1. Time between COVID-19 vaccine and IVF treatment with fresh embryo transfer impacts pregnancy rates, with lower pregnancy rates were seen within 61 days of COVID-19 vaccine

Evidence Rating Level: 2 (Good)

Study Rundown: Limited studies have been done investigating the association between time of COVID vaccination and rate of pregnancy in in vitro fertilization (IVF). Various guidelines exist in terms of recommendations for conceiving after receiving a COVID-19 vaccine, ranging from as soon as possible to delaying up to 2 months. Antibody generation against SARS-CoV-2 requires time and limited information exists on the association between the vaccine and oocytes, sperm, embryo development and early stages of pregnancy. Previous studies have found no association between the COVID-19 vaccine and fertility. Other studies have found there to be clear evidence of an immune response as well as differences in metabolite levels in follicular fluid of vaccinated individuals, as well as normal ovarian function. This observational cohort study aimed to investigate the association between time between first dose of inactivated COVID-19 vaccine and rate of pregnancy after a fresh embryo transfer in IVF treatment. It included a large sample from China of unvaccinated individuals, and vaccinated individuals who received an inactivated COVID-19 vaccine. The study noted that receiving a first inactivated COVID-19 vaccine dose 60 days or less before IVF treatment with fresh embryo transfer was associated with a significantly reduced rate in pregnancy. Further studies are needed to identify the mechanisms and to determine if these results are reproducible in those who received other COVID-19 vaccines, second doses of the vaccine, and to a broader population. This information may help guide patients on finding an ideal time between vaccination and fresh embryo transfer.

Click here to read the article in JAMA Network Open

Relevant Reading: IVF under COVID-19: treatment outcomes of fresh ART cycles

In-Depth [Observational cohort]: This observational cohort study included participants aged 20 to 47 undergoing IVF treatment. 3052 females undergoing IVG treatment were analyzed. Of these, 667 were vaccinated and 2385 were unvaccinated. The vaccinated group was broken into 4 subgroups based on time since vaccination: < 30 days, 31-60 days, 61-90 days, and > 90 days. Embryo transfer was done on either day 3 (cleavage stage) or day 5 (blastocyst stage) in the fresh embryo. 12 to 14 days following embryo transfer, a beta-human chorionic gonadotropin level was done, with a positive result indicating a biochemical pregnancy. Clinical pregnancy was defined as presence of an intrauterine gestation sac on ultrasound during the first trimester, and ongoing pregnancy was defined as a clinical pregnancy that continued for at least 12 weeks. Both groups were similar in terms of body mass index, stimulation protocol, gravidity, parity, and fertilization method however, patients in the vaccinated group were slightly older (median age 33 years) than the ones in the unvaccinated group (median age 31 years) and were also found to have lower antral follicle count (AFC), and a higher proportion of ovarian factors than the unvaccinated groups. Despite this, the number of mature follicles, number of normal fertilization oocytes and number of valid embryos on day 3 were similar among all groups. This study found that the rate of ongoing pregnancy increased with time interval from vaccine in each subgroup (< 30 days, 31-60 days, 61-90 days, and > 90 days) and the unvaccinated group, with rates of 34.3%, 36.2%, 51.4%, 56.3% and 60.3% respectively. Similar patterns were seen in the rates of biochemical pregnancy and clinical pregnancy. The rate of ongoing pregnancy was significantly lower in the 30 days or less subgroup (34.3% [12 of 35]; adjusted RR [aRR], 0.61; 95% CI, 0.33-0.91) and the 31 to 60 days subgroup ((36.2% [21 of 58]; aRR, 0.63; 95% CI, 0.42-0.85), suggesting that factors such as inflammatory changes post-vaccine may play a role in successful IVF pregnancy. This study was done in China where the main vaccine was the inactivated vaccine, and only those who received inactivated vaccines were compared unvaccinated individuals, making it difficult to broaden the results to other types of vaccine, such as mRNA vaccines. Some vaccinated patients additionally had a second dose of the COVID-19 vaccine during the time of embryo implantation, this was not monitored, and the effect of a second dose was not studied. It is to be noted that possible selection bias may have played a role in the study, different regions had different vaccine policies with essential workers being vaccinated first. Additionally, having further information on live birth data would be helpful in determining any effects of the vaccine on birth, however this information was not available due to the short follow-up period.

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