Diabet. Med. 29, 345–350 (2012)
Aims Plasma glucose levels influence growth hormone concentrations. Oral contraceptives are known to affect circulating growth hormone levels and glucose metabolism. ...While growth hormone plays an important role in hypoglycaemia counter‐regulation, it has been shown that oral contraceptives increase growth hormone concentrations. In this context, we tested if serum growth hormone concentrations display a differential response on glycaemic variations in healthy women using oral contraceptives and those not using contraceptives.
Methods Fifteen healthy women with oral contraceptive treatment and 10 without participated in a stepwise hyper‐ and hypoglycaemic glucose clamp procedure. Serum growth hormone concentrations were measured at euglycaemic baseline and subsequently at plasma glucose plateaus of 8.8, 6.8, 4.8 and 2.8 mmol/l.
Results Growth hormone values were significantly higher in women using oral contraceptives throughout the experiments (P = 0.001). Hyperglycaemia decreased growth hormone concentrations in women using oral contraceptives (P = 0.009), but not in those who were not using oral contraceptives (P = 0.241). Hypoglycaemia significantly elevated growth hormone concentrations in women using oral contraceptives (P = 0.009), but not in those not using oral contraceptives (P = 0.094). Maximum growth hormone values were reached at the end of the hypoglycaemic plateau, with significantly higher concentrations in the group using oral contraceptives than in the group not using oral contraceptives (P = 0.016).
Conclusion Healthy women on oral contraceptive treatment display an increased responsiveness of growth hormone to hypoglycaemic, as well as hyperglycaemic conditions and generally higher serum growth hormone concentrations than women without oral contraceptives. Given the known boosting effects of growth hormone on hypoglycaemic hormonal counter‐regulation, oral contraceptives may thus be a pharmacological candidate contributing to combat hypoglycaemia unawareness in women with diabetes in the future.
INTRODUCTION: This study was performed to evaluate whether a tailored approach to the administration of the GnRH antagonist cetrorelix acetate according to follicular size leads to a reduction in the ...amount of Cetrotide® vials used and/or an increased number of monitoring visits. METHODS: Sixty patients were prospectively randomized (using sealed envelopes) to receive either the fixed multiple dose antagonist protocol starting on day 6 of stimulation (group 1), or an individualized protocol with the time of antagonist start according to follicle size (14 mm, group 2), or an individualized single dose protocol (group 3). Recombinant human (rh)FSH was used. The primary endpoints were the number of Cetrotide vials and number of monitoring visits. Statistical power for the parameter Cetrotide vials was 80%. RESULTS: Patients in group 1 needed significantly more Cetrotide vials (6.81 ± 1.61) than patients of group 2 (4.59 ± 1.65; P < 0.01). The number of monitoring visits was similar between the three groups. Surprisingly, the number of retrieved oocytes was significantly higher in the individualized groups as compared with group 1. Despite a significantly lower total amount of rhFSH used, estradiol levels were significantly higher in group 2 as compared with group 1. CONCLUSION: Tailoring of GnRH antagonist protocols leads to an optimization of ovarian stimulation with more oocytes retrieved despite less rhFSH used, and the same number of monitoring visits.
Abstract Long-term follow-up studies on the health of children born after assisted reproduction technologies are mandatory. Vision and hearing are the most important senses that continue to develop ...during childhood. There are few reports on vision and hearing in preschool children born after assisted conception. This prospective controlled blinded follow-up study examined 276 term-born singleton intracytoplasmic injection (ICSI) children and 273 spontaneously conceived controls at a mean age of 5.5 years and performed detailed vision and hearing test and clinically examined eyes and ears. There was no significant difference between ICSI and control children regarding the occurrence of vision or hearing impairments. Unsurprisingly, children with abnormalities in otoscopy were more likely to have an abnormal hearing test compared with children without abnormalities. Only 8.5% of ICSI parents and 25.4% of control parents whose children showed an abnormal hearing test knew about the hearing problems of their child. In conclusion, there was no difference in the development of hearing and vision in ICSI children and spontaneously conceived controls. But only few parents knew about hearing problems of their child after undergoing routine screening examinations. Parental interviews would therefore not be sufficient in order to assess vision and hearing in follow-up studies.
