The COVID-19 crisis and ART activity in France.

RESEARCH QUESTION: What was the impact of the COVID-19 pandemic on assisted reproductive technology (ART) activity in public and private hospitals in France in 2020? DESIGN: All women who underwent oocyte retrieval in 2020 (study group, n = 40,759) or in 2019 (comparison group, n = 52,403) were selected from French national health insurance databases. The weekly ART activity in 2020 was compared with the weekly ART activity in 2019. RESULTS: In 2020, annual ART activity dropped by nearly 30% compared with 2019. Whereas weekly ART activity was at its normal level at the beginning of 2020, it sharply decreased and was almost non-existent during the first French lockdown (March-May 2020) in both public and private hospitals. After the first lockdown, private hospitals returned to their normal activity level within 1 month. In contrast, the activity of public hospitals remained well below normal until the summer break, before peaking at 40% of normal activity compared with an expected level of 57%. During the second French lockdown, ART activity was only slightly affected, principally in public hospitals where ART activity was around 48% compared with an expected level of 57%. CONCLUSIONS: In countries where intensive care units are principally in public hospitals, greater disruption in public than in private hospitals may have led to an increase in health inequalities for ART activity, as for other healthcare.

Pfizer SARS-CoV-2 BNT162b2 mRNA vaccination (BNT162b2) has no adverse effect on elective oocyte cryopreservation outcomes.

RESEARCH QUESTION: Do elective oocyte cryopreservation outcomes in women 1-13 months after SARS-CoV-2 vaccination alter compared with unvaccinated women and do different time intervals between vaccination and ovarian stimulation impact these outcomes? DESIGN: This retrospective cohort study, conducted in a university-affiliated IVF centre, included 232 elective oocyte cryopreservation cycles of vaccinated and unvaccinated patients, without previous infection with the SARS-CoV-2 virus, between December 2020 and January 2022. Two control groups - pre-pandemic (January 2019 to February 2020) and intra-pandemic (December 2020 to January 2022) unvaccinated groups - were compared with the vaccinated group, further divided into four subgroups (under 3, 3-6, 6-9 and 9-13 months). The primary outcome was the elective oocyte cryopreservation cycle outcomes - number of retrieved and number of mature oocytes. RESULTS: The vaccinated group demonstrated comparable outcomes with regards to number of retrieved and mature oocytes compared with the pre-pandemic and intra-pandemic unvaccinated groups (12.6 ± 8.0 versus 13.0 ± 8.2 and 12.5 ± 7.4 retrieved and 10.1 ± 6.9 versus 9.5 ± 6.4 and 10.1 ± 6.3 mature oocytes, respectively; not significant for both). Similar results were noted in a comparison between the intra-pandemic unvaccinated group and the four vaccinated subgroups. No correlation was found between the parameter of days from vaccination and cycle outcomes. Similarly, analysis of covariance showed no association between vaccination status and timing and number of mature oocytes. CONCLUSIONS: The SARS-CoV-2 vaccination does not alter the outcomes of elective oocyte cryopreservation procedures. This is true even in a relatively long time interval of 9 to 13 months from vaccination.

The use of oocyte cryopreservation for fertility preservation in patients with sex chromosome disorders: a case series describing outcomes.

PURPOSE: Characterize outcomes among adolescents and young adults (AYAs) with sex chromosome disorders (SCDs) after oocyte cryopreservation (OC) consultation. METHODS: Retrospective case series of all AYA (< 25 years) patients with SCDs seen for OC consultation from 2011 to 2019 at a large, urban, academic fertility center. All AYA patients with an SCD seen for OC consult in the study time period were reviewed and included. Data collected included patient age, SCD type, number of patients who attempted OC, number of cycles attempted, and cycle outcomes. RESULTS: Twenty-two patients were included: 9 with Turner syndrome, 12 with mosaic Turner syndrome, and 1 with 47,XXX. Mean age at consult was 14.7 ± 3.5 years. Fourteen patients elected for OC: 5 with Turner syndrome, 8 with mosaic Turner syndrome, and 1 47,XXX who pursued 31 OC cycles total. Of those 14 patients, 10 underwent retrieval, 9 froze oocytes, and 8 froze mature (MII) oocytes. Seven patients underwent > 1 cycle and 7 had ≥ 1 cancelation. 3/3 patients who pursued cycles after 1st cancelation never got to retrieval. Age, SCD type, and baseline FSH did not predict ability to freeze MIIs. One patient returned after OC and attempted 4 ovulation induction cycles and 2 IVF cycles; all were canceled for low response. CONCLUSIONS: AYA patients with SCDs have a high risk of poor response and cycle cancelation but the majority froze MIIs. Thus, setting expectations is important. A larger sample size is needed to evaluate possible clinical predictors of success.

