Female Infertility Research Articles

Comparison of the Mitophagy and Apoptosis Related Gene Expressions in Waste Embryo Culture Medium of Female Infertility Types

Mitochondria is an important organelle for the oocyte-to-embryo transition in the early embryonic development period. The oocyte uses mitochondria functionally and its mitochondrial DNA (mtDNA) content as the main energy source in the embryo development at the preimplantation stage. The aim of this study is to compare mitophagic, apoptotic and humanin gene expressions from the culture medium fluid in which embryos are developed and monitored among normoresponder (NOR), polycystic ovary syndrome (PCOS), young and older patients with poor ovarian reserve (POR). The study groups consisted of infertile patients who applied to the Bahçeci Umut IVF Center as NOR (Control), PCOS, POR-Advanced (POR-A) and POR-Young (POR-Y). After the isolation of total RNA from the collected samples, MFN1, MFN2, PINK1, PARKIN, SMN1, SMN2, p53 and Humanin gene expressions were determined by Real Time-PCR. The average age of only the POR-A was determined to be higher than the NOR (p < 0.001). The MFN1, SMN2 (p < 0.05), Humanin and p53 gene expressions (p < 0.001) increased, while PINK1 gene expression decreased (p < 0.05), in the POR-Y compared to the NOR. A decrease in MFN2, PARKIN (p < 0.05) and PINK1 gene expressions was determined in the PCOS compared to the NOR (p < 0.001). Furthermore, a decrease was observed in MFN2, PINK1 (p < 0.001) and Humanin gene expressions compared to the NOR (p < 0.05). The current data are the first in the literature determining the apoptotic and mitophagic status of the oocyte. The current results prove that waste embryo culture fluid may provide a non-invasive profile for important cellular parameters such as mitochondrial dysfunction in female infertility. The evaluation of significant cellular parameters can be performed much earlier without any intervention into the embryo.

Application of Additive Manufacturing in Assisted Reproductive Techniques: What Is the Evidence? A Clinical and Technical Systematic Review of the Literature

Background and Objectives: This article investigates the transformative impact of 3D and bio 3D printing technologies in assisted reproductive technology (ART), offering a comprehensive review of their applications in improving reproductive outcomes. Materials and Methods: Following PRISMA guidelines, we conducted a thorough literature search focusing on the intersection of ART and additive manufacturing, resulting in the inclusion of 48 research papers. Results: The study highlights bio 3D printing’s potential in revolutionizing female infertility treatments, especially in follicle complex culture and ovary printing. We explore the use of decellularized extracellular matrix (dECM) as bioink, demonstrating its efficacy in replicating the ovarian microenvironment for in vitro maturation of primordial oocytes. Furthermore, advancements in endometrial cavity interventions are discussed, including the application of sustained-release systems for growth factors and stem cell integration for endometrial regeneration, showing promise in addressing conditions like Asherman’s syndrome and thin endometrium. We also examine the role of conventional 3D printing in reproductive medicine, including its use in educational simulators, personalized IVF instruments, and microfluidic platforms, enhancing training and precision in reproductive procedures. Conclusions: Our review underscores both 3D printing technologies’ contribution to the dynamic landscape of reproductive medicine. They offer innovative solutions for individualized patient care, augmenting success rates in fertility treatments. This research not only presents current achievements but also anticipates future advancements in these domains, promising to expand the horizons for individuals and families seeking assistance in their reproductive journeys.

