Variable aneuploidy mechanisms in embryos from couples with poor reproductive histories undergoing preimplantation genetic screening

BACKGROUND: Preimplantation genetic screening (PGS) is used to determine the chromosome status of human embryos from patients with advanced maternal age (AMA), recurrent miscarriage (RM) or repeated implantation failure (RIF). METHODS: Embryos from 47 such couples were investigated for chromosomes 13, 15, 16, 18, 21 and 22 using fluorescence in situ hybridization with two rounds of hybridization. The investigation included parental lymphocyte work-up, the screening of blastomeres on day 3 and full follow-up on day 5/6 of untransferred embryos. RESULTS: The outcome of 60 PGS cycles is described, in which 523 embryos were biopsied; 91% gave results, of which 18% were diploid for all the chromosomes tested and 82% were abnormal. The pregnancy rate per cycle that reached the biopsy stage was 27%, and 30% per embryo transfer. Satisfactory follow-up was obtained from 353 embryos; all those diagnosed as abnormal were confirmed as such, although two false-positives were detected in relation to specific chromosome abnormalities. Meiotic errors were identified in 16% of embryos. Between the RM, AMA and RIF groups, there was a significant difference in the distribution of embryos that were uniformly abnormal and of those with meiotic errors; with an almost 3-fold increase in meiotic errors in the first two groups compared with the RIF group. CONCLUSIONS: This complete investigation has identified significant differences between referral groups concerning the origin of aneuploidy in their embryos.     

Contamination problem with sentinel node localization procedure: a case study

Lymphoscintigraphy for sentinel node (SN) localization was performed on a 60-y-old man with a melanoma on his back. Skin contamination occurred as a result of the radiopharmaceutical dose administration. Skin contamination could result in a misinterpretation of the SN location. Careful observation of the procedure avoided a misinterpretation with this study.     

Malignant myoepithelioma arising from recurrent pleomorphic adenoma of the soft palate

Malignant myoepithelioma is a rare salivary gland neoplasm that can arise either de novo or within a pre-existing pleomorphic adenoma. We report a case of malignant myoepithelioma arising from a pleomorphic adenoma of the soft palate. A 70-year-old woman presented in our department with a very large tumor of the soft palate. The patient had a history of a pleomorphic adenoma at the same location that was surgically removed 2 years ago. A second operation, with intraoral excision of the tumor was performed. Histological examination of the recurrence revealed a malignant spindle cell neoplasm with an infiltrative growth pattern and a high mitotic rate. Immunohistochemical investigation confirmed the diagnosis of a low-grade carcinoma of myoepithelial origin with free surgical margins. The patient remains free of disease for more than twelve months after the end of treatment.     

Preimplantation genetic diagnosis of chromosome abnormalities: implications from the outcome for couples with chromosomal rearrangements

OBJECTIVES: Chromosomal rearrangements can lead to infertility or repeated spontaneous or induced abortions. The use of preimplantation genetic diagnosis (PGD) allows the selected transfer of chromosomally balanced embryos. The aim of this study was to carry out detailed analysis of the outcome of 11 PGD cycles for 8 patients carrying various chromosomal rearrangements. METHODS: Patients underwent routine in vitro fertilisation with biopsy of embryos on day 3. Specific fluorescent in situ hybridisation protocols were developed for each couple. Embryo transfer was possible in all 11 cycles. RESULTS: The outcome was four pregnancies, leading to three live births and one biochemical pregnancy. Post-zygotic mosaicism was detected in 75% of untransferred embryos, the majority of which were chaotic. Detailed follow-up and analysis provided evidence for the co-existence of chromosomally balanced and abnormal cells in six embryos. The mechanisms involved included chromosome breakage and loss of material. CONCLUSIONS: Biopsy and analysis of two blastomeres, where possible, reduced the risk of misdiagnosis in cases of balanced/aneuploid mosaics. The three live births achieved for the eight couples treated in this series, despite the poor history in almost all cases, is further proof that a policy of biopsying two cells from embryos consisting of six or more cells and a single cell from four- or five-cell embryos is compatible with a positive outcome.     

