OBJECTIVE

To determine the threshold value for anti-Müllerian hormone (AMH) in the diagnosis of polycystic ovarian syndrome (PCOS) in infertile Filipino women and to ascertain the correlation of AMH with age and body mass index of PCOS women.

A retrospective cross-sectional study was carried out on infertile Filipino women at the Center for Advanced Reproductive Medicine and Infertility from August 2015 to March 2020. The women were separated into the PCOS group and male factor infertility group. Serum AMH was analyzed with Access AMH chemiluminescent immunoassay by Beckman Coulter. The AMH threshold for the diagnosis of PCOS was computed using Youden’s index.

There were 585 women included in the study, 311 (53.16%) were diagnosed with PCOS by the Rotterdam criteria, while 274 (46.84%) were non PCOS women. Mean serum AMH for PCOS was 5.88 ± 3.37 (p < 0.01). A threshold value of serum AMH above 3.86 ng/ml was predictive of PCOS by Youden’s index with a sensitivity of 67.2%, specificity of 77.7%, and correct classification rate of 72.1%. There was a negative correlation of AMH level with increasing age in both PCOS and non – PCOS group but the PCOS group had a higher AMH level. There was no correlation noted with AMH and body mass index in both groups.

AMH levels were higher in the PCOS women compared to those without the diagnosis. AMH threshold level could support the diagnosis of PCOS in infertile Filipino women.

Background: Current medical management of endometriosis leads to suppression of ovulation and will not be helpful for women with endometriosis who are desirous of pregnancy. Thus, drugs that can both treat endometriosis and its associated infertility are highly warranted. Objective: Anti-angiogenic agents are potential drugs for patients with endometriosis and infertility. Among these drugs, dopamine agonist (DA) is promising since it does not interfere with ovulation, is safe, and not teratogenic. The aim of the study is to determine the efficacy and safety of DA for improving reproductive outcomes in women with endometriosis and infertility. Methods: A qualitative narrative review was done from inception to July 31, 2022 using the appropriate MeSH terms in PubMed, Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, ClinicalTrial.gov, and World Health Organization International Clinical Trials Registry Platform. Date analysis was through qualitative analysis and synthesis of researches and their outcome measures. Results: No studies used the core outcomes for trials evaluating treatments for infertility associated with endometriosis. All the included articles in the review supported the possible anti-angiogenic effects of DA on the vascular endothelial growth factor [VEGF] /VEGF receptor system. The use of DA does not have an effect on ovulation and menstrual cyclicity. Studies on safety profile of DA were consistent with existing data. Conclusion Most of studies reviewed demonstrated that DA were effective in reducing endometriotic lesions. However, further research is required to establish whether this anti-angiogenic effect can improve reproductive outcomes in women with endometriosis-associated infertility.
Endometriosis ; Dopamine Agonists ; Infertility ; Angiogenesis Inducing Agents ; Angiogenesis Inhibitors

Objective: To investigate the relationship between magnetic resonance imaging (MRI) imaging characteristics and clinical symptoms and therapeutic efficacy in adenomyosis patients. Methods: The clinical characteristics of the adenomyosis questionnaire was self-designed. This was a retrospective study. From September 2015 to September 2020, totally 459 patients were diagnosed with adenomyosis and underwent pelvic MRI examination at Peking University Third Hospital. Clinical characteristics and treatment were collected, MRI was used to determine the lesion location, and to measure the maximum lesion thickness, the maximum myometrium thickness, uterine cavity length, uterine volume, the minimum distance between the lesion and serosa or endometrium, and whether combined with ovarian endometrioma. The difference of MRI imaging characteristics in patients with adenomyosis and its relationship with clinical symptoms and therapeutic efficacy were analyzed. Results: (1) Among the 459 patients, the age was (39.1±6.4) years. There were 376 patients (81.9%, 376/459) with dysmenorrhea. Whether patients had dysmenorrhea were related to uterine cavity length, uterine volume, ratio of the maximum lesion thickness to the maximum myometrium thickness, and whether patients had ovarian endometrioma (all P<0.001). Multivariate analysis suggested that ovarian endometrioma was the risk factor for dysmenorrhea (OR=0.438, 95%CI: 0.226-0.850, P=0.015). There were 195 patients (42.5%, 195/459) with menorrhagia. Whether patients had menorrhagia were related to age, whether patients had ovarian endometrioma, uterine cavity length, the minimum distance between lesion and endometrium or serosa, uterine volume, ratio of the maximum lesion thickness to the maximum myometrium thickness (all P<0.001). Multivariate analysis suggested that ratio of the maximum lesion thickness to the maximum myometrium thickness was the risk factor for menorrhagia (OR=774.791, 95%CI: 3.500-1.715×10⁵, P=0.016). There were 145 patients (31.6%, 145/459) with infertility. Whether the patients had infertility were related to age, the minimum distance between lesion and endometrium or serosa, and whether patients had ovarian endometrioma (all P<0.01). Multivariate analysis suggested that young and large uterine volume were risk factors for infertility (OR=0.845, 95%CI: 0.809-0.882, P<0.001; OR=1.001, 95%CI: 1.000-1.002, P=0.009). (2) The success rate of in vitro fertilization-embryo transfer (IVF-ET) was 39.2% (20/51). Dysmenorrhea, high maximum visual analogue scale score and large uterine volume affected the success rate of IVF-ET (all P<0.05). The smaller the maximum lesion thickness, the smaller the distance between the lesion and serosa, the larger the distance between the lesion and endometrium, the smaller the uterine volume, and the smaller the ratio of the maximum lesion thickness to the maximum myometrium thickness, the better the therapeutic efficacy of progesterones (all P<0.05). Conclusions: Concomitant ovarian endometrioma increases the risk of dysmenorrhea in patients with adenomyosis. The ratio of the maximum lesion thickness to the maximum myometrium thickness is an independent risk factor for menorrhagia. Young and large uterine volume may increase the risk of infertility. Severe dysmenorrhea and large uterine volume affect the success rate of IVF-ET. The therapeutic efficacy of progesterones is relatively better when the lesion is small and far away from the endometrium.
Female ; Humans ; Adult ; Middle Aged ; Adenomyosis/pathology* ; Dysmenorrhea/therapy* ; Menorrhagia/pathology* ; Endometriosis/therapy* ; Retrospective Studies ; Infertility/complications* ; Magnetic Resonance Imaging

