Cause Of Infertility Research Articles

Andrology laboratory technique for analysis of semen in men with azoospermia.

Discovery of spermatozoa during the 17th century led to developing technologies for semen analysis in the early 1900s, and then, standard techniques were implemented during the 20th century. Semen analysis has a pivotal role in the male infertility evaluation, and azoospermia is an important finding. Azoospermia is identified in 15% of infertile men. However, the accurate laboratory assessment of azoospermia poses certain technical challenges. Laboratories currently perform semen assessment with great variability; thus, a standard method should be used. Planning suitable management and determining the cause of infertility require a precise evaluation of azoospermia. This review aims to address the definition of azoospermia and highlight laboratory methods in the assessments of azoospermia. Basic methods such as centrifugation, repeat pellet analysis, and staining and advanced methods such as genetic testing and biomarkers have been discussed. These methods have helped in standardizing the protocol for accurate azoospermia assessments with less variability.

Successful pregnancy with intracytoplasmic sperm injection after bacterial contamination of embryo culture in in vitro fertilization: a case report

BackgroundBacterial infection of embryo culture medium is rare but may be detrimental. The main source of embryo culture contamination is semen. Assisted reproduction centers currently lack consensus regarding the methods for preventing and managing embryo culture infection. In our recent case, a successful pregnancy was achieved with intracytoplasmic sperm injection after failed conventional in vitro fertilization owing to bacterial contamination.Case presentationWe present a case report of two consecutive in vitro fertilization–intracytoplasmic sperm injection cycles with photo and video documentation of the bacterial growth. A 36-year-old Hungarian woman and her 37-year-old Hungarian partner came to our department. They had two normal births followed by 2 years of infertility. The major causes of infertility were a closed fallopian tube and asthenozoospermia. Bacterial infection of the embryo culture medium was observed during in vitro fertilization and all oocytes degenerated. The source was found to be the semen. To prevent contamination, intracytoplasmic sperm injection was used for fertilization in the subsequent cycle. Intracytoplasmic bacterial proliferation was observed in one of the three fertilized eggs, but two good-quality embryos were successfully obtained. The transfer of one embryo resulted in a successful pregnancy and a healthy newborn was delivered.ConclusionIntracytoplasmic sperm injection may be offered to couples who fail conventional in vitro fertilization treatment owing to bacteriospermia, as it seems to prevent infection of the embryo culture. Even if bacterial contamination appears, our case encourages us to continue treatment. Nevertheless, the development of new management guidelines for the prevention and management of bacterial contamination is essential.

Osthole exhibits the remedial potential for polycystic ovary syndrome mice through Nrf2-Foxo1-GSH-NF-κB pathway.

Polycystic ovary syndrome (PCOS) is the primary cause of female infertility with a lack of universal therapeutic regimen. Although osthole exhibits numerous pharmacological activities in treating various diseases, its therapeutic effect on PCOS is undiscovered. The present study found that application of osthole improved the symptoms of PCOS mice through preventing ovarian granulosa cells (GCs) production of more estrogen and alleviating the liberation of pro-inflammatory cytokineinterleukin(IL)-1β, IL-6, andtumor necrosis factor alpha. Meanwhile, osthole enhanced ovarian antioxidant capacity and alleviated intracellular reactive oxygen species (ROS) accumulation with a concurrent attenuation for oxidative stress, while intervention of antioxidant enzymic activity and glutathione (GSH)synthesis neutralized the salvation of osthole on GCs secretory disorder and chronic inflammation. Further analysis revealed that osthole restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)and forkhead box O 1 (Foxo1) whose repression antagonized the amelioration of osthole on the insufficiency of antioxidant capacity and accumulation of ROS. Moreover, Nrf2 served as an intermedium to mediate the regulation of osthole on Foxo1. Additionally, osthole restricted the phosphorylation of IκBα and nuclear factor kappa B (NF-κB)subunit p65 by DHEA and weakened the transcriptional activity of NF-κB, but this effectiveness was abrogated by the obstruction of Nrf2 and Foxo1, whereas adjunction of GSH renewed the redemptive effect of osthole on NF-κB whose activation caused an invalidation of osthole in rescuing the aberration of GCs secretory function and inflammation response. Collectively, osthole might relieve the symptoms of PCOS mice via Nrf2-Foxo1-GSH-NF-κB pathway.

