Obstetrics, Gynecology and Reproduction

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Vol 13, No 4 (2019)



279-288 675

Aim: to study the clinical and diagnostic manifestations of hyperandrogenism (HA) in women with subclinical thyrotoxicosis.

Materials and methods. Sixty three hyperthyroid women with clinical manifestations of HA were examined. Of these, 17 patients (27.0 %) were diagnosed with hyperthyroidism and HA. The control group included 20 practically healthy women of the similar age (20–44 years old) with no signs of HA or other hormonal disorders. All women under observation (patients with thyrotoxicosis and HA syndrome and women from the control group) underwent a thorough clinical examination and were assessed for their hormonal status using biochemical assays. The levels of follicle-stimulating (FSH), luteinizing (LH), thyroid-stimulating (TSH) hormones, prolactin, estradiol (E2), estrone, and total testosterone (Ttotal) were measured as well as the levels of dehydroepiandrosterone- sulfate (DHEA-S), 17-hydroxyprogesterone (17-OHP), free triiodothyronine (T3free), free thyroxin (T4free), sex hormone binding globulin (SHBG), androstenedione, and antimullerian hormone.

Results. Patients with hyperthyroidism and HA had significantly (р < 0.05) higher (than normal) levels of FSH, LH, LH/FSH, estrone, 17-OHP, Ttotal, androstenedione, DHEA-S, T3free , and T4free, as well as lower levels (р < 0,05) of TSH (0,390 ± 0,003 mU/ml), E2 (49.86 ± 4.00 pg/ml), and SHBG (49.65 ± 1.20 nmol/L). A course of pathogenetic therapy that included anti-hyperthyroidism treatment (tyrosol 5–10 mg/day for 3 months) followed by anti-HA treatment (combined oral contraceptives) resulted in significant (р < 0,05) reduction in LH, the LH/FSH ratio, estrone, 17-OHP, T3free, T4free, androstenedione (2.64 ± 0.008 ng/ml), DHEA-S (2.15 ± 0.14 pg/ml), Ttotal (1.32 ± 0.10 ng/ml) and in significant (р < 0,05) increase in E2 (69.46 ± 2.58 pg/ml), SHBG (59.59 ± 2.8 nmol/L), and TSH (1,79 ± 0,16 mU/ml).

Conclusion. Combined pathogenetic therapy reduces the clinical manifestations of hyperthyroidism and HA syndrome, and restores the menstrual and reproductive functions of women.

289-296 529

Aim: to identify clinical and histologic features of pure stromal ovarian tumors.

Materials and methods. We analyzed the clinical data from patients treated and followed up at the Blokhin National Medical Research Center of Oncology and the National Center of Oncology and Hematology of the Kyrgyz Republic.

Results. Data on necrobiotic changes, malignancy, stages of the disease and the survival of 14 patients with pure stromal ovarian tumors have been obtained.

Conclusion. The main factors of unfavorable prognosis in patients with ovarian tecoma are tumor necrosis, degree of malignancy and mitotic activity.

297-304 630

Aim: to characterize the function of the reproductive system in women after organ-preserving surgery for uterine myoma: hysteroresectoscopic (HRS) myomectomy and laparoscopic (LS) myomectomy.

Materials and methods. Forty one patients were examined and divided into 2 groups: Group 1 – 18 patients after HRS myomectomy and Group 2 – 23 patients after LS myomectomy. The control group included 20 healthy women of reproductive age.

Results. The HRS operation led to a significant decrease in the production of anti-Mullerian hormone (AMH), estradiol and progesterone, while the levels of luteinizing (LH) and follicle-stimulating (FSH) hormones increased. After myomectomy performed by the laparoscopic access, the levels of estradiol, progesterone, and AMH decreased but the levels of both LH and FSH increased so that the ratio LH/FSH remained unchanged. Almost all indices of gonadotropic and steroid hormone production became normalized over 6 months of the postoperative period.

Conclusion. The main factors of unfavorable prognosis in patients with ovarian tecoma are tumor necrosis, degree of malignancy and mitotic activity.

305-312 580

Aim: to identify new prognostic criteria of potential preeclampsia (PE) in pregnant women after assisted reproductive technologies (ART) for timely PE prophylaxis.

Materials and methods. A prospective study of 85 patients who entered the program of ART was conducted. All patients were examined for possible hemostatic abnormalities (genetic thrombophilia and chronic hypercoagulation) and also for granulocytemacrophage colony-stimulating factor (GM-CSF) in the serum during the most critical periods (4–6, 12–14, 22–24 и and 30–32 weeks) of the fetoplacental complex formation.

Results. The lowest level of GM-CSF was observed in patients with hemostatic disorders. Thus, in pregnant women who later developed PE, there was a decrease in GM-CSF level below the physiological: in those diagnosed with genetic thrombophilia – by 79.4 %, and those with hypercoagulation – by 63.6 %.

Conclusion. The determination of serum GM-CSF and identification of hemostatic abnormalities in pregnant women after ART has a prognostic importance for potential PE. This result is significant for the understanding of the pathogenesis of PE and also has a practical value: it allows the doctor to attribute the patient to a high risk group from the first trimester of her pregnancy and start preventive therapy rather early.

