F&S reviews最新文献

There is an increasing number of young men taking medications for chronic conditions, such as high blood pressure, psychiatric illness, and pain management. Furthermore, the prevalence of use for these medications only increases with age. However, despite the long-term indications for these treatments, the adverse effect on fertility is not well recognized. There are a plethora of clinical trials studying the effects of various medications on spermatogenesis in rodents; however, animal models do not fully translate to potential human side effects. Commonly prescribed medications may affect male fertility by altering hormone secretion or impairing testosterone secretion, sperm production, and ejaculation. Other drugs are known to increase erectile dysfunction and decrease libido. Although the evidence is not conclusive for many drug groups, this review presents the most compelling information on commonly prescribed drugs for male fertility. To our knowledge, this is the only review to compile information on commonly prescribed medications that may affect male fertility, sperm function, and libido. We believe that our review can help clinicians further personalize patient prescriptions based on their individual needs and goals as well as unveil an untapped area of research.

Spermatogenesis is a strictly regulated, complex process by which sperm cells are continuously produced throughout a person’s lifespan. This process includes 3 unique events: mitotic division, meiosis, and spermiogenesis. Many genes playing key roles in these events are mainly regulated by epigenetic mechanisms, especially DNA methylation and histone modifications. Histone methylation is one of the basic modifications in histones and contributes to the timely control of transcriptional activation and repression of the genes implicated in cell cycle progression, meiotic recombination, DNA repair, chromosome segregation, and chromatin condensation. For this purpose, specific histone methyltransferases perform methylation of the lysine and/or arginine residues of histones localized in nucleosomes. Added methyl groups can be removed by exclusive histone demethylases when necessary. Potential defects in correctly establishing histone methylation marks in H3K4, H3K9, H3K27, H3K36, H4R3, and H4K20 residues in male germline cells during spermatogenesis may result in the development of infertility. In this review, we comprehensively evaluate histone methylation dynamics in male germ cells, from spermatogonia to sperm cells. In addition, infertility development in males is discussed in terms of altered histone methylation accumulation because of altered expression of the histone methyltransferases and histone demethylases.

Objective

To investigate the relationship between the number of oocytes and both the live birth rate (LBR) after fresh embryo transfer and the cumulative live birth rate (CLBR).

Evidence Review

The optimal number of oocytes necessary to expect a live birth after in vitro fertilization remains unclear. A systematic review with meta-analysis was performed, searching for studies published between January 2004 and March 2021. Two independent reviewers performed study selection and data extraction according to Cochrane methods. The mean-weighted threshold of optimal oocyte number was estimated from documented thresholds, followed by a one-stage meta-analysis on articles with documented or estimable relative risks.

Results

After reviewing 1,090 records, 102 full-text articles were assessed for eligibility. A total of 45 studies were available for quantitative syntheses. Twenty-two and 21 studies were included in the meta-analyses evaluating the relationship between the number of retrieved oocytes and LBR or CLBR, respectively. For LBR, most studies reported a plateau or a peak effect, corresponding to a weighted mean of 13.5 oocytes, and the pooled dose-outcome showed a nonlinear relationship, with a plateau or even a drop beyond 15 oocytes. The meta-analysis of the relationship between the number of oocytes and CLBR found a nonlinear relationship, with a continuous increase in CLBR, including for high-oocyte yields.

Conclusion

Above a 15-oocyte threshold, LBR after fresh transfer plateaus, advocating for a freeze-all strategy. In contrast, the continuous increase in CLBR suggests that a strong response to controlled ovarian stimulation seems unlikely to impair oocyte quality. High numbers of oocytes could be offered to improve the chances of cumulative live births, after evaluating the benefit–risk balance.