Sequential FISH analysis of oocytes and polar bodies reveals aneuploidy mechanisms

OBJECTIVES: Constitutional aneuploidy occurs in at least 5% of recognised pregnancies, with apparent preferential involvement of the X chromosome and the smaller autosomes. Molecular cytogenetic investigations of cleavage-stage embryos have revealed anomalies affecting all sizes of chromosomes. The aim was to investigate the variety of anomalies arising during maternal meiosis I by analysis of unfertilised oocytes and polar bodies to gain insight into aneuploidy mechanisms. METHODS: Sequential FISH analysis was carried out with specific probes derived from eight chromosomes, representing all sizes. Only imbalance due to a gain of a whole chromosome or chromatid, represented by extra signals, was counted to avoid artefact. RESULTS: Data were obtained on 236 eggs from 124 patients of average age 32.5 years (range 22-44). Ten patients (average 32.6 years) had abnormal eggs. The abnormality rate for oocytes and for polar bodies was close to 4% for each. Fourteen hyperploidies were found, seven involving additional single chromatids. The abnormalities affected chromosomes 13,16,18, 21 and X but not chromosomes 1, 9 or 12. CONCLUSION: The data provide evidence for several mechanisms leading to aneuploidy, including classical non-disjunction of whole univalents; pre-division of chromatids prior to anaphase I, leading to imbalance detected at metaphase II; gonadal mosaicism for a trisomic cell line and preferential involvement of the smaller chromosomes. Monosomy for the large autosomes is not uncommon in cleavage-stage embryos and may additionally arise from anaphase lag preferentially affecting such chromosomes.     

Enhancement of soluble CD23 levels in the seminal plasma of infertile men with idiopathic testicular lesion.

Since increased levels of soluble CD23 (sCD23) were demonstrated in patients with autoimmune diseases, seminal plasma sCD23 levels were examined in 110 men divided into seven groups according to etiological diagnosis of infertility and two groups on the basis of normal or abnormal spermiogram. sCD23 was absent in the seminal plasma of normal men: According to the ANOVA results, all measurements were significantly different between the groups of patients examined (p<.01). Specifically, patients with idiopathic testicular lesion have a significantly higher mean value of sCD23 than all other patients. A statistically significant difference was noted in the sCD23 levels between men with normal and those with abnormal spermiograms, although with wide overlapping of the individual values. Men with idiopathic testicular lesion may be immunologically more active than other groups with subfertility.     

Tuning Mg(OH)2 Structural,Physical, and Morphological Characteristics for Its Optimal Behavior in a Thermochemical Heat-Storage Application

Thermochemical materials (TCM) are among the most promising systems to store high energy density for long-term energy storage. To be eligible as candidates, the materials have to fit many criteria such as complete reversibility of the reaction and cycling stability, high availability of the material at low cost, environmentally friendliness, and non-toxicity. Among the most promising TCM, the Mg(OH)₂/MgO system appears worthy of attention for its properties in line with those required. In the last few decades, research focused its attention on the optimization of attractive hydroxide performance to achieve a better thermochemical response, however, often negatively affecting its energy density per unit of volume and therefore compromising its applicability on an industrial scale. In this study, pure Mg(OH)₂ was developed using different synthesis procedures. Reverse deposition precipitation and deposition precipitation methods were used to obtain the investigated samples. By adding a cationic surfactant (cetyl trimethylammonium bromide), deposition precipitation Mg(OH)₂ (CTAB-DP-MH) or changing the precipitating precursor (N-DP-MH), the structural, physical and morphological characteristics were tuned, and the results were compared with a commercial Mg(OH)₂ sample. We identified a correlation between the TCM properties and the thermochemical behavior. In such a context, it was demonstrated that both CTAB-DP-MH and N-DP-MH improved the thermochemical performances of the storage medium concerning conversion (64 wt.% and 74 wt.% respectively) and stored and released heat (887 and 1041 kJ/kgMg(OH)2). In particular, using the innovative technique not yet investigated for thermal energy storage (TES) materials, with NaOH as precipitating precursor, N-DP-MH reached the highest stored and released heat capacity per volume unit, ~684 MJ/m³.