Cancellation Rate Research Articles

P–281 Is it worth to go to blastocyst when there are less than 4 embryos on day 3?

Abstract Study question Are pregnancy rates similar with blastocyst transfer compared to D3 transfer for patient with a poor embryo yield. Summary answer In poor prognosis patients, more D3 embryos are needed to result in similar outcome compared to single blastocyst and it increases the multiple pregnancy risk. What is known already Good prognosis patients benefit from a blastocyst transfer rather than cleavage-stage embryo because day 3 morphology has limited predictive value for subsequent developmental. A Cochrane meta-analysis in 2016 found a higher live birth rate per transfer in the blastocyst group compared to cleavage-stage and no difference in miscarriage and multiple pregnancies. However, in unselected patients, studies have yielded conflicting results and especially in poor prognosis patients at risk of transfer cancellation. A threshold of four good embryos on the third day has been previously correlated with blastocyst yield and live birth rate compared with cleavage-stage embryo transfer. Study design, size, duration We analyzed the outcome of 1115 cycles with less than 4 embryos during 2019–2020 and compared the results between two groups of D3 and D5 transfers. Participants/materials, setting, methods Amongst 1115 study cycles, in 691 cycles a D3 transfer was performed and in 424 cycles a D5 transfer was performed. We compared transfer cancellation rates, mean number of transferred embryos and ongoing pregnancy rates between the two groups and also in subgroups with female age <37 and female age >37. The statistical analyses were done by Chi square and t-test for paired samples. Main results and the role of chance In the overall study population, the mean female age was 36.3 ± 4.3 years, the mean number of obtained embryos was 2.4 ± 1.0, the mean number of transferred embryos was 1.4 ± 0.8. 17.2% of the cycles resulted in transfer cancellation (6.2% in D3 transfer group and 35.0% in D5 transfer group). After D3 transfer the ongoing pregnancy rate (OPR) per transfer was 21.5% compared to 39.7% in D5 transfers (p < 0.05). A similar pattern was observed in subgroups of age <37 years and >37 years with OPR per transfer significantly higher when D5 transfer was performed. Notably more embryos were transferred on D3 compared to D5 (mean number 1.4 for D3 and 1 for D5). Nonetheless, OPR were similar per cycle in both groups and subgroups of different ages. Limitations, reasons for caution A prospective randomized controlled trial is needed to confirm these results that are consistent with previously reports on retrospective and observational studies. Wider implications of the findings: In poor prognosis patients with low embryo yield, D3 and D5 transfers result in similar OPR per cycle. Transferring at blastocyst stage is not inferior to D3, despite the high cancellation rate, and appears safer permitting a single embryo transfer to avoid multiple pregnancy. Trial registration number Not applicable

P–453 Fertility preservation in endometriosis: Impact of the ovarian endometriosis and it’s surgical treatment on oocyte yield

Abstract Study question Does a previous history of surgery for ovarian endometriosis (OMA) has an impact on controlled ovarian stimulation (COS) response in case of fertility preservation (FP) for endometriosis? Summary answer After COS, a prior history for OMA surgery was associated with poorer ovarian responsiveness compared to non-previously operated women. What is known already Endometriosis is a chronic disorder that affects 10% of woman, which can be responsible for infertility. The presence of OMA and/or it’s excision could induce a reduction of the ovarian reserve (ROR), and for some women, an increased risk of premature ovarian failure. Therefore, FP with oocyte/embryo vitrification can be proposed for OMA-affected women, considering the relationship between endometriosis, infertility and ROR. Although a complete surgery excision of endometriosis lesions may be appropriate for some patients to relieve them from pain, the more efficient time to preserve fertility is still unknown in the management of women presenting OMA lesions. Study design, size, duration We conducted an observational multicentric study from April 2015 to December 2019, in two tertiary care university hospitals. Women presenting OMA or having a previous history of surgery for OMA that had performed a FP with COS for oocytes/embryo vitrification during the study period were included. Diagnosis of endometriosis was based on published imaging criteria using transvaginal sonography and magnetic resonance imaging or histologically proven in women who had past surgery. Participants/materials, setting, methods A total of 165 women were allocated to two groups, according to the presence of a previous history of surgery for endometrioma(s). Main outcome measure was the total number of oocytes retrieved. Main results and the role of chance Fifty-one (30,9%) women were included in the group ‘previous history of surgery’ and 115 (69,1%) in the group ‘no history of surgery’. Mean age was 31,6±4,4 years and was not significantly different between groups (p = 0.09). However, women in ‘No previous surgery’ group had higher AMH levels than women in ‘previous surgery’ group (2.27±1.70ng/ml versus 1.56±1.89ng/ml; p < 0,001). In the group ‘previous history of surgery’, 21(41.2%) women had a recurrence of OMA(s) and 31 (60.8%) had at least one deep infiltrating endometriosis (DIE) lesion at FP. In the group ‘no history of surgery’, 92(80.7%) of the women had DIE. In addition, women in ‘No previous surgery group’ had larger OMA than women in ‘previous surgery’ group (mean diameter size: 5.56±4.34cm versus 3.25±2.16cm, respectively; p:0,03). The mean number of COS with oocyte-retrieval was significantly higher in the group ‘previous history of surgery’ (2.0±1.02 versus 1.65±0.82 in the group ‘no surgery’, p = 0.03), however, the total number of oocytes retrieved per women was significantly higher in women ‘history of surgery’, compared to women ‘no previous surgery’ (13.7±8.4 versus 10.3±7.5, p = 0.02). In addition, the cancellation rate per cycle was significantly lower in ‘No previous surgery’ group compared to the ‘previous surgery’ group (0.09±0.31 versus 0.28±0.53; p < 0.001). Limitations, reasons for caution No data concerning the thawing of oocytes/embryo are available for now. Wider implications of the findings: FP is an essential component to integrate in ovarian endometriosis-management and should be proposed before surgery to optimize oocyte yield. Trial registration number Not applicable

P–688 Assessment of ovarian vascularity by three-dimensional vaginal power Doppler on day two of menstrual cycle to predict the number of mature eggs collected