DDX3 is critical for female fertility via translational control in oogenesis

AbstractDEAD-box RNA helicase 3 (DDX3) and its homologs play a vital role in translation initiation by unwinding secondary structures of selected mRNAs. The human DDX3 gene is located on the sex chromosomes, so there are DDX3X and DDX3Y. DDX3X is ubiquitously expressed in almost all tissues and critical for embryonic development, whereas DDX3Y is only expressed in the testis and essential for male fertility. Drosophila belle (bel) is the single ortholog of DDX3, and mutations in bel cause male and female infertility. Using Drosophila bel mutants and Ddx3x conditional knockout (cKO) mice, we confirmed the pivotal role of DDX3 in female fertility and ovarian development. Drosophila bel mutants exhibited female infertility and immature egg chambers. Consistently, oocyte-specific Ddx3x knockout in mice resulted in female infertility and impaired oogenesis. We further found that immature egg chambers in Drosophila bel mutants and impaired follicular development in oocyte-specific Ddx3x cKO mice were caused by excessive apoptosis. We also identified a set of DDX3 target genes involved in oocyte meiosis and maturation and demonstrated that DDX3 is involved in their translation in human cells. Our results suggest that DDX3 is critical for female fertility via translational control in oogenesis.

Myo-Inositol and Its Derivatives: Their Roles in the Challenges of Infertility

Myo-inositol (MYO) and D-chiro-inositol (DCI) are the two most significant isomeric forms of inositol, playing a critical role in intracellular signaling. MYO is the most abundant form of inositol in nature; DCI is produced from MYO through epimerization by an insulin-dependent enzyme. Recently, it has been demonstrated that inositol may influence oocyte maturation and improve intracellular Ca2+ oscillation in the oocytes, and it has been proposed as a potential intervention for restoring spontaneous ovulation. The MYO concentration in human follicular fluid is considered a bioindicator of oocyte quality. In the ovary, DCI modulates the activity of aromatase, thus regulating androgen synthesis. Under physiological conditions, the MYO/DCI ratio is maintained at 40:1 in plasma. In women with PCOS, the MYO/DCI ratio is lowered to 0:2:1, contributing to elevated androgen production. By regulating FSH signaling, MYO administration increases the number of high-quality embryos available for transfer in poor responder patients. Finally, by acting downstream to insulin signaling, inositol administration during pregnancy may represent a novel strategy for counteracting gestational diabetes. These findings show that diet supplementation with inositol may be a promising strategy to address female infertility and sustain a healthy pregnancy.

Association between serum unsaturated fatty acids levels and infertility among American women from the National Health and Nutrition Examination Survey 2013-2014.

Some research indicates that unsaturated fatty acids (UFAs) in the diet could enhance reproductive outcomes in infertile women. However, other research holds different views, possibly due to differences in the conversion rates of UFAs from various foods and bioavailability in the body. Therefore, this research examined the link between serum UFAs and infertility issues. This research included reproductive-age women participating in the 2013-2014 American National Health and Nutrition Examination Survey (NHANES). Serum levels of four UFAs, including palmitoleic acid (16:1n-7), vaccenic acid (18:1n-7), oleic acid (18:1n-9), and linoleic acid (18:2n-6) were measured through gas chromatography-mass spectrometry. Infertility data was collected by affirmative responses to targeted questionnaire items. Associations between serum UFA levels and infertility were evaluated utilizing Poisson regression models and smooth curve fitting methods. Sensitivity analysis was also conducted. This study included 535 women, aged between 18 and 45. Poisson regression analysis, both adjusted and unadjusted for confounders, revealed no associations between palmitoleic acid, vaccenic acid, oleic acid, or linoleic acid and female infertility (all P > 0.05). However, four UFAs all showed non-linear relationships with infertility in smooth curve fitting analysis. Sensitivity analysis confirmed the stability of the findings. This research established non-linear associations between serum UFAs and infertility in American women. Specifically, maintaining appropriate serum levels of these UFAs may lower infertility risk. These findings offer new insights and practical dietary recommendations for improving female fertility.

MGA loss-of-function variants cause premature ovarian insufficiency.

