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The sperm deformity and multiple anomalies indices: are they reliable in the identification of fertile and infertile semen?

DESIGN: Two new indices, the sperm deformity index and the multiple anomalies index, were evaluated in order to help identify fertile and infertile semen. RESULTS: It was found that only three out of 94 infertile men presented a sperm deformity index lower than the upper limits of normal. The sperm deformity index sensitivity and specificity were higher than those of the multiple anomalies index. CONCLUSION: The sperm deformity index is a reliable predictor in the identification of fertile and infertile semen, and therefore can help in the selection of patients who require assisted reproduction techniques.

Adult↗

A prospective multicentre study to develop universal immunochemical tests for predicting the fertile period in women. World Health Organisation Task Force on Methods for the Determination of the Fertile Period, Special Programme of Research, Development and Research Training in Human Reproduction.

Two immunochemical tests for predicting the fertile period have been adapted for application throughout the world. The estrone test involves the measurement of estrone-3-glucuronide (E1-3-G) in daily samples of early morning urine. The start of the fertile period is identified by a sustained rise in the concentration of E1-3-G (as determined by cumulative sum analysis); the end of potential fertility occurs 120 hours (5 days) after the peak level. Alternatively, the ratio of E1-3-G to pregnanediol-3 alpha-glucuronide (Pd-3 alpha-G) can be calculated and the fertile period identified between a defined rise in this index and the peak value plus 144 hours (6 days). One hundred thirty-one women from 10 countries provided samples from 557 menstrual cycles, and the results from 455 (82%) were accepted for statistical analysis. There were highly significant differences (P less than 0.0001) in the concentrations of the metabolites between centres, but the time intervals between both the rise and peak days and the day of the luteinizing hormone (LH) peak were less significantly different (P less than 0.05) for the estrone test and not significantly different for the ratio test. The fertile period was defined as the day of the LH peak -3 to the day of the LH peak +2. The estrone test successfully delineated this phase in 78% of menstrual cycles, and the ratio test, in 74%. The mean lengths of the derived fertile periods by both methods were 9.3 (SD 2.3) and 10.0 (SD 2.4) 24-hour periods (or days), respectively.

Adult↗

Reproductive effects of occupational DDT exposure among male malaria control workers.

To assess potential effects of human DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] exposure, we evaluated the reproductive history of 2,033 workers in the antimalaria campaign of Mexico. Data on occupational exposure to DDT and reproductive outcomes were gathered through a questionnaire, and workers provided information about 9,187 pregnancies. We estimated paternal exposure to DDT before each pregnancy using three approaches: a) a dichotomous indicator for pregnancies before and after exposure began, b) a qualitative index of four exposure categories, and c) an estimation of the DDT metabolite DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] accumulated in fat. To assess associations, we used logistic regression models that accounted for correlated observations and adjusted for parents' age at each child's birth, exposure to other pesticides, exposure to chemical substances in other employment, smoking, and alcohol consumption. The odds ratio for birth defects comparing pregnancies after and before the first exposure was 3.77 [95% confidence interval (95% CI), 1.19-9.52]. Compared with the lowest quartile of estimated DDE in fat, the ORs were 2.48 (95% CI, 0.75-8.11), 4.15 (95% CI, 1.38-12.46), and 3.76 (95% CI, 1.23-11.44) for quartiles 2, 3, and 4, equivalent to p,p -DDE in fat of 50, 82, and 298 microg/g fat, respectively. No significant association was found for spontaneous abortion or sex ratio. We found an increased risk of birth defects associated with high occupational exposure to DDT in this group of workers. The significance of this association at lower exposure levels found in the general population remains uncertain.

Abortion, Spontaneous↗

Angiogenesis during implantation, and placental and early embryonic development.

Angiogenesis, the development of new capillaries from pre-existing vessels, is induced by inflammation, wound healing, immune reactions and neoplasia, and is required for tumour growth and progression. Angiogenesis participates in a wide range of ovulatory-related and non-ovulatory-related reproductive processes. We present a review of current data pertaining to angiogenesis of pregnancy, with specific emphasis on implantation and placental and embryonic development in both normal physiology processes and various pathological conditions. To this goal, MEDLINE, Current Contents and Index Medicus were searched for studies published between 1966 and August 1999. Pertinent studies (including human and animal models) pertaining to angiogenesis of implantation and placental and embryonic development were reviewed. Current literature supports that angiogenesis is an essential physiological component of implantation, and placental and embryonic development. Angiogenesis also actively participates in abnormal implantation, and various pathological processes of the placenta including those observed in association with pre-eclampsia, growth restriction, maternal anaemia in the first-trimester and other hypoxia-related conditions during pregnancy. Finally, administration of an angiogenesis inhibitor (AGM-1470) in mice has been shown to result in complete failure of embryonic growth due to interference with decidualization, placental and yolk sac formation, and embryonic vascular development.

