Detection of SARS-CoV-2 in Follicular and Endocervical Fluid of in Vitro Fertilization Candidates with Positive Polymerase Chain Reaction Tests

Background: The coronavirus disease 2019 (COVID-19) pandemic was a unique global challenge with a wide range of severity extending from an asymptomatic form to a serious intense respiratory syndrome. This study aimed to detect SARS-CoV-2 in the follicular and endocervical fluid of in vitro fertilization (IVF) candidate patients with a positive polymerase chain reaction (PCR) test for SARS-CoV-2. Method(s): All participants and their partners, who were a candidate to start assisted reproductive technology (ART) from April 2020 to October 2020, completed a triage questionnaire two weeks before starting the ART cycle. According to Avicenna center protocol, a diagnostic test for COVID-19 using real-time PCR of nasopharyngeal swabs was performed on all ART candidates, 48 hours before the day of the oocyte trigger. In the operating room, sterile swabs were used to provide cervicovaginal specimens to determine SARS-CoV-2 in cervicovaginal fluid. Moreover, the first aspirated follicular fluid was referred to the lab to assess the presence of SARS-CoV-2. Result(s): A positive PCR test for SARS-CoV-2 was verified in 32 participants. In this study, virus particles were not detected in the follicular and endocervical fluid of the women with positive PCR tests. Conclusion(s): We are still at the beginning of the road and need reliable data on the safety of ART at the time of the pandemic. The risk of infection during all processes of ART including oocyte retrieval needs attention. The fluid from mature follicles is a potential site to be infected and the human cumulus cells could not be a deterrent factor to the entrance of the virus in the oocyte. This process may lead to gametes infection. We did not detect virus RNA in the follicular and endocervical fluid of the patients with a positive PCR test. Although, more studies with a larger sample size are mandatory in this field.

Detection of SARS-CoV-2 in Follicular Fluid of COVID-19 Infected Women

Background: The coronavirus disease-2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now spread all over the world. This study was designed to assess the possibility of SARS-CoV-2 presence in follicular fluid, which may have harmful effects on normal ovulation and fertility. Method(s): Five women who were candidates for Assisted Reproductive Technique (ART) and had a COVID-19 PCRpositive test on the day of oocyte retrieval participated in the study. SARS-CoV-2 tests were performed on the follicular fluid obtained from these women. Result(s): SARS-CoV-2 RNA was detected only in one follicular fluid sample, and other follicular fluid samples were negative. Conclusion(s): Because the COVID-19 effect on human reproduction is unknown, exact precautions should be taken during this pandemic, especially for women applying for ART.

Is There any Effect of COVID-19 on Follicular Environment in Women Underwent ART?

There is insufficient data on the impact of severe acute respiratory coronavirus-2 (SARS-CoV-2) on the reproductive tissues, its possible risk of cross-contamination, transmission and adverse effect on in vitro fertilization (IVF) outcome. Until today, there is no report associated with viral RNA in both follicular fluid and embryo culture medium from SARS-COV-2 positive women. In this case report, a 24-year-old woman with SARS-CoV-2 was presented. We investigated the SARS-COV-2 positivity in the follicular fluid and embryo culture medium of mildly symptomatic woman on oocyte pick up (OPU) day. We could not detect viral RNA in neither the follicular fluid nor the embryo culture medium. In addition, although the response of ovarian stimulation was normal, the number and maturity of the retrieved oocytes were low.

COVID-19 infection control protocol and acceptance in an ART in vitro fertilization hospital.

Purpose: In Tokyo, where the highest coronavirus disease 2019 (COVID-19) infection rates have been reported nationally, we introduced and performed polymerase chain reaction (PCR) testing on the patients prior to them coming for oocyte retrieval (OR) or embryo transfer (ET) procedures. In addition, we recommended that patients self-inject ovarian stimulation drugs to reduce the number of hospital visits required. We aimed to assess the patient acceptance of these measures and the change of treatment number. Methods: We conducted a retrospective study examining the patients coming for OR or ET, from the first time a state of emergency was declared in Japan, May 2020, until September 2021. Results: A total of 79 out of 94 (94%) patients complied with the measures. This may reflect that PCR universal screening was accepted by most patients as necessary for reducing infection spread. In addition, the number of patients receiving OR and ET increased. The widespread adoption of work-from-home practices during the pandemic has made outpatient visits more acceptable to the general public. Conclusions: Universal screening and self-injection are accepted and effective infection measures in patients presenting for OR and ET.