Although premature ovarian insufficiency (POI), a common cause of female infertility and subfertility, has a well-established hereditary component, the genetic factors currently implicated in POI account for only a limited proportion of cases. Here, using an exome-wide, gene-based case-control analysis in a discovery cohort comprising 1,027 POI cases and 2,733 ethnically matched women controls from China, we found that heterozygous loss-of-function (LoF) variants of MAX dimerization protein (MGA) were significantly enriched in the discovery cohort, accounting for 2.6% of POI cases, while no MGA LoF variants were found in the matched control females. Further exome screening was conducted in 4 additional POI cohorts (2 from China and 2 from the United States) for replication studies, and we identified heterozygous MGA LoF variants in 1.0%, 1.4%, 1.0%, and 1.0% of POI cases, respectively. Overall, a total of 37 distinct heterozygous MGA LoF variants were discovered in 38 POI cases, accounting for approximately 2.0% of the total 1,910 POI cases analyzed in this study. Accordingly, Mga+/- female mice were subfertile, exhibiting shorter reproductive lifespan and decreased follicle number compared with WT, mimicking the observed phenotype in humans. Our findings highlight the essential role of MGA deficiency for impaired female reproductive ability.

Correlation between cardiometabolic index and female infertility: a cross-sectional analysis.

Obesity and adverse lipid profile leads to female infertility. The cardiometabolic index (CMI) is a promising indicator for predicting obesity-related diseases. The correlation between CMI and female infertility merits further investigation. The data for this study were acquired from the 2013-2020 National Health and Nutrition Examination Survey (NHANES), with 2333 women enrolled. The cardiometabolic index (CMI) of each participant was calculated as the ratio of triglycerides and high-density lipoprotein cholesterol multiplied by waist-to-height ratio. Weighted multivariate logistic regression models were used to assess the independent correlation between the log-transformed CMI and infertility. Subgroup analyses were carried out to assess the reliability of the findings. Interaction tests were employed to determine whether variables affected infertility by interacting with log CMI. A total of 2333 participants aged 18-45 years were enrolled, 274 of whom were infertile. Log CMI of the infertility group was significantly higher than that of the non-infertility group (P < 0.001). After adjustment for potential confounders, women with higher CMI were at an increased risk of infertility (OR = 2.411, 95% CI: 1.416-4.112), and this correlation was still consistent in subgroups aged under 35 years (P < 0.001). Furthermore, restricted cubic spline analysis showed a positive non-linear relationship between log CMI and infertility. Cardiometabolic index levels are positively correlated with increased risk of infertility in American females. Our study demonstrates the predictive capacity of CMI for female infertility.

Effects of dietary quercetin on retrieved mouse oocytes and in vitro fertilization outcomes.

To investigate the effects of dietary quercetin on the retrieved mouse oocytes and IVF outcomes. Female mice were divided into two groups. Mice were given 0.2 mL water without (control group) or with quercetin 30 mg/kg (quercetin group) orally via gavage, once a day for 21 consecutive days. After that female mice were superovulated for in vitro fertilization. We observed the effect of dietary quercetin on the number of retrieved oocytes, oocyte degeneration rate, fertilization rate, blastocyst formation rate, and blastocyst cell numbers. There was no difference in the number of retrieved oocytes per mouse (27.3±6.7 and 27.2±5.8), oocyte fragmentation rate (28.4% and 25.0%), fertilization rate (47.4% and 50.6%) and blastocyst formation rate (34.8% and 34.7%) in the quercetin group compared to the control group. The proportion of hatching and hatched blastocyst was significantly lower in the quercetin group (17.2% and 27.8%, p=0.004) and significantly lower numbers of cells in TE (47.4±15.3 and 57.2±17.7) and total cells (66.2±18.5 and 77.5±20.7) compared to the control group (p=0.001). Dietary quercetin supplementation has a detrimental effect on mouse embryo quality. Moreover, it did not show any beneficial effect on the ovary in both quantity and quality. This finding raises awareness of the general use of dietary quercetin supplements in infertile females.

Preconception exposure to bisphenol A and its alternatives: Effects on female fecundity mediated by oxidative stress and ovarian reserve.