Abstract Study question Could ovarian vascularity indices, measured by 3-dimensional (3D) vaginal power Doppler, predict the number of mature oocytes collected after controlled ovarian stimulation? Summary answer Ovarian vascularity index (VI) may be an indicator of poor (<three mature eggs collected) and high (>ten mature eggs collected) ovarian responses to gonadotropins. What is known already Poor and/or hyper ovarian responses to gonadotropins may be related to cycle cancellation during controlled ovarian stimulation (COS). In this context, gonadotropin dose is often individualized using patient features that predict ovarian response (such as age, antral follicular count (AFC) and anti-Müllerian hormone (AMH)). In parallel, ovarian vascularity color doppler is a valuable evaluation method to predict the ovarian hyperstimulation syndrome and the growth/maturity of Graafian follicles. The aim of the present study is to estimate the utility of 3-dimensional vaginal power Doppler and ovarian vascular flow indices in the prediction of the number of mature occytes collected after COS. Study design, size, duration A prospective study was conducted on 200 couples undergoing intracytoplasmic sperm injection cycle at Al Hadi Laboratory and Medical center, Beirut, Lebanon. It was performed between January 2020 and July 2020. Couples were categorized into poor responders group (3 or less metaphase II (MII) eggs collected) (n = 43), high responders group (10 or more MII eggs collected) group (n = 66), and normal responders group (more than 3 and less than 10 MII eggs collected) (n = 66). Participants/materials, setting, methods On the second day of the menstrual cycle, ovarian volume and vascularity parameters (vascularity index (VI), flow index (FI), and vascularity flow index (VFI)) were measured using the 3D power Doppler and the Virtual Organ Computer-Aided Analysis. On the same day, the antral follicle count was evaluated and a blood sample for AMH testing was collected. Women included in the study have undergone COS using GnRH antagonist protocol. Main results and the role of chance Receiver operator characteristics (ROC) curve model was used to predict the number of mature eggs collected. 7 parameters were used to predict poor and high ovarian responses (Age, AMH, AFC, ovarian volume, VI, FI and VFI). Ovarian VI significantly predicted poor ovarian response to gonadotropins (p = 0.033 and area under the curve (AUC)=0.668). Subsequently, the cut off value was 0.0025 with 84% sensitivity and 83.3% specificity. In parallel, ovarian VI significantly predicted high ovarian response to gonadotropins (p = 0.036 and AUC (0.778)) with a cut off value 0.0375 and with 77.8% sensitivity and 78.3% specificity. Furthermore, VFI significantly predicted high ovarian response to gonadotropins (p = 0.045; AUC=0.677). Limitations, reasons for caution It will be necessary to perform a prospective analysis on a broad sample size to validate these findings. In addition, it will be interesting to assess the impact of ovarian vascularity on pregnancy outcomes. Wider implications of the findings: Assessing ovarian vascularity prior to ovarian stimulation can help reduce the rate of cycle cancellation. In addition, more studies are welcomed in the field to unravel the mechanisms behind altered ovarian vascularity and to test the possibility of restoring normal ovarian physiology. Trial registration number Not applicable

P–789 Obstetric and perinatal outcomes in poor ovarian responders and normal responders flowing fresh embryo transfer: a prospective, monocentric, observational study

Abstract Study question Whether women pregnant after a poor response in IVF have obstetric and perinatal complications more frequently than women with pregnancies after a normal response in IVF? Summary answer There were no statistically significant differences in obstetric and perinatal complications rate between poor responders and normal responders in Chinese women. What is known already Poor ovarian response usually indicates a reduction in follicular response, resulting in a reduced number of retrieved oocytes. Patients are less likely to conceive and have a higher risk of cycle cancellation and low clinical pregnancy rate. Whether poor ovarian response is associated with obstetric and perinatal complications is however debated. Study design, size, duration Design: Prospective, monocentric, observational study. Size: 1664 women with poor ovarian response and 1061 women with normal ovarian response duration : July 1, 2017 to Aug 15, 2019.Participants/materials, setting, methods: 1664 women with poor ovarian response and 1061 women with normal ovarian response undergoing IVF or ICSI were enrolled in this study. The primary outcome was obstetric and perinatal complications rate. Main results and the role of chance 1664 women with POR and 1061 women with NOR were enrolled in this study.Poor and normal responders did not have significantly different incidences in obstetric and perinatal complications(25.42% vs 25.45%), nor were there a significant difference in preeclampsia, gestational diabetes mellitus, postpartum hemorrhage or abruptio placentae. But POR group have a lower frequency of twin pregnancies(8.47% vs 28.66%,P<0.01),low birth weight(5.08% vs 14.23%,P<0.01)and prematurity (9.32% vs 17.03%,P<0.01). Limitations, reasons for caution Despite its size, an observational study such as this has a number of inherent limitations, and the best way to confirm its findings will be to compare obstetric and perinatal outcomes in different subgroup of pregnancies following ART in an adequately powered randomized, controlled trial. Wider implications of the findings: This prospective, monocentric, observational study suggests that women with poor ovarian response did not have higher perinatal complication rate than women with normal ovarian response. Oocyte quality and quantity may not affect the rate of perinatal complications. Trial registration number Not applicable

P–552 Delayed blastocyst development is associated with a higher risk of aneuploidy in patients of advanced maternal age

