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PubMed1993

Relationship between parental trinucleotide GCT repeat length and severity of myotonic dystrophy in offspring.

OBJECTIVE: To assess the relationship between the GCT repeat number in the myotonic dystrophy gene and the clinical phenotype and examine its predictive utility in prenatal testing. DESIGN: DNA from patients was examined for the length of the myotonic dystrophy GCT repeat region, using both Southern blot analysis and polymerase chain reaction. The results were compared with the clinical onset of disease, as well as with pregnancy outcomes. SETTING: Patient samples were referred to the Kleberg DNA Diagnostic Laboratory at the Baylor College of Medicine for DNA analysis by geneticists and genetic counselors (84%), neurologists (10%), and obstetricians and other specialists (6%). Clinical features including onset of disease and family pedigrees were determined by the referring centers. PATIENTS: A total of 241 patient samples from 118 families referred from primarily genetic or neurological centers for genetic linkage analysis or mutation analysis for myotonic dystrophy. This included 44 families referred for prenatal diagnosis. MAIN OUTCOME MEASURES: A relationship between myotonic dystrophy disease onset and length of the GCT repeat allele, parental origin of the disease allele, and results of prenatal diagnosis predictions of disease status were measured. RESULTS: There is a relationship between increasing repeat length and earlier clinical onset of disease. Essentially all (> 99%) myotonic mutations causing myotonic dystrophy are accounted for by GCT repeat amplification. Congenital myotonic dystrophy occurs with as few as 730 GCT repeats but only with alleles of maternal origin. Maternal GCT repeats were found as low as 75 (asymptomatic) that were amplified to result in a child with congenital myotonic dystrophy. Application of DNA diagnosis to 32 pregnancies provided an accurate method for identification of at-risk fetuses and allele enlargement. CONCLUSIONS: The GCT repeat in myotonic dystrophy is highly mutable. The triplet repeat amplification is highly specific for mutations involving the myotonin protein kinase gene accounting for myotonic dystrophy. The quantitation of triplet repeats can be more sensitive than physical, ophthalmologic, and electromyography examinations since the mutation can be detected in patients without evidence of myotonic dystrophy clinical findings. The length of the triplet expansion is influenced by the sex of the transmitting parent and is related to the clinical onset of disease features. Prenatal measurement of the GCT triplet repeat has utility for families with myotonic dystrophy risk since mutant and normal repeats are distinguishable and the length of mutant repeat alleles is associated with clinical severity. Thus, GCT triplet measurement provides a highly accurate means of detecting the myotonic dystrophy mutation in patients and offers a new reproductive option for families at risk for myotonic dystrophy.

Blotting, Southern↗
PubMed2003

[Association between ovarian stimulation regime and protein metabolism of patients undergoing IVF/ICSI therapy].

The aim of this study was to determine the relationship between the ovarian stimulation protocol (with HMG or FSH) after down-regulation with GnRH anologa and protein (total protein and albumin) as well as bilirubin and urea in serum. Furthermore, it was intended to find out the effect of these parameters on IVF/ICSI outcome. 50 patients were included in this study. All patients underwent controlled ovarian hyperstimulation for assisted reproduction therapy either with FSH (Gonal-F) or HMG (Menogon). Ovulation induction was induced by human chorionic gonadotrophine (HCG, Predalon) 10 000 IU i. m. The protein concentration (total protein, albumin) as well as bilirubin and urea concentrations were determined before down-regulation with GnRHa, at the beginning of ovarian stimulation with FSH or HMG, on the day of ovulation induction with HCG, during oocyte retrieval and fourteen days after embryo transfer. The age, body mass index and etiology of infertility showed no significant difference between patients stimulated with HMG or FSH. Total protein and albumin concentration decreased significantly (p=0.001) from 77.45 +/- 5.90 g/L and 47.02 +/- 3.41 g/L to 74.60 +/- 4.6 g/L and 45.04 +/- 2.39 g/L, respectively at the time of oocyte retrieval. Whereas, no significant change with bilirubin and urea concentration was observed. However, the mean concentration of total protein, albumin, bilirubin of patients who become pregnant was higher of those who did not. In conclusion, this study shows that total protein and albumin concentration in plasma decreased during the follicular phase significantly with the application of exogenous gonadotrophins and steroid hormones in comparison to the value before down-regulation. The mean value of total protein, albumin, bilirubin of patients who become pregnant was higher (but not significant) of those who did not. However, the high individual variation in the present results shows that these parameters are not useful as a predictor of IVF/ICSI outcome.

