Reproductive Medicine and Biology最新文献

Background: Numerous efforts have been undertaken to identify biomarkers associated with embryo and oocyte quality to improve the success rate of in vitro fertilization. Metabolomics has gained traction for its ability to detect dynamic biological changes in real time and provide comprehensive metabolite profiles. This review synthesizes the most recent findings on metabolomic analysis of follicular fluid (FF) in clinical conditions leading to infertility, with a focus on the dynamics of energy metabolism and oocyte quality, and discusses future research directions.

Methods: A literature search was conducted without time constraints.

Main findings: The metabolites present in FF originate from five primary pathways: glycolysis, oxidative phosphorylation, lipid metabolism and β-oxidation, nucleic acid synthesis, and ketogenesis. Metabolomic profiling can broadly categorize infertile women into two groups: those with infertility due to aging and endometriosis, and those with infertility associated with polycystic ovarian syndrome and obesity. In the former group, glycolysis and lipid metabolism are upregulated to compensate for mitochondrial dysfunction, whereas the latter group exhibits the opposite trend. Assessing the levels of glucose, pyruvate, lactate, and plasmalogens in FF may be valuable for evaluating oocyte quality.

Conclusion: Metabolomic analysis, particularly focusing on energy metabolism in FF, holds promise for predicting female reproductive outcomes.

Background: Dietary interventions, recommended as a primary approach globally, benefit women with polycystic ovary syndrome (PCOS) by inducing weight loss and improving clinical symptoms, metabolism, and pregnancy results. However, the impact of diet on PCOS in individuals with BMI ≥ 25 kg/m² is unclear. The aim of this review was to offer dietary guidance for these patients.

Methods: Six databases, CNKI, Wanfang, VIP, PubMed, Cochrane Library, and Web of Science, were searched systematically from inception to December 2023 for clinical randomized controlled trials (RCT) on dietary interventions for PCOS. Two researchers independently screened and extracted data following pre-defined inclusion criteria, with bias assessment using the Cochrane Handbook and Review Manager (version 5.4) software.

Results: Nine RCTs with 559 participants were included. Among women with PCOS and obesity, compared to the control group, individuals who underwent dietary interventions experienced improvements in weight-related Indicators, glycolipid metabolism, hormone-related indicators, and fertility-related outcomes. Subgroup analysis indicated that calorie-restricted diets (CRDs) and low-energy-low-carb combined diets had advantages over other dietary interventions. Moreover, the overweight period was the optimal intervention period.

Conclusions: Dietary interventions can improve the clinical manifestations of PCOS and pregnancy rates in patients with a BMI ≥ 25 kg/m². Particularly, CRDs, low-calorie-low-carb combined diets, and low-calorie-extract combined diets are recommended.

Case: A 40-year-old Japanese man with nonobstructive azoospermia (NOA) was found to carry rare variants in KCTD19, a newly identified causative gene for spermatogenic failure. This patient was identified through mutation screening of KCTD19 in 97 men with etiology-unknown isolated NOA.

Outcome: The patient had two heterozygous variants in KCTD19 that affect consensus sequences of splice-donor sites [c.300+2T>A and c.2667C>T (p.E889E)]. Both variants were predicted to cause exon skipping. Long-read sequencing confirmed the compound heterozygosity of the variants. The patient exhibited small testes and a mildly elevated level of follicle-stimulating hormone but no other phenotypic abnormalities. Testicular histology showed borderline findings between spermatocyte maturation arrest and severe hypospermatogenesis.

Conclusion: These results provide evidence that biallelic loss-of-function variants of KCTD19 represent rare causes of isolated NOA.

Purpose: The purpose of this study is to confirm whether in vitro fertilization (IVF) with spermatozoa from Odf4-deficient infertile males (Odf4 ^-/- spermatozoa) can lead to the development of zygotes, which was reported in a previous in vivo study.

Methods: In vitro capacitation and IVF were performed using Odf4 ^-/- spermatozoa in a small drop of TYH medium with pyruvate and glucose, for 60 min or up to 4 days. A capacitation test was performed by immunoblotting using an anti-p-Tyr antibody. A sperm movement test was performed using a computer-assisted sperm motility analysis system (SMAS). An IVF fertilization test was also performed to evaluate zygote production. Videos were taken by a DMi8 stereomicroscope equipped with a high-speed camera.

