Clinical and Experimental Reproductive Medicine-CERM最新文献

Objective: To evaluate the long-term effects of dutasteride on male fertility and determine the cutoff treatment duration that causes significant and persistent decreases in semen parameters.

Methods: This was a single-center, randomized, controlled study that evaluated 200 men (ages 28 to 39 years). Forty men were allocated to each study group, divided according to the duration of dutasteride treatment, as follows: <6 months (group 1), 6-12 months (group 2), 13-18 months (group 3), 19-24 months (group 4), and >24 months (group 5). All subjects received dutasteride 0.5 mg/day for management of androgenetic alopecia then discontinued dutasteride for 6 months.

Results: The baseline mean testosterone level in the study subjects was 4.8 ng/mL. No significant differences were found between study groups in sperm concentration, normal morphology, and vitality. Semen volume and sperm total/progressive motility were significantly reduced as the duration of dutasteride treatment increased. All study groups showed an increase in total sperm motility and semen volume after discontinuation of dutasteride. Compared with group 1, groups 2-5 showed significant decreases in semen volume and sperm total motility, with the odds ratios becoming smaller as the duration of dutasteride treatment increased. Receiver operating characteristic analysis showed the cutoff values for persistent impairment of semen volume and total sperm motility to be 17.8 and 20.3 months, respectively.

Conclusion: Long-term use of dutasteride may lead to male infertility by persistently impairing semen volume and sperm motility.

Objective: An undescended testis (UDT) is a testicle that has not moved into the scrotum before birth. UDTs are linked to reduced fertility, primarily due to compromised semen quality and potential dysfunction in Sertoli and Leydig cells. Additionally, the Wilms tumor 1 (WT1) gene is crucial for spermatogenesis, as it regulates the polarity of Sertoli cells and the steroidogenesis in Leydig cells. Our study aimed to identify novel UDT-causing WT1 variants within a cohort of 60 unrelated men with infertile hypergonadotropic hypogonadism.

Methods: In this case-control study, the coding regions and the intronic boundaries of the second and ninth exon of WT1 were sequenced using Sanger sequencing. DNA from 60 fertile men served as the control group. In silico analysis of the variants was also conducted.

Results: The study identified multiple intronic and exonic variations in both the patient and control groups. Notably, a haplotype consisting of two heterozygous C>T variations in the intronic region of the splice donor site of exon 9 was observed in 11 patients but was absent in the control group. Of these variations, only one has been previously reported in Single Nucleotide Polymorphism Database (dbSNP) as rs587776576 (NC_000011.10: g.32391967C>T; NM_000378.4:c.1372+14G>A).

Conclusion: The rs587776576 mutation is pathogenic. It exhibited a significant association (p=0.022), indicating its association with infertility and UDT in the Iranian population. This research could broaden the spectrum of WT1 variations and underscore the importance of these variants in the genetic etiology of UDT and infertility. These findings provide a foundation for clinical diagnosis and genetic counseling.

Objective: Mixed gonadal dysgenesis is characterized by abnormal genital appearance and chromosomal mosaicism. A wide spectrum of clinical manifestations can occur, ranging from females (with or without Turner syndrome) to phenotypically normal males with some degree of genital ambiguity. In this context, uncommon mosaic karyotypes are associated with distinctive phenotypic characteristics. Here, we present the case of an 18-year-old girl with primary amenorrhea, delayed puberty, and a rare mosaic karyotype pattern.

Methods: Clinical data were collected, and karyotyping was performed on peripheral blood samples. Polymerase chain reaction amplification for the sex-determining region Y protein (SRY) gene was also conducted.

Results: The patient presented with delayed puberty and primary amenorrhea. Her hormonal profile was consistent with hypergonadotropic hypogonadism. Pelvic magnetic resonance imaging revealed a small uterus. Echocardiography identified the presence of a bicuspid aortic valve. Karyotyping demonstrated a 46,XY/45,X/46,X,r(Y) pattern, indicating mosaicism for monosomy X and two cell lines: 45,X and 46,X,r(Y). The SRY gene was detected. Gonadal pathological investigation confirmed streak gonads consistent with gonadal dysgenesis and evidence of gonadoblastoma.

Conclusion: Complicated cases with mosaic chromosomal patterns can exhibit a wide range of phenotypic features, from apparently normal males with variable external genitalia to females with or without characteristics of Turner syndrome. These phenotypic discrepancies are not directly related to the number of mosaic cells or the specific location of Y chromosome breakage. Therefore, in cases of primary amenorrhea with genotype-phenotype discrepancies, a multidisciplinary approach is essential to guide appropriate sex determination and management.

Objective: This study aimed to investigate the effects of specific probiotic strains on the endocrine activity of Leydig cells, which are essential for testosterone production. We focused on the potential influence of probiotics on testosterone synthesis and mitochondrial functionality within these cells.