Coronavirus disease 2019 vaccination and infertility treatment outcomes.

OBJECTIVE: To assess the influence of coronavirus disease 2019 (COVID-19) messenger ribonucleic acid vaccine on ovarian response and in vitro fertilization (IVF) treatment outcomes. DESIGN: A retrospective cohort study. SETTING: A tertiary university-affiliated medical center and a private medical center. PATIENT(S): The study included a total of 400 patients, 200 vaccinated women and 200 age-matched unvaccinated women, who underwent IVF in January-April 2021. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The mean number of oocytes retrieved and clinical pregnancy rates in vaccinated vs. unvaccinated patients. RESULT(S): A total of 200 patients underwent oocyte retrieval 14-68 days after receiving COVID-19 vaccination. No difference was found in the mean number of oocytes retrieved per cycle (10.63 vs. 10.72) between vaccinated and unvaccinated patients. Among 128 vaccinated and 133 unvaccinated patients who underwent fresh embryos transfers, no difference was demonstrated in the clinical pregnancy rates (32.8% vs. 33.1%), with 42 and 44 clinical pregnancies, respectively. The fertilization rates and mean number of cryopreserved embryos were similar between the 2 groups in freeze-all cycles (55.43% vs. 54.29% and 3.59 vs. 3.28, respectively). Among vaccinated and unvaccinated patients who underwent fresh embryo transfers, no difference was noted in the fertilization rate (64.81% vs. 61.98%) and transferred embryos' quality. Regression models applied demonstrated no effect of the vaccine on oocyte yields and pregnancy rates. CONCLUSION(S): The COVID-19 messenger ribonucleic acid vaccine did not affect the ovarian response or pregnancy rates in IVF treatment. Women should be vaccinated for COVID-19 before attempting to conceive via IVF treatments, given the higher risk of severe illness in pregnant women.

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.

Absence of SARS-CoV-2 (COVID-19 virus) within the IVF laboratory using strict patient screening and safety criteria.

RESEARCH QUESTION: Is there a risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral exposure and potential cross-contamination from follicular fluid, culture media and vitrification solution within the IVF laboratory using strict patient screening and safety measures? DESIGN: This was a prospective clinical study. All women undergoing transvaginal oocyte retrieval were required to have a negative SARS-CoV-2 RNA test 3-5 days prior to the procedure. Male partners were not tested. All cases used intracytoplasmic sperm injection (ICSI). The first tube of follicular fluid aspirated during oocyte retrieval, drops of media following removal of the embryos on day 5, and vitrification solution after blastocyst cryopreservation were analysed for SARS-CoV-2 RNA. RESULTS: In total, medium from 61 patients, vitrification solution from 200 patients and follicular fluid from 300 patients was analysed. All samples were negative for SARS-CoV-2 viral RNA. CONCLUSIONS: With stringent safety protocols in place, including testing of women and symptom-based screening of men, the presence of SARS-CoV-2 RNA was not detected in follicular fluid, medium or vitrification solution. This work demonstrates the possibility of implementing a rapid laboratory screening assay for SARS-CoV-2 and has implications for safe laboratory operations, including cryostorage recommendations.

Undetectable viral RNA in oocytes from SARS-CoV-2 positive women.

A central concern for the safe provision of ART during the current coronavirus disease 2019 (COVID-19) pandemic is the possibility of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through gametes and preimplantation embryos. Unfortunately, data on SARS-CoV-2 viral presence in oocytes of infected individuals are not available to date. We describe the case of two women who underwent controlled ovarian stimulation and tested positive to SARS-CoV-2 infection by PCR on the day of oocyte collection. The viral RNA for gene N was undetectable in all the oocytes analyzed from the two women.

Assisted reproduction and thromboembolic risk in the COVID-19 pandemic.

The COVID-19 pandemic has significantly increased mortality in many countries, with the number of infected cases increasing exponentially worldwide. One of the main determining factors of the poor prognosis in these patients is the development of coagulopathy. Moreover, it is well known that assisted reproductive technology procedures confer a risk of thromboembolic complications. This commentary analyses specific aspects coexisting between the thrombotic risk described during virus infection and that reported in the context of assisted reproduction treatments. Based on known pathophysiological aspects of virus infection and of ovarian stimulation, there are common elements that deserve to be taken into account. In the present context, any risk of hyperstimulation should be avoided. Gonadotrophin-releasing hormone agonist triggering should be mandatory in high-responder patients and/or those with COVID-19 infection. In both cases, the cycle should be segmented. A proposal is made for the use of prophylactic low molecular weight heparin not only in those cases in which oocyte retrieval has been performed, but also in those in which cancellation has been decided. In addition, endometrial preparation for frozen-thawed embryo transfers should use the transdermal route in order to minimize the higher thrombotic risk associated with the oral route.