Y chromosome microdeletions are an important cause of male infertility. At present, research on the Y chromosome is mainly focused on analyzing the loss of large segments of the azoospermia factor a/b/c (AZFa/b/c) gene, and few studies have reported the impact of unit point deletion in the AZF band on fertility. This study analyzed the effect of sperm quality after sY1192 loss in 116 patients. The sY1192-independent deletion accounted for 41.4% (48/116). Eight patterns were found in the deletions associated with sY1192. The rate of sperm detection was similar in the semen of patients with the independent sY1192 deletion and the combined sY1192 deletions (52.1% vs 50.0%). The patients with only sY1192 gene loss had a higher probability of sperm detection than the patients whose sY1192 gene locus existed, but other gene loci were lost (52.1% vs 32.0%). The hormone levels were similar in patients with sY1192 deletion alone and in those with sY1192 deletion and other types of microdeletions in the presence of the sY1192 locus. After multiple intracytoplasmic sperm injection (ICSI) attempts, the pregnancy rate of spouses of men with sY1192-independent deletions was similar to that of other types of microdeletions, but the fertilization and cleavage rates were higher. We observed that eight deletion patterns were observed for sY1192 microdeletions of AZFb/c, dominated by the independent deletion of sY1192. After ICSI, the fertilization rate and cleavage rate of the sY1192-independent microdeletion were higher than those of other Y chromosome microdeletion types, but there was no significant difference in pregnancy outcomes.
Humans ; Female ; Pregnancy ; Male ; Chromosomes, Human, Y/genetics* ; Adult ; Chromosome Deletion ; Pregnancy Outcome/genetics* ; Infertility, Male/genetics* ; Spermatozoa/physiology* ; Semen Analysis ; Sex Chromosome Disorders of Sex Development/genetics* ; Sperm Injections, Intracytoplasmic ; Azoospermia/genetics* ; Sex Chromosome Aberrations

Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male patients whose semen was analyzed from March 2023 to July 2023. Their clinical data, including semen parameters and age, were also collected. Genetic analysis was used to determine whether the sex chromosome involved in male infertility was abnormal (including the increase, deletion, and translocation of the X and Y chromosomes), and subsequent semen analysis was conducted for clinical grouping purposes. The participants were categorized into five groups: normozoospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, and azoospermia. Patients were randomly selected for further study; 41 patients with normozoospermia were included in the control group and 117 patients with non-normozoospermia were included in the study group according to the proportions of all enrolled patients. Cytokinesis-block micronucleus (CBMN) screening was conducted through peripheral blood. Statistical analysis was used to determine the differences in micronuclei (MNi) among the groups and the relationships between MNi and clinical data. There was a significant increase in MNi in infertile men, including those with azoospermia, compared with normozoospermic patients, but there was no significant difference between the genetic and nongenetic groups in azoospermic men. The presence of MNi was associated with sperm concentration, progressive sperm motility, immotile spermatozoa, malformed spermatozoa, total sperm count, and total sperm motility. This study underscores the potential utility of MNi as a diagnostic tool and highlights the need for further research to elucidate the underlying mechanisms of male infertility.
Humans ; Male ; Infertility, Male/genetics* ; Adult ; Micronucleus Tests ; Semen Analysis ; Oligospermia/genetics* ; Azoospermia/genetics* ; Chromosome Aberrations ; Sperm Count ; Micronuclei, Chromosome-Defective ; Middle Aged

OBJECTIVE: To analyze the effect of Y chromosome AZFc microdeletion on pregnancy outcome of intracytoplasmic sperm injection (ICSI). METHODS: From 2016 to 2023, 6 765 cases of oligozoospermia in our hospital were selected as the research objects. The results of Y chromosome microdeletion test were retrospectively analyzed. According to the inclusion exclusion criteria and the principle of propensity distribution 1∶2, 180 patients were included in the study. Sixty patients with Y chromosome AZFc microdeletion and ICSI assisted pregnancy were enrolled into the experimental group. The other 120 patients without Y chromosome microdeletion and ICSI assisted pregnancy were included in the control group. Baseline characteristics, five male sex hormones, laboratory embryo culture and pregnancy outcomes were compared between the two groups. RESULTS: There was no significant difference in male age, female age, infertility years, gravidity and parity between the two groups (P>0.05). There was no significant difference in the five sex hormones of men (P>0.05). Except for transplantable embryos (P<0.05), there was no significant difference in other indicators in the process of embryo culture. There was no difference in pregnancy outcome indicators between the two groups except for the preterm birth rate (P<0.05). CONCLUSION ICSI assisted pregnancy with Y chromosome AZFc microdeletion has no significant effect on pregnancy outcome. And close follow-up of offspring is required.
Humans ; Sperm Injections, Intracytoplasmic ; Pregnancy ; Female ; Chromosomes, Human, Y ; Male ; Chromosome Deletion ; Pregnancy Outcome ; Retrospective Studies ; Sex Chromosome Disorders of Sex Development ; Sex Chromosome Aberrations ; Adult ; Infertility, Male/genetics* ; Oligospermia/genetics* ; Pregnancy Rate