Abstract Study question Is delayed blastocyst development, assessed by the day of trophectoderm (TE) biopsy, associated with higher rates of aneuploidy? Summary answer Our findings show an association between delayed blastocyst development and poorer prognosis, in terms of euploidy rates, in patients of advanced maternal age. What is known already Extended culture of embryos past day 5 of development has become routine practice in all freeze-all cycles, including those applying preimplantation genetic testing for aneuploidies (PGT-A). As healthy live births have been obtained from day 6 and day 7 blastocysts, increasing the pool of embryos available for PGT-A is beneficial, particularly for patients of advanced maternal age who face higher cancellation rates. Nevertheless, the association between delayed blastocyst development and aneuploidy rates remains unclear. As current studies have reported opposing findings, detailed analysis of the chromosomal constitution of slowly developing embryos remains paramount. Study design, size, duration Retrospective, international, multicentre cohort study of 4211 patients undergoing preimplantation genetic testing for aneuploidy (PGT-A) from January 2016 to July 2020. We evaluated the chromosomal status of 14757 blastocysts tested using TE biopsy and next generation sequencing (NGS). Both autologous and donation cycles were included in the analysis. Cycles were excluded if they utilised preimplantation genetic testing for monogenic disorders (PGT-M) or preimplantation genetic testing for structural rearrangements (PGT-SR). Participants/materials, setting, methods We evaluated euploidy, aneuploidy and mosaicism rates reported in day 5 (n = 9560), day 6 (n = 4753) and day 7 (n = 262) blastocysts, stratified by SART-defined maternal age categories (<35, 35–37, 38–40, 41–42, >42). We further assessed the type and frequency of abnormalities reported in all blastocysts classified as clinically unsuitable, according to the day of biopsy. Finally, we examined the specific chromosomes affected in embryos diagnosed with a single uniform (n = 3882) or single mosaic (n = 518) abnormality. Main results and the role of chance The mean maternal age within our patient cohort was 39.9±3.7. Overall, slowly developing blastocysts were significantly more likely to be classified as clinically unsuitable (60.6%) compared to day 5 embryos (55.2%; p < 0.0001). This correlation was also observed when stratified by age, with the exception of the <35 age group (p = 0.25). Markedly, the risk of aneuploidy in slowly developing blastocysts became progressively higher with advancing maternal age (p < 0.0001). We did not observe any significant differences in the types of abnormalities diagnosed in slowly developing embryos compared to day 5 blastocysts. Nevertheless, abnormalities affecting all chromosomes were present at the blastocyst stage. Single trisomies and monosomies were the most frequent across all age groups, and were equally prevalent in day 5, 6 and 7 blastocysts. These most commonly affected chromosomes 16, 22, 21 and 15. We observed no significant differences in the incidence of segmental aneuploidies in relation to the day of biopsy, across all age groups. When considered separately, day 7 blastocysts presented with higher rates of structural aberrations, however low numbers limited statistical power. Finally, delayed blastocyst development was not associated with higher mosaicism rates (p = 0.79). Interestingly, single mosaic trisomies and monosomies were most frequently associated with chromosome 19. Limitations, reasons for caution Due to the retrospective nature of the study, full elucidation of all potential confounders may not be possible in all instances. The low number of day 7 blastocysts limited statistical power. As such, the results from day 6 and day 7 embryos were evaluated together. Wider implications of the findings: Our findings offer an important clinical resource for counselling patients of advanced maternal age. Maternal aging may be associated with a higher incidence of aneuploidy in slowly developing blastocysts. Nevertheless, extended culture increases the pool of biopsiable blastocysts, ultimately improving the chance of having a euploid embryo for transfer. Trial registration number NA

P–707 Does the dose or type of gonadotropin affect the reproductive outcomes of poor responders undergoing modified natural cycle IVF (MNC-IVF)?

Abstract Study question Does the dose or type of gonadotropin affect the reproductive outcomes of poor responders undergoing MNC-IVF? Summary answer Neither the type nor the dose of gonadotropins affects the reproductive outcomes of poor responders undergoing MNC-IVF. What is known already Poor ovarian response (POR) to ovarian stimulation remains a major therapeutic challenge in routine IVF practice, because of the association with low live birth rates and high cancellation rates. Although high doses of gonadotropins are traditionally used to stimulate the ovaries in women with predicted POR, MNC-IVF has been proposed as a mild-approach alternative in this population. Typically, the MNC protocol includes GnRH-antagonists to avoid premature ovulation and gonadotropin add-back stimulation at the late follicular phase. However, evidence is sparse, and there is no consensus regarding a specific dose or type of gonadotropins in this mild stimulation protocol. Study design, size, duration This is a retrospective cohort study including patients attending a tertiary referral University Hospital from 1st January 2017 until 1st March 2020. Participants/materials, setting, methods All women who underwent MNC-IVF in our center were included. Gonadotropins [recombinant FSH (rFSH), urinary FSH (uFSH) or highly purified human menopausal gonadotrophin (hp-hMG)] were started when a follicle with a mean diameter of 12–14 mm was observed on ultrasound scan, followed by GnRH antagonists (0.25mg/day) from the next day onwards. Mature oocytes were inseminated using ICSI. Main results and the role of chance In total, 484 patients undergoing 1398 cycles were included. Mean (SD) age and serum AMH were 38.2 (3.7) years and 0.46 (0.78) ng/ml, respectively. The daily dose of gonadotropins was either <75 IU/d [11/1398 (0.8%)] or 75 to < 100 IU/d [1303/1398 (93.2%)] or ≥ 100 IU/d [84/1398 (6%)]. Patients were stimulated with: rFSH [251/1398 (18%)], uFSH [45/1398 (3.2%)] or hp-hMG [1102/1398 (78.8%)]. Biochemical and clinical pregnancy rates were 142/1398 (10.1%) and 119/1398 (8.5%). Live birth was achieved in 80/1398 (5.7%) of cycles. Live birth rates (LBR) were similar between the different type and doses of gonadotropins (p-value 0.3 and 0.51, respectively). The GEE multivariate regression analysis adjusting for relevant confounders (age, BMI, number of MII oocytes) showed that the type of treatment strategy (rFSH/uFSH/hp-hMG) and the dose of gonadotropins were not significantly associated with LBR (coefficient 0.01 and –0.02, p value 0.09 and 0.3, respectively). Limitations, reasons for caution The main limitation is the retrospective design of our study, with an inherent risk of bias. Wider implications of the findings: This is the first and largest study evaluating MNC-IVF protocol modalities. Our data demonstrate that any type of gonadotropin can be used and there is no benefit from daily doses beyond 75IU. Trial registration number N/A

P–330 Live birth after ART in patients with treated endometriosis versus those without endometriosis at laparoscopy

