Congenital malformations after intracytoplasmic injection of spermatids

Spermatid microinjection into oocytes was applied in cases of intracytoplasmic sperm injection (ICSI)/testicular sperm extraction (TESE) where no spermatozoa could be found in numerous testicular samples. Although several pregnancies were obtained with this procedure, serious concerns remain regarding its safety. Although the relevance of the injection of spermatids is by no means certain, we wish to report that from four pregnancies obtained after injection of elongated spermatids, two cases of major malformation resulted.     

Seminal plasma characteristics as indicators of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in men with obstructive azoospermia

Objective: To determine the prognostic value of seminal plasma volume, pH, fructose, and -glucosidase for the detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations.

Design: Retrospective data analysis.

Setting: University infertility clinic (referral center).

Patient(s): Fifty-nine men with obstructive azoospermia.

Intervention(s): Semen analysis including seminal plasma volume, pH, fructose, -glucosidase, molecular genetic diagnosis of CFTR mutations and FSH measurement.

Main Outcome Measure(s): Sensitivity and specificity of seminal plasma markers for the detection of CFTR mutations.

Result(s): A CFTR mutation was detected in 26 of 59 patients with obstructive azoospermia. Patients carrying a mutation had significantly lower seminal plasma volume (mean ± SEM: 1.5 ± 1.4 mL vs. 2.8 ± 2.2 mL), lower pH levels (25th percentile, median, 75th percentile: 6.5, 6.8, 7.5 vs. 7.7, 7.9, 7.9) and lower fructose content (1.0, 1.1, 3.7 vs. 5.8, 20.0, 83.0 μmol/ejaculate) than those without mutations. Diagnostic efficacy for detection of mutations was best (pH 81.4%, fructose 81.8%) at a cutoff level for pH of 7.4 and fructose of 2 μmol/ejaculate.

Conclusion(s): Seminal plasma markers provide an effective, noninvasive method to predict CFTR mutations in men with obstructive azoospermia.     

Useful marker for the estimation of a recombination pair in the partial azoospermia factor c (gr/gr) deletion using quantitative real-time polymerase chain reaction

Background and aims:  Azoospermia factor c (AZFc) microdeletions are associated with male infertility and are caused by intrachromosal recombination between homologous repetitive sequence segments. Partial AZFc deletion (gr/gr) has been reported in male factor infertility. In the present study, we established detecting the copy number using quantitative real-time polymerase chain reaction (qRT-PCR) with the genome DNA, and assessed the association of the recombination pair set of gr/gr deletion and deleted in azoospermia copies. Furthermore, we determined the clinical significance of differential recombination patterns of gr/gr deletion, and compared them with azoospermia and proven fertile volunteers, with both groups having gr/gr deleted Japanese subjects.
Materials and methods:  A total of 16 Japanese subjects with idiopathic azoospermia, and 13 proven fertile men with gr/gr deletion, were studied. qRT-PCR was used for the estimation of an identical site number.
Results:  The g1/g2 deletion was found in 69.2% (9/13) in proven fertile men and in 75% (12/16) of idiopathic infertile men. The gr/gr deletion could result in the recombination of g1/g2 segments. Furthermore, there was no difference in the position of deletion between azoospermic patients and controls ( P  = 0.59).
Conclusion:  There was no association between the loss of DAZ cluster and azoospermia in gr/gr deletion. This suggests that most of the partial deletions are neutral variants.     

粤东地区男性不育人群Y染色体无精子因子微缺失的检测及临床应用

目的:探讨粤东地区男性不育人群与Y染色体无精子因子(AZF)微缺失的关系和临床应用。方法:以PCR体外扩增和电泳检测技术检测粤东地区男性不育人群的Y染色体AZF微缺失情况。结果:实验组(46例)8例Y染色体AZF微缺失,对照组(10例)Y染色体AZF15个位点无缺失。结论:Y染色体AZF微缺失是造成男性无精子症或严重少精子症的病因之一,对男性不育人群进行Y染色体AZF微缺失检测是十分必要的。     

Clinical evaluation of the infertile male with respect to genetic etiologies

Severe male factor infertility may have a presently identifiable genetic basis. Y chromosomal microdeletions (e.g., an AZFc microdeletion), karyotypic anomalies (e.g., Klinefelter Syndrome), and mutations in both alleles of the cystic fibrosis transmembrane conductance regulator (CFTR) gene may be found, depending upon the etiology of the reproductive compromise. Which patients should be tested, what are the tests that can be performed, when should those tests be ordered, and what might a positive outcome mean, are all critically valuable clinical questions for the couple that help guide evaluation and management. It is imperative that they be asked and results discussed prior to any intervention such as testis tissue extraction, microsurgical epididymal sperm aspiration, or intracytoplasmic sperm injection so that the couple can incorporate them in their decisions moving forward vis-à-vis their reproductive choices and options. The role of reproductive medicine clinicians should not be limited to just helping couples establish a pregnancy, but instead be expanded to educating them about the reasons and causes of their reproductive failure that affect not only them as individuals but also may have implications for their offspring.     