Association between the length of in vitro embryo culture, mode of ART, and the initial endogenous hCG rise in ongoing singleton pregnancies.

Is there an association between the length of in vitro culture, mode of ART and the initial endogenous hCG rise, in cycles with a foetal heartbeat after single embryo transfer (ET) and implantation? Both the length of in vitro culture and the mode of ART have an impact on the initial endogenous rise in hCG in singleton pregnancies. Different factors have been identified to alter the kinetics of hCG in pregnancies. Current studies show conflicting results regarding the kinetics of hCG after different types of ART (fresh vs frozen ET (FET)), the inclusion or not of preimplantation genetic testing (PGT), and the length of time in in vitro culture. This was a multicentre cohort study, using prospectively collected data derived from 4938 women (5524 treatment cycles) undergoing IUI (cycles, n = 608) or ART (cycles, n = 4916) treatments, resulting a in singleton ongoing pregnancy verified by first-trimester ultrasound scan. Data were collected from the Danish Medical Data Centre, used by the three participating Danish public fertility clinics at Copenhagen University hospitals: Herlev Hospital, Hvidovre Hospital, and Rigshospitalet, from January 2014 to December 2021. The fresh ET cycles included cleavage-stage (2 or 3 days in vitro) and blastocyst (5 days in vitro) transfers. FET cycles included cleavage-stage (3 days in vitro before cryopreservation) or blastocyst (5 or 6 days in vitro before cryopreservation) transfers. The IUI cycles represented no time in vitro. To attain a comparable interval for serum-hCG (s-hCG), the ovulation induction time was identical: 35-37 h before oocyte retrieval or IUI. The conception day was considered as: the insemination day for pregnancies conceived after IUI, the oocyte retrieval day for fresh ET, or the transfer day minus 3 or 5 as appropriate for FET of Day 3 or 5 embryos. Multiple linear regression analysis was used, including days post-conception for the hCG measurement as a covariate, and was adjusted for the women's age, the cause of infertility, and the centre. For FET, a sensitivity analysis was used to adjust for endometrial preparation. The study totally includes 5524 cycles: 2395 FET cycles, 2521 fresh ET cycles, and 608 IUI cycles. Regarding the length of in vitro culture, with IUI as reference (for no time in in vitro culture), we found a significantly lower s-hCG in pregnancies achieved after fresh ET (cleavage-stage ET or blastocyst transfer). S-hCG was 18% (95% CI: 13-23%, P < 0.001) lower after fresh cleavage-stage ET, and 23% (95% CI: 18-28%, P < 0.001) lower after fresh blastocyst transfer compared to IUI. In FET cycles, s-hCG was significantly higher after blastocyst transfers compared to cleavage-stage FET, respectively, 26% (95% CI: 13-40%, P < 0.001) higher when cryopreserved on in vitro Day 5, and 14% (95% CI: 2-26%, P = 0.02) higher when cryopreserved on in vitro Day 6 as compared to Day 3. Regarding the ART treatment type, s-hCG after FET blastocyst transfer (Day 5 blastocysts) cycles was significantly higher, 33% (95% CI: 27-45%, P < 0.001), compared to fresh ET (Day 5 blastocyst), while there was no difference between cleavage-stage FET (Days 2 + 3) and fresh ET (Days 2 + 3). S-hCG was 12% (95% CI: 4-19%, 0.005) lower in PGT FET (Day 5 blastocysts) cycles as compared to FET cycles without PGT (Day 5 blastocysts). The retrospective design is a limitation which introduces the risk of possible bias and confounders such as embryo score, parity, and ovarian stimulation. This study elucidates how practices in medically assisted reproduction treatment are associated with the hCG kinetics, underlining a potential impact of in vitro culture length and mode of ART on the very early embryo development and implantation. The study provides clinicians knowledge that the type of ART used may be relevant to take into account when evaluating s-hCG for the prognosis of the pregnancy. No funding was received for this study. AP has received consulting fees, research grants, or honoraria from the following companies: Preglem, Novo Nordisk, Ferring Pharmaceuticals, Gedeon Richter, Cryos, Merck A/S, and Organon. AZ has received grants and honoraria from Gedeon Richter. NLF has received grants from Gedeon Richter, Merck A/S, and Cryos. MLG has received honoraria fees or research grants from Gedeon Richter, Merck A/S, and Cooper Surgical. CB has received honoraria from Merck A/S. MB has received research grants and honoraria from IBSA. MPR, KM, and PVS all report no conflicts of interest. The study was registered and approved by the Danish Protection Agency, Capital Region, Denmark (Journal-nr.: 21019857). No approval was required from the regional ethics committee according to Danish law.