Abstract Study question Is endometriosis related to worse outcome of assisted reproductive techniques (ART)? Summary answer Cumulative incidence of live birth in patients with and without endometriosis at laparoscopy was similar, although deep endometriosis and adenomyosis were negative prognostic factors. What is known already Whether endometriosis has a negative impact on the outcome of ART is still a matter of debate. Most published data report on one fresh cycle only, usually without taking frozen embryos into account. Further, a large heterogeneity in study population has been acknowledged by several meta-analyses, as in the control groups endometriosis was not always excluded by laparoscopy, and in case of endometriosis the prior treatment history was variable or unclear. Study design, size, duration Retrospective longitudinal cohort study of 1462 patients (779 with laparoscopically treated endometriosis of any rASRM stage, and 683 without endometriosis at laparoscopy) undergoing ART treatment between July 2003 and December 2014. Primary outcome studied was time to ART live birth. Secondary outcomes include -amongst others- number of cycles needed per ART live birth, time to ART or spontaneous live birth, cycle cancellation rate, and pregnancy outcomes like miscarriage and ectopic pregnancy, and per cycle analyses. Participants/materials, setting, methods All patients with a history of laparoscopy prior to the start of their first ART were included for analysis. The ART was performed in a tertiary referral center of a large University Hospital. Primary outcome studied was the time from initiation of the first ART cycle to delivery of the first live born. Survival analysis was conducted using cumulative incidence functions and cause-specific hazards regression. Main results and the role of chance The study included 1462 patients who initiated 4537 ART cycles, of which 3672 (81%) fresh and 857 (19%) frozen cycles. The unadjusted hazard ratio (HR) of live birth was 1.01 (95% CI 0.88–1.16). After adjustment for potential confounders (age, maternal BMI, maternal smoking, secondary infertility, duration of infertility, anovulation, reduced ovarian reserve, tubal factor, male factor and therapy started before 2007) the HR was 0.99 (95% CI 0.86–1.14). Within the endometriosis population (n = 779), covariate-adjusted analyses suggested that presence of adenomyosis (HR = 0.54; 95% CI 0.34–0.86) and a history of deep endometriosis (HR = 0.74 – 95% CI 0.58–0.94) were associated with a lower cumulative incidence of live birth. In contrast, there was little support of an association with diagnosis of stage III/IV (HR = 1.15; 95% CI 0.84–1.59) or a history of ovarian endometriosis (HR = 0.97; 95% CI 0.72–1.30). Beside the effect of the different variables directly linked to endometriosis, maternal BMI (HR = 0.80; 95%CI 0.71–0.91) and smoking (HR = 0.69; 95%CI 0.52–0.92) also negatively affected live birth delivery rate per patient. Limitations, reasons for caution Practices and success rates of ART may have changed during the 11-year recruitment period. Restricting to women who underwent laparoscopy, while providing evidence of the presence or absence of endometriosis, may have induced selection bias. However, the advantage of this time period, was the high rate of pre-ART laparoscopy (+/–50%). Wider implications of the findings: As deep endometriosis and adenomyosis represent negative prognostic factors within the endometriosis population, future studies should focus on optimalisation of ART in these subgroups. Trial registration number S57393

P–612 Transdermal testosterone vs. Placebo (lubricant gel) pre-treatment in improving IVF outcomes in diminished ovarian reserve patients (POSEIDON group 3 and 4): a randomised controlled trial

Abstract Study question To compare the efficacy of transdermal testosterone with placebo (lubricant gel) in improving IVF outcomes using GnRH antagonist protocol in POSEIDON group 3 and 4 patients. Summary answer Patients receiving pre-treatment with testosterone gel had higher mean number of oocytes retrieved and grade A embryos as compared to the patients receiving lubricant gel. What is known already Diminished ovarian reserve (DOR) is associated with suboptimal ovarian response, higher cycle cancellation rate and lower clinical pregnancy rate following IVF cycles. Various treatment regimens have been devised for management of such patients and use of adjuvants in the form of oral or transdermal androgen is one of them. Androgens improves follicular response to gonadotropin stimulation as well as increase FSH receptor expression in granulosa cells, in turn leading to better oocyte yield and pregnancy rate. Aim was to compare the effect of transdermal testosterone gel with placebo gel on ART outcome in DOR patients (POSEIDON Group 3 and 4). Study design, size, duration A prospective, randomised controlled trial was carried out from 1st September 2019 to 31st October 2020 at a tertiary infertility centre in India. 50 patients fulfilling the criteria of Group 3 and Group 4 of POSEIDON classification were included in the study. Patients with endocrine disorders (thyroid, prolactin), endometrioma, history of surgery on the ovaries, sensitivity to testosterone gel, male factor infertility and deranged liver and renal function tests were excluded. Participants/materials, setting, methods Enrolled patients were randomised into two groups of 25 patients each, one group was pretreated (TTG group) with transdermal testosterone gel, 12.5 mg/day from day 6th of previous cycle to day 2nd of stimulation cycle while patients in other group took lubricant gel for the same duration before stimulation with GnRH antagonist fixed protocol followed by fresh Day 3 transfer. Main results and the role of chance The baseline characteristics of the two groups were comparable. The primary outcome measures were the number of oocytes retrieved and number of grade A embryos formed (according to Istanbul consensus). The secondary outcome measures were implantation rate, clinical pregnancy rate, miscarriage rate and ongoing pregnancy rate. The mean number of oocytes retrieved in TTG group was 5±1.02 which was significantly higher than placebo group–3.5±1.2, (p < 0.001). The mean number of Grade A embryos were also significantly higher (4.78±0.54 vs 3.00±0.23, p < 0.001) in TTG group. The TTG group had higher implantation rate (28% vs 20%, p = 0.49), clinical pregnancy rate (32% vs 18%, p = 0.41), ongoing pregnancy rate (32% vs 16%, p = 0.38) and lower miscarriage rate (0% vs 20%, p = 0.38), however, these differences were not statistically significant. Limitations, reasons for caution The study was done at a single centre with small sample size, replication with more subjects and in different centers is needed. Wider implications of the findings: Pre-treatment with testosterone gel in DOR patients improves ovarian response to stimulation and results in higher number of oocytes retrieved and good quality embryos resulting in improved clinical pregnancy rates. Transdermal testosterone is advantageous because of better bioavailability, easy application, patient friendly and less adverse effects. Trial registration number MCDH/2019/54