Screening for Y chromosome microdeletions in 226 Slovenian subfertile men.

BACKGROUND: The objective of this study was to estimate the frequency of Y chromosome microdeletions in the Slovenian population of infertile men and to analyse the consequences of mutation in respect to clinical severity and prognosis. METHODS: In a controlled clinical study at the university-based medical genetics service and infertility clinic, 226 infertile men undergoing ICSI were tested. The main outcome measures included polymerase chain reaction amplification of 16 genes and gene families and 42 sequence-tagged sites in the non-recombining region of the Y chromosome, semen, testicular volume and testicular histological analysis, serum FSH concentrations, fertilization and respective pregnancy rates. RESULTS: The incidence of deletions was 4.4%: 8.6% in men with azoospermia and 1.5% in men with oligoasthenoteratozoospermia. Isolated gene deletions were not identified. No statistically significant differences in clinical outcome measures were found in patients with mutations versus patients without mutations. High fertilization (49%) and pregnancy (43%) rates with sperm of patients with Y chromosome deletions were obtained. CONCLUSIONS: Testing for gene-specific microdeletions does not contribute significantly to the sensitivity of microdeletion test. Fertilization and pregnancy rates obtained using sperm of patients with Y chromosome deletions were comparable with those achieved in conventional IVF.     

环磷酰胺诱导少精子/无精子症大鼠模型所致睾丸、附睾IGF-I的变化

目的:探讨环磷酰胺(CP)对大鼠附睾和睾丸组织中胰岛素样生长因子I(IGF-I)表达的影响;方法:96只8周龄成年雄性SD大鼠,分为6组,每组16只。第1~5组分别给予CP 10、20、40、80、100 mg/(kg.d),第6组为对照组,给予生理盐水2 m l。胃管给药2周和4周后,处死大鼠,采用ELISA法对附睾组织洗脱液IGF-I进行定量检测;同时采用SP免疫组化法检测睾丸组织IGF-I的表达。结果:随着CP处理时间的延长和剂量的增加,IGF-I在大鼠附睾中的浓度逐渐下降,大鼠睾丸组织中IGF-I的表达也降低。结论:CP在引起大鼠少精子/无精子症的同时,可以显著降低大鼠附睾、睾丸IGF-I的含量和表达水平。IGF-I的降低与CP降低大鼠生精功能明显相关。     

Myocardial infarction with non obstructive coronary arteries (MINOCA): a whole new ball game

Introduction: MINOCA is a clinical syndrome that encompasses a subgroup of heterogeneous patients who present with myocardial infarction yet do not have any significant coronary artery obstruction on angiogram. As many as one in ten patients with acute myocardial infarction (AMI) will not have an occluded coronary artery, and the reported prevalence keeps rising, in part due to better recognition of this syndrome. Current guidelines offer several diagnostic algorithms but MINOCA remains largely under-recognised and little is known about whether patients might benefit from a more specific treatment modality.

Areas covered: We review pathogenesis, diagnosis, prognosis, and management of MINOCA.

Expert commentary: Due to the significant heterogeneity of MINOCA patients, a more efficient management strategy may solely rely on an individualized approach in order to improve outcomes.     

A case of a rare variant of Klinefelter syndrome, 47,XY,i(X)(q10)

Klinefelter syndrome is a condition in which a male patient has one Y chromosome and one or more extra X chromosomes. It is the most common sex chromosome disorder. Klinefelter syndrome is distinguished by many clinical features, such as infertility, high gonadotropin and low testosterone levels, increased height, and sparse body and facial hair. We report the case of a 32‐year‐old man who visited our hospital complaining of male infertility. Semen analysis showed azoospermia, and chromosomal analysis revealed a 47,XY,i(X)(q10) karyotype, which is a rare variant of Klinefelter syndrome. No spermatozoon was found on microdissection testicular sperm extraction, and the testis biopsy histology showed only Sertoli cells and hyalinised seminiferous tubules. 47,XY, i(X)(q10) has an additional isochromosome made of the long arm of the X chromosome, which shares some features of classical Klinefelter syndrome in many aspects, but patients are usually shorter than average height and have normal intelligence. In addition, to the best of our knowledge, no successful sperm extractions from 47,XY, i(X)(q10) patients were reported in the literature. The reports of patients who have undergone microdissection testicular sperm extraction are very rare. Further reports and studies of this chromosomal abnormality are needed.