Development and Application of a Multidimensional Database for the Detection of Quaternary Ammonium Compounds and Their Phase I Hepatic Metabolites in Humans.

The COVID-19 pandemic has led to significantly increased human exposure to the widely used disinfectants quaternary ammonium compounds (QACs). Xenobiotic metabolism serves a critical role in the clearance of environmental molecules, yet limited data are available on the routes of QAC metabolism or metabolite levels in humans. To address this gap and to advance QAC biomonitoring capabilities, we analyzed 19 commonly used QACs and their phase I metabolites by liquid chromatography-ion mobility-tandem mass spectrometry (LC-IM-MS/MS). In vitro generation of QAC metabolites by human liver microsomes produced a series of oxidized metabolites, with metabolism generally occurring on the alkyl chain group, as supported by MS/MS fragmentation. Discernible trends were observed in the gas-phase IM behavior of QAC metabolites, which, despite their increased mass, displayed smaller collision cross-section (CCS) values than those of their respective parent compounds. We then constructed a multidimensional reference SQLite database consisting of m/z, CCS, retention time (rt), and MS/MS spectra for 19 parent QACs and 81 QAC metabolites. Using this database, we confidently identified 13 parent QACs and 35 metabolites in de-identified human fecal samples. This is the first study to integrate in vitro metabolite biosynthesis with LC-IM-MS/MS for the simultaneous monitoring of parent QACs and their metabolites in humans.

The effect of infertility and assisted reproduction on first-trimester placental and fetal development.

Our investigation of differences in first-trimester placentation and/or fetal biometry in pregnancies conceived spontaneously compared with those conceived through fertility treatment, and comparing less invasive fertility treatment with in vitro fertilization found no statistically significant difference in first-trimester abnormal placentation or fetal growth between pregnancies conceived spontaneously and those conceived through fertility treatment, or between the in vivo and in vitro subgroups.

The risk of cytogenetic abnormalities in the late first trimester of pregnancies conceived through assisted reproduction.

OBJECTIVE: To determine if pregnancies conceived through infertility treatment are at increased risk of cytogenetic abnormalities in the late first trimester compared with spontaneously conceived pregnancies, or if there is increased risk when comparing less invasive infertility treatment (in vivo group) to in vitro fertilization (in vitro group). DESIGN: Retrospective case-controlled study. SETTING: University hospital. PATIENT(S): A total of 1,606 women who spontaneously conceived and 559 women who conceived through infertility treatment undergoing chorionic villus sampling (CVS). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cytogenetic abnormalities diagnosed by CVS. RESULT(S): No difference in cytogenetic abnormalities was found when comparing spontaneously conceived pregnancies to those conceived through infertility treatment (7.0% versus 5.4%). We also found no difference in the prevalence of cytogenetic abnormalities when comparing in vivo and in vitro fertilization subgroups (4.7% versus 5.8%). Finally, no difference was found when comparing the prevalence of different types of cytogenetic abnormalities between groups. CONCLUSION(S): Infertility treatment does not increase the risk of carrying a cytogenetically abnormal fetus in the late first trimester, nor does it increase the preponderance for any specific type of abnormality.

Prevalence of chromosomal mosaicism in pregnancies from couples with infertility.

OBJECTIVE: To determine if mosaicism that occurs in infertility and assisted reproductive technologies continues in the late first trimester and if this is unique to infertility or occurs in all pregnancies. DESIGN: Retrospective case-controlled study. SETTING: University hospital. PATIENT(S): 5337 consecutive chorionic villus samplings (CVS). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Mosaic karyotypes at CVS. RESULT(S): We confirmed 69 mosaic karyotypes, a rate of 1.29%. Comparing spontaneous pregnancies with pregnancies from infertility treatment, no difference was found in the prevalence of mosaicism: 1.22% versus 1.32%, respectively. Subgroup analysis of infertile couples, comparing in vitro (assisted reproduction) with in vivo fertilization (other treatments) revealed a mosaicism rate of 1.84% and 0.41%, respectively. Confined placental mosaic (CPM) rates for infertility treated pregnancies and spontaneously conceived pregnancies were 0.88% and 0.92%, respectively. Subgroup analysis of infertile patients revealed a CPM rate of 1.15% for in vitro fertilization treatment and 0.41% for in vivo fertilization treatment. These results were not statistically significant. CONCLUSION(S): There was no difference in the prevalence of mosaicism at the end of the first trimester in pregnancies conceived spontaneously compared with those with infertility. There was no difference in the prevalence of mosaicism when in vitro and in vivo treatment were compared.