Male factor infertility continues to be a challenging condition with a significant proportion of men receiving no clear explanation for why they are unable to conceive. On the basis of the data presented in this review, there is now mounting evidence to support the role of the gut-testis axis in both healthy and diseased states, and at the core of this axis is the gut microbiome. Under nonpathological conditions, the gut microbiome maintains a symbiotic relationship with the testes. Disruption of the gut microbiome by diet or diseases initiates a chain reaction leading to diminishing fertility. Under dysbiotic conditions, there is an increase in inflammatory markers coupled with a loss of integrity of the gut epithelium leading to translocation of bacteria and inflammatory cytokines into systemic circulation. Ultimately, the testes along with the rest of the body are exposed to chronic inflammation because of this dysbiosis through pathways that remain to be fully elucidated. Eventually, this may also lead to loss of integrity of the blood-testis barrier causing impaired spermatogenesis and depressed semen parameters. Restoration of the gut microbiome to a symbiotic state via probiotics, fecal microbiota transplantation, bacteriophages, or small molecules may soon be able to decrease gut inflammation, rescue the integrity of the blood-testis barrier, and ultimately improve semen quality.

Spinal cord injury (SCI) is a prevalent problem, affecting nearly 288,000 people in the United States. Many men with SCI can present with erectile dysfunction (ED), anejaculation, and infertility, imputing profound impacts on quality of life for this population. Erectile dysfunction is generally well managed pharmacologically with phosphodiesterase-5 inhibitors and intracavernous injections or surgically with penile prosthesis. Additional treatment modalities, including vacuum constrictive devices and muscle stimulation, can be used to supplement pharmacological treatment of ED. Anejaculation is a prevalent problem, especially for men seeking to have children, but it is managed well with penile vibratory stimulation, electroejaculation, and testicular sperm extraction. Various sperm abnormalities are also prevalent in this population, with consensual support for the presence of hypospermia, asthenospermia, and necrospermia. Recent literature supports the potential use of probenecid and mirabegron to help improve these sperm abnormalities. The literature most consensually supports a high inflammatory state as the most likely pathological driver behind these sperm abnormalities. In all, ED, anejaculation, and infertility are managed relatively well in men with SCI. More work is needed to better understand the pathophysiology of sperm abnormalities to shed more light on better methods of treatment.

Objective

To evaluate whether the use of assisted reproductive techniques (ARTs) affected the gonadal function of the offspring. Numerous concerns have emerged over the years about the use of ARTs and their effects on the health of the offspring.

Evidence Review

Data were extracted through extensive searches in the PubMed and Scopus databases from their establishment until August 2022. Meta-analysis was performed following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. All eligible studies were selected according to the Population, Exposure, Comparison/Comparator, Outcomes, Study design model. All studies that analyzed pubertal development and testicular and ovarian function of offspring conceived using ARTs were included. The quality of the studies was assessed using the Cambridge Quality Checklists. For the different outcomes, the standardized mean difference (SMD), the mean difference, and the odds ratio were evaluated. Cochran-Q and I² statistics were used to evaluate statistical heterogeneity. Differences in pubertal development, hormone levels, and sperm function in ART-conceived subjects compared with spontaneously conceived (SC) control subjects.

Results

Children conceived using ART do not appear to have impaired pubertal development or achievement of pubertal milestones. From an endocrine point of view, ART-conceived males showed lower sex hormone-binding globulin levels than the control group (SMD = −0.25 [−0.44, −0.05]; I² = 29%) and a tendency to lower testosterone levels (SMD = −0.16 [−0.32, 0.01]; I² = 0). Lower levels of inhibin B, on the other hand, were present only in intracytoplasmic sperm injection-born males compared with the control group (SMD = −0.24 [−0.44, −0.04]; I² = 0). In females, higher luteinizing hormone levels were found in the ART group than in the control group (SMD = 0.33 [0.06, 0.59]; I² = 17%). In contrast, lower levels of 17ß-estradiol were observed only in the intracytoplasmic sperm injection group compared with girls with SC (SMD = −0.39 [−0.74, −0.03]; I² = 0). However, no definitive conclusions can be drawn considering the heterogeneity of hormonal assessments in females. Finally, young adults born from ART had a reduced sperm concentration (SMD = −0.34 [−0.57, −0.11]; I² = 0), total sperm count (SMD = −0.28 [−0.51, −0.05]; I² = 0), and normal sperm morphology (SMD = −0.35 [−0.58, −0.13]; I² = 0) compared with those SC.