Methods: The TM3 Leydig cell line was utilized to assess the effects of three probiotic strains: Lacticaseibacillus rhamnosus, Limosilactobacillus fermentum, and Bifidobacterium longum subsp. longum. The analyses evaluated key aspects of Leydig cell function, including endocrine signaling pathways, cellular proliferation, gene and protein expression related to testosterone biosynthesis, and mitochondrial function.

Results: The probiotic strains significantly enhanced the expression of key proteins involved in testosterone synthesis and upregulated mitochondrial activity compared to control cells. Notably, these effects were observed across all three probiotic strains, suggesting a positive impact on both testosterone production and mitochondrial function.

Conclusion: The findings suggest that probiotic supplementation can modulate testosterone synthesis and improve mitochondrial functionality in Leydig cells. These results underscore the potential of probiotics as modulators of male reproductive health, with possible therapeutic applications in conditions such as male hypogonadism.

Objective: This study aimed to evaluate reproductive outcomes according to the timing of testicular sperm retrieval.

Methods: The study included 282 infertile couples divided into three groups: group A (freeze-thawed testicular sperm extraction [TESE] sperm, n=233), group B (fresh TESE sperm collected 1 day before ovum pickup, n=22), and group C (fresh TESE sperm collected on the same day as ovum pickup, n=27). The indications for TESE were surgically uncorrectable azoospermia or ejaculation failure, often accompanied by medical comorbidities such as diabetes mellitus and spinal cord injury. The outcome parameters assessed were fertilization rates, embryo quality, and clinical pregnancy rates.

Results: The mean paternal age was 36.8±5.7 years, and the mean maternal age was 32.6±3.5 years. The mean duration of infertility was 2.9±1.8 years. The fertilization rates were 70.7%, 78.9%, and 73.0% for groups A, B, and C, respectively (p=0.047). The percentages of good-quality embryos were 68.2%, 65.3%, and 48.4%, respectively (p=0.007); specifically, the percentage of good-quality embryos was significantly lower in group C compared with the other two groups. Clinical pregnancy rates per transfer were similar at 51.1%, 50.0%, and 48.1% (p=0.958), with no differences observed in miscarriage rates.

Conclusion: Testicular sperm retrieval can be safely performed 1 day before ovum pickup, resulting in favorable fertility outcomes.

Objective: Although various studies have linked environmental toxins, mumps infections, alcohol consumption, and abnormal body mass index (BMI) to impaired semen quality, the precise causes of infertility remain unclear. This study investigates the impact of BMI on oxidative stress markers in semen analysis among infertile men, illuminating the role of oxidative stress in cases of unexplained infertility.

Methods: In this cross-sectional study, 280 patients exhibiting infertility symptoms were recruited. Comprehensive semen analysis was conducted, evaluating reactive oxygen species (ROS) levels, sperm plasma membrane lipid peroxidation via flow cytometry, total antioxidant capacity (TAC), and results from the sperm chromatin structure assay. Participants were categorized based on their BMI, facilitating comparisons between obese and non-obese individuals.

Results: Both BMI and age significantly influenced male fertility, particularly in obese individuals. Strong correlations were identified between elevated BMI, increased ROS levels, and decreased TAC. The obese infertile group exhibited substantially lower TAC compared to controls, highlighting obesity's detrimental effect on antioxidant defenses. Furthermore, significant reductions in sperm count, motility, and normal morphology were observed, alongside an increase in non-motile sperm. These outcomes demonstrate the complex relationship among oxidative stress, BMI, and fertility, emphasizing the necessity for targeted interventions addressing obesity's effects on reproductive health.

Conclusion: This study underscores the importance of managing obesity and understanding its impact on oxidative stress as essential components in improving reproductive outcomes among affected men.

Objective: Anogenital distance (AGD) is a sexually dimorphic marker of genital development and fetal androgen activity. Shortened AGD has been linked to impaired male fertility. The distinct phenotypic and reproductive characteristics associated with Klinefelter syndrome (KS) may influence AGD. This study aimed to investigate AGD measurements in men with KS and evaluate their clinical significance.

Methods: A case-control study was conducted involving 87 male participants categorized into three groups: normospermic (n=51), KS (n=18), and idiopathic non-obstructive azoospermia (iNOA; n=21). AGD was measured as the anoscrotal distance (AGDAS) using a digital caliper. Physical and hormonal evaluations, semen analyses, and karyotyping were performed. Group differences were analyzed using analysis of variance with post hoc testing, and Pearson correlations were calculated between AGD and clinical variables.