Anaesthesia for Assisted Reproductive Technology (ART): A Narrative Review

Assisted reproductive technology (ART) is used primarily to address the treatment of infertility which includes medical procedures such as in vitro fertilisation (IVF), intra-cytoplasmic sperm injection (ICSI), gamete intra-fallopian transfer (GIFT) or zygote intra-fallopian transfer (ZIFT). IVF has revolutionised infertility treatment and is nowadays widely accepted all over the world. The IVF is carried out as a daycare procedure and many anaesthetic regimens have been studied, tried and tested so far. An anaesthesiologist's role mainly comes into play during trans- vaginal oocyte retrieval and embryo transfer (ET) process of IVF. Various techniques of anaesthesia are practised which include general or regional anaesthesia, conscious sedation or monitored anaesthesia care, patient-controlled analgesia, acupuncture and transcutaneous electrical nerve stimulation (TENS). The anaesthetic management needs careful consideration of the effect of drugs on the maturation of oocytes or embryonic development, fertilisation and pregnancy rates. In view of the Coronavirus disease-19 (COVID-19) pandemic, ART clinics have been affected and due to the ambiguity of its effects on the reproductive outcome, anaesthesiologists need to be vigilant and cautious with anaesthetic management during pandemic times. This review includes a discussion of various anaesthetic options and agents along with their advantages or disadvantages if any. The literature sources for this review were obtained via PubMed, Medline, Cochrane Library and Google Scholar. The results of 82 out of 110 articles discussing different methods of anaesthesia for ART procedures over 25 years were compiled.

EXPOSURE OF OVARIES TO COVID-19 VACCINATION DOES NOT IMPAIR FERTILITY

OBJECTIVE: Misinformation regarding Covid vaccination has contributed to vaccine hesitancy. Initially, there were claims that immune cross reactivity between the SARS CoV-2 spike protein and syncytin-1 would prevent embryo implantation. We previously demonstrated no difference in implantation and sustained implantation rates between previously vaccinated or infected women compared to other women.1 More recently, misinterpretation of vaccine biodistribution data has led to a second claim that mRNA containing lipid nanoparticles are concentrated in the ovaries and spike protein produced there would also cause infertility. The purpose of this study is to determine whether prior in vivo ovarian exposure to lipid nanoparticle-mRNA vaccination against SARS-CoV2 spike protein reduces subsequent fertility in women. MATERIALS AND METHODS: This is an ongoing observational study of women undergoing frozen embryo transfer with a single expanded blastocyst. This is an interim report (n =128) encompassing transfers between Jan 1 and Jul 02. All patients had serum analyzed prior to starting stimulation for egg retrieval to quantitatively determine the level of AntiSARS-CoV-2 Spike IgG. Reactive (antibody positive) patients were questioned to determine a history of vaccination or infection. Patients were divided into three groups based on their status. Women who were vaccinated (n = 26);women who had previous infection with SARS-CoV-2 (n=11) and women without a history of either vaccination or infection (n=91). Only patients receiving the mRNA vaccines from BioNTech / Pfizer (BNT162b2) and Moderna (mRNA-1273) were analyzed. Outcome measure for the three groups were initial implantation rate (serum hCG level > 5 mIU/mL obtained 8 days after embryo transfer followed by a rising level two to three days later), sustained implantation rate (transvaginal ultrasound documented positive FHTs at two time points at least one week apart) and miscarriage rate (the difference between initial and sustained implantation rates). Baseline characteristics were analyzed using ANOVA. Chi square analysis was used to compare pregnancy rates. RESULTS: CONCLUSIONS: Embryos produced from oocytes exposed in vivo to lipid nanoparticles containing mRNA for the SARS CoV-2 spike protein are not less likely to produce pregnancy or more likely to miscarry. IMPACT STATEMENT: This data refutes the rumors that Covid-19 vaccinations are “toxic” to the ovaries & adds to the growing body of evidence that vaccinations do not cause infertility. (Table Presented).