Amphiregulin secreted by umbilical cord Multipotent Stromal Cells protects against ferroptosis of macrophages via the Activating Transcription Factor 3-CD36 axis to alleviate endometrial fibrosis.

Endometrium fibrosis is the leading cause of uterine infertility. Macrophages participated in the occurrence and development of endometrial fibrosis. We previously reported that human umbilical cord multipotent stromal cells (hUC-MSCs) exerted their therapeutic effect in a macrophage-dependent manner in endometrial fibrosis. However precise mechanisms by which hUC-MSCs may influence macrophages in endometrial fibrosis remain largely unexplored. Here, we demonstrated that abnormal iron and lipid metabolism occurred in intrauterine adhesions (IUA) patients and murine models. Ferroptosis has been proven to contribute to the progression of fibrotic diseases. Our results revealed that pharmacological activation of ferroptosis by Erastin aggravated endometrial fibrosis, while inhibition of ferroptosis by Ferrostatin-1 ameliorated endometrial fibrosis in vivo. Moreover, ferroptosis of macrophages was significantly upregulated in endometria of IUA murine models. Of note, transcriptome profiles revealed that CD36 gene expression was significantly increased in IUA patients and immunofluorescence analysis showed CD36 protein was mainly located in macrophages. Silencing CD36 in macrophages could reverse cell ferroptosis. Dual luciferase reporter assay revealed that CD36 was the direct target of activation transcription factor 3 (ATF3). Furthermore, through establishing coculture system and IUA murine models, we found that hUC-MSCs had a protective role against macrophage ferroptosis and alleviated endometrial fibrosis related to decreased CD36 and ATF3. The effect of hUC-MSCs on macrophage ferroptosis was attributed to the upregulation of amphiregulin (AREG). Our data highlighted that macrophage ferroptosis occurred in endometrial fibrosis via the ATF3-CD36 pathway and hUC-MSCs protected against macrophage ferroptosis to alleviate endometrial fibrosis via secreting AREG. These findings provided a potential target for therapeutic implications of endometrial fibrosis.

Major Reproductive Disorders Causing Infertility of Dairy Herds in West Shoa Zone, Ethiopia

Reproduction is a complex process in which individuals produce their offspring to perpetuate life. Breeding efficiency depends on the normal function of the reproductive system. Reproductive disorders are the most common problems affecting the reproductive efficiency and productivity of dairy cows. Although, major reproductive disorders are greatly responsible for high economic losses in dairy herds, there is a scarcity the research done and consistent information on the prevalence and relative importance of these problems causing infertility in dairy herds in the West Shoa Zone. Therefore, the current study was conducted in the West Shoa Zone of Oromia regional state to assess the major reproductive disorders of dairy cows in the areas. These districts, namely Adeaberga, Ambo, and Walmera were purposively selected based on their accessibility and potential for dairy production. A total of 180 dairy producers (60 households from each) were randomly selected for individual interviews using a semi-structured questionnaire. The major reproductive disorders found were 82.2% repeat breeding, 22.2% calf mortality, 27.2% retention of the fetal membrane, 23.3% abortion and 16.3% stillbirth. The prevalence of reproductive problems showed a significant difference within the woredas. The prevalence of repeat breeding, retained fetal membrane and calf mortality were severe in Walmera districts compared to the remaining two districts whereas the prevalence of abortion and stillbirth were severe in Adeaberga. Repeat breeding shows a higher prevalence whereas the stillbirth rates show a lower prevalence. The ultimate goal of dairy herd production is to increase milk yield and manipulate early first service and calving, lower the calving interval and days open and decrease the number of services per conception. However, repeat breeding, retained fetal membrane, abortion, calf mortality and stillbirth were the major causes of infertility in dairy cows in the study areas. Proper breeding strategies and keeping the health conditions of dairy cattle should be employed to ensure improvements in fertility traits.

