Dariko A. Niauri

Ectopic pregnancy following in vitro fertilization: meta-analysis and single-center experience during 6 years

Abstract Background: Ectopic pregnancy (EP) has been reported to occur in 1.4–5.4% of all clinical pregnancies resulting from in vitro fertilization (IVF) and embryo transfer (ET). Data on factors associated with abnormal embryo implantation following assisted conception are limited. Materials and methods: A systematic review and meta-analysis was performed to determine whether there is an association between the day (cleavage-stage, D3, versus blastocyst, D5) or the type (fresh versus frozen/thawed) of ET and EP rate. Risk factors for EP were evaluated in a retrospective study of 1194 women, who achieved pregnancy at our IVF unit between 2010 and 2016. Results: Sixteen papers were considered for the meta-analysis. EP rate did not differ between D3 and D5 fresh ET groups (RR = 0.99, 95%CI: 0.76–1.30) and was higher after fresh versus frozen ET (RR = 1.56, 95%CI: 1.25–1.95). At our clinic, 21 (1.76%) pregnancies were documented as ectopic. The risk of EP was associated with tubal pathology (OR = 3.37, 95%CI: 1.39–8.2), previous appendectomy and past chlamydial infection. Conclusions: Present meta-analysis suggests that EP rate is similar following fresh blastocyst and cleavage ETs, but is significantly reduced after frozen compared with fresh ET. Our own findings demonstrate that tubal pathology has the major impact on EP occurrence following assisted conception.

Catechol-O-methyltransferase Val158Met polymorphism is associated with increased risk of multiple uterine leiomyomas either positive or negative for MED12 exon 2 mutations

Aims To study the possible association of catechol-O-methyltransferase (COMT) Val158Met polymorphism with multiple and solitary uterine leiomyomas (ULs) and to check whether the COMT Val/Val genotype is associated with MED12 exon 2 mutations in fibroids. Methods The COMT Val158Met allele and genotype frequencies were compared between age-matched women with ULs (n=104) and controls (n=59). Patients with UL were subcategorised by diagnosis of solitary (n=59) or multiple (n=45) fibroids and by the presence of somatic MED12 exon 2 mutations in at least one fibroid (n=32) or in neither fibroid (n=26). The association of COMT Val/Val genotype with the presence of any ULs, solitary/multiple ULs and ULs positive/negative for MED12 exon 2 mutations was evaluated by χ2 tests using a dominant genotype model (G/G vs G/A+A/A) and expressed as ORs and 95% CIs. Results The COMT Val/Val genotype frequency did not differ between the patients with UL and the controls (28.8% vs 18.6%, p=0.149, OR 1.77; CI 0.81 to 3.86). However, it was significantly higher in the patients who had multiple UL compared with the solitary UL (40% vs 20.3%, p=0.028, OR 2.61; CI 1.09 to 6.24) and to the controls (40% vs 18.6%, p=0.016, OR 2.91; CI 1.20 to 7.06). No association of the COMT Val/Val genotype with UL-specific MED12 exon 2 mutations was found (p=0.662, OR 0.77; CI 0.23 to 2.53). Conclusions Women with COMT Val/Val genotype are at high risk of developing multiple uterine fibroids either positive or negative for MED12 exon 2 mutations. These data are important to design new strategies for UL prophylaxis and treatment.

Growth hormone co-treatment in IVF/ICSI cycles in poor responders.

Abstract To estimate the efficacy of growth hormone (GH) co-treatment within an antagonist protocol in IVF/ICSI cycles in poor responders. A prospective observational study involving 50 patients underwent a standard antagonist protocol with or without GH co-treatment. GH was administered by a daily subcutaneous injection of 1,33 mg (equivalent to 4 IU) starting from day 1 of ovarian stimulation until the day of 10,000 human chorionic gonadotropin (hCG) triggering . Concentrations of GH, insulin-like growth factor I (IGF-I) and IGF binding protein-3 (IGFBP-3) in serum and follicular fluid were the subject matter of analysis. The GH co-treatment significantly lowered the effective dose of gonadotropins, duration of stimulation, IGFBP-3 level in serum and follicular fluid on the day of oocyte retrieval. The total number of oocytes as well as the number of metaphase II stage (MII) oocytes, two pronucleus (2 pn) zygotes, good-quality transferred embryos was significantly higher in the GH + group. Pregnancy was achieved in patients GH + group only. Positive correlation was found between IGF-I level in follicular fluid, dynamics of IGFBP-3 level changes during stimulation protocol and the number of good-quality transferred embryos in the GH + group. GH administration in IVF/ICSI cycles for poor responders raises ovarian sensitivity to the gonadotropin exogenous influence, increasing number of high-quality embryos and the probability of pregnancy.