OBJECTIVES: Chromosomal abnormalities are the most common cause of spontaneous abortion (SA). This study aims to analyze the association between SA and chromosomal abnormalities in products of conception, and to compare the impact of different pregnancy modes and different numbers of previous abortions on chromosomal abnormalities, providing clinical consulting references. METHODS: A total of 1 345 SA patients treated at the Affiliated Women's Hospital of Jiangnan University (Wuxi Maternity and Child Health Care Hospital) between January 2019 and December 2023 were enrolled. According to the mode of conception, patients were divided into 2 groups: a spontaneous pregnancy group (S group, n=1242) and an assisted reproductive technology (ART)-conceived group (ART group, n=103). Based on the number of miscarriages, the S group was further subdivided into a spontaneous sporadic abortion group (S-1 group, n=780) and a spontaneous recurrent abortion group (S-2 group, n=462); the ART group was subdivided into an ART sporadic abortion group (ART-1 group, n=68) and an ART recurrent abortion group (ART-2 group, n=35). Chromosomal microarray analysis (CMA) was performed on products of conception. RESULTS: The incidence of numerical chromosomal abnormalities was 56.79% (443/780) in the S-1 group and 52.38% (242/462) in the S-2 group, while the incidence of structural abnormalities was 4.36% (34/780) and 7.36% (34/462), respectively. There was a statistically significant difference in structural abnormalities between the 2 groups (P<0.05). Among the spontaneous pregnancy SA cases, the incidence of numerical abnormalities decreased with increasing numbers of miscarriages, and was significantly lower in the group with ≥4 miscarriages compared to those with 1 or 2 miscarriages (both P<0.05). The incidence of structural abnormalities in groups with 1, 2, 3, and ≥4 miscarriages was 3.46%, 5.65%, 5.88%, and 4.35%, respectively, with no statistically significant differences among groups (all P>0.05). The incidence of pathogenic copy number variants (pCNVs) plus likely pathogenic copy number variants (LP-CNVs) gradually increases in the group with 1-3 miscarriages, and there was a statistically significant difference between the group with 1 miscarriage and the group with 2 miscarriages (P<0.05). In the ART group, the incidence of numerical abnormalities was 47.06% (32/68) in ART-1 and 37.14% (13/35) in ART-2, while structural abnormalities occurred in 2.94% (2/68) and 11.43% (4/35), respectively, with no significant differences between the groups (both P>0.05). There were no statistically significant differences in the incidence of numerical or structural abnormalities between the S-1 and ART-1 groups, or between the S-2 and ART-2 groups (all P>0.05). CONCLUSIONS Chromosomal numerical and structural abnormalities are common in SA patients from both spontaneous and ART-conceived pregnancies. Attention should be paid to patients with recurrent miscarriage in genetic investigation.
Humans ; Female ; Pregnancy ; Chromosome Aberrations/statistics & numerical data* ; Abortion, Spontaneous/epidemiology* ; Adult ; Reproductive Techniques, Assisted/adverse effects* ; Abortion, Habitual/genetics* ; Fertilization

Multiple myeloma (MM) is a common hematologic malignancy that originates from precursor conditions such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Identifying its risk factors is crucial for early intervention. The etiology of MM is multifactorial, involving race, familial clustering, gender, age, obesity, cytogenetic abnormalities, and environmental exposures. Among these, cytogenetic abnormalities and modifiable factors play pivotal roles in MM pathogenesis and progression. 1) cytogenetic abnormalities. Primary abnormalities [e.g., hyperdiploidy, t(11;14), t(14;16)] emerge at the MGUS stage, while secondary abnormalities [e.g., 1q+, del(17p)] drive disease progression. The accumulation of 1q+ promotes clonal evolution, and del(17p) is associated with significantly reduced survival. 2) modifiable risk factors. Obesity promotes MM via the acetyl-CoA synthetase 2 (ACSS2)-interferon regulatory factor 4 (IRF4) pathway. Vitamin D deficiency weakens immune surveillance. Exposure to herbicides such as Agent Orange and glyphosate increases MGUS incidence. Insufficient UV exposure, by reducing vitamin D synthesis, elevates MM risk. Gut microbiota dysbiosis (enrichment of nitrogen-cycle bacteria and depletion of short-chain fatty acids producers) induces chromosomal instability through the ammonium ion-solute carrier family 12 member 22 (SLC12A2)-NEK2 axis. Therefore, risk-based screening among high-risk populations (e.g., those who are obese, elderly, or chemically exposed), along with early interventions targeting cytogenetic abnormalities [e.g., B cell lymphoma 2 (Bcl-2) inhibitors for t(11;14), ferroptosis inducers for t(4;14)] and modifiable factors (e.g., vitamin D supplementation, gut microbiota modulation), may effectively delay disease progression and improve prognosis.
Humans ; Multiple Myeloma/epidemiology* ; Risk Factors ; Obesity/complications* ; Chromosome Aberrations ; Monoclonal Gammopathy of Undetermined Significance/etiology* ; Gastrointestinal Microbiome ; Vitamin D Deficiency/complications* ; Precancerous Conditions/genetics*