The Effect of Elevated Basal Follicle Stimulating Hormone Levels on Assisted Reproductive Technology Cycle Outcomes

OBJECTIVE: Despite the availability of better biomarkers, basal day 3 follicle-stimulating hormone is widely available and often used as the first-line test in ovarian reserve evaluation. The aim of this study was to evaluate the outcomes of cycles with elevated (>12 IU/mL) basal follicle-stimulating hormone values. STUDY DESIGN: Cycles with basal day 3 follicle-stimulating hormone values >12 IU/mL were divided into four cohorts according to follicle-stimulating hormone levels: group I, follicle-stimulating hormone between 12-15 IU/m, group II between 15-20 IU/mL, group III between 20-25 IU/mL and group IV >25 IU/mL. Both demographic characteristics and controlled ovarian stimulation parameters were retrospectively reviewed. RESULTS: Total antral follicle count was significantly higher in group I compared to the other three groups (p=0.001). Number of follicles ≥17 mm on human chorionic gonadotropin (hCG) day, number of retrieved oocytes, mature oocytes and fertilized oocytes were significantly higher in group I compared to the other groups (p=0.003, p=0.001, p=0.001, and p=0.001, respectively). No significant difference was found between groups regarding cancellation rates. The rate of embryo transfer per started cycle was significantly higher in group I compared to group III and group IV (p=0.001). Clinical pregnancy rates per embryo transfer were comparable among the groups.CONCLUSION: Despite the retrieval of lower quantities of oocytes, reasonable pregnancy rates could be achieved if embryo transfer was performed in cycles with follicle-stimulating hormone values over 12 IU/mL.

The Negative Impact of the COVID-19 Pandemic on Oncology Care at an Academic Cancer Referral Center.

Objectives: COVID-19 created unexpected delays in oncologic treatment. This study sought to assess the volume of missed cancer-related services due to the pandemic. Methods: This case-controlled trial evaluated more than 345,000 oncologic clinic, lab, and radiation appointments from January 1, 2019, through December 31, 2020, and surgery appointments from January 1, 2019, through October 31, 2020. All patients at the Seidman Cancer Center with a cancer diagnosis based on a comprehensive list of 2178 International Classification of Diseases, Ninth Edition (ICD-9) and ICD-10 codes were included in the analysis. Subgroup analyses based on age, race, and sex were also performed. Results: Clinic, lab, and surgical visit cancellations increased by 4.20% (P <.001), 4.84% (P <.001), and 5.22% (P <.001), respectively. In the first 10 months of 2020, there were 703 (9.2%) fewer surgeries compared with the same time period in 2019. The following cancellation rates peaked in March 2020: clinic visits (26.53%), labs (43.66%), surgery (34.00%). Radiation oncology (12.53%) cancellations peaked in April 2020. Prior to the emergence of COVID-19, the group aged 0 to 39 years had the highest clinic cancellation rate (17.85%) compared with patients aged 40 to 64 years (15.95%) and 65 years and older (14.52%; P <.001). Men cancelled (15.63%) significantly more often than women (14.93%; P <.001) in 2019. This reversed during the pandemic: Women (19.56%) cancelled more frequently than men (19.20%; P <.036). Conclusions: There was a large increase in cancelled oncologic care in 2020, which has implications for delayed diagnosis and treatment. This was especially true for patients older than 65 years and for women. These delays could result in patients presenting with more advanced disease, complicating morbidities, and ultimately worse long-term outcomes.

Telemedicine during COVID-19: who gets left behind?

Objectives:COVID-19 resulted in rapid implementation of telemedicine. It is critical to explore patient factors that drive telemedicine use to recognize any disparities in healthcare access that may emerge with remote healthcare. Our objective was to compare the characteristics and subsequent health care utilization of gynecologic oncology patients who had a scheduled telemedicine visit from 3/23/20-5/18/20.Methods:We conducted a retrospective study of women whose scheduled in-person office visits were converted to telemedicine. Video visits were encouraged and telephone visits were the default option. We compared patient factors between women who cancelled versus those who completed their telemedicine visits. Subsequent health care utilization included in-person office appointments, emergency department (ED) or operative care was compared between those who cancelled versus completed telemedicine visits. We also evaluated patient differences in completion of video vs telephone visits. Cancellation rates were compared to a historical control of in-person gynecologic oncology office visits (3/23- 5/18/19). Multivariate logistic regression analyses were performed to assess odds of completing a telehealth appointment.Results:Of the 185 women with scheduled telemedicine visits, 158 (85%) completed and 27 (15%) cancelled. Telemedicine had significantly higher cancellations compared to office visits a year ago, 15% vs. 3% (p<0.001). Women who completed telemedicine visits tended to be older than those who cancelled (p=0.008). No other patient characteristics differed between those who completed versus cancelled telemedicine visits, and no differences were observed in subsequent health care utilization between groups. A total of 30% of patients had not activated their electronic patient portals prior to the study period. 124 (75%) of women had telephone visits. Being employed and a new, rather than established patient, was associated with video visits, p=0.009 and 0.003, respectively. In univariate analyses, older patients (OR 0.96; 95% CI 0.93, 0.99) and Medicare insurance (OR 0.21, 95% CI 0.05, 0.90) were less likely to cancel a visit. No patient characteristics were associated with visit cancellation in multivariate analyses.Conclusions:Telemedicine implementation faces ongoing challenges. High cancellation rates and patient's reluctance to use video or activate their electronic patient portals may limit a durable telemedicine platform. No patient characteristics were associated with the successful completion of telemedicine visits, and completion of telemedicine visits was not associated with subsequent healthcare utilization. More in-depth studies of patient engagement with telemedicine are needed to optimize healthcare delivery beyond the COVID-19 pandemic.

