Impaired Fertility Research Articles

FSHB Genotype Identified as a Relevant Diagnostic Parameter Revealed by Cluster Analysis of Men With Idiopathic Infertility.

Introduction and ObjectivesAbout 30-75% of infertile men are diagnosed with idiopathic infertility, thereby lacking major causative factors to explain their impaired fertility status. In this study, we used a large cohort of idiopathic infertile men to determine whether subgroups could be identified by an unbiased clustering approach and whether underlying etiologic factors could be delineated.Patients and MethodsFrom our in-house database Androbase®, we retrospectively selected patients (from 2008 to 2018) with idiopathic male infertility (azoo- to normozoospermia) who fit the following selection criteria: FSH ≥ 1 IU/l, testosterone ≥ 8 nmol/l, ejaculate volume ≥ 1.5 ml. Patients with genetic abnormalities or partners with female factors were excluded.For the identified study population (n=2742), we used common andrologic features (somatic, semen and hormonal parameters, including the FSHB c.-211G>T (rs10835638) single nucleotide polymorphism) for subsequent analyses. Cluster analyses were performed for the entire study population and for two sub-cohorts, which were separated by total sperm count (TSC) thresholds: Cohort A (TSC ≥ 1 mill/ejac; n=2422) and Cohort B (TSC < 1 mill/ejac; n=320). For clustering, the partitioning around medoids method was employed, and the quality was evaluated by average silhouette width.ResultsThe applied cluster approach for the whole study population yielded two separate clusters, which showed significantly different distributions in bi-testicular volume, FSH and FSHB genotype. Cluster 1 contained all men homozygous for G (wildtype) in FSHB c.-211G>T (100%), while Cluster 2 contained most patients carrying a T allele (>96.6%). In the analyses of sub-cohorts A/B, two clusters each were formed too. Again, the strongest segregation markers between the respective clusters were bi-testicular volume, FSH and FSHB c.-211G>T.ConclusionWith this first unbiased approach for revealing putative subgroups within a heterogenous group of idiopathic infertile men, we did indeed identify distinct patient clusters. Surprisingly, across all diverse phenotypes of infertility, the strongest segregation markers were FSHB c.-211G>T, FSH, and bi-testicular volume. Further, Cohorts A and B were significantly separated by FSHB genotype (wildtype vs. T-allele carriers), which supports the notion of a contributing genetic factor. Consequently, FSHB genotyping should be implemented as diagnostic routine in patients with idiopathic infertility.

Changes in morphofunctional and genetic indicators of ejaculate in men with disorders of reproductive function depending on kind of alcohol drinks consumed

Purpose of the study. Due to the scanty information and the lack of precise data on etiology and pathogenesis of fertility in men consuming alcohol this research was aimed at studying the changes in morphofunctional and genetic parameters of ejaculate in men with impaired ejaculate fertility depending on the type and amount of alcohol consumed&#x0D; Materials and methods. The article contains the data of researching ejaculate fertile properties and features of spermatozoa DNA fragmentation in 110 men being divided into three groups depending on kind and amount of alcohol consumed.&#x0D; Results. According to the obtained data the degree of spermatogenesis disorder and tendency to increase level of spermatozoa DNA fragmentation depends on the kind, rate and an amount of alcohol consumed. Thus, the low level in consumption of alcoholic drinks was accompanied by variations of admissible values in spermogram. The most evident changes in ejaculate fertile properties were being observed at middle and high risk in consumption of beer and alcohol mixed, as teratozoospermia has been revealed as a result not only from the ethanol effect but from the impact of components free alcohol character. Revealed tendency of increasing spermatozoa DNA fragmentation level extends our view concerning disorders of ejaculate fertile properties that is obviously connected with alcohol consumption.&#x0D; Conclusions. Thus, alcohol consumption in great amounts, especially, consuming beer with mixed strong alcohol and also pattern of consuming alcohol as “great doses for short time” contribute to a considerable damage to ejaculate fertile properties.

Aneuploidy in sperm of fertile men and patients with impaired fertility

The review presents generalized current data on sperm aneuploidy in healthy (fertile) men and infertile male patients with a normal karyotype and with chromosomal abnormalities. The mechanisms of aneuploidy in germ cells, factors affecting of its level, the relationship with defects of spermatogenesis, meiosis, decreased sperm parameters, as well as the effect of sperm aneuploidy on male fertility, embryo development and gestation are discussed.