OBJECTIVE: To explore the coincidence rate of G-banding karyotype analysis and fluorescence in situ hybridization (FISH) for the diagnosis of children with sex chromosome mosaicisms. METHODS: A retrospective analysis was carried out for 157 children with suspected sex chromosome abnormalities who had presented at Shenzhen Children's Hospital from April 2021 to May 2022. Interphase sex chromosome FISH and G-banding karyotyping results were collected. The coincidence rate of the two methods in children with sex chromosome mosaicisms was compared. RESULTS: The detection rates of G-banding karyotype analysis and FISH were 26.1% (41/157) and 22.9% (36/157) , respectively (P > 0.05). The results of G-banding karyotype analysis showed that 141 cases (89.8%) were in the sex chromosome homogeneity group, of which only 5 cases (3.5%) were inconsistent with the results of FISH. There were 16 cases (10.2%) in the sex chromosome mosaicism group, of which 11 cases (68.8%) were inconsistent with the results of FISH. There was a statistical difference between the two groups in the coincidence rate of the results of the two methods (P < 0.05). CONCLUSION No significant difference was found between G-banding karyotype analysis and FISH in the detection rate of chromosome abnormalities. The coincidence rate in the mosaicism group was lower than that in the homogeneity group, and the difference was statistically significant. The two methods should be combined for clinical diagnosis.
Humans ; Mosaicism ; In Situ Hybridization, Fluorescence/methods* ; Retrospective Studies ; Karyotyping ; Chromosome Aberrations ; Sex Chromosome Aberrations ; Karyotype ; Chromosome Banding ; Sex Chromosomes

OBJECTIVE: To assess the application value of copy number variation sequencing (CNV-seq) for women with a high risk for fetal anomalies. METHODS: Based on the results of non-invasive prenatal testing (NIPT), 271 high-risk pregnant women were divided into NIPT positive group (n = 83) and other anomaly group (advanced age, high risk by serological screening, repeated NIPT failure, adverse pregnancy history, abnormal ultrasound finding, and abnormal phenotype) (n = 188). CNV-seq was carried out to detect copy number variations (CNVs) in amniocytic DNA from the two groups of pregnant women, and karyotyping analysis of the amniotic cells was carried out for verification and comparison. RESULTS: The amniocytes from 271 pregnant women were detected. The detection rate was 20.66% (56/271) for pathogenic CNVs by CNV-seq and 19.19% (52/271) for pathogenic karyotypes by karyotyping analysis. The difference was statistically significant (P < 0.05). CNV-seq had shown that, compared with NIPT positive group, the detection rates for likely pathogenic CNVs and variants of unknown significance (VUS) in other abnormality group were significantly higher [2.41%(2/83) vs. 5.32%(10/188)](P < 0.05). CONCLUSION CNV-seq can well suit the first-tier diagnosis for pregnant women suspected for fetal abnormality. In prenatal diagnosis settings, CNV-seq can identify additional and clinically significant cytogenetic abnormalities. In those with other abnormalities, the detection rates for likely pathogenic CNVs and VUS are higher than with the NIPT positive cases.
Female ; Pregnancy ; Humans ; DNA Copy Number Variations ; Pregnancy, High-Risk ; Prenatal Diagnosis/methods* ; Chromosome Aberrations ; Chromosome Disorders/genetics*