Blood Proteins↗
PubMed1995

A case-control study of maternal risk factors for thyroid cancer in young women (California, United States).

A population-based case-control interview study investigated whether reproductive factors are related to the striking female-over-male excess of thyroid cancer among women of reproductive age in Los Angeles County, CA (United States). As a separate component of that study, mothers of 153 cases and 140 controls who were age 40 or younger at diagnosis or reference date were interviewed by telephone to determine the significance of family and maternal risk factors in the subsequent development of thyroid cancer among the daughters. More case than control mothers experienced miscarriage prior to the index pregnancy (odds ratio [OR] = 2.0, 95 percent confidence interval [CI] = 1.1-3.5). Increased risk was associated with family history of thyroid cancer or other thyroid disease (OR = 2.1, CI = 1.2-3.6). More control than case mothers smoked during the index pregnancy (OR = 0.6, CI = 0.4-1.0); however, among mothers who smoked, case mothers smoked more. Case mothers experienced a greater increase in weight from minimum adult weight to weight at index pregnancy (P for trend = 0.01). Reports from mothers also confirmed the risk associated with the daughter's exposure to ionizing radiation from birth through adolescence; ionizing radiation remains the best-established risk factor for thyroid cancer.

Adolescent↗
PubMed1995

Reproductive and other factors and risk of epithelial ovarian cancer: an Australian case-control study. Survey of Women's Health Study Group.

Of the few factors known to be associated with epithelial ovarian cancer, the most consistently observed relate to women's reproductive function, although even here uncertainties remain. We have undertaken a case-control study involving personal interviews with over 1,600 women, the largest of its kind to date, to investigate further the associations between women's reproductive histories and other factors and the development of ovarian cancer. Cases were drawn from women diagnosed with epithelial ovarian cancer in 3 Australian states, Queensland, New South Wales and Victoria, between August 1990 and December 1993, and controls were drawn at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed information about women's reproductive and contraceptive histories and other factors of interest, such as smoking and family history of ovarian or other cancer. Findings were based on data from 824 cases and 860 controls and confirmed the reduced risk of ovarian cancer associated with increasing parity and duration of use of the oral contraceptive pill (OCP), hysterectomy and tubal ligation. The strongest association of all was seen with use of the OCP for 10 years or more. An inverse association between ovarian cancer and age at first birth was observed, but this was not statistically significant. There were no associations between development of ovarian cancer and number of incomplete pregnancies, use of hormone replacement therapy or menstrual history. Among other factors considered, education after leaving school was negatively associated and high body mass index, family history of ovarian cancer, use of talc in the abdominal or perineal region and smoking were positively associated with occurrence of ovarian cancer.

Adolescent↗
PubMed2006

Congenital vaginal obstructions: varied presentation and outcome.

