No 4-2 (2012)

Sleep apnea is a common, but often unrecognized condition that may have serious negative health consequences for women of childbearing age. Recently, there has been an increase in the number of investigations for sleep apnea syndrome in pregnant women. The review presents the past 10-year data on the impact of sleep apnea on the occurrence of complications, such as preeclampsia and placental insufficiency, and the possibility of performing pathogenetic treatment.

Our previous studies revealed the essential role of local inflammation and neoangiogenic processes in the pathogenesis of uterine scar incompetence after prior cesarean section. Objective. To study associations between the basic morphological signs of uterine scar incompetence and cytokine gene polymorphism. Subjects and methods. The study encompassed 160 patients aged 18 to 45 years with a uterine scar after cesarean section. During repeat cesarean section, the scar was excised and the tissues of the scar and adjacent myometrium were histologically studied. All the patients were divided into 2 groups according to the results of a morphological study of myometrial biopsy specimens: 1) 80 patients with defective scars (DS) of the uterus and 2) 80 with its adequate scars. The polymorphism of the IL-6 (-174 C>G) and IL-10 (-819 C>T and -592 C>A) genes was determined. Results. The morphological study of scar tissue showed that the signs of inflammation and neoangiogenesis had the maximum sensitivity with a high specificity in detecting DS. At the same time, the presence of hematoma or signs of disorganization, by having a high specificity, may be used only as a confirmatory test due to its insufficient sensitivity. A study of the distribution of IL-6 alleles and genotypes revealed no significant associations with the status of a scar. An analysis of IL-10 haplotype (-819 C>T and-592 C>A) revealed that in the presence of inflammation, the genotypic frequency of the TA allele was 39 versus 17% in the absence of inflammation (OR=3.02 (1.25—7.29), р=0.01). Scar tissue neoangiogenesis was also more common in carriers of the TA allele (OR=2.55 (1.0— 6.50), p=0.05). Conclusion. The allelic variants of the IL-10 gene were shown to be associated with the formation of DS of the uterus after cesarean section.

Objective. To define the role of MBL2 codon 34 polymorphism in the development of gestosis. Subjects and method. A study group included 78 patients with gestosis and 77 women with physiological pregnancy formed a control group. The diagnosis of gestosis was made according to the Goecke scale modified by G.M. Savelyeva. MBL2 codon 34 polymorphism was analyzed using polymerase chain reaction/restriction. Results. In our study, homozygotes for allele A were significantly less common in the women with gestosis than those in the controls (59 and 76.6%, respectively;p=0.0252). The variant allele was associated with the development of gestosis (26.9 and 15.6 % in the study and control groups, respectively; p=0.0181), which was also confirmed by comparing the frequency of hetero- and homozygous variant alleles (AB+BB) in the women with gestosis and in the control group (41 and 23.4%, respectively, p=0.00252). Conclusion: The maternal carriage of the mutant MBL allele may lead to reduced MBL levels and hence to inadequate utilization of trophoblast fragments, to increased tumor necrosis factor production, by giving rise to a systemic inflammatory response and endothelial dysfunction.

Objective. To reveal, on the basis of hemogram, hemostasiogram, and thromboelastogram readings, the pattern of anemia, thrombocytopenia, and hemocoagulation disorders in HIV-infected pregnant women receiving chemopreventive agents and to define ways of their correction. Subjects and methods. In the period December 2009 to November 2011, a prospective controlled clinical trial covering 162 pregnant women with V.I. Pokrovsky Classification Stage III HIV infection was conducted at the Interdistrict Perinatal Center, Clinical Hospital Five, Togliatti. The findings were statistically processed and analyzed at the Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia. Results and discussion. The authors’ laboratory data suggest that the HIV-infected pregnant women receiving chemopreventive agents have macrocytic anemia. The synthesis of red blood cells and hemoglobin is impaired due to suppressed erythropoiesis, as confirmed by the morphological pattern of red blood cells. The significant increase in the count of red blood cells and hemoglobin in the HIV-infected patients points to the positive impact of preoperative preparation. Preoperative specific therapy leads to a significant reduction in activated partial thromboplastin time, international normalized ratio, prothrombin time, and D-dimer and to an increase in spontaneous euglobulin lysis time and fibrogen levels, which is indicative of the normalization of the hemostatic system and the adequacy of chosen treatment policy. The significantly low coagulation indices lead to the conclusion that the HIV-infected pregnant women show a propensity to have hypocoagulation shifts due to the use of antiretroviral drugs. Conclusion. Both the data available in the literature and the authors’ observations suggest that the administration of antiviral agents causes certain changes in the homeostatic system, by most commonly inducing anemia, thrombocytopenia, and hypocoagulation shifts. Impaired erythropoiesis is a cause of anemia. The development of coagulopathy is associated with hepatic synthetic dysfunction and decreased formation of clotting factors. The authors’ preoperative goal-oriented preparation of HIV-infected pregnant women assists in leveling the occurred changes. Prednisolone therapy caused no significant increase in the count of platelets; consequently, it is necessary to have alternative ways of correcting these disorders. The performed studies underline the need for further investigations of the problem and the appropriateness of choosing alternative chemopreventive regimens.