Patients characteristics related to screening mammography cancellation and rescheduling rates during the COVID-19 pandemic

PurposeTo identify patient characteristics associated with screening mammography cancellations and rescheduling during the COVID-19 pandemic. MethodsScheduled screening mammograms during three time periods were retrospectively reviewed: state-mandated shutdown (3/17/2020-6/16/2020) during which screening mammography was cancelled, a period of 2 months immediately after screening mammography resumed (6/17/2020-8/16/2020), and a representative period prior to COVID-19 (6/17/2019-8/16/2019). Relative risk of cancellation before COVID-19 and after reopening was compared for age, race/ethnicity, insurance, history of chronic disease, and exam location, controlling for other collected variables. Risk of failure to reschedule was similarly compared between all 3 time periods. ResultsOverall cancellation rate after reopening was higher than before shutdown (7663/16595, 46% vs 5807/15792, 37%; p < 0.001). Relative risk of cancellation after reopening increased with age (1.20 vs 1.27 vs 1.36 for ages at 25th, 50th, and 75th quartile or 53, 61, and 70 years, respectively, p < 0.001). Relative risk of cancellation was also higher among Medicare patients (1.41) compared to Medicaid and those with other providers (1.26 and 1.21, respectively, p < 0.001) and non-whites compared to whites (1.34 vs 1.25, p = 0.03). Rescheduling rate during shutdown was higher than before COVID-19 and after reopening for all patients (10,658/13593, 78%, 3569/5807, 61%, and 4243/7663, respectively, 55%, p < 0.001). Relative risk of failure to reschedule missed mammogram was higher in hospitals compared to outpatient settings both during shutdown and after reopening (0.62 vs 0.54, p = 0.005 and 1.29 vs 1.03, p < 0.001, respectively). ConclusionMinority race/ethnicity, Medicare insurance, and advanced age were associated with increased risk of screening mammogram cancellation during COVID-19.

The role of the Advanced Clinical Practitioner (ACP) in triaging patients with Non ST-Elevation acute coronary syndromes (NSTE-ACS) patients for coronary angiographic procedures

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The introduction of the ACP role to a cardiology service with emphasis on measuring the effect of this role on improving the Inter-hospital transfer pathway for patients with ACS by improving patient outcomes ACPs triage a large number (estimated n = 2500 per year) of cardiology IHT referrals from these hospitals and ensure effective transfer to our centre for ACS treatment whilst supporting staff in the care of those patients who do not meet our transfer criteria or are acutely unwell for transfer but cardiovascular stable Patients are listed in order of presenting symptoms, presence or absence of chest pain on admission, relevant blood results such as infection markers, kidney function, and troponin a cardiac biomarkers, ECG findings, drug history , past medical history and arrival to hospital rather than clinical urgency . Purpose Therefore the purpose of this evaluation was to measure the patient outcomes of introduction of an ACP in triaging patients with NSTE-ACS)patients for coronary angiographic procedures. Methods Quantitative design approach with a specialist cardiology setting using a 2-year observational analysis of the data.The study population included all patients referred for angioplasty or PCI via the Inter-hospital transfer acute coronary syndrome network including all patients referred for PCI following NSTE-ACS. Results : There were a total of n= 4976 patients referred for coronary angiogram +/-proceed procedures between Feb 2018 and Feb 2020. Overall significant positive outcomes were noted across a consistent patient group based on presenting symptoms and patient characteristics when comparing data in the year preceding ACP led triage. A 2-sided p-value &amp;lt;0.05 defined statistical significance and to reject the null hypothesis. There was a significant reduction in waiting time post introduction of ACP led triage (p &amp;lt; 0.0001) equating to one day Comparison from pre ACP to post ACP led triage and clinical cancellation rates was reduced significantly (p = 0.0062). Rates of revascularisation were significantly higher post ACP led triage with a corresponding decrease in those managed medically (47.2% pre vs 43.1% post, p = 0.0037). These higher rates consisted of increased rates of both CABG (12.4% pre vs 13.5% post, p = 0.04) and PCI 40.4% vs 43.4%, p = 0.0216) Conclusion ACP led triage of ACS patients requiring urgent treatment demonstrates improved patient outcomes with economic benefits for healthcare providers, enhancing the service provided and opens up discussions for further quality improvement and implications to practice. Evidence of the benefits of advanced practice and the role of the advanced clinical practitioner is demonstrated within the cardiology setting and for the clinical triage of a patient group.

The impact of cancellations in waiting times analysis: evidence from scheduled surgeries in the Portuguese NHS.

BackgroundEquity in access to scheduled surgery has been a topic of attention of researchers and decision-makers on healthcare. Most studies analyse the number of days that patients wait before undergoing surgery, and ignore patients that have been on the waiting list but have not benefited from surgery. This study contributes to the existing literature on waiting lists by analysing cancellations along with surgery episodes.MethodsWe use a database comprising all patients that entered the waiting list for scheduled surgeries in the Portuguese National Health Service from 2011 to 2015 (around 3 million observations) and estimate survival models to explain waiting times, where cancellations are introduced as censored data.ResultsThe cancellation rate is significant (around 14%), and has a considerable impact on results: ignoring cancellations biases estimates, in particular for gender differences (that are overestimated without cancelations), and for the age effect (that is underestimated).ConclusionThus, our approach provides a more accurate understanding of the impact that several factors have on overall access to scheduled surgery.