OBJECTIVE: To explore the genetic basis for a Fra(16)(q22)/FRA16B fragile site in a female with secondary infertility. METHODS: The 28-year-old patient was admitted to Chengdu Women's and Children's Central Hospital on October 5, 2021 due to secondary infertility. Peripheral blood sample was collected for G-banded karyotyping analysis, single nucleotide polymorphism array (SNP-array), quantitative fluorescent polymerase chain reaction (QF-PCR) and fluorescence in situ hybridization (FISH) assays. RESULTS: The patient was found to harbor 5 mosaic karyotypes involving chromosome 16 in a total of 126 cells, which yielded a karyotype of mos 46,XX,Fra(16)(q22)[42]/46,XX,del(16)(q22)[4]/47,XX,del(16),+chtb(16)(q22-qter)[4]/46,XX,tr(16)(q22)[2]/46,XX[71]. No obvious abnormality was found by SNP-array, QF-PCR and FISH analysis. CONCLUSION A female patient with FRA16B was identified by genetic testing. Above finding has enabled genetic counseling of this patient.
Female ; Humans ; In Situ Hybridization, Fluorescence ; Chromosome Fragile Sites ; Karyotyping ; Karyotype ; Infertility

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.
Humans ; Male ; Mice ; Animals ; Orchitis ; Uropathogenic Escherichia coli/metabolism* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Macrophages/metabolism* ; Phenotype ; Infertility, Male/metabolism*

Coronavirus disease 2019 (COVID-19) has yet to be proven to alter male reproductive function, particularly in the majority of mild/asymptomatic patients. The purpose of this study was to explore whether mild/asymptomatic COVID-19 affects semen quality and sex-related hormone levels. To find suitable comparative studies, a systematic review and meta-analysis was done up to January 22, 2022, by using multiple databases (Web of Science, PubMed, and Embase). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to identify and choose the studies. Meta-analysis was used to examine the semen parameters and sex-related hormones of mild/asymptomatic COVID-19 patients before and after infection. The effects of semen collection time, fever, and intensity of verification on semen following infection were also investigated. A total of 13 studies (n = 770) were included in the analysis, including three case-control studies, six pre-post studies, and four single-arm studies. A meta-analysis of five pre-post studies showed that after infection with COVID-19, sperm concentration (I² = 0; P = 0.003), total sperm count (I² = 46.3%; P = 0.043), progressive motility (I² = 50.0%; P < 0.001), total sperm motility (I² = 76.1%; P = 0.047), and normal sperm morphology (I² = 0; P = 0.001) decreased. Simultaneously, a systematic review of 13 studies found a significant relationship between semen collection time after infection, inflammation severity, and semen parameter values, with fever having only bearing on semen concentration. Furthermore, there was no significant difference in sex-related hormone levels before and after infection in mild/asymptomatic patients. Mild/asymptomatic COVID-19 infection had a significant effect on semen quality in the short term. It is recommended to avoid initiating a pregnancy during this period of time.
Pregnancy ; Female ; Humans ; Male ; Semen Analysis ; Semen ; Infertility, Male ; Sperm Motility ; COVID-19 ; Sperm Count ; Spermatozoa ; Testosterone ; Gonadal Steroid Hormones

Male ; Humans ; Azoospermia/genetics* ; Infertility, Male/genetics* ; Mutation ; Homozygote