Congenital obstructing lesions of vagina, hydrometrocolpos, and hematocolpos, present at a variable time during early childhood and adolescence to different medical and surgical specialties. Twenty-six cases presenting over an 18-years period (1987-2005) were divided into three groups; Group A: neonates (6), Group B: adolescents (18), and Group C: adults (2). Common presentations in neonates (Group A) were abdominal mass (5), neonatal sepsis (3), and respiratory distress (2); whereas abdominal pain (18), voiding dysfunctions (13), and backache (7) were prevalent in adolescents (Group B). Adults (Group C) presented with inability to consummate and infertility (2). Four patients received erroneous treatment; exploratory laparotomy (1) and appendectomy (3). Urinary symptoms and associated urinary abnormalities were present in more than 50% of cases, especially those with complex anomalies. Management included excision of imperforate hymen (16) and transverse vaginal septum (8) through perineal (20) and abdominoperineal approach (4). Patients with urogenital sinus (1) and cloacal malformation (1) had staged reconstruction at 2.5 years of age following preliminary vesicostomy and colostomy at birth. On follow up (range 1-15 years; mean 7) more than 60% patients have menstrual irregularity (11), endometriosis (5), and infertility (4). In conclusion, rarity and variable presentation of congenital vaginal obstructions can lead to delayed diagnosis and erroneous management. A high index of suspicion and cross-sectional imaging help in early diagnosis and associated renal anomalies. A comprehensive management is imperative to preserve the reproductive potentials, as significant proportion of patients may experience sexual difficulties, menstrual irregularity, and infertility.

Abnormalities, Multiple↗
PubMed2006

Factors influencing gestational age at antenatal booking at the University College Hospital, Ibadan, Nigeria.

In order to achieve the aim of improved outcome of pregnancy for mother and fetus, early booking (first antenatal visit), prior to 14 weeks' gestation is usually recommended. A survey of information on personal data, index pregnancy, reasons for booking at a particular gestational age, past obstetric history and medical history of 205 pregnant women attending the antenatal booking clinic at the University College Hospital, Ibadan, Nigeria was carried out using a structured questionnaire. The mean gestational age at booking was 21.82 (+/-7.0) weeks. Only 29 patients (14.1%) booked before 14 weeks. The reasons given for early booking among them were the perceived benefits of such practice (41.4%), physician's recommendation (34.5%) and occurrence of complication(s) in previous pregnancy (24.1%). Illness in the index pregnancy and nulliparity were the only factors found to significantly favour early booking. The need to educate women of the reproductive age group, who are potential mothers, on the benefits of early booking was recommended.

Adolescent↗
PubMed2004

Reliability of self-reports: data from the Canadian Multi-Centre Osteoporosis Study (CaMos).

Reliable questions enhance study design. We assessed the reliability of questions that gather demographic, sun exposure, reproductive history, and physical activity information. Subjects were participants in the Canadian Multicentre Osteoporosis Study (CaMos), a cohort study of Canadian adults recruited January 1996 to September 1997 in nine cities, stratified by sex, age, and location. Following personal interviews, 367 subjects were re-administered part of the questionnaire by telephone. Reliability was assessed using kappa and intra-class correlation. Reliability was excellent for employment status, reproductive history, weight and height (0.91 to 0.97), not differing greatly when stratified by age group or sex. Physical activity and sun exposure were reported with fair to good reliability (0.44 to 0.58), except for moderate activity (kappa = 0.30, 95% confidence interval 0.23, 0.37). Stratification by body mass index did not show significant differences. Many items can be reported reliably, especially those of height, weight, employment status and reproductive history, and, to a lesser extent, physical activity and sun exposure. Similar questions might be used reliably in future studies.

Aged↗
PubMed1980

Reproductive hormones in aging men. I. Measurement of sex steroids, basal luteinizing hormone, and Leydig cell response to human chorionic gonadotropin.

Although alterations of circulating sex steroids have been reported in aging men, it is not known to what extent reported changes may represent effects of variables other than aging. We have measured sex hormone levels, serum binding, the testosterone (T) response to hCG, and basal LH levels in 69 male volunteers, aged 25-89 yr, without alcoholism, obesity, chronic illness, or severe prostatic disease, and not using potentially interfering medications. In our study there was no effect of age on serum T, 5 alpha-dihydrotestosterone, estrone, or estradiol. Binding of T to T-binding globulin increased slightly with age, but not enough to decrease the free T index (fraction free X T concentration). Basal serum LH rose significantly. The T response to hCG suggested a somewhat diminished Leydig cell reserve with age, a conclusion consistent with the LH elevation. Our failure to detect the decreased T and free T index or increased estrogens reported by others could reflect afternoon rather than morning sampling, but is more likely to be due to our use of exceptionally healthy volunteers. We suggest that factors other than aging might have influenceed the data previously reported, and that aging per se need not be associated with altered sex steroid levels in the human male.