Objective. To optimize an in vitro fertilization and embryo transfer (IVF and ET) program for patients at high risk for ovarian hyperstimulation syndrome (OHSS), by using a modified mild superovulation induction protocol. Subjects and methods. One hundred and forty-six married couples of reproductive age, who needed an IVF program, were examined. Group 1 (a study group) consisted of 75 patients who had a mild superovulation induction regimen on day 5 of their menstrual cycle (MC). Group 2 (a comparison group) comprised 71 patients whose superovulation induction was carried out according to the standard protocol using gonadotropin-releasing hormone antagonists on days 2-3 of MC. ET in the induction cycle was done in 46 patients from the comparison group; embryo cryopreservation and transfer in the following MC were performed in 25 patients due to the high risk of OHSS. Results. The patients at high risk for OHSS who were treated by a mild superovulation induction protocol were found to have a significant increase in the average count of mature oocytes by 1.3 times and that of good-quality embryos by 1.4 times despite a 1.6-fold reduction in the total number of obtained oocytes as compared to those who received the standard protocol. With the use of the mild induction protocol as compared to the protocol, the significant (3.4 and 2.5-fold) increases in HLA-G1 and HLA-G5 mRNA expressions, respectively, in the follicular fluid cells were associated with the good outcome of the IVF and PE program. The patients with endometrial implantation failures in the implantation window after VF and PE program were noted to have an increase in gene mRNA expressions in the proinflammatory cytokines: tumor necrosis factor-α by 5 times, IL-18 by 3.2 times, and IL-1β by 6.2 times in the cycle preceding induction, which is a poor prognostic sign for pregnancy occurrence. The application of the mild superovulation induction versus standard protocol could reduce the incidence of OHSS by 1.8-fold. After the use of the standard protocol versus the mild one, the elevation of vascular endothelial growth factor (VEGF) receptors type 1 and 2 by 1.3 times on the day of administration of an ovulation trigger and that of VEGF by 1.2 times on the ET day are prognostically significant in the development of OHSS. With the mild and standard protocols, the pregnancy rate per ET has no statistically significant differences (36.5 and 32.7%, respectively). The efficiency of the mild protocol is 1.4 times higher than that of transfer of the cryopreserved embryos obtained due to ET withdrawal because of a high risk for OHSS in the patients receiving the standard protocol. Conclusion. It is reasonable to use the mild superovulation induction protocol in patients with a high ovarian reserve due to the fact that the protocol shows a higher efficiency and has low drug, psychological, and economic loads than the standard protocol involving the transfer of the cryopreserved embryos due to transfer withdrawal because of a high risk for OHSS.

Objective. To define the importance of allelic variants of cytokine genes in the impaired processes of implantation for infertility of unknown genesis or tuboperitoneal infertility in patients with multiple in vitro fertilization (IVF) failures. Subjects and methods. The study covered 65 patients (a study group) who had undergone 2 to 5 failed IVF attempts, including 35 for primary infertility of unknown genesis and 30 for tuboperitoneal infertility. A comparison group included 70 women with realized reproductive function. In all the patients, the polymorphism of the cytokine genes IL-1ß (-511C/T), IL-6 (-174G/C), IL-10 (-1082 G/A), TNF-α (-238G/A) was studied using polymerase chain reaction- restriction fragment length polymorphism. Results. The patients with multiple failed IVF attempts were found to have a proinflammatory and antiinflammatory cytokine imbalance that manifested itself as the higher frequency of allelic variants in the genotypes of the IL-1ß and TNF-α genes. Conclusion. On examining patients with multiple IVF failures, it is appropriate to perform a molecular genetic study to reveal their predisposition to impaired implantation and, possibly, to make pregravid preparation.

