Female Infertility Research Articles

NSUN2 is critical for mouse oocyte meiosis and early embryonic development.

The mechanism by which the NSUN2 mutation causes female infertility is still unclear. This study reveals the role and potential mechanism of NSUN2 in mouse oocyte maturation and early embryonic development, and provides a resource for elucidating female infertility with NSUN2 mutations. Biallelic variants in the NSUN2 gene cause a rare intellectual disability and female infertility in humans. However, the function and mechanism of NSUN2 during mouse oocyte meiotic maturation and early embryonic development are unknown. Here, we show that NSUN2 is important for mouse oocyte meiotic maturation and early embryonic development. Specifically, NSUN2 is required for ovarian development and oocyte meiosis, and deletion of Nsun2 reduces oocyte maturation and increases the rates of misaligned chromosomes and aberrant spindles. In addition, Nsun2 deficiency results in a low blastocyst rate and impaired blastocyst quality. Strikingly, loss of Nsun2 leads to approximately 35% of embryos being blocked at the 2-cell stage, and Nsun2 knockdown impairs zygotic genome activation at the 2-cell stage. Taken together, these findings suggest that NSUN2 plays a critical role in mouse oocyte meiotic maturation and early embryonic development, and provide key resources for elucidating female infertility with NSUN2 mutations.

The Causal Relationship Between Immune Cells and Infertility: A Mendelian Randomisation Study.

Infertility has emerged as a significant global public health concern, with a multitude of complex underlying causes. Epidemiological evidence indicates that immunological factors are significant contributors to the aetiology of infertility. However, previous studies on the relationship between immune inflammation and infertility have yielded inconclusive results. Mendelian randomisation (MR) is an emerging statistical method that employs exposure-related genetic variation as an instrumental variable (IV) to infer causal relationships between immune cells and infertility by modelling the principle of random assignment in Mendelian genetics. In this study, MR was employed to assess the causal relationship between 731 immune cell signatures and infertility. The data utilized in this study were obtained from publicly available genome-wide association studies (GWAS) and validated IVs, which were employed to fulfil the essential assumptions of MR analysis. The Mendelian randomisation analysis revealed a total of 27 statistically significant immune cell phenotypes out of 731. The risk factor with the largest odds ratio (OR) was CD28- CD25++ CD8+ %T cell [OR, 1.21; 95% confidence interval (CI), 1.04-1.42], while the protective factor with the largest OR was activated and resting Treg AC (OR, 0.89; 95% CI, 0.82-0.97). The present study has demonstrated a correlation between certain characteristics of immune cells and female infertility. These results provide clues for further research into the immune mechanisms of infertility and may inform the development of novel therapeutic strategies.

Genetics of female and male infertility.

Infertility is defined as the inability to conceive within one year of unprotected intercourse, and the causes are equally distributed between both sexes. Genetics play a crucial role in couple infertility and respective diagnostic testing should follow available guidelines. Appropriate tiered genetic analyses require comprehensive physical examination of both partners in an infertile couple. A wide range of chromosomal and monogenic variants can be the underlying genetic cause of infertility in both women and men. Accurate clinical phenotyping, together with identification of the genetic origin, helps to recommend the proper treatment and to counsel couples on the success rates and potential risks for offspring.

Impact of sperm DNA fragmentation in couples with unexplained recurrent pregnancy loss: A cross-sectional study.

