Giovanni Buzzaccarini, M.D., Loris Marin, M.D., Marco Noventa, M.D., Flavia Filippi, Ludovica Nuzzi, Arianna Riva, M.D., Guido Ambrosini, M.D., Alessandra Andrisani, M.D.
Gynaecologic and Obstetrics Clinic, Department of Women’s and Children’s Health, University of Padua, 35100, Padua, Italy
The worldwide pandemic emergency that characterized the late 2019 and 2020 has been caused by the novel SARS-CoV-2 infection. It is currently believed that this virus originated in China before rapidly spreading all over the world, reaching a lethality rate between 1% and 3% with some notable peaks in specific countries. The Italian contagion is a specific and extremely relevant case, which by May 2020 had resulted in more than 27,000 deaths with lethality rates above 10% in some regions (1). In the context of this emergency, the allocation of health resources and the risk to the population forced the Italian Government to initiate drastic containment measures (2). In particular, assisted reproduction technique (ART) treatments have been considered deferrable and, therefore, interrupted (3) in accordance with international ART societies. There is currently insufficient evidence to accurately assess whether COVID-19 poses a danger to pregnancy. Recent studies suggest that COVID-19 might not have detrimental effects on fetuses and a vertical transmission has not yet been elucidated (4-6). However, viral infections could be more dangerous in pregnant women compared to women who are not pregnant and treatments against viral infections might be not recommended in order to ensure fetus health. Moreover, some case reports have recently showed premature membrane rupture and preterm delivery in women affected by COVID-19 (7). It is this uncertainty that physicians and scientists worldwide are trying to solve; from and ethical and rational standpoint ART treatments have been halted until there is a better understanding of COVID-19 risks for pregnancy (8). In addition to IVF/ICSI cycles, intrauterine insemination (IUI) and embryo transfers (ET) have also been interrupted. Oncofertility preservation treatments are the only IVF procedures that are still ongoing, due to their urgency and the impossibility of postponement (3). However, the need for restarting ART treatments has resulted in recent guidelines aimed at helping centers to plan their activity without compromising safety (9). In this historical contest, the IVF centre of the University of Padua initiated compelling operative protocols, in order to provide the continuation of the activities whilst improving patients’ and operators’ safety. This study aims to clarify the internal procedure of our IVF public centre in order to re-start ART treatments.
We collated all the operative protocols of the IVF centre of the University of Padua and divided them according to the different procedures. In particular, we summarized medical protocols, stressing the relevant role of the internal job organization, the healthcare professional’s responsibility and the efficacy of video-consultations.
Results and Discussion:
In order to clarify our results, we divided them according to the procedures in the following paragraph.
In order to reduce the patients’ need to make a visit in person, which poses a risk of contagion, our center is now able to offer video-consultation. Video consultation is a new model of care that reduces the need for face-to-face contacts between clinicians and patients (10).
A validated informatic program allows patients to upload the results of their tests so that the physician can subsequently download and check them. On the day of the video-consultation, the physician performs an appointment, highlights reasons for infertility, requests other exams if needed, proposes a treatment, clarifies the informed consent to the next infertility treatment and schedules the ART pathway. The introduction of video-consultation has two main advantages: firstly, safety is improved, the need to commute to and from the centre is reduced and the risk of contagion is avoided, and secondly, couples who live far away can easily access to the center with the minimum of risk and also reduce costs related to the journey, means of transport and hours lost from work. Subsequently, not only the health of individuals is protected but also ecological issues are involved. Moreover, video-consultations avoid the problem of available spaces: rooms are no longer needed in order to perform an interview. This seems a great advantage, especially in this pandemic period when people must maintain a safe distance from others. In addition, considering the fact that infertility interviews are administered with couples and not with single patients, this solution seems quite efficient. Additionally, technology reduces waiting times, because the couple is asked to wait in their home for the video-consultation appointment. This approach greatly increases the couples’ satisfaction. Infertility is a very stressful condition for couples, therefore a medical interview can represent a trying moment (11). For this reason, the couple may feel more comfortable if the dialogue is performed inside their own home rather than in a clinic. Indeed, this could probably help couples to accept ART treatments, since dropouts are often caused by excessive stress and anxiety (12). Because video-consultations provide a visual contact that can be more tailored to the couple’s feelings rather than via phone calls or e-mails, they can be easily performed when a physician also needs to relay information that can have a major impact on couples’ emotionality. Finally, video-consultations reduce the waiting-list of patients accessing the center, especially of public centers, accelerating the start of treatments. In the “experience age”, where people want to experience everything, where the digital transformation of healthcare is becoming mainstream, telemedicine allows us to overcome the risk of viral transmission, while empowering patients to engage with their health in a truly preventive way. All the video-consultations are codified as effective medical interviews guaranteeing privacy policies, as required by Italian law.
