National survey of the current management of infertility in women aged 40 and over in the UK.

We conducted a national survey to identify the variation in the management of infertility in women aged 40 and over among the assisted conception units in the UK. A total of 44 out of 69 IVF units replied by filling in a questionnaire. Nearly half of the units (49%) offer treatment to this age group 6 months after trying for a pregnancy. As first-line management, 71.7% would offer conventional in vitro fertilisation (IVF) and 17.9% intrauterine insemination (IUI). On average, the doctors would move on from IUI to the next step after three attempts. The survey revealed a mean age of 45 as the upper limit for application of IVF (own eggs), and 43% of the units will recommend three cycles of IVF using own eggs before moving to egg donation. Among interventions to improve outcome, 33.3% would consider blastocyst transfer, 5.9% pre-implantation genetic screening (PGS) and 3.9% assisted zona hatching (AZH).

Anterior mandible canal communications: a potential portal of entry for tumour spread.

OBJECTIVES: CT is often used to assess the fine anatomy of the anterior mandible. The objectives of this study were to (1) investigate the presence of communications between the inner and outer bone plates in this area, (2) localize these communications in relation to surgical-anatomical landmarks and (3) review the literature related to mandibular cancer invasion. METHODS: CT images of 50 patients were used for the identification of the intrabony canals and for the localization of canalicular communications connecting the labial and lingual mandibular plates, in relation to the mental foramen. RESULTS: Communications between the labial and lingual mandibular plates were found in 14 (28%) of 50 patients. These communications mainly appeared as a crossing of the lateral lingual with the incisive canal, but also as an extension of the median lingual canal to the labial plate. CONCLUSION: There is radiological evidence for the presence of a canalicular network bringing into communication the inner and outer bone plates in the anterior mandible. There are also indications that such a finding could assist in the better understanding of bone tumour invasion and spread. Further studies are required to verify and evaluate these findings.

Impaired insulin-dependent glucose metabolism in granulosa-lutein cells from anovulatory women with polycystic ovaries.

BACKGROUND: Insulin resistance and hyperinsulinaemia are well-recognized characteristics of anovulatory women with polycystic ovary syndrome (PCOS) but, paradoxically, steroidogenesis by PCOS granulosa cells remains responsive to insulin. The hypothesis to be tested in this study is that insulin resistance in the ovary is confined to the metabolic effects of insulin (i.e. glucose uptake and metabolism), whereas the steroidogenic action of insulin remains intact. METHODS: Granulosa-lutein cells were obtained during IVF cycles from seven women with normal ovaries, six ovulatory women with PCO (ovPCO) and seven anovulatory women with PCO (anovPCO). Mean body mass index was in the normal range in all three groups. Granulosa-lutein cells were cultured with insulin (1, 10, 100 and 1000 ng/ml) and LH (1, 2.5 and 5 ng/ml). Media were sampled at 24 and 48 h and analysed for glucose uptake, lactate production and (48 h only) progesterone production. RESULTS: Insulin-stimulated glucose uptake by cells from anovPCO was attenuated at higher doses of insulin (100 and 1000 ng/ml) compared with that by cells from either ovPCO (P=0.02) or controls (P=0.02). Insulin and LH stimulated lactate production in a dose-dependent manner, but insulin-dependent lactate production was markedly impaired in granulosa-lutein cells from anovPCO compared with either normal (P=0.002) or ovPCO (P<0.0001). By contrast, there was no difference in insulin-stimulated progesterone production between granulosa-lutein cells from the three ovarian types. CONCLUSIONS: Granulosa-lutein cells from women with anovPCOS are relatively resistant to the effects of insulin-stimulated glucose uptake and utilization compared with those from normal and ovPCO, whilst maintaining normal steroidogenic output in response to physiological doses of insulin. These studies support the probability of a post-receptor, signalling pathway-specific impairment of insulin action in PCOS.

Early ovarian ageing: are women with polycystic ovaries protected?