Recurrent pregnancy loss (RPL) has a multifactorial etiology, with a majority of cases remaining unexplained. To account for these unexplained cases, possible male factors are being explored. Conventional semen analysis lacks a qualitative assessment of sperms and information regarding sperm DNA integrity. Sperm DNA fragmentation (SDF) has diagnostic value in unexplained RPL, and it may account for a number of unexplained cases. Hence, we planned a study to explore and evaluate the impact of sperm DNA fragmentation in couples with unexplained recurrent pregnancy losses. Analytical cross-sectional study was conducted at a tertiary-level referral facility in India between August 2021 and July 2023. Participants (n = 70) were divided into two groups-male partners of couples with unexplained RPL (following spontaneous conceptions) (n = 35) and men with at least one previous live birth (spontaneous or following fertility treatments for female factor infertility such as ovulation induction or intrauterine insemination) as controls (n = 35). Neither of the two groups of couples recruited for this study had undergone ART as fertility treatment. Primary outcome assessed was mean DNA fragmentation index (DFI). Secondary outcomes included differences in semen parameters such as sperm concentration, progressive sperm motility and morphology, proportion of men with high (≥30%) and low DFI in the two groups, and the association between various semen parameters and DFI. Univariate logistic regression revealed that sperm DNA fragmentation was higher in men with unexplained RPL (30.0; IQR (interquartile range) 19.0, 46.0) as compared to controls (22.0; IQR 14.0, 30.0) although it was not statistically significant (OR, odds ratio, 1.02; 95% CI 1.0-1.1, p = 0.08). A higher proportion of men with unexplained RPL had DFI ≥30% compared to controls (54.2% vs. 25.7%; OR 3.43 (95% CI 1.2-9.4); p = 0.02). No statistically significant differences were observed in semen volume, sperm concentration, progressive motility, and morphology between the two groups. Sperm DNA fragmentation index also showed a weak but significant inverse relationship with sperm morphology (r = -0.336, p = 0.004). The current study did not show any significant difference in the mean sperm DNA fragmentation levels in male partners of couples with unexplained RPL compared to controls. However, a higher proportion of men with DFI ≥30% were observed in unexplained RPL population when compared to controls.

Impact of overweight and obesity on live birth rate in single euploid frozen embryo transfers: the key is in the preparation protocol!

Research questionDoes endometrial preparation using a natural cycle (NC) lead to higher live birth rates (LBR) in single euploid frozen embryo transfers (seFET) compared to programmed cycles (PC), for women across normal, overweight, and obese body mass index (BMI) categories? DesignRetrospective study of 845 seFETs. Patients were stratified by BMI into 3 categories (Normal weight, Overweight, and Obesity Class I/II). Outcome was LBR. ResultsA total of 845 seFET cycles of 688 couples were included in the analysis. After achieving covariate (female age, AMH, embryo quality and infertility type) balance in each stratum, the effective sample size was 481 and 262 for the PC and NC, respectively. The PC approach, in which patients received vaginal luteal phase support with 3×100 mg micronized vaginal progesterone (MVP)/day, were associated with significantly lower LBR in the weighted regression analysis of the cohort (RR: 0.80, 95%CI: 0.73 – 0.88, p<0.001), compared to the NC approach. The effect was significantly modified by BMI (P=0.003). While the effect was significant for all BMI categories, the reduction in live birth was less pronounced in patients with normal or overweight BMI (RR: 0.87, 95%CI: 0.78-0.97, p=0.014) compared to patients with class I/II obesity (RR: 0.61, 95%CI: 0.49-0.75, p<0.001). ConclusionA natural cycle endometrial preparation approach leads to overall better live birth rates in single euploid FET, and the most significant difference is observed in women with higher BMI. Furthermore, overweight / obese patients in a PC may require a higher dosage of progesterone for luteal phase support.

