Point-of-Care Testing in Primary Care

Point-of-care testing (POCT) in pediatric primary care is essential for clinicians to make a timely and accurate diagnosis. The COVID-19 pandemic has highlighted the importance of timely and accurate testing strategies to correctly identify the etiology of upper and lower respiratory infections. Additionally, pediatric POCT continues to be important in rural and underserved communities where access to hospital laboratories may be less available. This chapter will focus on seven rapid tests: Group A streptococcus (GAS), influenza A & B, SARS-CoV-2 (COVID-19), human immunodeficiency virus (HIV), C-reactive protein (CRP), human chorionic gonadotropin (hCG), and hemoglobin A1c (HbA1c). © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Successful hysteroscopic management of two cases of interstitial pregnancy

Introduction. Interstitial pregnancy (IP) is the rarest type of tubal pregnancy with a high rupture rate and often remains asymptomatic in the first 10-12 gestational weeks. Therefore, the timing of the diagnosis is crucial for successful management. Case report. Two patients, aged 28 and 22, were diagnosed with IP using transvaginal ultrasound. Both patients were asymptomatic, with initial serum betahCG of 6,664 mIU/mL and 4,641 mIU/mL, respectively. Since they refused treatment with methotrexate and wanted to preserve their fertility, we performed operative hysteroscopy with resection and evacuation of the gestational tissue. The procedures were uneventful. The betahCG levels dropped significantly, and the patients were discharged after three and four hospital days, respectively. Conclusion. Using hysteroscopic procedures, we successfully treated two asymptomatic patients with IP of gestational age < 10 weeks by ultrasonography and levels of serum betahCG < 7,000 mIU/mL. With the occurrence of IP but also the numerous advantages of hysteroscopy, large, multicenter studies are necessary to further investigate the place of this approach as a single treatment method for IP. Trends and consequences observed during the COVID-19 pandemic correlate with the importance of timely diagnosis of ectopic pregnancies, the benefits of a minimally invasive approach in their treatment, and epidemiologically justified shorter hospital stays.Copyright © 2023 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Sarcomatoid urothelial carcinoma accompanied by elevated serum beta-HCG: Two case reports

Sarcomatoid urothelial carcinoma is a rare and aggressive variant. Serum beta-hCG levels are used as a tumor marker in gestational trophoblastic diseases and germ cell tumors, but may also be elevated in high-grade bladder cancers. Here, we report two urothelial carcinoma cases with sarcomatoid differentiation that relapsed early after surgery with elevated serum beta-hCG levels. The first case was a 65-year-old female and the second case was a 67-year-old man with sarcomatoid urothelial carcinoma located in the ureter and renal pelvicalyceal system, both of them relapsed with elevated beta-hCG serum level to 146.8 mIU/ mL and 242 mIU/mL, respectively. They died a few months after initial diagnosis;4.9 and 2.5 months respectively. Both sarcomatoid variant and beta-hCG expression were associated with poor prognosis and advanced stage. However, beta-hCG is not used as a tumor marker in urinary tract cancers yet, and its relationship with variant pathologies has not been clarified. We need multi-centered studies to reveal this relationship.Copyright © 2023, Derman Medical Publishing. All rights reserved.

The Effect of COVID-19 on the Human Reproductive System: A Review Study

Background: Evidence reveals that COVID-19, in addition to impacting the respiratory system, affects other organs, including the male and female reproductive systems. The purpose of this study was to examine the impact of COVID-19 on the human reproductive system. Method(s): Data were collected in SID, Science Direct, PubMed, and Google Scholar databases. The Keywords including COVID- 19, reproductive system, fertility, and factors related to mesh term utilization and Boolean strategy were used. Papers from 2019 to 2022 were extracted. Finally, out of 58 searched articles, 20 articles related to the purpose of the study were reviewed. Result(s): The results were organized into two categories. The first category deals with the effect of COVID-19 on the female reproductive system including Sleep disorders following quarantine on gonadotropin release and its effect on the ovaries and menstrual cycle, preterm delivery, increased cesarean delivery, the possibility of intrauterine infection of the fetus and dysfunction of the reproductive glands. The second category concerns the effect of COVID-19 on the male reproductive system including abnormal semen quality, possible effect on gonocyte differentiation in the early stages of spermatogenesis, negative effect on spermatogenesis, testicular dysfunction, and changes in testosterone concentration by increasing serum LH, testicular inflammation, decreased sperm concentration in semen, impaired sperm motility, dysfunction of the reproductive glands, significant damage to the seminiferous tube, swelling of Sertoli cells, decreased Leydig cells, significant disorder on semen volume and impaired sperm morphology. Conclusion(s): The findings revealed that COVID-19 has an impact on various aspects of the human reproductive system. Midwives and gynecologists should alleviate couples' fears about infertility by recognizing these cases and offering suitable counseling to couples infected with COVID-19.

