Cryobiology and fertility preservation: a perspective on past, current and future studies.

Cryopreservation has been used over many decades for the maintenance of viable biological specimens. Its expansion into the area of fertility preservation has been a natural outcome of the increased risks to human fertility from diseases, such as cancer and its treatment protocols, including radiation and chemo-therapy, and the general lifestyle trend to later marriages. The use of assisted reproductive techniques (ART) in preserving fertility have benefitted significantly from new scientific approaches, such as cryostorage, in which live cells and tissues are stored at low temperatures and revived when necessary. This review focuses on "cryopreservation science monitoring in reproductive biomedicine" to evaluate knowledge, trends, driving forces, impetus, and emerging technologies in order to draw a future roadmap for this field. Our analysis of the field of cryobiology emphasizes the significance of strategic planning of cryobiology research to support more its extensive use in therapeutics in the future. The Royan Institute (Tehran, Iran) recognises this need and has developed a strategic plan to engage in multidisciplinary research on the application of cryobiology, including cryobioengineering, in disease mitigation. We hoped that this study can help improve the quality and quantity of public discourse and expert awareness of the role for cryopreservation in fertility preservation within ART. DOI: 10.54680/fr23410110112.

Myocardial perfusion SPECT in Germany from 2012 to 2021: insights into development and quality indicators.

PURPOSE: This paper summarises the results of 4 national surveys on the numbers, utilisation and technique of myocardial perfusion SPECT (MPS) from 2012 to 2021. METHODS: A one-page questionnaire for information on MPS in 2012, 2015, 2018 and 2021 was sent to German centres practising nuclear medicine. To check for representativeness, the numbers obtained were related to official annual data and furthermore to the numbers of invasive coronary angiography procedures (ICA). RESULTS: MPS examinations increased by > 40% from 2012 to 2021 and showed a centralisation with increasing MPS per centre. In 2020, a mild impact of the COVID-19 pandemic could be observed in the form of only a slight MPS increase, which was compensated in the following year. Outpatient care cardiologists represent the most important referrer (70%). Mostly, 2-day protocols were used. One-day protocols and stress-only protocols showed insignificant changes. The use of exercise stress decreased steadily. In 2021, exercise stress was replaced by pharmacological stress as the most frequent stress modality. Camera systems showed a shift to more SPECT-CT systems. The use of gated SPECT increased to almost 90%. Quantitative scoring showed an increasing acceptance. The ratio of invasive coronary angiographies (ICA) to MPS was between 3.9 and 4.5. A significant proportion of ICA in the context of CCS (chronic coronary syndrome) was performed without prior testing for ischaemia. CONCLUSION: The 2012 to 2021 MPS surveys reveal a continuously growing number of examinations with only a mild temporary effect of the COVID-19 pandemic and a centralisation with increasing numbers per centre. Performance and technical data reveal a high-grade adherence of MPS practice to the current ESC guideline. A large potential of non-invasive diagnostics remains for the future.

Bi-allelic variants in DNA mismatch repair proteins MutS Homolog MSH4 and MSH5 cause infertility in both sexes.

