Reproductive Medicine and Biology最新文献

Purpose: Sperm DNA fragmentation (SDF) has recently received attention as a cause of male infertility. However, SDF cannot be fully assessed using conventional semen parameter evaluations alone. Therefore, the authors aimed to elucidate the relationship between SDF and sperm parameters via computer-assisted sperm analysis (CASA) to improve treatment strategies in reproductive medicine.

Methods: This retrospective observational study analyzed the relationship between sperm parameters assessed by CASA and SDF values determined by the TUNEL assay in 359 patients who visited the Mie University Hospital for infertility treatment. The methodology involved semen analyses covering concentration, motility, and morphology, followed by SDF quantification using the flow cytometry.

Results: Statistical analysis revealed significant correlations between SDF and various factors, including age, sexual abstinence period, and specific CASA-measured parameters. Notably, lower sperm motility rates and abnormal head dimensions were associated with higher SDF values, indicating that these parameters were predictive of SDF.

Conclusions: This study highlights the importance of sperm motility and head morphology as indicators of SDF, suggesting their usefulness in assessing male fertility. These findings demonstrate the efficacy of detailed sperm analysis, potentially increasing the success rate of assisted reproductive technologies by improving sperm selection criteria.

Background: In vitro fertilization (IVF) has revolutionized infertility treatment. Nevertheless, male infertility requires more effective solutions. In 1992, the first-ever case of human birth via intracytoplasmic sperm injection (ICSI) was reported. ICSI involves microscopically injecting a sperm into an ovum. Successful ICSI has become a reliable therapy for couples facing infertility, a significant milestone. However, it has also introduced various challenges. This study also delves into ethical dilemmas arising from widespread ICSI use.

Methods: This review traces the history of ICSI, presenting pioneering attempts, first successful attempts, and critical reports on account of the initial skepticism toward the technology. The review also focuses on chronological progress until ICSI was recognized as effective and became widely applied.

Main findings: The review reveals that ICSI, although transformative, presents challenges. Successes include addressing male infertility and aiding fertilization. However, concerns arise regarding optimal sperm and embryo selection, genetic mutations, and long-term health implications. Ethical considerations surrounding ICSI's broad applications also surface.

Conclusions: Despite its success and effectiveness, ICSI is still evolving as a therapeutic method. By comprehensively evaluating the historical progress and the current status of ICSI and exploring its future prospects, this study highlights the importance of ICSI in infertility treatment.

Purpose: This study compared the clinical outcomes of men with Klinfelter syndrome based on karyotype.

Methods: The authors analyzed the outcomes of microdissection testicular sperm extraction (micro-TESE) performed on 57 patients with Klinfelter syndrome (KS) at our clinic.

Results: The average ages of the non-mosaic and mosaic KS groups were 32.2 ± 4.8 and 45.9 ± 13.1 years, respectively. The sperm retrieval rates of the non-mosaic and mosaic KS groups were 46.5% (20/43) and 50.0% (7/14), respectively. The fertilization rates after intracytoplasmic sperm injection did not significantly differ between the non-mosaic and mosaic KS groups. The mosaic KS group had higher cleavage and blastocyst development rates than the non-mosaic KS group (72.2% vs. 96.2% and 30.5% vs. 44.7%, respectively). The group using motile sperm had better outcomes than the group using immotile sperm. The embryo transfer outcomes of the non-mosaic and mosaic KS groups did not significantly differ (clinical pregnancy rate: 28.0% vs. 20.7%, miscarriage rate: 14.3% vs. 33.3%, production rate per transfer: 22.0% vs. 13.8%, and production rate per case: 58.8% vs. 57.1%).

Conclusions: Compared with the non-mosaic KS group, the mosaic KS group had significantly better intracytoplasmic sperm injection outcomes because of the higher utilization rate of motile sperm.

Purpose: Decidualization is an important event for embryo implantation and successful pregnancy. Impaired decidualization leads to implantation failure and miscarriage. However, it is unclear how often decidualization failure occurs in infertile women. By analyzing the endometrium at late-secretory phase, we investigated the incidence and pathogenesis of decidualization failure among infertile women.

