One center experience with a personalized frozen-thawed embryo transfer in patients with recurrent implantation failure.

PURPOSE: Displaced endometrial receptivity has been discussed as a possible cause of recurrent implantation failure in patients undergoing assisted reproductive technology. The aim of this study was to document our experience with the endometrial receptivity analysis in patients with recurrent implantation failure. METHODS: This retrospective cohort study, conducted at the Fertility Centre of the University Hospital, Duesseldorf Germany, presents the results of the endometrial receptivity analysis in 67 patients with recurrent implantation failure and compares the clinical outcome between these 67 patients who underwent a personalized frozen-thawed embryo transfer guided by the results of the endometrial receptivity analysis and 32 patients with recurrent implantation failure who performed a standardized frozen-thawed embryo transfer. RESULTS: The data analysis revealed a displaced endometrial receptivity in 73% (49/67) of all tested patients. Out of these patients, 24% (12/49) were early receptive, 74% (36/49) were pre-receptive, and 2% (1/49) were post-receptive. Comparison of pregnancy rate, clinical pregnancy rate, and live-birth rate between personalized (49%, 39%, 27%, respectively) and standardized embryo transfer (44%, 31%, 19%, respectively) reveals no statistically significant difference. In both groups, patients had an average of four unsuccessful embryo transfers. CONCLUSION: In this cohort of patients with recurrent implantation failure, the endometrial receptivity analysis showed a high incidence of displaced endometrial receptivity. However, a personalized embryo transfer did not increase reproductive outcome. Displaced endometrial receptivity might not be the main cause for recurrent implantation failure in this cohort.

Mild COVID-19 has no detrimental effect on semen quality.

BACKGROUND: As of today, the effect of coronavirus disease 2019 (COVID-19) on male fertility remains unclear. Studies published so far have partly contradictory results, likely due to very small sample sizes and heterogeneous populations. To gain a deeper understanding of the impact of COVID-19 on male fertility, we performed a prospective case-control study, in which we examined the ejaculate of 37 subjects, including 25 subjects in the acute phase of mild COVID-19 and 12 subjects who did not suffer from COVID-19. Determination of semen parameters, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) qPCR, and infectivity analysis were performed in the acute phase of the disease and in series. RESULTS: Semen parameter values did not differ significantly between subjects with mild COVID-19 and the control group. The serial examination of semen parameters revealed no significant changes between 4, 18, and 82 days after the onset of symptoms. SARS-CoV-2 RNA or infectious particles could not be detected in any ejaculate. CONCLUSION: Mild COVID-19 seems to have no detrimental effect on semen parameter values.

RéSUMé: CONTEXTE: À ce jour, l'effet de la maladie due au coronavirus 2019 (COVID-19) sur la fertilité masculine reste incertain. Les études publiées jusqu'à présent ont des résultats partiellement contradictoires, ce qui est probablement dû à la très petite taille des échantillons et l'hétérogénéité des populations. Pour mieux comprendre l'impact de la COVID-19 sur la fertilité masculine, nous avons réalisé une étude cas-témoins prospective, dans laquelle nous avons examiné l'éjaculat de 37 sujets, dont 25 sujets en phase aiguë de COVID-19 légère et 12 sujets qui ne souffraient pas de la COVID-19. La détermination des paramètres séminaux, la qPCR du coronavirus du syndrome respiratoire aigu sévère de type 2 (SRAS-CoV-2), et l'analyse de l'infectiosité ont été effectuées dans la phase aiguë de la maladie et dans la série. RéSULTATS: Les valeurs des paramètres du sperme ne différaient pas significativement entre les hommes atteints de la COVID-19 légère et ceux du groupe témoin. L'examen en série des paramètres du sperme n'a révélé aucun changement significatif entre 4, 18 et 82 jours après l'apparition des symptômes. L'ARN du SARS-CoV-2 ou les particules infectieuses n'ont été détectés dans aucun des éjaculats. CONCLUSION: La COVID-19 de forme légère ne semble pas avoir d'effet néfaste sur les valeurs des paramètres du sperme.

