Effectiveness of recombinant human FSH: recombinant human LH combination treatment versus recombinant human FSH alone for assisted reproductive technology in women aged 35-40 years.

RESEARCH QUESTION: According to real-world data, is recombinant human FSH (r-hFSH) combined with recombinant human LH (r-hLH) or r-hFSH alone more effective for women of advanced maternal age (AMA) in terms of live birth? DESIGN: Non-interventional study comparing the effectiveness of r-hFSH and recombinant r-hLH (2:1 ratio) versus r-hFSH alone for ovarian stimulation during ART treatment in women aged 35-40 years, using real-world data from the Deutsches IVF-Register. RESULTS: Overall clinical pregnancy (29.8%, 95% CI 28.2 to 31.6 versus 27.8%, 95% CI 26.5 to 29.2) and live birth (20.3%, 95% CI 18.7 to 21.8 versus 18.0%, 95% CI 16.6 to 19.4) rates were not significantly different between the combined r-hFSH and r-hLH group and the r-hFSH alone group (P = 0.269 and P = 0.092, respectively). Treatment effect was significantly higher for combined r-hFSH and r-hLH compared with r-hFSH alone for clinical pregnancy (33.1%, 95% CI 31.0 to 35.0 versus 28.5%, 95% CI 26.6 to 30.4; P = 0.001, not adjusted for multiplicity) and live birth (22.5%, 95% CI 20.5 to 24.2 versus 19.4%, 95% CI 17.6 to 20.9; P = 0.014, not adjusted for multiplicity) in a post-hoc analysis of women with five to 14 oocytes retrieved (used as a surrogate for normal ovarian reserve), highlighting the potential benefits of combined r-hFSH and r-hLH for ovarian stimulation in women aged 35-40 years with normal ovarian reserve. CONCLUSIONS: Women of AMA with normal ovarian response benefit from treatment with combined r-hFSH and r-hLH in a 2:1 ratio versus r-hFSH alone in terms of live birth rate. The effectiveness of treatments is best assessed by RCTs; however, real-world data are valuable for examining the effectiveness of fertility treatment, especially among patient groups that are not well represented in clinical trials.

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.

Artificial Intelligence in Reproductive Medicine - An Ethical Perspective.

Artificial intelligence is steadily being integrated into all areas of medicine. In reproductive medicine, artificial intelligence methods can be utilized to improve the selection and prediction of sperm cells, oocytes, and embryos and to generate better predictive models for in vitro fertilization. The use of artificial intelligence in this field is justified by the suffering of persons or couples who wish to have children but are unable to conceive. However, research into the use of artificial intelligence in reproductive medicine is still in the early experimental stage and furthermore raises complex normative questions. There are ethical research challenges because evidence of the efficacy of certain pertinent systems is often lacking and because of the increased difficulty of ensuring informed consent on the part of the affected persons. Other ethically relevant issues include the potential risks for offspring and the difficulty of providing sufficient information. The opportunity to fulfill the desire to have children affects the welfare of patients and their reproductive autonomy. Ultimately, ensuring more accurate predictions and allowing physicians to devote more time to their patients will have a positive effect. Nevertheless, clinicians must be able to process patient data conscientiously. When using artificial intelligence, numerous actors are involved in making the diagnosis and deciding on the appropriate therapy, raising questions about who is ultimately responsible when mistakes occur. Questions of fairness arise with regard to resource allocation and cost reimbursement. Thus, before implementing artificial intelligence in clinical practice, it is necessary to critically examine the quantity and quality of the data used and to address issues of transparency. In the medium and long term, it would be necessary to confront the undesirable impact and social dynamics that may accompany the use of artificial intelligence in reproductive medicine.

[Fertility preservation options before gonadotoxic antirheumatic treatment : A review]. / Fertilitätserhaltende Optionen vor gonadotoxischer antirheumatischer Therapie : Ein Überblick.

Cyclophosphamide is still clinically used in rheumatic diseases with severe disease courses. Cyclophosphamide has a pronounced gonadotoxic effect largely depending on the cumulative dose. The risk of amenorrhea is reported to be in the range of 12-54% and is dependent on the age of the patient at initiation of treatment. Every patient of reproductive age should therefore be offered counseling on options for fertility protection. There are 3 options for fertility protection: oocyte harvesting and cryopreservation after a hormonal stimulation of 10-14 days, ovarian wedge resection and cryopreservation and administration of a gonadotropin-releasing hormone (GnRH) agonist. The decision whether and, if so, which treatment should be performed is made in close consultation between the patient, rheumatologists and reproductive physicians and depends on the available treatment time window, the age of the patient and the severity of the underlying disease.