Screening asymptomatic women in the general population for 'early ovarian ageing' will be more effective in high-risk groups. Recent findings support the hypothesis that women with polycystic ovaries (PCO) may have actually been born with a larger pool of resting follicles. The mechanism is almost certainly genetic and occurs in fetal life. If, as is widely accepted, the rate of depletion of the ovarian reserve depends primarily on the size of the remaining pool of small follicles, women with PCO will be unlikely to undergo an accelerated depletion of their follicle pool, normally seen in the late thirties, significantly earlier. In terms of asymptomatic screening for early ovarian ageing in the general population, women with PCO constitute a low-risk group and should therefore be excluded.

Early ovarian ageing.

Observations from reproductive biology, epidemiology, and clinical assisted reproduction support the hypothesis that the time interval between the onset of accelerated decline of the ovarian reserve and the menopause is more or less fixed. Thus, it is estimated that women who become menopausal by the age of 45 may have experienced an accelerated decline of their fertility before the age of 32. Up to 10% of women in the general population may fall into this category, which has been described as "early ovarian ageing". Because of the long latent phase and predictable natural history, this condition is suitable for screening. High-risk groups include, women with a family history of early menopause. IVF has provided a model for the development of ovarian reserve tests, some of which appear promising as potential screening tools for the detection of early ovarian ageing in asymptomatic women in the general population.

Early ovarian ageing: a hypothesis. Detection and clinical relevance.

An important scientific breakthrough of the 20th century, IVF helped open new horizons in medicine, such as pre-implantation genetic diagnosis and embryonic stem-cell therapy. A further contribution of assisted reproduction technology has been the better understanding of reproductive ageing. Data from IVF cycles suggest that there is a fixed time-interval between accelerated decline of fertility and the menopause. This leads to the hypothesis that a significant proportion of asymptomatic women in the early thirties may be at risk of early onset of subfertility. IVF provides a model for the development of ovarian reserve tests, some of which appear promising as potential screening tools for early ovarian ageing in the general population.

In vitro fertilisation for unexplained subfertility.

BACKGROUND: In vitro fertilisation (IVF) is now a widely accepted treatment for unexplained infertility (RCOG 1998). However, with estimated livebirth rates per cycle varying between 13% and 28%, it's effectiveness has not been rigorously evaluated in comparison with other treatments. With increasing awareness of the role of expectant management and less invasive procedures such as intrauterine insemination, concerns about multiple complications and costs associated with IVF, it is extremely important to evaluate the effectiveness of IVF against other treatment options in couples with unexplained infertility. OBJECTIVES: The aim of this review is to determine, in the context of unexplained infertility, whether IVF improves the probability of livebirth compared with 1. expectant management 2. clomiphene citrate (CC) 3. intra uterine insemination (IUI) alone 4. IUI with controlled ovarian stimulation and 5. Gamete IntraFallopian Transfer (GIFT). SEARCH STRATEGY: RCTs were identified using the search strategies developed for the Menstrual Disorders and Subfertility Group. See Review group for more information. SELECTION CRITERIA: Only randomised controlled trials were included. Livebirth rate per woman was the primary outcome of interest. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed eligibility and quality of trials. MAIN RESULTS: Nine randomised controlled trials were identified. In two we could not extract data separately for unexplained infertility cases, two were non-randomised, one reported no valid rates (included in the review and not in the meta-analysis), leaving four trials for analysis. One trial compared two different interventions (IVF versus IUI with or without ovarian stimulation) and one study compared three interventions (IVF versus IUI with ovarian stimulation and GIFT). The number of trials assessing the effectiveness of IVF with the other treatments were as follows: IVF versus expectant management (one), IVF versus IUI (one), IVF versus IUI with ovarian stimulation (two) and IVF versus GIFT (three). Livebirth rate per woman was reported in two studies and three studies determined clinical pregnancy rate per woman. Multiple pregnancy rate was reported in three trials. Two studies reported ovarian hyperstimulation syndrome (OHSS) as an outcome measure. There were no comparative data for clomiphene citrate, and no comparative data on livebirth rates for expectant management or GIFT. There was no evidence of a difference in livebirth rates between IVF and IUI either without (OR 0.51, 95% CI 0.23 to 1.1) or with (OR 0.87, 95% CI 0.42 to 1.8) ovarian stimulation. There was no evidence of a difference in clinical pregnancy rates between IVF and expectant management. There was no significant difference in the clinical pregnancy rates between IVF and GIFT (OR 0.47, 95% CI 0.24 to 0.92). There was no evidence of a difference in the multiple pregnancy rates between IVF and either IUI with ovarian stimulation (OR 1.59, 95% CI 0.68 to 3.70) or GIFT (OR 0.47, 95% CI 0.08 to 0.58). Clinical heterogeneity was present among the studies included. However, there was no evidence of statistical heterogeneity, which allowed the studies to be combined for statistical analysis. REVIEWER'S CONCLUSIONS: Any effect of IVF relative to expectant management, clomiphene citrate, IUI with or without ovarian stimulation and GIFT in terms of livebirth rates for couples with unexplained subfertility remains unknown. The studies included are limited by their small sample size, so that even large differences might be hidden. Livebirth rates are seldom reported. Adverse effects such as multiple pregnancies and ovarian hyperstimulation syndrome have also not been reported in most studies. Larger trials with adequate power are warranted to establish the effectiveness of IVF in these women. Future trials should not only report rates per woman /couple but also include adverse effects and costs of the treatments compared as outcomes. Factors that have a major effect on these outcomes such as fertility treatment, female partner's age, duration of infertility and previous pregnancy history should also be considered.