Adult↗
PubMed1989

[The effect of hydroxyprogesterone caproate and its combination with tamoxifen on steroid hormone receptors in the tumor and on the basic parameters of reproductive homeostasis in patients with cancer of the corpus uteri].

Oxyprogesterone capronate (OPC) was administered preoperatively to 46 patients with endometrial tumors and tamoxifen (T) + OPC--to 72 patients. Complex treatment was followed by more pronounced pathomorphosis in tumor. Both schedules inhibited gonadotropin secretion and lowered colpocytoscopic indexes. Dual effect of complex treatment (T + OPC) on the level of cytoplasmic receptors to progesterone was observed. Initially low levels rose while high ones dropped by the end of a 20-day course. Progestin treatment in endometrial carcinoma patients with relatively low estrogen levels should be complemented with tamoxifen to stimulate tumor sensitivity to progestagens.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed1990

[Analysis of the structure of the urban and rural populations of the central portion of Krasnodar Krai].

The structure of the populations in Korenovsk and Ust-Labinsk districts--sexual, age, family and migrant is described Reproduction is low in these populations. The after-reproduction age class in rural populations prevailed, which affects the ratio of recessive and dominant forms in hereditary pathology of these populations. Family planning in towns accounts for small size of the families and decrease of the role of natural selection. Gametic and endogamy indexes for these populations indicate that intensive migrant processes take place in populations studied, as shown by the level of recessive pathology. The results obtained can be used in the medical-genetic studies for this territory.

Age Factors↗
PubMed2003

Fluoride-induced disruption of reproductive hormones in men.

Fluoride-induced reproductive effects have been reported in experimental models and in humans. However, these effects were found in heavily exposed scenarios. Therefore, in this work our objective was to study reproductive parameters in a population exposed to fluoride at doses of 3-27 mg/day (high-fluoride-exposed group-HFEG). Urinary fluoride levels, semen parameters, and reproductive hormones in serum (LH, FSH, estradiol, prolactin, inhibin-B, free and total testosterone) were measured. Results were compared with a group of individuals exposed to fluoride at lower doses: 2-13 mg/day (low-fluoride-exposed group-LFEG). A significant increase in FSH (P<0.05) and a reduction of inhibin-B, free testosterone, and prolactin in serum (P<0.05) were noticed in the HFEG. When HFEG was compared to LFEG, a decreased sensitivity was found in the FSH response to inhibin-B (P<0.05). A significant negative partial correlation was observed between urinary fluoride and serum levels of inhibin-B (r=-0.333, P=0.028) in LFEG. Furthermore, a significant partial correlation was observed between a chronic exposure index for fluoride and the serum concentrations of inhibin-B (r=-0.163, P=0.037) in HFEG. No abnormalities were found in the semen parameters studied in the present work, neither in the HFEG, nor in the LFEG. The results obtained indicate that a fluoride exposure of 3-27 mg/day induces a subclinical reproductive effect that can be explained by a fluoride-induced toxic effect in both Sertoli cells and gonadotrophs.

Adult↗
PubMed1998

[Long-term ecological and genetic consequences of use of dioxin-containing environmental agents].

The long-term consequences of the use of dioxine-containing ecotoxic agents in the USA in 1961-1972 are ecologically and genetically characterized. There were increases in the incidence of pathological reproductive events in the contaminated region. It is concluded that there will be higher probability of abnormalities in the families of individuals born at war or just thereof. An association of impaired reproduction with functional disorders and women's poorer health, with higher incidence of somatic and gynecological diseases (chronic ones in particular) is shown. Cytogenetic changes in the lymphocytes were found in individuals from exposure risk groups. The contribution of chromosomal alterations observed in the contaminated area to immunodeficiency is appreciated. The systemic pattern of the action of biologically active properties of dioxine was demonstrated from the morphofunctional changes of different cell types. Cluster analysis revealed associations of cytogenetic parameters with the integrated index of health status in individuals from different contaminated areas. The ecological and genetic consequences may be regarded as part of homeostatic changes at many levels, as suggested by a correlation between the genetic instability and the changes occurring in other tissues, organs, and systems.