REDUCING IVF CYCLE MONITORING TO MAINTAIN SOCIAL DISTANCING PRACTISES DURING THE COVID-19 PANDEMIC

OBJECTIVE: To significantly reduce the number of in person visits during an IVF cycle without compromising cycle outcomes, patient safety, or patient satisfaction. MATERIALS AND METHODS: This was a multi-modal QI initiative at an academic fertility centre. After the temporary closure of many fertility services across IVF clinics in North America in March 2020, we identified that new policies and procedures were necessary in order to safely resume patient care during a pandemic. The primary intervention of this study was a change in our IVF monitoring protocol. Our default settings in our electronic medical record order sets were changed, and education sessions were held for clinic staff. Baseline data was collected from 2019 for comparison. A patient satisfaction survey using a 5-point likert scale was created and sent to every patient undergoing IVF on the day of their oocyte retrieval. The number of in person visits during an IVF cycle were counted for each patient undergoing treatment from June 2020 to August 2020. This was compared to the number of in person visits during the same time frame in 2019. Balancing measures included patient satisfaction, pregnancy rates, risk and incidence of ovarian hyperstimulation syndrome (OHSS), incidence of cycle cancellation, and number of eggs retrieved per cycle. Pre- and postintervention data was compared using univariate and multivariate poisson models to control for patient characteristics such as age, AMH, and BMI. RESULTS: A significant reduction in the number of in person visits (8 vs 4, p<0.001) during an IVF treatment cycle was observed post-intervention compared with the previous year. There was no significant difference in pregnancy rates, risk or incidence of OHSS, cycle cancellation, or number of eggs retrieved per cycle. Patient surveys were reassuring that the intervention did not change patient experience or satisfaction. CONCLUSIONS: IVF Monitoring Protocol changes aimed at reducing the number of in person visits allowed our team to continue to provide ongoing care for patients during the Covid-19 pandemic without compromising IVF outcomes or patient satisfaction. IMPACT STATEMENT: This study allows for safer and socially distanced care for patients undergoing IVF cycles during a pandemic, and will also shape our future practise of cycle monitoring during IVF stimulation as we have shown that a reduction in bloodwork and ultrasound does not negatively impact patient outcomes.

ASSISTED REPRODUCTIVE TECHNOLOGY PROCEDURES IN THE US PRIOR TO AND DURING THE COVID-19 PANDEMIC

OBJECTIVE: The COVID-19 pandemic has created many uncertainties for those pursuing fertility care and assisted reproductive technology (ART) procedures, due to ever-changing healthcare restrictions. There is a lack of research on large-scale data for ART procedures during the pandemic. The objective of our study is to evaluate ART procedures, specifically oocyte retrieval and in vitro fertilization (IVF) cycles, prior to and during the pandemic. MATERIALS AND METHODS: Claims data from Symphony Health, one of thelargest databases of patient-level data on morethan 280 million patientsin the US, was examined from May 1, 2019 to February 28, 2021. Reproductiveaged women were included in the analysis. March - April 2020 was used as a threshold for when healthcare restrictions became widespread. We compared 10 months prior to the pandemic (May 2019 - Feb 2020) and the same time period after the start of the pandemic (May 2020 - Feb 2021). ART procedures were identified using CPT codes (58970 for oocyte retrieval, and S4011, S4015, and S4016 for IVF) under ICD-10. Data analysis was conducted in Stata, version 16.1, using 2-sided t-tests with significance set at P < 0.05. RESULTS: Our search yielded 39,087 oocyte retrievals and 14,365 IVF cycles. The average age of patients who started an IVF cycle (36±4.2 vs 35±4.4 years) as well as the age of those who had an oocyte retrieval (36.2±4.6 vs 35.3±4.7 years) prior to and during the pandemic was statistically different. Time series plots show that, after a substantial drop in focal variables in March - April 2020, ART procedures quickly recovered to pre-pandemic baseline by June 2020. Afterwards, oocyte retrievals increased from 1,703 per month pre-pandemic to 2,010 per month during the pandemic, and this difference approached significance (P=0.06). There was not a significant difference in IVF cycles (677 per month pre-pandemic vs 686 per month during the pandemic, P=0.88). CONCLUSIONS: Despite concerns regarding suspension of ART and delivery of infertility care during the pandemic, our study shows no significant difference in oocyte retrievals and IVF cycles prior to and during the COVID-19 pandemic. IMPACT STATEMENT: These results suggest reassuring outcomes despite a health crisis in the US. There was no significant delay or interruption of fertility care and ART procedures in the US. Further research should examine how other social determinants such as ethnicity, income and geographic location affected access to and utilization of infertility care.

Oocyte and Sperm Cryopreservation In Oncological Patients During Covid-19 Pandemic

