Clinical and Experimental Reproductive Medicine-CERM最新文献

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.

Objective: Follicular fluid (FF) oxidation-reduction potential (ORP) has shown promise as a predictor for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes has been demonstrated. This study aimed to determine the association between the ORP in FF and IVF/ICSI outcomes.

Methods: This cross-sectional study involved data collection from 341 couples undergoing IVF/ICSI treatment. The FF sample was taken from the first follicle to exceed 18 mm during oocyte retrieval and was analyzed for ORP using the MiOXSYS system (Caerus Biotechnologies).

Results: ORP in FF exhibited a statistically significant negative correlation with the fertilization rate (correlation coefficient, -0.126; p=0.019). The ORP levels in the FF from the group with a lower fertilization rate (<80%) were significantly higher than those in the group with a higher fertilization rate (≥80%) (89.90 mV vs. 78.98 mV, p=0.030). No significant correlations were found between ORP in FF and other outcomes.

Conclusion: Our findings suggested that the ORP in FF may be correlated with the fertilization rate and could be evaluated as a predictor of fertilization in ICSI.

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.

Objective: Ovarian tissue vitrification is widely utilized for fertility preservation in prepubertal and adolescent female patients with cancer. The current literature includes reports of successful pregnancy and live birth following autografting. However, the effects of the vitrification process on cumulus-mural granulosa cells (C-mGCs)-somatic cells in ovarian tissue crucial for oocyte maturation and early embryonic development-remain unclear. This study was conducted to explore the impact of vitrification on the cellular function of C-mGCs by quantifying the expression of growth differentiation factor 9 (GDF-9), bone morphogenetic protein 15 (BMP-15), follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), connexin 37, survivin, and caspase 3.

Methods: Mature and immature C-mGCs were obtained from 38 women with polycystic ovary syndrome who participated in an in vitro fertilization program. The C-mGCs were then divided into two groups: fresh and vitrified. The expression levels of target genes were assessed using real-time quantitative polymerase chain reaction.

Results: After vitrification, GDF-9 expression was significantly decreased among both mature and immature C-mGCs, with 0.2- and 0.1-fold changes, respectively (p<0.01). Similarly, FSHR expression in the mature and immature groups was reduced by 0.1- and 0.02-fold, respectively, following vitrification (p<0.01). The expression levels of the other genes, including BMP-15, LHR, connexin 37, survivin, and caspase 3, remained similar across the examined groups (p>0.05).

Conclusion: Vitrification may compromise oocyte maturation through reduced GDF-9 and FSHR expression in C-mGCs after warming.

Objective: Diabetes mellitus induces fertility problems in men, mainly because of increased free radicals. Natural resources are effective for male infertility treatment. This study investigated the effects of harmine, an alkaloid available in Peganum harmala L., on the male reproductive system of diabetic rats.

Methods: We divided 32 rats into four groups, and eight were randomly placed in each group. For diabetes induction, the animals received 50 mg/kg of streptozotocin intraperitoneally. After 1 week, animals received 15 mg/kg of harmine (28 days; intraperitoneal). Histopathological examinations, serum levels of male hormones, levels of nitric oxide (NO) and malondialdehyde (MDA) in the testes, total antioxidant capacity (TAC), insulin serum levels, fasting blood glucose levels, the apoptotic index, and semen analysis were assessed.

Results: The diabetes group exhibited morphological changes in testicular tissue, significant decreases in the diameter of the seminiferous tubule, the Johnsen score, testosterone, luteinizing hormone, follicle-stimulating hormone, insulin serum levels, and TAC in testicular tissue (p<0.01). Harmine treatment ameliorated the morphological changes in the testes and improved sperm parameters relative to the diabetes group (p<0.05). The NO and MDA levels in the testes, fasting blood glucose serum levels, and apoptotic index parameters were significantly elevated in the diabetes group, while in the diabetes+harmine group, these parameters were reduced (p<0.01).

Conclusion: Harmine protects testicular tissue and sperm against diabetes-induced damage. This effect of harmine is associated with a rebalancing of the antioxidant capacity that subsequently decreases apoptosis in the testes.

Objective: Osteocalcin (OCN) influences spermatogenesis in conjunction with testosterone and estrogen. OCN facilitates the secretion of testosterone by engaging with G protein-coupled receptor class C group 6 member A (GPRC6A) on Leydig cells and with androgen receptors on Sertoli cells.

Methods: Adult mice were assigned to the following groups: control; sham I, which received dimethyl sulfoxide for 5 weeks followed by phosphate-buffered saline for 1 month; azoospermia, which was treated with busulfan (40 mg/kg); sham II, which consisted of azoospermic animals that received phosphate-buffered saline for 1 month beginning at the 5-week mark; and the experimental group, which included azoospermic mice treated with OCN (3 ng/g/day) for 1 month.