Frequency and characteristics of Y chromosome microdeletions and karyotypic abnormalities among 4 278 infertile male patients from southwest China

To determine the frequency and characteristics of AZF microdeletions of Y chromosome and karyotypic abnormalities among infertile male patients from southwest China. 4 278 infertile male patients treated at West China Second University Hospital of Sichuan University from September 2018 to July 2023 were selected as the study subjects. Results of Y chromosome microdeletion detection and G-banded karyotyping analysis were retrospectively reviewed. Clinical data of the patients were collected, which have included 2 048 patients with azoospermia, 1 536 patients with oligozoospermia, 310 patients with mild to moderate oligozoospermia, and 384 patients with infertility but normal sperm concentration. An abnormal karyotype was found in 213 (8.80%) of 2 421 patients who had undergone karyotyping analysis. The frequency of Y chromosome microdeletions was 9.86% (422/4 278), which had occurred in 10.4%, 13.28%, 0.97% and 0.52% of the cases with azoospermia, severe oligozoospermia, mild to moderate oligozoospermia, and infertility with normal sperm concentration, respectively. Y chromosome microdeletion detection and karyotyping analysis are crucial for assessing the cause of male infertility. Early diagnosis can facilitate the selection of reproductive methods.

Where do obesity and male infertility collide?

The parallel rise in obesity and male infertility in modern societies necessitates the identification of susceptibility genes underlying these interconnected health issues. In our study, we conducted a comprehensive search in the OMIM database to identify genes commonly associated with male infertility and obesity. Subsequently, we performed an insilico analysis using the REVEL algorithm to detect pathogenic single nucleotide polymorphisms (SNPs) in the coding region of these candidate genes. To validate our findings in vivo, we conducted a comprehensive analysis of SNPs and gene expression of candidate genes in 200 obese infertile subjects and 240 obese fertile individuals using ARMS-PCR. Additionally, we analyzed 20 fertile and 22 infertile obese individuals using Realtime-qPCR. By removing duplicated queries, we obtained 197 obesity-related genes and 102 male infertility-related genes from the OMIM database. Interestingly, the APOB gene was found in common between the two datasets. REVEL identified the rs13306194 variant as potentially pathogenic with a calculated score of 0.524. The study identified a significant association between the AA (P value = 0.001) genotype and A allele (P value = 0.003) of the APOB rs13306194 variant and infertility in obese men. APOB expression levels were significantly lower in obese infertile men compared to obese fertile controls (p < 0.01). Moreover, the AA genotype of rs13306194 APOB was associated with a significant decrease in APOB gene expression in obese infertile men (p = 0.05). There is a significant association between the Waist-to-Hip Ratio (WHR) and LH with infertility in the obese infertile group. These results are likely to contribute to a better understanding of the causes of male infertility and its association with obesity.