Adult↗

Preclinical development of antiviral drugs.

The early preclinical development of an antiviral agent is accomplished essentially in two stages. The first stage consists of gathering data to estimate the potential therapeutic index of the agent. This process includes testing for antiviral activity and for cytotoxicity in vitro and performing preliminary pharmacokinetic and toxicology studies in vivo. The second stage consists of carrying out more-extensive safety (toxicology) studies to determine any significant potential toxicities before the agent is used in humans. Chronic-toxicity studies, reproductive toxicity studies, and carcinogenesis bioassays are performed to support clinical trials of longer duration and, ultimately, approval of efficacious antiviral agents. It is essential to identify toxicities early in the developmental process for both safety and economic reasons. Progress in determining the mechanisms of specific toxicities will greatly aid in risk assessment and in our ability to predict and avoid these toxicities.

Animals↗

'Interoception' of heart rate, blood pressure, and myocardial metabolism during ergometric work load in healthy young subjects.

In a laboratory experiment intensities of 25, 50, and 75% of the individual range of a cardiovascular parameter (heart rate, blood pressure, and Robinson-index as an index of myocardial metabolism) were demonstrated during bicycle ergometer testing with healthy young subjects. In a subsequent phase they had to reproduce the same value of the parameter in question by regulating the physical work load of the ergometer. Reproduction accuracy was taken as an interoceptive index. We concluded from our data that subjects reproduced heart rate with high internal consistency but with a systematic bias. There is no linear consistency in blood pressure reproduction, and a moderate one in the reproduction of the index of myocardial metabolism. The physiological processes, upon which the interoception and reproduction is based, remain a question of further research.

Adult↗

Association of endometrial blood flow as determined by a modified colour Doppler technique with subsequent outcome of in-vitro fertilization.

An endometrial thickness of 10 mm or more has been reported to be favourable for embryo implantation. Nevertheless, many women participating in in-vitro fertilization (IVF) programmes have adequate endometrial thickness but do not achieve satisfactory implantation. With the aid of power Doppler sonography, we examined the association between intra-endometrial vascularity and reproductive outcome. For this study, we enrolled only women with endometrial thickness >/=ISOdia>/=10 mm and excluded those with apparent endometrial pathologies. Of 95 women undergoing IVF cycles, there resulted 37 intrauterine pregnancies. The women were of similar age, body mass index, peak oestradiol concentration and endometrial thickness, and a similar number of embryos were transferred. Those women with an intra-endometrial power Doppler area (EPDA) <5 mm2 achieved a significantly lower pregnancy rate (23. 5 versus 47.5%, P = 0.021) and implantation rate (8.1 versus 20.2%, P = 0.003) than those with an EPDA >/=ISOdia>/=5 mm2. We conclude that, in addition to endometrial thickness, EPDA may serve as a factor indicative of endometrial receptivity. Women with adequate endometrial thickness but a small EPDA tended to have an unfavourable reproductive outcome.

Adult↗

Serum leptin in children with obesity: relationship to gender and development.

BACKGROUND: The identification of the ob gene and its adipocyte-specific protein leptin has provided the first physiologic links to the regulatory system controlling body weight. In adults, elevations of serum leptin concentrations were closely correlated with the percentage of body fat. This study investigated whether leptin concentrations were elevated in obese children and the relationship between leptin concentrations and gender, pubertal stage, and race. METHODS: Seventy-seven children (44 girls and 33 boys), mean age, 11.3 years, with a body mass indices (BMIs) greater than 95% for age, race, and gender (mean BMI, 34.4) constituted the obese group. Thirty children (20 girls and 10 boys), mean age, 13.3 years, with BMIs less than 85% for age, race, and sex formed the control group. Radioimmunoassay for serum leptin was performed on a blood sample collected from each child after an overnight fast. RESULTS: The mean serum concentration of leptin in the obese group was 38.6 (SD, 21) ng/mL compared with 7.8 (SD, 6.5) ng/mL in the control group. Serum leptin concentrations were highly correlated with BMI (r = .88). Analysis of covariance revealed a main effect for Tanner stage and gender. CONCLUSIONS: As in adults, obese children have high concentrations of serum leptin, which were highly correlated with arm fat and BMI. Increased adipose tissue in children is associated directly with serum leptin concentration. Leptin concentrations were found to vary with Tanner stage independent of adiposity. Compared with boys, girls had increased leptin concentrations independent of adiposity. It was hypothesized that children manifest a relative "leptin resistance" to support increased growth and development of reproductive capacity.