STUDY QUESTION: Do bi-allelic variants in the genes encoding the MSH4/MSH5 heterodimer cause male infertility? SUMMARY ANSWER: We detected biallelic, (likely) pathogenic variants in MSH5 (4 men) and MSH4 (3 men) in six azoospermic men, demonstrating that genetic variants in these genes are a relevant cause of male infertility. WHAT IS KNOWN ALREADY: MSH4 and MSH5 form a heterodimer, which is required for prophase of meiosis I. One variant in MSH5 and two variants in MSH4 have been described as causal for premature ovarian insufficiency (POI) in a total of five women, resulting in infertility. Recently, pathogenic variants in MSH4 have been reported in infertile men. So far, no pathogenic variants in MSH5 had been described in males. STUDY DESIGN, SIZE, DURATION: We utilized exome data from 1305 men included in the Male Reproductive Genomics (MERGE) study, including 90 males with meiotic arrest (MeiA). Independently, exome sequencing was performed in a man with MeiA from a large consanguineous family. PARTICIPANTS/MATERIALS, SETTING, METHODS: Assuming an autosomal-recessive mode of inheritance, we screened the exome data for rare, biallelic coding variants in MSH4 and MSH5. If possible, segregation analysis in the patients' families was performed. The functional consequences of identified loss-of-function (LoF) variants in MSH5 were studied using heterologous expression of the MSH5 protein in HEK293T cells. The point of arrest during meiosis was determined by γH2AX staining. MAIN RESULTS AND THE ROLE OF CHANCE: We report for the first time (likely) pathogenic, homozygous variants in MSH5 causing infertility in 2 out of 90 men with MeiA and overall in 4 out of 902 azoospermic men. Additionally, we detected biallelic variants in MSH4 in two men with MeiA and in the sister of one proband with POI. γH2AX staining revealed an arrest in early prophase of meiosis I in individuals with pathogenic MSH4 or MSH5 variants. Heterologous in vitro expression of the detected LoF variants in MSH5 showed that the variant p.(Ala620GlnTer9) resulted in MSH5 protein truncation and the variant p.(Ser26GlnfsTer42) resulted in a complete loss of MSH5. LARGE SCALE DATA: All variants have been submitted to ClinVar (SCV001468891-SCV001468896 and SCV001591030) and can also be accessed in the Male Fertility Gene Atlas (MFGA). LIMITATIONS, REASONS FOR CAUTION: By selecting for variants in MSH4 and MSH5, we were able to determine the cause of infertility in six men and one woman, leaving most of the examined individuals without a causal diagnosis. WIDER IMPLICATIONS OF THE FINDINGS: Our findings have diagnostic value by increasing the number of genes associated with non-obstructive azoospermia with high clinical validity. The analysis of such genes has prognostic consequences for assessing whether men with azoospermia would benefit from a testicular biopsy. We also provide further evidence that MeiA in men and POI in women share the same genetic causes. STUDY FUNDING/COMPETING INTEREST(S): This study was carried out within the frame of the German Research Foundation sponsored Clinical Research Unit 'Male Germ Cells: from Genes to Function' (DFG, CRU326), and supported by institutional funding of the Research Institute Amsterdam Reproduction and Development and funds from the LucaBella Foundation. The authors declare no conflict of interest.

Efficacy of single-dose 500 mg mebendazole in soil-transmitted helminth infections: a review.

Soil-transmitted helminthiasis (STH) is caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm), and Ancylostoma duodenale and Necator americanus (hookworms). Mebendazole is one of the recommended preventive chemotherapy agents for STH. This review summarizes the efficacy data from 29 studies with single-dose 500 mg mebendazole in STH treatment and compares the results with those of a recently conducted phase 3 study of a 500 mg mebendazole chewable tablet against A. lumbricoides and T. trichiura infections. Studies that reported efficacy results against at least one STH infection were selected from the literature and efficacy data by each STH type were abstracted and pooled. Single-dose 500 mg mebendazole treatment resulted in a cure rate of 92.6% (range: 72.5-100%) for A. lumbricoides, 27.6% (range: 8.4-100%) for T. trichiura and 25.5% (range: 2.9-91.1%) for hookworms. Egg reduction rate for A. lumbricoides was 97.9% (range: 89.8-100%), for T. trichiura it was 72.9% (range: 31.6-93.0%) and for hookworms it was 72.0% (range: -6.5% (denoting an increase in egg count) to 98.3%). Similar results were observed in the studies that were placebo-controlled. In the phase 3 study, the cure rate and egg reduction rate reported was 83.7% and 97.9%, respectively, for A. lumbricoides and 33.9% and 59.7%, respectively, for T. trichiura. In conclusion, single-dose 500 mg mebendazole showed a high cure rate against A. lumbricoides and a substantial reduction in faecal egg count for all STH types. These results are consistent with the recently conducted phase 3 study of a new 500 mg chewable mebendazole tablet.

