Obstetrics, Gynecology and Reproduction

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Vol 15, No 1 (2021)

Original articles 

5-21 1692

Introduction. The efficacy and safety of biosimilar follitropin alpha have been demonstrated in randomized blinded prospective clinical trials of phases I and III. Unfortunately, there is a gap between the clinical trials and real clinical practice data. The real-world patient data helps to create an evidence-based background for successful implementation of medicine at everyday practice in a nonselected population.
Aim: to investigate the efficacy of follitropin alpha biosimilar therapy (Primapur®) in nonselected real-world population.
Materials and Methods. A retrospective observational anonymized cohort study of follitropin alpha biosimilar (Primapur®) as a pre-filled pen injector with a dose adjustment of 5 IU, aimed to investigate its efficacy and safety in a nonselected population with indications to assisted reproductive technologies (ART) was carried out. The ovarian stimulation (OS) protocols included: monotherapy protocols with using only Primapur®; mixed protocols (recombinant and urinary-derived gonadotropins); short protocols with using antagonists of gonadotropin-releasing hormone (GnRH) and long protocols with GnRH agonists. The stimulation protocols were analyzed with Primapur® application for at least 5 days.
Results. The overall clinical efficacy of ovarian stimulation cycles (N = 5484) was: oocytes retrieved - 9.5 ± 7.2, mature (MII) - 6.8 ± 6.6, fertilized (2PN) - 6.1 ± 5.8, clinical pregnancy per ET (PR) - 38.4 %. Mixed gonadotropin protocols (N = 2625) vs. monotherapy with Primapur® (N = 2859): oocytes retrieved - 8.6 ± 6.8 vs. 10.3 ± 7.4 (p < 0.001), mature (MII) - 6.7 ± 6.2 vs. 7.7 ± 6.9 (p < 0.001), fertilized (2PN) - 5.8 ± 5.2 vs. 7.2 ± 6.2 (p < 0.001). There were statistically significant differences between oocyte yields in mixed vs. monotherapy protocols due to subgroup differences, including age, body mass index (BMI) and IVF/ICSI attempts. No statistically significant differences were found for PR: 39.3 % vs. 37.6 % (p = 0.314). Monotherapy protocols with GnRH antagonist OS (N = 2183) vs. GnRH agonist (N = 676) revealed: oocytes retrieved - 10.5 ± 7.5 vs. 9.6 ± 7.0 (p = 0.032), mature (MII) - 7.6 ± 6.9 vs. 6.7 ± 5.7 (p < 0.001), fertilized (2PN) - 7.3 ± 6.3 vs. 5.7 ± 5.0 (p < 0.001). There were statistically significant differences between BMI and IVF/ICSI attempts. No statistically significant differences were found for PR: 37.9 % vs. 35.9 % (p = 0.482). All medicines were well tolerated and no serious adverse reactions were reported.
Conclusion. This was the largest retrospective observational study conducted in the field of fertility in Russia and involved 5484 ovarian stimulation protocols at 35 IVF clinics. The obtained results demonstrated similar clinical efficacy for follitropin alpha biosimilar Primapur® in different OS protocols in real clinical practice.


22-31 472

Aim: to evaluate efficacy of plasmapheresis combined with low molecular weight heparins (LMWH) and acetylsalicylic acid (ASA).