Increased use of 6-monthly gonadotropin-releasing hormone agonist therapy for prostate cancer: a capacity and cost-minimization analysis for England.

AIMS: The National Health Service (NHS) in England is facing extreme capacity pressures. The backbone of prostate cancer care is gonadotropin-releasing hormone agonist (GnRHa) therapy, commonly administered every month or 3 months. We estimated the cost and capacity savings associated with increased use of 6-monthly GnRHa therapy in England. METHODS: A capacity and cost-minimization model including a societal perspective was developed (in Microsoft Excel) to generate cost and capacity estimates for GnRHa drug acquisition and administration for "Current practice" and for a "Base case" scenario. In the "Base case" scenario, 50% of patients who were receiving monthly or 3-monthly GnRHa therapy in "Current practice" switched/transitioned to a 6-monthly formulation. Cost/capacity estimates were calculated per patient per administration and scaled to annualized population levels. Sensitivity analyses were conducted to assess the impact of individual model assumptions: 1 tested the impact of drug acquisition costs; 2 and 3 tested the level of nurse grade and the time associated with treatment administration, respectively; 4 tested the rate of switch/transition to 6-monthly GnRHa therapy; and 5 tested differing diagnostic patterns following the coronavirus disease 2019 pandemic. RESULTS: Compared with "Current practice", the "Base case" scenario was associated with annual cost savings of £5,164,296 (148,478 fewer appointments/year and 37,119 fewer appointment-hours/year). The largest savings were in drug administration (£2.2 million) and acquisition (£1.6 million) costs. Annual societal cost savings totaled £1.4 million, mainly in reduced appointment-related travel, productivity and leisure time opportunity losses. Increased use of 6-monthly versus monthly or 3-monthly GnRHa therapy consistently achieved system-wide annual cost and capacity savings across all sensitivity analysis scenarios. CONCLUSIONS: Our holistic model suggests that switching/transitioning men from monthly or 3- monthly GnRHa therapy to a 6-monthly formulation can reduce NHS cost and capacity pressures and the societal and environmental costs associated with prostate cancer care.

Men with prostate cancer often receive hormone injections to slow their cancer progression and relieve their symptoms. In England, most men who are prescribed hormone injections receive them once every month or 3 months; however, a 6-monthly option would reduce the number of injection appointments required each year. If some men who are receiving hormone injections every month or every 3 months switched to treatment once every 6 months, it could reduce the impact of prostate cancer treatment on their lives. It might also reduce the demands of prostate cancer treatment on the National Health Service (NHS). We developed a computer-based model to assess how NHS costs and nursing would be affected if half of the men in England who are receiving hormone injections every month or 3 months switched to injections every 6 months. According to our model, this change could save the NHS about £5.2 million each year. The main cost savings would be in reduced nursing costs. The change would also benefit the NHS because nurses would have almost 150,000 fewer injections to give, meaning that they could spend their time providing care elsewhere. Given that men would have to attend fewer appointments, they would also benefit from reduced time traveling, which would benefit the environment as well. Overall, these benefits to society would contribute about £1.4 million of savings per year. Given how stretched the NHS is in England, particularly after the COVID-19 pandemic, opportunities to reduce time and staffing pressures are very important.

GONADOTROPIN AND SEX STEROID HORMONES IN MALES WITH POST COVID-19 INFECTION.