Adolescent↗
PubMed2004

Life course breast cancer risk factors and adult breast density (United Kingdom).

OBJECTIVE: To determine whether risk factors in childhood and early adulthood affect later mammographic breast density. METHODS: Subjects were 628 women who attended a medical examination at the University of Glasgow Student Health Service (1948-1968), responded to a questionnaire (2001) and had a screening mammogram in Scotland (1989-2002). Mammograms (median age of 59 years) were classified using a six category classification (SCC) of breast density percent. Logistic regression was used to determine associations between risk factors and having a high-risk mammogram (>or = 25% dense). RESULTS: In multi-variable analyses, high-risk mammograms were associated with parity (adjusted odds ratio (OR) per child: 0.77 (95% confidence interval (CI) 0.61-0.99)), age at first birth, OR per year: 1.05 (0.99-1.11), smoking at university, OR smokers versus non-smokers: 0.58 (0.36-0.92) and body mass index (BMI) while at university, OR per 1 kg/m2 0.75 (0.69-0.82). No associations with SCC were found for age at menarche, birth weight, oral contraceptive (OC) use, height, leg length or exercise at age 20. CONCLUSIONS: We confirm previous findings that breast density is affected by reproductive events and some anthropometric measures, however most of the risk factors acting throughout the life course which we examined were not closely related to adult breast density.

Adolescent↗
PubMed2005

Ovarian aging and bone metabolism in menstruating women aged 35-50 years.

OBJECTIVES: The aim of this study was to investigate the relationships between the levels of gonadotrophins, estradiol, inhibin-b and bone mass and turn-over in regularly menstruating women aged 35-50 years. METHODS: The study group included 87 healthy volunteers from the community aged 35-50 years. Bone mineral density of lumbar vertebras, wards triangle, throchanter, femur neck, bone resorption and formation markers were studied as well as the serum levels of gonadotrophins, estradiol and inhibin-b on the day 3 of menstrual cycle. RESULTS: The gonadotrophin levels showed significant positive relation with age, whereas inhibin-b and estradiol levels showed significant negative correlation with age. The gonadotrophins and estradiol levels had no significant association with bone mass and bone formation markers. Increased gonadotrophin (p < 0.001) levels and decreased inhibin-b (p < 0.01) levels independent from age were correlated with increased bone resorption. Gonadotrophins, estradiol, age, inhibin-b, body mass index (BMI) were the confounding factors for bone resorption (p = 0.015, R(2) = 0.190) and lumbar bone mass (p = 0.041, R(2) = 0.148). Multivariate analysis showed an independent contribution of inhibin-b and BMI in the prediction of lumbar bone mass. CONCLUSION: This findings suggested that estradiol was not the only factor responsible for bone loss and decrease in reproductive function because increased gonadotrophins and decreased inhibin-b levels might trigger some changes in bone metabolism prior to the menopause.

Adult↗
PubMed2000

Risk factors among young women with endometrial cancer: a Danish case-control study.

OBJECTIVE: This study was undertaken to identify and quantify risk factors for endometrial cancer among young women. STUDY DESIGN: This case-control study included all Danish women <50 years old who had endometrial cancer diagnosed during the period 1987 to 1994. A total of 237 case patients and 538 population control subjects matched with the case patients for age and residence were included in the analysis. RESULTS: Women with a family history of endometrial cancer had an odds ratio for endometrial cancer of 2.1 (95% confidence interval, 1.1-3.8)). Completion of 1 term pregnancy implied an odds ratio of 0.6 (95% confidence interval, 0.3-1.1). The risk of endometrial cancer decreased significantly with increasing age at first birth and with the number of induced abortions. Use of oral contraceptives for 1 to 5 years decreased the risk of endometrial cancer (odds ratio, 0.2; 95% confidence interval, 0.1-0.3). The odds ratio for endometrial cancer among women who received hormone replacement therapy for 1 to 5 years was 3.1 (95% confidence interval, 1.4-7.0). Body mass index was not demonstrated to be an independent risk factor in this study. The protective impacts of the different exposures (risk factors) can be expressed as etiologic fractions, which indicate how much each exposure reduces the occurrence of endometrial cancer compared with a situation without the existence of that particular exposure. These fractions were as follows: oral contraceptive use for > or =1 year, -45%; 2 term pregnancies, -88%; age > or =30 y when giving birth for the first time, -38%; and a history of incomplete pregnancy, -16%. CONCLUSION: A number of risk factors for endometrial cancer are common to premenopausal and postmenopausal women: family history, reproductive history, hormone replacement therapy, and the use of oral contraceptives. Among young women reproductive variables imply the greatest prophylactic potential.

