Clinical and Experimental Reproductive Medicine-CERM最新文献

Objective: While obesity has been associated with poor reproductive outcomes, the specific factors affecting gametes remain unclear. Our primary objective was to assess the relationship between a couple's pre-pregnancy body mass index (BMI), the morphokinetic characteristics of embryos, and their potential for implantation. We analyzed standard semen parameters, sperm chromatin integrity, and oxidative stress levels in men undergoing assisted reproductive techniques (ART).

Methods: A total of 1,320 couples were categorized into nine different weight classes. Following the incubation of embryos in a time-lapse device, we evaluated embryo development and ART outcomes.

Results: Significant differences were observed in the percentage of sperm with normal morphology, as well as in the levels of reactive oxygen species, malondialdehyde, and total antioxidant capacity, between overweight and normal-weight men. Overweight men also showed a higher percentage of motile spermatozoa with altered chromatin. After adjusting for parental age and infertility causes, t5 and t8 durations were longer in obese women. In overweight men, t2 and t8 were delayed compared to those in normal-weight couples. Additionally, overweight couples experienced faster time of pronuclei appearance and time of pronuclei fading, along with longer t2, t5, and t8, compared to their normal-weight counterparts. Moreover, overweight males exhibited a lower fertility rate than normal-weight men. Overweight couples also demonstrated significantly lower rates of clinical pregnancy and fertilization, which correlated with higher miscarriage rates.

Conclusion: This time-lapse study revealed that the combined pre-pregnancy BMI of parents is associated with slower pre-implantation embryo development.

In cases of severe oligospermia and non-obstructive azoospermia, few spermatozoa with appropriate motility and viability are detected in epididymal and testicular samples. Sperm cryopreservation is performed to avoid multiple testis biopsies and to maintain samples. Consequently, various sperm retrieval methods are employed together with intracytoplasmic sperm injection. Common cryopreservation techniques are not ideal if there are few spermatozoa because sperm may be lost during the freezing and thawing procedures. Single sperm cryopreservation was first developed in 1997 and has since evolved in various aspects, including cryo-devices, freezing methods, cryoprotectants, and clinical and neonatal outcomes, as discussed in this comprehensive review. The CENTRAL, Embase, MEDLINE, PubMed, Scopus, and Web of Science databases were searched for relevant studies published during 1997-2023. Single sperm cryopreservation has been applied successfully for individuals with a limited number of spermatozoa. First, cryo-devices and their advantages and disadvantages are discussed. Furthermore, different aspects of this technique-including the use of testicular sperm rather than ejaculated sperm, proper cryoprotectants with ideal freezing outcomes, optimal cooling and warming rates, and testicular sperm selection prior to freezing-require more attention. This technique has been applied in clinical settings, and clinical outcomes have been reported using various carriers such as empty zonae pellucidae, straws, cell sleepers, cryotops, cryopieces, the sperm vitrification device (Sperm VD), and stripper tips. Furthermore, delivery rates have also been reported using this method. Nonetheless, more clinical trials are required to facilitate biological offspring through a practical platform.

In an era where male infertility poses significant challenges for many couples, intracytoplasmic sperm injection (ICSI) is becoming increasingly common. Microscopic evaluation of sperm head morphology can contribute to the development of healthier embryos. A comprehensive literature search was conducted using the PubMed, Scopus, Web of Science, and Cochrane databases. A meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) for randomized controlled trials. Eligible studies were selected based on the PICOS (Population, Intervention, Comparison/Comparator, Outcomes, Study type) model. The pregnancy outcomes considered after artificial reproductive technology (ART) procedures included the fertilization rate (FR), high-quality embryo rate (HQER), implantation rate (IR), and clinical pregnancy rate (CPR). This study was registered on PROSPERO (CRD42023423108). Of 105 records evaluated, three studies met the inclusion criteria. Our analysis indicated that birefringence sperm selection significantly improved HQER and IR after ART, although no significant differences were observed for FR and CPR. The use of birefringence for sperm selection in ICSI cycles may represent a straightforward strategy to improve ART outcomes, particularly for couples with abnormal sperm parameters.

Objective: Di(2-ethyl-hexyl) phthalate (DEHP) is a widely used plasticizer that adversely affects sperm quality and function by inducing DNA damage and caspase-independent cell death (CICD). Nuclear glutathione peroxidase 4 (nGPx4) has been implicated in maintaining the structural integrity of sperm chromatin. However, it remains unclear whether nGPx4 can counteract the DNA damage caused by DEHP exposure.