Is the MIND diet useful for polycystic ovary syndrome? A case-control study

BackgroundPolycystic ovary syndrome (PCOS) is the most prevalent cause of ovulatory infertility and endocrine abnormalities in reproductive-age women. Although the MIND diet has been introduced to improve brain function, evidence shows that the MIND diet is rich in beneficial food groups that can have a preventive effect on other metabolic disorders. The present study was conducted to investigate the association between adherence to the MIND diet and PCOS.MethodsThis age and BMI frequency-matched case-control study was conducted on 216 women between January 2018 and March 2019 in Yazd, Iran. PCOS was diagnosed based on Rotterdam criteria. Participants were selected by convenience sampling method. The validated 178-item food frequency questionnaire was used to assess the usual dietary intake. Logistic regression was used to estimate the association between the MIND diet and PCOS.ResultsThe findings of the present study showed a significant inverse association between adherence to the MIND diet and PCOS in the crude model (OR for T3 vs. T1: 0.12 (95% CI: 0.05–0.25), P-value < 0.001) and multivariable-adjusted model including energy intake, age, BMI, waist circumference, marital status, pregnancy history, drug use history, education and physical activity (OR for T3 vs. T1 = 0.08 (95% CI: 0.03–0.19), P-value < 0.001). Adherence to the MIND diet had a protective effect of 92%.ConclusionAlthough the results of the present study showed that higher adherence to the MIND diet is associated with a lower risk of PCOS, more studies are needed to confirm these findings in the future.

Sperm epigenetics and sperm RNAs as drivers of male infertility: truth or myth?

Male infertility represents a complex clinical condition that often challenges the ability of reproductive specialists to find its etiology and then propose an adequate treatment. The unexplained decline in sperm count, as well as the association between male infertility and mortality, morbidity, and cancer, has prompted researchers toward an urgent need to better understand the causes of male infertility. Therefore, molecular biologists are increasingly trying to study whether sperm epigenetic alterations may be involved in male infertility and embryo developmental abnormalities. In this context, research is also trying to uncover the hidden role of sperm RNAs, both coding and non-coding. This narrative review aims to thoroughly and comprehensively present the relationship between sperm epigenetics, sperm RNAs, and human fertility. We first focused on the technological aspects of studying sperm epigenetics and RNAs, relating to the complex role(s) played in sperm maturation, fertilization, and embryo development. Then, we examined the intricateconnections between epigenetics and RNAs with fertility measures, namely sperm concentration, embryo growth and development, and live birth rate, in both animal and human studies. A better understanding of the molecular mechanisms involved in sperm epigenetic regulation, as well as the impact of RNA players, will help to tackle infertility.

Changes in characteristics of spermatogonial stem cells in response to heat stress in stallions

Spermatogonial stem cells (SSCs) are essential for the maintenance of male fertility and survival of species. Environmental conditions, notably heat stress, have been identified as important causes of male infertility and have a negative impact on SSCs. Animals with cryptorchid testes (CT) are optimal models for the study of long-term heat stress-related changes in germ cells. The effect of heat stress on germ cells differs depending on the spermatogenesis stage. Thus, verifying whether the specific phase of spermatogenesis is dependent or independent of heat stress in stallions is important. We evaluated the heat stress-related response of SSCs by comparing the relative abundance of mRNA transcripts and expression patterns of the undifferentiated embryonic cell transcription factor 1 (UTF-1) and deleted in azoospermia-like (DAZL) in the seminiferous tubules of CT and normal testes (NT) of stallions using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, and western blotting. We also analyzed the relative abundance of mRNA of different proliferative markers, including minichromosome maintenance 2 (MCM2), marker of proliferation Ki-67 (MKI-67), and proliferating cell nuclear antigen (PCNA). Testicular tissues from four Thoroughbred unilateral cryptorchid postpubertal stallions were used in this study during the breeding season. The relative abundance of the mRNA transcripts of UTF-1 and MCM2 was significantly upregulated in the CT group than that of those in the NT group. In contrast, the relative abundance of the mRNA transcripts of DAZL was significantly downregulated in the CT group than that of those in the NT group. Western blot quantification showed that the relative intensity of UTF-1 protein bands was significantly higher, while that of DAZL protein bands was significantly lower in the CT group than in the NT group. Immunofluorescence studies showed that the number of germ cells immunostained with UTF-1 was significantly higher while immunostained with DAZL was significantly lower in the CT group than that in the NT group. The higher expression level of UTF-1 in the CT group shows that undifferentiated SSCs are not affected by long-term exposure to heat stress. These results also indicate that germ cells after differentiation phase are directly affected by heat-stress conditions, such as cryptorchidism, in stallions.