Clinical Efficacy of Follitropin Alfa in GnRH-Antagonist Protocols: A Prospective Observational Phase IV Study on the Use of Biosimilar Follitropin Alfa r-hFSH in Assisted Reproductive Technology in a Routine Care Setting.

BACKGROUND: This phase IV routine care study evaluated ovarian responses when using a biosimilar follitropin alfa r-hFSH (Bemfola®) for controlled ovarian stimulation (COS) in women undergoing assisted reproductive technology (ART) treatment who were pituitary-suppressed with a gonadotrophin-releasing hormone (GnRH) antagonist. METHODS: This multicenter, prospective, non-comparative, non-interventional study (Germany/Austria) was conducted with 885 women (Mean age of 34.0±4.4 years) for whom COS with Bemfola® and GnRH-antagonist for pituitary suppression were applied as part of in vitro fertilization (IVF) treatment with/without intracytoplasmic sperm injection (ICSI) observing routine clinical-practice protocols. Primary endpoint was the number of retrieved cumulus-oocyte-complexes (COCs). RESULTS: Among 986 ART cycles, COS was given for 9.9±1.8 days (First-day r-hFSH dose of 220.7±68.9 IU; mean total dose of 2184.3±837.5 IU). It was revealed that 99.1% of cycles resulted in follicular puncture, with mean of 10.7±6.6 oocytes retrieved. Successful fertilization took place after IVF/ICSI in 93.8% of follicular punctures. Freeze-all was performed in 14.2% of cycles. Fresh embryo transfer was performed in 76.9% of cycles with follicular puncture; mean day of transfer was 3.5±1.3 and average number of transferred embryos was 1.76±0.50. Clinical pregnancy rate was 30.2% of embryo-transfer cycles and 23.4% of started cycles. Sixty-nine reports of ovarian hyperstimulation syndrome (7.0% of started cycles) were documented. CONCLUSION: COS with Bemfola® in GnRH-antagonist IVF/ICSI protocols in a routine care setting led to an appropriate ovarian response allowing oocyte retrieval in 99.1% of initiated cases.

Empathetic application of machine learning may address appropriate utilization of ART.

The value of artificial intelligence to benefit infertile patients is a subject of debate. This paper presents the experience of one aspect of artificial intelligence, machine learning, coupled with patient empathy to improve utilization of assisted reproductive technology (ART), which is an important aspect of care that is under-recognized. Although ART provides very effective options for infertile patients to build families, patients often discontinue ART when further treatment is likely to be beneficial and most of these patients do not achieve pregnancy without medical aid. Use of ART is only in part dependent on financial considerations; stress and other factors play a major role, as shown by high discontinuation rates despite reimbursement. This commentary discusses challenges and strategies to providing personalized ART prognostics based on machine learning, and presents a case study where appropriate use of such prognostics in ART centres is associated with a trend towards increased ART utilization.

Diagnosis and Therapy Before Assisted Reproductive Treatments. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Register Number 015-085, February 2019) - Part 1, Basic Assessment of the Woman.

Introduction Supporting and counselling couples with fertility issues prior to starting ART is a multidisciplinary diagnostic and therapeutic challenge. The first German/Austrian/Swiss interdisciplinary S2k guideline on "Diagnosis and Therapy Before Assisted Reproductive Treatments (ART)" was published in February 2019. This guideline was developed in the context of the guidelines program of the German Society of Gynecology and Obstetrics (DGGG) in cooperation with the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). Aims One third of the causes of involuntary childlessness are still unclear, even if the woman or man have numerous possible risk factors. Because the topic is still very much taboo, couples may be socially isolated and often only present quite late to a fertility center. At present, there is no standard treatment concept, as currently no standard multidisciplinary procedures exist for the diagnostic workup and treatment of infertility. The aim of this guideline is to provide physicians with evidence-based recommendations for counselling, diagnostic workup and treatment. Methods This S2k guideline was developed on behalf of the Guidelines Commission of the DGGG by representative members from different professional medical organizations and societies using a structured consensus process. Recommendations The first part of this guideline focuses on the basic assessment of affected women, including standard anatomical and endocrinological diagnostic procedures and examinations into any potential infections. Other areas addressed in this guideline are the immunological workup with an evaluation of the patient's vaccination status, an evaluation of psychological factors, and the collection of data relating to other relevant factors affecting infertility. The second part will focus on explanations of diagnostic procedures compiled in collaboration with specialists from other medical specialties such as andrologists, human geneticists and oncologists.