Effect of some biochemical factors on female reproductive function

The study aimed to determine the effect of certain biochemical factors on the female reproductive function. Analysis showed that two biochemical factors classified as inflammatory markers have a significant difference in their concentrations in women with impaired fertility and those without fertility disorders. These are C-reactive protein (CRP) and lactoferrin (LF). It is reasonable to assume that these inflammatory markers are associated to some extent with the development of reproductive disorders due to possible formation of inhibin A/LF complexes, which may reduce the biological activity of inhibin A, in patients’ serum. The effect of CRP on inhibin A activity is most likely to be systemic and associated with the effect of CRP high concentrations on inhibin A function on the body level. In particular, it is possible that CRP has an effect on IL-1βsynthesis in ovarian follicles.

Care of Women with Chronic Inflammatory Bowel Disease (Chronic IBD) During Pregnancy

The incidence of chronic inflammatory bowel disease (chronic IBD) in persons of reproductive age is high. Chronic IBD does not typically lead to impaired fertility. Nevertheless, the percentage of women suffering from chronic IBD who have children is lower than that of the general population, due to self-imposed childlessness. Providing women with open, unbiased information and, if necessary, helping them to overcome baseless fears should therefore be an essential part of preconception counseling. With the exception of methotrexate, most standard drugs can and should be continued during pregnancy. If the pregnancy occurs during an inactive phase of disease, the rate of complications in pregnancy should, in principle, not be higher than normal. Nevertheless, pregnant women with chronic IBD are classed as high-risk pregnancies. Organ screening in accordance with DEGUM II criteria should be carried out in every case, and women must be monitored for the potential development of placental insufficiency. Any flare-ups which occur during pregnancy should be treated in full. Vaginal delivery can be considered if there is no perianal manifestation of disease; however, the individual risk must be carefully weighed up.

Primary Ciliary Dyskinesia: A Review

Primary ciliary dyskinesia (PCD) is a disease involving the cilia of the body. First identified as Kartagener’s syndrome (a constellation of findings of chronic sinusitis, bronchiectasis, and situs inversus), the genetic basis has been increasingly uncovered over time. It is now recognized as an autosomal recessive condition due to a mutation in one of several dozen genes, and more is still being discovered as we continue to have ever-expanding access to genetic sequencing technology. These mutations can affect different parts of the creation, structure, or effector mechanisms of the cilia, with the common result being the impairment of ciliary function. Thus, the primary pathology in PCD is immotile or reduced motility of the cilia in various organs, which leads to the principal manifestation of impaired muco-ciliary clearance in the respiratory tract. These cilia are responsible for the constant movement of mucus upwards, often termed the muco-ciliary escalator, to prevent mucus stasis and eliminate the natural collection of airway debris. When this fails, it provides a nidus for bacterial growth, leading to both chronic bacterial colonization and acute bacterial respiratory exacerbations, defined as an acute worsening of respiratory symptoms. In relation to other manifestations, rotary cilia play a role in embryonal development and lateralization of the organs; hence the possibility of situs inversus/ambiguus developing in PCD. Normal ciliary movement is also required for spermatozoan motility, leading to infertility in males with PCD; females can also experience impaired fertility and higher rates of ectopic pregnancy due to reduced ciliary function in the fallopian tubes.

Wolbachia cifB induces cytoplasmic incompatibility in the malaria mosquito vector

Wolbachia, a maternally inherited intracellular bacterial species, can manipulate host insect reproduction by cytoplasmic incompatibility (CI), which results in embryo lethality in crosses between infected males and uninfected females. CI is encoded by two prophage genes, cifA and cifB. Wolbachia, coupled with the sterile insect technique, has been used in field trials to control populations of the dengue vector Aedes albopictus, but CI-inducing strains are not known to infect the malaria vector Anopheles gambiae. Here we show that cifA and cifB can induce conditional sterility in the malaria vector An. gambiae. We used transgenic expression of these Wolbachia-derived genes in the An. gambiae germline to show that cifB is sufficient to cause embryonic lethality and that cifB-induced sterility is rescued by cifA expression in females. When we co-expressed cifA and cifB in male mosquitoes, the CI phenotype was attenuated. In female mosquitoes, cifB impaired fertility, which was overcome by co-expression of cifA. Our findings pave the way towards using CI to control malaria mosquito vectors.

