High-risk pregnancy: effectiveness of personalized pregravid preparation and positive perinatal experience

Research objective: to study the possibilities of improving perinatal results by optimizing pergravid preparation in women with high perinatal risk.Materials and methods. The first stage – a cross-sectional study – consisted in determining the vitamin D (VD) status and assessing the course of pregnancy in 459 women in the II and III trimester; the second stage was a randomized controlled study of women with VD deficiency in group IIA (planning stage, 54 women) and IIB (I trimester, 60 women), who received the vitamin and mineral complex (VMC) Pregna-5 with a high calcitriol content and perinatal results were evaluated. VD in the blood was determined by the enzyme-linked immunosorbent assay.Results. VD level was optimal only in 30.7% of pregnant women (group ІА), in 69.3% of women its insufficiency or deficiency was found (group ІB). The frequency of threatened termination (9.9 vs. 45.6%; p < 0.01), preeclampsia (2.0 vs. 11%; p < 0.05), intrauterine growth retardation (7% only in group IIB, p < 0.01) was significantly higher against the background of BD deficiency. Normalization of the VD level (groups IIA and IIB) after VMC administration was observed within 1–3 months. Pregnancy complications value was higher in the group where the VMC was started in the first trimester: early gestosis (15 vs. 28.57%; p < 0.05), the threat of termination (22.2 vs. 36.7%; p < 0.05), bacterial vaginosis (7.4 vs. 31.7%; p < 0.05), placental dysfunction (18.5 vs. 40.0%; p <0.01), placental pathology in group IIB was detected 2–3 times more often. The differences between the preeclampsia (1.9 vs. 6.7%; p > 0.05) and anemia (16.6 vs. 28.3%; p > 0.05) were insignificant. Analysis of the childbirth results showed a significantly higher frequency of cesarean sections in group IIB (38.3 vs. 22.2%; p < 0.05), the average weight of newborns was less (3299.11 ± 128 g vs. 3643.24 ± 136 g; p < 0.01). The most effective was the VMC start at the stage of pregnancy planning (F = 13.35482; p = 0.000016); a significant difference was revealed in the course of pregnancy in the groups where VMC started in the first, second and third trimesters of pregnancy (Q = 4.67, p = 0.00458).Conclusions. Timely donation of VMC with a high content of cholecalciferol in women with high perinatal risk may lead to a positive course of pregnancy. Further research is required to obtain a convincing evidence base.

Clinical case: pregnancy-associated breast cancer

This article presents a clinical case of pregnancy-associated breast cancer. We have analyzed the features of the diagnostic algorithm, considered the radiological manifestations and presented the main literature sources about this pathology.Pregnancy-associated breast cancer is breast cancer that occurs during pregnancy or within the first year after a baby birth. It is most often diagnosed only after first clinical symptoms, the most characteristic of which is a feeling of compaction in the breast, less often bloody discharge from the nipple, pain, breast deformation and baby's refusal to breastfeed.Radiological signs of pregnancy-associated breast cancer are not pathognomonic and may mimic benign changes associated with pregnancy and lactation at early stage: lactation adenoma, mastitis, abscess, galactocele, fibroadenoma. Uncertainty of physicians about the harm of radiological methods of examination for pregnant women and the fetus and, consequently, incorrect diagnostic algorithms can delay the early detection of pathology, establish an accurate diagnosis and worsen the prognosis for the patient.Compliance with a sequential diagnostic algorithm using sonographic diagnostics, X-ray mammography with digital breast tomosynthesis, magnetic resonance imaging in accordance with the diagnostic categories of the BI-RADS scale allows you to verify breast tumors. Diagnosis should be consistent with American College Radiology guidelines.In case of detection of suspicious breast pathology in a pregnant woman or woman in labor, a doctor of any specialty should refer the patient to specialized specialists in the diagnosis and treatment of breast diseases. Adherence to the correct algorithms for the appointment, conduct and interpretation of radiological studies, taking into account changes in the breast structure, will allow timely diagnosis, proper treatment and save the lives and health of childbearing aged women.