Seminal plasma S100A8/A9 as a potential biomarker of genital tract inflammation

Abstract Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%–10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.

Predictors of partnership and sexual satisfaction and dyadic effects in couples affected by endometriosis and infertility.

Endometriosis and infertility are associated with impaired partnership and sexuality of the patients, but also of their male partners. Also, endometriosis is one of the most common causes of infertility, resulting in a large overlap of both pathologies. The aim of this study was to determine the association of different predictors of partnership and sexual satisfaction and dyadic effects in couples with endometriosis and infertility. A cross-sectional study was conducted with n = 62 women with endometriosis and n = 46 partners, including a total of n = 44 couples, some of whom were affected by infertility. The questionnaire included items on partnership, sexuality, depression, social support, and desire for a child. Multiple linear regression and the actor-partner-interdependence-model were used for analysis. Significant dyadic effects only occurred in couples with both endometriosis and infertility. Depression showed a significant negative actor effect in men for partnership satisfaction and a negative actor and partner effect in women for sexuality satisfaction (p < .05). For women, social support showed a significant positive actor effect for partnership satisfaction (p < .05), age showed a significant actor and partner effect for sexuality satisfaction (p < .05). The results show a significant association of endometriosis and infertility with partnership and sexuality satisfaction. Infertility could be a decisive factor. However, the large overlapping of both endometriosis und infertility in many couples support the importance of further studies to differentiate between the both effects. German Clinical Trials Register DRKS00014362 on the 29.03.2018.

The Territorial Distribution of Incidence with Urogenital Chlamydia, Gonorrhea, and their Associated Complications in the Russian Federation

Relevance. Urogenital chlamydia is one of the most common sexually transmitted infections. Chlamydia often presents with minimal or no symptoms. However, it can be a major cause of pelvic inflammatory disease (PID), infertility, and ectopic pregnancy in women, as well as epididymitis, orchitis, and infertility in men. Aim. To study the territorial patterns of incidence of urogenital chlamydia, gonorrhea, and their associated complications in the Russian Federation in 2011 to 2019. Materials and methods. Official statistics on the incidence of urogenital chlamydia, gonorrhea, PID, female and male infertility in the Russian Federation were analyzed. Statistical analysis, graphing, table creation, data visualization, and research results analysis were conducted using Microsoft Excel 2010 and IBM SPSS Statistics 22 software. GIS mapping was performed using the GIS «Axioma». Results and discussion. From 2011 to 2019, the Russian Federation observed a decrease in the incidence of urogenital chlamydia, gonorrhea, and PID, while there was an increase in the incidence of male and female infertility. The geographical distribution remained stable, with areas characterized by consistently low and high incidence rates. A correlation was found between the incidence of urogenital chlamydia, gonorrhea, and their complications. The association between gonorrhea and PID was found to be more significant than the association between chlamydia and PID, possibly due to the higher risk of complications associated with gonorrhea. However, no correlation was found between gonorrhea and infertility, possibly because this complication manifests with a time delay and has multifactorial causes. Conclusions. Based on the presented data, it can be concluded that the incidence of urogenital chlamydia and gonorrhea affects the frequency of male and female infertility. Therefore, the implementation of screening examinations for sexually active individuals of reproductive age using appropriate laboratory diagnostic methods, along with the development of preventive measures for sexually transmitted infections, including urogenital chlamydia, is justified and should be widely practiced.

Fungal-bacteria interactions provide shelter for bacteria in Caesarean section scar diverticulum.

