To mask or not to mask mosaicism? The impact of reporting embryo mosaicism on reproductive potential.

PURPOSE: To evaluate euploidy rates and probability of having at least one euploid embryo for transfer per cycle when mosaicism is reported compared to when it is masked. METHODS: Women age 18-46 years who underwent PGT-A with next generation sequencing of blastocyst biopsies were analyzed. When reported, mosaic embryos were classified as low-level, 20-40% mosaic, or high-level, 41-80% mosaic. When masked, low-level mosaics were categorized as euploid and high-level mosaics were considered aneuploid. Comparative analyses were performed with χ2 tests and t-tests. RESULTS: A total of 22,504 PGT-A biopsy cycles from 18,401 patients were included. These cycles were from 293 different clinics with a mean of 1.22 cycles per patient. The majority of cycles (94.8%) reported mosaicism, and only 5.2% cycles were masked. The euploidy rate was significantly lower when mosaicism was reported versus masked (38.7% v 47.4%, p < 0.0001), which remained significant for age 40 years old and younger. The mosaic reporting cohort was less likely to have at least one euploid embryo for transfer (68.8%) compared to the masked cohort (75.7%) (p < 0.0001); however, this was no longer significant after stratification by age. CONCLUSION: Mosaicism reporting shows an overall expected reduction in euploidy rate. In turn, the probability of having a euploid embryo to transfer depends on clinic transfer practices and patient preference. If mosaic embryos are not transferred, we observe a reduction in probability of having an embryo for transfer. Although the magnitude of these differences is small, our data show that mosaic reporting may contribute to embryo attrition rate.

Simultaneous gas chromatographic-mass spectrometric determination of dopamine, norsalsolinol and salsolinol enantiomers in brain samples of a large human collective.

Using a solid-phase extraction procedure, an enantioselective derivatization and a gas chromatographic-mass spectrometric method, the levels of dopamine (DA) and of the dopamine-derived tetrahydroisoquinoline alkaloids (R)/(S)-salsolinol (SAL) and norsalsolinol (NorSAL) were determined in human brain samples. A complex pre-analytical synthesis of reference substances as well as deuterated internal standards allowed the standardized and reproducible analysis. In this study, to our best knowledge for the first time, the regional distribution of (R)-SAL and (S)-SAL, as well as NorSAL is examined systematically in a large collective of human brain samples obtained by autopsy. The material comprises 91 brains and 8 standardized specimens in each case. Anatomical concentration differences and no ubiquitous occurence were encountered. Significant amounts of (R)-SAL, (S)-SAL and NorSAL were only found in dopamine-rich areas of the basal ganglia, whereas in other regions of the brain no tetrahydroisoquinolines were detected. These findings suggest that the concentration of the substrate dopamine may determine the alkaloid level during in vivo formation. In our opinion, non-enzymatic formation of SAL via the Pictet-Spengler reaction reveals both the SAL enantiomers. An additional enzymatic synthesis of only (R)-SAL could explain the predominant occurrence of this enantiomer. Especially in the nucleus caudatus, the concentrations of DA, SAL and NorSAL decreased significantly with rising age, which may be consistent with apoptotic effects of ageing. Our data can serve as reference for other studies in humans concerning the etiology of alcoholism or other neurodegenerative diseases with the involvement of tetrahydroisoquinolines.