Screening for diabetes and prediabetes: the newest communication opportunities

Type 2 diabetes mellitus (DM-2) and prediabetes are serious diseases that can lead to early disability and death. DM-2 can remain undiagnosed for many years; therefore, screening is one of the main assistants of a doctor in establishing a diagnosis, allowing to start treatment as early as possible.Research objective: early identification of patients with prediabetes and DM-2 using an online questionnaire.Materials and methods. The study was carried out online using the Google Forms platform, where a questionnaire was created based on Appendix 3 “Form of risk assessment of diabetes mellitus-2” of the Unified clinical protocol of primary and secondary (specialized) medical care “Type 2 diabetes mellitus”, approved by order of the Ministry of Health of Ukraine No. 1118 dated 12.21.2012, as well as additional questions on nutrition and physical activity. As of June 2021, the study involved 209 patients (151 women and 58 men) who did not have a documented diagnosis of DM-2 or prediabetes.Results. Most of the respondents (89 people) were overweight. 51 respondents had grade I obesity, 31 respondents had grade II, and 7 patients had a body mass index > 40 kg/m2, which corresponds to grade III obesity. Only 49 respondents had a healthy weight, which corresponds to a body mass index 18.5–24.9 kg/m2. 29 (19.21%) women had a history of childbirth with a child weighing more than 4 kg. The diagnosis of polycystic ovary disease (a risk factor for the DM-2) was in 34 (22.52%) women. Upon receipt of laboratory tests, we established a diagnosis of prediabetes in 28 (13.40%) patients, and a diagnosis of DM-2 in 17 (8.13%) people.Conclusions. It is necessary to search for new opportunities in communicating with patients during the COVID-19 pandemic, one of which is online questionnaires based on regulatory documents.

Insulin resistance in the ХХІ century: multimodal approach to assessing causes and effective correction

In a broad sense, insulin resistance (IR) is the impairment of the biological response of target tissues to insulin stimulation. IR plays a leading role in the development of metabolic syndrome, the global prevalence of which continues to grow, despite the significant efforts of medical systems. The multicomponent nature of metabolic syndrome implies its complex and heterogeneous pathogenesis, knowledge about which is annually updated with new details as a result of scientific research.This review systematizes the results of recent studies on risk factors and pathogenetic links in the development of IR, prospects and existing experience of using these data in clinical practice with an emphasis on assessing the level of melatonin and vitamin D. The issue of timely and reliable laboratory confirmation of IR is relevant not only for endocrinologists, but also for specialists in almost all areas. In clinical use apart from indirect methods of IR-assessment like HOMA-IR, there is an informative test intact proinsulin.Recently, the increasing attention of researchers is attracted by such factors of the development of IR as vitamin D deficiency and disturbances in chrono- and biorhythms. Today, their role in the pathogenesis of IR can be considered proven, which makes it possible to consider vitamin D and melatonin as therapeutic agents in an integrated approach to the prevention and correction of IR. Statistical analysis of the research results of the “DILA” Medical Laboratory and clinical data provided by the Department of Endocrinology of the O.O. Bogomolets National Medical University also showed an association of vitamin D and melatonin levels with IR.Thus, a review of scientific sources over the last 5 years clearly demonstrates the growing urgency of the problem of IR and metabolic syndrome, the need to reconsider their management from assessing traditional etiopathogenetic factors (alimentary) to taking into account the maximum spectrum of genetic aspects and exogenous impacts. An important place among the latter belongs to an objective assessment of the vitamin D and melatonin levels for adequate pharmacological correction.

Resolution of the 1st Ukrainian expert forum on abnormal uterine bleeding

The menstrual cycle is an important indicator not only of the female reproductive system health but also an integral part of women's health. The issues of therapeutic approaches for menstrual disorders, considering the general trend towards an increase in the proportion of this pathology among the total gynecological disorders in Ukraine, are susceptible and require close attention. The problem of abnormal uterine bleeding (AUB) has a significant impact on women and health care worldwide. Algorithms for the diagnosis and therapy of AUB need to be regularly revised as international recommendations are updated, clinical trials are published, and a new look at pathogenetic mechanisms is made.The prerequisites for holding of this Expert Forum were the updating of the FIGO classification of uterine bleeding in 2018, the NICE guidelines “Heavy menstrual bleeding: assessment and management” in 2018 and 2021, as well as the new conditions of the pandemic era, which has taken its toll on the care of patients with AUB.The Resolution summarized all data unaccounted for in the current clinical protocol for AUB issued in 2016 and updated data from international guidelines and key studies in patients with AUB; highlighted in detail current thinking on the pathogenetic therapy of functional AUB, with an emphasis on chronic AUB associated with ovulatory dysfunction (AUB-O) and endometrial disorders (AUB-E), as the most common; provided modern approaches to the management of chronic AUB associated with non-structural causes (ovulatory dysfunction and endometrial factors), and prevention of acute AUB for implementation in clinical practice and improving the provision of evidence-based medical care and individualized patient care.The Resolution aims to optimize clinical approaches to patient management and ensure therapy personalization, which together will improve the reproductive health and general well-being of Ukrainian women.