Various 'Bisphenol A (BPA)-free' alternatives have emerged in numerous personal products in recent years. However, it remains unclear whether BPA analogs affect female fecundity and possible biological mechanisms. We aimed to evaluate the relationships of bisphenol analogs with female fecundability and infertility and whether oxidative stress, inflammation, and ovarian reserve may play a mediation role in such associations. This prospective preconception cohort study included 957 couples who attempted pregnancy. BPA and six alternatives were measured in women's urine samples. Bisphenol analogs-outcome associations were estimated using discrete-time Cox hazards and logistic regression models. A quantile g-computation (QGC) methodology was further applied to assess the joint effects of co-exposure to bisphenol analogs on fecundity. We also quantified three biomarkers, including malondialdehyde (MDA), C-reactive protein and Anti-Müllerian hormone (AMH), to explore possible biological pathways. Using an integrated analytical approach consisting of both single-pollutant and mixture models, we found that BPA and bisphenol AP (BPAP) were significantly associated with decreased fecundability (adjusted fecundability ratio (aFR) = 0.87, 95%CI:0.81, 0.94 for BPA; aFR = 0.64, 95%CI: 0.48, 0.84 for BPAP) and increased risk of infertility (adjusted odd ratio (aOR) = 1.23, 95%CI:1.06, 1.44 for BPA; aOR = 2.27, 95%CI:1.29, 3.99 for BPAP) after controlling for other bisphenol analogs. The link between BPA and prolonged time to pregnancy was more prominent in overweight or obese women and those who had regular menstrual cycles. Bisphenol AF was associated with impaired fecundity in women aged 35 years or older. The mixed effects of bisphenol analogs on fecundity were statistically non-significant. Mediation analysis revealed a significant indirect effect of urinary MDA and serum AMH in bisphenol analogs-induced impaired fecundity, with all average causal mediation effects (ACME) showing statistical significance (PACME < 0.05). Our prospective preconception cohort study suggests that BPA and BPAP may be associated with impaired female fecundity. Increased oxidative stress and decreased ovarian reserve may be the underlying pathways.

Fertiloscopy and its place in the gynaecologist's armamentarium.

Infertility is a prevalent issue worldwide. Current investigation of female pelvic infertility uses transabdominal laparoscopy, exposing patients to its associated risks. An alternative method is fertiloscopy, comprising hysteroscopy, tubal dye studies, and transvaginal hydrolaparoscopy (TVHL), falling under the broader category of VNOTES. This study reviews fertiloscopy cases in Australia to assess its role in managing infertility. Retrospective analysis of 76 cases was performed with review of imaging results, fertiloscopy findings and interventions, and fertility outcomes. Statistical analysis was conducted via R Studio v4.1 with means and averages used for descriptive data and a Kruskal-Wallis analysis of variance test used to evaluate differences in continuous variables. Kaplan-Meier curves were constructed to describe cumulative pregnancy incidence, with differences evaluated using log-rank tests. Statistical tests were two-tailed, and a P-value < 0.05 was considered significant. Of 76 cases, 70 underwent fertiloscopy and 35 an intra-operative intervention. Of the cohort, 53 conceived, 18 spontaneously. The highest chance of spontaneous conception was 44% by day 283. The failure rate of fertiloscopy was 5.3%, and complications occurred in 1.3% of cases. The highest chance of spontaneous conception post-fertiloscopy was 44% by day 283, possibly indicating the time between the procedure and referral to reproductive therapies. This study identified a low associated failure and complication rate, supporting fertiloscopy as a low-risk procedure. Despite limitations, this study highlights spontaneous pregnancy outcomes and associated low complication and failure rates, emphasising fertiloscopy's role in managing infertility in Australia as a lower risk surgical alternative to standard laparoscopy.