The introduction of optical coherence tomography angiography (OCTA) provides new insights into the retinal vasculature. The aim of this study was to explore the value of OCTA in imaging retinal ...hemangioblastomas and monitoring laser treatment in patients with von Hippel-Lindau (VHL) disease.
Ten eyes of 10 patients with VHL disease were included in this retrospective case series. All patients underwent complete ophthalmological work-up including OCTA for retinal and optic nerve head hemangioblastoma.
Two patients showed retinal scars and no recurrence of hemangioblastoma in OCTA. Three patients revealed recurrent hemangioblastomas. Two patients demonstrated a new hemangioblastoma. Three patients showed hemangioblastomas of the optic nerve head. Successful laser photocoagulation could be monitored with OCTA.
Screening for retinal hemangioblastomas with OCTA alone is not possible. OCTA may help to distinguish hemangioblastomas and other lesions in VHL disease, especially after treatment and allows the differentiation from harmless non-vascular lesions in questionable cases. Ophthalmic Surg Lasers Imaging Retina. 2016;47:935-946..
BACKGROUND Insulin resistance and obesity play an important role in the pathogenesis of polycystic ovary syndrome (PCOS). It is known that experimentally induced insulin resistance diminishes the ...stimulatory effect of insulin on leptin secretion. It is not yet known whether the long-term insulin resistance as found in PCOS patients alters the leptin response to hypo- and hyperglycaemia. METHODS We induced hyper- and hypoglycaemia by glucose clamp technique in 7 patients with PCOS and 20 healthy controls. After a plasma glucose level of 8.8 mmol/l was reached, the plasma glucose level was reduced stepwise to 6.8, 4.8 and 2.8 mmol/l. RESULTS The PCOS patients required lower glucose infusion rates to reach the glycaemic targets (P < 0.05). Serum insulin and C-peptide concentrations increased significantly during the clamp compared with the baseline in both groups (P < 0.001 for insulin, and P < 0.001, P < 0.005 for C-peptide control and PCOS, respectively) and increased significantly more in PCOS patients compared with the control group (both P < 0.05). Basal leptin levels were significantly higher in the PCOS group than in the control group (P = 0.005). In the controls, the leptin concentration increased significantly during the clamp (P < 0.001 for each glycaemic target), whereas in the PCOS group, leptin secretion increased only during hypoglycaemia (P = 0.04). CONCLUSIONS Compared with the healthy controls, the response of leptin secretion to hyper- and hypoglycaemia was diminished in PCOS patients. Changes in leptin secretion seem not to be caused by hyper- and hypoglycaemia, but rather by hyperinsulinaemia. Reduced insulin sensitivity seems to be responsible for the diminished leptin response, which might contribute to the obesity found in PCOS patients.
Zusammenfassung
Drei bis 5 % aller Kinder werden nach einer Form der assistierten Reproduktion geboren. Die Schwangerschaften verlaufen komplizierter und mit mehr perinatalen Komplikationen als ...solche, die spontan bei fertilen Paaren eintreten. Ursache dafür scheint auch ein nicht näher fassbares, mit der Subfertilität assoziiertes Hintergrundrisiko zu sein. Allerdings spielen möglicherweise weitere Faktoren wie die ovarielle Stimulation und die damit einhergehende unphysiologische Entwicklung des Endometriums eine relevante Rolle. Wenn Kinder am Termin gesund geboren werden, sprechen die Daten dafür, dass diese Kinder sich postnatal weitestgehend unauffällig entwickeln. Nach wie vor wird ein diskret erhöhtes onkologisches Risiko diskutiert, das sich zwar von dem spontan konzipierter signifikant unterscheidet, sich aber kaum in absoluten Zahlen niederschlägt. Erste Daten zur Pubertätsentwicklung und Surrogatparameter für nach einer ICSI (intrazytoplasmatische Spermieninjektion) konzipierten Jungen lassen vermuten, dass ggf. mit einer geringeren Fertilität im späteren Leben zu rechnen ist. Weitere Daten dazu sind notwendig.