Is there a link between an extremely poor response to ovarian hyperstimulation and early ovarian failure?

BACKGROUND: It has been previously reported that a group of 12 infertile women, who had a normal baseline hormonal profile and did not respond to repeated ovarian stimulation with gonadotrophins, developed ovarian failure within a few months. Based on this observation, we carried out a controlled retrospective cohort study to examine whether non-response to ovarian stimulation is linked to early ovarian failure. METHODS: All patients aged 35-40 years who had cancelled IVF cycles for non-response between 1991 and 1993 in our centre were asked to report on the subsequent development of menopausal symptoms, menopause or commencement of hormone replacement therapy. A control group consisted of patients with the same age and similar medical history, who had IVF the same year and responded well. RESULTS: Eleven out of the 12 patients of the non-response group developed menopausal symptoms within 7 years, compared with only four out of 24 in the control group. Similarly, eight out of 12 non-responders either went into menopause or started using hormone replacement therapy compared with one out of 24 in the control group. Using Fisher's exact test, the differences were highly significant (P < 0.0001). The median age at development of menopausal symptoms in the study group was 40 years (range 38-45). The median time between non-response and development of menopausal symptoms was 4 years (range 1-7). CONCLUSION: We carried out a controlled retrospective cohort study that showed a strong association between an extremely poor response to ovarian hyperstimulation and early ovarian failure.

Differences in effective dose estimation from dose-area product and entrance surface dose measurements in intravenous urography.

In this study, measurements of dose-area product (DAP) and entrance surface dose (ESD) were carried out in a sample of 25 adult patients who underwent intravenous urography (IVU). These measured quantities were used to estimate the effective dose E from the IVU examination, a quantity closely correlated to radiation risk. Estimating E involves the use of conversion coefficients that have been determined for specific X-ray views in a mathematical phantom. These are obtained under conditions which are not usually met in clinical practice. As a result, the E estimates using the two different measurable quantities can be quite different. Analysis of the calculation procedure suggests that the E estimate using the DAP measurements, in addition to being more practical, could be more accurate than using ESD measurements, as DAP is sensitive to the X-ray field size settings. Furthermore, it is shown that in the absence of the appropriate equipment, a reliable E estimate can be obtained from the ESD calculated using the exposure data for each X-ray view.