Couples infected with the COVID-19 virus while receiving assisted reproductive technology treatment had lower quality embryo and blastocyst rates when compared to non-infected couples, a retrospective cohort study in China showed.

In nearly 600 couples who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment at a reproductive center, SARS-CoV-2–positive couples had significantly lower top-quality embryo rates (OR 0.83, 95% CI 0.71-0.96), top-quality blastocyst rates (OR 0.59, 95% CI 0.45-0.77), available blastocyst rates (OR 0.70, 95% CI 0.59-0.82), and blastocyst formation rates (OR 0.61, 95% CI 0.52-0.71) versus those testing negative for the virus.

“SARS-CoV-2 infection during controlled ovarian stimulation (COS) was associated with embryo and blastocyst quality,” Jing Zhao, MD, of the Xiangya Hospital, Central South University in Changsha, China, and colleagues reported in JAMA Network Open. “This study suggests that reproductive physicians should pay attention to patients with SARS-CoV-2 infection during COS and should give these couples adequate counseling.”

The researchers said the exact mechanisms of the effect of SARS-CoV-2 infection on embryo quality remain unclear. In previous studies, both messenger RNA and protein expression of ACE2 were upregulated in human ovulatory follicles after human chorionic gonadotropin injection, and in vitro experiments showed human ovarian cells were susceptible to SARS-CoV-2 infection. All of this suggested a potential adverse effect of SARS-CoV-2 infection on female fertility. Later tests, however, did not find the virus in follicular fluid in SARS-CoV-2–positive women.

In men, variable results have been reported, with some studies showing high testicular expression of both ACE2 and TEMPRSS2, and others finding expression only of ACE2. Semen samples have been positive for SARS-CoV-2 in some studies and not others, making this “even more controversial” than in female reproductive studies, Zhang and co-authors wrote.

“Regrettably, semen quality on the day of oocyte retrieval was not analyzed in the present study. Intracytoplasmic sperm injection is performed when the sperm quality is too poor, and similar outcomes are obtained with IVF.”

Results were consistent whether the female or male partner was infected, Zhang and colleagues said.

In addition to the direct effect of viral invasion of cells, oxidative stress and aberrant systemic inflammation may be other possible mechanisms by which SARS-CoV-2 affects female reproduction at the molecular level, Zhang and co-authors added. “Reactive oxidative stress affects multiple aspects of reproductive physiologic processes, including oocyte maturation, fertilization, and embryo development … [A] large amount of proinflammatory cytokines might also interfere with these processes, which may be a possible explanation for why the blastocyst formation rate and top-quality embryo and blastocyst rates were much lower in couples with SARS-CoV-2 infection.”

The study was performed in 585 heterosexual couples with infertility (median age 33) in seven reproductive centers across four Chinese provinces. Infertility was a female factor in 341 (58%) of the couples; median duration of infertility was 2 years, slightly longer in the SARS-CoV-2 negative group (median 3 years).

If either member of a couple tested positive, the couple was considered positive. Thus, 135 couples were deemed positive.

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

There were no significant differences in oocyte- and oocyte-related outcomes in the fertilization methods selection, mature oocyte rate for intracytoplasmic sperm injection (ICSI fertilization), oocyte degeneration rate, normal fertilization (two pronuclei observed on day 1 after insemination [2PN rate]), 2PN cleavage rate, or available embryo rate.

The study was limited by possible bias, as data collection was not uniformly gathered. Moreover, COVID-19 symptom severity, outcomes, and viral load information were not collected.

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