key: cord-0729340-07hbfryc
authors: Vastis, Vasilia; Hussaini, Sofia; Neal, Michael; Karnis, Megan; Taerk, Evan; Amin, Shilpa; Deniz, Stacy; Faghih, Mehrnoosh
title: Impact of Protocol Adjustments due to the COVID-19 Pandemic on Infertility Treatment Outcomes
date: 2022-05-05
journal: J Obstet Gynaecol Can
DOI: 10.1016/j.jogc.2022.03.021
sha: 01798dc5df371af47be22ddbd6091937dd89b37d
doc_id: 729340
cord_uid: 07hbfryc

As a result of the COVID-19 pandemic, our centre made adjustments that reduced the number of patient visits, ultrasound scans, laboratory investigations, and face-to face instructions. The objective of this study was to evaluate whether these changes had any effect on the pregnancy rate for patients undergoing infertility treatment. The primary outcome was clinical pregnancy rates from intrauterine insemination and frozen embryo transfer. Clinical pregnancy rates were not statistically different between patients who underwent either procedure before and after the protocols were put in place. It is reassuring to know our pandemic protocol adjustments did not have a negative impact on infertility treatment outcomes.

The COVID-19 Pandemic has impacted many different domains of the health care system. As of March 2020, the CFAS, the American Society for Reproductive Medicine (ASRM) (1) , and the European Society for Human Reproduction and Embryology (ESHRE) (2) , recommended that ART should stop to prevent overburdening healthcare systems. Infertility services were deemed 'non-essential'. Specifically in Ontario, to implement Health and Safety recommendations from the College of Physicians and Surgeons of Ontario (CPSO) guidelines and the Ministry of Health's COVID-19 Operational Requirements, multiple changes were made in treatment protocols and patient care at ONE Fertility, Burlington, Ontario, Canada (3) . Operational changes included fewer: i) in person visits per patient; ii) ultrasound scans; iii) laboratory investigations; and iv) face-to-face instructions.

The purpose of this study was to evaluate and compare pregnancy rates among patients who had ovarian stimulation with intrauterine insemination (IUI) and frozen embryo transfers (FET) cycles prior to the pandemic with those who were treated during the COVID-19 pandemic to understand if the temporary shutdown and newly developed protocols affected their overall success rates.

This is a retrospective cohort study with Hamilton integrated Research Ethics Board (HIREB) approval (Number: 45999). Patients in this study who underwent IUI, IVF and FET at ONE Fertility were divided into two groups. The pre-pandemic group (IUI n=617, IVF n=226, and FET n=260) were treated between June 2019 -December 2019. The pandemic group (IUI n= 634, IVF n=224 and FET n=318) were treated between June 2020 -December 2020. The primary outcome was clinical pregnancy rate, defined as the presence of a gestational sac and fetal heart at ultrasound examination at 6-7 weeks gestation. IVF cycles were freeze-all and were not included in the primary outcome. The secondary outcome was biochemical PR (positive serum beta HCG 12-14 days post procedure) from IUI and FET, as well as number of eggs retrieved and fertilization rate from IVF cycles. Statistical analysis was performed and reported J o u r n a l P r e -p r o o f as mean + standard deviation of the mean. T-test and Classical Chi-square calculations where appropriate were conducted to determine significance (P<0.05) between groups. Protocol adjustments included the following: i) visits per patient Pre-pandemic, 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.

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

iii) semen collection

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 (U/S) and Estrogen/LH level. If the follicle size was <15mm, they would return in 2 days to have another U/S and hormone check. If the follicle was >15mm they would return for U/S and blood work in 1 day. The clinic would schedule IUI's based on LH surge or Ovidrel trigger when the follicle was >20mm with good endometrial lining and appropriate estrogen level. For patient's undergoing FSH + IUI, blood work and an ultrasound would be done on cycle day 3 and day 8. The rest of the monitoring was like letrozole + IUI cycle.

During the pandemic, the number of visits were significantly reduced. For letrozole + IUI cycles, patients were seen for 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 positive OPK and take their Ovidrel. Their insemination would be scheduled for the following day. The J o u r n a l P r e -p r o o f 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.

In vitro Fertilization

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 day 6, 7, and 8. Once follicles were >15mm, patients would come in for daily bloodwork and ultrasound until they were ready for Ovidrel trigger shot. During the pandemic, blood work and ultrasound were done on cycle day 3, 8, 10 and 12 and trigger shot was administered at home.

We only included ovulatory protocols. These remained similar pre-and post-pandemic. Pre-pandemic, 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 BMI, duration of infertility, and the number of dominant follicles > 16mm were similar between the two groups ( Table 1 ). The total motile count of sperms in IUI sample were higher in the prepandemic group with a mean of 56.5 M compared to 32.5 M. Patients' AMH were slightly higher in the pre-pandemic group with a mean of 18.9 pmol/L compared to 14.1 pmol/L, however this result was not statistically significant. The IUI clinical PR (pre-pandemic 12.3% vs pandemic 11.7%) and biochemical PR (pre-pandemic 14.4% vs pandemic 13.1%), were not statistically different between the pre-pandemic and pandemic group ( Table 2 ).

The average patients' age was slightly higher in the pandemic group, and they had higher estrogen level on the day of booking for egg retrieval (Table 1) . When comparing the two groups, there were 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 pre-pandemic 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 pre pandemic 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 ( pandemic 46.9%) and biochemical pregnancy rate (pre-pandemic 55.8% vs pandemic 57.5%) were not statistically different between the pre-pandemic and pandemic group of patients ( Table 2 ). The embryos in the pre-pandemic group were created from June 2019 to December 2019. The embryos in the pandemic group were created between June 2020

to December 2020.

The COVID-19 pandemic has been responsible for radical changes in the delivery of fertility treatment globally. Smith J o u r n a l P r e -p r o o f LIMITATIONS 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.

Treatment protocol adjustments due to COVID-19 did not adversely affect IUI, IVF or FET outcomes at ONE Fertility.

We can conclude that IUI and FET pregnancy rates at ONE Fertility were similar pre-pandemic and during the pandemic given less clinic visits, ultrasounds, and bloodwork. Interestingly, fertilization rate was better, and the number of cleaved embryos were higher in patients who had IVF treatment during the pandemic. It is reassuring to know the pandemic protocol adjustments did not have a negative impact on infertility treatment outcomes in our clinic and allows us to potentially keep these protocols in place.

J o u r n a l P r e -p r o o f 

ASRM Patient management and clinical recommendations During the coronavirus (COVID-19) pandemic

Assisted reproduction and COVID-19. A statement from ESHRE for phase 1 -Guidance on fertility services during pandemic

CPSO -COVID-19 FAQs for Physicians

Live-Birth Rate Associated with Repeat In Vitro Fertilization Treatment Cycles

First trimester pregnancy outcomes in a large IVF center from the Lombardy County (Italy) during the peak COVID-19 pandemic