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*

After the promulgation of the first edition of expert consensus on the application of chromosomal microarray analysis (CMA) technology in prenatal diagnosis in 2014, after 8 years of clinical and technical development, CMA technology has become a first-line diagnosis technology for fetal chromosome copy number deletion or duplication abnormalities, and is widely used in the field of prenatal diagnosis in China. However, with the development of the industry and the accumulation of experience in case diagnosis, the application of CMA technology in many important aspects of prenatal diagnosis, such as clinical diagnosis testimony, data analysis and genetic counseling before and after testing, needs to be further standardized and improved, so as to make the application of CMA technology more in line with clinical needs. The revision of the guideline was led by the National Prenatal Diagnostic Technical Expert Group, and several prenatal diagnostic institutions such as Peking Union Medical College Hospital were commissioned to write, discuss and revise the first draft, which was discussed and reviewed by all the experts of the National Prenatal Diagnostic Technical Expert Group, and was finally formed after extensive review and revision. This guideline is aimed at the important aspects of the application of CMA technology in prenatal diagnosis and clinical diagnosis, from the clinical application of evidence, test quality control, data analysis and interpretation, diagnosis report writing, genetic counseling before and after testing and other work specifications are elaborated and introduced in detail. It fully reflects the integrated experience, professional thinking and guidance of the current Chinese expert team on the prenatal diagnosis application of CMA technology. The compilation of the guideline for the application of CMA technology in prenatal diagnosis will strive to promote the standardization and advancement of prenatal diagnosis of fetal chromosome diseases in China.
Female ; Humans ; Pregnancy ; Asian People ; Chromosome Aberrations ; Chromosome Deletion ; Chromosome Duplication/genetics* ; DNA Copy Number Variations/genetics* ; Fetal Diseases/genetics* ; Genetic Counseling ; Microarray Analysis ; Prenatal Care ; Prenatal Diagnosis ; Practice Guidelines as Topic

Objective To explore the clinical significance of non-invasive prenatal testing(NIPT)for fetal chromosomal abnormalities in the cases of twin pregnancy and its relationship with age and other related factors.Methods A total of 3733 women with twin pregnancy of 12-26⁺⁶ weeks who voluntarily underwent NIPT in the Ningbo Women and Children's Hospital from January 2018 to December 2022 were selected.The results of NIPT and amniocentesis were compared and all the participants were followed up.The detection rate of chromosomal abnormalities by NIPT was calculated,and its correlations with age,gestational weeks,chorionicity,and pregnancy type were analyzed.Results Among the 3733 cases,71 cases of fetal chromosome abnormality were indicated by NIPT,including 13 cases of trisomy 21,19 cases of trisomy 18,5 cases of trisomy 13,18 cases of sex chromosome abnormality,and 16 cases of chromosome microdeletion/duplication(excluding 21,18,13,and sex chromosomes),among which 34 cases were true positive and 37 cases were false positive.The overall sensitivity,specificity,and positive predictive value(PPV)of NIPT for chromosomal abnormalities in the cases of twin pregnancy were 100%,98.99%,and 47.89%(34/71),respectively.NIPT showed the sensitivity,specificity,and PPV of 100%,99.78%,and 78.38%(29/37)for trisomy 21,18,and 13,100%,99.56%,and 16.67%(3/18)for sex chromosome abnormalities,and 100%,99.62%,and 12.5%(2/16)for chromosome microdeletion/duplication,respectively.In the age group of ≥40 years,the NIPT for chromosomal abnormalities showed the PPV of 66.67%,the sensitivity of 100%,and the misdiagnosis rate of 30%。However,the NIPT for trisomy 21,18,and 13 showed the PPV of 100%,the misdiagnosis rate of 0,and the sensitivity and specificity of 100%.In terms of grouping based on gestational weeks,the NIPT for chromosomal abnormalities showed the highest PPV(51.28%)in the women with twin pregnancy for 14-17⁺⁶ weeks,followed by that(50.00%)in the women with twin pregnancy for 22-26⁺⁶ weeks;the NIPT for trisomy 21,18,and 13 showed the highest PPV of 94.74% in the gestation group of 14-17⁺⁶ weeks,followed by that(83.33%)in the gestation group of 18-21⁺⁶ weeks.The rate of dichorionic diamniotic twins was higher in assisted pregnancies than in natural pregnancies,and NIPT showed the same detection efficiency for dichorionic diamniotic twins and monochorionic diamniotic twins and the same detection efficiency for different pregnancy types.Conclusions NIPT has high accuracy in the diagnosis of twin pregnancy and high sensitivity and high specificity for different ages and gestational weeks,especially for trisomy 21,18,and 13.NIPT is suitable for assisted pregnancy and natural pregnancy,and it is of high value in clinical application.However,extensive application needs a large population-based study.
Pregnancy ; Child ; Female ; Humans ; Adult ; Down Syndrome/genetics* ; Pregnancy, Twin ; Prenatal Diagnosis ; Trisomy ; Chromosome Aberrations