Mesh-covered embolic protection stent implantation in ST-segment-elevation myocardial infarction: final 1-year clinical and angiographic results from the MGUARD for acute ST elevation reperfusion trial

The MGuard, a bare metal stent covered with a polymer mesh, was designed to reduce distal embolization during percutaneous coronary intervention in ST-segment-elevation myocardial infarction. In the MGUARD for Acute ST Elevation Reperfusion trial, the primary end point of complete ST-segment resolution was significantly improved with the MGuard compared with control. We evaluated 1-year clinical and angiographic results.METHODS AND RESULTS:Patients with ST-segment-elevation myocardial infarction ≤12 hours undergoing primary percutaneous coronary intervention of a single de novo native lesion were randomized to the MGuard versus any commercially available metallic stent (39.8% drug-eluting). Clinical follow-up was performed through 1 year, and angiography at 13 months was planned in 50 MGuard patients. There was no difference in major adverse cardiac events (1.8% versus 2.3%; P=0.75) at 30 days between the groups. Major adverse cardiac events at 1 year were higher with the MGuard, driven by greater ischemia-driven target lesion revascularization (8.6% versus 0.9%; P=0.0003). Conversely, mortality tended to be lower with the MGuard at 30 days (0% versus 1.9%; P=0.04) and at 1 year (1.0% versus 3.3%; P=0.09). Late lumen loss at 13 months in the MGuard was 0.99±0.80 mm, and binary restenosis was 31.6%.CONCLUSIONS:In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, a trend toward reduced 1-year mortality was present in patients treated with the MGuard stent. Target lesion revascularization and major adverse cardiac events rates during follow-up were higher in the MGuard group than in the control stent group, and angiographic late loss of the MGuard was consistent with that expected from bare metal stents.

[Differentiated antiplatelet therapy for acute coronary syndromes]. / Differenzierte antithrombozytäre Therapie bei akutem Koronarsyndrom.

Dual antiplatelet therapy is the cornerstone of maintenance medication following invasive treatment of patients with acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable angina). Over the last decade, P2Y12 inhibition in addition to low-dose acetylsalicylic acid has been intensively debated. The debate was enriched by the results of the large phase III clinical trials for prasugrel (TRITON) and ticagrelor (PLATO) compared to clopidogrel in patients with acute coronary syndromes. This article summarizes the critical details und subanalyses of both study programmes and highlights on clinical decision making when using the three P2Y12 blockers in acute coronary syndromes. A special focus is on higher risk patients such as those with ST elevation myocardial infarction and those with coexisting diabetes, but also on minimizing relevant bleedings, which are common during more intense platelet inhibition.

Scientific molecular basis for treatment of reproductive failure in the human: an insight into the future.

PURPOSE: The purpose of this review is to summarize science-based new treatments for human reproductive failure and future developments. RESULTS: First will be discussed popular but erroneous myths of current non-science based treatments. Then will be discussed new treatments and their scientific base, including ovary and egg freezing, and transplantation to preserve fertility in young women undergoing gonadotoxic chemotherapy and radiation for cancer; new perspectives on human epididymal sperm maturation based on a comparison between ICSI (intracytoplasmic sperm injection) with testis sperm versus epididymal sperm; simplifying IVF and reducing cost by more intelligent and milder ovarian stimulation; improving pregnancy rate in older women; searching the genome to find genes which control spermatogenesis and whose deletion or mutation causes spermatogenic failure; and human spermatogenic stem cell culture to treat azoospermia, and to preserve fertility in pre-pubertal boys undergoing cancer treatment. CONCLUSION: With stem cell biology and molecular understanding of reproductive failure, new therapies for previously untreatable infertility are currently on the near horizon. Conversely our clinical results with new therapeutic approaches are adding to our understanding of the basic science of reproduction. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure.

Differences in cardiovascular risk factors and clinical outcomes between Western European and Southeast Asian patients treated with the Genous Bio-engineered R stent: an e-HEALING worldwide registry substudy.