OBJECTIVE: The aim: To understand the effects of COVID-19 infection on gonadotropins and sex steroid hormones in males. PATIENTS AND METHODS: Materials and methods: This is a cohort study conducted in fifty males, who had been previously infected with COVID-19 with normal hormonal profile. Fifty Iraqi males were attending the male clinic at Higher Institute of Infertility Diagnosis and Assisted Reproductive Technologies, diagnosed with standard methods. The assessment of serum hormonal levels including (FSH, LH, Prolactin and Testosterone) was done 3 times: 1st time after one-month post recovery after COVID-19, 2nd time after 2 months post recovery and 3rd time - after 3 months post recovery. RESULTS: Results: There was no significant change in the mean level of serum FSH during the first, second and third months (p = 0.630). LH serum level was highly significantly reduced during follow up (p< 0.001). Serum prolactin level, reduced significantly during follow up (p< 0.001). Serum testosterone level was the lowest in the first month and increased during the second month and then during the third month in a highly significant manner (p< 0.001). CONCLUSION: Conclusions: Sub-clinical hypogonadism may be suspected as a consequence of COVID-19 infection in males as its first presentation characterized by increased LH & decreased testosterone production.

Misdiagnosis of intramural ectopic pregnancy and invasive gestational trophoblastic disease on ultrasound: A challenging case at Tu Du Hospital in Vietnam in COVID-19 pandemic peak and mini-review of literature.

Differentiation between intramural ectopic pregnancy and molar ectopic pregnancy is very difficult because of their exceptional rarity. Herein, we present a misdiagnosed case of intramural pregnancy and invasive trophoblastic disease on ultrasound. A 45-year-old female patient was admitted to our tertiary referral hospital due to abdominal pain and unusual ultrasonography findings. Initially, a diagnosis of intramural ectopic pregnancy was identified based on transvaginal color Doppler ultrasonography, 3-dimensional ultrasound, and serial serum beta-human chorionic gonadotropin, thus the patient underwent laparotomy with hysterectomy. However, the histopathological endpoint showed an invasive trophoblastic disease. Clinically, this pathology should be included in the differential diagnosis of intramural ectopic pregnancy since an imaging scan remains quite unclear.

HEMOPTYSIS AS PRIMARY MANIFESTATION IN A WOMAN WITH CHORIOCARCINOMA WITH PULMONARY METASTASIS

SESSION TITLE: Systemic Diseases Causing Pulmonary Havoc SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Choriocarcinoma is the most common type of gestational trophoblastic neoplasm (GTN) and can occur in association with any pregnancy [1]. The main risk factors are advanced or very young maternal age, ethnicity, ectopic pregnancy, abortion, and prior molar pregnancy. The most common sites of choriocarcinoma metastasis are lungs, liver, and brain [2]. This case describes a patient with choriocarcinoma that presented with hemoptysis. CASE PRESENTATION: The patient is a 22 year-old G2P1 female presenting at 36 weeks-gestation with one week of hemoptysis. She denied any other symptoms. On presentation, she was tachycardic. Physical examination demonstrated bibasilar crackles. Admission chest x-ray revealed diffuse bilateral infiltrates (Fig 1). Hs-troponin was elevated to 144 ng/L;however, EKG did not show ischemic changes. Cultures were obtained prior to empirically initiating antibiotics. Despite antibiotic treatment, hemoptysis worsened over her course and oxygen requirements increased. Infectious workup was negative. CT obtained for pulmonary embolism revealed bilateral patchy airspace opacities in lungs, suspected due to multifocal pneumonia (Fig 2). AFB smear and quantiferon were negative. After an emergent C-section for increased oxygen requirements, bronchoscopy with BAL was obtained and demonstrated diffuse alveolar hemorrhage. BAL was only positive for mildly increased CD4:CD8 ratio. Transbronchial biopsy was aborted due to bleed risk. Subsequent right lobe wedge biopsy confirmed metastatic choriocarcinoma. Her serum human chorionic gonadotropin (ß-hCG) level was found to be 20,713 milli-international units/mL. DISCUSSION: The etiology of hemoptysis was initially thought to be secondary to pneumonia. Differential diagnoses also included an acute COVID infection, alveolar hemorrhage, tuberculosis in a recently-immigrated patient, myocarditis, autoimmune etiology, and malignancy. Patient's risk factors included a prior miscarriage. Rarely, bleeding can occur as a result of metastatic lesions and may result in abdominal pain, hemoptysis, melena, or evidence of increased intracranial pressure from intracerebral hemorrhage [2]. Patients, such as the one described in this case, can exhibit pulmonary symptoms of dyspnea, cough, and chest pain caused by lung metastases. Upon closer examination of the CT scans, several of the opacities are nodular and consistent with GTN. Patients treated with surgery, chemotherapy, or a combination of both demonstrated similar treatment outcomes;chemotherapy may still be the preferred option. The overall cure rate in treating these tumors is currently > 90% [2]. CONCLUSIONS: GTN, although rare, should be considered as a differential diagnosis in women with a pregnancy history and risk factors that present with the primary symptom of hemoptysis. High index of suspicion and awareness of these neoplasms are necessary for timely diagnosis. Reference #1: Savage P. Winter M. Parker V. et al. Demographics, natural history and treatment outcomes of non-molar gestational choriocarcinoma: a UK population study. BJOG. 2020;127: 1102-1107 Reference #2: Lurain, J., 2010. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. American Journal of Obstetrics and Gynecology, 203(6), pp.531-539. DISCLOSURES: No relevant relationships by Crystal Ajja No relevant relationships by Heba Osman No relevant relationships by James Rowley