Center access and triage
Every patient accessing our center has an appointment. The day before, patients are called by phone in order to assess the presence or not of respiratory symptoms or fever. Moreover, they are asked if potential Covid-19 contacts have occurred in the previous 14 days. Every patient is invited to wear personal protective equipment PPE (gloves and mask). For every communication we use phone calls, e-mail and video-consultation. When the patients reach our center, they are required to stop at a checkpoint at a specific nursing station. A dedicated nurse performs the following actions:
1. patient hygienic hand-washing procedure is shown;
2. a mask and disposable gloves are given to those patients who require them;
3. body temperature is checked;
4. an anamnestic screening is performed by asking the patient whether respiratory symptoms are present and by searching for possible contacts with COVID-19 positive cases in the previous 14 days.
When there are no clinical suspicions, the patient is accompanied to the waiting room of the IVF centre, where patients must maintain a distance of one meter from each other, which is facilitated by logistic furniture placement.
Ultrasound monitoring must be performed whilst still respecting the social distance of at least one meter, as stated by Italian law. Patients receive scheduled appointments in order to avoid interpersonal contacts as much as possible. The patient must also undress in a separate room and during the ultrasound scan, the patient must wear a face mask, disposable shoes and gloves. At the end of each procedure, all ultrasound devices must be carefully disinfected, all the surfaces cleaned, and the physician must wash his hands. The room is adequately aerated before the next procedure. According to ESHRE guidelines, hormonal panel dosages of oestradiol, progesterone and LH is not beneficial in terms of efficacy and safety over monitoring by ultrasound alone. The hormonal assessment does not appear to increase the likelihood of pregnancy, the number of oocytes retrieved nor the decrease in OHSS rates (13). For this reason, we assess hormonal dosage only when doubts (i.e. about hyperstimulation response regarding progesterone levels at ovulation induction or risk of OHSS) arise from the controlled ovarian stimulation, in order to reduce patients’ movements inside the hospital. When performed, hormonal levels are tested in the central laboratory of our hospital. Since the aim of our center is to protect the patient’s health, women arrive at the laboratory at 7:00 am where they will receive priority access, in order to shorten waiting-list times.
The pick-up procedure takes place in the operating theatre in sterile conditions and healthcare care professionals and patients must wear personal protective equipment (PPE) during the procedure. Every patient accessing the operating theatre must have performed a COVID-19 swab between 24 and 72 hours before entering the operating room. If the COVID-19 swab is positive, the patient undergoes oocyte retrieval in a dedicated surgical theater and the healthcare care professionals who assist the women must wear appropriate PPE. During the recovery, patients are not allowed visitors, except healthcare professionals.
Considering the fact that there are no available studies which state that if the virus is detected inside the follicular fluid in COVID-19 positive women, we are starting a study pertaining to this argument. In the meantime, we consider oocytes retrieved from a COVID-19 positive patient as infected and we do not fertilize them. Furthermore, we store vitrified oocytes through a closed system in a separated tank. If in the future it is reasonable to check oocytes for virus presence, safety against contamination will be maximized. If oocytes present the virus, they will be eliminated.
