Are there specific patients candidate for oocyte collection during COVID-19 pandemic?
The perspective of the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR)
Alberto Vaiarelli1, Carlo Bulletti1, Danilo Cimadomo1, Andrea Borini1, Cindy Argento1, Carlo Alviggi1, Silvia Ajossa1, Paola Anserini1, Gianluca Gennarelli1, Maurizio Guido1, Paolo Emanuele Levi-Setti1, Antonio Palagiano1, Roberto Palermo1, Valeria Savasi1, Antonio Pellicer1, Luca Gianaroli1, Laura Rienzi1, Filippo Maria Ubaldi1
1On behalf of the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR)
At the beginning of January 2020, China announced a new major epidemic foci of coronavirus disease 2019 (COVID-19), now rapidly expanding throughout the world. On March 11 2020, the General Director of the World Health Organization (WHO) declared the COVID-19 disease situation pandemic (https://www.who.int/emergencies/diseases/novel-coronavirus-2019).
With regard to the infertility and to the use of Assisted Reproductive Techniques (ART), actions to further limit the outbreak of the infection vary between countries and are based on both national risk assessments and different bioethical balance between the risk of not being able to conceive and that of getting affected by Covid19. This risk is influenced by the different population growth trends, being the Italian one already negative (-0.2%) since many years and with an average age of the population among the oldest in the world. This trend has serious socio-economic implications. Furthermore the morbidity and mortality of women in the reproductive age is about a third of that of males (https://www.epicentro.iss.it/coronavirus/bollettino/ReportCOVI2019_20_marzo_eng.pdf).
The Authority for ART in Italy “Superior Institute of Health” (ISS) and the “National Center of Transplants” (CNT) established their “Prevention measures of transmission of new Coronavirus infection (SARS-CoV-2) in Italy for reproductive cells and treatments of ART” on March 17, 2020 (Prot.605/CNT2020: http://www.trapianti.salute.gov.it/imgs/C_17_cntAvvisi_233_0_file.pdf) after that the majority of both public and private clinics have already modified their treatment protocols. The two authorities recommand: i) to avoid gamete donation programs which are not urgent; ii) to postpone IVF programs and activities for couples that have not yet started ovarian stimulation and whose treatment was not defined urgent; iii) to initiate new treatments only for urgent fertility preservation cases, i.e. for oncological patients.
The aim of these documents is to mitigate the risks for the patients and for the professionals involved. Since no data on newborn were available at that time these recommendations were based on the principles of responsibility and solidarity and had the aim of preventing the spread of the virus, as well as the establishment of a pregnancy that could be easily delayed due to the unknown risks of the pandemic situation.
A precautionary approach is strongly recommended until reliable data will be published (1). For these reasons SIFES-MR suggests to infertile patients to consider postponing embryo transfer through oocyte/embryo cryopreservation. Indeed it is strongly recommended to postpone pregnancy until sufficient data will be published on the relationship between COVID-19 and gestation. (http://www.pma-italia.it/IT/news.xhtml/news/258-comunicazione-congiunta-fondazione-pma-italia-e-sifes). On the other hand, in the international scenario, ESHRE suggested on March 19 to prevent the establishment of novel pregnancies through deferred embryo transfer, to prevent the patients from travelling for fertility treatments, and to avoid additional stress to healthcare systems. On March 23, the annual meeting has been canceled and 2 days later a “COVID-19 working group to monitor scientific reports relevant to reproductive medicine” has been established (https://www.eshre.eu/Press-Room/ESHRE-News#COVID19WG) The ASRM Task Force instead released an official document on March 17 (https://www.asrm.org/news-and-publications/covid-19/) then updated on March 30 (https://www.asrm.org/globalassets/asrm/asrm-content/news-and-publications/covid-19/covidtaskforceupdate1.pdf) suggesting to minimize inter-person interaction, to increase the adoption of tele-medicine. Moreover it has been recommended to postpone all new treatments, to cancel embryo transfers, while continuation of the care for patients already in treatment or requiring urgent stimulation and cryopreservation has been strongly recommended, while elective surgery and non-urgent diagnostic procedures should have been strongly discouraged
However in some couples for whom timely treatment is crucial, delaying ovarian stimulation and the time to oocyte retrieval could have severe effects on their reproductive outcome in particular in women with advanced maternal age and reduced ovarian reserve.
In this situation SIFES-MR suggests that, in the absence of stringent rules from the competent authority to stop all IVF treatments, the procedures of ovarian stimulation and IVF/ICSI in specific patient groups such as poor prognosis couples, should not be considered elective but urgent. Advanced maternal age (AMA) and reduced ovarian reserve women should be considered critical patients in which postponing egg retrieval may compromise future fertility (3). Nevertheless, during this pandemic, three important aspects become essential in ART: i) the identification of the infertile women fulfilling the “time-sensitive” criteria; ii) the personalization of the stimulation regimes based on maternal age and ovarian reserve is even more important to predict the ovarian response; iii) the prevention of the ART-related risks (ovarian hyperstimulation syndrome, OHSS; complications associated with the oocyte retrieval; multiple gestations). All these measures are of utmost importance to reduce the risk of hospitalization in such a critical period.