Fertility status among long-term childhood acute lymphoblastic leukaemia survivors enrolled between 1971 and 1998 in EORTC CLG studies: results of the 58 Late Adverse Effects study.

What are the fertility outcomes of male and female childhood acute lymphoblastic leukaemia (ALL) long-term survivors? We observed similar fertility outcomes in both male and female childhood ALL survivors compared with the general population, with the exception of a higher proportion of miscarriages among partners of male survivors. Survival after childhood ALL is currently >90% and fertility impairments are among the main concerns of the long-term survivors. Few studies have focused on the fertility issues within this selected population and the existing data are difficult to interpret due to the different treatment regimens received by the patients, the small sample sizes and the unavailability of control data in many studies. Childhood ALL patients enrolled in European Organisation for Research and Treatment of Cancer (EORTC) studies between 1971 and 1998 in France and Belgium, <18 years old at diagnosis and alive and ≥18 years at follow-up were eligible. Among 1418 eligible survivors, 507 (35.8%) participated (277 females, 230 males). Controls from the general population matched one to one by age, province, level of urbanization and sex could be identified for 503 survivors. Survivors and controls were invited to fill out a questionnaire including information about their menstrual cycles (for females), intention to have children, having children, use of medical help to become pregnant and occurrence of negative pregnancy outcomes (birth defect, miscarriage, medical abortion or stillbirth). The results were analysed separately for females and males. The association between age at diagnosis and fertility outcomes, adjusted by age at follow-up, study and country were investigated using logistic regression. The median time since diagnosis was 20.1 years and the median age at follow-up was 25 years. There were 144 survivors (97 females, 47 males) who wanted to have children. Among these, craniospinal radiotheraphy (CRT) and haematopoietic stem cell transplantation (HSCT) were administered to 18% and 4%, respectively. Of these who tried to have children, 75% of females and 69% of males succeeded, compared with 72% and 61% of the controls, respectively. These differences were not statistically significant (P = 0.73 for females and P = 0.50 for males). Overall, fertility outcomes were comparable between survivors and controls, except that a higher proportion of miscarriages occurred in partners of male survivors (28.1% versus 5.9%, P = 0.021). Among female survivors, an older age at diagnosis (10-17 years) was associated with a greater risk of pregnancy problems (adjusted OR 5.61, P = 0.046). The interpretation of the incidence of miscarriage among the partners of male survivors is limited by the lack of data regarding the males' partners and by a possibly higher tendency to recall and disclose fertility issues among male survivors compared with male controls. Fertility outcomes were similar in childhood ALL survivors and controls, and the low proportion of patients treated with CRT or HSCT might explain this. Further studies should confirm the higher proportion of miscarriages in partners of male survivors. This publication was supported by donations from the Fonds Cancer (FOCA) from Belgium and the KU Leuven from Belgium. G.R. has been awarded a fellowship by the EORTC Cancer Research Fund (ECRF). C.P. has been awarded a fellowship by Fonds Cancer (FOCA) from Belgium and the Kinderkankerfonds from Belgium (a non-profit childhood cancer foundation under Belgian law). No competing interests were declared. NCT01298388 (clinicaltrials.gov).

Clinical advances in the pharmacotherapy of congenital adrenal hyperplasia.

BackgroundPatients with 21-hydroxylase deficiency congenital adrenal hyperplasia (21OHD-CAH) have poor health outcomes with increased mortality, short stature, impaired fertility, and increased cardiovascular risk factors such as obesity. To address this, there are therapies in development that target the clinical goal of treatment, which is to control excess androgens with an adrenal replacement dose of glucocorticoid.MethodsNarrative review of publications on recent clinical developments in the pharmacotherapy of congenital adrenal hyperplasia.SummaryTherapies in clinical development target different levels of the hypothalamo–pituitary–adrenal axis. Two corticotrophin-releasing factor type 1 (CRF1) receptor antagonists, Crinecerfont and Tildacerfont, have been trialled in poorly controlled 21OHD-CAH patients, and both reduced ACTH and androgen biomarkers while patients were on stable glucocorticoid replacement. Improvements in glucocorticoid replacement include replacing the circadian rhythm of cortisol that has been trialled with continuous s.c. infusion of hydrocortisone and Chronocort, a delayed-release hydrocortisone formulation. Chronocort optimally controlled 21OHD-CAH in 80% of patients on an adrenal replacement dose of hydrocortisone, which was associated with patient-reported benefits including restoration of menses and pregnancies. Adrenal-targeted therapies include the steroidogenesis-blocking drug Abiraterone acetate, which reduced adrenal androgen biomarkers in poorly controlled patients.ConclusionsCRF1 receptor antagonists hold promise to avoid excess glucocorticoid replacement in patients not controlled on standard or circadian glucocorticoid replacement such as Chronocort. Gene and cell therapies are the only therapeutic approaches that could potentially correct both cortisol deficiency and androgen excess.