БЕРЕМЕННОСТЬ, РОДЫ И ПЕРИНАТАЛЬНЫЕ ИСХОДЫ У БЕРЕМЕННЫХ ПОСЛЕ ЭКСТРАКОРПОРАЛЬНОГО ОПЛОДОТВОРЕНИЯ

Almost every day we face the problem of infertility among married couples. It should also be noted that currently male and female infertility occur with approximately the same frequency. According to information provided by the World Health Organization, one in six people in the world faces the problem of infertility. Assisted reproductive technologies for the treatment of infertile couples are considered a serious medical intervention worldwide. The updated data confirmed the absence of significant differences in the prevalence of infertility among different regions of the world. Thus, high-, middle- and low-income countries have comparable infertility rates. This means that this problem is a worldwide health problem. At the same time, there are significant differences in the availability, quality and provision of infertility treatment services between high-income and low-income countries. The purpose of the study: to study the features of the course of pregnancy, childbirth and perinatal losses in pregnant women after in vitro fertilization. Materials and methods of research. A retrospective analysis of the course of pregnancies, childbirth and perinatal outcomes was performed in 155 patients whose pregnancy occurred after the use of assisted reproductive technologies (in vitro fertilization). Only women whose pregnancy ended in childbirth were included in the study. Results. Further clinical studies are needed to reduce the incidence of pregnancy complications and improve perinatal outcomes. In addition, it is necessary to expand the availability of all necessary low-cost and high-quality methods of infertility treatment.

Efficacy of platelet-rich plasma in the treatment of thin endometrium: a meta-analysis of randomized controlled trials

BackgroundThin endometrium (TE) is a common cause of female infertility in clinical practice. Platelet-rich Plasma (PRP) therapy becomes a novel treatment for thin endometrium; however, its clinical application remains controversial. This meta-analysis aims to evaluate the therapeutic effects of intrauterine autologous PRP infusion in women with thin endometrium through relevant randomized controlled trials (RCTs).MethodsWe systematically searched studies published in English from inception until June 2024 in databases such as PubMed, The Cochrane Library, Embase, Web of Science, and MEDLINE. Search terms included “Platelet-Rich Plasma,” “thin endometrium,” “endometrial thickness,” “infertility,” “pregnancy,” “reproduction,” and “adverse reactions”. RCTs identified through the search were subjected to systematic review and meta-analysis, and data were analyzed using fixed-effects or random-effects models based on heterogeneity.ResultsEight RCTs involving 678 patients with thin endometrium were included. Patients receiving PRP infusion demonstrated significantly superior outcomes compared to the control group in endometrial thickness (MD: 1.23, 95%CI: 0.87 to 1.59, P = 0.000), clinical pregnancy rate (RR: 2.04, 95%CI: 1.52 to 2.76, P = 0.000), live birth rate (RR: 2.46; 95%CI: 1.57 to 3.85, P = 0.000), cycle cancellation rate (RR: 0.46, 95%CI: 0.23 to 0.93, P = 0.000), and embryo implantation rate (RR: 2.71; 95%CI: 1.91 to 3.84, P = 0.000). There were no statistically significance in spontaneous abortion rate (RR: 0.85, 95%CI: 0.40 to 1.78, P = 0.659), chemical pregnancy rate (RR: 1.84, 95%CI: 0.72 to 4.72, P = 0.204) and endometrial vascular improvement rate (RR: 1.10; 95%CI: 0.89 to 1.38, P = 0.367) between the two groups. The limitations of this study includes that, we only included single lauguage for literature research, the sample size and heterogeneity which could cause criteria bias.ConclusionIntrauterine PRP infusion may be an effective and safe treatment for women with thin endometrium. Further high-quality, large-sample, randomized controlled trials are needed to validate the reliability of our results.Trial registrationThe review protocol is registered on PROSPERO with registration number CRD42023490421, and no modifications were made to the information provided at registration.

Biallelic variants in α-tubulin isotypes cause female infertility characterised as recurrent preimplantation embryo arrest

BackgroundRecurrent preimplantation embryo developmental arrest (RPEA) is the most common phenotype in assisted reproductive technology treatment failure associated with identified genetic abnormalities. Currently known maternal genetic variants explain only a...