A Case of Autosarcophagy in a Pediatric Patient With Depression

BACKGROUND: Self-mutilating behavior in the pediatric population is associated with psychiatric and psychosocial factors. Autosarcophagy, or self-cannibalism, is an extremely rare form of self-mutilation and is predominantly seen with psychosis or substance use.1 We report a case of oral autosarcophagy in a pediatric patient in the absence of substance use or psychosis. OBJECTIVE: To learn about autosarcophagy and its treatment in the pediatric population and to explore other neuropsychiatric disorders in which it is a predominant manifestation. METHODS: Review of a case using electronic medical records and relevant literature. Key terms: 'autosarcophagy,' 'body focused repetitive behavior,' 'oral self injury,' 'pediatric self-mutilation' using Medscape and Google Scholar. RESULTS: We present a 14-year-old female with history of seizure disorder in full remission, depression, self-cutting behavior, and suicidal ideation with 2 psychiatric hospitalizations, who presented to the pediatric emergency department with oral bleeding after eating one-third of her tongue over the course of a month. Evaluation was notable for poverty of speech and constricted affect. Patient stated she was 'trying to remove an infection' and alleviate discomfort. She denied that this behavior was an attempt to end her life but endorsed past suicidal ideations and cutting behavior. History revealed emergency room evaluation for aggressive behavior and episodes of volitional enuresis. We diagnosed major depressive disorder, recurrent episode in remission without psychosis. Drug screen, complete blood count, complete metabolic panel, COVID-19, urinalysis, thyroid-stimulating hormone, head computed tomography, and beta-human chorionic gonadotropin were negative. Patient continued home oral medications aripiprazole 10 mg daily, fluoxetine 30 mg daily, and levetiracetam 500 mg twice daily and was discharged the next day. CONCLUSIONS: Self-harm is observed in 17.2% of adolescents, 13.4% of young adults, and 5.5% of older adults.2 Cases of self-mutilation in pediatric patients typically present as cutting, burning, or head banging.3 Our differential diagnoses include borderline personality disorder due to repeated impulsivity and self-harm, and body focused repetitive behavior disorder (obsessive-compulsive disorder-related disorder), which presents with repetitive strain injuries and dental malocclusions. Treatment of self-mutilation involves treating the underlying psychiatric condition with psychotropic medications.4,5 In pediatric patients, dialectical behavioral therapy has been shown to reduce parasuicidal behaviors after 1 year of therapy.6 Our patient, under constant 24-hour observation, was cleared by medical, psychiatric, and dental teams. The patient followed up with outpatient psychotherapy and psychiatry. We are presenting this rare case for clinicians to identify and manage pediatric patients presenting with unique forms of self-harm tendencies.