313-325 975

Of significant scientific and practical interest is the relationship between the blood plasma levels of folic acid at preconception and the outcome of pregnancy. A phase III clinical trial on the efficacy and safety of the biosimilar follitropin alfa has recently been completed within the ongoing assisted reproductive technology (ART) programs. The results confirmed the therapeutic equivalence of the investigational agent to the reference drug. In this trial, women with tubal infertility or male factor infertility were included. The study did not include women with endometriosis and polycystic ovary syndrome. A total of 118 patients were recruited; of those, 110 were randomized; then the 110 women underwent hormonal stimulation and 98 of them underwent embryo transfer. Blood samples were taken within a period not exceeding 28 days before the start of the stimulation; the samples were analyzed for folic acid (FA), trace elements and hormones. The results were grouped by quartiles (Q) according to the levels of FA in the blood serum: Q1 – 2.9–10.7 ng/ml, Q2 – 10.8–20.5 ng/ml, Q3 – 20.6–32.9 ng/ml, and Q4 ≥ 33.0 ng/ml. In addition, group distribution was also made according to the WHO recommendations: possible FA deficiency – 3.0–5.9 ng/ml, normal – 6.0–20.0 ng/ml, and elevated levels – more than 20 ng/ml. A significant decrease in the number of fertilized oocytes, clinical pregnancies and live births in Q4 (increased FA) compared with Q1 was found. Also, in women with high levels of FA, the number of aspirated oocytes was significantly lower than that in women with normal or decreased FA levels. We also found a significant inverse relationship between the number of aspirated oocytes and the levels of estradiol and serum FA. Plasma FA levels > 20 ng/ml detected prior to the IVF procedure may be associated with a low number of aspirated oocytes, and FA levels > 33 ng/ml – with a reduced number of fertilized oocytes, clinical pregnancies and live births. Thus, the excessive content of FA in the body can contribute to a worse outcome of IVF programs.


326-336 1329

This review addresses the concept of ontogenetic origin of health and disease (DOHaD) and the new concept of paternal origin of health and disease (POHaD). These concepts are based on scientific evidence that environmental factors impacting mother or father can play a role in reprogramming the health of their off springs throughout their life span. Moreover, the changes that have arisen can be transmitted through generations via diverse epigenetic mechanisms. Terms, such as epigenetics (a kind of “driver” for these concepts), epigenetic inheritance (including Intergenerational Inheritance – from generation to the next generation and Transgenerational Inheritance – through generations), epigenetic changes caused by the environment (Environmental Epigenetics) are discussed. Vulnerable periods towards epigenetic changes (Windows of Susceptibility) that occur in male germ cells responsible for epigenetic inheritance are considered. Epigenetic epidemiological studies in the field of reproductology are described; their advantages and disadvantages are discussed. These studies can serve as the basis for obtaining new knowledge about the causes of epigenetic variations in germ cells that occur in health and upon exposure to environmental factors as well as the inherited phenotypic outcomes.

337-344 2423

Introduction. Maintaining women's reproductive health is an important task that requires safe approaches based on the pathogenesis. More and more studies address the role of the pineal gland (epiphysis) hormone melatonin (МТ) in the functioning of the reproductive system, as well as the impact of МТ deficiency on the women’s health.

Aim: to analyze and summarize the available literature about the role of the pineal gland hormone МТ in the pathogenesis of gynecological diseases in women of reproductive age (infertility, endometriosis, polycystic ovary syndrome, premenstrual syndrome), and also about the impact of МТ deficiency on the health of women working night shifts.

Materials and methods. The relevant publications were searched in domestic (eLibrary, and international (Pubmed, Cochrane Library) databases; we looked up the materials published in the recent 7 years. In our search, we prioritized the free access to full text articles. The selection of sources was limited to the period from 2012 to 2019.

Results. МТ is involved in the development of follicles by causing the oocytes maturation, promoting the development of embryos, inhibiting the synthesis of steroids in the ovaries and, therefore, reducing the level of steroids in the blood. MT delays ovarian aging through a variety of mechanisms, including the antioxidant action, the maintenance of the due length of the telomere, the upregulated expression of the aging-related SIRT genes, and also the regulation of the ribosome functioning. As MT protects germ cells from oxidative stress, it is essential for normal ovulation, fertilization and further development of the embryo; this hormone has an impact on the duration of the woman's fertility and the onset of menopause. MT has a potential therapeutic effect on endometriosis. The oncostatic role of MT in hormone-dependent breast tumors has been described. Disruption of normal MT production during night shifts is associated with the risk of developing breast cancer in shift workers. MT deficiency leads to circadian desynchronosis and may cause both somatic disorders (metabolic syndrome, obesity, oncopathology) and neuroendocrine dysregulation of the female reproductive system.

Conclusion. The variety of physiological functions of the pineal gland hormone MT emphasizes the pathogenetic role of its deficiency in many gynecological and somatic diseases. Of particular relevance is the increased risk of cardiovascular disorders, the development of metabolic syndrome and breast cancer in women who work night shifts. Therefore, it is important both to maintain normal endogenous level of MT and also use its therapeutic potential to maintain the health of women of reproductive age.

