A novel cystic fibrosis-pregnancy service: Two-year review after introduction of elexacaftor/tezacaftor/ivacaftor

Background: As a quality service improvement response since elexacaftor/ tezacaftor/ivacaftor (ELX/TEZ/IVA) became available and the yearly average number of cystic fibrosis (CF) pregnancies (n = 7 pre-2020, n = 33 in 2021) increased significantly at an adult CF center (~600 people with CF), a monthly multidisciplinary CF-maternal health virtual clinic was established with antenatal virtual CF exercise classes dedicated to providing adaptive, specialist support to this cohort, aswell as outreach guidance and education to local obstetric teams. Method(s): This was a single-center retrospective reviewof Royal Brompton Hospital CF-Maternal Health multidisciplinary team clinic records and a patient survey from March 2020 to March 2022. Result(s): Of 47 pregnancies in 41 women (median age 30;) eligible for ELX/ TEZ/IVA at start of pregnancy, 40% (n = 19) were unplanned, and 19% (n = 9) used assisted conception. Three women with a history of infertility conceived naturally, having required assisted conception for previous pregnancies, and five women had multiple pregnancies during the study period. ELX/TEZ/IVA was continued in 60% (n = 28), delayed in 28% (n = 13), and stopped in 13% (n = 6) of pregnancies through maternal choice and careful clinical counselling. Pre-pregnancy pulmonary status was poorer in women who continued than in those who delayed or stopped (Table 1). Of those who stopped, 85% (n = 5) restarted because of pulmonary deterioration by the third trimester. Prenatal CF complications included at least one episode of minor hemoptysis in 21% (n = 9/41) of women, at least one infective exacerbation in 55% of pregnancies (n = 26/47), and noninvasive ventilation in one woman. Other pregnancy-associated complications included one case of ovarian hyperstimulation syndrome, one case of sub-segmental pulmonary embolism, and two cases of pregnancy-induced hypertension. Excluding 10 first trimester terminations, 10 current pregnancies, and one patient relocation, obstetric outcomes available for 26 pregnancies confirmed a live birth rate of 85% (n = 22/26) and a 15% first-trimester miscarriage rate (n = 4). Obstetric complications included preterm delivery rate of 23% (n = 6/26), including two cases of COVID infection resulting in two neonatal intensive care unit admissions, one case of endometritis after cesarean section, and a fourthdegree perineal tear. There were no ectopic pregnancies, maternal or neonatal deaths, or reports of infant cataracts or congenital malformations. Median gestational age was 37/40 weeks (range 29-40). Mode of delivery was via cesarean section in 45% (n = 10/22, of which twowere emergency) and vaginal in 55% (n = 12/22), of which 83% (n = 10/12) were via induction of labor for diabetes (CF or gestational) indication. Deliveries were supported and occurred equally at local obstetric units and in tertiarycare obstetric hospital settings (50%, n = 11/22). Patient-experience survey responses cited high levels of confidence in health optimization and prioritization during pregnancy and praised excellent inter-health care provider communication and peer-to-peer emotional support provided among expectant mothers in the virtual prenatal exercise groups. Table 1. Baseline demographic and clinical characteristics of elexacaftor/tezacaftor/ivacaftoreligible expectant mothers according to therapeutic decision (Table Presented) Conclusion(s): In the absence of clinical trial safety data, the novel approach of a dedicated CF-maternal health multidisciplinary team clinic with local obstetric outreach support has ensured regular specialist clinical and emotional peer-to-peer support for this cohort of women eligible for ELX/ TEZ/IVA to ensure optimal outcomes and experiences of their pregnancies, where appropriate, close to home.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

22nd International Congress of Iranian Society for Reproductive Medicine

The proceedings contain 158 papers. The topics discussed include: the success of various endometrioma treatments in infertility: a systematic review and meta-analysis;cell therapy accompanied by natural biomaterials, a novel therapeutic strategy for primary ovarian insufficiency treatment;ovarian hyperstimulation syndrome: a new look at an old problem;role of doppler ultrasonography and 3D ultrasound in female infertility;clinical outcome of artificial oocyte activation following intracytoplasmic sperm injection;the research priorities in infertility;how old is too old for infertility treatment?;the role of sexual dysfunction in men's health;recombinant follicle-stimulating hormone in treatment of sperm DNA fragmentation;the effect of zinc on tetrahydrocannabinol-induced Sertoli cells apoptosis;and detection of SARS-CoV-2 in follicular and endocervical fluid of in vitro fertilization candidates with positive polymerase chain reaction tests.

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.