Abortion, Induced↗
PubMed2004

Impact of genetic testing for breast-ovarian cancer susceptibility.

Previously, we have reported a clinical trial in which any woman in a defined geographic region who had a qualifying family history and who was referred by her physician or who was identified through a regional cancer registry was offered free genetic counseling, BRCA testing, and recommendations based on test results. Each family was represented by one affected and one unaffected person. Of the 87 families actually tested, 13 were found to have deleterious mutations. To assess the impact of the counseling and testing process, we contacted the tested individuals 1 month and 1 year after receiving the test result and those with an abnormal test result after 4 years. Index subjects, we found, differed significantly from relatives. Before coming for counseling, index subjects perceived both their general health and emotional health as worse than did their relatives. After counseling and testing, index subjects continue to worry more about breast cancer than do relatives. Affected subjects, we found, differed significantly from unaffected subjects. Before counseling, affected subjects knew more about breast cancer, perceived their general health as poorer, and reported greater adherence to recommended breast cancer surveillance than did unaffected subjects. After counseling and testing, affected subjects were less satisfied than unaffected subjects with having been tested. This study indicates that the group most prone to distress by cancer risk genetic counseling and testing is not the recruited relatives, nor even those affected with cancer, but rather the index patients themselves. The index patients, i.e., the ones who want the risk information most, appear to undergo the most stress in obtaining it.

Breast Neoplasms↗
PubMed1993

Fat and female fecundity: prospective study of effect of body fat distribution on conception rates.

OBJECTIVES: To study the effect of body fat distribution in women of reproductive age on fecundity. DESIGN: Prospective cohort study of all women who had entered a donor insemination programme. SETTING: One fertility clinic serving a large part of the midwest of the Netherlands. SUBJECTS: Of 542 women attending the clinic for artificial insemination for the first time, 500 women were eligible for study. MAIN OUTCOME MEASURES: Probability of conception per cycle and number of insemination cycles before pregnancy or stopping treatment. RESULTS: A 0.1 unit increase in waist-hip ratio led to a 30% decrease in probability of conception per cycle (hazard ratio 0.706; 95% confidence interval 0.562 to 0.887) after adjustment for age, fatness, reasons for artificial insemination, cycle length and regularity, smoking, and parity. Increasing age was significantly related to lower fecundity (p < 0.05); very lean and obese women were less likely to conceive (p < 0.10) as were women with subfertile partners (p < 0.10). All other exposure variables were not significantly related to fecundity. CONCLUSIONS: Increasing waist-hip ratio is negatively associated with the probability of conception per cycle, before and after adjustment for confounding factors. Body fat distribution in women of reproductive age seems to have more impact on fertility than age or obesity.

Adipose Tissue↗
PubMed2001

[Bilateral hydatid cyst of the fallopian tubes: a case report].

We report an exceptional case of bilateral hydatid cysts that developed solely in the fallopian tubes of a young girl. The diagnosis was suggested by the clinical history, the patient's residence in an endemic area, and the ultrasound findings and was confirmed peroperatively. Due to the extensive damage bilateral salpingectomy was required compromising future reproduction potential. We discuss the pathogenesis of pelvic localizations and the ultrasound aspects of pelvic hydatid cysts.

Adult↗