Clinical and Experimental Reproductive Medicine-CERM最新文献

Objective: This study aimed to investigate the prevalence of human papillomavirus (HPV) in semen samples from Korean men and to examine its effects on seminal parameters, anti-sperm antibody (ASA) levels, and sperm DNA integrity, thereby exploring a potential association with male infertility.

Methods: Sixty-seven healthy Korean men aged 20 to 50 years underwent physical examination, sex hormone testing, and semen analysis according to the World Health Organization manual. ASA was evaluated using the mixed antiglobulin reaction test, sperm DNA fragmentation index (DFI) was measured by acridine orange staining, and HPV DNA detection and genotyping were performed using real-time polymerase chain reaction.

Results: The mean age of participants was 34.7±4.8 years. HPV DNA was identified in 10 of 67 semen samples (14.9%). HPV-positive men demonstrated significantly lower sperm concentration (p<0.020) and total sperm numbers (p<0.002) than HPV-negative men, although both measures remained within the clinically normal range. Other seminal parameters, including motility, morphology, and hormone levels, showed no significant differences. ASA and DFI values were higher in HPV-positive men, but these differences were not statistically significant. Subgroup analysis comparing high-risk HPV-positive men with HPV-negative men yielded similar findings, particularly regarding reduced total sperm counts.

Conclusion: The observed HPV prevalence was higher than previously reported in Korean studies. This preliminary investigation suggests a potential association between HPV infection and reductions in sperm concentration and total sperm numbers, although causality cannot be inferred. Given the small sample size, especially the limited number of HPV-positive cases, larger studies are required to clarify the precise role of HPV infection in male infertility.

Objective: The aim of this study is to evaluate the potential protective effects of myricitrin and chebulinic acid against gamma radiation-induced testicular damage.

Methods: Thirty-six 12-week-old Wistar Albino male rats were randomly divided into six groups: control, gamma, myricitrin, chebulinic acid, gamma+myricitrin, and gamma+chebulinic acid. The gamma groups were exposed to 16 mGy of radiation for 1 hour daily over 10 days. Antioxidants were administered intraperitoneally at 0.033 mg/kg for 10 days. Testes were analyzed using stereological and histopathological techniques, and bioinformatic analyses were performed to evaluate gene expression and signaling pathway alterations.

Results: In the stereological analyses, a decrease in the volume of the testes and seminiferous tubules and in the number of spermatogenic and Leydig cells was observed in the gamma group. Cell numbers and testicular volumetric values were increased in the groups treated with myricitrin (particularly) or chebulinic acid. In the histopathological analyses, degenerated cells and irregular seminiferous tubule structures were noted in the gamma group. In contrast, the seminiferous tubule architecture in both antioxidant-treated groups resembled that of the control group, and the number of degenerated cells was reduced compared to the gamma group. Bioinformatic analyses highlighted significant involvement of tumor necrosis factor-α and related intracellular proteins in radiation-induced damage.

Conclusion: Overall, both antioxidants alleviated testicular injury caused by gamma radiation, with myricitrin demonstrating comparatively greater protective efficacy.

The family with sequence similarity (FAM) gene family links pathological mechanisms of male infertility and oncogenesis. This review focuses on five key FAM members (FAM71D, FAM46C, FAM170A, FAM83D, and FAM172A), which were selected based on: clinical relevance (FAM83D as a breast cancer prognostic biomarker, hazard ratio, 1.29, p<0.05; FAM71D homozygous mutation c.440G>A associated with asthenoteratospermia); adequate experimental validation (in vitro assays, in vivo models, and clinical samples-for example, FAM170A knockout mice exhibit male infertility, with reduced transcription observed in patients); and recent impact (≥30 PubMed-indexed studies within 5 years and clearly defined mechanisms). In reproduction, FAM71D maintains sperm motility via calmodulin- plasma membrane Ca2+-ATPase (PMCA)- Ca2+ signaling, FAM46C anchors the sperm head-flagellum junction, and FAM170A regulates chromatin remodeling through ubiquitin- specific protease 7 (USP7)-mediated H2B deubiquitination. In oncology, FAM83D activates mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling to drive hepatocellular carcinoma, whereas FAM172A dysregulates p38 mitogen-activated protein kinase in thyroid cancer. Translational advances include FAM83B nanodetection, the Fam20C inhibitor FL-1607 (IC50=2.1 μM), and clustered regularly interspaced short palindromic repeats (CRISPR)-corrected FAM170A. Cross-species functional divergence remains a challenge. FAM genes enable novel diagnostics and targeted therapies for reproductive and oncological care, with near-term clinical applications in personalized assisted reproductive technology and cancer precision medicine.

Objective: Previous studies indicate that intracytoplasmic sperm injection (ICSI) holding pipettes can be replaced by a three-dimensional printed device (microICSI) that supports oocytes during injection. Use of microICSI reduced the size of the injection funnel in porcine oocytes, suggesting less trauma and resulting in increased blastocyst rates. This study measured changes in oocyte shape using donated human oocytes matured overnight.

Methods: Donated human oocytes not suitable for clinical use and matured in vitro overnight were subjected to sham ICSI using conventional methods (cICSI, n=39) or microICSI (n=38). Procedures were video recorded, and oocyte shape during injection was measured.