OBJECTIVE: Percutaneous coronary interventions (PCIs) are increasingly being performed worldwide to treat patients with coronary artery disease. However, studies on the influence of ethnicity on clinical outcomes after PCI are scarce. In our current analysis, we evaluate the differences in baseline clinical, angiographic and procedural characteristics, and 12-month clinical outcomes in patients undergoing nonurgent PCI in Western Europe and in Asia. METHODS: We analyzed all patients enrolled in the worldwide e-HEALING (electronic Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth) registry living in Western Europe and Asia. All patients were treated with at least one endothelial progenitor cell capturing stent. The main study outcome was target vessel failure at the 12-month follow-up, defined as the composite of cardiac death or myocardial infarction and target vessel revascularization. RESULTS: A total of 3504 patients, 2873 living in Western Europe and 731 living in Asia, were assessed in the current analysis. Almost all of the baseline clinical and angiographic characteristics differed significantly between both populations. Target vessel failure at the 12-month follow-up occurred in 11.4% of the Western Europe patients and in 5.6% of the Asian patients (P<0.01). CONCLUSION: We conclude that differences exist in the baseline, angiographic, and procedural characteristics between Western European and Asian patients undergoing nonurgent PCI. In addition, the 1-year clinical outcomes differ significantly after PCI between Western European and Asian patients. Our results indicate that reports from studies performed worldwide should include both overall and regional subgroup outcomes.

Health economic evaluation of the use of drug-eluting stents : First results from the Drug-Eluting Stent Registry (DES.de).

OBJECTIVE: The purpose of the economic evaluation of the German Drug-Eluting Stent (DES) registry includes the investigation of the economic impact and cost-effectiveness of DES compared to bare-metal stents (BMS) and between paclitaxel-eluting (PES) and sirolimus-eluting stents (SES). Here, methodology and initial results are presented. METHODS: Patients were recruited in 2005 and 2006 in 87 centres across Germany. Selection of PES, SES, or BMS was made at the discretion of the cardiologists in charge. Clinical, economic, and quality of life (QoL) data were collected at baseline and up to 12 months. Group comparisons were conducted using Fisher's exact and t test. RESULTS: Overall, 3,930 patients were enrolled: 3,471 (75% male, 65 ± 11 years) received DES and 458 (74% male, 67 ± 11 years) BMS. Among the DES patients, 1,821 received PES (75% male, 65 ± 10 years) and 1,600 SES (76% male, 65 ± 11 years). There were baseline differences in clinical and procedural characteristics but not in QoL. During the hospital stay, major adverse cardiac and cerebrovascular events occurred in 1.6% of DES (PES 1.9%, SES 1.1%) and 2.2% of BMS patients (BMS vs. DES, PES, and SES p = 0.327, 0.706, and 0.098, respectively). Hospital treatment costs were 4,989 ± 1,284  and 3,609 ± 924 , respectively, in DES and BMS patients (p < 0.001) with no significant difference between PES and SES. CONCLUSION: The economic evaluation of the large DES registry demonstrates increased initial hospitalisation costs associated with DES compared to BMS. Further analysis of the economic impact and cost-effectiveness of DES will provide estimates on large "real world" patient populations for decision makers and aid in reimbursement decisions of DES within the German and other health care systems.

Ovary cryopreservation and transplantation for fertility preservation.

The aim of this review is to summarize the state-of-the-art of ovarian transplantation and cryopreservation. This field has progressed over the last half century from simple animal experiments to sophisticated application in humans. The initial poor results in humans began to improve when a series of nine monozygotic (MZ) twin pairs discordant for premature ovarian failure (POF) underwent ovary transplantation at one center. All of these fresh ovary transplants were successful, resulting in 11 healthy babies in 7 of the 9 recipients. The same surgical techniques were then applied to 3 frozen ovary tissue transplants, up to 14 years after the ovary had been frozen, resulting in 3 more healthy babies. Around the world, the number of healthy babies has now risen to 28. Even ovary allotransplantation is being attempted in the not so uncommon situation where a previous bone marrow donor is now willing to donate ovarian tissue to the same recipient. Recipients routinely reinitiated ovulatory menstrual cycles and normal Day 3 serum FSH levels by 4.5 months. Most conceived naturally (three of them twice or three times from the same graft). The duration of function of fresh ovarian grafts, contrary to initial expectations, indicated minimal oocyte loss from ischemia time. Grafts of just modest portions of ovarian tissue have lasted >7 years. In vitro studies suggest that vitrification of ovarian tissue may be an improvement over the 70% oocyte viability loss from slow freeze.