Moreover, it is implicit that only ART clinics with high expertise (SIERR; https://www.sierr.it/comunicazioni-news-embriologia-ricerca/emergenza-covid-19-raccomandazioni-sierr-per-il-laboratorio-di-pma.html) should be allowed to perform oocyte retrievals in this emergency situation.
Furthermore, any ART clinic is also considered a tissue center which works in a protected setting and environment and should constantly safeguard both patients and operators. Clearly, infected (or suspected to be infected) patients must be excluded from any ART treatment. In the same way, operators that are infected or suspected to be, must be isolated from the ART clinic.
Recommendations by SIFES- MR
To guarantee the prosecution of ART treatments and reduce the time to oocyte retrieval and potential drop-out in time-sensitive patients, SIFES-MR suggests:
- To use telemedicine (consultations via phone or videoconferencing) In case face-to-face consultations are required, it is recommended to minimize the number of people attending, to limit the number of people in the waiting room, ensuring one meter distance between them, rescheduling the appointments when needed. Patients will be offered face masks, gloves and overshoes when entering the clinic. Generally, consider reducing the number of non-essential monitoring visits.
- To prioritize the access to new ART treatments priority should be given to oncologic patients, then AMA and reduced ovarian reserve women soon after the peak of infections in each Country should be prioritized
- To screen the patients for putative symptoms of infection both via telephone interview before they attend any clinical space and in-person on their arrival (chaperones should also be screened).
- To avoid treating patients at higher risk for COVID-19 infection due to pre-existing clinical conditions, e.g. renal disease, diabetes, hypertension, liver disease, heart problems and all diseases causing immune compromise, such as AIDS, malnutrition.
- Intensify the cleaning and apply sanitization protocols of spaces in fertility clinics according to relevant recommendations of authorities. Refer to good Clinical Practice and guidelines for mitigation of infection should be considered mandatory.
- Avoid procedures like ovulation induction for timed sexual intercourse and intrauterine inseminations as these procedures are more used in younger women for whom the “time” variable is less important.
- Adopt personalized ovarian stimulation protocols based on AMH and antral follicle count with fixed dose of gonadotrophins and fixed antagonist protocol, agonist trigger for oocyte maturation, freeze-all approach and eventually dual stimulation strategy. These actions aim to minimize the need for ultrasound monitoring, the risk for OHSS and to avoid embryo transfer procedures.
- Emergency plans should be in place for the management of potential staffing shortages, supply shortages and unintended exposure of staff members to the risk of COVID-19 infection. In particular, the whole IVF team (clinicians, embryologists, nurses, technicians, secretariats) should be organized in teams always working together in order to guarantee the quality and safety levels of the procedures and the continuity of care in case of quarantine.
- Support the couples via objective counseling regarding the still unknown COVID-19 effects on a putative gestation.
- Offer clinical and psychological support to infertile patients seeking a pregnancy, to avoid that a feeling of uncertainty and frustration (depending on or additional to this pandemic scenario) might negatively affect their future reproductive choices, thereby resulting in an increased prevalence of treatment drop-out (2)
After this disclosure and use of cautions, the final decision is always up to the couple because the lockdown could last for a period of time that may have minimal impact on the reproductive possibilities or for a longer period with instead serious consequences. This turns out to be different throughout the world since each country has a different population candidate for ART. For example the Chinese population that refers to ART has an average age of the woman of 33 years old. In Italy on the other hand the mean age of women requiring ART treatments is 37 years and over 30% of couples have women aged around 40 years old. (http://old.iss.it/rpma/?lang=1&id=1063&tipo=5)
COVID-19 disease is an unprecedented global situation which is drastically changing our daily life and perspective. SIFES- MR society suggests some recommendations, carefully following the situation whilst contributing by sharing novel evidence to counsel patients, both pregnant women and would-be mothers. However, time to egg collection and drop-out rates are two critical points to consider for future ART treatments once the curve of this pandemic will have plateaued and finally decreased. In order to reduce them both, infertile patients now require even more medical and psychological support by their clinicians and by the whole IVF team. Urgent oocyte collections could be an option to consider not only for oncologic patients but also for all time-sensitive patients such as women with advanced maternal age and reduced ovarian reserve. It is our duty towards our patients, since infertility is increasing over time and simultaneously towards our country which is suffering a constant decline in live birth rates.
1.Schwartz DA, Graham AL. Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections. Viruses 2020;12.
2.Gameiro S, Boivin J, Peronace L, Verhaak CM. Why do patients discontinue fertility treatment? A systematic review of reasons and predictors of discontinuation in fertility treatment. Hum Reprod Update 2012;18:652-69.
3. Ubaldi FM, Cimadomo D, Vaiarelli A, Fabozzi G, Venturella R, Maggiulli R, Mazzilli R, Ferrero S, Palagiano A, Rienzi L. Advanced Maternal Age in IVF: Still a Challenge? The Present and the Future of Its Treatment. Front Endocrinol (Lausanne). 2019 Feb 20;10:94. doi: 10.3389/fendo.2019.00094.