LAPAROSCOPIC DIAGNOSIS OF ENDOMETRIOSIS-ASSOCIATED INFERTILITY

The purpose of the study – to generalize the laparoscopic manifestations of genital andextragenital endometriosis in women with infertility, followed by the determination of itsbelonging to international classifications of pathology for the possibility of choosing fullfledged methods of influencing the focus of the disease.Materials and methods. The study was conducted in two stages: a detailed analysis ofscientific studies on the issue of classification of endometriosis R-AFS, Enzian, EFI witha generalization of the main search criteria during laparoscopy; a study based on themedical center «Yuzko» in Chernivtsi, in which 42 women who contacted about infertilitytook part. In the practical part of the work, clinical and paraclinical methods of diagnosis,laparoscopic revision were used, followed by the formation of diagnoses according to themain classifiers of endometriosis, determination of the fertility index and generalizationof the form of endometriosis as a cause of infertility.Research results. Endometriosis is a chronic pathology of the female reproductive system,which often leads to infertility and is accompanied by various clinical manifestations inthe form of pain and menstrual dysfunction. For the purpose of a complete diagnosis ina specific case, an important stage is the determination of the depth and stage of developmentof the endometrioid focus based on the results of laparoscopy according to the classificationproposed by the American Fertility Society (R-AFS classification), Enzian, followed bythe determination of the fertility index (EFI) in order to choose individual managementtactics of each patient. A study was conducted at Yuzko Medical Center, in which 42 womenof various ages who complained of infertility took part. In the course of laparoscopicoperations, various methods of removing endometrioid foci were implemented depending onthe specific clinical case, after which the stage of endometriosis was determined according to the Enzian, R-AFS classification, and a conclusion was formed about the directdependence of the risk of infertility and the depth of the spread of endometriosis foci.Conclusion. The stage and depth of endometriosis plays a decisive role in the developmentof female infertility, which requires careful diagnosis according to modern classificationsand the implementation of a specific treatment program with the aim of developinga natural pregnancy or successful embryo transfer during in vitro fertilization.

Impact of pre-conception diet on female infertility

Introduction and purpose Infertility is defined as a condition characterized by the inability to become clinically pregnant after 12 months of regular, unprotected sexual intercourse, or because a person's ability to reproduce, either as an individual or with his or her partner, is impaired. Infertility affects between 8% and 12% of couples of reproductive age worldwide. Fertility decline in women begins as early as age 25-30. The purpose of this article is to present the problem of infertility in women, possible diagnostic options, methods of prevention and treatment of infertility. We draw attention to the important role of a proper lifestyle, including diet in the fight against infertility. State of knowledge The article reviews the literature on infertility with special attention to the problem of infertility in women. Knowing the causes of infertility, it is possible to implement targeted diagnosis and then treatment. Attention is paid to the influence of proper diet on female fertility. Material and method A review of the literature available on PubMed and Google Schoolar was conducted. We focused on presenting different causes of infertility in women, diagnostic options, treatment methods depending on the cause of the problem. We paid special attention to proper diet and its impact on female fertility. Summary In our review, we presented how big a problem female infertility is. We managed to describe the current state of knowledge on the definition, epidemiology of fertility and infertility, and the main causes of female infertility. Based on a number of studies, we have proven the beneficial effects of a proper lifestyle with emphasis on a proper diet.

Stanniocalcin Protein Expression in Female Reproductive Organs: Literature Review and Public Cancer Database Analysis.

Stanniocalcin (STC) 1 and 2 serve as antihyperglycemic polypeptide hormones with critical roles in regulating calcium and phosphate homeostasis. They additionally function as paracrine and/or autocrine factors involved in numerous physiological processes, including female reproduction. STC1 and STC2 contribute to the pathophysiology of several diseases, including female infertility- and pregnancy-associated conditions, and even tumorigenesis of reproductive organs. This comprehensive review highlights the dynamic expression patterns and potential dysregulation of STC1 and STC2, restricted to female fertility, and infertility- and pregnancy-associated diseases and conditions, such as endometriosis, polycystic ovary syndrome (PCOS), abnormal uterine bleeding, uterine polyps, and pregnancy complications, like impaired decidualization, preeclampsia, and preterm labor. Furthermore, the review elucidates the role of dysregulated STC in the progression of cancers of the reproductive system, including endometrial, cervical, and ovarian cancers. Additionally, the review evaluates the expression patterns and prognostic significance of STC in gynecological cancers by utilizing existing public datasets from The Cancer Genome Atlas to help decipher the multifaceted roles of these pleiotropic hormones in disease progression. Understanding the intricate mechanisms by which STC proteins influence all these reviewed conditions could lead to the development of targeted diagnostic and therapeutic strategies in the context of female reproductive health and oncology.