Risk factors associated with the metabolic syndrome in abdominal obesity.

Obesity is associated with the metabolic syndrome. However, not all obese individuals have cardiovascular risk factors (CVRF). It is not clear how many abdominally obese individuals are free of CVRF and what distinguishes them from the group of obese individuals with CVRF. In this study, we aimed to assess the associated factors and prevalence of abdominal obesity without CVRF. In our cross-sectional analysis, we included n = 4244 subjects from the Study of Health in Pomerania (SHIP), a population-based study and n = 6671 subjects from the Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment (DETECT) study, a representative primary care study in Germany. We defined abdominal obesity by waist-to-height ratio (WHtR) of 0.5 or greater. We assessed how many subjects with abdominal obesity had CVRF based on the definition of the metabolic syndrome. We analysed which conditions were associated with the absence of CVRF in abdominal obesity. In SHIP and DETECT, 2652 (62.5%) and 5126 (76.8%) subjects had a WHtR ≥ 0.5. Among those with a WHtR ≥ 0.5, 9.0% and 13.8% were free of CVRF and 49.9% and 52.7% had at least two CVRF in SHIP and DETECT, respectively. In both studies, after backward elimination, age, male sex, body mass index and high liver enzymes and unemployment were consistently inversely associated with the absence of CVRF. Among abdominally obese subjects, the prevalence of metabolically healthy subjects is low. Conditions consistently associated with the absence of CVRF in abdominal obesity are younger age, female sex, low BMI, and normal liver enzymes, the latter likely reflecting the absence of steatohepatitis.

Vitrification of oocytes from endangered Mexican gray wolves (Canis lupus baileyi).

Careful genetic management, including cryopreservation of genetic material, is central to conservation of the endangered Mexican gray wolf. We tested a technique, previously used to vitrify human and domestic animal oocytes, on oocytes from domestic dogs as a model and from the endangered Mexican wolf. This method provided a way to conserve oocytes from genetically valuable older female Mexican wolves as an alternative to embryos for preserving female genes. Oocytes were aspirated from ovaries of 36 female dogs in December and March (0 to 65 oocytes per female) and from six female wolves (4 to 73 per female) during their physiologic breeding season, or following stimulation with the GnRH agonist deslorelin. Oocytes from dogs were pooled; half were immediately tested for viability and the remainder vitrified, then warmed and tested for viability. All oocytes were vitrified by being moved through media of increasing cryoprotectant concentration, placed on Cryotops, and plunged into liquid nitrogen. There was no difference in viability (propidium iodide staining) between fresh and vitrified, warmed dog oocytes (65.7 and 61.0%, respectively, P = 0.27). Oocyte viability after warming was similarly assessed in a subset of wolves (4 to 15 oocytes from each of three females; total 29 oocytes). Of these, 57.1% of the post-thaw intact oocytes were viable, which was 41.4% of all oocytes warmed. These were the first oocytes from a canid or an endangered species demonstrated to have maintained viability after vitrification and warming. Furthermore, our results demonstrated that vitrification of oocytes with the Cryotop technique was an option for preserving female gametes from Mexican wolves for future use in captive breeding programs, although in vitro embryo production techniques must first be developed in canids for this technique to be used.

[Evidence-based management of ST-segment elevation myocardial infarction (STEMI). Latest guidelines of the European Society of Cardiology (ESC) 2010]. / Evidenzbasiertes Vorgehen beim ST-Strecken-Hebungsinfarkt (STEMI). Neueste Leitlinien der Europäischen Gesellschaft für Kardiologie (ESC) 2010.