Caesarean section scar diverticulum (CSD) is a significant cause of infertility among women who have previously had a Caesarean section, primarily due to persistent inflammatory exudation associated with this condition. Even though abnormal bacterial composition is identified as a critical factor leading to this chronic inflammation, clinical data suggest that a long-term cure is often unattainable with antibiotic treatment alone. In our study, we employed metagenomic analysis and mass spectrometry techniques to investigate the fungal composition in CSD and its interaction with bacteria. We discovered that local fungal abnormalities in CSD can disrupt the stability of the bacterial population and the entire microbial community by altering bacterial abundance via specific metabolites. For instance, Lachnellula suecica reduces the abundance of several Lactobacillus spp., such as Lactobacillus jensenii, by diminishing the production of metabolites like Goyaglycoside A and Janthitrem E. Concurrently, Clavispora lusitaniae and Ophiocordyceps australis can synergistically impact the abundance of Lactobacillus spp. by modulating metabolite abundance. Our findings underscore that abnormal fungal composition and activity are key drivers of local bacterial dysbiosis in CSD.

Fungal–bacteria interactions provide shelter for bacteria in Caesarean section scar diverticulum

Caesarean section scar diverticulum (CSD) is a significant cause of infertility among women who have previously had a Caesarean section, primarily due to persistent inflammatory exudation associated with this condition. Even though abnormal bacterial composition is identified as a critical factor leading to this chronic inflammation, clinical data suggest that a long-term cure is often unattainable with antibiotic treatment alone. In our study, we employed metagenomic analysis and mass spectrometry techniques to investigate the fungal composition in CSD and its interaction with bacteria. We discovered that local fungal abnormalities in CSD can disrupt the stability of the bacterial population and the entire microbial community by altering bacterial abundance via specific metabolites. For instance, Lachnellula suecica reduces the abundance of several Lactobacillus spp., such as Lactobacillus jensenii, by diminishing the production of metabolites like Goyaglycoside A and Janthitrem E. Concurrently, Clavispora lusitaniae and Ophiocordyceps australis can synergistically impact the abundance of Lactobacillus spp. by modulating metabolite abundance. Our findings underscore that abnormal fungal composition and activity are key drivers of local bacterial dysbiosis in CSD.

A randomized controlled trial comparing pioglitazone and metformin prior to in vitro fertilization in polycystic ovary syndrome - associated infertile women: impact on pregnancy rates.

Polycystic ovarian syndrome (PCOS) is one of the significant causes of infertility. Impaired glucose metabolism and insulin resistance add chiefly to the pathogenesis of PCOS. This study aimed to evaluate the efficacy of metformin and pioglitazone (insulin sensitizers) on the quality of the ovum and pregnancy rate in the IVF cycle. In this randomized clinical trial study, 172 infertile women with PCO were enrolled and randomly assigned to receive either 15mg pioglitazone (case group) or 1000mg metformin (control group) twice a day for 6 weeks before IVF, and the pregnancy rate was compared across the groups. The number of ovum and embryos were also accessed and compared between the two groups. In the study, 172 patients participated. The mean age in the control and case groups was 32.09±3.9 years and 32.12±3.9 years, respectively, with no significant age difference. In both groups, the mean number of IVF eggs retrieved was 11.76±3.7 (control) and 11.86±3.7 (case), and the number of embryos formed was 7.43±2.8 (control) and 7.87±3.5 (case), with no significant disparities (P<0.05). Regarding positive pregnancies, 28 out of 86 (32.6%) occurred in the control group, while 42 out of 86 (48.8%) happened in the case group, demonstrating a significant difference (P=0.03). According to the results obtained in this study, it may be concluded that pioglitazone is superior to metformin in IVF cycles in PCOS-associated infertile women leading to a higher pregnancy rate.

Metabolic contribution to age-related chromosome missegregation in mammalian oocytes.