The use of plant extracts to control tilapia reproduction: Current status and future perspectives

AbstractControl of prolific reproduction is vital for a profitable tilapia aquaculture enterprise. All‐male tilapia culture is a popular method used to control prolific breeding, because the male individuals grow faster than female and mixed‐sex populations. Presently, most farmers use 17α‐methyl testosterone (MT) to produce all‐male tilapia individuals, although synthetic hormones are linked to human health and environmental risks. Recently, considerable attention has focused on plant‐based products as alternatives to MT, because they are affordable, safe, and eco‐friendly. Despite the growing interest in using plant extracts to prevent frequent spawning in tilapia production, the available information is not collated to standardize application guidelines. Accordingly, this review article consolidates existing knowledge on the use of plant extracts to control prolific breeding in tilapia culture systems. In addition, limitations to commercial application of the extracts are identified. To date, seed, root, and leaf extracts of 20 plant species, most notably, Tribulus terrestris, Mucuna pruriens, and Carica papaya, exhibit potential for controlling unwanted breeding in tilapia production systems. The extracts are mainly administered orally, incorporated in fish feeds. Saponins and flavanoids are the main bioactive compounds in the phytoextracts, which induce sex inversion and fertility impairment in tilapia. The commercialization of plant extracts is, however, hampered by lack of standardized information on extract preparation, optimal dosages, and mechanism of action. Thus, future studies should address these technical limitations and highlight economic incentives for commercial use of plant extracts in tilapia aquaculture.

Multivariate Optimization of Pb2+ Adsorption onto Ethiopian Low-Cost Odaracha Soil Using Response Surface Methodology.

Lead pollution is a severe health concern for humankind. Utilizing water contaminated with lead can cause musculoskeletal, renal, neurological, and fertility impairments. Therefore, to remove lead ions, proficient, and cost-effective methods are imperative. In this study, the Odaracha soil which is traditionally used by the local community of the Saketa District was used as a novel low-cost technology to adsorb lead ions. Odaracha adsorbent was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The adsorption process followed the batch adsorption experiment. The response surface method was implemented to derive the operating variables’ binary interaction effect and optimize the process. According to the study’s experimental result, at optimum experimental conditions Odaracha adsorbent removes 98.17% of lead ions. Based on the result of the central composite design model, the Pb2+ ion removal efficiency of Odaracha was 97.193%, indicating an insignificant dissimilarity of the actual and predicted results. The coefficient of determination (R2) for Pb2+ was 0.9454. According to the factors’ influence indicated in the results of the central composite design model, all individual factors and the interaction effect between contact time and pH has a significant positive effect on lead adsorption. However, other interaction effects (contact time with dose and pH with dose) did not significantly influence the removal efficiency of lead ions. The adsorption kinetics were perfectly fitted with a pseudo-second-order model, and the adsorption isotherm was well fitted with the Freundlich isotherm model. In general, this study suggested that Odaracha adsorbent can be considered a potential adsorbent to remove Pb2+ ions and it is conceivable to raise its effectiveness by extracting its constituents at the industrial level.

Prognostic value of the location of submucosal uterine leiomyomas in infertility.

Submucosal fibroid location and size are predictive factors of impaired fertility. Submucosal fibroids cause infertility through several mechanisms including distortion of the endometrial cavity, increased uterine contractility, local inflammation and remodeling of the endometrial blood supply. This is a monocentric, retrospective, cross-sectional study, conducted in the Department of Obstetrics and Gynecology of 'Sf. Pantelimon' Clinical Emergency Hospital, analyzing patients from a 5-year period (January 2015-December 2019). In the present study, the relationship between different characteristics of the submucosal fibroids (among others, location and dimensions) and fertility (birth rates, early pregnancy loss rates) were investigated. This study identified that submucosal and intramural fibroids are risk factors for reduced birth rate compared with subserosal fibroids (P=0.02, RR=2.58, 95% CI 1.03-6.47; P=0.005, RR=1.18, 95% CI 1.02-1.35, respectively). In addition, G2 leiomyomas are risk factors for low birth rate compared with G0 and G1 fibroids (P=0.01, RR=1.95, 95% CI 1.05-3.60). Moreover, the presence of a subserosal fibroid was associated with an increased early pregnancy loss rate (P=0.01, RR=2.14, 95% CI 1.05-4.35). In conclusion, the location and degree of uterine cavity distortion are important factors that alter the normal development of a pregnancy and the birth rate.