Diagnosis and Treatment Before Assisted Reproductive Treatments. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Register Number 015-085, February 2019) - Part 2, Hemostaseology, Andrology, Genetics and History of Malignant Disease.

Introduction Supporting and counselling couples with fertility issues prior to starting ART is a multidisciplinary diagnostic and therapeutic challenge. The first German-language interdisciplinary S2k guideline on "Diagnosis and Therapy Before Assisted Reproductive Treatments (ART)" was published in February 2019. The guideline was developed in the context of the guidelines program of the German Society of Gynecology and Obstetrics (DGGG) in cooperation with the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). Aim In one third of cases, the cause of involuntary childlessness remains unclear, even if the woman or man have numerous possible risk factors. Because the topic is still very much taboo, couples may be socially isolated and often only present quite late to a fertility center. There is no standard treatment concept for these patients at present, as there are currently no standard multidisciplinary procedures for the diagnostic workup and treatment of infertility. The aim of this guideline is to provide physicians with evidence-based recommendations for counselling, diagnosis and treatment. Methods This S2k guideline was developed on behalf of the Guidelines Commission of the DGGG by representative members from different professional medical organizations and societies using a structured consensus process. Recommendations This second part of the guideline describes the hematological workup for women as well as additional diagnostic procedures which can be used to investigate couples and which are carried out in cooperation with physicians working in other medical fields such as andrologists, geneticists and oncologists.

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.

Physiological and anatomical aspects of the reproduction of mice with reduced Syndecan-1 expression.

BACKGROUND: Syndecan-1 is a heparan sulfate proteoglycan acting as a co-receptor for cytokines and growth factors mediating developmental, immunological and angiogenic processes. In human, the uteroplacental localization of Syndecan-1 and its reduced expression in pregnancy-associated pathologies, such as the intrauterine growth restriction, suggests an influence of Syndecan-1 in embryo-maternal interactions. The aim of the present study was to identify the effect of a reduced expression of Syndecan-1 on the reproductive phenotype of mice and their progenies. METHODS: Reproductive characteristics have been investigated using animals with reduced Syndecan-1 and their wildtype controls after normal mating and after vice versa embryo transfers. Female mice were used to measure the estrus cycle length and the weight gain during pregnancy, as well as for histological examination of ovaries. Male mice were examined for the concentration, motility, viability and morphology of spermatozoa. Organs like heart, lung, liver, kidney, spleen, brain and ovaries or testes and epididymis of 6-month-old animals were isolated and weighed. Statistical analyses were performed using two-tailed students t-test with P < .05 and P < .02, chi square test (P < .05) and Fisher's Exact Test (P < .05). A linear and a non-linear mixed-effects model were generated to analyze the weight gain of pregnant females and of the progenies. RESULTS: Focusing on the pregnancy outcome, the Syndecan-1 reduced females gave birth to larger litters. However, regarding the survival of the offspring, a higher percentage of pups with less Syndecan-1 died during the first postnatal days. Even though the ovaries and the testes of Syndecan-1 reduced mice showed no histological differences and the ovaries showed a similar number of primary and secondary follicles and corpora lutea, the spermatozoa of Syndecan-1 reduced males showed more tail and midpiece deficiencies. Concerning the postnatal and juvenile development the pups with reduced Syndecan-1 expression remained lighter and smaller regardless whether carried by mothers with reduced Syndecan-1 or wildtype foster mothers. With respect to anatomical differences kidneys of both genders as well as testes and epididymis of male mice with reduced syndecan-1 expression weighed less compared to controls. CONCLUSIONS: These data reveal that the effects of Syndecan-1 reduction are rather genotype- than parental-dependent.

Overnight ovarian tissue transportation for centralized cryobanking: a feasible option.

RESEARCH QUESTION: Is overnight transportation of ovarian tissue before cryopreservation in a centralized cryobank from the FertiPROTEKT network feasible? DESIGN: Data from 1810 women with cryopreserved ovarian tissue after overnight transportation from December 2000 to December 2017 were analysed with a focus on transportation, tissue activity parameters and pregnancy, and delivery rates after transplantation. RESULTS: A total of 92.4% of tissue samples arrived at ideal temperatures of 2-8°C, 0.4% were transported at temperatures lower than ideal and 6.4% were transported at temperatures that were too high, generally due to mishandling of the inlayed cool packs of the transportation boxes. In 62 women, 78 tissue transplantations were carried out. A subgroup of 30 women who underwent a single orthotopic transplantation with fulfilled criteria of a complete follow-up after transplantation until the end of study, a premature ovarian insufficiency after gonadotoxic therapy as well as the absence of pelvic radiation, was further analysed. In this group, transplantations into a peritoneal pocket accounted for 90%. Transplants were still active at 1 year and above after transplantation in 93.3%. Pregnancy and delivery rates were 46.7% and 43.3%, respectively, with one ongoing pregnancy at the end of the study. CONCLUSIONS: Overnight transportation for central cryobanking is a feasible concept that results in high reproducible success rates through standardized professional tissue freezing and storage.