Materials and Methods. 327 plasmapheresis sessions were performed for 75 patients: 17 (22.6 %) patients during preparation for pregnancy, 11 (19.0 %) pregnant women in the first trimester, 33 (56.9 %) pregnant women in the second trimester, and 34 (58.6 %) pregnant women in the third trimester. Study inclusion criteria were as follows: high titers of antiphospholipid antibodies (APA) as well as included non-inclusion criteria in pregnant women with miscarriages and unfavorable anamnestic pregnancy outcome. 36 (62.1 %) women had pregnancy loss in anamnesis. All patients received low-dose ASA and LMWH therapy; 15 (25.86 %) pregnant women also received courses of intravenous immunoglobulins in the first and second trimesters.
Results. 47 pregnant women had delivery, whereas 10 of women had pregnancy in progress. Term delivery was in 40 (85.1 %) patients, so that 23 (48.9 %) pregnant women had delivery per vias naturales. The average weight of the fetus was 3364.00 ± 393.76 g, height - 52.13 ± 1.82 cm. In 100 % cases, Apgar score was 8 points. 24 (51.1%) pregnant women had delivery via cesarean section. The average blood loss comprised 528.64 ± 166.10 ml. The average fetal weight in group after surgical delivery was 2982.14 ± 582.88 g, average height - 49.14 ± 4.09 cm, the Apgar score - 7.69 ± 0.47 points. Preterm births were observed in 7 (14.9%) cases, all via cesarean section. In 1 case, early fetal death was at gestational age of 8/9 weeks; according to the karyotyping data, a fetal chromosomal abnormality was detected. No severe obstetric complications were observed.
Conclusions. Combining plasmapheresis with low dose LMWH and ASA therapy demonstrated high efficacy in treating obstetric APS manifested as high percentage of favorable pregnancy outcomes and low number of obstetric complications.


32-40 378

Introduction. Despite a long history of the disease, genital prolapse still have not been definitively solved. A relevance of pelvic organ prolapse in women has been increasing in recent years largely due to a change in the quality of life and desire to sustain their youth. The number of studies pinpointing the cause of the disease in connective tissue dysplasia (CTD) has been increasing annually.
Aim: to conduct a systematic analysis and determine most common signs of CTD in women with genital prolapse.
Materials and methods. CTD criteria and the relationship with genital prolapse were analyzed. The study was conducted using questionnaires and including clinical studies examining residents of the Belgorod region (135 women). The main group included 91 patients who had signs of pelvic organ prolapse, and control group consisted of 44 healthy women. CTD intensity score proposed by T.Yu. Smolnova et al. (2003) was used to assess signs of dysplasia in women examined allowing to build up three groups in which each symptom was evaluated as severity score.
Results. Asthenic constitution was noted in high percentage of women suffering from genital prolapse (16.70 ± 0.38 %) compared with healthy women (2.30 ± 0.15 %; p = 0.016). Mild bruising, increased tissue bleeding tended to rise in main vs. control group (16.50 ± 0.37 % in main group and 0.0 in control group; p = 0.016). Signs of varicose veins and hemorrhoids requiring no surgical treatment were found in 33.00 ± 0.47 % and 4.50 ± 0.21 % in main vs. control group (p = 0.0002), respectively. Genital prolapse and hernia in first-line relatives were recorded in 9.90 ± 0.30 % in main group (p = 0.031), women without signs of prolapse did not indicate prolapse in close relatives.
Conclusion. Asthenic constitution, hernias, varicose veins and hemorrhoids, female pelvic and hernial prolapse in close female relatives, a tendency to mild bruising, skeletal anomalies, elastosis skin were among common CTD signs in women with genital prolapse.

41-50 357

Aim: to study a role of undifferentiated connective tissue dysplasia (uCTD) in etiology of cervical incompetence and its effect on pregnancy and childbirth course.
Material and Methods. There were enrolled 60 patients with cervical incompetence. Patients were divided into 3 groups according to the modified CTD scale: group 1 - patients without uCTD (n = 21); group 2 - patients with mild uCTD (n = 25); group 3 - patients with moderate-to-severe uCTD (n = 14). Intensity of CTD clinical signs was assessed based on health status, gynecological and obstetric history, the course of pregnancy, labor and the postpartum period.
Results. It was found that patients with more prominent CTD developed earlier (r-Spearman = -0.26) and more marked (r-Spearman = -0.29) cervical shortening and opening of the internal orifice of the uterus (r-Spearman = 0.28). It was also noted that likelihood of occurring preterm labor was significantly higher in patients with CTD (p = 0.02).
Conclusion. The data obtained evidence that uCTD affects intensity of manifested cervical insufficiency and rate of preterm delivery.

