Fertility treatment may be less effective in COVID-infected couples

Couples infected with SARS-CoV-2 while receiving assisted reproductive technology (ART) treatment had lower quality embryo and blastocyst rates compared with uninfected couples in a  multicentre cohort study.

In 585 heterosexual couples with infertility who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment, those positive for SARS-CoV-2 had significantly lower quality embryo rates (odds ratio [OR], 0.83), lower quality blastocyst rates (OR, 0.59), available blastocyst rates (OR, 0.70), and blastocyst formation rates (OR, 0.61) relative to couples negative for the virus. [JAMA Netw Open 2023;doi:10.1001/jamanetworkopen.2023.23219]

“Our findings have implications for couples seeking infertility treatment. These suggest that reproductive physicians should be more attentive to patients with SARS-CoV-2 infection during controlled ovarian stimulation [COS],” said study author Dr Jing Zhao from the Xiangya Hospital, Central South University, Changsha, China. “They should give these couples adequate counselling.”

The effects of SARS-CoV-2 infection on embryo quality remain unclear. Studies have shown that both messenger RNA and protein expression of ACE2 were upregulated in human ovulatory follicles after human chorionic gonadotropin injection. In vitro experiments showed human ovarian cells were susceptible to SARS-CoV-2 infection. Overall, this pointed to a potential adverse effect of COVID-19 on female fertility.

Additionally, Zhang said oxidative stress and aberrant systemic inflammation may be other possible mechanisms by which SARS-CoV-2 affects female reproduction at the molecular level. “Reactive oxidative stress affects multiple aspects of reproductive physiologic processes, including oocyte maturation, fertilization, and embryo development.”

Many pro-inflammatory cytokines might also interfere with the processes, which may explain why the blastocyst formation rate and quality of embryo and blastocyst rates were much lower in couples with COVID-19, Zhang explained.

In men, COVID-19 also disrupts the hypothalamic-pituitary-gonadal axis, which has negative impacts on spermatogenesis and the epididymis. [J Endocrinol Invest 2023;46:1491-1507]

The study included couples with infertility from seven reproductive centres in China. Infertility was a female factor in 58 percent of the couples. The median duration of infertility was 2 years.

Couples were considered positive if either one of them tested positive for COVID-19. Overall, there were 135 couples deemed as positive.

Ovarian reserve and ovarian response characteristics were not significantly different in the two groups, including basal follicle-stimulating hormone, antral follicle count, and antimüllerian hormone. Similarly, the duration of COS, the dosage of gonadotropin, estradiol, progesterone, and luteinizing hormone on the trigger day, and the number of oocytes retrieved were comparable between groups.

There were no significant differences in oocyte- and oocyte-related outcomes in the fertilization methods selection, mature oocyte rate for intracytoplasmic sperm injection, oocyte degeneration rate, normal fertilization, cleavage rate, or available embryo rate.

The study did not assess COVID symptom severity, outcomes, and viral load. More studies are warranted to establish the adverse effects of COVID-19 on fertility treatment.