Mutations in the spindle checkpoint genes can cause improper chromosome segregations and aneuploidies, which in turn may lead to reproductive problems. Two of the proteins involved in this checkpoint are Aurora kinase B (AURKB), preventing the anaphase whenever microtubule-kinetochore attachments are not the proper ones during metaphase; and synaptonemal complex protein 3 (SYCP3), which is essential for the formation of the complex and for the recombination of the homologous chromosomes. This study has attempted to clarify the possible involvement of both proteins in the reproductive problems of patients with chromosomal instability. In order to do this, we have performed a screening for genetic variants in AURKB and SYCP3 among these patients using Sanger sequencing. Only one apparently non-pathogenic deletion was found in SYCP3. On the other hand, we found six sequence variations in AURKB. The consequences of these changes on the protein were studied in silico using different bioinformatic tools. In addition, the frequency of three of the variations was studied using a high-resolution melting approach. The absence of these three variants in control samples and their position in the AURKB gene suggests their possible involvement in the patients' chromosomal instability. Interestingly, two of the identified changes in AURKB were found in each member of a couple with antecedents of spontaneous pregnancy loss, a fetal anencephaly and a deaf daughter. One of these changes is described here for the first time. Although further studies are necessary, our results are encouraging enough to propose the analysis of AURKB in couples with reproductive problems.