Adamts9 is required for the development of primary ovarian follicles and maintenance of female sex in zebrafish†.

Previous studies have suggested that adamts9 (a disintegrin and metalloprotease with thrombospondin type-1 motifs, member 9), an extracellular matrix (ECM) metalloprotease, participates in primordial germ cell (PGC) migration and is necessary for female fertility. In this study, we found that adamts9 knockout (KO) led to reduced body size, and female-to-male sex conversion in late juvenile or adult zebrafish; however, primary sex determination was not affected in early juveniles of adamts9 KO. Overfeeding and lowering the rearing density rescued growth defects in female adamts9 KO fish but did not rescue defects in ovarian development in adamts9 KO. Delayed PGC proliferation, significantly reduced number and size of Stage IB follicles (equivalent to primary follicles) in early juveniles of adamts9 KO, and arrested development at Stage IB follicles in mid- or late-juveniles of adamts9 KO are likely causes of female infertility and sex conversion. Via RNAseq, we found significant enrichment of differentially expressed genes involved in ECM organization during sexual maturation in ovaries of wildtype fish; and significant dysregulation of these genes in adamts9 KO ovaries. RNAseq analysis also showed enrichment of inflammatory transcriptomic signatures in adult ovaries of these adamts9 KO. Taken together, our results indicate that adamts9 is critical for development of primary ovarian follicles and maintenance of female sex, and loss of adamts9 leads to defects in ovarian follicle development, female infertility, and sex conversion in late juveniles and mature adults. These results show that the ECM and extracellular metalloproteases play major roles in maintaining ovarian follicle development in zebrafish.

Variants in NLRP2 and ZFP36L2, non-core components of the human subcortical maternal complex, cause female infertility with embryonic development arrest.

The subcortical maternal complex (SCMC), which is vital in oocyte maturation and embryogenesis, consists of core proteins (NLRP5, TLE6, OOEP), non-core proteins (PADI6, KHDC3L, NLRP2, NLRP7), and other unknown proteins that are encoded by maternal effect genes. Some variants of SCMC genes have been linked to female infertility characterized by embryonic development arrest. However, so far, the candidate non-core SCMC components associated with embryonic development need further exploration and the pathogenic variants that have been identified are still limited. In this study, we discovered two novel variants [p.(Ala131Val) and p.(Met326Val)] of NLRP2 in patients with primary infertility displaying embryonic development arrest from large families. In vitro studies using 293T cells and mouse oocytes, respectively, showed that these variants significantly decreased protein expression and caused the phenotype of embryonic development arrest. Additionally, we combined the 'DevOmics' database with the whole exome sequence data of our cohort and screened out a new candidate non-core SCMC gene ZFP36L2. Its variants [p.(Ala241Pro) and p.(Pro291dup)] were found to be responsible for embryonic development arrest. Co-immunoprecipitation experiments in 293T cells, used to demonstrate the interaction between proteins, verified that ZFP36L2 is one of the human SCMC components, and microinjection of ZFP36L2 complementary RNA variants into mouse oocytes affected embryonic development. Furthermore, the ZFP36L2 variants were associated with disrupted stability of its target mRNAs, which resulted in aberrant H3K4me3 and H3K9me3 levels. These disruptions decreased oocyte quality and further developmental potential. Overall, this is the first report of ZFP36L2 as a non-core component of the human SCMC and we found four novel pathogenic variants in the NLRP2 and ZFP36L2 genes in 4 of 161 patients that caused human embryonic development arrest. These findings contribute to the genetic diagnosis of female infertility and provide new insights into the physiological function of SCMC in female reproduction.