The impact of indomethacin on the number of oocytes retrieved and IVF outcomes in patients with poor ovarian response

ObjectiveThe aim of this retrospective case-control study was to analyze the effect of administering indomethacin after triggering final oocyte maturation in patients with poor ovarian response (POR) on the cycle cancellation rate due to premature ovulation (PO), the number of oocytes retrieved and the clinical outcomes of IVF cycles. Study DesignA total of 214 patients with POR, diagnosed according to the Bologna criteria, who underwent fresh IVF cycle via flexible gonadotrophin-releasing hormone antagonist (GnRH-ant) protocol were enrolled in the study. The control group consisted of 100 patients, whereas the indomethacin group included 114 patients who received 100 mg rectal indomethacin administered twice within the same day (twelve hours apart) –starting at twelve hours after triggering. Cycle cancelation rates (CCR), number of oocytes retrieved (nOR), implantation rates (IR), biochemical pregnancy (BP) and clinical pregnancy loss rates (CPL), ongoing pregnancy rates (OPR) and live birth rates (LBR) were compared between the indomethacin and control groups. ResultsThe CCR rate was significantly lower in the indomethacin group (1.8%) compared to the control group (1.8% vs %12%, p = 0.01). In the control group, those with cycle cancellation were older than those without cycle cancellation (mean age 42.2 ± 2.3 years vs. 39.36 ± 4.3 years, p = 0.001) and had lower anti-Müllerian hormone levels and lower antral follicle count (0.59 ± 0.2 ng/mL vs 0.79 ± 0.2 ng/mL, p = 0.001 and 4 ± 0.6 vs 5.7 ± 1.7, p = 0.001, respectively). In multivariable analysis, when the dependent variable in the logistic regression model was coded as the absence of cycle cancellation, it was observed that only indomethacin had a statistically significant effect on cycle cancellation (β = −1.931, standard error = 0.832, Exp(B) = 0.145, p = 0.020). nOR was higher in the indomethacin group than control group but the difference did not reach significance (p = 0.07). Moreover, the IR, OPR and LBR, BP and CPL values were similar in the indomethacin and control groups (p > 0.05). ConclusionsBased on data from this study, it can be concluded that indomethacin reduces cycle cancelation due to PO in patients with POR –without compromising implantation and pregnancy rates. However, further randomized controlled trials with larger sample sizes are required to clarify the definitive effect of indomethacin in the treatment of patients with POR.

Female Fertility Clock Closes to Tick around the Age of 43

Objective: To investigate if attempting In Vitro Fertilization (IVF) in women over 40 is of worth. Materials & Methods: Two hundred and thirty nine women over 40 years of age undergoing IVF were enrolled. Long protocol was used for downregulation followed by stimulation and IVF-ET. The primary outcome measure was live-birth rate. Secondary outcomes included rates of miscarriage, cycle cancellation, obstetrical complications, and maternal and fetal adverse events. Results: Clinical pregnancy rates per cycle were 42.85 %, 39.34 %, 34.09 %, 27.27 % and 16.66 % for 40, 41, 42, 43 and 44 years old, respectively. Absolute difference in live birth rate in age 40 - 44 vs control, -15 percentage points; 95 % Confidence Interval (CI) -45 to 15.1, -18.77 percentage points; 95 % CI,(-56.31 to 18.79), -23.77 percentage points; 95 % CI,(-71.31 to 23.81), -25.82 percentage points; 95 % CI, (-77.48 to 25.84) and, - 27.72 percentage points; 95 % CI, (-83.16 to 27.76), respectively. Intra-uterine growth restriction and preterm delivery occurred significantly more frequently in the age group of 42 and above. Only one IVF cycle in patients aged 44 resulted in delivery. Conclusion: It appears that IVF treatment should be limited to patients not older than 43 years, with adequate ovarian response.

New patient access via telehealth in neuromuscular medicine during COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has changed the face of health care delivery. Health care institutions rapidly transitioned to telehealth to provide care to patients. Prior to the pandemic, telehealth services extended mostly to patients with established diagnoses. Driven by a necessity to provide care to all patients during the pandemic, neurologists started evaluating new patients also via telehealth. To explore opportunities, challenges, and feasibility of telehealth for new patients with neuromuscular disorders. New patient visits performed in our neuromuscular clinic were analyzed from March 18, 2020 - July 31, 2020. Data collected included visit volume, demographics, geographic distance of patient's residence from our institution, and no-show and cancellation rates. Total number of patients seen was 1,471; 472 (32%) were new patients. No-show and cancellation rates for telehealth visits were lower than historical in-person visits. There was a wide range of ages (35-74 years) with representation of new patients from a large geographical territory. This study advances our understanding regarding the adoption and implementation of telehealth for new patients. Our clinic was able to provide timely access and care to a significant number of patients who could not travel to our institution during COVID-19.

Patients With Deep Ovarian Suppression Following GnRH Agonist Long Protocol May Benefit From a Modified GnRH Antagonist Protocol: A Retrospective Cohort Study.

ObjectiveTo verify if patients with deep ovarian suppression following gonadotropin releasing hormone (GnRH) agonist long protocol may benefit from a modified GnRH antagonist protocol based on luteinizing hormone (LH) levels.DesignRetrospective cohort study.SettingUniversity-based hospital.Patients110 patients exhibited ultra-low LH levels during ovarian stimulation using GnRH agonist long protocol.Intervention(s)As all the embryos in the first cycle were exhausted without being pregnant, these patients proposed to undergo a second cycle of ovarian stimulation. 74 of them were treated with a modified GnRH antagonist protocol based on LH levels. Other 36 patients were still stimulated following GnRH agonist long protocol.Main Outcome MeasureThe primary outcome was live birth rate (LBR). The second outcomes were biochemical pregnancy rate, clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR) and cancellation rate.ResultsReproductive outcomes were much better in the modified GnRH antagonist protocol. The OPR and LBR were much higher in the GnRH antagonist protocol group than in the GnRH agonist long protocol group [odds ratio (OR) 3.82, 95% confidence interval (CI) 1.47, 10.61, P=0.018; OR 4.33, 95% CI 1.38, 13.60, P=0.008; respectively]. Meanwhile, the cancellation rate was much lower in the GnRH antagonist protocol group (OR 0.13, 95% CI 0.02, 0.72; P=0.014). Mean LH level during stimulation did not have a predictive value on live birth. However, it was independently associated with the occurrence of ongoing pregnancy (OR 2.70, 95% CI 1.25, 5.85; P=0.01). The results of sensitivity analyses were consistent with the data mentioned above. The patients got completely different and excellent clinical outcomes in their second cycles stimulated with the modified GnRH antagonist protocol.ConclusionPatients with deep ovarian suppression following GnRH agonist long protocol may benefit from a modified GnRH antagonist protocol based on LH levels.