Conclusion

A slight alteration in the function of the male germinal epithelium appears to be associated with the use of ART, as shown by the reduced levels of inhibin B and the altered sperm parameters.

Objective

Endometriosis is a chronic, incurable condition associated with debilitating pain and subfertility affecting over 190 million women worldwide, which has no reliable noninvasive diagnostic tool. We aimed to determine the state-of-the-art in noninvasive liquid biopsy biomarker detection and predict the most promising biomarkers for endometriosis detection.

Evidence Review

A systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted using the PubMed, MEDLINE, Scopus, and Cochrane Library databases. Primary research studies examining blood or urine biomarkers in humans published in English up until August 2022 were included. Studies with more than 10 patients with clear methodology and surgical staging of endometriosis were included, whereas studies that included gynecological malignancies or who did not perform laparoscopy in the control group were excluded. The articles were assessed for the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. One investigator extracted the data, and 2 investigators checked the accuracy. Extracted data were analyzed descriptively, the box plots of pooled data were calculated using RStudio, and the likelihood ratios were determined.

Results

A total of 8,244 and 3,619 manuscripts for blood and urine biomarkers were identified. After screening on the basis of the title, abstract, full text, and quality assurance, 18 of these studies assessing blood biomarkers and 15 examining urine biomarkers were eligible for data extraction. However, there were inconsistencies in the results indicating that standardized techniques would be essential for direct comparisons to be made in the future. In 4 of the eligible studies, the urine biomarkers were juxtaposed with blood markers; however, in most cases, the combination of blood and urine biomarkers resulted in an increase in the area under the curve value, sensitivity, and specificity. One study presented biomarkers with a likelihood ratio of >10. However, currently, none of the biomarkers have been shown to be clinically useful, and further research is necessary to determine their utility in clinical practice.

Conclusion

Multiple biomarkers described here provide exciting avenues for further study particularly as part of diagnostic panels, including the endometrial antigens tropomyosin 3, stomatin-like protein 2, and tropomodulin 3, microribonucleic acids, and interleukins. There is a need for standardized protocols to be used to achieve consistent, reproducible results that will facilitate the development of a clinically applicable noninvasive test for endometriosis.

Implantation failure is the most common cause of pregnancy loss after in vitro fertilization and embryo transfer. Recurrent implantation failure (RIF) after in vitro fertilization has devastating consequences for some patients with infertility. Recent studies have reported that microribonucleic acids (miRNAs) can regulate embryo implantation events and may be involved in RIF. MiRNAs are small, single-stranded, noncoding ribonucleic acids that can regulate gene expression in a posttranscriptional manner through degradation or suppression of messenger ribonucleic acids. MiRNAs are generated as long primary miRNA transcripts that are processed by a nuclear RNase III enzyme into precursor miRNAs. After transport to the cytoplasm, the precursor miRNAs are processed into functional miRNAs. MiRNAs have a critical role in normal development and are involved in several biologic processes, including cell proliferation, apoptosis, and differentiation, as well as embryo implantation. MiRNAs also have a role in the down-regulation of several cell cycle genes in the epithelium of the secretory-phase endometrium. This review aimed to discuss the possible roles of miRNAs in RIF. According to published data, miRNAs secreted by the endometrium and embryos can contribute to regulating embryo-endometrium cross talk and impact embryo implantation in patients with RIF. An improved understanding of molecular mechanisms underlying RIF may help to advance diagnosis and treatment of this clinical condition. Although several studies have provided evidence that miRNAs play important roles in RIF, further research is essential to evaluate the function of miRNAs and their target genes and understand the mechanisms by which miRNAs control the molecular events involved in RIF.