Prolactin level correction in restoration of menstrual cycle in obese women

Obesity is a common problem among women of reproductive age. There are data from clinical and experimental studies indicating the role of hyperprolactinemia in the development of metabolic syndrome, as well as the metabolic benefits of treating hyperprolactinemia.Research objective: to evaluate the clinical efficacy of Vitex Agnus Castus standardized extract on hormonal and metabolic status in women with menstrual cycle disorders and obesity.Materials and methods. 60 women aged 19 to 35 years with obesity and menstrual cycle disorders with laboratory-confirmed insulin resistance and prolactin near the upper limit of the reference values or was slight increase were examined. All the patients were given recommendations for lifestyle modification. 30 of them, who formed the main group, received Cyclodynon. 30 patients of the control group were not prescribed Cyclodynon therapy.Results. At the end of the treatment, the menstrual cycle was normalized in 93.3% patients of the main group, and in 66.3% patients of the control group (p < 0.05). Ovulation signs were detected in 86.67% women of the main group and only in 30.0% women of the control group (p < 0.05). The mean prolactin value and the HOMA index were significantly lower in the main group; prolactin level did not exceed the physiological values in 86.67% women in the main group after 6 months, and in 40.0% of the control group, p < 0.05. There was a decrease in body mass index and waist/hip circumference ratio in patients of the studied groups; the dynamics was slightly higher in the main group but did not differ significantly. Conclusions. Cyclodynon is effective for the treatment of menstrual cycle disorders and metabolic disorders in women with obesity and metabolic syndrome. Good tolerability, absence of side effects, and sufficient efficacy of Cyclodynon allow it to be recommended as the drug of choice in patients with prolactin levels near the upper limit of the reference values or a slight increase of it and in patients with intolerance to synthetic dopamine agonists.

Vitamin D level and hormonal status association in adolescent girls with oligomenorrhea

Research objective: to determine the frequency of vitamin D deficiency and insufficiency to identify its association with reproductive hormones in adolescent girls with oligomenorrhea.Materials and methods. The work was carried out according to the results of clinical and instrumental examination of 68 adolescent girls 12–18 years old with oligomenorrhea, who were treated at the Department of Pediatric Gynecology of the State Institution “Institute for Children and Adolescents Health Care of the NAMS of Ukraine”. Patients were divided into two groups depending on the body mass index (BMI): group I – with a body weight deficit (BMI 16.31 ± 0.18 kg/m2), group II – with a BMI within physiological norm (20.0 ± 0.25 kg/m2). All patients underwent a comprehensive clinical and laboratory examination: luteinizing, follicle-stimulating hormones, prolactin, estradiol, testosterone, cortisol, 25(OH)D were determined in blood serum. Multivariate regression analysis was using for analyze the association of gonаdotropic, steroid hormones with vitamin D. The main characteristics of the object discrimination model are presented in the form of tables.Results. The article provides a comparative analysis of the hormonal profile and vitamin D level depending on BMI. It was revealed that a reduced 25(OH)D value was characteristic not only in patients with menstrual dysfunction, but also in peers with normal menstrual function. Schemes that characterize the pituitary-gonadal association with vitamin D were constructed based on the results of multiple regression analysis. Their features were determined in girls with different body weights. In patients with low energy resources there were direct associations between individual indicators of gonadotropins (follicle-stimulating hormone), steroid hormones (estradiol, cortisol) and vitamin D. An inverse association was observed between vitamin D and cortisol and prolactin in girls with balanced energy status.Conclusions. The reduced content of vitamin D is characteristically for patients with menstrual dysfunctions by the type of oligomenorrhea. Associations of gonadotropic, steroid hormones and vitamin D, depending on the energy status (nutrition) of patients with oligomenorrhea were revealed.

