Vol 72, No 4 (2023)

BACKGROUND: Recurrent pregnancy loss is a serious clinical problem that complicates about 2% of pregnancies. There is evidence that thrombophilia and disorders of folate-methionine metabolism may cause recurrent pregnancy loss.

AIM: The aim of this study was to evaluate the contribution of polymorphic variants of the genes of the hemostasis system and the folate-methionine cycle in women with recurrent pregnancy loss.

MATERIALS AND METHODS: Clinical examination of 406 pregnant women divided into two study groups was carried out. The main study group consisted of 206 women with two or more pregnancy losses known up to 12 weeks of pregnancy; the control group included 200 apparently healthy women with a known history of two or more live births, no spontaneous or induced abortions, infertility, or endometriosis. All patients underwent a molecular genetic study of 12 single nucleotide polymorphisms in the genes of the hemostasis system and the folate-methionine cycle performed by real-time polymerase chain reaction.

RESULTS: We studied single nucleotide polymorphisms in eight genes involved in the hemostasis system and in four genes of the folate-methionine cycle. An association of presence of alternative variants such as 1565C (rs5918) of the ITGB3 integrin beta-3 gene and A66G (rs1801394) of the MTRR methionine synthase reductase gene with the development of recurrent pregnancy loss was found. The frequency of their occurrence was 29.1 and 77.7% in the recurrent pregnancy loss group vs. 12.0 and 49.0% in the control group, respectively (p < 0.01). The combined carriage of the alternative variants 1565C (rs5918) of the ITGB3 gene and A66G (rs1801394) of the MTRR gene in the recurrent pregnancy loss group was diagnosed more often than in the control group and amounted to 47 (22.8%) vs. 12 (6.0%) cases (φ = 5.047; p < 0.01; odds ratio 3.631; 95% confidence interval 2.374–9.034). We have thus developed a three-locus model of the synergetic action of allelic variants of the above genes in the development of recurrent pregnancy loss in early pregnancy [10976 G>A (rs6046) of the F7, −455 G>A (rs1800790) of the FGB, 1565 T>C (rs5918) of the ITGB3] with reproducibility of 8/10, sensitivity of 65.6%, and specificity of 68.8% (χ² = 15.7415, p < 0.0001; odds ratio 3.341, 95% confidence interval 1.824–6.118).

CONCLUSIONS: This study allows for confirming the hypothesis that the status of genetic variants of the ITGB3 and MTRR genes and the association of three single nucleotide polymorphisms: rs6046 of the F7, rs1800790 of the FGB, and rs5918 of the ITGB3 may be used as predictors of recurrent pregnancy loss development.

BACKGROUND: Type 1 diabetes mellitus and genital endometriosis have a negative impact on female reproductive system. There is an opinion that kisspeptin plays an important role in the pathogenesis of ovarian insufficiency in patients with diabetes and endometriosis.

AIM: The aim of this study was to evaluate the role of the kisspeptin gene (KISS1) polymorphism in the pathogenesis of ovarian insufficiency in patients with type 1 diabetes mellitus, genital endometriosis and in women with combination of these diseases.

MATERIALS AND METHODS: The allele and genotype frequencies of the polymorphic variants rs5780218 (c.–145delT) and rs3924587 (c.–89G>A) of the KISS1 gene were evaluated in 258 women using polymerase chain reaction-restriction fragment length polymorphism technique. This study included 73 patients with type 1 diabetes mellitus, 83 patients with genital endometriosis, 35 patients with combination of type 1 diabetes mellitus and genital endometriosis, and 67 control subjects. The control group is represented by women of the population.

RESULTS: The analysis of the KISS1 gene showed that incidence rates of type 1 diabetes mellitus, genital endometriosis and combination of these diseases do not differ in the presence of the ins/del, del/del, and ins/ins (rs5780218) genotypes. Thus, the del allele and the ins/del and del/del genotypes are not associated with an increased risk of these diseases. It was found that in patients with type 1 diabetes mellitus, the frequency of normogonadotropic ovarian insufficiency was higher (odds ratio 15.955; 95% confidence interval 4,47–57,0; p < 0.05) in the presence of the G/A genotype according to the polymorphic variant rs3924587 compared to the G/G genotype.

CONCLUSIONS: The data obtained allow for explaining the high incidence of ovarian insufficiency in women with type 1 diabetes mellitus. In patients with type 1 diabetes mellitus with the G/A genotype who are planning pregnancy, even in case of regular menstrual cycle, it is advisable to perform hormone blood tests in dynamics for timely diagnosis of ovarian insufficiency and prescription of hormonal therapy.