During the pandemic, most infertility and IVF Units decided to keep fertility preservation active as an urgent procedure. It is well established that chemotherapy is gonadotoxic and impact negatively on quality of life. The American Society of Reproductive Medicine (ASRM) and European Society of Human Reproduction and Embryology (ESHRE) recommend to offer fertility preservation before cancer treatment. Oocyte cryopreservation and sperm cryopreservation are the best treatments of the choices to preserve fertility in cancer patients. This is a prospective study performed at Infertility and IVF Unit, Sant’Orsola University Hospital, University of Bologna, Italy, from February 2020 to January 2021. 149 cancer patients underwent gamete cryopreservation to preserve their fertility. All patients tested for realtime (RTPCR) analysis of throat swab specimens for Sars-Cov-2 48 hours before cryopreservation. The viral RNA detection was provided only in case of positive swab and no treatment was interrupted. 59 women underwent ovarian stimulation with gonadotropins followed by oocyte retrieval. Women’s basal characteristics were: Age (m±sd) 31.0 ± 7.0 years, FSH (m±sd) 14 ±9IU/l, AMH (m±sd) 2.4 ± 1.3 ng±ml, AFC (m±sd) 9 ±5. 90 men underwent spermatozoa rapid cryopreservation. Men’s basal characteristics were: Age (m±sd) 34±7 years;Total Sperm count x 106 (m±sd) 52.3±49.6, Sperm x 106/ml 28.1±25.5, Total motility (m±sd) 48.0±26.7 %, Progressive motility (m±sd) 22.2±20.5 %, normal morphology (m±sd) 22.3±11.1 %. 296 oocyte were cryopreserved: 5.5±4.3 (mean±sd per patient). Vitrification with closed devices (High-Security Vitrification™ - HSV) was used for oocyte cryopreservation to minimize the risk of viral contamination. 403 Sperm samples were frozen with slow freezing: 5.7±2.1 (m±sd) per patient. All patients tested negative for realtime (RTPCR) analysis of throat swab specimens for Sars-Cov-2. The oncofertility activity must be maintained even in pandemic periods by implementing adequate safety measures to protect the health of patients and healthcare professionals. Funding: Supported by Italian Ministry of Health "Fertility Preservation in gonadotoxic treatments” project code RF-2011-02348826 Conflict of Interest: None to disclose

Failure to Detect Viral RNA in Follicular Fluid Aspirates from a SARS-CoV-2-Positive Woman.

Although there is no known difference between the clinical manifestations of SARS-CoV-2 in pregnant and non-pregnant women based on the studies published until now, in vitro fertilization (IVF) treatments were suspended during the pandemic due to uncertainties with the suggestions of associated societies. However, we do not have enough data on the exact effects of SARS-CoV-2 on fertility and pregnancy and whether there are damaging effects on IVF outcome. There is no available evidence about the transmission of SARS-CoV-2 by either sexual way or through intrauterine insemination (IUI) or IVF. Up until now, there is no report to document the presence or absence of viral RNA in follicular fluid of SARS-CoV-2-positive women. In this paper, we present a case of oocyte retrieval from a SARS-CoV-2-positive woman and the search for viral RNA by polymerase chain reaction (PCR) in the follicular fluid aspirates.

Hemothorax after oocyte retrieval in a patient with a history of COVID-19: a case report.

Spontaneous hemothorax is a rare disorder characterized by pleural fluid hematocrit greater than 50% of the peripheral blood hematocrit without natural or iatrogenic trauma to the lungs or pleural space. Since the first case of COVID-19, more than 85 million cases have been confirmed and most patients have sustained symptoms after more than six months of acute infection. This paper reports the case of a 38-year-old woman without signs of endometriosis and a history of COVID-19 infection who developed spontaneous hemothorax after oocyte retrieval. Three months before undergoing assisted reproductive technology (ART) treatment, the patient had a symptomatic COVID-19 infection with a negative PCR test and a positive IgG test four weeks after the onset of symptoms. Controlled ovarian stimulation and oocyte retrieval were conducted uneventfully. Two hours after oocyte retrieval, the patient developed nausea and mild hypogastric pain. Ten hours after the procedure, the patient went to the emergency department with abdominal pain. Chest computed tomography scans revealed moderate right pleural effusion and laminar left pleural effusion. Since the patient had respiratory symptoms, the choice was made to drain the pleural fluid. Fluid analysis confirmed the patient had right hemothorax (400 mL). After drainage, the patient's clinical and imaging signs improved gradually without complications. The patient was asymptomatic one week after the procedure.

Reproductive medical providers' behaviors, considerations, and plans for fertility treatments during the COVID-19 pandemic in Japan: A nationwide web-based survey.

PURPOSE: This study was conducted to investigate how the COVID-19 pandemic has impacted reproductive medical providers' behaviors and considerations, including their concerns regarding the necessity of fertility treatments. METHODS: A web-based questionnaire was distributed to Japan Society of Fertilization and Implantation (JSFI) members from May 18 through May 31, 2020 to survey their professional behaviors and concerns during the COVID-19 pandemic. RESULTS: Most survey participants reported a decrease in the number of patients and a decrease in their workload. Most also believe that the use of fertility treatments will return to the pre-pandemic levels after the COVID-19 pandemic ends. Additionally, more than half of the participants reported that they consider fertility treatment neither necessary nor unnecessary during the COVID-19 pandemic. CONCLUSIONS: At the institute where reproductive medical providers worked in Japan, the number of outpatients and the working time tended to decrease during the COVID-19 pandemic. However, amid fears of infection during the COVID-19 pandemic, the reproductive medical providers working at fertility institutes in Japan have remained engaged in their work with a sense of mission and hope.