Granulocyte Colony-Stimulating Factor Restored Impaired Spermatogenesis and Fertility in an AML-Chemotherapy Mice Model.

Leukemia and treatment of male patients with anticancer therapy (aggressive chemotherapy and/or radiotherapy) may lead to infertility or even permanent male sterility. Their mechanisms of spermatogenesis impairment and the decrease in male fertility are not yet clear. We showed that under acute myeloid leukemia (AML) conditions, alone and in combination with cytarabine (CYT), there was significant damage in the histology of seminiferous tubules, a significant increase in apoptotic cells of the seminiferous tubules, and a reduction in spermatogonial cells (SALL and PLZF) and in meiotic (CREM) and post-meiotic (ACROSIN) cells. In addition, we showed a significant impairment in sperm parameters and fertilization rates and offspring compared to control. Our results showed a significant decrease in the expression of glial cell line-derived neurotrophic factor (GDNF), macrophage colony-stimulating factor (MCSF) and stem cell factor (SCF) under AML conditions, but not under cytarabine treatment compared to control. In addition, our results showed a significant increase in the pro-inflammatory cytokine interleukin-1 (IL-1) alpha in whole testis homogenates in all treatment groups compared to the control. Increase in IL-1 beta level was shown under AML conditions. We identified for the first time the expression of GCSF receptor (GCSFR) in sperm cells. We showed that GCSF injection in combination with AML and cytarabine (AML + CYT + GCSF) extended the survival of mice for a week (from 6.5 weeks to 7.5 weeks) compared to (AML + CYT). Injection of GCSF to all treated groups (post hoc), showed a significant impact on mice testis weight, improved testis histology, decreased apoptosis and increased expression of pre-meiotic, meiotic and post- meiotic markers, improved sperm parameters, fertility capacity and number of offspring compared to the controls (without GCSF). GCSF significantly improved the spermatogonial niche expressed by increased the expression levels of testicular GDNF, SCF and MCSF growth factors in AML-treated mice and (AML + CYT)-treated mice compared to those groups without GCSF. Furthermore, GCSF decreased the expression levels of the pro-inflammatory cytokine IL-12, but increased the expression of IL-10 in the interstitial compartment compared to the relevant groups without GCSF. Our results show for the first time the capacity of post injection of GCSF into AML- and CYT-treated mice to improve the cellular and biomolecular mechanisms that lead to improve/restore spermatogenesis and male fertility. Thus, post injection of GCSF may assist in the development of future therapeutic strategies to preserve/restore male fertility in cancer patients, specifically in AML patients under chemotherapy treatments.

SC159 - Increased mortality among men diagnosed with impaired fertility: analysis of us claims data

SC159 - Increased mortality among men diagnosed with impaired fertility: analysis of us claims data

Systematic Review and Meta-Analysis of treatment of Palpable Undescended Testis

Abstract Background Undescended testis is the most common endocrinological disease in the male newborn period. Incidence varies between 1.0% and 4.6% in full-term neonates, with rates as high as 45% in preterm neonates. Failure or delay of treatment can result in reduced fertility and/or increased testicular cancer risk in adulthood. Aim and objectives : To establish, through the available literature, which is the best technique, either hormonal therapy or surgical orchiopexy for treatment of palpable undescended testis through systematic review and meta-analysis. Subjects and methods : The review considered case-control studies, case report studies, and retrospective case follow-up evaluating the effectiveness or efficacy of a certain technique of treatment of palpable undescended testicles over other techniques either hormonal therapy and surgical orchiopexy according to age of the patient, This review considered all studies that involve infants with palpable undescended testicles, Search strategy is designed to include both manual and electronic data available. Electronic searches involved searching databases of PubMed (from Jan. 1987 till July 2017), EMbase, CINAHL and Cochrane database. Results The overall success rate of primary orchiopexy is 96.4% and the overall success rate for 2- stage FS is 86%. Conclusion There is good evidence for early placement of undescended testes in the scrotal position to prevent potential impairment of fertility and reduce the risk of testicular malignancy.

