Polyploidy is a rare lethal cytogenetic anomaly in pregnancies, generally leading to pregnancy termination. This study aims to compare first and second trimester polyploidy in pregnancies and describe the underlying mechanisms. A retrospective study was conducted in three medical genetics laboratories, collecting cases from Eastern, Southern, and Western Romania. The period of interest was January 2008 to December 2018. Prenatal samples (chorionic villi and amniotic fluid) and miscarriage samples were tested by standard karyotyping, as well as QF-PCR or FISH as complementary or alternative techniques. In first trimester pregnancies, we report cytogenetic results of chorionic villi samples from miscarriages: 25 triploid cases and 13 tetraploid cases. In second trimester samples obtained by amniocentesis, cytogenetic findings were positive for 17 triploid cases. Maternal age, age of the pregnancy, and fetal gender identified by ultrasound were recorded in all cases and, additionally, data on biochemical risk and ultrasonographic findings for second trimester pregnancies. Cytogenetic investigations of spontaneous abortions provide valuable information on the cause of abortion. This information is crucial for genetic counseling and may also contribute to prenatal diagnosis in subsequent pregnancies.