Barriers to Telemedicine for First-Trimester Medical Abortion Provision in Canada in 2019

Objectives: In 2017, mifepristone became available for first trimester medical abortion (FTMA) in Canada. Shortly after, regulations permitted pharmacies to dispense mifepristone to patients, facilitating telemedicine provision. Our objective was to explore the barriers to providing FTMA using telemedicine in Canada in 2019. Methods: We conducted a cross-sectional, national, self-administered, anonymized survey of physicians and nurse practitioners who provided abortion care in Canada in 2019. Online invitations were sent through professional health organizations using a modified Dillman technique to optimize recruitment. Questions elicited provider demographics and perceived barriers to offering telemedicine FTMA. We used R software for descriptive statistics. Results: Four hundred sixty-five clinicians were included for analyses, of which 388 reported providing FTMA. Among those, 44.0% reported using telemedicine (for consultations, while often obtaining testing) for FTMA. British Columbia respondents reported the highest proportion of telemedicine use at 63.8%;the lowest was in Québec (10.7%). The majority of FTMA respondents (77.7%) reported barriers to telemedicine. The most common barriers were inability to confirm gestational age with ultrasound (43.0%), and lack of provincial fee code to pay practitioners (30.2%), timely access to serum hCG testing (24.6%), and nearby emergency services (23.3%). Few reported facility regulations (8.9%) and provincial regulations (4.9%) as barriers to providing telemedicine-based care;provincial regulation barriers were most common in Québec (16.1%). Conclusions: Less than half of respondents reported providing some abortion care via telemedicine and the majority perceived barriers. Low-test medical abortion protocols developed during COVID-19 have the potential to overcome some barriers. Keywords: telemedicine;abortion, induced;surveys and questionnaires;Canada;delivery of health care;mifepristone

Socio-economic Barriers to Care and Medical Complexity Leading to a 5-year Diagnostic Delay of Untreated Chronic Diabetes Insipidus and Rapidly Progressive Puberty in a 10-year-old Venezuelan Immigrant

Introduction: Germ cell tumors, including germinomas, account for 10% of pediatric chronic Diabetes Insipidus (DI) cases. Delays in diagnosis of germinomas are generally longer than six months, however, no reported cases of suprasellar germinomas causing chronic DI and precocious puberty have been known to exceed a 5-year delay in both treatment of DI symptoms and a definitive diagnosis. Case Description: A 10-year-old Hispanic male presented with a 5-year history of polydipsia and polyuria. He underwent evaluation in Venezuela, where DI was reportedly 'ruled out';however, no head MRI was performed. After two years in the US struggling to acquire insurance, he presented to his pediatrician with worsening symptoms. A head MRI, ordered to evaluate dilute high-volume urine output, revealed a suprasellar mass. He was admitted for diagnostic evaluation and met the criteria for DI. Notably, he had an elevated Beta-Human Chorionic Gonadotropin (B-HCG) level. Biopsy confirmed the diagnosis of a Central Nervous System (CNS) germinoma. He was treated with DDAVP and proton therapy with subsequent remission of his tumor. Discussion: Throughout the patient's disease course, there were multiple delays in seeking and receiving care. These include a 5-year delay in seeking care despite worsening symptoms, a one-month delay in completing a 24-hour urine collection, a one-month delay in consulting pediatric nephrology, and another month delay before completing a retroperitoneal ultrasound. Multiple medical and socio-economic factors led to these delays. The patient did not present with symptoms more typical of CNS Germinomas like headaches, nausea, and vomiting. He had no visual disturbances despite mass effect on his optic chiasm. His increased stretched penis length and Tanner staging, which were identified later in his disease course, were contradicted by his pre-pubertal testicular volume and bone age. The patient is from a Spanishspeaking/Limited English Proficiency (SSLEP) household. While Spanish interpreters were present at each appointment, the language barrier proved to be a consistent issue. Initially, the child's mother indicated that the diagnosis of DI was 'ruled out' in Venezuela. In reality, the recommended imaging was never performed. Mychart messages left by his father further highlighted communication difficulties. Without access to an interpreter, he was forced to use broken English to relay his concerns. These frantic messages indicated misunderstandings regarding scheduling with various services and completing vital labs. Care only proceeded after significant physician intervention. Poverty in Venezuela, lack of insurance, and anxiety regarding COVID-19 also contributed to these delays. Conclusion: To our knowledge, this is the first case report of a pediatric patient presenting with a 5-year history of untreated polyuria and polydipsia due to undiagnosed DI with a B-HCG secreting CNS germinoma, without spinal metastasis. This study also illustrates the importance of supporting SSLEP families as they grapple with the complicated process of navigating our healthcare system. Sagittal T1 post gadolinium contrast image (A) and axial T2 FLAIR image (B) show an enigmatic, homogeneous, briskly enhancing mass in the suprasellar cistern (red arrow) with mass effect on the optic chiasm which is displaced upward and anteriorly (green arrow).