Objective. To improve the outcomes of surgical treatment for genital prolapse (GP) in women over 60 years of age. Subject and methods. Three hundred and sixty-five 365 women over 60 years of age who had been operated on at the Unit of Gynecology, City Clinical Hospital Sixty-Four for GP in 2005—2010 were examined. Based on the data of clinical examination, ultrasonography and questionnaire surveys, the results of treatment were retrospectively assessed in the patients who had received different procedures for surgical correction of GP. Particular attention was given to patients with somatic manifestations or those with complete uterine prolapse and hernial sac formation. Results. The long-term results were traced in 89 patients. 97.7% of the patients achieved a satisfactory result. The best outcomes were achieved by the patients operated on using the Neugebauer-Le Fort technique of midline colporrhaphy both alone and as the second stage of the authors’ modified vaginal hysterectomy. Conclusion. The success of sugical treatment for POP in elderly and senile women depends on the adequate individual choice of the type of an operation. The proposed types of surgical treatment for different forms of genital prolapse in genital hernia could considerably improve quality of life in the patients and reduce recurrence rates.

Objective. To study the kinetics of 5-aminolevulinic acid-induced protoporphyrin IX in the vulvar skin, mucosa, and condylomata acuminata (CA) of women after oral administration of alasens solution and to choose optimal time regimens for the fluorescence diagnosis and photodynamic therapy of vulvar CA. Subjects and methods. The study covered 14 patients with CA. Alasens was orally given in a dose of 25 mg/kg body weight. A Spectr-Cluster computerized fluorescence spectral diagnostic system was used to measure spectra before and 1, 2, 3, 5, 7 hours after oral administration of alasens. To estimate tissue protoporphyrin accumulation, the authors employed the index D f that was determined from the integral intensity of the spectrum recorded in the area of the maximum protoporphyrin IX autofluorescence (620— 660 nm) in reference to that (470—520 nm). The mean values of D f in the vulvar skin, mucosa, and CA were calculated for each patient. The resultant mean values were used to estimate the mean values of D f for each time point in all the patients. The fluorescence contrast (C) of CA in the surrounding intact tissue was determined from the averaged (for all the patients) value of D f for CA with respect to that in intact tissue. Results. Local fluorescence spectroscopy has shown that the optimal time for the fluorescence diagnosis of vulvar CA is 3 to 7 hours after use of alasens solution. Photodynamic therapy may be performed in the above period, by causing minimal damage to the surrounding intact tissues.

Objective. To study maternal deaths from indirect causes to elaborate measures to prevent maternal losses. Material and methods. The statistic data of the Federal State Statistics Service of Russia and those of the Ministry of Health and Social Development of Russia, information (explanatory notes of the principal obstetricians and gynecologists of the subjects of the Russian Federation to their sectoral annual reports according to Form No. 32 «Information on medical care to pregnant women, parturients, and puerperas»), report cards on maternal deaths per 101 maternal fatal outcomes from indirect causes in 2010 were analyzed. Methods for retrospective clinical and statistical analysis and those of examination of the quality of medical care were used. Results. Indirect causes, among which diseases of circulatory (35.6%), respiratory (27.7%), and digestive (8.9%) systems are prominent, have a lead in the pattern of causes of maternal deaths. The percent of urban and rural mothers who had died from indirect causes was 67.3 and 32.7%, respectively. The proportion of premature births (at 28 weeks) was in more than half (56.3%) of the study group women with a population frequency of 3.7%; that of cesarean section was 66.7 and 21.0, respectively. The proportion of deceased women was 19.8% in first-level obstetric care facilities, 27.7% in municipal facilities, 45.6% in regional ones, and 6.9% at home. Conclusion. Among the indirect causes of death, 88 (87.1%) were listed as medical indications for artif icial termination of pregnancy. If contraceptive devices had been timely chosen for women with severe extragenital diseases in the antenatal clinics and, in the occurrence of pregnancy, its termination had been decided, 68 (67.3) fatal outcomes would have been prevented.