Results: AGD measurements differed significantly between groups (F(2,87)=15.2, p<0.0005). AGD was longer in the normospermic group compared to the iNOA group (p<0.0005) and longer in the KS group than in the iNOA group (p=0.015). No significant difference was observed between normospermic and KS groups (p=0.153). Hormonal analyses showed lower testosterone and estradiol levels in KS patients compared to iNOA. Correlation analyses did not identify significant associations between AGD and clinical or hormonal parameters.

Conclusion: AGD in men with KS is comparable to normospermic individuals and longer than in iNOA patients. In clinical assessments, the presence of small testes in individuals with AGD measurements similar to normospermic men may raise suspicion for KS.

Endometrial cancer (EC) in young women is relatively likely to be early-stage, low-grade, and without risk factors. Fertility-sparing treatment with progestin is a potential primary approach for certain patients. However, several factors should be considered according to available guidelines. The potential indication for fertility-sparing treatment in patients with EC, as recommended by various societies of gynecologic oncology, includes young women with grade 1 endometrioid adenocarcinoma confined to the endometrium. Magnetic resonance imaging should be performed to rule out myometrial invasion and extrauterine disease before initiating fertility-sparing treatment. Other imaging modalities may also be used to exclude extrauterine disease. Various fertility-sparing therapies exist, the most common of which is high-dose oral progestin. After initiating fertility-sparing treatment, pathological re-evaluation of the endometrium at 3 to 6 months is recommended. The optimal duration of fertility-sparing treatment is up to 15 months, but guidelines recommend continuing progestin therapy until attempting conception. Ovarian stimulation drugs used for pregnancy are considered safe after a complete response is achieved. Hysterectomy is recommended after childbearing, while oophorectomy is not mandatory for young women. Close surveillance should continue for women who do not wish to undergo surgery after childbirth. Based on existing evidence, fertility-preserving treatments have demonstrated effectiveness and do not appear to negatively impact prognosis. If a qualified patient expresses a strong desire for fertility preservation despite the potential for recurrence, the physician should consider fertility-sparing treatment while maintaining vigilant monitoring.

Objective: Hydroxyethyl piperazine ethane sulfonicacid (HEPES)-buffered media have long been employed in assisted reproductive technology (ART) procedures; however, concerns persist regarding the impact of zwitterionic buffers on intrinsic cellular mechanisms. Limited studies have compared ART outcomes using bicarbonate media versus HEPES-buffered media during intracytoplasmic sperm injection (ICSI). This study compared the efficacy of two media used in ICSI: bicarbonate medium (one-step) and HEPES-buffered medium (SynVitro Flush).

Methods: This retrospective study analyzed data from 200 ICSI cycles performed in 2023. Metaphase II oocytes were allocated to a bicarbonate medium (SAGE 1-STEP; Origio) or a HEPES-buffered medium (SynVitro Flush) during the ICSI procedure. Outcomes including fertilization rate, embryo quality and development, implantation rate, clinical pregnancy rate, miscarriage rate, and live birth rate were compared between the two groups.

Results: The fertilization rate was significantly higher in the one-step medium (89.04%) than in the SynVitro medium (82.30%; p<0.001). The one-step medium also yielded more cleaved embryos and higher-quality blastocysts (class A/B; p<0.05). Consequently, more embryos were frozen in the one-step group (264 vs. 151), and higher embryo utilization rates were observed. Clinical pregnancy and live birth rates were significantly higher in the one-step group (p<0.05). No significant differences were found in chemical pregnancy rates or live birth rates among cycles utilizing frozen embryos (p>0.05). Additionally, there were no differences observed in miscarriage rates or multiple pregnancy rates.

Conclusion: The one-step bicarbonate medium improved cycle efficiency during the ICSI procedure compared to the SynVitro Flush medium. This finding underscores the importance of selecting an appropriate medium.

Artificial intelligence (AI) has rapidly advanced in healthcare, demonstrating significant potential in analyzing large, heterogeneous datasets using optimized algorithms for disease prediction and personalized treatment. Assisted reproductive technology (ART), particularly in vitro fertilization (IVF) and embryo transfer, generates extensive data, making it especially suitable for AI-driven analysis. AI-based applications aim to improve clinical outcomes through personalized ART strategies and predictive algorithms, with potential applications categorized into various procedural stages. Despite its promising nature, most AI-related ART studies appear in general scientific journals rather than core obstetrics and gynecology publications. Moreover, limited clinician understanding of AI methodologies, strengths, and limitations represents a barrier to clinical implementation. This review summarizes recent advancements in AI applications within ART, covering areas such as clinical counseling, outcome prediction, IVF workflow management, controlled ovarian stimulation and follicular monitoring, oocyte and semen analysis, and embryo assessment. It also addresses future considerations for the responsible integration of AI technologies in ART, emphasizing the importance of multidisciplinary collaboration. Integrating AI into ART holds substantial promise and, with targeted research and development, is expected to meaningfully advance the achievement of successful pregnancies.