51-60 299

Introduction. Multifetal pregnancy is associated with an increased risk of perinatal morbidity and mortality. Type of placentation and discordant fetal growth may be risk factors of adverse pregnancy outcomes.
Aim: to compare an impact of dichorionic and monochorionic twin pregnancies with symmetric and discordant fetal growth on perinatal outcomes, as well as morbidity and mortality.
Materials and Methods. There was conducted a retrospective study of 485 pregnant women and paired 959 newborns. Depending on the type of chorionicity, subjects were stratified into two study groups being further subdivided into based on describing fetal weight discordance. The antenatal period and the neonatal outcome of newborns in groups and subgroups were compared.
Results. We analyzed 308 dichorionic and 177 monochorionic twin pregnancies. It was found that neonate discordant growth was observed in 5.4 % and 13.4 % (p < 0.001), respectively. The incidence of assisted reproductive technologies was higher in dichorionic than in monochorionic twins comprising 66.5 and 40.7 % (р < 0.001). Antenatal mortality in monochorionic vs. dichorionic twins was by 8-fold higher. The preterm birth rate in monochorionic vs. dichorionic twins was 74.6 and 62.7% (p = 0.009), respectively. Neonate body weight in monochorionic vs. dichorionic twins was lowered comprising 1991 and 2430 gr. (р < 0.001), respectively. Low Apgar scores were more common for monochorionic twins with discordant body weight. The rate of early neonatal mortality in monochorionic vs. dichorionic twins was 4.4 % vs. 1.5 % (p = 0.009), whereas in dichorionic vs. monochorionic twins with weight discordance it was up to 5.8 and 10.5% (р < 0.001), respectively.
Conclusion. Monochorionic twin pregnancy complicated with growth discordance is associated with a higher risk of adverse antenatal period as well as neonatal morbidity and mortality compared to symmetric DCDA twins. Chorionicity and growth discordancy represent important predictors for outcome of twin pregnancy.

61-69 345

Aim: to assess peripheral blood NK cell (pNK) counts in women with recurrent pregnancy loss.
Materials and Methods. There were examined 102 women: 28 non-pregnant (immediately after repeatedly terminated pregnancy, group IA) and 34 pregnant women with history of previous recurrent pregnancy loss (group IB). Control and comparison groups were consisted of healthy women lacking any recorded miscarriage: 20 non-pregnant (group IIA) and 20 pregnant women (group IIB), respectively. Along with assessing complete blood count range, all subjects were analyzed percentage of pNK cell CD16bright(+) CD56dim(-) cytotoxic phenotype by using fluorescence microscopy as well as level of cytokines IL-2, IL-6, IL-10, tumor necrosis factor (TNF-α), vascular endothelial growth factor (VEGF) and interferon-gamma (IFN-γ) using ELISA.
Results. It was found that the level of NK cell cytotoxic phenotype - percentage of CD16+CD56- was elevated in both groups: groups: group IA - 36.5 % collared with the control group IIA - 27.5% (р < 0.05); in group IB up to 37.0 %, in comparison group IIB - 27.4% (р < 0.01). It was further corroborated by increased level of serum cytokine IL-6 IL-6 comprising in group IA vs. IIA - 28.5 pg/ml vs. 14.2 pg/ml (р < 0.01) as well as in group IB vs. IIB up to 16.7 pg/ml vs. 12.2 pg/ml (р < 0.01), respectively. However, level of serum IL-2 and IL-10 did not significantly differ in all groups examined. Interestingly, level of VEGF in subjects aged 21-30 years was elevated: in non-pregnant (group IA) vs. control (group IIA) - up to 548.5 pg/ml vs. 310.8 pg/ml (р < 0.01); pregnant women (IB) vs. comparison group (IIB) - insignificantly elevated up to 476.1 pg/ml vs. 381.5 pg/ml, respectively. In contrast, no significant changes were observed in 31-40-year group. Concentration of IFN-γ in group IA vs. control group (IIA) was increased up to 9.2 pg/ml vs.8.64 pg/ml; group IB vs. comparison group - up to 8.36 pg/ml vs. 7.56 pg/ml, respectively.
Conclusion. Elevated percentage of cytotoxic CD16+CD56- NK cells in peripheral blood results in imbalance of immune-related parameters that directly correlated with increased serum level of IL-2, IL-6, TNF-α that may alter maternal immune tolerance to the fetus and subsequently resulting in recurrent pregnancy loss. Hence, the aforementioned data may be used as diagnostic and prognostic criteria in recurrent pregnancy losses.