Results: In in vitro condition, Odf4 ^-/- spermatozoa with hairpin flagella harboring large cytoplasmic droplets (CDs) underwent capacitation, about 30% of large CDs were removed from spermatozoa, and the flagella became straight (capacitation test). The Odf4 ^-/- spermatozoa with straight flagella swam forward (movement test) and fertilized Odf4 ^+/+ oocytes, which eventually developed into zygotes (fertilization test).

Conclusions: By conventional IVF, spermatozoa from Odf4-deficient male mice can fertilize oocytes that then develop into zygotes. These findings can be translated to human males with infertility caused by ODF4 deficiency.

Purpose: This study aimed to evaluate the protective effects of edible bird nest (EBN) against the detrimental impact of Wi-Fi on male reproductive health. Specifically, it examines whether EBN can mitigate Wi-Fi-induced changes in male reproductive hormones, estrogen receptors (ER), spermatogenesis, and sperm parameters.

Methods: Thirty-six adult male rats were divided into six groups (n = 6): Control, Control EBN, Control E2, Wi-Fi, Wi-Fi+EBN, and Wi-Fi+E2. Control EBN and Wi-Fi+EBN groups received 250 mg/kg/day EBN, while Control E2 and Wi-Fi+E2 groups received 12 μg/kg/day E2 for 10 days. Wi-Fi exposure and EBN supplementation lasted eight weeks. Assessments included organ weight, hormone levels (FSH, LH, testosterone, and E2), ERα/ERβ mRNA and protein expression, spermatogenic markers (c-KIT and SCF), and sperm quality.

Results: Wi-Fi exposure led to decreased FSH, testosterone, ERα mRNA, and sperm quality (concentration, motility, and viability). EBN supplementation restored serum FSH and testosterone levels, increased serum LH levels, and the testosterone/E2 ratio, and normalized mRNA ERα expression. Additionally, EBN increased sperm concentration in Wi-Fi-exposed rats without affecting motility or viability.

Conclusions: EBN plays a crucial role in regulating male reproductive hormones and spermatogenesis, leading to improved sperm concentration. This could notably benefit men experiencing oligospermia due to excessive Wi-Fi exposure.

Purpose: Recently, noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) using cell-free deoxyribonucleic acid has been developed; however, there are few reports on this and the results are inconsistent. This study was conducted to optimize the cultural environment.

Methods: We used 35 blastocysts that had been discarded after in-vitro fertilization. The concordance rate of karyotype analysis results between whole embryos (WEs), spent culture mediums (SCMs), and trophectoderms after 8, 16, and 24 h of culture was examined. Next, zona pellucida (ZP)-free blastocysts and then early blastocysts were cultured for 24 h each.

Results: Regarding the optimal culture times, the concordance rate between WEs and SCMs was 20%, 60%, and 100% at 8, 16, and 24 h, respectively. Significant differences were found between 8 and 24 h. The concordance rate with ZP cultures was 40.0%, and no significant differences were found. The concordance rate of early blastocysts thawed and cultured for 24 h was 40.0%, which was significantly lower than that of day 5 blastocysts.

Conclusions: The optimal culture times for niPGT-A were 24 h, and the concordance rate with free ZP was higher. The concordance rate for early blastocysts was low, suggesting that optimization of the conditions may be necessary.

Purpose: Several studies investigated endometrial patterns, with respect to pregnancy rates following the transfer of embryos but did not distinguish between single- and multiple-blastocyst procedures. We clarified how the endometrial pattern imaged to transfer a frozen embryo is associated with pregnancy outcomes in single-blastocyst frozen-embryo transfer (sbFET).

Methods: Patients ≤35 years who underwent sbFET on the hormone replacement protocol. We analyzed endometrial patterns' associations with pregnancy outcomes in relation to blastocyst grade and pregnancy-related factors.

