Impact of Protocol Adjustments Due to the COVID-19 Pandemic on Infertility Treatment Outcomes

Prepandemic, every new patient referred to ONE Fertility underwent diagnostic cycle monitoring, involving a series of blood tests and ultrasounds to monitor one menstrual cycle. During the pandemic, diagnostic cycle monitoring and monitoring for intercourse cycles stopped.

With the decrease in patient visits came the decrease in number of ultrasound scans for purpose of cycle monitoring.

Our study did not objectively collect data on whether men provided semen samples at home versus in clinic. If home collection was done, our patients provided their sperm sample within 1 hour of collection.

This was substituted with online IVF e-modules created by the staff at ONE Fertility. These were sent to all patients by email and were required to be completed prior to starting an IVF cycle. All consents were obtained by phone and forms were signed electronically via DocuSign.

Before the pandemic, patients would call on cycle day 1. For letrozole + IUI, patients would be seen on cycle day 10 to monitor follicular growth by doing an ultrasound and estrogen/luteinizing hormone level. If the follicle size was <15 mm, they would return in 2 days to have another ultrasound and hormone check. If the follicle was ≥15 mm they would return for ultrasound and blood work in 1 day. The clinic would schedule IUIs based on luteinizing hormone surge or Ovidrel trigger when the follicle was >20 mm with good endometrial lining and appropriate estrogen level. For patients undergoing follicle stimulating hormone (FSH) + IUI, blood work and an ultrasound would be done on cycle days 3 and 8. The rest of the monitoring was like the letrozole + IUI cycle. During the pandemic, the number of visits were significantly reduced. For letrozole + IUI cycles, patients were seen for the first time on cycle day 10. Patients were provided information about their Ovidrel injection and/or progesterone suppository, ovulatory predictor kits (OPK), and collection cup for sperm sample. Patients were instructed to call the clinic once they had a positive OPK and take their Ovidrel. Their insemination would be scheduled for the following day. The morning of the IUI, a sperm sample would be collected in the collection cup provided and delivered to the clinic at body temperature within an hour of production. If there was no positive OPK by cycle day 20, the patient was instructed to call for an ultrasound and blood work. For FSH + IUI cycles, patients had blood work on cycle day 3 and were given all required information as above about the cycle on that visit. The next visit was cycle day 10. Once patients had a positive OPK, insemination was booked for the next day.

Before the pandemic, patients would call on cycle day 1 and schedule cycle day 3 IVF start. Blood work and ultrasound would be done on cycle days 6, 7, and 8. Once follicles were ≥15 mm, patients would come in for daily bloodwork and ultrasound until they were ready for the Ovidrel trigger shot. During the pandemic, blood work and ultrasound were done on cycle days 3, 8, 10, and 12 and the trigger shot was administered at home.

We only included ovulatory protocols. These remained similar pre- and postpandemic. Prepandemic, patients called the clinic cycle day 1 and booked their bloodwork and ultrasound for cycle day 10. Continuous monitoring with blood work and ultrasound was done until transfer. During the pandemic, patients would attend clinic on cycle day 10 for bloodwork and an ultrasound, then were instructed to do OPK testing at home. Once there was a positive result, the transfer would be scheduled.

Patient characteristics including body mass index, duration of infertility, and the number of dominant follicles >16 mm were similar between the two groups (Table 1). The total motile count of sperm in the IUI sample was higher in the prepandemic group, with a mean of 56.5 compared with 32.5 M. Patients’ anti-Müllerian hormone (AMH) levels were slightly higher in the prepandemic group, with a mean of 18.9 pmol/L compared with 14.1 pmol/L; however, this result was not statistically significant. The IUI clinical PR (prepandemic 12.3% vs. pandemic 11.7%) and biochemical PR (prepandemic 14.4% vs. pandemic 13.1%) were not statistically different between the prepandemic and pandemic groups (Table 2).

The average patient’s age was slightly higher in the pandemic group, and they had higher estrogen levels on the day of booking for egg retrieval (Table 1). When comparing the two groups, there was higher egg maturity, a greater number of eggs injected with sperm, better fertilization rate, and a higher number of cleaved embryos in pandemic groups versus the prepandemic group. Despite this, the blastocyst development rate was not different between two groups. The AMH level in the pandemic group was slightly higher, at 16.5 pmol/L versus 14 pmol/L in the prepandemic group; however, these results were not statistically significant. Additionally, the total FSH dose was similar in both groups.

Among patients who underwent FET, the baseline characteristics were similar in both groups (Table 1). The average age in the prepandemic group was 36.2 compared with 35.8. The AMH level and number of embryo transfers were also similar between both groups and not statistically significant. The clinical pregnancy rate (prepandemic 43.5% vs. pandemic 46.9%) and biochemical pregnancy rate (prepandemic 55.8% vs. pandemic 57.5%) were not statistically different between the prepandemic and pandemic group of patients (Table 2). The embryos in the prepandemic group were created from June 2019 to December 2019. The embryos in the pandemic group were created between June 2020 and December 2020.

Our sample size is small and not representative of the general population or other clinics. Our study is also more prone to selection bias. As mentioned, all IVF cycles were freeze-all, so we cannot comment on the pregnancy rates for IVF. We did not record sperm collection sites. We also did not collect patient and staff perceptions on the effects the different protocols could have.