OBJECTIVE: To explore the incidence of azoospermia factor c (AZFc) microdeletion among patients with azoospermia or severe oligospermia, its association with sex hormone/chromosomal karyotype, and its effect on the outcome of pregnancy following intracytoplasmic sperm injection (ICSI) treatment. METHODS: A total of 1 364 males with azoospermia or severe oligospermia who presented at the Affiliated Maternity and Child Health Care Hospital of Jiaxing College between 2013 and 2020 were subjected to AZF microdeletion and chromosome karyotyping analysis. The level of reproductive hormones in patients with AZFc deletions was compared with those of control groups A (with normal sperm indices) and B (azoospermia or severe oligospermia without AZFc microdeletion). The outcome of pregnancies for the AZFc-ICSI couples was compared with that of the control groups in regard to fertilization rate, superior embryo rate and clinical pregnancy rate. RESULTS: A total of 51 patients were found to harbor AZFc microdeletion, which yielded a detection rate of 3.74%. Seven patients also had chromosomal aberrations. Compared with control group A, patients with AZFc deletion had higher levels of PRL, FSH and LH (P < 0.05), whilst compared with control group B, only the PRL and FSH were increased (P < 0.05). Twenty two AZFc couples underwent ICSI treatment, and no significant difference was found in the rate of superior embryos and clinical pregnancy between the AZFc-ICSI couples and the control group (P > 0.05). CONCLUSION The incidence of AZFc microdeletion was 3.74% among patients with azoospermia or severe oligospermia. AZFc microdeletion was associated with chromosomal aberrations and increased levels of PRL, FSH and LH, but did not affect the clinical pregnancy rate after ICSI treatment.
Child ; Humans ; Male ; Female ; Pregnancy ; Azoospermia/genetics* ; Oligospermia/genetics* ; Incidence ; Chromosome Deletion ; Chromosomes, Human, Y/genetics* ; Semen ; Infertility, Male/genetics* ; Chromosome Aberrations ; Follicle Stimulating Hormone/genetics*

Chromosomal aberrations including numerical abnormalities and segment duplications/deletions, as genome-wide copy number variations (CNVs), are a leading cause for spontaneous abortion. Analysis of abortive tissues for such CNVs can detect potential genomic variations in the couple and provide guidance for the choice of appropriate method to avoid further miscarriage or birth of child with chromosomal disorders. With evidence-based clinical data, an expert group jointly formed by the Genetic Disease Prevention and Control Group, Committee for Birth Defects Prevention and Control, Chinese Association of Preventive Medicine; the Clinical Genetics Group, the Society of Medical Genetics, Chinese Medical Association; the Professional Committee for Prenatal Diagnosis of Genetic Diseases, the Society of Medical Geneticists, Chinese Medical Doctor Association has discussed and formulated this consensus, with an aim to provide guidance for the application of genomic CNVs detection for the abortive tissue and genetic counseling for family reproduction.
Pregnancy ; Child ; Female ; Humans ; DNA Copy Number Variations ; Consensus ; Chromosome Aberrations ; Chromosome Disorders/genetics* ; Abortion, Spontaneous/genetics*

OBJECTIVE: To assess the clinical efficacy and health economic value of non-invasive prenatal testing (NIPT) for the prenatal screening of common fetal chromosomal aneuploidies. METHODS: 10 612 pregnant women from October 2017 to December 2019 presented at the antenatal screening clinic of the General Hospital of Tianjin Medical University were selected as the study subjects. Results of NIPT and invasive prenatal diagnosis and follow-up outcome for the 10 612 pregnant women were retrospectively analyzed and compared. Meanwhile, NIPT data for two periods were analyzed for assessing the health economic value of NIPT as the second- or first-tier screening strategy for the prenatal diagnosis of fetal trisomies 21, 18 and 13. RESULTS: The NIPT was successful in 10 528 (99.72%) subjects, with the sensitivity for fetal trisomies 21, 18 and 13 being 100%, 92.86% and 100%, and the positive predictive value (PPV) being 89.74%, 61.90% and 44.44%, respectively. The PPV of NIPT for sex chromosome aneuploidies was 34.21%. Except for one false negative case of trisomy 18, the negative predictive value for trisomy 21, trisomy 13 and other chromosomal abnormalities were 100%. For pregnant women with high risk by serological screening, advanced maternal age or abnormal ultrasound soft markers, NIPT has yielded a significantly increased high risk ratio. There was no statistical difference in the PPV of NIPT among pregnant women from each subgroup. NIPT would have higher health economic value as a second-tier screening until 2019, while compared to 2015 ~ 2017, its incremental cost-effectiveness ratio as a first-tier screening had declined clearly. CONCLUSION The screening efficacy of NIPT for trisomies 21, 18 and 13 for a mixed population is significantly better than conventional serological screening, but it is relatively low for sex chromosomal abnormalities. NIPT can also be recommended for populations with relatively high risks along with detailed pre- and post-test genetic counselling. From the perspective of health economics, except for open neural tube defects, it is possible for NIPT to replace the conventional serological screening in the future as its cost continues to decrease.
Pregnancy ; Female ; Humans ; Trisomy/genetics* ; Retrospective Studies ; Prenatal Diagnosis/methods* ; Down Syndrome/genetics* ; Aneuploidy ; Chromosome Aberrations ; Trisomy 18 Syndrome/genetics* ; Sex Chromosome Aberrations ; Fetus