70-79 879

Aim: to systematize the data on rehabilitation methods and management tactics for women with external form of genital endometriosis.
Materials and Methods. We searched for publications in the international scientific databases: scientific electronic library eLibrary, Scholar, ScienceDirect, Cochrane Library, PubMed/MEDLINE released for the last 5 years. The data on the current approach to the therapy and rehabilitation of women with external genital endometriosis are presented in the study. Search queries in Russian and English were used as follows: «endometriosis», «rehabilitation», «gynecology», «quality of life».
Results. Endometriosis is considered an independent risk factor for the development of malignant tumors not only targeting the reproductive system, but also affecting large intestine, bladder, and mammary glands. Moreover, such patients often suffer from emotional and psychosexual disorders as well as impaired socialization. Special attention should be paid to diagnostics of disease relapses to avoid potential malignant transformation of endometrioid tissue. We also provide a current view on the treatment and rehabilitation of women with external genital endometriosis. Endometriosis is a polyetiological disease that can be manifested as dysmenorrhea, dyspareunia, chronic pelvic pain, as well as dysuria and dyschesia upon affecting adjacent organs in the pathological process. Finally, we provide insights into potential therapeutic approaches for solving such manifestations.
Conclusion. It is necessary not only to conduct a combination treatment, but also develop personalized rehabilitation programs allowing to improve the quality of patient life as well as create comfortable conditions for social adaptation of women with endometriosis.

80-92 547

Aim: to summarize up-to-date world data on current opportunities of drug therapy in treatment of symptomatic myoma accompanied with heavy menstrual bleeding and anemia.
Materials and Methods. A search of publications was carried out in the main international databases published in Russian and English: PubMed/MEDLINE, The Cochrane Library, Embase, and eLibrary. The analysis included studies published over the last 10 years examining the clinical efficacy and safety of various groups of pharmacological agents used for treatment of uterine myoma combined with heavy menstrual bleeding in women of reproductive age.
Results. Currently, treatment of uterine fibroids consists of the three major approaches: surgical, minimally invasive organpreserving methods, and pharmacotherapy. Until now, surgical intervention remains the main method of treatment, unfortunately being often performed in a foem of hysterectomy. However, today it is important to apply a personalized approach to the management of a female patient with symptomatic uterine myoma, taking into account her wish to preserve reproductive function. Advances in drug therapy greatly contributed to optimizing management of such patients.
Conclusion. Treatment of symptomatic uterine fibroids globally tends to lowering the number of radical interventions, as well as develop and improve new therapeutic approaches for. Currently, pharmacotherapy of leiomyoma can substantially improve the quality of patients' life, lower number of radical surgical interventions, optimize surgical treatment, and even fully negate, in some cases, a need for surgery.

93-106 505

ADAMTS-13 is a crucial metalloproteinase involved in liberating fragments of von Willebrand factor (vWF) into the plasma as well as regulating its activity by cleaving "ultra-large" multimers into smaller and less active counterparts. Many pathological conditions, including those emerged during pregnancy are characterized by increased level of vWF and decreased ADAMTS-13 activity. In this regard, it is necessary to monitor the levels of vWF and ADAMTS-13 activity to prevent thrombotic thrombocytopenic purpura (Moschcowitz disease) as one of the most severe forms of thrombotic microangiopathy.



107-116 285

Neutrophil Extracellular Traps (NETs) represent the networks consisting of DNA, histones, and proteins produced by activated neutrophils. Such structures have been proved to play a crucial role in inducing neutrophil innate immune response in the pathogenesis of such autoimmune conditions as systemic lupus erythematosus, rheumatoid arthritis, psoriasis, as well as in the pathogenesis of other non-infectious processes, e. g., clotting disorders, thrombosis, diabetes, atherosclerosis, vasculitis and oncology diseases. Recent studies on animal models and human pathologies have uncovered a tremendous role for NETs in tumor progression and metastasis. In this regard, NETs should be considered as pro-oncogenic substances, which further investigation will provide an opportunity to develop new therapeutic strategies.

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