Methods: We employed a germ cell line (GC-1) spg mouse cell model engineered to overexpress nGPx4 (OE-nGPx4). The cells were subsequently exposed to DEHP and its metabolite mono-2-ethylhexyl phthalate (MEHP) to simulate the DNA-damaging effects of environmental factors on reproductive cells. Following treatment, we assessed the proportion of apoptotic cells and the extent of DNA damage using molecular biological analyses, in addition to evaluating the expression of proteins associated with the apoptotic pathway in germ cells.

Results: nGPx4 overexpression protected against DEHP-induced DNA damage in germ cells, reducing the incidence of CICD and potentially preserving sperm quality. This protective effect was mediated by enhanced chromatin condensation in mouse sperm cells and downregulation of phosphorylated H2A histone variant (γ-H2A.X). The reduction in DNA degradation is attributed to a diminished formation of the complex between γ-H2A.X and apoptosis-inducing factor (AIF), resulting in decreased DNA fragmentation. Additionally, compared to MEHP-treated cells, OE-nGPx4 cells exhibited reduced expression of Bcl 2-associated X (Bax), thereby diminishing activation of the γ-H2A.X/AIF axis.

Conclusion: Our findings suggest that nGPx4 is involved in chromatin condensation and may contribute to downregulating the AIF/γ-H2A.X axis in male germ cells, ultimately reducing DNA damage-induced CICD.

Objective: Levofloxacin (LVFX), a fluoroquinolone antibiotic, is used in the treatment of urogenital tract diseases affecting the reproductive system. This study aimed to examine the protective effects of coenzyme Q10 (CoQ10) against LVFX-induced side effects using stereological methods.

Methods: Eighty rats were divided into eight groups: control (distilled water), CoQ10 (10 mg/kg/day), and low dose (25 mg/kg/day), medium dose (50 mg/kg/day), and high dose (100 mg/kg/day) of LVFX (low dose [LD]-LVFX, medium dose [MD]-LVFX, and high dose [HD]-LVFX) with or without CoQ10 administration. Treatments were performed daily for 4 weeks. Sperm parameters, serum testosterone levels, testicular oxidative stress markers, and testicular histology were evaluated.

Results: Sperm count, motility, normal morphology, and viability, as well as serum testosterone levels, were reduced, while malondialdehyde concentrations increased in MD-LVFX and HD-LVFX treated animals compared to controls. MD-LVFX and HD-LVFX treatments produced a 6% to 56% reduction in the volumes, lengths, and diameters of seminiferous tubules and their epithelium, whereas the interstitial tissue volume increased by 43% to 53% in these groups. The numbers of spermatogonia, spermatocytes, spermatids, Sertoli cells, and Leydig cells were reduced by 23% to 76% in animals treated with MD-LVFX and HD-LVFX compared to controls. Notably, all changes observed in the rats receiving CoQ10 were similar to those in the control group, and although most parameters decreased in animals that received LD-LVFX, the differences were not statistically significant relative to controls.

Conclusion: LVFX treatment for 28 days, regardless of dose, adversely affected sperm parameters and testicular tissue. CoQ10 exhibited a protective effect by mitigating the structural and functional impairments induced by LVFX.

Objective: Tramadol is a centrally acting analgesic with a modest opioid effect similar to morphine and codeine, but less potent; it is mainly prescribed for the treatment of mild to moderate pain. Tramadol exhibits both opioid and non-opioid properties, primarily affecting the central nervous system. Accordingly, the present study was designed to investigate the effects of tramadol on female reproductive function and ovarian toxicity, as well as to examine oocyte survival and follicular development in mice exposed to tramadol.

Methods: Mice were treated with tramadol at 50 mg/kg daily for 3 weeks. Blood levels of the hormones estrogen and progesterone were measured. The ovaries of the mice were subjected to histological, immunohistochemical, and molecular studies.

Results: Our results revealed that tramadol provoked ovarian atrophy by inducing oxidative stress, while also decreasing oocyte survival and impairing follicular development.

Conclusion: Although further research is necessary, the findings indicate that tramadol could reduce fertility in female mice.

Objective: To compare the outcomes of microscopic subinguinal varicocelectomy versus oral antioxidants in managing male infertility associated with isolated teratozoospermia.

Methods: This multicenter randomized controlled trial was conducted between January 2022 and January 2024. A total of 81 patients with isolated teratozoospermia and clinical varicoceles completed the study; 40 patients underwent varicocele ligation (group A), and 41 patients received oral antioxidants (L-carnitine, vitamin C, and vitamin E) (group B). Sperm morphology, sperm DNA fragmentation (SDF), and the achievement of natural pregnancy were compared between the two groups. Additionally, predictive factors for improvement were analyzed.