Acute myocardial infarction and its consequences (death, chronic ischemic coronary artery disease, heart failure) are still the number 1 causes of death and of cardiovascular diseases in Germany. In this context, patients with STEMI are at the highest risk. The first-line management of STEMI patients often determines if the outcome is life or death. This overview presents the current optimal evidence-based management of STEMI patients as a practice-oriented extract according to the latest ESC guidelines, fully published some weeks ago (http://www.escardio.org).All efforts must be made to keep the respective time intervals between the onset of symptoms and the beginning of reperfusion therapy as short as possible, i.e. best within a dedicated STEMI network. Two of the time intervals are particularly essential: the time delay between the onset of symptoms and the first medical contact (FMC) and the time delay between FMC and the beginning of reperfusion. The time delay between the onset of symptoms and FMC depends on the patient as well as on the organization of the emergency medical service (EMS). Unfortunately, too many patients/bystanders still hesitate to immediately call the EMS. More intense measures must therefore be taken to educate the public. The optimal FMC by medical doctors or paramedics reacts quickly and ideally arrives with ECG equipment for immediate diagnosis of STEMI (persistent ST-segment elevation or presumably new left bundle branch block) before hospital admission. Unfortunately in many cases, the FMC is the emergency room of a hospital. Further decisions can be made without laboratory findings. In Germany, the average time delay between onset of symptoms and FMC is 100 min and therefore longer than in some other European countries.The next critical time interval is that between FMC and the beginning of reperfusion: this interval depends solely on the EMS organization and the distance to the next catheter laboratory with 24 h PCI (percutaneous coronary intervention) availability. The key question for further decisions is whether a primary PCI can be performed within 120 min after FMC. If so, the primary PCI should definitively be preferred. In patients <75 years presenting with a large anterior infarction within 2 h after onset of symptoms, this time interval should not exceed 90 min. For primary PCI an often used measure of quality is the "door-to-balloon" time, which should of course be as short as possible. Therefore, patients with STEMI should be admitted directly to the catheterization laboratory bypassing the emergency room or intensive care unit. In Germany, the average time interval between FMC and start of primary PCI is approximately 120 min just at the upper limit of the guideline recommendations. Some other European countries report a significantly shorter corresponding time delay.If primary PCI is not possible within 120 min (or 90 min) after FMC, thrombolysis must be initiated within 30 min after FMC, either in the EMS ambulance or in a nearby non-PCI hospital. A thrombolytic therapy, however, even if "successful", is not the final therapy: within 24 h (but not before 3 h) cardiac catheterization has to be performed with PCI, if applicable. Analyzing the overall revascularization rates in Germany, 81% receive primary PCI, 7% thrombolysis and 12% no reperfusion therapy. Regarding any reperfusion in STEMI, Germany holds the third place after the Czech Republic and Belgium.Patients presenting at 12-24 h after onset of symptoms or later may possibly benefit from a PCI, even if already asymptomatic, if signs of ischemia/viability in the infarct artery-related area are demonstrable. If this cannot be shown, PCI in these patients is not indicated.The first-line medication aims at dual antiplatelet therapy (DAPT) and anticoagulation. For DAPT, the combination of ASA with a thienopyridine is mandatory. If primary PCI is feasible, DAPT with prasugrel (loading dose of 60 mg, independent of age and weight) is preferred due to its faster onset of action and superior effectiveness over clopidogrel (loading dose of 600 mg). In patients with STEMI, prasugrel when compared to clopidogrel significantly reduced nonfatal myocardial infarction after 15 months from 9.0% to 6.8% and stent thrombosis significantly from 2.8% to 1.6% (ARC definite/probable). If, however, there are contraindications against prasugrel (s/p stroke or TIA) or if thrombolysis had to be performed, clopidogrel is the choice for DAPT.The i.v. administration of glycoprotein IIb/IIIa inhibitors (GPI) has been limited to only those patients with a high intracoronary thrombus burden. The upstream application of GPI is not recommended. Recommendations for the mechanical treatment of thrombus burden include manual thrombus aspiration (which was upgraded) and a mesh-based protection stent device (MGuard™). For anticoagulation, unfractionated heparin (UFH) is recommended as always but bivalirudin is an upcoming alternative, either in the catheterization laboratory on top after an EMS-delivered UFH bolus or as a possible first-line monotherapy. Bivalirudin may be preferred in STEMI patients with a high risk of bleeding. To prevent possible thrombotic events after PCI, bivalirudin should be continued for several hours after primary PCI.Regardless of whether PCI or thrombolysis was the first-line therapy and regardless of whether a stent (BMS or DES) was implanted, DAPT should be continued for 12 months with prasugrel 10 mg/day (or 5 mg/day, if ≥75 years old and/or <60 kg body weight) or clopidogrel (75 mg/day). There is no evidence that higher maintenance doses of clopidogrel may circumvent possible clopidogrel resistance. The usefulness of so far non-standardized in-vitro platelet aggregation measurements or the practice-oriented interpretation of genetic tests for CYP2C19 polymorphism is unknown. With the 12 months DAPT the patient is treated not the stent.

