Huiying Li1, Ling Zhang1, 2, Yanping Zheng2, Dongli Chen2, Wenzheng Wang2, Ping Su1, 2, Xianjin Xiao1, 2, Honggang Li, 1,2 Chengliang Xiong1, 2, Wenpei Xiang, Ph.D.1, 2
1 Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
2 Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
The outbreak of the COVID-19 epidemic has resulted in unprecedented containment measures and has posed serious risks for the sexual and reproductive health of women and adolescent girls everywhere (1-4). Worldwide, reproductive centers have had to adjust the diagnosis and treatment process following their respective guidelines. The Chinese Society of Reproductive Medicine (CSRM) has released revised guidelines on its WeChat official account platform (cma-csrm) on April 21. In March of 2020, the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR) and the European Society of Human Reproduction and Embryology (ESHRE) presented their position in outlining Assisted Reproductive Technology (ART) priorities during and after this emergency (5, 6). On March 17, 2020, the American Society for Reproductive Medicine (ASRM) issued guidance for patient and clinical management during the coronavirus (COVID-19) pandemic and then updated these measures three times (7).
Being in the main area where the COVID-19 epidemic first occurred, most of the reproductive centers in China, especially in Wuhan, were closed or delayed during the outbreak. Recently, COVID-19 in China has declined quickly. The number of new confirmed cases, new suspected cases, and existing suspected cases in Wuhan dropped to zero after March 18, 2020 (8). However, we must still contend with the likelihood of asymptomatic patients, since Qiu J reported that more than 60% of COVID-19 patients were asymptomatic (9). It is necessary to implement effective management and appropriate preventive measures to safely restore assisted reproductive technology treatments. The Center of Reproductive Medicine has been reopened for 50 days, and everything is running well. The following is a series of strategies and suggestions based on our experiences:
A) Establishing an epidemic prevention and control expert team. The hospital established an experienced COVID-19 control team composed of medical and management experts. The team formulated standardized operating procedures and emergency plans during the COVID-19 pandemic. The team also trained the staff of the reproductive center and managed the rotation of the medical staff’s work.
B) Formulating the workflow of the reproductive center. The director of the reproductive center organized the writing of the workflow during the COVID-19 pandemic on March 28 (Figure 1A). On the basis of the previous version, the SARS-CoV-2 infection screening for patients and the informed conversation content were added into the workflow. With the mitigation of the epidemic, all districts in Hubei Province were defined as low-risk areas; we revised the workflow on April 30, 2020 (Figure 1B).
Figure 1. The workflow of reproductive center during stabilized period of COVID-19. (A) 1st version (March 28, 2020). (B) 2nd version (April 30, 2020). All of the examination results submitted must be within seven days, and all of the patients must finish a handwritten COVID-19 examination informed consent. If there is no special instruction, both husband and wife must take the mentioned examinations. Intrauterine insemination cycle included the artificial insemination by husband (AIH) and artificial insemination by donor semen (AID). Examination (two items) or two items means examination of SARS-CoV-2 quantitative RT-PCR, SARS-CoV-2 antibodies (IgM and IgG). Examination (three items) or three items means examination of chest computed tomography (CT), SARS-CoV-2 quantitative RT-PCR, SARS-CoV-2 antibodies (IgM and IgG). Grey solid arrow means there is/are positive result/results in the examination, we should cancel this assisted treatment cycle; Blue solid arrow means all of the examinations associated with COVID-19 are negative, the cycle could be continued. The blue dotted lines represent the subsequent embryo freezing or transfer procedure. Abbreviations：D2-3, Day 2-3 of the menstrual cycle; Gn, gonadotropin; HCG, human chorionic gonadotrophin.
C) Training and assessment of medical staff. Job positions were set up according to basic demands. Medical staff was required to learn basic theoretical knowledge about pandemic prevention; theoretical testing was carried out by questionnaire, and the ideal score was 100%. 66 staff members completed the test (with a response rate of 100 %), with 33.33% (22/66) being doctors, 19.70% (13/66) being nurses, 21.21% (14/66) being technicians, and 25.76%（17/66）being assisting staff. The average scores of doctors (94.32 ± 3.67) and technicians (95.5 ± 1.743) were higher than the scores of nurses (87.92 ± 5.515) and assisting staff (87.35 ± 5.82) with statistical significance (p < 0.01) (Figure 2). Therefore, we mainly focused on these two groups in subsequent training. The staff will not be permitted to work unless they have attended all trainings and passed the test. The staff were screened for SARS-CoV-2 infection and needed to test negative before being allowed to resume work.
Figure 2. The rate of correct answers on the online examination among doctors, nurses, technicians and assisting staffs. The data presented as the mean ± SD, were analyzed with SPSS ver. 18.0. The normally distributed numerical variance was performed by one-way ANOVA with homogeneity of variance, and Chi Square tests (χ2 test) were employed for the differences between two or more rates. The statistical significance was set at p <0.05. *p ＜0.01 significant vs Doctors and technicians.