Concept Paper on the Technique of Cryopreservation, Removal and Transplantation of Ovarian Tissue for Fertility Preservation.

The cryopreservation of ovarian tissue with subsequent transplantation of the tissue represents an established method of fertility protection for female patients who have to undergo gonadotoxic therapy. The procedure can be performed at any point in the cycle and thus generally does not lead to any delay in oncological therapy. With the aid of this procedure, more than 130 births to date worldwide have been able to be recorded. The birth rate is currently approximately 30% and it can be assumed that this will increase through the further optimisation of the cryopreservation and surgical technique. The concept paper presented here is intended to provide guidance for managing cryopreservation and transplantation of ovarian tissue to German-speaking reproductive medicine centres.

A Proteome Approach Reveals Differences between Fertile Women and Patients with Repeated Implantation Failure on Endometrial Level⁻Does hCG Render the Endometrium of RIF Patients?

BACKGROUND: The molecular signature of endometrial receptivity still remains barely understood, especially when focused on the possible benefit of therapeutical interventions and implantation-related pathologies. Therefore, the protein composition of tissue and isolated primary cells (endometrial stromal cells, ESCs) from endometrial scratchings of ART (Assisted Reproductive Techniques) patients with repeated implantation failure (RIF) was compared to volunteers with proven fertility during the time of embryo implantation (LH + 7). Furthermore, an analysis of the endometrial tissue of fertile women infused with human chorionic gonadotropin (hCG) was conducted. METHODS: Endometrial samples (n = 6 RIF, n = 10 fertile controls) were split into 3 pieces: 1/3 each was frozen in liquid nitrogen, 1/3 fixed in PFA and 1/3 cultured. Protein lysates prepared from fresh frozen tissue were processed for mass spectrometric analysis. RESULTS: Three proteins (EPPK1, BCLAF1 and PTMA) showed a statistically altered abundance in the endometrial tissue of RIF patients. Furthermore, pathways like metabolism, immune system, ferroptosis and the endoplasmic reticulum were altered in RIF patients. Remarkably, endometrial tissues of RIF patients showed a significantly higher (p-value = 9 × 10-8) protein intensity correlation (Pearson's correlation coefficient = 0.95) compared to fertile women (Pearson's correlation coefficient = 0.88). The in vivo infusion of hCG stimulated proteins of endocytosis, HIF1 signalling and chemokine production. Notably, patients suffering from RIF had a clinical pregnancy rate of 19% after the intrauterine infusion of hCG before embryo transfer (ET) compared to their failed previous cycles. CONCLUSION: Our study showed for the first time that the endometrial proteome composition of RIF patients differs from fertile controls during the window of implantation. The intrauterine infusion of hCG prior to an embryo transfer might improve the chemokine triggered embryo-endometrial dialogue and intensify the angiogenesis and immune response. From a clinical point of view, the hCG infusion prior to an embryo transfer might increase the pregnancy rate of RIF patients.

Possible Reasons for Discontinuation of Therapy: an Analysis of 571 071 Treatment Cycles From the German IVF Registry.

Introduction Numerous couples discontinue fertility treatment before achieving the objective, the birth of a child. The aim of this retrospective data analysis is to identify the reasons for early discontinuation of therapy (drop-out). Materials and Methods Retrospective data analysis. With the aid of the German IVF Registry (D·I·R ® ), a total of 122 560 "last cycles" in Germany in the period 2012 - 2015 were identified and the courses were analysed. Results From the named cohort of "last cycles", 37.3% of the female patients (45 699) gave birth to a child and ended the therapy. The remaining 76 861 discontinued the treatment before having a child. The fertility treatment was conducted due to a purely male indication in 46.27% of cases and in 17.96% the cause lay exclusively with the woman. 4.53% of the drop-outs suffered a miscarriage in the last cycle. 73.56% of the drop-out patients ended the therapy after the lack of a positive pregnancy test. After the third therapy cycle, 67% of the couples ended their treatment. Conclusion The results make it possible to provide couples with individual counselling. They offer an option for preparing for the emotional and physical hurdles.

Fertility protection: complications of surgery and results of removal and transplantation of ovarian tissue.

