Female and male partner age and menotrophin requirements influence pregnancy rates with human menopausal gonadotrophin therapy in combination with intrauterine insemination

This study analyses the influence of female and male patient age and human menopausal gonadotrophin (HMG) requirements on clinical pregnancy rates and live birth rates with ovulation stimulation using HMG in combination with intrauterine insemination (IUI). In this study, 363 consecutive HMG/IUI treatment cycles in 184 patients carried out at a university fertility centre were analysed in a retrospective fashion. The main outcomes measured were clinical pregnancy rates and live birth rates. Increased female partner age (> or = 35) and male partner age (> or = 40) were found to negatively influence pregnancy rates with HMG/ IUI therapy. In addition, this study demonstrated a critical threshold of HMG requirements beyond which pregnancy did not occur. No pregnancies occurred in treatment cycles requiring > 25 ampoules (1875 IU) of menotrophins to achieve follicular maturity, irrespective of patient age. In conclusion, female partner age, male partner age, and HMG requirements all significantly influence pregnancy rates with HMG/IUI therapy.      

METHYLATION STATUS OF BCL6 DISTINGUISHES DNA SAMPLES FROM BENIGN AND MALIGNANT LYMPHOPROLIFERATIVE DISORDERS

INTRODUCTION: Core biopsy of the breast has become the method of choice for tissue diagnosis of screen detected microcalcifications and some mass lesions in many breast assessment centres. Biopsy results are not available until the following day. Imprint cytology of fresh breast core samples allows same-day reporting and patient counselling.
AIM: To determine the accuracy of core imprint cytology when compared with core biopsy diagnosis when used in a breast assessment centre setting.
METHODS: Core imprints (CI) were prepared and reported on all fresh core biopsies (CB) performed at the Sir Charles Gairdner Hospital Breast Centre from May to December 2000. Fresh core samples were placed on a glass microscope slide. Core radiographs were taken for microcalcification lesions (MC). A laboratory technician gently and quickly rolled the cores on the slide with fine forceps. The cores were fixed in formalin, processed and reported next day. The imprint slide was air dried and stained with DiffQuik. CI were reported using four categories: Insufficient, Benign, Indeterminate and Malignant. Counselling and planning for management were possible on the same day in women with malignant diagnoses. Clinicians were advised not to discuss negative or indeterminate CI results with women and to defer to the final CB report.
RESULTS: Cores were performed on 381 lesions. There were 83 carcinomas (38 in MC and 45 in masses) and 56 were called malignant on CI (absolute sensitivity 67.5%; 78.9% for MC and 57.8% for masses). 3 malignancies on CB were negative on CI giving a false negative rate of 3.6%. There were no false positive diagnoses. The predictive value of a benign diagnosis was 95.3%. There were no adverse effects in the histology of CB.
CONCLUSION: CI was an accurate method of providing an immediate diagnosis of malignancy in two thirds of malignancies confirmed on CB.     

Cloning and expression of the gene involved in Sanfilippo B syndrome (mucopolysaccharidosis III B)

Sanfilippo B syndrome is caused by a deficiency of alpha-N- acetylglucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulphate. Accumulation of the substrate in lysosomes results in degeneration of the central nervous system with progressive dementia often combined with hyperactivity and aggressive behaviour. In order to clone the deficient gene, we purified the enzyme from human placenta and obtained amino acid sequence information. Alignment of one of the CNBr generated internal peptides to sequence from the database revealed the chromosomal location of the gene in the 5' upstream flanking region of the gene for 17-beta-hydroxysteroid-dehydrogenase at 17q21.1. The available DNA sequence was used to clone the cDNA coding for alpha-N- acetylglucosaminidase and analyse its gene structure. The gene is fully contained in the 5' upstream flanking region of the gene for 17-beta- hydroxysteroid-dehydrogenase and interrupted by five introns. The cDNA clone has a length of 2575 bp and encodes a protein of 743 amino acids. Chinese hamster ovary cells transfected with the cDNA construct show alpha-N-acetylglucosaminidase activity about 17-fold over background. This will allow correction studies with NAG deficient Sanfilippo B cell lines and facilitate the development of enzyme replacement therapy for these patients.