D) Rooms setting, disinfection, and staff protection. We chose ventilated rooms as the consultation rooms, and we sterilized the rooms with ultraviolet light for 30 minutes every 3 hours. All staff strictly followed the standard operating procedures and working procedures of the COVID-19 pandemic protection, which were formulated by the Center. Doctors and nurses in the consultation room wore disposable hats, medical surgical masks, single-use protective clothing, and latex gloves. Doctors, embryo laboratory technicians, and nurses all wore disposable hats, N95 masks, isolation gowns, and sterile gloves when performing egg retrieval and embryo transfer. Only one retrieval could be done per room on a daily basis, and only one embryo transfer (ET) operation was completed in another room each day. After the operation was completed, all surfaces were wiped and disinfected with 75% alcohol. In addition, we used ultraviolet light to disinfect all office rooms, archives, and public areas, such as aisles, toilets, and other areas; we also used 84 Disinfectant solution to treat the public areas’ surfaces, door handles, stair handrails, etc., every 3 hours.
E) Patient selection and screening：We recommended that patients with urgent fertility needs or those unable to wait to come to the hospital for treatment. All patients made appointments in advance and learned online the science education given by professionals regarding how to protect against the SARS-CoV-2 Each patient came to the hospital on the appointment day, and we measured their temperature, scanned their health code, and ensured that patients wore disposable surgical masks, disinfected the soles of the feet and hands, and then entered the reproductive center. It is worth noting that before starting the ART treatment, each patient underwent chest CT scans to make sure if there was typical signs of ground-glass opacity (GGO) in the lungs, SARS-CoV-2 quantitative RT-PCR and SARS-CoV-2 antibodies (IgM and IgG) examinations. Only healthy people started the treatment. At 3-4 days before egg retrieval (when follicles were 14-16mm in size) or 6-7 days before embryo transplantation, SARS-CoV-2 quantitative RT-PCR and SARS-CoV-2 antibodies (IgM and IgG) were checked again in patients.
F）Patient protection and management. We only allowed one person or a couple to enter the clinic room at the same time. Gathering must be avoided in the hospital. A series of services, such as fee-paying and inspection-report-taking were completed online. Patients implemented strict protection, including hand disinfection and the wearing of disposable hats, medical surgical masks, foot covers when undergoing gynecological examinations, ultrasound examinations, and additionally wore single-use protective clothing and latex gloves when undergoing egg retrieval and transplantation operations. We recommended patients to avoid hospitalization except in cases of complications, such as bleeding or ovarian hyperstimulation syndrome (OHSS). We strongly recommended vaginal progesterone soft capsules combined with oral progesterone tablets (Dupbaton) or progesterone sustained-release gel (Crinone, Merck Serono, Germany) combined with oral progesterone tablets (Dupbaston) instead of intramuscular progesterone combined with oral progesterone tablets (Dupbaston) for luteal support. Intramuscular injection was prohibited during COVID-19 epidemic in order to prevent patients from going to hospitals or clinics for injections; the desired effect is to greatly reduce the chance of infection.
According to the above workflow, from March 30, 2020 to May 20, 2020, a total of 673 patients (including first-time and re-visiting patients) were consulted by the reproductive center. 394 people were screened for COVID-19 in other hospitals or in our hospital. The SARS-CoV-2 IgG and IgM of one patient were positive and treatment was terminated; all others were negative. During this period, 24 patients underwent egg retrieval operation, 28 patients underwent embryo transfer, and 10 people underwent intrauterine insemination (IUI) operation. No COVID-19 cases occurred in any patients during their treatment period, and no medical staff became infected (Table 1).
Adequate preparations before work can resume include the preparation of protective equipment, prevention and control measures suitable for the ART center, personnel training and testing, strict staff protection, and relatively strict protection and effective management of patients; these are key to preventing COVID-19 from recurring while attempting to continue normal operations. We hope that the strategy in this dialog will help guide the resumption of other reproductive centers and prevent another outbreak in the future.
We would like to thank all the staff who participated writing the strategy mentioned in this paper. Especially, we want to express our deep respect to all first-line healthcare workers for their dedication in the fight against SARS-CoV-2.
COVID-19: Coronavirus Disease-2019
SARS-CoV-2: 2019 novel Coronavirus
ART: Assisted Reproductive Technology
SIFES-MR: Italian Society of Fertility and Sterility and Reproductive Medicine
ESHRE: European Society of Human Reproduction and Embryology
ASRM: American Society for Reproductive Medicine
CSRM: Chinese Society of Reproductive Medicine
OHSS: Ovarian Hyperstimulation Syndrome
ET: Embryo Transfer
FET: Frozen-thawed Embryo Transfer
IUI: Intrauterine Insemination
OPU: Oocyte Pick Up
GGO : ground-glass opacity
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