Ovarian function 6 years after cryopreservation and transplantation of whole sheep ovaries.

Whole ovary cryopreservation and transplantation has been proposed as a method for preserving long-term ovarian function. This work reports ovarian function 6years post transplantation of frozen-thawed whole sheep ovaries. Three 9-month-old Assaf sheep underwent unilateral oophorectomy to provide organs for the experiments. After perfusing with cold University of Wisconsin solution supplemented with 10% dimethyl sulphoxide, ovaries were cryopreserved using unidirectional solidification freezing technology. After thawing, ovaries were re-perfused and re-transplanted orthotopically by microvascular re-anastomosis, to the contralateral ovarian pedicle after removing the remaining ovary. Six years following transplantation and after inducing superovulation, the sheep were killed and the ovaries analysed. Two ovaries had normal size and shape showing some recent corpora lutea, while the third showed atrophic changes. A total of 36 antral follicles were counted by transillumination and four germinal vesicle oocytes were aspirated and matured in vitro to metaphase II. Serum progesterone concentrations were indicative of ovulatory activity in one of the three sheep. Histological evaluations revealed normal tissue architecture, intact blood vessels and follicles at various stages. Currently, this is the longest recorded ovarian function after cryopreservation and re-transplantation. Cryopreservation of whole ovaries, using directional freezing combined with microvascular anastomosis, is a promising method for preserving long-term reproductive capacity and endocrine function.

[Position paper nuclear cardiology: update 2008]. / Positionsbericht Nuklearkardiologie Update 2008: Aktueller Stand der szintigraphischen Methodik.

Nuclear cardiology is well established in clinical diagnostic algorithms for many years. This is an update 2008 of the first common position paper of the German Association of Nuclear Medicine and the German Association of Cardiology, Heart and Circulation Research published in 2001 aiming at an overview of state-of-the-art scintigraphic methods.

A series of monozygotic twins discordant for ovarian failure: ovary transplantation (cortical versus microvascular) and cryopreservation.

BACKGROUND: A series of monozygotic (MZ) twin pairs discordant for premature ovarian failure presented an unusual opportunity to study ovarian transplantation. METHODS: Ten MZ twin pairs requested ovarian transplantation and eight have undergone transplantation with cryopreservation of spare tissue. Seven had a fresh cortical tissue transplant, one of whom received a second frozen-thawed transplant after the first ceased functioning at three years. One had a fresh microvascular transplant. RESULTS: All recipients reinitiated ovulatory menstrual cycles and normal Day 3 serum FSH levels by 77-142 days. Six have already conceived naturally (one twice). Currently, two healthy babies have been delivered, and another three pregnancies are ongoing. The oldest transplant functioned for 36 months, resulting in one child and one miscarriage. She conceived again after a frozen-thawed secondary transplant. There was no apparent difference in return of ovarian function between the eight fresh ovarian grafts and the one frozen graft. CONCLUSIONS: Ovarian transplantation appears to restore ovulatory function robustly. Successful pregnancies, including one after cryopreservation, bode well for application to fertility preservation.