Dilemma on Indonesian adult with micropenis during COVID-19 pandemic: A case report and review article.

Background: Micropenis usually has a series of causative factors that must be identified to determine the treatment modality. Case presentation: A 24-years-old Indonesian male complained of a small penis since infancy. The patient has a short penis size (3 cm), no pubic hair, small scrotum, both testes cannot hide palpable, and tanner scale 2. The hormonal examination includes testosterone hormone of 14.94 ng/dL, luteinizing hormone of 14.89 mUI/mL, and follicle-stimulating hormone of 67.51 mUI/mL. Ultrasound showed no testicular location and only a prostate-like appearance of a size of 0.6 × 2.07 cm on the abdomen. The patient will receive therapy but was constrained by the COVID-19 pandemic. Discussion: diagnosis of micropenis and gonadotropin hormone disorders must be detected early and receive treatment immediately for better results. Conclusion: Micropenis is a medical diagnosis that depends on proper examination and management, and early diagnosis is essential to improve prognosis.

Effect of hydroxychloroquine on an overactive endometrial immune profile: A Pilot Case Study

Problem: A37 y.o, P1+1 presented with a 1.5 year Hx of secondary infertility. Initial ovulation induction with clomifene citrate was unsuccessful, followed by a single IUI attempt with gonadotropin stimulation. The couple progressed to IVF treatment with 3 failed embryo transfers. There were no endocrinological abnormalities, endometrial/ uterine anatomy was normal on transvaginal USS and saline infusion sonograpy, so an Endometrial Immune Profile(EIP) and Receptivity Array(ERA) were performed prior to further treatment. ERA was in the receptive range, and EIP demonstrated an overactive profile with high IL15:Fn14, suggestive of NK overactivation. In the absence of other pathology this was hypothesised as a potential cause for implantation failure. Immunotherapy options were discussed, including IVIG and adalumimab. Risks of these during the Covid pandemic resulted in the decision to try oral hydroxychloroquine, with cost benefits and potentially less adverse side effects. Unfortunately there is a paucity of published data and outcomes, but proposed benefits of this treatment were based on demonstration of improvemed serum TH1:TH2 cytokine ratios (reduction in TNFa and increase in IL:10), and demonstration of a reduction in miscarriage rate. Method of Treatment: Hydroxycholoroquine 200mgPOBD was commenced 6 weeks prior to commencing treatment, followed by a frozen transfer of a single blastocyst (5AA). Unfortunately this transfer after 8/52 treatment was unsuccessful. A repeat cycle was scheduled after a further 8 weeks, continuing the hydroxychloroquine for >3 months. Initial hCG 13 days post transfer was 2934, but the patient presented with sudden PV bleeding after 6 days, follow up hCG was only 3650. Transvaginal USS demonstrated a collapsed intrauterine gestation sac in keeping with a non-viable pregnancy. Onward referral to an Early Pregnancy unit for follow up confirmed a miscarriage. PGS was not incorporated into the cycles to assess for embryo aneuploidy. Results: Overall the implantation rate had increased from 0 (0/3) to 50% (1/2), but due to sample size this was not statistically significant (p = 0.81). Pregnancy rate per embryo transfer also increased form 0/3 to 1/2, but again was not significant because of low numbers. Due to the failure to achieve an ongoing pregnancy, a repeat biopsy was performed while using hydroxychloroquine to assess its effects on the endometrial immunological environment. This showed a normalisation of the IL15:Fn14 ratio (5.680 to 0.831), but with a slight elevation in the IL18:Tweak ratio (0.088 to 0.114).CD56 remained in the normal range (0.993 to 1.344). Conclusion: Although prescribed for inconsistent indications, there is little published data on hydroxychloroquine use for adverse reproductive outcome. This case report demonstrates the effect of oral hydroxychloroquine therapy on an overactive endometrial profile, leading to a major reduction in IL15:Fn4 ratio, suggesting a potential role in reducing uNK cytotoxicity. Anecdotally a 3 month course is recommended prior to transfer, which would be supported by these events. Unfortunately there is limited ability to make treatment recommendations based on a single sample, however, the findings suggest that a larger study to explore if this pattern is reproducible would have important clinical value.