345-353 14849

This article reviews the studies published over the recent 10 years about diagnostic imaging of ovarian lesions (OL). We discuss the current classification systems considering the imaging criteria and the risks of malignancy as well as the ways of optimizing the treatment of patients. There are a number of methods of evaluation and interpretation of diagnostic data obtained using ultrasound as a first line method for OL visualization. To report the results, there is a unified terminology system O-RADS (Ovarian-Adnexal Reporting and Data System) developed specifically for ultrasound examinations. In 2013, the ADNEX MR (adnexal lesions magnetic resonance imaging) scoring system (AMRSS) was developed to standardize magnetic resonance data. That system combines the analysis of both basic-anatomical and functional MR-images and allows one to classify ovarian tumors by the risk of malignancy. Although O-RADS and AMRSS are based on different diagnostic modalities, they complement each other for the diagnostic purpose. In this review, we analyze correlations between the results obtained with these two methods; we also address the possibility of using the above methods in combination in order to pursue a more comprehensive approach to diagnosis of ovarian cancer.

354-368 1543

Aim: to systematize scientific data on the frequency and pathogenesis of retrochorial and retroroamniotic hematomas in early pregnancy, including the recently published data.

Materials and methods. We used sources from the electronic databases PubMed, Embase, eLibrary and articles in peerreviewed open access journals. The search was conducted using the keywords in Russian and English: retrochorial hematoma, retrochorial hemorrhage, subamniotic hematoma, pregnancy outcomes in subamniotic haematoma, pregnancy outcomes in subchorial haematoma, angiogenesis, embryogenesis, placentogenesis. The analysis included sources from the recent 30 years. We excluded publications on multiple pregnancies, ectopic pregnancy, and other sources that did not focus on the pathogenesis of chorionic detachment.

Results. The following factors play a role in the occurrence of chorionic detachment: intrauterine malformations, bacterial/viral infection, chronic endometritis, immunological factors, maternal coagulation disorders (hemorrhagic diathesis, genetic thrombophilia, antiphospholipid syndrome, chronic forms of DIC), severe arterial hypertension, and habitual miscarriages.

Conclusion. Knowledge of the pathogenetic mechanisms of chorionic detachment is necessary for a differential diagnosis and subsequent successful preservation of pregnancy.


369-383 1066

Introduction. Most pelvic tumors originate from reproductive organs. Even using the up-to-date imaging techniques, radiologists experience difficulties in determining the source of the lesion since a wide range of tumors look similar to each other on the distorted backdrop of pelvic anatomy, large invasive formations, and an active inflammatory reaction of the pelvic peritoneum.

Aim: to evaluate “pitfalls” in the preoperative noninvasive diagnosis of female pelvic tumors by applying the clinical diagnostic tools.

Materials and methods. Four rare clinical cases were analyzed; all of them posed difficulties in interpreting the diagnostic examination due to their atypical characteristics. There were 2 cases of ovarian cancer, initially identified by an experienced team of radiologists as benign pelvic pathology. Also, there were fibroids with degeneration, marked proliferative activity, and a massive inflammatory reaction of the peritoneum – that was diagnosed as a malignant ovarian tumor. Tumor biopsies were examined using morphological and immunohistochemical methods (with the р16, Ki-67, p53, CD 117, S 100, CD 34 markers). Immunohistochemical (IHC) studies were performed with formalin-fixed paraffin materials using the avidin-biotin-peroxidase method. Antibodies to estrogen receptor (ER), progesterone receptor (PR), cytokeratin 7 (CK7), cytokeratin 20 (CK20) and Wilms tumor protein 1 (WT1) were also used.

Results. A thorough analysis of the clinical picture and a joint multidisciplinary discussion (gynecologist, oncologist, radiologist, etc.) made it possible to avoid diagnostic errors.

Conclusion. These observations demonstrate the difficulties of differential diagnosis between ovarian metastases of uterine cancer and primary multiple ovarian and uterine cancer, as well between leiomyosarcoma and uterine myoma with high mitotic activity. Obviously, the change in diagnosis calls for a change in the treatment strategy.


384-387 925

Professor Gustav Adolf Michaelis was an outstanding German obstetrician-gynecologist, one of the founders of scientific obstetrics. He gained worldwide recognition for his studies on the “sacral rhombus”, named after him the “rhombus of Michaelis”. Dr. Michaelis was an honest, hardworking and rather critical person, so in 1847, he did not instantly accept the ideas of Ignaz Philipp Semmelweis’s on “preventing puerperal fever”. Only in 1848, Michaelis introduced the compulsory chlorine hand washing in his clinic and made sure that mortality had dropped significantly. He was very depressed when he realized how many women (including his beloved niece) died from postpartum fever due to unsanitary obstetric practices. On August 8, 1848, Gustav Adolf Michaelis committed suicide.



ISSN 2313-7347 (Print)
ISSN 2500-3194 (Online)