Adipose Tissue↗

Plasma leptin concentrations are increased in women with premenstrual syndrome.

Leptin is a metabolic regulator of the hypothalamic- pituitary-gonadal axis, and plays an important role in human reproduction. Its neuro-endocrine effects are mediated by interactions with receptors in the hypothalamus, where emotional drive is also controlled. We postulated that circulating leptin concentrations are increased in premenstrual syndrome (PMS), and that this may be associated with the psychological symptoms of the disease. We obtained fasting venous samples from 32 women with PMS and 28 women with asymptomatic menstrual cycles, matched for age, body mass index and menstrual cycle length. Leptin concentrations were measured by radioimmunoassay. Leptin concentrations increased significantly during the luteal phases of the menstrual cycles of the control and PMS groups as compared with the follicular phase, having excluded the 11 women with PMS and six controls found to be anovulatory on the basis of mid-luteal plasma progesterone concentrations from the analysis. A greater increase was observed in women with PMS than the controls (P: = 0.00006 and 0.003 respectively). Although leptin concentrations in the follicular and luteal phases were higher in PMS than the controls, the difference was only statistically significant between the follicular phases (P: = 0.001). There was no clear relationship between leptin and oestradiol or progesterone in this study. These findings suggest that leptin may play a role in the pathophysiology of the disease, and requires further evaluation.

Adult↗

Clinics in diagnostic imaging (98). Heterotopic pregnancy with an intrauterine blighted ovum and a live tubal ectopic pregnancy.

A 26-year-old woman who was six weeks amenorrhoeic presented with vaginal spotting and mild abdominal pain. She had been coming to the 24 hours women's clinic at two-day intervals for the past week with the same symptoms. Ultrasonography two days ago showed one intrauterine gestational sac (IUGS) with a yolk sac within. Her pregnancy was clomiphene-related. Repeat transvaginal ultrasonography during this admission showed an IUGS, together with a left live tubal ectopic pregnancy. Heterotopic pregnancies used to be a rare entity. Now, given the increasing rise in assisted reproduction techniques, there should be a high index of suspicion for heterotopic pregnancy as this would impact upon clinical management. The ultrasonographical features of heterotopic pregnancy and its differential diagnoses are discussed.

Abortion, Missed↗

Development of a new Delayed Memory Index for the WMS-III.

This paper presents the Delayed Memory Index (DMI) as an alternative to the General Memory Index (GMI) of the Weschler Memory Scale-Third Edition (WMS-III). The WMS-III Immediate Memory Index (IMI) and the GMI are not parallel in structure, making a direct comparison between these index scores (i.e., immediate vs. delayed memory variables) difficult. The IMI is composed of the sum of scaled scores of four subtests (Logical Memory I, Verbal Paired Associates I, Faces I, and Family Pictures I) while the GMI is composed of the sum of scaled scores of five subtests (Logical Memory II, Verbal Paired Associates II, Faces II, Family Pictures II and Auditory Recognition Delayed). Inclusion of Auditory Recognition Delayed in the GMI is also problematic as it is highly skewed and limited by extreme ceiling effects (see Tulsky, Chiaravalloti, Palmer, & Chelune, 2003). To remedy these problems, we present a new index score that does not include auditory recognition, the Delayed Memory Index. Normative tables for the new Delayed Memory Index based on the inclusion of the Faces subtest, or alternatively the Visual Reproduction subtest, are presented, and initial estimates of their psychometric properties are described.

Abstracting and Indexing↗

Preliminary indication of a high prevalence of polycystic ovary syndrome in indigenous Australian women.

We aimed to estimate the likely prevalence of polycystic ovary syndrome (PCOS) in indigenous Australian women in a cross-sectional survey based on structured interviews. In the Kimberley region of Western Australia and south-western Victoria, between February and June 1999, women over the age of 18 available for interview and willing to participate were included. Menstrual status, anthropometric measures, fasting blood biochemistry and hirsutism were assessed. A total of 38 premenopausal women completed the survey. Of these, 50% had regular menstrual cycles of normal duration and no hirsutism; seven had oligomenorrhea and hirsutism/hyperandrogenemia; and of the nine women with hirsutism and regular menses, three had hyperandrogenemia. Thus, possibly ten women fulfilled the criteria of PCOS. This unique data set suggests a high prevalence of PCOS in indigenous Australian women. Further research to document this formally is warranted, in view of the potential adverse effects of PCOS on reproduction and metabolism.