LOCKDOWN UPTICK: DID THE SARS-COV-2 PANDEMIC GENERATE AN INCREASE IN PLANNED OOCYTE CRYOPRESERVATION (POC)?

OBJECTIVE: The rise of the SARS-CoV-2 pandemic and temporary closures of fertility centers made the effect on POC cycles uncertain but garnered national attention1,2. We sought to assess the impact of the pandemic on POC cycles in a pandemic epicenter. MATERIALS AND METHODS: This is a retrospective cohort study of all POC cycles at an academic fertility center in New York City from 1/1/2019- 12/31/2020. Primary outcomes were number of POC patients (pts) and cycles. Secondary outcomes were pt relationship status, payment method, AMH, and cycle parameters;with subgroup analyses by age groups. We also examined the relationship between monthly number of POC cycles and national SaRS-CoV-2 cases. Statistical analyses included z-score analysis, Mann-Whitney, and Chi-squared, with p<0.05 significant. RESULTS: Despite a 5.5 week center closure in 2020, POC pts increased 14% and POC cycles increased 16% from 2019 to 2020 (Table), with a 32% increase seen between June-Dec, 2020 . There was a 28% increase in POC pts <37yo in 2020 (252 pts vs. 323 pts, p<0.04) and no change in pts >37yo in 2020 (p=0.9). Relationship status did not differ between years (16% partnered, 76% single, 8% unknown in 2019 vs. 16% partnered, 73% single, 11% unknown in 2020;p=0.6). Fewer patients in 2020 had insurance coverage (16% vs. 24%, p<0.001). AMH was higher in 2020 (2.3 vs. 2.1, p<0.03), but days of stimulation, oocytes retrieved, oocytes frozen, total gonadotropins, and maximum estradiol (E2) were not different (Table). While national SARS-CoV-2 cases peaked in April, July, and November 2020, monthly POC cycles at our center did not decrease with surges in SARS-CoV-2 after our center reopened in May (p=0.24). In 2020 there were 23 cycles cancelled, none due a positive SARS-CoV-2 test. CONCLUSIONS: POC volume increased at our center in 2020, especially in young patients, despite center closures and SARS-CoV-2 surges. IMPACT STATEMENT: More young people pursued POC despite the SARS-CoV-2 pandemic. Further research is needed to understand POC pt motivations and experiences during a pandemic. (Table Presented).

DOES ZYMOT SPERM SEPARATION IMPROVE EM- BRYO DEVELOPMENT OUTCOMES WHEN APPLIED TO ALL INFERTILITY PATIENTS COMPARED TO DENSITY GRADIENT WASHING OR SURGICALLYATTAINED SPERM?

