Abstract Study question How does treatment with GnRH-agonist (GnRH-a) prior to frozen embryo transfer (FET) in women with adenomyosis affect immune cell populations in endometrium and peripheral blood? Summary answer GnRH-a induces a decrease in monocytes and an increase in CD4+T-cells in peripheral blood and a decrease classical monocytes and T-regulatory cells in the endometrium What is known already Adenomyosis is associated with lower implantation and higher miscarriage rates. Observational studies have reported improved pregnancy outcomes in women with adenomyosis after assisted reproductive technologies (ART) and pre-treatment with GnRH-a prior to FET. However, the specific mechanisms of GnRHa action beyond central hormonal suppression remain unclear, but may be mediated through local and/or systemic immunomodulation. Study design, size, duration Prospective cohort study including infertile women with adenomyosis and GnRH-a treatment ≥3 months prior to FET. Pre- and post-treatment analysis of blood and endometrium samples were compared. Recruitment is ongoing with n = 30 women included thus far, 16 of whom have completed the study, while the remaining are still undergoing GnRH-a therapy. Participants/materials, setting, methods Adenomyosis was diagnosed sonographically if ≥ 2 criteria published by the MUSA group were met. Peripheral blood and endometrial samples were obtained before and after treatment with GnRH-a. Plasma cells and uterine Natural Killer (uNK) cells in endometrial biopsies were quantified with immunhistochemistry (IHC), and leukocyte populations in all samples were analysed using flow cytometry (FC). Pre- and post-treatment levels of immune cells and percentage of leukocyte populations were compared using Wilcoxon rank-sum tests (p < 0.05 significant) Main results and the role of chance Interim analysis of immune cell populations in peripheral blood and endometrium of the 16 women who already completed the study was performed. At baseline, IHC showed elevated plasma cell concentrations indicating chronic endometritis in 3/30 patients (10%), while uNK cells were elevated (>300/mm2) in 13/30 patients (43.3%). FC analysis of peripheral blood showed a significant decrease in percentage of monocytes (p = 0.01) and increase in percentage of T-cells (p = 0.03), specifically concentration of CD4+T-cells (p = 0.03), after treatment with GnRH-a as compared to pre-treatment levels. In the endometrium, following GnRH-a therapy, we observed a decrease in both the percentage of classical monocytes (p = 0.03) and T-regulatory cells (p = 0.03). All 16 participants who completed the study already underwent FET, resulting in ten pregnancies (62.5%), although four resulted in miscarriage, while the outcome of the remaining pregnancies is still pending. Limitations, reasons for caution These are preliminary results whose generalizability needs to be confirmed in a larger study population. No correction for multiple comparisons was performed and significant findings have to be interpreted with caution. Wider implications of the findings Elevated uNK on IHC cells seen at baseline may be associated with implantation failure, miscarriage. CD4+ and DN T-cells are important mediators of reproductive immune tolerance. In women with adenomyosis, GnRH-a may have a positive impact on these regulatory immune cells in peripheral blood as well as in the endometrium. Trial registration number Not applicable

Einleitung Die Begriffe "Transgender" (TGD) und Geschlechtsinkongruenz beschreiben die Diskrepanz zwischen dem angeborenen und dem erlebten Geschlecht.

Hintergrund Die verbesserte Überlebensfähigkeit von Krebspatienten führt zu neuen Herausforderungen, einschließlich einer möglichen Beeinträchtigung der Lebensqualität, der sexuellen Funktion und der Fruchtbarkeit. Ziel dieser Studie war es, die sexuelle Dysfunktion (SD) und die psychische Belastung bei weiblichen Krebsüberlebenden zu untersuchen, die sich in der Vergangenheit einer Fertilitätserhaltung unterzogen haben.

Natürliche Killerzellen (NK-Zellen) spielen eine entscheidende Rolle bei der Etablierung einer erfolgreichen Schwangerschaft. Sie sind sowohl im peripheren Blut als auch im Endometrium nachweisbar. Im Rahmen dieser Arbeit werden Informationen zu uterinen NK-Zellen zusammengetragen mit dem Ziel, einen umfassenden Überblick über ihre Herkunft, Eigenschaften und Funktionen sowie über diagnostische Verfahren zu vermitteln. Gleichzeitig sollen potenzielle Therapieoptionen aufgezeigt werden. NK-Zellen weisen signifikante Unterschiede hinsichtlich ihrer immunmodulatorischen Aktivitäten auf. Etwa 90

Einleitung Adenomyose ist mit einer niedrigeren Einnistungsrate und höheren Fehlgeburtenraten verbunden. GnRH-Agonisten (GnRH-a) vor dem Transfer kryokonservierter Embryonen (frozen embryo transfer, FET) scheinen die reproduktiven Ergebnisse zu verbessern [1]. Die genauen Mechanismen sind jedoch unklar, könnten aber mit veränderten Immunzellpopulationen zusammenhängen. In dieser Studie sollen die Immunzellpopulation im Endometrium und peripheren Blut von Frauen mit Adenomyose vor und nach der Behandlung mit GnRH-a vor Durchführung eines FET charakterisiert werden.