Methods: Endometrial dating was performed on the endometria obtained in the late-secretory phase from 33 infertile women. Endometrial dating of more than 2 days delay was taken as an indication of decidualization failure. The expression of essential transcription factors for decidualization (FOXO1, WT1, and C/EBPβ) was examined by immunohistochemistry.

Results: Among 32 cases, 20 cases (62.5%) showed decidualization failure. These patients tended to have a history of more frequent miscarriages than those without decidualization failure. The percentage of cells that immunostained positive for the expression of three transcription factors was significantly lower in the patients with decidualization failure than in those without decidualization failure. Serum progesterone levels measured in the mid- and late-secretory phase were not significantly different between the cases with and without decidualization failure.

Conclusions: The incidence of decidualization failure is high in infertile women.

Background: The pioneering work by Dr. Payne et al. in time-lapse cinematography for observation of the morphokinetic features of human embryos inspired us to develop a new in vitro culture system with high-resolution time-lapse cinematography (hR-TLC) back in 2001.

Methods: This in vitro culture system was capable of maintaining stable culture and was constructed on an inverted microscope stage. Embryos were observed and photographed noninvasively for an extended period, up to 7 days. The obtained images were displayed at a speed of 30 frames per second and individually analyzed.

Results: Using hR-TLC, human fertilization and subsequent embryonic development were visualized, revealing the time course of phenomena and many unusual dynamics.

Conclusion: In this review, we summarize the results of our hR-TLC analysis of early human embryonic development over the past 20 years. In the near future, it is expected that the vast amount of information obtained by hR-TLC will be integrated into the AI system for further analysis and to provide feedback that will have the potential to improve clinical practice. In the era of SDGs and environmental awareness, we should be cautious about the direction in which AI can be utilized to avoid any further harm to the planet.

Background: Endometriosis is a common gynecological condition, with symptoms including pain and infertility. Regurgitated endometrial cells into the peritoneal cavity encounter hypoxia and nutrient starvation. Endometriotic cells have evolved various adaptive mechanisms to survive in this inevitable condition. These adaptations include escape from apoptosis. Autophagy, a self-degradation system, controls apoptosis during stress conditions. However, to date, the mechanisms regulating the interplay between autophagy and apoptosis are still poorly understood. In this review, we summarize the current understanding of the molecular characteristics of autophagy in endometriosis and discuss future therapeutic challenges.

Methods: A search of PubMed and Google Scholar databases were used to identify relevant studies for this narrative literature review.

Results: Autophagy may be dynamically regulated through various intrinsic (e.g., PI3K/AKT/mTOR signal transduction network) and extrinsic (e.g., hypoxia and iron-mediated oxidative stress) pathways, contributing to the development and progression of endometriosis. Upregulation of mTOR expression suppresses apoptosis via inhibiting the autophagy pathway, whereas hypoxia or excess iron often inhibits apoptosis via promoting autophagy.

Conclusion: Endometriotic cells may have acquired antiapoptotic mechanisms through unique intrinsic and extrinsic autophagy pathways to survive in changing environments.

Background: Euploid blastocyst implantation failure may result from embryonic factors undetectable by preimplantation genetic testing for aneuploidy (PGT-A); however, various nonembryonic factors can also intricately interfere with implantation. This review seeks to clarify evidence-based testing and treatments for implantation failure after euploid embryo transfer.

Methods: We conducted a review of the literature on implantation failure after euploid embryo transfer or multiple embryo transfer cycles, which mainly included systematic reviews and meta-analyses.

Results: The recommended tests for implantation failure include (1) hysteroscopy, (2) endometrial CD138 immunohistochemistry and bacterial culture, (3) serum 25-hydroxyvitamin D₃, and (4) thrombophilia screening. Based on diagnostic findings, the following treatments have been recommended: (1) antibiotics for chronic endometritis, (2) vitamin D replacement, (3) lifestyle modification, and (4) low-dose aspirin starting from the postimplantation period for thrombophilia. Moreover, frozen-thawed single euploid blastocyst transfer using assisted hatching and hyaluronan-enriched transfer medium may support embryo implantation.