OBJECTIVE: To validate a fetus with high risk for trisomy 13 suggested by non-invasive prenatal testing (NIPT). METHODS: The fetus was selected as the study subject after the NIPT detection at Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences on February 18, 2019. Clinical data of the pregnant woman was collected. Fluorescence in situ hybridization (FISH), chromosomal karyotyping analysis and chromosomal microarray analysis (CMA) were carried out on amniotic fluid and umbilical cord blood and the couple's peripheral blood samples. Copy number variation sequencing (CNV-seq) was also performed on the placental and amniotic fluid samples following induced labor. RESULTS: The pregnant woman, a 38-year-old G4P1 gravida, was found to have abnormal fetal development by prenatal ultrasonography. NIPT test suggested that the fetus has a high risk for trisomy 13. Chromosomal karyotyping analysis of fetal amniotic fluid and umbilical cord blood were 46,XN,add(13)(p10). The result of CMA was arr[hg19]1q41q44(223937972_249224684)×3, with the size of the repeat fragment being approximately 25.29 Mb, the fetal karyotype was thereby revised as 46,XN,der(13)t(1;13)(q41;p10). Chromosomal karyotyping analysis and CMA of the parents' peripheral blood samples showed no obvious abnormality. The CNV-seq analysis of induced placenta revealed mosaicisms of normal karyotype and trisomy 13. The CNV-seq test of induced amniotic fluid confirmed a duplication of chr1:22446001_249220000 region spanning approximately 24.75 Mb, which was in keeping with the CMA results of amniotic fluid and umbilical cord blood samples. CONCLUSION NIPT may yield false positive result due to placenta mosaicism. Invasive prenatal diagnosis should be recommended to women with a high risk by NIPT test. And analysis of placenta can explain the inconsistency between the results of NIPT and invasive prenatal diagnosis.
Humans ; Female ; Pregnancy ; Trisomy 13 Syndrome/genetics* ; DNA Copy Number Variations ; Placenta ; Chromosomes, Human, Pair 1 ; In Situ Hybridization, Fluorescence ; Prenatal Diagnosis/methods* ; Fetus ; Amniotic Fluid ; Chromosome Aberrations ; Trisomy/genetics*

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for detecting fetal chromosomal microdeletion/microduplication syndromes by carrying out prenatal diagnoses for two fetuses with Xp22.31 microdeletion indicated by NIPT. METHODS: Two pregnant women suspected for fetal Xp22.31 microdeletion syndrome who presented at Zaozhuang Maternal and Child Health Care Hospital on December 5, 2017 and October 15, 2020 were selected as the study subjects. Clinical data of the two women were collected, and peripheral venous blood samples were collected for NIPT testing. Amniotic fluid samples were taken for G-banding chromosomal karyotyping analysis and copy number variation sequencing (CNV-seq) for fetus 1, while G-banding chromosomal karyotyping and single nucleotide polymorphism microarray analysis (SNP array) were carried out for fetus 2. Peripheral venous blood samples of couple 1 were collected for CNV-seq to verify the origin of copy number variation . RESULTS: NIPT indicated that fetus 1 had harbored a 1.3 Mb deletion in the Xp22.31 region, while G-banding chromosomal karyotyping had found no abnormality. CNV-seq analysis verified the fetus to be seg[GRCh37]del(X)(p22.31)chrX:g.6800001_7940000del, with a 1.14 Mb deletion at Xp22.31, which was derived from its mother. NIPT indicated that fetus 2 had harbored a 1.54 Mb deletion in the Xp22.31 region, while G-banding chromosomal karyotyping had found no abnormality. SNP array analysis indicated arr[GRCh37]Xp22.31(6458940_8003247)×0, with a 1.54 Mb deletion in Xp22.31 region. CONCLUSION NIPT not only has a good performance for detecting fetal trisomies 21, 18 and 13, but also has the potential for detecting chromosomal microdeletion/microduplications. For high risk fetuses indicated by NIPT, prenatal diagnosis needs to be carry out to verify the chromosomal abnormalities.
Child ; Female ; Pregnancy ; Humans ; DNA Copy Number Variations ; Prenatal Diagnosis ; Down Syndrome/diagnosis* ; Chromosome Aberrations ; Fetus

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, chromosomal microdeletions and microduplications using cell-free fetal DNA from peripheral blood samples of pregnant women. METHODS: A total of 15 237 pregnant women who had undergone NIPT testing at the Maternity and Child Health Care Hospital of Zaozhuang from February 2015 to December 2021 were enrolled in this study. For those with a high risk by NIPT, amniotic fluid samples were collected for G-banding chromosomal karyotyping analysis and chromosomal microarray analysis to verify the consistency of NIPT with results of prenatal diagnosis. All of the women were followed up by telephone for pregnancy outcomes. RESULTS: Among the 15 237 pregnant women, 266 (1.75%) were detected with a high risk for fetal chromosomal abnormality were detected. Among these, 79 (29.7%) were at a high risk for T21, 26 (9.77%) were at a high risk for T18, 9 (3.38%) were at a high risk for T13, 74 (27.82%) were at a high risk for sex chromosome aneuploidies, 12 (4.51%) were at a high risk for other autosomal aneuploidies, and 66 (24.81%) were at a high risk for chromosomal microdeletions or microduplications. 217 women had accepted invasive prenatal diagnosis and respectively 50, 13, 1, 25, 1 and 18 were confirmed with T21, T18, T13, sex chromosome aneuploidies, autosomal aneuploidies and microdeletions/microduplications, and the positive predictive values were 75.76%, 68.42%, 11.11%, 40.32%, 10% and 35.29%, respectively. For 13 042 women (85.59%), the outcome of pregnancy were successfully followed up. During the follow-up, one false negative case of T21 was discovered. No false positive cases for T13 and T18 were found. CONCLUSION NIPT has a sound performance for screening T13, T18 and T21, and is also valuable for screening other autosomal aneuploidies, sex chromosome aneuploidies and chromosomal microdeletions/microduplications.
Child ; Female ; Pregnancy ; Humans ; Retrospective Studies ; Cell-Free Nucleic Acids ; Chromosome Disorders/genetics* ; Prenatal Diagnosis/methods* ; Down Syndrome/genetics* ; Sex Chromosome Aberrations ; Trisomy 18 Syndrome/genetics* ; Trisomy 13 Syndrome/diagnosis* ; Aneuploidy ; DNA/genetics* ; Trisomy/genetics*