BACKGROUND: Sufficient endometrial blood supply in the mid-secretory phase of the menstrual cycle is a key to a successful pregnancy achievement, and a decreased spiral artery blood flow resistance determined by the Doppler is known to be positively associated with successful in vitro fertilization outcome. Particular aspects of endometrial blood flow in women with uterine fibroids might affect the efficiency of in vitro fertilization and intra cytoplasmic sperm injection cycles.

AIM: The aim of this study was Doppler-based determination of the uterine and spiral artery blood flow resistance in women with uterine fibroids throughout controlled ovarian stimulation in in vitro fertilization cycles, depending on the clinical pregnancy rate.

MATERIALS AND METHODS: Doppler ultrasound spiral artery blood flow evaluation was performed in 83 women throughout the in vitro fertilization cycle. Intramural uterine fibroids were detected in 44 women, and 39 women with no uterine fibroids comprised the comparison group. All women underwent a Doppler study of spiral artery blood flow on the second or third day of the menstrual cycle (at the start of the in vitro fertilization protocol) and on the day of embryo transfer. The in vitro fertilization efficiency was determined by the onset of clinical pregnancy after visualizing the gestational sac in the uterine cavity during ultrasound examination on the 20–25th day after embryo transfer.

RESULTS: The values of the uterine and spiral artery blood flow resistance in the uterine fibroids group were determined to be significantly lower than those in the comparison group. Considering the identified influence of decreased spiral artery blood flow resistance on the results of in vitro fertilization cycles in the comparison group, we have analyzed the dependence of the efficiency of the cycles based on the rate of the spiral artery blood flow resistance decline. Thus, a significantly more reliable decline in the pulsatility index was revealed in pregnant women from the comparison group throughout the in vitro fertilization cycle compared to women with negative results. In women with uterine fibroids, the pulsatility index decline did not differ depending on the onset of pregnancy, and the decline rate differed significantly from that in the comparison group.

CONCLUSIONS: Uterine fibroids are associated with a stable decline in the uterine and spiral artery blood flow resistance. This leads in turn to increased endometrial vascularization throughout the stimulation cycle in in vitro fertilization programs and negatively affects the blastocyst implantation ability.

Overcoming the problem of miscarriage still remains relevant today. Its' significant contribution to the structure of premature birth is due to the invasion of conditionally pathogenic microflora from the lower parts of the genital tract into the amniotic cavity. It can thus trigger an inflammatory reaction, causing early termination of pregnancy. The microbiota of the genital tract is characterized by the least diversity and high stability over time compared to any other location of the body. The dominance of certain types of lactobacilli in the vaginal biotope may be a marker of well-being, or a harbinger of termination of pregnancy. The aim of this review article is to summarize the current understanding of the vaginal microbiota during pregnancy in order to determine the relationship between its composition and stability throughout pregnancy, as well as the risk of early termination of pregnancy.

To date, there is no doubt that taking folic acid at the perigravid stage in an adequate dosage has a positive effect on fetal development and the course and outcome of pregnancy. There is extensive evidence that during pregnancy, folate deficiency is associated with spontaneous miscarriages, premature birth, and premature detachment of the normally positioned placenta, and it can cause intrauterine malformations of the nervous and cardiovascular systems of the fetus.

Understanding the need to reduce such severe complications, which have both medical and social significance, has contributed in a number of countries to the introduction of programs for food fortification and routine prescribing of folic acid preparations to pregnant women. The measures taken significantly reduced the incidence of fetal congenital malformations, but at the same time, this strategy had a negative effect, resulting in a chronic overdose of synthetic folic acid. Recent studies have shown that the accumulation of non-metabolized folic acid in a pregnant woman may be associated with obstetric pathology and impaired development of fetuses and newborns. There is growing evidence that prolonged folic acid overdose during pregnancy, especially in the presence of altered levels of other vitamins, may lead to such diseases in children as autism and multiple amyotrophic sclerosis. Thus, this issue requires in-depth study in order to move from the routine prescription of folic acid preparations to personalized nutritional support for women at the preconception stage and during pregnancy.

This article describes a clinical case of managing pregnant women with ovarian cysts in the fetus and further monitoring and treatment of the child. Ovarian cysts are the most common abdominal abnormalities diagnosed in female fetuses. We herein discuss the tactics in relation to the female fetus, intrauterine risks and prognosis of her survival in this pathology, as well as the possibility of choosing a method for correcting ovarian cysts in the fetus and their complications during pregnancy and after childbirth. In the case of complex and / or large ovarian cysts, timely prenatal diagnosis is extremely important, which significantly improves the prognosis and allows prenatal measures aimed at stabilizing the condition of the fetus and the pregnant woman. On the example of this clinical case, we assessed the possibility of preserving the unchanged ovarian tissue and reducing the risks of life-threatening complications in the case of a significant amount of cystic formation. This article describes in detail the stages of the management of pregnancy, childbirth and the neonatal period, as well as the therapeutic and surgical correction of this severe pathology with further early rehabilitation.