A. M. Gzgzyan

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.

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.

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.

THE PLACENTA AS THE EPIDEMIC FACTOR OF VERTICAL HIV TRANSMISSION RISK IN CONDITIONS OF COMORBIDITY

A multifactorial in-depth study of 78 placentas obtained during delivery of HIV infected women in St. Petersburg between 2009 and 2011. We studied clinical anamnestic and laboratory parameters on the basis of the retrospective analysis, respectively, in 78 HIV-positive postpartum women (mean age 27,1±4,1 years) and their newborn children, of whom 12 have mother-to-child transmission of HIV. Most of the women who gave birth to infected children who were users of psychoactive drugs all took place co-infection with hepatitis C virus, about half of them were observed chronic urogenital infections. The complexity of communication, contacts instability did not allow any of the women who have realized the vertical transmission of HIV, antiretroviral therapy to conduct in full. In obstetrical establishment turned 11 women, but due to the onset of labor and/or premature rupture of membranes that are not allowed to use the elective caesarean section as a method of prevention of vertical transmission of HIV. All infants were signs posthypoxic encephalopathy. It was noted that in HIV infection in the placental tissue is imbalance between pro-angiogenic (VEGF, bFGF, CD31) and anti-angiogenic (TGF-β1, Tsp-1) factors in favor of the latter, which is the basis of a dissociated maturation chorionic villi and chronic placental insufficiency. With the implementation of intrauterine infection of HIV in placental tissue sharply reduced macrophage content, primarily CD68+ and, to a lesser extent, CD14+. Violation placental barrier greatly facilitates and determines the penetration of HIV to the fetus. In this case, targeted prevention, treatment for opportunistic infections and drug correction of placental insufficiency in HIV-infected women should, obviously, be regarded as justified pathogenetic approaches to reduce mother-to-child transmission of HIV.

Immunohistochemical criteria for endometrial receptivity in I/II stage endometriosis IVF-treated patients

Abstracts Background: Implantation failure of in vitro fertilization (IVF) cycles is recognized as one of key problems in contemporary reproductive medicine. Implantation itself is a multifactorial process and one can hardly expect to find a single criterion for the endometrium receptivity. Endometrium biopsy still remains the most applicable technique to diagnose abnormalities causing decrease or complete loss of endometrial receptivity. Materials and methods: We have studied 95 endometrial biopsy samples from 45 patient with I/II stage endometriosis and 40 controls from October 2014 to December 2015. Immunohistochemical analysis of key biological molecules participating in implant window formation (LIF, ER, PR, integrin, TGF-β1 and VEGF) was done to assess their predicting value for endometrial receptivity troubles. Results: The discriminant analysis demonstrated that highest information capacity was characteristic for LIF expression percent area, integrin αVβ3 both percent area and optic density in endometrial stroma and glands and finally TGFβ1 and VEGF-А percent area expression in endometrial stroma. The model test done on a checking group showed 89.1% correct discrimination. Cross-checking in a teaching group showed a bit lower but still high correct answer percentage (88.8%). A decision-making classification tree was worked out. Conclusion: The produced model is sufficient for predicting IVF treatment failure and allows producing reasonable treatment tactics as well as encourages IVF treatment effectiveness improvement in patients with endometriosis.

Successful Pregnancy Outcome in Women with Recurrent IVF Failure and Anti-hCG Autoimmunity: A Report of Three Cases

We report three cases of effective management of infertility in women with a history of repeated unsuccessful IVF attempts, who have developed antibodies to hCG. A novel approach to conservative treatment of immunologic reproductive failure, suggested for selected patients, included membrane plasmapheresis, combined prednisolone, and intravenous immunoglobulin therapy. No adverse side effects were observed; all cases resulted in pregnancy and subsequent life births. In order to be given an adequate efficient treatment, women with recurrent implantation failure should be suspected for autoimmune factor of infertility and its possible association with anti-hCG autoimmunity.

The effeciency of IVF protocols in patients with moderate to severe endometriosis after adjuvant therapy

Преодоление бесплодия при эндометриозе представляет собой одну из наиболее трудных проблем репродуктивной медицины. Это связано с высокой частотой заболевания, его хроническим течением, мультифакториальностью нарушения репродуктивной функции, возможностью рецидива после лечения. Многолетние исследования, клинический опыт ведения таких пациентов сформулировали хорошо известную основную парадигму лечения заболевания — комбинированный подход, включающий хирургическое вмешательство и гормональную терапию [1, 3]. При этом необходимость назначения гормональных средств после лапароскопии у больных, у которых степень тяжести заболевания позволяет планировать естественное зачатие или внутриматочную инсеминацию с индукцией овуляции, до настоe-mail: ikogan@mail.ru doi: 10.17116/repro20152123944