Objective: To investigate whether prior COVID-19 infection and time interval after infection affect the in vitro fertilization (IVF) outcomes. Design: A prospective observational cohort. Setting: Reproductive center in China. Population: Participants recovered from COVID-19 and healthy controls. Methods: All participants received normal IVF treatment. The oocyte and embryo quality as well as pregnancy outcome data were collected and analyzed. Main outcome measure: Oocytes and embryo quality, clinical pregnancy outcomes. Results: The oocyte and embryo quality were comparable between the two groups, including the number of oocytes, 2PN zygotes, fertilization rate, cleavage embryos, day 3 good-quality embryos, blastocyst formation rate, and good-quality blastocysts. Nevertheless, the study group exhibited more degenerated oocytes (0.15±0.40 vs. 0.10±0.33, P=0.035). Further regression analysis indicated that prior COVID-19 infection is positively related to the number of degenerated oocytes (Adjusted β: 0.06, 95% confidential interval (CI): 0 -0.10, P=0.032). No significant differences were observed in clinical pregnancy rate, implantation rate, early miscarriage rate, ectopic pregnancy rate, and ongoing pregnancy rate. Similarly, we observed no difference in oocyte and embryo quality as well as pregnancy outcomes across various post-infection time intervals. Conclusions: Preceding COVID-19 could increase the number of degenerated oocytes. However, it does not affect subsequent pregnancy outcomes. Additionally, post-infection time interval plays no significant role in IVF outcomes.

Tubulin beta 8 class VII (TUBB8), a primate oocyte/embryo-specific β-tubulin isotype, is a preferentially analyzed gene in the genetic diagnosis of infertile women. Studies have currently identified 47 variants of this gene. However, the evaluation of its pathogenicity and the resulting phenotypes vary, and this gene requires further study in order to be included in genetic counseling analyses. We have performed a whole exome sequencing (WES) screening of 385 infertile female subjects and 400 controls, identifying 29 TUBB8 variants (of which 23 were novel). These variants may be responsible for female infertility, especially in the case of embryonic arrest, and their identification further expands the variant spectrum of TUBB8. Our findings are the first to report a new phenotype of large polar body in TUBB8 variant patients and determine some recurrent variants that were specific for complete cleavage failure. We have also illustrated some phenotypes of TUBB8 variant patients and recommended using computational modeling approach to assess the pathogenicity of novel TUBB8 variants, particularly for maternally inherited variants. Our studies will contribute in laying the foundation for the genetic counseling of infertile women in the future.