Results: Of the 1383 cycles, 483 were Lf, 840 were partial-Lf, and 60 were non-Lf. Leaf pattern (Lf): central echogenic line present and continuous. Overall, decreasing distinctness of the central echogenic line was associated with significantly lower rates of clinical pregnancy (Lf: 70.4%; partial-Lf: 58.1%; non-Lf: 28.3%) and live birth (56.3%, 45.5%, and 15.0%) and a higher miscarriage rate (20.0%, 21.7%, and 47.1%). Logistic regressions showed pregnancy and live birth to be significantly more likely and miscarriage less likely in Lf than non-Lf: OR (95% CI): 6.07 (3.24-11.37), 7.43 (3.47-15.39), and 0.20 (0.07-0.57).

Conclusions: Non-Lf presentation was associated with lower rates of pregnancy and live birth, suggesting it signals unsuitable conditions for embryo transfer. We provide information on the pregnancy outcomes of sbFET for endometrial patterns.

Purpose: Controlled ovarian stimulation (COS) is vital for IVF. We have developed an AI system to support the implementation of COS protocols in our clinical group.

Methods: We developed two models as AI algorithms of the AI system. One was the oocyte retrieval decision model, to determine the timing of oocyte retrieval, and the other was the prescription inference model, to provide a prescription similar to that of an expert physician. Data was obtained from IVF treatment records from the In Vitro Fertilization (IVF) management system at the Asada Ladies Clinic, and these models were trained with this data.

Results: The oocyte retrieval decision model achieved superior sensitivity and specificity with 0.964 area under the curve (AUC). The prescription inference model achieved an AUC value of 0.948. Four models, namely the hCG prediction model, the hMG prediction model, the Cetrorelix prediction model, and the Estradiol prediction model included in the prescription inference model, achieved AUC values of 0.914, 0.937, 0.966, and 0.976, respectively.

Conclusion: The AI algorithm achieved high accuracy and was confirmed to be useful. The AI system has now been implemented as a COS tool in our clinical group for self-funded treatments.

Background: Increased oxidative stress (OS), resulting from the delicate balance between reactive oxygen species (ROS) production and antioxidant defense, is closely linked to sperm abnormalities and male subfertility. Elevated ROS levels particularly affect sperm quality. The vulnerability of spermatozoa to ROS is due to the absence of DNA repair mechanisms and the high presence of polyunsaturated fatty acids in their membranes.

Methods: This article updates and advances our understanding of the molecular damage caused by OS in spermatozoa, including lipid peroxidation, DNA damage, motility, and functionality. Additionally, the review discusses the challenges in diagnosing OS in semen and recommends accurate and sensitive testing methods. Case studies are utilized to demonstrate the effective management of male infertility caused by OS.

Main findings: Highlighting the need to bridge the gap between research and clinical practice, this review suggests strategies for clinicians, such as lifestyle and dietary changes and antioxidant therapies. The review emphasizes lifestyle modifications and personalized care as effective strategies in managing male infertility caused by OS.

Conclusion: This review calls for early detection and intervention and interdisciplinary collaboration to improve patient care in male infertility cases related to increased OS.

Background: Immune cells play an important role in the establishment of pregnancy, and abnormalities in the immune system can cause implantation failure and miscarriage.

Methods: Previous papers have been summarized and the role of immune cells in reproduction is reviewed.

Results: The immune environment in the uterus changes drastically from before implantation to after pregnancy to maintain pregnancy. In allogeneic pregnancies, immature dendritic cells (DCs) that induce immune tolerance from outside the uterus flow into the uterus, and mature DCs that remain in the uterus express programmed cell death ligand 2, which suppresses the immune response. Macrophages are classified into M1-macrophages, which induce inflammation, and M2-macrophages, which suppress inflammation; M1-macrophages are required for luteinization, and M2-macrophages induce the differentiation of endometrial epithelial cells to enable implantation. Regulatory T cells, which suppress rejection, are essential for the implantation and maintenance of allogeneic pregnancies. Implantation failure and fetal loss are associated with decreased numbers or qualitative abnormalities of DCs, macrophages, and regulatory T cells. The clinical usefulness of immunomodulatory therapies in patients with repeated implantation failure and recurrent pregnancy loss has been reported.

Conclusion: The provision of individualized medical care in cases of implantation failure or miscarriage may improve clinical outcomes.