Cumulus cell DNA damage linked to fertilization success in females with an ovulatory dysfunction phenotype

Intracytoplasmic sperm injection (ICSI) is a widely used technique in fertility centers. ICSI success depends on both nuclear and cytoplasmic oocyte maturation. Cumulus cells, which surround the oocytes, play a pivotal role in oocyte competence. However, the significance of DNA damage in cumulus cells as a marker of fertilization success remains largely unexplored. This study aims to investigate the relationship between DNA damage in cumulus cells of females undergoing ICSI, and oocyte competence, with a focus on in vitro fertilization (IVF) outcomes. We employed the alkaline comet assay to assess DNA damage levels (%TDNA) in cumulus cells and whole blood from 22 potentially fertile females and 35 infertile females, including 20 with an ovulatory disfunction phenotype. Our results revealed significant differences between the levels of %TDNA in cumulus cells and blood. Females with an ovulatory dysfunction phenotype exhibited higher levels of %TDNA in cumulus cells compared to potentially fertile females. Additionally, within the group of females with ovulatory dysfunction, a significant correlation was observed between %TDNA levels and the number of oocytes with two pronuclei. Our findings suggest that blood does not accurately reflect DNA damage in cumulus cells, which was correlated with the fertilization success in females with ovulatory dysfunction. High levels of %TDNA in cumulus cells were associated with a higher likelihood of successful fertilization. Moreover, our results imply that low levels of %TDNA may be linked to oocytes that fail to complete maturation and, consequently, do not fertilize (oocytes with zero pronuclei). Further research with larger cohorts is necessary to validate these findings and to explore potential applications in female fertility. However, our study provides evidence that DNA damage in cumulus cells may serve as a valuable biomarker for predicting fertilization success and oocyte competence.

Association between estimated glucose disposal rate and female infertility: a cross-sectional study

BackgroundInsulin resistance (IR) can lead to infertility in women. The primary objective of this research was to examine how estimated glucose disposal rate (eGDR) correlates with infertility in women, assessing its validity as an indicator of IR.MethodsData from the National Health and Nutrition Examination Survey spanning 2013 to 2018 were analyzed in this study. In order to investigate the correlation between eGDR and the prevalence of female infertility, this study used a combination of weighted multivariate regression analysis, restricted cubic spline (RCS) analysis, subgroup analyses, sensitive analysis, and receiver operating characteristic (ROC) curves.ResultsThis study enrolled 2541 women, with an average age of (32.52 ± 0.23) years. The overall infertility rate was 14.27%. A negative relationship was observed between eGDR levels and female infertility. Each increment of one unit in eGDR was linked to a 14% reduction in infertility incidence (OR = 0.86, 95% CI 0.80–0.94). RCS analysis revealed a nonlinear, inverse correlation between eGDR and female infertility. Subgroup analyses indicated that age influenced the association between eGDR and female infertility. The ROC curve suggested that eGDR was significantly better than HOMA-IR in predicting infertility [eGDR: 0.632 (95% CI: 0.603, 0.660) vs. HOMA-IR: 0.543 (95% CI: 0.514, 0.572)].ConclusionThere was an observed association where lower eGDR levels were linked with higher rates of female infertility. These results emphasize the significance of implementing measures to manage IR to protect women’s reproductive health.

Refining MRI Protocols for Endometriosis: A Comparative Study of Abbreviated and Full MRI Sequences.

Endometriosis is a significant cause of chronic abdominal pain and infertility in females, often overlooked due to its resemblance to other abdominopelvic pathologies. This study aims to compare the diagnostic performance and agreement rate between an abbreviated MRI protocol (aMRI) and a full MRI protocol (fMRI) for detecting pelvic endometriosis. We retrospectively analyzed 446 consecutive MRI exams, including both full (fMRI) and abbreviated (aMRI) protocols, performed for suspected pelvic endometriosis. An expert radiologist assessed the presence of endometriosis at 14 distinct anatomical sites. Each MRI protocol was interpreted in random order, with a minimum two-week interval between sessions to minimize recall bias. Agreement between the protocols was evaluated using kappa statistics. The average age of the patients was 34.13 years. The highest incidences of endometriosis were found in the ovaries (88.8%) and the rectouterine pouch (65%). The MRI protocols demonstrated perfect agreement (kappa coefficient = 1) for the ovaries, bladder, uterus, and cesarean section scar. High agreement was also observed in the rectum and uterine ligaments (kappa coefficients of 0.98 and 0.97). Detection of malignant transformation in existing ovarian endometriomas showed substantial concordance with a kappa coefficient of 0.66. An abbreviated non-contrast MRI protocol exhibits diagnostic accuracy comparable to that of a comprehensive protocol in detecting pelvic endometriosis, with similar confidence and reproducibility. This study demonstrates that an abbreviated MRI protocol is as effective as a full protocol in diagnosing pelvic endometriosis, potentially allowing for quicker, cost-effective imaging without compromising diagnostic accuracy.