There is growing public concern that both the SARS-CoV-2 virus infecLon and the corona vaccinaLon could lead to inferLlity or increased miscarriage rates. Especially women and men during reproducLve years raise concerns. We reviewed the current literature on the impact of SARS-CoV-2 infecLon as well as Covid vaccinaLon on female and male ferLlity in animal models and in humans. Method of Study: A systemaLc literature search was performed using the keywords "COVID 19, SARSCoV-2, ferLlity, semen, sperm, oocyte, male ferLlity, female ferLlity, inferLlity" (Pubmed, Embase, Web of Science). Subsequently, original papers from October 2019 to February 2022 were selected and reviewed. Results: With regard to animal models, despite the use of very high vaccine dosages, no negaLve impact on ferLlity, pregnancy outcome, and fetal development was present. In humans, studies to date showed also no negaLve impact on male or female ferLlity aXer Covid-19 vaccinaLon. No virus RNA was detected in human oocytes/follicular fluid in SARS-CoV2-posiLve women; likewise, no differences were found between recovered, vaccinated, and controls with respect to pregnancy or miscarriage rates. Furthermore, vaccinaLon did not affect the live birth rate aXer ART. In infected and sLll infecLous males, no viral RNA was detected in the ejaculate in the majority of cases; however, severe infecLon was associated with low sperm concentraLon and decreased sperm moLlity. Few longLme studies showed a recovery of sperm parameters in the follow up of most cases. Conclusions: Current studies provide no evidence for negaLve effects on male or female ferLlity following Covid vaccinaLon, neither in animals nor in humans. In contrast, adverse effects of a severe SARS-CoV-2 infecLon on male ferLlity was shown and only few longLme follow up studies are currently available. Counseling of young people should therefore take fears and concerns seriously and discuss the current data in a structured manner.

Einleitung Die Ovarkryokonservierung zum Zwecke des Fertilitätserhalts vor einer Chemo- oder Strahlentherapie gehörte lange Zeit zu einem experimentellen Verfahren und ist erst seit kurzem international etabliert [1] [2] [3]. In Innsbruck wird dies bereits seit 2003 angewandt, wobei die Technik der Kryokonservierung innerhalb der letzten 17 Jahren vielfach modifiziert wurde.

Einleitung Vor allem junge Frauen und Männer mit (zukünftigem) Kinderwunsch äußern die Angst, dass eine Corona Impfung zu einer Infertilität bzw. einer erhöhten Abortrate und negativen Langzeitfolgen für das Kind führen könnte. Ärztliche Kolleg:innen sorgen sich hingegen mehr hinsichtlich der Auswirkungen einer SARS-CoV-2 Infektion auf die Reproduktion.

Abstract Study question What is the effect of low dose radiation on follicle count in sheep ovaries? Summary answer Even low dose radiation has a negative impact on the follicle count in sheep ovaries. What is known already Radiotherapy is a corner stone of state-of-the-art cancer treatment, especially in young cancer patients. Survival rates are constantly rising, resulting in long-term survivors with potential child wish. High doses of radiation lead to a permanent damage to the ovaries. Little is known about the damage after low dose radiation to the ovaries including both follicles and stroma. Study design, size, duration Prospective ongoing study, including n = 41 sheeps and 942 ovarian punches (Ø 3mm). So far, n = 12 sheep and n = 120 punches were analysed between April 2020 and January 2022. After finishing the experiments with sheep ovarian tissue, we will continue with a mouse model and human ovarian tissue. Participants/materials, setting, methods 942 cortex punches out of a total of n = 41 sheep were obtained and cryopreserved. After thawing the punches were radiated with a dose of 0.0, 0.5, or 9.0 Gy using a cesium 137 radionuklide source (GSR C1, GammaService Medical GmbH). The punches were fixed in formalin, embedded in paraffin, cut into serial sections of 3-5 µm and stained with Hematoxylin and Eosin for follicle counting as well as Caspase 3 and Ki67. Main results and the role of chance Follicle loss was already observed after low dose radiation (0.5 Gy). Mean follicle count after 0 Gy, 0.5 Gy, and 9 Gy were 7.5, 2.3 and 1.8, respectively. While after 0 Gy, no signs of degeneration were visible, after radiation with 9 Gy follicles showed strong signs of degeneration including disorganization of granulosa cells, pyknosis and stromal irregularities. Limitations, reasons for caution Limitations of our study include the pilot character and therefore small sample size. The presented data only display part of the overall project including also an in-vivo mouse model. Wider implications of the findings As even low dose radiation seems to damage ovarian follicles, further in-vivo studies are needed to confirm these results. Moreover, fertility preservation methods need to be offered consequently to young cancer patients receiving radiotherapy. Trial registration number 25

Case Report: A 15- year- old girl with Ullrich- Turner- Syndrome (Mosaic with 50% X0) was referred to our clinic to discuss fertility preservation.

Gonadotoxic treatment in female cancer patients can lead to reversible or permanent impaired fertility. Different methods of fertility preservation are offered, including cryopreservation of (non-) fertilized oocytes, cryopreservation of ovarian tissue, and GnRH analogues.

Einleitung Eine gonadotoxische Behandlung im Rahmen einer Krebserkrankung kann bei den Patientinnen zu einer reversiblen oder dauerhaften Beeinträchtigung der Fertilität führen. Das Risiko der Auswirkung auf die Fruchtbarkeit ist abhängig von der Art der Chemotherapie, der Dosis, der Anzahl der Zyklen und dem Alter der Patientin. Zum Fertilitätserhalt werden verschiedene Methoden, wie die Kryokonservierung von Ovarialgewebe oder fertilisierten/unfertilisierten Eizellen und GnRH-Analoga, angeboten. In dieser Follow-up Studie wird untersucht, ob Frauen nach einer fertilitätserhaltenden Maßnahme und einer gonadotoxischen Therapie zu einem normalen Menstruationszyklus zurückkehren. Außerdem wird die Erfüllung des Kinderwunsches der Patientinnen untersucht.