Adult↗

A multicentred phase III comparative clinical trial of depot-medroxyprogesterone acetate given three-monthly at doses of 100 mg or 150 mg: 1. Contraceptive efficacy and side effects. World Health Organization Task Force on Long-Acting Systemic Agents for Fertility Regulation. Special Programme of Research, Development and Research Training in Human Reproduction.

Two dosages of depot-medroxyprogesterone acetate (DMPA), 100 mg and 150 mg given every 90 days, were compared in two groups of women with regard to effectiveness, reported complaints and reasons for discontinuation. A total of 1216 women were recruited into a seven-centre, multinational, randomized clinical trial. Follow-up was for a period of one year and resulted in a total of 5507 woman-months of experience of 100 mg DMPA and 5429 woman-months of experience of the 150 mg dose. The study showed little difference in efficacy and side effects between the two treatment groups. Two pregnancies occurred in women receiving 100 mg DMPA giving a Pearl Index of 0.44 per 100 woman-years. None occurred in the 150 mg group. There was no difference in the overall continuation rates between the two groups at one year, being 59.3% in the 100 mg group and 58.8% in the 150 mg group. Except for discontinuation of method use for amenorrhea, the rates of all medical and non-medical reasons given for discontinuation were comparable between the two treatment groups. Women's perception of lack of bleeding was reported as amenorrhea and resulted in discontinuation rates at 12 months for amenorrhea of 7.2% for women receiving 100 mg of DMPA and 12.5% for those receiving the 150 mg dose. Three centres, Alexandria, Karachi and Szeged, made the major contributions to this difference.

Adult↗

Combined intrauterine triplet and ectopic pregnancy following pronuclear embryo transfer in a patient with elevated serum progesterone during ovulation induction.

We present a case of heterotopic pregnancy occurring after ET of pronuclear-stage embryos. This case demonstrates that pronuclear embryos have a good implantation potential and suggests that the potentially adverse effect of high follicular-phase serum progesterone levels on endometrial development might be offset by early ET of pronuclear embryos. This, however, is speculative and deserving of formal scientific evaluation. Finally, we are reminded that heterotopic pregnancy complicates 1 to 3% of IVF-ET pregnancies and that, even with a high index of suspicion, most heterotopic pregnancies are diagnosed after rupture. All assisted reproductive programs should be reminded frequently that ectopic and heterotopic pregnancies do occur and can lead to serious consequences if left undetected.

Adult↗

Obesity in 21-hydroxylase deficient patients.

OBJECTIVES: To evaluate the natural history and timing of adiposity rebound (nadir of body mass index (BMI)) in children with congenital adrenal hyperplasia 21-hydroxylase deficiency (CYP21). STUDY DESIGN: A retrospective mixed longitudinal study. METHODS: Height and changes in body composition (BMI; weight (kg)/height2 (m)), triceps and subscapular skinfolds) were analysed in 22 (14 girls, eight boys) prepubertal patients with CYP21 for whom continuous anthropometric data were available for at least seven years. BMI and height SD scores were compared at 1, 5, and 10 years of age. Skinfold SD scores were compared at 2.5 and 5.5 years. Thirteen children (nine girls, four boys) had records available from birth which allowed the estimation of the age at adiposity "peak" and "rebound". RESULTS: A significant increase in BMI SD score was found at 5 and 10 years compared with those at 1 year. No significant change in height SD score was observed at these ages. Triceps and skinfold SD score were increased significantly at 5.5 compared with 2.5 years. The "rebound" in BMI SD score took place at 1.74 years (range 0.71-4.57) compared with 5.5 years (range 3.5-7.0) in the normal UK populations. CONCLUSIONS: Normally growing patients with CYP21 increased their BMI throughout childhood. Adiposity rebound took place on average three years earlier than in the general population. These findings suggest that even when well controlled in terms of their disease process, patients with CYP21 are at risk of obesity, which may have important implications for the evolution of reproductive function (polycystic ovaries), diabetes, hypertension, and cardiovascular disease in these subjects.

Adolescent↗

Cesarean and postpartum hysterectomy in Enugu, 1973-1986.

Obstetric hysterectomies were performed on 163 patients over a period of 13 years out of 56,823 deliveries. Seventy-one percent of the patients received no antenatal care in the index pregnancies. The majority were of high parity. Ruptured uterus was the commonest indication. Inadequate transfusion and late presentation affected the prognosis adversely. Ignorance, availability of suitable maternity care units and uncontrolled reproductive patterns were the main predisposing factors.

Cesarean Section↗