Causal relationship between genetically predicted antibody-Mediated Immune Responses and female infertility

ObjectiveThis study aims to explore the causal relationship between Antibody-Mediated Immune Response (AIR) and female infertility using Mendelian randomization analysis, providing new targets and insights for treating female infertility. MethodsExposure data from a genome-wide association study (GWAS) involving 9724 participants provided information on 46 types of AIR. Outcome data were sourced from a large-scale meta-analysis of female infertility, which included 899 cases and 246,641 controls. Five different Mendelian randomization analysis methods were used to assess the genetic causal relationship between AIR and female infertility, with the inverse variance-weighted method as the primary approach. The robustness of the study results was evaluated through heterogeneity analysis, pleiotropy tests, and leave-one-out validation. Replication and meta-analysis were conducted using FinnGen data to further identify AIR. ResultsThrough rigorous genetic variant screening, IVW, sensitivity analysis, replication, and meta-analysis, the results indicate that only seropositivity of anti-polyomavirus 2 IgG shows significant evidence of association with female infertility. The reverse MR analysis did not reveal a genetic causal association between female infertility and this antibody-influencing relationship. Sensitivity analysis showed no evidence of pleiotropy or heterogeneity. Replication and meta-analysis using FinnGen data further supported that only anti-polyomavirus 2 IgG seropositivity has a significant association with female infertility. ConclusionUsing Mendelian randomization analysis in two independent samples, this study presents evidence of a genetic association between anti-polyomavirus 2 IgG seropositivity and female infertility. These findings carry significant implications for the prevention and treatment of female infertility in clinical practice.

Fertility protection during chemotherapy treatment by boosting the NAD(P)+ metabolome.

Chemotherapy induced ovarian failure and infertility is an important concern in female cancer patients of reproductive age or younger, and non-invasive, pharmacological approaches to maintain ovarian function are urgently needed. Given the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) as an essential cofactor for drug detoxification, we sought to test whether boosting the NAD(P)+ metabolome could protect ovarian function. We show that pharmacological or transgenic strategies to replenish the NAD+ metabolome ameliorates chemotherapy induced female infertility in mice, as measured by oocyte yield, follicle health, and functional breeding trials. Importantly, treatment of a triple-negative breast cancer mouse model with the NAD+ precursor nicotinamide mononucleotide (NMN) reduced tumour growth and did not impair the efficacy of chemotherapy drugs in vivo or in diverse cancer cell lines. Overall, these findings raise the possibility that NAD+ precursors could be a non-invasive strategy for maintaining ovarian function in cancer patients, with potential benefits in cancer therapy.

Luteinizing Hormone Receptor Mutation (LHRN316S) Causes Abnormal Follicular Development Revealed by Follicle Single-Cell Analysis and CRISPR/Cas9

Abnormal interaction between granulosa cells and oocytes causes disordered development of ovarian follicles. However, the interactions between oocytes and cumulus granulosa cells (CGs), oocytes and mural granulosa cells (MGs), and CGs and MGs remain to be fully explored. Using single-cell RNA-sequencing (scRNA-seq), we determined the transcriptional profiles of oocytes, CGs and MGs in antral follicles. Analysis of scRNA-seq data revealed that CGs may regulate follicular development through the BMP15-KITL-KIT-PI3K-ARF6 pathway with elevated expression of luteinizing hormone receptor (LHR). Because internalization of the LHR is regulated by Arf6, we constructed LHRN316S mice by CRISPR/Cas9 to further explore mechanisms of follicular development and novel treatment strategies for female infertility. Ovaries of LHRN316S mice exhibited reduced numbers of corpora lutea and ovulation. The LHRN316S mice had a reduced rate of oocyte maturation in vitro and decreased serum progesterone levels. Mating LHRN316S female mice with ICR wild type male mice revealed that the infertility rate of LHRN316S mice was 21.4% (3/14). Litter sizes from LHRN316S mice were smaller than those from control wild type female mice. The oocytes from LHRN316S mice had an increased rate of maturation in vitro after progesterone administration in vitro. Furthermore, progesterone treated LHRN316S mice produced offspring numbers per litter equivalent to WT mice. These findings provide key insights into cellular interactions in ovarian follicles and provide important clues for infertility treatment.Graphical