THE EFFECT OF TELEMEDICINE DURING THE COVID-19 PANDEMIC ON IVF TREATMENT

OBJECTIVE: To assess the effect of telemedicine during the COVID-19 pandemic year on the treatment decision of new patient for IVF (in-vitro fertilization) protocols, medication doses and clinical outcomes compared to new patients seen in-person during the previous year, in an academic fertility practice. MATERIALS AND METHODS: This is a retrospective cohort study, in a university-based fertility clinic. All new patients seen via telemedicine between March 11, 2020, and March 10, 2021, were compared with all new patients seen in person between March 11, 2019, and March 10, 2020. Statistical analysis included t-test, Fisher exact test and Pearson chi square. The primary outcome was clinical pregnancy rate. Secondary outcomes included protocol type, dosage of Gonadotropins, duration of stimulation, type of trigger medication (HCG vs. GnRH- agonist), number of oocytes retrieved, fresh embryo transfer rate, “freeze all” rate due to OHSS reduction and implantation rate. RESULTS: The study included 715 new patient in the fertility clinic;365 patients seen in person (March 11, 2019 - March 10, 2020), and 350 patients seen via telemedicine (March 11, 2020 - March 10, 2021). The following were similar between the Covid year and the previous year: Female age (35.9±5.06 vs. 36.4±4.9, P=0.21), number of oocytes retrieved at the first IVF cycle (12.8±9.0 vs. 12.77±8.5, P=0.92), and stage of embryo transferred (cleavage stage 66 (41.3%) Vs. 86 (47.3%) and Blastocyts 94 (58.7%) vs. 96 (52.7%) P=0.27). There were more cases of male factor infertility and less cases of unexplained infertility in Covid year compared to the previous year (29% vs. 19%, P=0.001 and 9% vs. 16%, P=0.003 respectively), however, there was no difference in other diagnoses made at new-patient visit. There were no differences between the groups in the following outcomes: type of protocol (P=0.41), FSH dosage (P=0.25), number of days of stimulation (P=0.10), maximal estradiol value (P=0.97) type of trigger medication (Hcg 227 (72.8%) vs. 266 (74.9%), P=0.38 Agonist 86 (27.2%) vs. 89 (25.1%), P=0.3), and fresh embryo transfer rate (47.7% vs. 51.2%, P=0.36). There were less cases of “freeze all” to reduce OHSS risk in the Covid year (3.1% vs. 13.4%, P<0.0001). There was no difference between the groups in the clinical pregnancy rates (35.3% vs. 36.3%, P=0.91) and implantation rates (29.2% vs. 32.7%, P=0.42). CONCLUSIONS: New patients seen in person and those evaluated via telemedicine are likely to receive similar treatment protocols, medication doses and are likely to have similar duration of stimulation. IVF outcomes are not affected by telemedicine consultation, either. IMPACT STATEMENT: Telemedicine consultation for new-patient visits is feasible in an academic fertility practice for IVF treatment and may be particularly useful during the pandemic.

BILATERAL PLEURAL EFFUSIONS WITHOUT SIGNIFICANT ASCITES IN AN OVARIAN HYPERSTIMULATION PATIENT RECOVERED FROM COVID-19: A CASE REPORT

OBJECTIVE: To describe a patient who developed severe ovarian hyperstimulation syndrome (OHSS) with uncharacteristic features after recent COVID-19 infection. MATERIALS AND METHODS: A patient with prior mild COVID-19 developed an atypical case of OHSS with significant bilateral pleural effusions requiring bilateral thoracentesis and only minimal abdominal ascites. Isolated pleural effusions without significant ascites in not frequently found in patients with OHSS, with only one case with an effusion requiring a thoracentesis in 771 patients in a 1995 Canadian study. COVID-19 is known to cause inflammatory responses in the lung, however, pleural effusions are a rare symptom and usually only in those with severe disease. Long-standing damage from COVID-19, or ''post-COVID conditions'' is still under active investigation but can occur in patients even with mild disease. RESULTS: A 25yo G0 (BMI 27, AMH 9) without significant past medical or surgical history underwent IVF due to male factor infertility and polycystic ovarian syndrome (PCOS). She was diagnosed with COVID-19 5 weeks prior to stimulation and reported a mild course not requiring hospitalization. She underwent a long agonist protocol with a peak E2 of 6700 on day of HCG trigger (5000u) and had 42 oocytes retrieved. On POD #3, she presented with abdominal pain with distension and shortness of breath. A therapeutic paracentesis was performed with 500 ml drained and minimal improvement of symptoms. Due to significant response, she had a freeze all embryo cycle. On POD #5, she had worsening shortness of breath and underwent a CT pulmonary embolism (PE) protocol which did not demonstrate a PE but did show significant bilateral pleural effusions without abdominal ascites. She then underwent a bilateral thoracentesis with 800 ml drained from left lung and 1000 ml drained from right lung. She had significant improvement and returned to baseline after two days. CONCLUSIONS: OHSS is an uncommon side effect of gonadotropin stimulation, but this patient had multiple risk factors including age, PCOS diagnosis, AMH level, peak E2 level and number of oocytes retrieved. Ascites typically appears before pleural effusions. We postulate that the recent COVID-19 infection may have increased fluid accumulation preferentially to the lungs rather than the abdomen. IMPACT STATEMENT: With the ever increasing knowledge of post- COVID conditions, one must consider its potential long-term sequalae. Unexpected or atypical presentations may be due to COVID-19. The physiologic changes that occur with fertility treatment may be exacerbated by recent, even mild, COVID-19 illness.