Endometrial receptivity evaluation in IVF cycles

Abstract Endometrial receptivity formation in in vitro fertilization (IVF) cycles was assessed both on molecular level: leukemia-inhibitory factor (LIF), transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), granulocyte macrophage colony stimulating growth factor (GM-CSF) together with hemodynamic characteristics of uterine (Ua) arteries. Aim: Aim of study was to working out an endometrial receptivity evaluation-based prognostic model for IVF efficacy in examined patients. Materials and methods: A total of 97 infertility patients in IVF cycles enrolled in the study. Тwo groups were formed, retrospectively. Group I included 50 women with ultrasound-confirmed pregnancy (51.55%), while the second one embraced 47 women with failed pregnancy. Within the pre-supposed “window of implantation” (WOI) in the preceding IVF cycle, endometrial biopsy was done, succeeded by immunohistochemical assessment of LIF, VEGF and TGF-β1 expression in endometrial samples. The VEGF, GM-CSF and TGF-β1 content in the cervical mucus (CM) was measured by multiplex analysis on transvaginal puncture (TVP) and embryo transfer (ET) day. Hemodynamic characteristics (systolic/diastolic rate, S/D), resistance index (RI) and pulsation index (PI) of Ua arteries on the 2nd–3rd day of menstrual cycle, ovulation triggering (OT) and ET day were assessed. Results: Based on logistic regression analysis, it was found that LIF expression in endometrial epithelium obtained on WOI period of the preceding IVF cycle; VEGF content in the CM on the TVP day, S/D rate and RI of spiral arteries on the OT day are of significant importance in endometrial receptivity formation. Built math model allows high accuracy (85.6%) prediction for pregnancy achieved through IVF by means of applying the suggested parameters.

Pathogenetic justification of possibility of antidiuretic hormone use in incontinent women

Hypothesis/aims of study. Urine incontinence seems to include several pathogenetic forms, as efficient therapy is provided by different medications. Commonly used in the treatment of female patients with overactive bladder and nocturnal polyuria is desmopressin which normalizes the water excretion of the kidney, which is disturbed by a presumed inverted rhythm of vasopressin secretion in these patients. The current analysis was undertaken to evaluate the clinical efficiency of desmopressine in incontinent patients with nocturnal polyuria and polyuria. Study design, materials and methods . A total of 84 patients with complaints of urinary incontinence, polyuria (24-urine volume of 40 mL/kg bodyweight or above) or nocturnal polyuria (nocturnal volume/24-h urine volume of 0.33 or above) and 14 control subjects were included. Mean patient age was 43.6 ± 4.6 years, in control subjects 38.5 ± 6.4 (p > 0.05). All participants performed 24h-urinecollection to determine the voided volumes and the levels of creatinine, osmolality, sodium, magnesium and potassium for each sample. A blood sample was taken during the 24-urinecollection to determine the levels of creatinine, osmolality, sodium, magnesium and potassium. The examination of patients with polyuria and nocturnal polyuria was performed twice: in the initial state and one month after the start of treatment with optimal dose of desmopressin. Optimal dose was established through an open-label dose-titration using 0.1 mg, 0.2 mg and 0.4 mg of desmopressin (Minirin). Safety parameters assessed included incidence of adverse events, vital signs and serum sodium levels. Results . In patients with polyuria and nocturnal polyuria the glomerular filtration rate was normal, whereas diuresis and solute (sodium, magnesium, potassium) excretion in night samples in nocturnal polyuria and both in night and day samples in polyuria were increased. The higher diuresis and the higher solute excretion observed in nocturnal polyuria and polyuria are accompanied by an increase of free water reabsorption. In nocturnal polyuria and polyuria a high correlation was found between the free water reabsorption and solute excretion. This occurs against the background of the high night and day osmotic concentration. The statistically significant recovery of renal function occurred in 12 incontinent women with polyuria and 18 with nocturnal polyuria. In these papients there was a statistically significant decrease in diuresis, osmolar clearance and excretion of sodium, potassium and magnesium. Concluding message . As desmopressin affects cells of the thick ascending limb of Henle’s loop, it is likely that nocturnal polyuria and polyuria result from a disturbed regulation of the function of these cells. Normalization can be achieved by desmopressin administration to stimulate V2-receptors, which increase water permeability and water reabsoption in collecting ducts as well as ion reabsorption by cells of the thick ascending limb of Henle’s loop.

