Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial

BACKGROUND: To test whether ovarian stimulation for in-vitro fertilization (IVF) affects oocyte quality and thus chromosome segregation behaviour during meiosis and early embryo development, preimplantation genetic screening of embryos was employed in a prospective, randomized controlled trial, comparing two ovarian stimulation regimens. METHODS: Infertile patients under 38 years of age were randomly assigned to undergo a mild stimulation regimen using gonadotrophin-releasing hormone (GnRH) antagonist co-treatment (67 patients), which does not disrupt secondary follicle recruitment, or a conventional high-dose exogenous gonadotrophin regimen and GnRH agonist co-treatment (44 patients). Following IVF, embryos were biopsied at the eight-cell stage and the copy number of 10 chromosomes was analysed in 1 or 2 blastomeres. RESULTS: The study was terminated prematurely, after an unplanned interim analysis (which included 61% of the planned number of patients) found a lower embryo aneuploidy rate following mild stimulation. Compared with conventional stimulation, significantly fewer oocytes and embryos were obtained following mild stimulation (P < 0.01 and < 0.05, respectively). Consequently, both regimens generated on average a similar number (1.8) of chromosomally normal embryos. Differences in rates of mosaic embryos suggest an effect of ovarian stimulation on mitotic segregation errors. CONCLUSIONS: Future ovarian stimulation strategies should avoid maximizing oocyte yield, but aim at generating a sufficient number of chromosomally normal embryos by reduced interference with ovarian physiology.     

Infections along trans-mucosal fixation wires

In a retrospective investigation the frequency and reasons for infections along internal fixation wires used in trauma patients was studied. A group of 628 trauma patients of the period 1985-1990 was reviewed. In 50 patients out of this group internal wires were used that perforate the oral mucosa. In 11 cases an infection was noted. The trauma group was than compared with 634 patients who underwent orthognathic surgery in the same period. In this group only 3 patients developed an infection along an internal fixation wire. After analysis of the date it seemed that the use of preventive antibiotics and a good oral hygiene prevents infections along intern wires.     

Pancreaticoduodenectomy for pancreatic trauma. A case report

Pancreatic trauma is uncommon and severe, combined pancreaticoduodenal injuries are rare. Different surgical techniques for the management of these injuries have been used. In this article a case of severe pancreaticoduodenal injury which required pancreaticoduodenectomy is reported. This case is unusual because there was no history of trauma, the serum amylase level and abdominal radiograph were normal and the abdominal findings on admission to hospital were minimal. A system of grading pancreatic trauma in terms of severity is advocated and the management of pancreaticoduodenal injuries is discussed.     

Unusual behaviour of periapical cementous dysplasia

A case of periapical cementous dysplasia is reported that over the course of 12 years developed into a progressive bone lesion. The diagnostic and therapeutic aspects are discussed.     

Diazepam induces meiotic delay, aneuploidy and predivision of homologues and chromatids in mammalian oocytes

The tranquilizer and anti-convulsant diazepam (DZ) is a suspectedaneugen. In order to assess its aneugenic potential in mammalianoogenesis we exposed in vitro maturing mouse oocytes to thedrug. Spindle formation and cell cycle progression, the behaviourof chromosomes and the distribution of mitochondria were characterizedwith respect to induction of numerical chromosomal aberrations.A concentration of 25 µg/ml DZ induced a pronounced delayin maturation and blocked a high percentage of oocytes in meiosisI. This arrest was partly reversible. Hyperploidy was slightlyincreased in oocytes matured in the presence of 5 µg/mlDZ and became significantly elevated in oocytes matured with25 µg/ml DZ, relative to controls. Concomitantly, DZ inducedspindle aberrations and displacement of chromosomes from theequator, but unlike in mitosis and in male meiosis most oocytesstill possessed bipolar spindles. A significant fraction ofmeiotically delayed, metaphase I-blocked oocytes exposed to25 µg/ml DZ contained univalents. Some DZ-treated oocytesprogressing to meiosis II exhibited one or multiple single chromatids.Precocious chiasma resolution and equational segregation ofchromatids from functional univalents in first anaphase (predivision)may be responsible for this condition, a mechanism also discussedin the aetiology of maternal age-related aneuploidy. DZ disturbedthe spatiotemporal distribution of mitochondria during oocytematuration, possibly by binding to peripheral-type benzodiazepinereceptors on mitochondria, thus affecting the availability ofATP and calcium homeostasis. Blocks in maturation may also relateto binding of DZ to calmodulin. Data suggest that DZ exposesmammalian oocytes to predivision and aneuploidy. Thresholds,long lasting effects of DZ in vivo and sex-specific sensitivitiesin chemically induced aneuploidy of mammalian germ cells arecritically evaluated. ¹Present address: Department of Genetics Wageningen AgriculturalUniversity, 6703 HA Wageningen, The Netherlands ^*To whom correspondence should be addressed. Tel: +49 521 106 4727; Fax: +49 521 106 6015; Email: eiri{at}biologie.uni-bielefeld.de      

Patient participation in fundamental psychiatric genomics research: a Dutch case study

Objective To analyse the results of an action research process, the aim of which is to involve patients in fundamental psychiatric genomics research, against theoretical backgrounds that formulate a Dialogue Model for patient involvement. Background Mixed views continue to exist about the value, appropriateness and potential of involving consumers and patients in basic medical research. There is a need to learn from practical examples. Design An action research process was set up to facilitate and stimulate the involvement of a Dutch patient organization and a family organization in a psychiatric research consortium. Findings The premises and procedures of the Dialogue Model constitute good guidelines for involvement in fundamental research. However, the normative core features for patient involvement underlying the model prove problematic due to: (i) properties of complex psychiatric genomics research; (ii) the entanglement of subjectivity and basic psychiatric science; (iii) universal notions of citizenship and difficulties of delineating the patient in psychiatric genomics research. Conclusion Interaction and dialogue among scientists, patients and family members are possible in fundamental genomics research. The best approach for involvement would seem to be based on the creation of common ground and an evolving dialogue, which the guidelines of the Dialogue Model can provide. The challenge here will be to create also a dialogue on the normative anchor points of the dialogue process and to identify and monitor power relations inherent in these (tangible) dialogues.