Consensus between niche experts was achieved on all items regarding ultrasonographic niche measurement.

Telomeres play a key role in upholding the integrity of the genome, and telomerase expression in spermatogonial stem cells is responsible for the maintenance of telomere length in the human male germline. We have previously described extensive allelic variation in somatic cell telomere length that is set in the zygote, the ultimate source of which may be the germline. This implies that despite telomerase activity, substantial telomere length variation can be generated and tolerated in the germline; in order to investigate this further, we have examined the nature of telomere length variation in the human male germline. Here, we describe an analysis of both genome-wide telomere length and single molecule analysis of specific chromosome ends in human sperm. We observed individual specific differences in genome-wide telomere length. This variation may result from genetic differences within the components that determine the telomere length setting of each individual. Superimposed on the genome wide telomere length setting was a stochastic component of variation that generates germ-cells containing severely truncated telomeres. If not re-lengthened during early embryogenesis, such telomeres may limit the replicative capacity of cells derived from the zygote and have the potential to create fusagenic chromosomes, unbalanced translocations and terminal micro-deletions. These data may have implications for the genetic determination of ageing, genetic disease and fertility.

ObjectiveTo determine the effect of infertility-linked sperm phospholipase Cζ (PLCζ) mutations on their ability to trigger oocyte Ca2+ oscillations and development, and also to evaluate the potential therapeutic utility of wild-type, recombinant PLCζ protein for rescuing failed oocyte activation and embryo development.DesignTest of a novel therapeutic approach to male factor infertility.SettingUniversity medical school research laboratory.Patient(s)Donated unfertilized human oocytes from follicle reduction.Intervention(s)Microinjection of oocytes with recombinant human PLCζ protein or PLCζ cRNA and a Ca2+-sensitive fluorescent dye.Main Outcome Measure(s)Measurement of the efficacy of mutant and wild-type PLCζ-mediated enzyme activity, oocyte Ca2+ oscillations, activation, and early embryo development.Result(s)In contrast to the wild-type protein, mutant forms of human sperm PLCζ display aberrant enzyme activity and a total failure to activate unfertilized oocytes. Subsequent microinjection of recombinant human PLCζ protein reliably triggers the characteristic pattern of cytoplasmic Ca2+ oscillations at fertilization, which are required for normal oocyte activation and successful embryo development to the blastocyst stage.Conclusion(s)Dysfunctional sperm PLCζ cannot trigger oocyte activation and results in male factor infertility, so a potential therapeutic approach is oocyte microinjection of active, wild-type PLCζ protein. We have demonstrated that recombinant human PLCζ can phenotypically rescue failed activation in oocytes that express dysfunctional PLCζ, and that this intervention culminates in efficient blastocyst formation.

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Objective To evaluate the safety and efficacy of thermal balloon therapy for menorrhagia.Design Prospective, observational study. Setting Fifteen centres in Canada and Europe.Population Two hundred and ninety-six eligible women for whom follow up data were available for three months or more. Eligible women included those for whom further fertility was not a concern, were not postmenopausal, suffered from intractable menorrhagia, had a normal uterine cavity, and who were fully informed regarding the investigational nature of uterine thermal balloon therapy.Methods Three hundred and twenty-one procedures of balloon endometrial ablation were performed using the same protocol between June 1994 and August 1996. Exclusion criteria included structural uterine abnormality or (pre) malignant lesions. Treatment entailed controlled heating of fluid in an intrauterine balloon. General anaesthesia was employed in the 61% of procedures while local anaesthesia with or without sedation was used in 39% of cases.Analysis Follow up data at 3 and/or 6, and/or 12 months were required for inclusion in the analysis. A paired t test, Wilcoxon signed-ranks test, and multiple and logistic regression analyses were used to evaluate the changes in bleeding and dysmenorrhoea patterns, and possible confounding variables, respectively. Success was defined as the subjective reduction of menses to eumenorrhoea or less.Results No intra-operative complications occurred, and post-operative morbidity was minimal. Success of the procedure was constant over the year (range 88%-91%). Treatment led to a significant decrease in the duration of menstrual flow and severity of pain (P < 0.0001). Increasing age, higher balloon pressure, smaller uterine cavity, and a lesser degree of pre-procedure menorrhagia were associated with significantly improved results. Pre-treatment with gonadotrophin releasing hormone agonists increased amenorrhoea and spotting rates (P = 0-03), but was only used in 5% of cases.Conclusion Thermal balloon endometrial ablation appears to be safe, as well as effective in properly selected women with menorrhagia and is potentially an outpatient procedure.