Teratozoospermia is a rare disease associated with male infertility. Several recurrent genetic mutations have been reported to be associated with abnormal sperm morphology, but the genetic basis of tapered-head sperm is not well understood. In this study, whole-exome sequencing (WES) identified a homozygous WD repeat domain 12 (WDR12; p.Ser162Ala/c.484T>G) variant in an infertile patient with tapered-head spermatozoa from a consanguineous Chinese family. Bioinformatic analysis predicted this mutation to be a pathogenic variant. To verify the effect of this variant, we analyzed WDR12 protein expression in spermatozoa of the patient and a control individual, as well as in the 293T cell line, by Western blot analysis, and found that WDR12 expression was significantly downregulated. To understand the role of normal WDR12, we evaluated its mRNA and protein expression in mice at different ages. We observed that WDR12 expression was increased in pachytene spermatocytes, with intense staining visible in round spermatid nuclei. Based on these results, the data suggest that the rare biallelic pathogenic missense variant (p.Ser162Ala/c.484T>G) in the WDR12 gene is associated with tapered-head spermatozoa. In addition, after intracytoplasmic sperm injection (ICSI), a successful pregnancy was achieved. This finding indicates that infertility associated with this WDR12 homozygous mutation can be overcome by ICSI. The present results may provide novel insights into understanding the molecular mechanisms of male infertility.
Humans ; Pregnancy ; Female ; Male ; Animals ; Mice ; Teratozoospermia/pathology* ; Semen/metabolism* ; Infertility, Male/metabolism* ; Spermatozoa/metabolism* ; Mutation ; RNA-Binding Proteins/metabolism* ; Cell Cycle Proteins/genetics*

The process of semen collection plays a key role in the quality of semen specimens. However, the association between semen collection time and semen quality is still unclear. In this study, ejaculates by masturbation from 746 subfertile men or healthy men who underwent semen analysis were examined. The median (interquartile range) semen collection time for all participants was 7.0 (5.0-11.0) min, and the median time taken for semen collection was lower in healthy men than that in subfertile men (6.0 min vs 7.0 min). An increase in the time required to produce semen samples was associated with poorer semen quality. Among those undergoing assisted reproductive technology (ART), the miscarriage rate was positively correlated with the semen collection time. After adjusting for confounders, the highest quartile (Q4) of collection time was negatively associated with semen volume and sperm concentration. A longer time to produce semen samples (Q3 and Q4) was negatively correlated with progressive and total sperm motility. In addition, there was a significant negative linear association between the semen collection time and the sperm morphology. Higher risks of asthenozoospermia (adjusted odds ratio [OR] = 2.06, 95% confidence interval [CI]: 1.31-3.25, P = 0.002) and teratozoospermia (adjusted OR = 1.98, 95% CI: 1.10-3.55, P = 0.02) were observed in Q3 than those in Q1. Our results indicate that a higher risk of abnormal semen parameter values was associated with an increase in time for semen collection, which may be related to male fertility through its association with semen quality.
Male ; Humans ; Semen Analysis ; Semen ; Sperm Motility ; Sperm Count ; Asthenozoospermia ; Spermatozoa

Male infertility caused by idiopathic oligoasthenospermia (OAT) is known as idiopathic male infertility. Glutathione S-transferase (GST) and fluoride may play important roles in idiopathic male infertility, but their effects are still unknown. Our study examined the relationship between GST polymorphisms and fluoride-induced toxicity in idiopathic male infertility and determined the underlying mechanism. Sperm, blood, and urine samples were collected from 560 males. Fluoride levels were measured by a highly selective electrode method, and GST genotypes were identified using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Semen parameters, DNA fragmentation index (DFI), mitochondrial membrane potential (MMP), and oxidative stress (OS) biomarkers were statistically assessed at the P < 0.05 level. Compared with healthy fertile group, semen parameters, fluoride levels, OS biomarkers, sex hormone levels, and MMP and DFI levels were lower in the idiopathic male infertility group. For glutathione S-transferase M1 (GSTM1[-]) and glutathione S-transferase T1 (GSTT1[-]) or glutathione S-transferase P1 (GSTP1) mutant genotypes, levels of semen fluoride, OS, MMP, and DFI were considerably higher, and the mean levels of sperm parameters and testosterone were statistically significant in GSTM1(+), GSTT1(+), and GSTP1 wild-type genotypes. Both semen and blood fluoride levels were associated with oxidative stress in idiopathic male infertility patients. Elevated fluoride in semen with the genotypes listed above was linked to reproductive quality in idiopathic male infertility patients. In conclusion, GST polymorphisms and fluorine may have an indicative relationship between reproductive quality and sex hormone levels, and OS participates in the development of idiopathic male infertility.
Humans ; Male ; Fluorides/adverse effects* ; Semen ; Polymorphism, Genetic ; Glutathione Transferase/genetics* ; Glutathione S-Transferase pi/genetics* ; Infertility, Male/genetics* ; Genotype ; Biomarkers ; Genetic Predisposition to Disease ; Case-Control Studies