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Study question What is the reproductive outcome from ovarian tissue transplantation (OTT) from a single, experienced center. Summary answer The overall delivery rate was 41% (16/39) per woman and a total of 20 children to 39 women is expected. What is known already Ovarian tissue cryopreservation (OTC) is a well-established procedure for fertility preservation in girls and young women prior to gonadotoxic treatment and has shown to be a safe and promising method to restore fertility, with more than 200 healthy children born worldwide. Initial recovery of endocrine function is very high, although the longevity of the grafted tissue varies. The success of OTT is multifactorial, and important factors such as high age and poor ovarian reserve at OTC, as well as pelvic radiation are known to impair the chances of success. Study design, size, duration This is a single center, combined retro- and prospective cohort study including 40 women undergoing a total of 53 OTTs from the Fertility Clinic at Rigshospitalet University Hospital of Copenhagen, Denmark between 2003 and 2021. Participants/materials, setting, methods All women, who underwent OTT, were included in the study. End of follow up was December 31st, 2021. Information about diagnoses, gonadotoxic treatment, gynecologic (incl. endocrine parameters) and obstetric history was retrieved from medical records. Permission to obtain retrospective data from 1999 to 2020 was given by the Danish Patient Safety Authorities (jrn 3-3013-2790/1) and prospective data-collection was given by informed consent from the patients from 2020 and onwards. Main results and the role of chance Mean age at OTC was 28.5+5.5 years. Indications for OTC were malignant (n = 34) or benign diseases (n = 6). Mean time to first OTT was 4.2 years and mean age 33.0+5.4 years. At OTT, 19 women had POI (FSH>25 IU/L and amenorrhea), 10 were perimenopausal (intermittent FSH >25 IU/L) and 11 were low responders (AMH From 39 women with a pregnancy wish, 11 (28%) gave birth to a total of 15 children. In addition, 5 pregnancies are currently ongoing in the last trimester. The overall delivery rate was 51% (20/39) (including 5 ongoing) and 41% (16/39) per woman. Of 20 deliveries, 60% were conceived naturally and 40% from ART. Nineteen children were delivered following the first OTT. Four women had 2 children, of whom one had her second child following the second OTT. Initial activation of the grafted tissue, defined by a drop of FSH to Data on endocrine function of the grafted tissue will be presented at the meeting. Limitations, reasons for caution This study is based on information from medical records in public Danish hospitals, where information of all deliveries in Denmark is available. Pregnancies and deliveries outside Denmark might therefore not be included, why the total number could be slightly underestimated. Wider implications of the findings OTC with OTT is an efficient and encouraging way to restore fertility in a selected group of young women with a high risk of infertility following gonadotoxic treatment. Further, our data, from a specialized and experienced center, shows a good chance of livebirth and initial recovery of endocrine function. Trial registration number 3-3013-2790/1

Introduction There are substantial individual differences (resilience and vulnerability) in neurobehavioral performance from psychosocial stress and sleep loss. However, the time course of heart rate variability (HRV) across baseline, total sleep deprivation (TSD), the combination of TSD + psychological stress, and recovery has not been investigated; in addition, it remains unknown whether HRV and blood pressure (BP) differ in resilient vs. vulnerable individuals and predict individual differences in cognitive performance. Methods Thirty-one healthy adults (ages 27–53; mean±SD, 35.4±7.1y; 14 females) participated in a five-day experiment consisting of two 8h time-in-bed (TIB) baseline nights, 39h TSD, and two 8h-10h TIB recovery nights. A modified Trier Social Stress Test (TSST) induced psychological stress on the TSD day. Systolic and diastolic BP and HRV (derived from echocardiographic R-R interval) were obtained at six time points (pre-study, baseline, during TSD, during TSD after the TSST, after recovery, and post-study). Cognitively resilient (n=15) and vulnerable (n=16) groups were defined by a median split on 10-minute Psychomotor Vigilance Test (PVT) TSD performance [total lapses (>500ms response time) and errors]. Repeated measures ANOVA and post-hoc comparisons corrected for multiple testing, examined BP and HRV across time points between groups. Results HRV showed a significant time*group interaction: while resilient individuals had significantly lower HRV at pre-study compared to vulnerable individuals, their HRV increased above that of vulnerable individuals with TSD and with TSD + psychological stress. By contrast, systolic and diastolic BP did not show significant time*group interactions and did not predict cognitive vulnerability during TSD. Conclusion HRV differed between resilient and vulnerable individuals across TSD, psychological stress and recovery sleep and predicted individual differences in cognitive performance, whereby lower HRV during full-rested conditions predicted resilience to TSD and TSD + psychological stress. HRV, but not BP, is a reliable biomarker of sleep deprivation, psychological stress, and neurobehavioral vulnerability. Support NASA NNX14AN49G.

Introduction Individuals show robust resilience and vulnerability in neurobehavioral performance to sleep loss and stress. For the first time, we investigated the time course of two cardiovascular measurements, stroke volume (SV) and cardiac index (CI), both derived from echocardiography, across baseline, total sleep deprivation (TSD), the combination of TSD+psychological stress, and recovery. We also determined whether these variables differ in resilient vs. vulnerable individuals and whether they predict differential vulnerability in cognitive performance. Methods Thirty-one healthy adults (ages 27–53; mean±SD, 35.4±7.1y; 14 females) participated in a five-day experiment consisting of two 8h time-in-bed (TIB) baseline nights, 39h TSD, and two 8h-10h TIB recovery nights. A modified Trier Social Stress Test (TSST) was conducted on the TSD day to induce psychological stress. Echocardiographic measures of SV and CI were obtained at six time points (pre-study, baseline, during TSD, during TSD after the TSST, after recovery, and post-study). A median split of TSD performance [total lapses (>500 ms response time) and errors] on the 10-minute Psychomotor Vigilance Test (PVT), defined cognitively resilient (n=15) and vulnerable (n=16) groups. Repeated measures ANOVA and post-hoc comparisons corrected for multiple testing, examined SV and CI across time points between groups. Results There was a significant time*group interaction for SV: cognitively resilient individuals had greater SV during the five-day experiment. In addition, in both resilient and vulnerable individuals, SV increased with TSD and with TSD+psychological stress compared with baseline. Like SV, there was a significant time*group interaction for CI: resilient individuals had greater CI at all points of the experiment. Conclusion SV and CI differed between resilient and vulnerable individuals across TSD, psychological stress and recovery sleep. Greater SV and greater CI at baseline predicted resilience to TSD and TSD+psychological stress. CI and SV are novel physiological biomarkers of sleep loss, stress, and individual differences in cognitive performance. Support NASA NNX14AN49G.