Fertility-preserving measures are becoming important for patients receiving oncological treatment. One method involves cryopreservation of ovarian tissue and transplanting it when treatment is completed. We report complications resulting from surgical and fertility medicine, and the results of procedures for the removal and transplantation of ovarian tissue carried out within the FertiProtekt network. A survey using a structured questionnaire was conducted among the FertiProtekt network centres between November 2015 and June 2016. The analysis included surgical techniques used to remove and transplant ovarian tissue, surgical complications and results. Laparoscopic removal and transplantation of ovarian tissue have a low risk of complications. Surgical complications occurred in three of the network's 1373 ovarian tissue removals (n = 1302) and transplantations (n = 71); two complications (0.2%) occurred during removal and one during transplantation. Menstruation resumed in 47 out of 58 women (81%) who underwent ovarian tissue transplantation. Hormonal activity occurred in 63.2% of transplantations with a follow-up of 6 months or over. Sixteen pregnancies occurred in 14 patients, with nine births. The risks and complications of removal and transplantation of ovarian tissue are similar to those of standard laparoscopy. These procedures are becoming standard for fertility protection in cancer patients.

Endometriosis doubles odds for miscarriage in patients undergoing IVF or ICSI.

OBJECTIVE: To identify and estimate the importance of risk factors on pregnancy loss until the end of the second trimester after clinical pregnancy was achieved by either in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection (ICSI). STUDY DESIGN: Retrospective cohort study including 588 cycles with fresh embryo transfers and 150 cycles with frozen-thawed embryo transfers using logistic regression. RESULTS: The rate of miscarriages subsequent to a fresh embryo transfer was significantly increased by a diagnosis of endometriosis (p=0.02), as well as significantly influenced by the age of the female patient at the time of oocyte retrieval (p<0.01) and the serum level of testosterone (p=0.02). The time between freezing and thawing of the pronuclear stages for a frozen-thawed embryo transfer revealed a trend to a higher rate of miscarriages (p=0.06). CONCLUSION: Endometriosis significantly decreases the chance of having a baby even with IVF or ICSI.

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.

hCG stimulates angiogenic signals in lymphatic endothelial and circulating angiogenic cells.

Human chorionic gonadotropin (hCG) has long been associated with the initiation and maintenance of pregnancy, where angiogenesis plays an important role. However, the function of hCG in angiogenesis and the recruitment of vascular active cells are not fully understood. In this study, the role of hCG and its receptor in circulating angiogenic and human endothelial cells, including lymphatic, uterine microvascular, and umbilical vein endothelial cells, was examined. Immunohistochemistry and immunoblot analysis were used to detect LH/hCG receptor expression and the expression of hCG-induced angiogenic molecules. HIF-1α was determined via ELISA and downstream molecules, such as CXCL12 and CXCR4, via real-time PCR. Chemotaxis was analyzed using Boyden chambers. Our results show that the LH/hCG receptor was present in all tested cells. Furthermore, hCG was able to stimulate LH/hCG-receptor-specific migration in a dose-dependent fashion and induce key angiogenic molecules, including HIF-1α, CXCL12, and CXCR4. In conclusion, our findings underscore the importance of hCG as one of the first angiogenic molecules produced by the conceptus. hCG itself alters endothelial motility, recruitment, and expression of pro-angiogenic molecules and may therefore play an important role in vascular adaption during implantation and early placental formation.

Xenotransplantation of cryopreserved human ovarian tissue--a systematic review of MII oocyte maturation and discussion of it as a realistic option for restoring fertility after cancer treatment.

OBJECTIVE: To systematically review the reporting of MII (MII) oocyte development after xenotransplantation of human ovarian tissue. DESIGN: Systematic review in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): Formation of MII oocytes after xenotransplantation of human ovarian tissue. MAIN OUTCOME MEASURE(S): Any outcome reported in Pubmed. RESULT(S): Six publications were identified that report on formation of MII oocytes after xenotransplantation of human ovarian tissue. CONCLUSION(S): Xenografting of human ovarian tissue has proved to be a useful model for examining ovarian function and follicle development in vivo. With human follicles that have matured through xenografting, the possibility of cancer transmission and relapse can also be eliminated, because cancer cells are not able to penetrate the zona pellucida. The reported studies have demonstrated that xenografted ovarian tissue from a range of species, including humans, can produce antral follicles that contain mature (MII) oocytes, and it has been shown that mice oocytes have the potential to give rise to live young. Although some ethical questions remain unresolved, xenotransplantation may be a promising method for restoring fertility. This review furthermore describes the value of xenotransplantation as a tool in reproductive biology and discusses the ethical and potential safety issues regarding ovarian tissue xenotransplantation as a means of recovering fertility.