Fertility and pregnancy complications following chorioamnionitis

Acute chorioamnionitis complicates 1–2% of all pregnancies and might increase the prevalence of endometritis that can cause Asherman syndrome or adhesions, but little is known about the direct effects of chorioamnionitis on future fertility. We aimed to evaluate the effect of chorioamnionitis on future fertility and obstetrics complications in patients diagnosed with chorioamnionitis during their pregnancy. We performed an observational, case–control retrospective study of pregnant women aged 18–40 years old, hospitalized with a diagnosis of chorioamnionitis between January 2013 and December 2017. The control group consisted of patients with similar demographic/obstetrics characteristics, matched with a ratio of 1:2 without chorioamnionitis. The prevalence of post gestational diagnostic hysteroscopy was significantly higher in the study group as compared to the control group (22.9% versus 9.0%, respectively; p = 0.005). Moreover, the study group underwent significantly more operative hysteroscopy compared to the control group (10.8% versus 3.6%, respectively; p = 0.04). The patients in the study group had significantly higher prevalence of miscarriages (27% versus 13.2%, respectively; p < 0.01). We conclude that chorioamnionitis may cause endometritis with the consequent impaired fertility, necessitating comprehensive evaluations for secondary infertility, including hysteroscopy aiming to treat intrauterine adhesions that may affect and impair fertility.

Uterine Injury Caused by Genotype 4 Hepatitis E Virus Infection Based on a BALB/c Mice Model.

To evaluate whether uterine injury caused by hepatitis E virus (HEV) infection is responsible for adverse pregnancy outcomes. HEV-infected female BALB/c mice were coupled with healthy male BALB/c mice at 0, 7, 14, 21, and 91 dpi to explore the uterine injury caused by HEV infection. Mice were euthanized after 10 days of copulation, and uteruses were collected for HEV RNA and antigen detection and histopathological analysis. Inflammatory responses; apoptosis; and estrogen receptor ɑ (ER-ɑ), endomethal antibody (ERAb), cytokeratin-7 (CK7), vimentin (VIM), and vascular endothelial growth factor (VEGF) expression levels were evaluated. After 10 days of copulation, miscarriage and nonpregnancy, as well as enlarged uteruses filled with inflammatory cytokines, were found in HEV-infected mice. HEV RNA and antigens were detected in the sera and uteruses of HEV-infected mice. Significant endometrial thickness (EMT) thinning, severe inflammatory responses, and aggravated apoptosis in the uteruses of HEV-infected mice that experienced miscarriage might contribute to adverse pregnancy outcomes. Furthermore, significantly suppressed ER-ɑ expression and increased ERAb, CK7, VIM, and VEGF expression levels were found in the uteruses of HEV-infected mice that had miscarried. However, uterine damage recovered after complete HEV clearance, and impaired fertility was improved. EMT injury, severe inflammatory responses, and aggravated apoptosis in the uterus caused by HEV infection are responsible for poor pregnancy outcomes.

Features of clinical and anamnestic characteristics of patients with different ovary reserve

The objective: conduct a clinical and statistical analysis of anamnestic data in infertile women with a predicted weak response of the ovaries to gonadotropins stimulation. Materials and methods. A prospective study of the clinical and statistical analysis of anamnestic data in infertile women with a predicted weak response of the ovaries to gonadotropins stimulation was carried out on the base of CRT USIR Shupyk National Healthcare University of Ukraine, for the period from 2020–2021. Group I consisted of 55 of reproductive aged women with chronic endometritis and repeated unsuccessful attempts of IVF, and control group consisted of 40 reproductive aged women without impaired fertility. Scope of research: pH-metric of vaginal discharge, assessment of vaginal microbiocenosis by microscopic data of a smear stained by Gram, endometrial biopsy and examination of polymerase chain reaction (PCR) of vaginal discharge culture and cervical canal microflora. Results. According to obtained data, in both groups, primary infertility was 43.6% and 55.5%, secondary – 53.4% and 44.4%, respectively. In both groups, there was a high level of artificial abortions (21.8% and 31.1%) and spontaneous early abortions (14.5% and 13.3%) (p&lt;0.05). Among gynecological pathology, the main place is occupied by chronic inflammatory diseases (56.3% of women in group I and 62.2% in group II) and endometriosis (29.1% in the first group and 26.7% in group II). All women with a predicted weak ovarian response to gonadotropin stimulation had surgical interventions on the pelvic organs in anamnesis; 78.0% (78/100) of cases were performed laparoscopic approach. Analysis of surgical intervention structure in women of both groups revealed high frequency of ovarian resection due to the presence of functional cysts and benign formations (27.0%, 27/100). Conclusions. Thus, the predisposing factors for a «weak» response in IVF programs were an older reproductive age, a high frequency of surgical interventions on the pelvic organs and, as a consequence, a change in the blood supply of the ovarian cortical layer, a decrease in stroma volume and follicular reserve reduction. According to main clinical and anamnestic characteristics, groups were comparable and revealed intergroup differences were statistically insignificant that allows us to compare them with each other in a further study.

