dr. Shterev" Hospital, Sofia, Bulgaria between May 2020 and September 2020. The patients were divided into two groups according to the type of vitamin D3 supplementation: either a microencapsulated liposomal form (n=35), or a conventional oil-based form (n=35). The following clinical measures were analysed and compared: BMI, serum levels of 25(OH)D, fasting plasma glucose levels, fasting immunoreactive insulin (IRI), homeostatic model assessment (HOMA) index, levels of antimullerian hormone (AMH) II generation, and testosterone. In all selected patients, these measurements were performed at baseline and 3 months after initiation of vitamin D supplementation. RESULTS: Significantly increased serum levels of 25(OH)D were observed in patients supplemented with the microencapsulated form of vitamin D3 in the third month from the beginning of therapy, compared with the control group (p=0.003). In the microencapsulated vitamin D group, there was a decrease in IRI serum levels (p=0.023), HOMA-IR (p=0.021), serum AMH (p=0.010) and testosterone levels (p=0.006). The fasting plasma glucose levels did not change significantly. CONCLUSION: The results of our study show that the patients supplemented with a microencapsulated form of vitamin D3 achieved faster compensation of 25(OH)D levels, which in turn, under equal conditions, led to significant improvement in the metabolic profile, in particular insulin sensitivity.

Study of clinical experience with different approaches to controlled ovarian hyperstimulation: a focus on safety and efficacy.

OBJECTIVES: Current retrospective cohort study analyses clinical database records of 4792 assisted reproduction procedures to assess the significance of target effectiveness endpoints from a safety perspective. METHODS: Stimulation protocols with urinary, recombinant or combination of both types gonadotrophin preparations are compared according to the following primary endpoints: incidence of ovarian hyperstimulation syndrome (OHSS), cycle cancellation, follicle count, induced estradiol values, clinical pregnancy achieved and cycles reached embryo transfer/freezing. We have investigated the incidence of cases evaluated as 'risky for OHSS' by secondary efficacy endpoints (exogenous gonadotrophin exposure, luteinising hormone and progesterone values, oocyte yield, eggs with normal maturation). The following statistical methods were applied: descriptive statistics, Mann-Whitney U test, Kruskal-Wallis test, Pearson chi-square test, Fisher's exact test, binary logistic regression. RESULTS: Only 16 cases (0.42%) of moderate and delayed OHSS were established. Three hundred and seven (8.6%) stimulation cycles have been cancelled, principally among urinary protocols. Although the clinical pregnancy rate does not differ significantly in compared groups, punctured follicle count, oocyte yield and progesterone level were higher for recombinant preparations, followed by combined and urinary protocols. Follicle count, mean estradiol and luteinising hormone levels are within the 'safe window' for all investigated groups, associated with minimised risk of stimulation cancellation. The mean follicle-stimulating hormone (FSH) dose was highest in urinary protocols at the same duration of stimulation compared with recombinant products. The younger age, bigger follicle count, oocytes yield, mature oocytes count, percentage of fertilised oocytes, more embryos transferred and the later day of embryo transfer are critical for both assisted reproduction techniques (ART) success rate and the safety profile of sterility treatment. CONCLUSIONS: Safety surveillance of ART exceeds the incidence of OHSS. Suboptimal effectiveness of stimulation protocols may also jeopardise the well-being of ART patients. Gonadotrophin exposure, induced values of sex hormones, and quantity and quality of extracted oocytes should be considered to minimise any unintended suffering of treated couples.