OBJECTIVE: The ZyMot sperm separation device has proven favorable for use in elevated DNA fragmentation index (DFI) male factor patients, as an alternative to density gradient (DG) washing or surgically attained testicular sperm. In 2020, without fully understanding the infectivity and transmission potential of SARS-CoV2 in semen, a more liberal application of a timed ZyMot microfluidic swim-up was applied to our IVF patients to dilute out and minimize potential pathogens. This study aimed to evaluate whether the use of ZyMot sperm improved normal embryo development. MATERIALS AND METHODS: Retrospective analysis of PGT-A/ICSI cycles (N= 3219) between 2016-2020 was conducted to assessed fertilization rates (FR), blastocyst development/utilization rates (BUR) and genetic outcomes. Sperm preparations were performed per standard operating or manufacturer advised (i.e., ZyMot) procedures. Cumulus oocyte complexes were harvested 36h post-hCG, stripped and ICSI performed 3-5hr later. Zygotes were assessed at 16-18hr post-ICSI, and embryos cultured under humidified tri-gas incubation for up to 7 days. Blastocyst (BL) development as evaluated, and expanded BL or greater were biopsied on Days 5, 6 or 7. All BL were vitrified and genetics determinations for euploidy, aneuploidy and mosaicism were contrast. Applying Chi-squared analysis, we compared potential differences (p<0.05) between oocytes inseminated by DG wash (n=23,549), ZyMot wash (n=7,331) or testicular sperm (n=815). RESULTS: No difference in FR (76%), D5 BL formation (52-56%) or BUR (52-53%) was detected between DG and ZyMot washed sperm, respectively. Meanwhile, testicular sperm had a lower FR (70%;p<0.05), fewer BL forming on D5 (48%;p<0.05) and a lower overall BUR (41%;p<0.05). In addition, fewer testicular-derived BL were euploid (39%;p<0.05) with more aneuploidy (54%;p<0.05) than DG wash (50%, 39%;respectively) or ZyMot swim-up (45%, 37%;respectively) derived-embryos. No difference in potentially viable BL (Euploidy+Mosiac outcome) was observed between DG or ZyMot wash groups (63-64%). CONCLUSIONS: Application of the ZyMot device in the general IVF population offered no benefit to embryo development outcomes compared to standard sperm wash procedures. Our data does support that microfluidic separation of sperm using ZyMot for male factor patients with elevated DFI is a more favorable and cost-effective approach to surgically attaining testicular sperm when ejaculated sperm is possible. However, when insufficient motile and or morphologically normal sperm are available in an ejaculate further analysis is needed to elucidate the benefit of testicular biopsy treatment, as our assessments in this study may be biased by including men with non-obstructive azoospermia. IMPACT STATEMENT: The timed selection of morphologically normal, highly progressive sperm by ICSI, PVP-swim-out likely mimics the potential benefits the ZyMot device may offer infertile men with elevated sperm DNA fragmentation generating similar blastocyst development and euploidy outcomes.

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).

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.

Panhypopituitarism Induced by COVID-19 Infection

Introduction: Coronavirus disease 2019 (COVID-19) infection has led to multiple endocrinopathies. We present a case of panhypopituitarism induced by COVID -19 infection. Case Description: 76 yo male with history of type 2 diabetes, hypertension, and 1.5 cm stable, nonfunctioning, pituitary macroadenoma diagnosed in 2017 had multiple admissions for altered mental status and hyponatremia following COVID-19 infection in April 2020. Workup revealed low free T4 0.60 ng/dL (0.8-1.8), low random cortisol 1.8 mcg/dL(2.9-19.4), high prolactin 33.5 ng/mL (2-18), low total testosterone < 10 ng/dl (175-781), SHBG 32.7 nmol/L (13.3-89.5), and low gonadotropins. While hospitalized, he was diagnosed with pan-hypopituitarism and started on glucocorticoids and levothyroxine. Repeat MRI pituitary done after discharge, documented stability of the macroadenoma without hemorrhage. To date, the patient remains on glucocorticoid replacement and thyroid hormone replacement in stable state. Discussion: Hypopituitarism from any etiology has an incidence of 4.2 per 100,000. Hormone replacement therapy remains the mainstay of treatment. This case represents a patient who had unexplained recurrent hyponatremia after COVID-19 infection and later diagnosed with pan-hypopituitarism. Given the continued pandemic, more endocrinopathies related to the COVID-19 infection have been reported. We have data for other viral infections, such as SARS and Dengue, documenting pituitary dysfunction. Review of literature documents SARS infection leading to post infectious hypophysitis with resulting secondary hypocortisolism and hypothyroidism. The cause was thought to be virus binding to pituitary angiotensin-converting enzyme 2 (ACE2) receptors. There is also data supporting COVID-19 infection leading to pituitary apoplexy and hypophysitis, though the number of cases reported is limited. The pathophysiology is thought to be the COVID 19 virus binding to pituitary ACE2 receptors for which it has a 10-20-fold higher affinity. Furthermore, the hypothalamus also expresses ACE2 receptors making it a target for the virus. The binding leads to cellular destruction and autoimmune collateral damage. Hypothalamic pituitary dysfunction could be due to direct effect of virus. The virus can also lead to reversible hypophysitis.