Microbiotes of the vagina, cervical canal and uterine cavity in chronic endometritis

The objective: to determine the profile of vaginal, cervical and uterine microbiota in chronic endometritis in patients with failed ART attempts in history. Materials and method. A prospective study and clinical laboratory analysis of vaginal microbiocenosis, cervical canal and uterine cavity in women with chronic endometrite in a history on the basis of MC LLC «ISIDA - IVF», in the period from 2020 to 2021 was carried out. The group consisted of 55 women of reproductive age with chronic endometritis and repeated failed ART attempts, and 40 women of reproductive age without fertility impairment who formed the control group. Amount of research – Vaginal Secretion PH, Vaginal Microbial Estimation of Pap Smear Microscopy, Polymerase Chain Reaction Study (PCR), Culture Study of Vaginal Secretions, Study of microflora of the cervical channel and bioptat of endometrium. Results. In women with infertility, against the background of chronic endometritis in history, as a result of bacterial sowing from the uterine cavity, the predominance of mixed bacterial flora, which is represented by various associations of opportunistic and pathogenic micro-organisms, has been detected. Chronic inflammatory endometry is caused by a persistent viral bacterial infection in the uterine cavity, which differs in species composition from the microflora of the lower genital tract. Conclusions. The characteristic feature of the vaginal flora in chronic endometritis is a high level of dissbiotic changes, combined with high values of the notional pathogenic flora. The microbiotopes of the cervical channel and endometrium in the inflammatory processes of endometry are characterized by the predominance of obligatory-anaerobic micro-organisms in the form of associations with viral infection much more than twice as frequently detected in endocervix as compared to endometrium.

Obesity induces morphological and functional changes in female reproductive system through increases in NF-\u03baB and MAPK signaling in mice

BackgroundRecently, human infertility incidence is increasing in obese women causing it to become an emerging global health challenge requiring improved treatment. There is extensive evidence that obesity caused female reproductive dysfunction is accompanied by an endocrinological influence. Besides, systemic and tissue-specific chronic inflammatory status are common characteristics of obesity. However, the underlying molecular mechanism is unclear linking obesity to infertility or subfertility.MethodsTo deal with this question, we created an obese mouse model through providing a high fat diet (HFD) and determined the fertility of the obese mice. The morphological alterations were evaluated in both the reproductive glands and tracts, such as uterus, ovary and oviduct. Furthermore, to explore the underlying mechanism of these functional changes, the expressions of pro-inflammatory cytokines as well as the activations of MAPK signaling and NF-κB signaling were detected in these reproductive tissues.ResultsThe obese females were successful construction and displayed subfertility. They accumulated lipid droplets and developed morphological alterations in each of their reproductive organs including uterus, ovary and oviduct. These pathological changes accompanied increases in pro-inflammatory cytokine expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in all of these sites. Such effects also accompanied increases in nuclear factor kappa B (NF-kB) expression and mitogen-activated protein kinase (MAPK) signaling pathway stimulation based on uniform time dependent increases in the NF-κB (p-NF-κB), JNK (p-JNK), ERK1/2 (p-ERK) and p38 (p-p38) phosphorylation status.ConclusionsThese HFD-induced increases in pro-inflammatory cytokine expression levels and NF-κB and MAPKs signaling pathway activation in reproductive organs support the notion that increases of adipocytes resident and inflammatory status are symptomatic of female fertility impairment in obese mice.