Results: In the mice receiving OCN treatment, immunohistochemical analysis revealed increased expression of androgen receptors and GPRC6A, indicative of enhanced spermatogenesis. Additionally, the expression levels of the cyclic adenosine monophosphate-responsive element binding protein 1, steroidogenic acute regulatory protein, and cytochrome P450 family 11 genes were elevated. However, testosterone levels exhibited no significant differences across groups. Morphometric analysis suggests that OCN may play a crucial role in spermatogenesis, as evidenced by its positive effects on germinal cells and the germinal epithelium in the azoospermia group (p<0.05).

Conclusion: We conclude that OCN may serve as a beneficial therapeutic agent for male infertility.

Objective: Autophagy is a major intracellular catabolic pathway governed by the sequential actions of proteins encoded by autophagy-related genes (Atg). ATG9, the only transmembrane protein involved in this process, regulates phospholipid translocation to autophagosomes during the early phases of autophagy. In mammals, two Atg9 isoforms have been reported: Atg9a and Atg9b. In this study, we examined whether the molecular and cellular characteristics of these two isoforms differed in mice.

Methods: Whole uteri were collected on days 1, 4, and 8 of pregnancy and from ovariectomized mice injected with vehicle, progesterone, or 17β-estradiol. Cells from reproductive tissues, such as granulosa cells, uterine epithelial cells (UECs), uterine stromal cells (USCs), and oocytes were collected. Two human uterine cell lines were also used in this analysis. Reverse transcription-polymerase chain reaction tests, Western blotting, and immunofluorescence staining were performed. Serum starvation conditions were used to induce autophagy in primary cells.

Results: Atg9a and Atg9b were expressed in multiple mouse tissues and reproductive cells. Neither Atg9A nor Atg9B significantly changed in response to steroid hormones. Immunofluorescence staining of the UECs and USCs showed that ATG9A was distributed in a punctate-like pattern, whereas ATG9B exhibited a pattern of elongated tubular shapes in the cytoplasm. In human cancer cell lines, ATG9B was undetectable, whereas ATG9A was found in all cell types examined.

Conclusion: The Atg9 isoforms exhibited distinct subcellular localizations in UECs and may play different roles in autophagy. Notably, human uterine cells exhibited reduced ATG9B expression, suggesting that this suppression may be due to epigenetic regulation.

Objective: This study compared the outcomes of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in patients with polycystic ovarian syndrome (PCOS), tubal factor (TF) infertility, and unexplained infertility whose partners had normal semen parameters.

Methods: This retrospective study included 360 couples diagnosed with infertility involving PCOS (n=157), unexplained infertility (n=140), and TF infertility (n=63). Sibling oocytes were randomly assigned to undergo ICSI or conventional IVF insemination. The fertilization rate and embryo morphology were evaluated as outcomes.

Results: Retrieved cumulus-oocyte complexes from patients with PCOS (2,974), unexplained infertility (1,843), and TF infertility (844) were split and inseminated by conventional IVF and ICSI respectively. In comparison to the ICSI method, the conventional IVF approach was linked to a significantly higher fertilization rate in groups with PCOS (68.81% vs. 77.49%), unexplained infertility (67.62% vs. 78.84%), and TF issues (69.23% vs. 78.63%) (p<0.05). The proportion of embryos with grade A produced by the conventional IVF method was significantly higher than that produced using the ICSI method in the PCOS and unexplained infertility groups (p<0.05). Additionally, the percentage of grade B embryos produced with the ICSI method was significantly higher than that produced with the conventional IVF method in PCOS patients (p=0.002).

Conclusion: Our results indicated that the conventional IVF method was associated with higher zygote production and a higher proportion of grade A embryos when all infertile groups were evaluated together. Thus, ICSI is not suggested for patients with these causes of infertility if their partner has normal semen parameters.

Objective: To investigate whether long non-coding RNA (lncRNA) Gm8097 (LncGm8097) is associated with male infertility.

Methods: The expression and bilogical role of LncGm8097 were investigated.

Results: LncGm8097 expression was down-regulated in the testis tissues with moderate and severe hypospermatogenesis compared with those with normal spermatogenesis and mild hypospermatogenesis (p<0.05). LncGm8097 down-regulation significantly promoted apoptosis and inhibited proliferation in GC1 and GC2 cells. In addition, LncGm8097 was significantly down-regulated in mouse model of hypospermatogenesis and correlated with cell apoptosis and proliferation. LncGm8097 was located immediately upstream of PRPS2, and correlated with Bcl-2/P53/caspase 6/caspase 9 signal pathway.

Conclusion: LncGm8097 down-regulation correlates with hypospermatogenesis, which may offer new insights into the pathogenesis of male infertility.