Fear of fertility side effects is a major cause for COVID-19 vaccine hesitance in infertile patients.

Introduction: This study aims to investigate the acceptance, hesitance and attitudes of infertile female patients toward the COVID-19 vaccination. Methods: An anonymous cross-sectional online survey was conducted between 28th of January to 10th of August 2022. The questionnaire consisted of 35 questions on demographics, COVID-19 vaccination status, prior concerns of the vaccinated participants and reasons for not vaccinating among unvaccinated participants, and factors influencing the decision not to vaccinate. Results: Of 406 participants who answered all questions, 92.1% reported having received at least one dose of COVID-19 vaccine, 7.9% were unvaccinated. Factors associated with the decision for vaccination were full time or part time employment (p = 0.05), high trust in the principle of vaccination (p < 0.001), high willingness for other vaccination during fertility treatment (p < 0.001) and risk factors for severe COVID-19 (p = 0.007). Concerns about directly occurring adverse effects after vaccination (42.0%), about impact on own fertility (21.9%) or on the fertility treatment (27.5%) were the main concerns beforehand of vaccinated participants. Correlations between fertility concerns and mistrust in the general principle of vaccination were found. Beside general health concerns, unvaccinated participants reported fears about fertility impairment as the most important arguments against a COVID-19 vaccination (median of 5.0 on a five-point-Likert scale). Conclusion: Both vaccinated and unvaccinated participants stated having concerns and fears about side effects of the COVID-19 vaccination on their fertility. To increase patients' trust in medical recommendations, such as vaccination, to avoid mistrust in the medical system and to maintain patient's compliance, there should be additional educational services that address infertile patients and their needs.

An eight centre, retrospective, clinical practice data analysis of algorithm-based treatment with follitropin delta.

RESEARCH QUESTION: Can efficacy and success rates of the first recombinant FSH expressed in a human cell line with an individualized dosing algorithm based on body weight and anti-Müllerian hormone (AMH) as shown in the ESTHER-1 trial be confirmed in routine clinical practice? DESIGN: In eight reproductive medicine centres in Germany, observational data of 360 women who underwent ovarian stimulation with follitropin delta were evaluated as part of the quality control from January 2018 to June 2019. The data were analysed retrospectively. RESULTS: Mean age of patients was 33.5 (±3.8) years. Pretreatment AMH concentrations ranged from <0.5 ng/ml or 3.6 pmol/l (2.5%) to >5.6 ng/ml or 40 pmol/l (19.7%), with 79.7% of all AMH measurements above 2.0 ng/ml or 14.5 pmol/l. The mean number of oocytes obtained in n = 359 first follitropin delta cycles was 11.2 (±6.7) oocytes with 42.1% of patients having between eight and 14 oocytes retrieved at oocyte retrieval. The average clinical pregnancy rate in the first cycle with a fresh embryo transfer was 38.2% with a mean of 1.4 embryos per transfer. The cumulative pregnancy rate was 49.4% for the first stimulation cycle (including cryopreservation cycles generated from the first stimulation cycle). CONCLUSION: The goal of obtaining an adequate number of oocytes (8-14 oocytes) using the follitropin delta dosing algorithm was reached in 42.1% of patients despite a wide range of pretreatment AMH values, while achieving very good clinical pregnancy rates. Hence, algorithm-based ovarian stimulation with follitropin delta remains highly effective in clinical practice.

Assessment of SARS-CoV-2 in human semen-a cohort study.