Abstract There are only scarce data on the incidence of spontaneous pregnancy in infertility patients. Contraception after infertility treatment is another topic that has been neglected so far. ...Therefore, a questionnaire was sent to 1614 couples with a child conceived by intracytoplasmic sperm injection (ICSI) aged 4–6 years. A total of 899 couples responded (response rate 55.7%). A total of 10.9% of couples had used contraception. Of the couples that had actively tried to conceive, 20.0% had conceived spontaneously, resulting in a live-birth rate of 16.4%. 74.5% of these pregnancies were conceived within 2 years after delivery. A further 26.6% of couples conceived again by ICSI, with a live-birth rate of 20.9%. Maternal age was the only prognostic factor for spontaneous conception. Parents of multiples after ICSI did not have a higher chance of spontaneous conception than parents of singletons. Couples can be counselled that one out of five couples conceive spontaneously after successful ICSI. Even when assuming that none of the families that were lost to follow-up had conceived spontaneously, one out of eight couples would have conceived spontaneously. Therefore, it is important to counsel patients about the possibility of natural conception and necessity to use contraception despite their history of subfertility.
Cumulative pregnancy rates are useful in counselling couples on their chance of conceiving during infertility treatment. Patients also have to be counselled about the physical and psychological ...stress of infertility treatment. Beside the pregnancy rates, drop-out rates are a direct, and may be the most important, marker of physician quality in an IVF programme. Data from 4102 IVF cycles in 2130 patients in Germany were analysed retrospectively. Data were analysed using descriptive statistics as well as the Kaplan–Meier procedure. A real cumulative pregnancy rate of 31.2% was achieved after four cycles with an expected cumulative pregnancy rate (ECPR) of 53.3%. Age was a significant factor regarding pregnancy rates (ECPR after four cycles: 57.1% <35 years, 44.8% ≥35 years, 35.4% ≥40 years). The drop-out rate of non-pregnant patients increased from 39.9% after the first cycle to 62.2% after the fourth cycle, indicating the enormous stress and frustration that increased during the course of treatment. The drop-out rate should be used as an important marker of quality control. The presented data give, for the first time, a good basis for this counselling procedure in Germany.
The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain.
In this multicenter, randomized, ...open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding.
A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval CI, 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46).
Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).
Background: Posterior cruroplasty repair of a large paraesophageal hiatus hernia has a higher than desirable rate of recurrence attributable to the inexorable cyclic negative intrathoracic pressure ...of respiration and positive intraabdominal pressure produced by straining, physical exertion, and coughing. To reduce the risk of recurrence after repair of a large hiatus hernia and intrathoracic stomach, we have used posterior cruroplasty reinforced with an onlay polypropylene mesh prosthesis. This paper reviews the feasibility of this technique.
Study Design: We did a retrospective review of 44 patients with large hiatus hernia and intrathoracic stomach who had posterior cruroplasty and onlay of polypropylene mesh prosthesis applied to the crura and adjacent diaphragm to repair the hiatal defect.
Results: Preoperative symptoms (mean duration, 26 months) included pain (33 patients), vomiting (21), dysphagia (19) and anemia (8). The typical patient (28 men and 16 women, mean age, 60) had two-thirds or more of the stomach above the diaphragm. Organoaxial gastric volvulus and herniated large or small bowel were present in 10 and 9 patients, respectively. A gastrostomy was performed for temporary drainage in 38 patients in addition to the hernia repair; 11 patients underwent a concomitant Nissen fundoplication. Postoperative complications included pleural effusion (four patients), atrial dysrhythmia (three patients), and superficial wound infection (two patients). Mean followup for 43 patients was 52 months. There have been no clinical recurrences.
Conclusions: Mesh prosthesis reinforced hiatus hernia repair is effective, appears to have a low clinical recurrence rate, and should be an option in the treatment of a large hiatus hernia with intrathoracic stomach.
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