Objective. To evaluate the efficiency of combination organ-saving treatment in patients with cervical pregnancy. Subjects and methods. A follow-up study was made in 23 women with cervical pregnancy, admitted to the Department of Operative Gynecology of the Center from 2005 to September 2011. The studies encompassed ultrasound using a transvaginal color Doppler probe, magnetic resonance imaging to visualize an ovum; determination of the borders between the chorion and the cervical stroma, as well as the degree of blood flow in the chorionic area; estimation of the time course of changes in the β-subunit of human chorionic gonadotropin (β-HCG) in the serum; general clinical examinations; endoscopic studies, such as hysteroscopy, hysteroresectoscopy with a diagnostic examination of the material removed. The patients’ mean age was 35±5.9 years (range 25—43 years). The gestation length on admission was 5 to 9 weeks and averaged 6.2 ±0.9 weeks. Results. The patients with cervical ovum location received an average of 50 mg of methotrexate intravenously every 48 hours; leucovorin was given in a dose of 6 mg intramuscularly 28 hours after methotrexate administration. The total dose of the administered methotrexate ranged from 200 to 300 mg and depended on patient weight, gestation length, and chorionic blood flow intensity. During the cytostatic treatment, 19 women of this group could achieve decreases in serum β-HCG and chorionic blood flow to the minimum values (less than 7000 IU/l) and a significant reduction in chorionic vascularization, as evidenced by Doppler study. The ovum was removed using histeroresectoscopy under intravenous anesthesia. The surgical duration averaged 20. In the period 2005—2011, the long-term results were traced in 10 of the 15 women receiving the combination therapy for cervical pregnancy. Four of them were found to have spontaneous pregnancy giving birth to healthy babies, no pregnancy occurred in 5 women. One woman had in vitro fertilization failure. A recurrent cervical pregnancy occurred in none of the cases examined. Conclusion. The results of organ-saving treatment in patients with cervical pregnancy demonstrated the high efficiency of a differential approach to managing this group of patients, by using preoperative chemotherapy and monitoring β-HCG levels, blood parameters, and the status of the chorion and embryo in combination of mini-invasive surgical techniques for removal of the ovum and its bed coagulation.

Objective. To study the frequency and pattern of intra- and postoperative complications during pelvic repair using a Prolift prolene system in women with internal genital prolapse (IGP), to develop methods for preventing these complications and to estimate quality of life in patients operated on. Subjects and methods. The D.O. Ott Research Institute of Obstetrics and Gynecology, Northwestern Branch, Russian Academy of Medical Sciences, examined and treated 300 patients with POP-Q classification (ICS, 1996) Stages II—IV pelvic organ prolapse. The basic volume of surgery consisted in retroperitoneal vaginal colpopexia using the Prolift system. In the late postoperative period, follow-ups were carried out at 1, 6, and 12 months and then once a year. The postoperative management protocol of 40 patients operated on during 2010—2011 involved the local prophylactic use of the ascorbic acid preparation Vaginorm-C in order to correct/prevent bacterial vaginosis and to create optimal conditions for implant attachment and vaginal wound epithelization. Results. During 12—20-month postoperative follow-ups, no vaginal mucosal erosions were noted in the patients receiving Vaginorm-C in the postoperative period, then topical lactoflora agent (acylact). Following 12-month follow-up, the quality of life in these patients turned out to be significantly higher than that in the patients who did not receive Vaginorm-C or lactoflora agents. Conclusion. The use of the Prolift prolene system for the surgical treatment of IGP may cause a number of intra-and postoperative complications. The administration of the agents for the pre- and postoperative correction of bacterial vaginosis along with a package of preventive measures permits the rate of vaginal mucosal erosions to be substantially reduced. The authors have developed a package of measures to prevent and eliminate infectious complications, including those using Vaginorm-С for the correction of vaginal dysbiosis, and a postoperative management protocol for patients with vaginopexia along with the Prolift system, which comprises of a few stages (a patient management algorithm on postoperative days 2—10, 10—20, and 20—40).

Objective. To prevent infectious complications after hysteroscopy on early hospital discharge. Subjects and methods. Seventy patients who had undergone therapeutic and diagnostic hysteroscopy in inpatient settings were examined. To prevent postoperative infectious complications, the combined drug safocid was used on the day of hysteroscopy and, if there was a high infectious risk, reused on day 7 after surgery. The results were compared with those obtained from the patients who traditionally received prophylactic antibiotic therapy with second-to-third-generation cephalosporins for 5—7 days. Effectiveness was evaluated from clinical data, analyses of blood, vaginal smears, and Toll-receptor expression. Results. The postoperative period was complicated by an inflammatory process in none of the examined patients, which suggests that safocid is highly effective in preventing infectious complications after hysteroscopy and that it is comparable with a course of cephalosporin therapy. Laboratory and special studies confirm its clinical effect. Conclusion. When safocid is administered to prevent inflammatory complications after hysteroscopy, there may be an early hospital discharge and there is no need for any additional use of antifungal drugs.