Embryo transfers are performed in a very similar way to ultrasound monitoring. In order to reduce any possible contact between patients and hospital staff, only the woman, and not the partner, can access the clinic. All the physicians, biologists and nurses wear PPE, and every surface is disinfected at the end of the procedure.
Frozen/Thawed Embryo transfer
All embryos cryopreserved before the start of the COVID-19 pandemic are assumed not to have encountered the virus. For this reason, we perform frozen/thawed embryo transfer of embryos cryopreserved before January 2020. Because we want to guarantee the security of the future pregnant woman, the patient performs an anamnestic screening and her body temperature is checked before starting endometrial preparation protocol and she undergoes a nasopharyngeal swab between 24 and 72 hours before embryo transfer. If any result is positive, the frozen/thawed embryo cycle is cancelled.
In conclusion, COVID-19 pandemic has made the usage of strict protocols necessary, aimed at adequate public health requests to infertile couple needs when accessing ART treatments. Although some decisions may reduce the supply of public services, new approaches in consultation, such as video-consultation, allows our IVF center to continue its activity. It is likely that at the end of this emergency, some of the protocols applied in order to face this contingent situation might be routinely used, not only for public health, but also in order to improve the quality of our center services.
Strict protocols in the use of PPE, hygienic rules, video-consultations and the re-organization of the rooms and the activities of our IVF center provide results in protecting public health and allow safer and more efficient IVF treatments. In particular, ours is the first IVF public center in Veneto, and one of the first in Italy to perform video-consultation.
2. Decreto del Presidente del Consiglio dei Ministri. Ulteriori disposizioni attuative del decreto-legge 23 febbraio 2020, n. 6, recante misure urgenti in materia di contenimento e gestione dell’emergenza epidemiologica da COVID-19. (20A01522) (GU Serie Generale n.59 del 08-03-2020). https://www.gazzettaufficiale.it/eli/gu/2020/03/08/59/sg/pdf
3. Italian Society of Embryology, Reproduction and Research. EMERGENZA COVID-19: raccomandazioni SIERR per il Laboratorio di PMA https://www.sierr.it/images/Documenti/Raccomandazioni. SIERR_per_COVID-19.pdf, 2020.
4. Zeng L, Xia S, Yuan W, et al., Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China. JAMA Pediatr, 2020. https://doi.org/10.1001/jamapediatrics.2020.0878
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7. Liu Y, Chen H, Tang K, et al., Clinical manifestations and outcome of SARS-CoV-2 infection during pregnancy. J Infect, 2020. https://doi.org/10.1016/j.jinf.2020.02.028
8. European Society of Human Reproduction and Embryology. News and Statements. Coronavirus Covid-19: Assisted reproduction and COVID-19. An updated statement from ESHRE https://www.eshre.eu/Press-Room/ESHRE-News, 17 apr 2020.
9. European Society of Human Reproduction and Embryology. News and Statements. Coronavirus Covid-19: Assisted reproduction and COVID-19. A statement from ESHRE for phase 2 https://www.eshre.eu/Press-Room/ESHRE-News, 23 apr 2020.
10. Greenhalgh Trisha, Wherton Joe, Shaw Sara, Morrison Clare. Video consultations for covid-19 BMJ 2020; 368 :m998
11. Klitzman R. Impediments to communication and relationships between infertility care providers and patients. BMC Womens Health. 2018 Jun 5;18(1):84. doi: 10.1186/s12905-018-0572-6. PubMed PMID: 29871622; PubMed Central PMCID:PMC5989459.
12. Domar AD, Smith K, Conboy L, Iannone M, Alper M. A prospective investigation into the reasons why insured United States patients drop out of in vitro fertilization treatment. Fertil Steril. 2010 Sep;94(4):1457-9. doi: 10.1016/j.fertnstert.2009.06.020. Epub 2009 Jul 9. PubMed PMID: 19591985.
13. ESHRE guidelines. Ovarian stimulation for IVF/ICSI. 2019