Exploring lncRNA expression in follicular fluid exosomes of patients with obesity and polycystic ovary syndrome based on high-throughput sequencing technology.

Infertility is a reproductive health problem that attracts worldwide attention. Polycystic ovary syndrome (PCOS) is a major cause of female infertility and patients with obesity and PCOS are particularly common in clinical practice. Long non-coding RNA (lncRNAs) are a functional core in cells that regulate gene expression, transcription, and chromatin modification processes, and participate in epigenetics, cell cycle, and cell differentiation. LncRNAs are assumed to play a role in the occurrence and development of PCOS; however, their specific mechanism of action remains to be elucidated. High-throughput sequencing technology has been used to sequence and analyze lncRNAs in exosomes from the follicular fluid of patients with obesity and PCOS and those who underwent assisted reproductive therapy owing to male factors. Specific expression profiles of patients with obesity and PCOS were obtained and functional information analysis combined with a literature review were performed to screen for differentially expressed lncRNAs, which were validated using real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR). High-throughput sequencing analysis revealed that compared to normal patients with male infertility, patients with obesity and PCOS had a total of 20 lncRNAs with significant expression differences in follicular fluid exosomes. Among them, 17 lncRNAs were upregulated and three were downregulated. Functional analysis showed that differentially expressed genes were mainly enriched in "cell metabolism," "cell adhesion," and other aspects: related gene pathways mainly involved Huntington's disease, Parkinson's disease, spliceosomes, non-alcoholic fatty liver disease, and ribosomes. Verification of differentially expressed lncRNAs revealed that the expression of lncRNAs TPT1-AS1, PTOV1-AS1, PTPRG-AS1, and SNHG14 in follicular fluid exosomes was consistent with the sequencing results. A preliminary differential expression profile of lncRNAs in exosomes of patients with obesity and PCOS was established by transcriptomic analysis of these individuals. Our bioinformatics analysis results may be applicable to further study of the impact mechanism involving obesity and PCOS. These differentially expressed lncRNAs maybe served as potential biomarkers for in-depth studies of the occurrence, development on Follicle quality and function for patients with PCOS in the future.

Role of Laparoscopy in Diagnosis of Tuboperitoneal and Pelvic Factors of Female Infertility

Role of Laparoscopy in Diagnosis of Tuboperitoneal and Pelvic Factors of Female Infertility

A Delphi Study on the Management of Female Infertility by Homeopaths in South Africa

ackground: Infertility affects millions of people worldwide and has a negative social and psychological impact on the lives of infertile couples. Homeopathy offers an alternative treatment option for female infertility; however, there is currently no research describing how homeopaths manage this condition in their practice.Aim: To determine homeopathic practitioners’ approaches to managing female infertility.Method: The electronic Delphi technique consisting of three rounds was used to establish consensus among homeopaths. Twelve registered homeopaths with a minimum of 5 years of clinical experience in managing female infertility participated, 11 of whom completed the study. In round one, participants elaborated on interventions found beneficial in clinical practice for female infertility. Responses were qualitatively analysed to create a structured list of items; participants rated their level of agreement with these items on a 5-point Likert scale in the second and third rounds. Consensus was determined for items that reached an agreement level of 75% or more.Results: Thirty-two statements achieved expert consensus, which were placed into the following categories: homeopathic treatment, dietary and lifestyle modifications, supplementation and referrals.Conclusion: The results of this study provide a baseline depicting the homeopathic approach to treating female infertility. Several research gaps have been identified and further studies are necessary to explore these interventions to improve future patient care.Contribution: This study highlights the various approaches used by homeopathic practitioners in the management of female infertility.