Results: Immediately before injection, the area, perimeter, and x-axis diameter of cICSI oocytes were larger than those of microICSI oocytes, and cICSI oocytes were less circular and round, indicating that the holding pipette distorted oocyte shape. Mid-injection, cICSI oocytes showed greater changes in x-axis and y-axis diameter than microICSI oocytes relative to pre-injection shape, and they were less round. There was no difference in injection funnel depth. Post-injection, microICSI oocytes showed a greater decrease in x-axis diameter and area compared to pre-injection shape than cICSI oocytes. There was no difference in the rate of lysis or degeneration after injection. Needle set-up time was faster with microICSI, but the time required to move oocytes in and out of the device was slower. Total procedure time was unchanged.

Conclusion: The microICSI device reduced distortion in oocyte shape caused by the holding pipette before and during injection, although it did not reduce injection funnel size or overall procedure time.

Objective: In the application of assisted reproductive technologies (ART), selection of the optimal sperm presents a challenge. This study introduces an innovative microfluidic device that utilizes rheotaxis to efficiently sort sperm, offering superior selection of high-quality sperm compared to conventional methods.

Methods: We analyzed 30 normal samples from couples undergoing intracytoplasmic sperm injection cycles at the Infertility Center of Fatemieh Hospital in Hamadan, Iran. Each sample was divided into three groups: the initial sample, representing the control group; direct swimup sperm selection; and sperm selection using rheotaxis. A syringe pump connected to the microfluidic device generated optimal flow conditions. Spermatozoa were evaluated regarding concentration, motility, morphology, mitochondrial membrane potential (MMP), and sperm DNA fragmentation index (DFI). Statistical significance was determined using one-way analysis of variance and the Student t-test.

Results: The concentration (7.46±2.84 million cells/mL vs. 56.67±18.27 million cells/mL, p<0.0001) and DFI (2.93±2.70 vs. 21.13±5.27, p<0.0001) were significantly lower in the sperm selected using the rheotaxis microfluidic device than in the control sperm. Progressive motility (98.10%±2.41% vs. 44.13%±7.06%, p<0.0001), normal morphology (8.36%±1.47% vs. 5.20%±1.15%, p<0.0001), and MMP (99.63%±0.71% vs. 81.13%±9.19%, p<0.0001) were significantly higher with the device than in the control group.

Conclusion: The use of a rheotaxis-based microfluidic device appeared effective in selecting high-quality sperm, demonstrating improvements in motility, morphology, and MMP and a reduction in DFI. This advancement has the potential to improve the outcomes of ART.

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.

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: Clomiphene citrate (CC) is the first-line treatment for ovulation induction in women with polycystic ovary syndrome (PCOS), yet a substantial proportion exhibit CC resistance. This study compares clinical outcomes following treatment with gonadotropins, letrozole, or unilateral laparoscopic ovarian drilling (LOD) in women with CC-resistant PCOS.

Methods: In this prospective, randomized clinical trial conducted at the infertility clinic of the Maternity Hospital from May 2021 to May 2024 (Clinical Trial No. NCT06486870), 183 middle-aged, anovulatory infertile women with CC-resistant PCOS, diagnosed using the Rotterdam criteria, were included. Participants were randomly assigned to one of three groups: letrozole (n=61), gonadotropins (n=61), or unilateral LOD (n=61). The primary outcome was the cumulative pregnancy rate over 6 months. Statistical analyses were performed using IBM SPSS Statistics ver. 24.

Results: Baseline demographics were comparable across groups. The gonadotropin-treated cohort achieved the highest cumulative pregnancy rate (41%), followed by letrozole (32.8%) and LOD (18%). Gonadotropin therapy also yielded the highest ovulation rate and the lowest incidence of oligo/amenorrhea. In contrast, LOD produced greater reductions in luteinizing hormone, anti-Müllerian hormone, and antral follicle count, and more patients attained menstrual regularity. Although LOD was associated with a lower pregnancy rate, it conferred a reduced risk of multiple gestations and ovarian hyperstimulation syndrome (OHSS).

Conclusion: Gonadotropins and letrozole are more effective than unilateral LOD for inducing ovulation and achieving pregnancy in women with CC-resistant PCOS. Nevertheless, LOD remains a viable alternative, offering the advantage of lower rates of multiple pregnancy and OHSS.

Objective: This study investigated the effects of pentoxifylline (PTX) and α-lipoic acid (ALA) on ovulation and pregnancy rates in women with clomiphene citrate (CC) resistant polycystic ovary syndrome (PCOS).

Methods: A prospective, randomized, controlled, open-label study was conducted on women with CC-resistant PCOS. In total, 120 PCOS patients were randomly assigned to four groups of 30 patients each, as follows: group 1 was the control group; group 2 received 400 mg of PTX twice daily; group 3 received 600 mg of ALA twice daily; and group 4 received a combination of PTX and ALA, following the same regimen as the previous groups. All groups were administered 150 mg of CC, the standard therapy for ovulation induction (ClinicalTrials.gov: NCT05231980).

Results: The cumulative ovulation rate was highest in the combined PTX-ALA group at 77% (23 cases), followed by the PTX group at 70% (n=21), the ALA group at 40% (n=12), and the control group at 30% (n=9) (p=0.0003). The cumulative pregnancy rates were 40% (n=12), 37% (n=11), 10% (n=3), and 3% (n=1) for the PTX-ALA, PTX, ALA, and control groups, respectively (p=0.0005). Endometrial thickness (ET) was significantly greater in the PTX group than in the control group.

Conclusion: Co-administration of PTX with CC significantly improved the ovulation rate, pregnancy rate, ET, and ovarian response to stimulation in patients with anovulatory PCOS. This combination may provide an effective, affordable, and safe treatment protocol for women with CC-resistant PCOS.