HUMSCs restore ovarian function in POI mice by regulating GSK3β-mediated mitochondrial dynamic imbalances in theca cells

Premature ovarian insufficiency (POI), a major cause of female infertility, is defined as follicular atresia and a rapid loss of germ cells in women of reproductive age due to ovarian failure. Recently, findings from several studies have indicated that human umbilical cord mesenchymal stem cells (hUMSCs) can alleviate ovarian dysfunction resulting from POI. However, the mechanisms underlying this effect require further clarification. In this study, a mouse model of POI was established as achieved with an intraperitoneal injection of cyclophosphamide (CTX) into female C57BL/6J mice in vivo. These POI mice received a 1-week intervention of hUMACs. In addition, an in vitro POI model was also included. The cultured supernatants of hUMSCs and glycogen synthase kinase 3 beta (GSK3β) inhibitor (SB216763) were used to treat theca cells (TCs) exposed to CTX. Hematoxylin and Eosin (H&E) staining and Enzyme-linked immunosorbent assay (ELISA) were used to assess ovarian structure and morphology, as well as endocrine function in these POI mice. Based on results from the ELISA and JC-1 labeling, CTX exerted significant detrimental effects on testosterone levels and the mitochondrial membrane potential in TCs. Subsequently, Western Blot, Immunofluorescence staining (IF), and Quantitative real-time polymerase chain reaction (qRT-PCR) were used to evaluate various indicators of testosterone synthesis function and mitochondrial dynamics in ovaries and TCs of POI mice. In vivo, dysfunctions in ovarian structure and function in the POI mouse model were effectively restored following hUMSCs treatment, and abnormalities in hormone synthesis were significantly reduced. Furthermore, when the stem cell supernatants of hUMSCs were applied to TCs in vitro we found that GSK3β expression was reduced, the imbalance of mitochondrial dynamics was alleviated, and the ability of mitochondrial testosterone synthesis was increased. Taken together, our results indicate that hUMSCs treatment can restore the imbalance of mitochondrial dynamics and restart testosterone synthesis of TCs by suppressing GSK3β expression, ultimately alleviating POI damage.

Autophagy and Female Fertility: Mechanisms, Clinical Implications, and Emerging Therapies.

Autophagy, an evolutionarily conserved cellular mechanism essential for maintaining internal stability, plays a crucial function in female reproductive ability. In this review, we discuss the complex interplay between autophagy and several facets of female reproductive health, encompassing pregnancy, ovarian functions, gynecologic malignancies, endometriosis, and infertility. Existing research emphasizes the crucial significance of autophagy in embryo implantation, specifically in the endometrium, highlighting its necessity in ensuring proper fetal development. Although some knowledge has been gained, there is still a lack of research on the specific molecular impacts of autophagy on the quality of oocytes, the growth of follicles, and general reproductive health. Autophagy plays a role in the maturation, quality, and development of oocytes. It is also involved in reproductive aging, contributing to reductions in reproductive function that occur with age. This review explores the physiological functions of autophagy in the female reproductive system, its participation in reproductive toxicity, and its important connections with the endometrium and embryo. In addition, this study investigates the possibility of emerging treatment approaches that aim to modify autophagy, using both natural substances and synthetic molecules, to improve female fertility and reproductive outcomes. Additionally, this review intends to inspire future exploration into the intricate role of autophagy in female reproductive health by reviewing recent studies and pinpointing areas where current knowledge is lacking. Subsequent investigations should prioritize the conversion of these discoveries into practical uses in the medical field, which could potentially result in groundbreaking therapies for infertility and other difficulties related to reproduction. Therefore, gaining a comprehensive understanding of the many effects of autophagy on female fertility would not only further the field of reproductive biology but also open new possibilities for diagnostic and treatment methods.