OBJECTIVE: To investigate the presence of viral RNA in human semen of patients with severe acute-respiratory syndrome coronavirus 2 (SARS-CoV-2) and to evaluate its presence and relevance in semen parameters. DESIGN: Pilot cohort study. SETTING: University hospital. PATIENT(S): Thirty-four men were distributed as: 1) patients in convalescence (patients with confirmed SARS-CoV-2 infection in pharyngeal swab according to reverse-transcription polymerase chain reaction [RT-PCR] or antibodies); 2) negative control group (no antibodies); and 3) patients with an acute infection (detection of SARS-CoV-2 in pharyngeal swab). INTERVENTION: Semen and a blood sample were collected from each individual. MAIN OUTCOME MEASURE(S): Analysis of semen quality according to the World Health Organization standards. Detection of SARS-CoV-2 by RT-PCR in the native semen sample and after density gradient preparation. Confirmation of immunoglobulin (Ig) A und IgG antibodies in the blood. RESULT(S): Eighteen semen samples from recovered men were obtained 8-54 days after absence of symptoms, 14 from control subjects, and 2 from patients with an active COVID-19 infection. No RNA was detected by means of RT-PCR in the semen, including semen samples from two patients with an acute COVID-19 infection. Subjects with a moderate infection showed an impairment of sperm quality. CONCLUSION(S): A mild COVID-19 infection is not likely to affect testis and epididymis function, whereas semen parameters did seem impaired after a moderate infection. SARS-CoV-2 RNA could not be detected in semen of recovered and acute COVID-19-positive men. This suggests no viral transmission during sexual contact and assisted reproductive techniques, although further data need to be obtained.

Metabolic and behavioral parameters of mice with reduced expression of Syndecan-1.

Energy balance is essential for all species. Ligand-receptor interactions mediate processes that regulate body activities like reproduction and metabolism based on the energy status. Such receptors are the heparan sulfate proteoglycans and specifically the family of syndecans. Therefore we investigated the differences of metabolic parameters of heterozygous Syndecan 1 mice (Sdc1+/-) with reduced expression of Sdc1 and the corresponding wild type mice. Sdc1+/- mice have a reduced body weight although they show increased leptin and decreased corticosterone levels. Furthermore, their food and water intake is increased. This is accompanied with less adipose tissue, smaller adipocytes and thus an increased density of adipocytes. For the detailed analysis of the metabolism the automated PhenoMaster system has been used, which allowed continuous and undisturbed recording of food and water intake, energy expenditure and movement. The reason for the lower body weight was the higher energy expenditure of these animals compared to controls. Additionally, female Sdc1+/- mice showed an increased locomotor activity. Referring to organs, the intestine in Sdc1+/- mice was heavier and longer, but no differences at the cellular level could be observed. These findings were independent of normal mating or vice versa embryo transfers of Sdc1+/- and wild type embryos in recipient females of the other genotype. Herein we showed that the reduced expression of Sdc1 led to an altered metabolism on fetal as well as on maternal side, which may play a role in the growth restriction observed in human pregnancy pathologies and in mice lacking Sdc1.

Syndecan-1 Acts as an Important Regulator of CXCL1 Expression and Cellular Interaction of Human Endometrial Stromal and Trophoblast Cells.

Successful implantation of the embryo into the human receptive endometrium is substantial for the establishment of a healthy pregnancy. This study focusses on the role of Syndecan-1 at the embryo-maternal interface, the multitasking coreceptor influencing ligand concentration, release and receptor presentation, and cellular morphology. CXC motif ligand 1, being involved in chemotaxis and angiogenesis during implantation, is of special interest as a ligand of Syndecan-1. Human endometrial stromal cells with and without Syndecan-1 knock-down were decidualized and treated with specific inhibitors to evaluate signaling pathways regulating CXC ligand 1 expression. Western blot analyses of MAPK and Wnt members were performed, followed by analysis of spheroid interactions between human endometrial cells and extravillous trophoblast cells. By mimicking embryo contact using IL-1ß, we showed less ERK and c-Jun activation by depletion of Syndecan-1 and less Frizzled 4 production as part of the canonical Wnt pathway. Additionally, more beta-catenin was phosphorylated and therefore degraded after depletion of Syndecan-1. Secretion of CXC motif ligand 1 depends on MEK-1 with respect to Syndecan-1. Regarding the interaction of endometrial and trophoblast cells, the spheroid center-to-center distances were smaller after depletion of Syndecan-1. Therefore, Syndecan-1 seems to affect signaling processes relevant to signaling and intercellular interaction at the trophoblast-decidual interface.