The Maribor consensus: report of an expert meeting on the development of performance indicators for clinical practice in ART.

STUDY QUESTIONIs it possible to define a set of performance indicators (PIs) for clinical work in ART, which can create competency profiles for clinicians and for specific clinical process steps?SUMMARY ANSWERThe current paper recommends six PIs to be used for monitoring clinical work in ovarian stimulation for ART, embryo transfer, and pregnancy achievement: cycle cancellation rate (before oocyte pick-up (OPU)) (%CCR), rate of cycles with moderate/severe ovarian hyperstimulation syndrome (OHSS) (%mosOHSS), the proportion of mature (MII) oocytes at ICSI (%MII), complication rate after OPU (%CoOPU), clinical pregnancy rate (%CPR), and multiple pregnancy rate (%MPR).WHAT IS KNOWN ALREADYPIs are objective measures for evaluating critical healthcare domains. In 2017, ART laboratory key PIs (KPIs) were defined.STUDY DESIGN, SIZE, DURATIONA list of possible indicators was defined by a working group. The value and limitations of each indicator were confirmed through assessing published data and acceptability was evaluated through an online survey among members of ESHRE, mostly clinicians, of the special interest group Reproductive Endocrinology.PARTICIPANTS/MATERIALS, SETTING, METHODSThe online survey was open for 5 weeks and 222 replies were received. Statements (indicators, indicator definitions, or general statements) were considered accepted when ≥70% of the responders agreed (agreed or strongly agreed). There was only one round to seek levels of agreement between the stakeholders.Indicators that were accepted by the survey responders were included in the final list of indicators. Statements reaching less than 70% were not included in the final list but were discussed in the paper.MAIN RESULTS AND THE ROLE OF CHANCECycle cancellation rate (before OPU) and the rate of cycles with moderate/severe OHSS, calculated on the number of started cycles, were defined as relevant PIs for monitoring ovarian stimulation. For monitoring ovarian response, trigger and OPU, the proportion of MII oocytes at ICSI and complication rate after OPU were listed as PIs: the latter PI was defined as the number of complications (any) that require an (additional) medical intervention or hospital admission (apart from OHSS) over the number of OPUs performed. Finally, clinical pregnancy rate and multiple pregnancy rate were considered relevant PIs for embryo transfer and pregnancy. The defined PIs should be calculated every 6 months or per 100 cycles, whichever comes first. Clinical pregnancy rate and multiple pregnancy rate should be monitored more frequently (every 3 months or per 50 cycles). Live birth rate (LBR) is a generally accepted and an important parameter for measuring ART success. However, LBR is affected by many factors, even apart from ART, and it cannot be adequately used to monitor clinical practice. In addition to monitoring performance in general, PIs are essential for managing the performance of staff over time, and more specifically the gap between expected performance and actual performance measured. Individual clinics should determine which indicators are key to the success in their organisation based on their patient population, protocols, and procedures, and as such, which are their KPIs.LIMITATIONS, REASONS FOR CAUTIONThe consensus values are based on data found in the literature and suggestions of experts. When calculated and compared to the competence/benchmark limits, prudent interpretation is necessary taking into account the specific clinical practice of each individual centre.WIDER IMPLICATIONS OF THE FINDINGSThe defined PIs complement the earlier defined indicators for the ART laboratory. Together, both sets of indicators aim to enhance the overall quality of the ART practice and are an essential part of the total quality management. PIs are important for education and can be applied during clinical subspecialty.STUDY FUNDING/COMPETING INTEREST(S)This paper was developed and funded by ESHRE, covering expenses associated with meetings, literature searches, and dissemination. The writing group members did not receive payment.Dr G.G. reports personal fees from Merck, MSD, Ferring, Theramex, Finox, Gedeon-Richter, Abbott, Biosilu, ReprodWissen, Obseva, PregLem, and Guerbet, outside the submitted work. Dr A.D. reports personal fees from Cook, outside the submitted work; Dr S.A. reports starting a new employment in May 2020 at Vitrolife. Previously, she has been part of the Nordic Embryology Academic Team, with meetings were sponsored by Gedeon Richter. The other authors have no conflicts of interest to declare.DISCLAIMERThis document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and where relevant based on the scientific evidence available at the time of preparation.The recommendations should be used for informational and educational purposes. They should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type.Furthermore, ESHREs recommendations do not constitute or imply the endorsement, recommendation, or favouring of any of the included technologies by ESHRE.

Assessing Quality and Safety of an Advanced Practice Provider-led Active Surveillance Clinic for Men with Prostate Cancer.

We implemented an advanced practice provider (APP)-led clinic to aid in managing the growing population of men on active surveillance (AS) for prostate cancer. Our objective was to evaluate the quality and safety of an established APP-led AS clinic by comparing outcomes with urologist-led biopsies, defined in terms of adherence to scheduled visits and biopsy complications. We performed a retrospective review of 2341 consecutive patients treated in an AS clinic at a high-volume referral center between 2000-2019. We examined the rate of no-show or same-day cancellation of visits for APPs versus urologists and compared the risk of biopsy complications between these providers. Generalized estimating equations were used to account for repeated visits and biopsies. There were significantly more no-shows at APP visits (odds ratio [OR] 1.40, 95% confidence interval [CI] 1.16-1.70, p <0.001); however, this only amounted to one no-show every 41 visits. There was no evidence of increased biopsy complications with APPs (OR 0.37, 95% CI 0.05-2.49, p =0.3). Patients were not prospectively assigned to APP or urologist management; therefore, unmeasured patient differences could bias our results. We demonstrated that in an established APP-led AS clinic at a high-volume center, APPs achieved acceptable patient adherence to scheduled visits and biopsy complications. Because patients were not continuously managed by one type of provider, further prospective studies are needed to establish equivalent pathologic outcomes in APP-managed AS.