Dienogest treatment after ovarian endometrioma removal in infertile women prior to IVF

Abstract Background: Severe forms of genital endometriosis are known to be associated with infertility and its subsequent treatment failure. Both gonadotropin-releasing hormone analogs (a-GnRH) and dienogest have been suggested as additional hormone therapy for patients with endometriomas. However, the result of hormonal suppression before an in vitro fertilization (IVF) cycle remains undetermined. Materials and methods: A prospective cohort study of 144 infertile women planning IVF after laparoscopic surgery of ovarian endometriomas was conducted at our department in 2012–2015. Patients were divided into three groups: group I (N = 38) with dienogest course, group II (N = 70) with a-GnRH group III (N = 70) without any hormonal therapy within 6 months preceding IVF. Results: The study groups did not differ by removed endometriomas size and ovarian reserve indicators. The gonadotropin dose per Cycle was higher, while the number of retrieved oocytes was lower in group III patients (p < .001). In women with dienogest pretreatment, clinical pregnancy rate was 2.5 times (44.7% versus 16.7%, p = .012) and delivery rate – three times higher (36.8% versus 11.1%, p = .013) as compared with those from group III. Conclusions: The present study confirms the necessity of pre-cycle medical interventions in women with ovarian forms of endometriosis undergoing IVF. We suggest dienogest to be possibly more efficient treatment option for this kind of patients.

Catechol-O-methyltransferase polymorphism in women with uterine leiomyoma and adenomyosis

The aim of this research was to study the frequency of polymorphic variants Val158Met (rs4680) of catechol-O-methyltransferase (COMT) gene in patients with uterine leiomyoma. A polymerase chain reaction was performed to figure out the frequency of polymorphic alleles of COMT gene in 54 patients with uterine leiomyoma and 103 women from the general population. It is shown that the presence of the genotype G/G of the COMT gene is associated with 2.5 times-increased risk of uterine leiomyoma (RR 2,44, Cl95: 1,168-5,103) , whereas the genotype A/A is not associated with the development of leiomyoma. At the same time, a comparative analysis of the genotypes frequencies of the COMT gene polymorphism between groups with different combinations of hyperplastic processes of reproductive system (uterine leiomyoma, adenomyosis, hyperplastic processes of endometrium), showed no statistically significant differences. Refs 26. Tables 3.

Uterine fibroids and effiency of in vitro fertilization programs

The aim of this review is to estimate etiologic role of uterine fibroids in female infertility; it based on the results of current studies of infertility in various cases of fibroids (submucous, intramural and subserous). In article was analyzed the efficiency of the treatment of infertility in women with uterine myoma in IVF programs. Conclusion : a detailed study of endometrial receptivity in women with uterine fibroids is necessary to for personalized strategy in patients with uterine fibroids (myoma) and infertility.

Renal ionoregulation function in incontinent women

Renal ionoregulation function was studied in 143 women with stress incontinence, in 43 with urge incontinence and in 91 with mixed incontinence. Total polyuria was diagnosed in 8,7 ± 1,7% and nocturnal polyuria in 21,7 ± 2,5% incontinent wonen. Changes in kidney function in total and nocturnal polyuria appear to be due not to a decrease in water reabsorption in the renal collecting duct but to reduction of ion reabsorption in the thick ascending limb of the Henle loop. Due to this defect, reabsorption of ions and water is decreased; as a result, lager volumes of fluid enter the collecting ducts.

Endometrial stem cells expansion capability for local and systemic routes of administration in a model of experimentally injured endometrium

Endometrial stem cells due to their therapeutic characteristics could to be an effective tool of cell technologies in reproductive medicine. The aim of the study was to determine the most therapeutically effective route of administration for endometrial stem cells suspension. The study was conducted in approved animal model of injured endometrium. To create the experimental model tissue pieces of autologous endometrium were implanted on the anterior abdominal wall peritoneum using general surgical techniques. Experimental group animals were treated with endometrial stem cells suspension; in the control animal group a placebo was used. Local and systemic routes of endometrial stem cells administration were compared. The direct injections of stem cells suspension in the endometrial implants were used as the local route of administration, the intravenous injections of stem cells suspension were used as a systemic route. Endometrial stem cells expansion didn’t depend on the routes of administration, whereas therapeutic effects of stem cells was more obvious in tissue pieces after local injection of stem cells.