Advanced maternal age is a major cause of infertility, miscarriage, and congenital abnormalities. This is principally caused by a decrease in oocyte quality and developmental competence with age. Oocyte ageing is characterised by an increase in chromosome missegregation and aneuploidy. However, the underlying mechanisms of age-related aneuploidy have not been fully elucidated and are still under active investigation. In addition to chromosome missegregation, oocyte ageing is also accompanied by metabolic dysfunction. In this review, we integrate old and new perspectives on oocyte ageing, chromosome segregation and metabolism in mammalian oocytes and make direct links between these processes. We consider age-related alterations to chromosome segregation machinery, including the loss of cohesion, microtubule stability and the integrity of the spindle assembly checkpoint. We focus on how metabolic dysfunction in the ageing oocyte disrupts chromosome segregation machinery to contribute to and exacerbate age-related aneuploidy. More specifically, we discuss how mitochondrial function, ATP production and the generation of free radicals are altered during ageing. We also explore recent developments in oocyte metabolic ageing, including altered redox reactions (NAD+ metabolism) and the interactions between oocytes and their somatic nurse cells. Throughout the review we integrate the mechanisms by which changes in oocyte metabolism influence age-related chromosome missegregation.

Use of equine embryo -derived mesenchymal stromal cells and their extracellular vesicles as a treatment for persistent breeding-induced endometritis in susceptible mares

Persistent breeding induced endometritis (PBIE) is a significant cause of infertility in mares. The development of a safe, universal, readily available therapeutic to manage PBIE and facilitate an optimal uterine environment for embryo development may improve pregnancy rates in susceptible mares. Mesenchymal stromal cells (MSCs) are being used increasingly as a therapeutic mediator for inflammatory conditions such as endometritis, and early gestational tissue provides a unique source of multipotent stem cells for creating MSCs. Extracellular vesicles (EVs) are mediators of cell communication produced by many different cell types. This study utilized embryo-derived mesenchymal stromal cells (EDMSCs) and their EVs as a potential therapeutic modality for PBIE in two groups: a) PBIE-susceptible mares challenged with pooled dead sperm (n=5); and b) client-owned mares diagnosed as susceptible to PBIE (n=37 mares and 40 estrous cycles). Mares pre-treated with intrauterine EDMSCs or their EVs resulted in a significant reduction in the accumulation of intrauterine fluid post-breeding. Nine of 19 (47%) mares treated with EDMSCs prior to natural breeding and 13 of 20 (65%) mares treated with EDMSC derived EVs were pregnant after the first cycle and 12 of 18 (67%) mares treated with EDMSCs, and 15 of 19 (79%) mares treated with EVs conceived by the end of the breeding season. These preliminary clinical studies are the first reports of the use of EDMSCs or their EVs as a potential intrauterine therapy for the management of PBIE susceptible mares.

Loss of function variant in CIP2A associated with female infertility with early embryonic arrest and fragmentation

BackgroundEarly embryonic arrest and fragmentation (EEAF) is a common cause of female infertility, but the genetic causes remain to be largely unknown. CIP2A encodes the cellular inhibitor of PP2A, playing a crucial role in mitosis and mouse oocyte meiosis. MethodsExome sequencing and Sanger sequencing were performed to identify candidate causative genes in patients with EEAF. The pathogenicity of the CIP2A variant was assessed and confirmed in cultured cell lines and human oocytes through Western blotting, semi-quantitative RT-PCR, TUNEL staining, and fluorescence localization analysis. FindingsWe identified CIP2A (c.1510C > T, p.L504F) as a novel candidate disease-causing gene in human EEAF from a consanguineous family. L504 is highly conserved throughout evolution. The CIP2A variant (c.1510C > T, p.L504F) reduced the expression level of the mutant CIP2A protein, leading to the abnormal aggregation of mutant CIP2A protein and cell apoptosis. Abnormal aggregation of CIP2A protein and chromosomal dispersion occurred in the patient's oocytes and early embryos. We further replicated the patient phenotype by knockdown CIP2A in human oocytes. Additionally, CIP2A deficiency resulted in decreased levels of phosphorylated ERK1/2. InterpretationWe first found that the CIP2A loss-of-function variant associate with female infertility characterized by EEAF. Our findings suggest the uniqueness and importance of CIP2A gene in human oocyte and early embryo development. FundingThis work was supported by National Key Research and Development Program of China (2023YFC2706302), the National Natural Science Foundation of China (81000079, 81170165, and 81870959), the HUST Academic Frontier Youth Team (2016QYTD02), and the Key Research of Huazhong University of Science and Technology, Tongji Hospital (2022A20).