Fertility protective effects of Brillantaisia patula leaf extract against cyclophosphamide-induced ovarian damage in Wistar rats

BackgroundThe primary indication of infertility is the incapacity to conceive, and in females, the majority of instances of female infertility stem from ovulation disorders. This study evaluated the female fertility-enhancing effects and safety of aqueous leaf extract of Brillantaisia patula (ALEBP) in a cyclophosphamide (CYP) model of sterility in Wistar rats.MethodSixty-six female rats randomly allotted to six groups (n = 11) were administered with the appropriate regimen for 21 days and then mated with male rats. Group 1 (control) received distilled water. Groups 2–6 were treated with a single dose (200 mgkg− 1 body weight) of cyclophosphamide intraperitoneally and, in addition, received the same volume (0.5 mL) of distilled water, 18, 36, 72 mgkg− 1 body weight of ALEBP and 200 mg per body weight of vitamin C orally. Mating lasted 11 days; on day 20, the female Wistar rats were sacrificed. Data were analysed using One-way Analysis of Variance (ANOVA) followed by Dunett’s posthoc analysis, and GraphPad (at p < 0.05).ResultsResults herein showed that ALEBP significantly (p < 0.05) increased the diminution in activities/levels of glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant capacity (TAC), cholesterol, alkaline phosphatase (ALP), acid phosphatase (ACP), estrogen (ES), and luteinising hormone (LH) induced by cyclophosphamide. ALEBP further reversed the increased level of malondialdehyde (MDA), tumour necrosis factor-α (TNFα), interleukin 8 (IL-8), and follicle-stimulating hormone (FSH) caused by cyclophosphamide (p < 0.05). In addition, ALEBP, while it significantly increased the cyclophosphamide-induced reduction in the number of implantations in each animal, the total number of viable fetuses, the total number of corpora lutea, and the fertility index, also significantly reduced the number of fetal resorptions in each animal and pre-implantation loss that was increased by cyclophosphamide. Moreover, the cyclophosphamide-induced degenerative and necrotic changes in the ovarian cells and uterus were reversed by ALEBP.ConclusionsConsidered as a whole, the aqueous leaf extract of Brillantaisia patula reversed oxidative stress and inflammatory side effects of cyclophosphamide, preserving ovarian function and fertility in the rats. This may suggest its exploration as a safe agent against toxic side effects of chemotherapy and fertility-related disorders of the uterus and ovary.

THERAPEUTIC USE OF ALPHA-LIPOIC ACID SUPPLEMENTATION: A REVIEW ON CURRENT USE AND FUTURE PROSPECTIVE

Alpha-lipoic acid (ALA, thioctic acid, 5-(1,2-dithiolan-3-yl) pentanoic acid) is an organosulfur compound produced by plants, humans, and animals. ALA plays a crucial role in mitochondrial bioenergetics reactions. It is a natural antioxidant and a dithiol compound. ALA is a coenzyme that plays a crucial role in the function of pyruvate and Alpha-ketoglutarate dehydrogenase complexes found in mitochondria. ALA has cytotoxic and antiproliferative effects on several cancers, including Polycystic Ovarian Syndrome (PCOS). Most of ALA's clinical applications come from its antioxidant properties, but it also shows potential in treating female and male infertility. Although ALA can potentially be a therapeutic agent, its pharmacokinetic profile limits its effectiveness. Research suggests that ALA has a short half-life and low bioavailability (around 30%) because it gets broken down in the liver, has reduced solubility, and is unstable in the stomach. Liquid formulations have higher bioavailability and plasma concentration than solid dose forms. This review covers the current clinical evidence on using ALA to prevent, manage, and cure numerous disorders, including diabetic neuropathy, obesity, central nervous system-related ailments, and pregnancy abnormalities.