Results: All sperm parameters improved significantly following either varicocele ligation or antioxidant treatment. SDF decreased significantly in both groups (p<0.001). The increase in the percentage of normal sperm forms and the reduction in SDF were significantly greater in the varicocele surgery group compared to the antioxidant group (p=0.007 and p=0.013, respectively). The natural pregnancy rate was higher in the varicocele ligation group, with nine patients (22.5%) achieving pregnancy compared to five patients (12.5%) in the antioxidant group. Moreover, the presence of pinpoint and round head abnormalities predicted significantly poorer outcomes following varicocele ligation (p=0.003).

Conclusion: Varicocelectomy appears to be more effective than antioxidants in improving sperm morphology, reducing SDF, and enhancing the natural pregnancy rate in male infertility due to isolated teratozoospermia.

Objective: Mechanical trauma to the testicles poses a potential risk of tissue destruction, disruption of local blood supply, and impairment of spermatogenesis, which can ultimately lead to infertility. Therefore, investigating this topic is crucial. The study aimed to identify cytological and morphological changes in the testicular tissue of laboratory rats following mechanical trauma to the organ.

Methods: Observations were recorded on days 7, 14, 30, and 90 post-trauma. The experiment involved two groups of animals: a control group of healthy animals and an experimental group that sustained blunt mechanical trauma. Tissue samples were collected, fixed, dehydrated, and embedded in paraffin; subsequently, sections were prepared and stained. Structural changes in tissues and cells were documented using light and transmission electron microscopy.

Results: In the experimental sample, notable changes included a decrease in organ weight, thickening of the protein shell and tubule walls, sclerotisation of the tubule membrane, narrowing of tubule diameter, reduced spermatozoa and spermatids titre, diminished capillary network and spermatogenic epithelium, uneven blood vessel lumen expansion, and decreased volume of Leydig cell nuclei. Additionally, in cells under different functional loads, the cytoplasm was vacuolated, mitochondrial cristae and the Golgi apparatus were diminished, cytoplasm volume decreased, karyopyknosis was observed, and uncharacteristic protrusions appeared on the surface of the cytoplasmic membrane. The severity of destruction at the cellular and tissue levels showed a positive correlation with time.

Conclusion: The data obtained from these model sites can be predictive for clinical trials.

Objective: For successful embryo implantation in women with high pulsatility, uterine vascular resistance and pulsatility must be reduced. We examined the effects of amlodipine on uterine pulsatility index (PI), resistance index (RI), and embryo transfer (ET) outcomes in women with prior implantation failure and at least one elevated uterine PI measurement (especially higher than 3).

Methods: Between February and November 2023, our reproductive facility conducted a single-center randomized clinical trial, enrolling 100 patients with previous implantation failure and at least one uterine PI measurement exceeding 3. Participants were randomly assigned to receive either amlodipine (5 mg) or placebo (n=50 per group). Hormone replacement therapy was the predominant method for endometrial preparation. Transvaginal ultrasonography was used to measure uterine artery resistance and pulsatility on day 1 or 2 of menstruation. Women in the amlodipine group received 5 mg nightly. Following repeat transvaginal ultrasound to assess PI and RI, ET was performed. If a positive pregnancy test was obtained, treatment continued for a total of 7 weeks.

Results: Amlodipine reduced blood flow indices in the uterine artery. Among placebo recipients, 18% tested positive for beta-human chorionic gonadotropin, compared to 26% of medication recipients. However, this difference was statistically insignificant (p=0.472). Gestational sacs were observed in 12% of the placebo group and 22% of the medication group, but this difference was also insignificant (p=0.28).

Conclusion: Amlodipine appears to reduce uterine pulsatility and resistance during ET. Despite the absence of significant differences in pregnancy outcomes, this promising drug merits further study in women with implantation failure.

With the advent of metagenomics and 16S ribosomal RNA sequencing, growing attention has been dedicated to the endometrial microbiome. Research involving a relatively large cohort of healthy female participants has reported Lactobacillus dominance (LD) in the endometrial microbiome. Multiple studies have also shown that the loss of LD and/or increased microbial diversity within the endometrium are associated with reproductive failure. This phenomenon may stem from the loss of the immunomodulatory effects of Lactobacillus and the rise of proinflammatory responses triggered by pathogenic proliferation. Recent research has employed personalized antibiotic therapy followed by probiotic supplementation, tailored to the endometrial microbial composition of women with repeated implantation failure. The findings suggest that metagenomic analysis of the endometrial microbiome could be a valuable tool in addressing reproductive failure.