Innovative methods for solving the problem of female infertility associated with endocrine disorders

Aim: to analyze the publications assessing innovative methods of diagnostics and treatment used to solve the problem of female infertility associated with endocrine disorders.Materials and Methods. There was conducted a search for publications in electronic databases PubMed, Google Scholar, and eLibrary, which were selected in accordance with the PRISMA guidelines. All relevant articles published up to January 2024 were included in thereview. As a result, 374 publications retrieved from PubMed, 147 – from eLibrary, and 33– from Google Scholar were extracted. Duplicates and non-full-text versions of articles were excluded. After the selection procedure, 72 publications were included in the review.Results. During the data analysis, we identified key aspects providing deeper understanding of endocrine disorders affecting female infertility. In particular, new correlations were demonstrated between the level of select hormones and treatment success, as well as pathogenetic mechanisms were also identified influencing the conception and pregnancy process. These results will allow to develop more accurate diagnostic criteria and effective treatment methods able to increase women's chances of successful conception and pregnancy.Conclusion. The data analysis identified the hallmark aspects for diagnostics and treatment of female endocrine infertility, with new diagnostic criteria and effective treatment methods identified able to markedly improve outcomes. The crucial potential of the innovative approaches and methods considered contributes to improving reproductive health and increasing the chances of successful conception. We strongly encourage the introduction of such advanced technologies into clinical practice to optimize reproductive success.

The effectiveness of pulsed magnetic therapy, high-intensity magnetic stimulation of the pelvic floor muscles and intrauterine plasma therapy to restore endometrial receptivity after intrauterine interventions in patients of different age

Abstract. Objectives. Advanced age is the cause of female infertility. Restoring endometrial receptivity, especially after intrauterine interventions in women of different reproductive ages, is an unsolved problem of modern rehabilitation. The aim of the study was to evaluate the effectiveness of non-drug methods for restoring endometrial receptivity after intrauterine interventions in women of different reproductive ages. Material and methods. A prospective study was conducted with the participation of 120 women planning pregnancy and undergoing various surgical interventions for endometrial diseases. All patients were randomly divided into three equal groups according to the method of exposure: group 1 — patients received combined pulsed magnetic therapy and intrauterine plasma therapy of the endometrium; group 2 — patients underwent high-intensity magnetic stimulation of the pelvic floor muscles andintrauterine plasma therapy of the endometrium; group 3 — patients underwent pulsed magnetic therapy. Subsequently, in eachgroup, the patients were divided by age into two subgroups: up to 34 years and over 35 years. Results. According to the medical history, patients in the advanced age group were characterized by a significantly greater amount of pathology and a less active lifestyle. The pregnancy rate is twice higher in patients under 34 years of age. Normalization of the menstrual cycle and the rate of increase in blood flow through the uterine arteries occurred twice as fast in younger patients than in older ones. Endometrial thickness and normalization of pipell biopsy data after a course of treatment with high-intensity magnetic stimulation of the pelvic floor muscles and intrauterine plasma therapy were statistically significantly higher in the group of patients under 34 years of age. An increase in the speed of blood flow through the uterine arteries in patients over 35 years of age occurs more effectively with the help of pulsed magnetic therapy and intrauterine plasma therapy of the endometrium. Conclusion. Endometrial receptivity restoration in patients underwent intrauterine interventions using combined non-pharmacological methods is safe and effective. In patients under 34 years of age, the technique of choice may be high-intensity magnetic stimulation of the pelvic floor muscles with intrauterine plasma therapy. In patients over 35 years of age, the method of pulsed magnetic therapy with intrauterine plasma therapy of the endometrium is more effective.