Effect of Paternal Body Mass Index on Cumulative Live Birth Rates: Retrospective Analysis of 3048 Embryo Transfers in Couples Using Autologous Gametes

Obesity is a multifactorial disease present worldwide and correlated with hormonal alterations that may cause a decrease in reproductive outcomes and seminal quality. However, the specific mechanisms involved are unknown. This led us to examine the relationship between paternal body mass index (BMI) and clinical reproductive outcomes by evaluating the cumulative live birth rates (CLBRs) per number of embryo transfers (ETs), embryos replaced (EmbRs), and oocytes used (OUs) in consecutive treatments until achieving the first newborn. A retrospective study was performed, and Kaplan–Meier survival curves were created to observe CLBRs with regard to the paternal BMI, adjusted by relevant confounders through Cox regression models. The participants were couples undergoing intracytoplasmic sperm injection (ICSI) and ET in Spanish IVIRMA clinics using autologous gametes. The cohort was subdivided based on paternal BMI: normal (18.5–24.99 kg/m2) (N), overweight (25–29.99 kg/m2) (OV), or obese (≥30 kg/m2) (OB) patients. A total of 4750 ICSI cycles were included, encompassing 49,485 mature oocytes, 23,963 blastocysts, and 3048 ETs. When calculating CLBRs based on the number of ETs carried out until live birth was achieved, no statistically significant differences were found (p = 0.72). After adjusting for maternal age and BMI, female infertility diagnosis, the use of preimplantation genetic testing, and the number of ETs, Cox regression showed that there were no statistically significant differences between the BMI groups (HR: 0.94 [95% CI: 0.7–1.2]; p = 0.59). When calculating CLBRs considering EmbRs, there was a similarity between the BMI groups (p = 0.57). However, there were no statistically significant differences in the adjusted Cox regression (HR: 0.93 [95% CI: 0.7–1.2]; p = 0.51). Finally, when calculating CLBRs considering OUs, the results were comparable among BMI subgroups (p = 0.75), and there were no statistically significant differences with adjusted Cox regression (HR: 0.95 [95% CI: 0.8–1.2]; p = 0.66). In conclusion, paternal BMI was not associated with clinical reproductive outcomes when considering the ETs, EmbRs, or OUs needed to reach the first liveborn (LB).

Genetic Landscape of a Cohort of 120 Patients with Diminished Ovarian Reserve: Correlation with Infertility

Diminished ovarian reserve (DOR) and primary ovarian insufficiency (POI) are major causes of female infertility. We recently found a monogenic etiology in 29.3% of POI, leading to personalized medicine. The genetic landscape of DOR is unknown. A prospective study (2018–2023) of an international cohort of 120 patients with unexplained DOR was performed using a large custom targeted next-generation sequencing panel including all known POI-causing genes. The diagnostic yield, based on the American College of Medical Genetics, was 24, 2%. Genes belong to different pathways: metabolism and mitochondria (29.7%), follicular growth (24.3%), DNA repair/meiosis (18.9%), aging (16.2%), ovarian development (8.1%), and autophagy (2.7%). Five genes were recurrently found: LMNA, ERCC6, SOX8, POLG, and BMPR1B. Six genes identified in single families with POI were involved in DOR, GNAS, TGFBR3, XPNPEP2, EXO1, BNC1, ATG, highlighting their role in maintaining ovarian reserve. In our cohort, 26 pregnancies were recorded, but no pregnancy was observed when meiosis/DNA repair genes were involved, suggesting severely impaired oocyte quality. Additional studies should confirm these preliminary results. This study with a large NGS panel defines the genetic landscape of a large cohort of DOR. It supports routine genetic diagnosis. Genetics could be a biomarker predicting infertility and progression to POI.