NICE guideline “Ectopic pregnancy and miscarriage”: new changes and importance for the clinicist

The purpose of this publication is to summarize the current data on the effectiveness of progestogens in patients with threatened miscarriage (vaginal bleeding in the first trimester of pregnancy) and to review the updated UK National Institute for Health and Care Excel (NICE) clinical guidelines on ectopic pregnancy and miscarriage.In accordance with the opinion of the Cochrane Society experts and the updated NICE clinical guidelines for 2021, vaginal progesterone at a dose of 800 mg/day is the only intervention that has been shown to be effective in increasing live births compared to placebo for women with one or more previous miscarriages and early vaginal bleeding (relative risk 1.08, 95% confidence interval 1.02–1.15, high certainty evidence). Upon confirmation of fetal heartbeat, this treatment should be extended until 16 weeks of gestation.There is still uncertainty over the effectiveness and safety of alternative progestogen treatments (as dydrogesterone) for threatened and recurrent miscarriage. There is also no evidence of benefit of any other preparations or doses of progesterone in patients at risk of miscarriage.

Role of inositol and its isomers in glucose metabolism

Despite the chemical similarities between myo-inositol and D-chiro-inositol and their synergistic effects on insulin sensitivity, they serve different functions. Insulin resistance is one of the etiological factors in the development of polycystic ovary syndrome (PCOS), diabetes mellitus, metabolic syndrome, infertility, menstrual irregularities and ovulation disorders, pregnancy complications, in particular, gestational diabetes. Myo-inositol plays an important role in the insulin transfer and hormone synthesis in the ovaries, in oocyte maturation, fertilization, implantation and post-implantation development.Many studies confirm the positive effect of inositol isomers on metabolic, hormonal and reproductive disorders, both in the form of monotherapy and in combination with other drugs to enhance the therapeutic effect and bioavailability. Myo-inositol has a favorable safety profile. Studies have shown that in patients with PCOS myo-inositol improves ovarian function and fertility, reduces the manifestations of hyperandrogenism, insulin resistance and normalizes weight.Myo-inositol and D-chiro-inositol have different mechanisms of action on insulin sensitivity and have different functions. The balance of the two isomers ensures the normal secretion of hormones and ovarian functioning, but it is currently unknown what the optimal ratio of these two isomers due to the small number of high quality studies and the difficulty of studying their isolated action.There are currently different combinations of myo- and D-chiro-inisotol, but they also have not been supported by enough high quality studies. When prescribing various isomers of inositol, it should be remembered that doses above 4000 mg are the most studied in patients with PCOS, but D-chiro-inositol concentration above 1200 mg/day has undesirable effects. Most studies indicate that D-chiro-inositol value is increased in PCOS, therefore oocytes are more sensitive to its overdose, and combination drugs require more study. Currently, there is no consensus in the literature on the advantage of combined supplements of myo- and D-chiro-inositol compared to monotherapy with myo-inositol. Today, myo-inositol monotherapy is more researched and safer.

Nutritional status disorders in women with lichen sclerosus of the vulva

Research objective: to determine the characteristics of nutritional status (NS) in women of reproductive age with typical clinical signs of lichen sclerosus of the vulva (LSV) using key NS parameters. Materials and methods. The study included 75 women with average age 31.3 ± 1.3 years. 50 women were diagnosed with LSV and NS disorders (main group), and 25 women were practically healthy (control group). Information about all patients was collected through direct interviews, clinical examination and study of medical records. The presence of anogenital pruritus, soreness or burning, dryness, dyspareunia, urinary disturbances, perianal and/or intestinal symptoms, inflammatory bowel disease, thyroid dysfunction and tenderness, and other comorbidities were recorded. NS evaluated using anthropometric, laboratory and clinical studies. Body mass index, index of nutritional risk (nutritional deficiency), vitamins, micro- and macroelements value, scatological parameters were determined in all patients, and the intestinal microflora was examined.Results. The results of the study showed a disorder of NS in most patients with LSV by all studied parameters in comparison with the control group. Thus, it was found that 60% of patients with LSV had abnormal body mass index as well as NS was observed in 72% of patients. In addition, patients with LSV also had a higher deficiency of vitamins D and B12, and some important micro- and macronutrients. The results of the coprological study showed the neutral fats in feces, unchanged muscle fibers, extracellular and intracellular starch, decreased levels of bifidobacteria and lactobacilli in 68–74% of patients and opportunistic bacteria and fungi in 30–46% of women in the main group.Conclusions. Thus, the results of this study indicate the association between the abnormal NS and LSV. However, further research is needed to assess the course of the underlying disease and to analyze the metabolic pathways that lead to disorders of lipid, carbohydrate and protein metabolism in target patients, to select of the correct nutrients and alternative treatments.