Conclusion: To ensure a successful pregnancy in subsequent embryo transfers, simple, inexpensive, and evidence-based tests and treatments should be selected.

Purpose: To examine the association between semen characteristics and outcomes of intrauterine insemination (IUI).

Methods: This retrospective analysis examined 1380 IUI procedures involving 421 couples. The association of clinical pregnancy with pre- and post-wash sperm characteristics was assessed.

Results: Pre- and post-wash sperm characteristics did not differ between IUI cycles that resulted in pregnancy and those that did not. When the motility of pre-wash sperm was below the normal range (<42%) established by the World Health Organization (WHO), the pregnancy rate was significantly lower. In the IUI cycles when post-wash sperm motility was below the WHO standard, pregnancy was not achieved. The frequency of improvement in post-wash sperm motility in repeated IUI cycles appeared to correlate with the success of future IUI cycles. At the fourth IUI cycle, pregnancy was not achieved unless the post-wash sperm motility was normal in at least two of three attempts. When post-wash sperm concentration was below the normal range, the woman's age did not affect the IUI outcomes.

Conclusions: Sperm motility above the lower limit of the WHO criteria in post-wash semen samples is an important factor in IUI outcomes.

Purpose: To investigate whether long noncoding RNAs (lncRNAs) are involved in the development or malignant behavior of ovarian high-grade serous carcinoma (HGSC), we attempted to identify lncRNAs specific to HGSC.

Methods: Total RNAs were isolated from HGSC, normal ovarian, and fallopian tube tissue samples and were subjected to a PCR array that can analyze 84 cancer-associated lncRNAs. The lncRNAs that were upregulated and downregulated in HGSC in comparison to multiple samples of normal ovary and fallopian tube were validated by real-time RT-PCR. To infer the function, ovarian cancer cell lines that overexpress the identified lncRNAs were established, and the activation of cell proliferation, migration, and invasion was analyzed.

Results: Eleven lncRNAs (ACTA2-AS1, ADAMTS9-AS2, CBR3-AS1, HAND2-AS1, IPW, LINC00312, LINC00887, MEG3, NBR2, TSIX, and XIST) were downregulated in HGSC samples. We established the cell lines that overexpress ADAMTS9-AS2, CBR3-AS1, or NBR2. In cell lines overexpressing ADAMTS9-AS2, cell proliferation was suppressed, but migration and invasion were promoted. In cell lines overexpressing CBR3-AS1 or NBR2, cell migration tended to be promoted, although cell proliferation and invasion were unchanged.

Conclusion: We identified eleven lncRNAs that were specifically downregulated in HGSC. Of these, CBR3-AS1, NBR2, and ADAMTS9-AS2 had unique functions in the malignant behaviors of HGSC.

Background: The last phase of folliculogenesis is driven by follicle-stimulating hormone (FSH) and locally produced insulin-like growth factors (IGFs), both essential for forming preovulatory follicles.

Methods: This review discusses the molecular crosstalk of the FSH and IGF signaling pathways in regulating follicular granulosa cells (GCs) during the antral-to-preovulatory phase.

Main findings: IGFs were considered co-gonadotropins since they amplify FSH actions in GCs. However, this view is not compatible with data showing that FSH requires IGFs to stimulate GCs, that FSH renders GCs sensitive to IGFs, and that FSH signaling interacts with factors downstream of AKT to stimulate GCs. New evidence suggests that FSH and IGF signaling pathways intersect at several levels to regulate gene expression and GC function.

Conclusion: FSH and locally produced IGFs form a positive feedback loop essential for preovulatory follicle formation in all species. Understanding the mechanisms by which FSH and IGFs interact to control GC function will help design new interventions to optimize follicle maturation, perfect treatment of ovulatory defects, improve in vitro fertilization, and develop new contraceptive approaches.