Cystic fibrosis Δf508 mutation screening in Brazilian women with altered fertility

Cystic Fibrosis (CF) is an autosomal recessive disease, caused by mutations in the Cystic Fibrosis Transmembrane Regulator gene (CFTR). The most frequent mutation in CF is ΔF508. The disease is clinically characterized by elevated concentrations of sweat chlorides and abnormally thick mucus. It affects organs such as lung, pancreas, gastrointestinal and reproductive tract. Women with CF commonly present delayed puberty and amenorrhea due to malnutrition. Our objective was to screen the presence of ΔF508 mutation in 24 women with altered fertility. Nine of these women presented reduced fertility without a known cause, four showed polycystic ovaries and two had early menopause. One woman with early menopause was a carrier of the ΔF508 mutation. Our study demonstrates that it is possible that the frequency of CF mutations among patients with altered fertility may be higher than expected. Previous data showed that fibrocystic women can show reduced fertility, maternal mortality associated with pregnancy and increased incidence of spontaneous abortion. We therefore recommend that women with reduced fertility undertake genetic tests for a better evaluation of pregnancy risks and clinical monitoring.     

Natural selection among Kinnaura of the Himalayan highland: A comparative analysis with other Indian and Himalayan populations

The present investigation on fertility and mortality differential among Kinnaura of the Himalayan highland is based on data collected from 160 post-menopausal women belonging to the middle and high altitude region of Kinnaur district of Himachal Pradesh (Indian Himalayas). Selection potential based on differential fertility and mortality was computed for middle-and high-altitude women. Irrespective of the methodology, the total index of selection was found to be highest among middle-altitude women (0.386) as compared with high-altitude (0.370) women, whereas for the total population it is estimated to be 0.384. It was found that the Kinnaura of the Himalayan highland showing moderate index of total selection and relative contribution of the mortality component (Im) to the index of total selection is higher than the corresponding fertility component (If). The analysis of embryonic and post-natal mortality components shows that the post-natal mortality components are higher in comparison with the embryonic mortality components among highlanders and needs special intervention and health care. The present findings are compared with other Indian tribes as well as non-tribes of the Himalayan region and other parts of the country. It reveals that this index among Kinnaura is moderate than the other population groups; among the Himalayan population, the highest was reported for Galong (It = 1.07) of Arunachal, whereas the lowest was reported from Ahom (It = 0.218) of Manipur. The correlation and regression analysis between total index of selection (It) and fertility (If) and mortality (Im) components for pooled data of populations of the Indian Himalayan states show that If and Im account for 21.6 and 29.1% variability, respectively. In Crow's total index of selection (It) along with strong association, which is significant at the 1% level, this indicates that mortality plays a greater role in natural selection in comparison with fertility among populations of the Indian Himalayas.     

Early influences on the tempo of puberty

Fetal growth retardation appears to be associated with an increased risk of premature adrenarche, early puberty, polycystic ovary syndrome and associated fertility problems. In a rat model of intrauterine growth retardation, based on ligation of the uterine arteries, the onset of puberty was delayed in female pups, with anovulation during the first cycle. The ovaries showed a lower number of follicles. The onset of puberty was also delayed in male pups. Testosterone production was lower in these growth-retarded rats compared with controls. The relationship between birth weight and the onset of puberty and pubertal progression in different cohorts of healthy children has been examined. In girls, no differences were observed in timing and progression of puberty, including age of menarche, between groups of different birth weights. In boys, a relatively delayed onset of puberty was observed in those with low birth weight, with a normally timed progression. In children with low birth weight, particularly boys, higher dehydroepiandrosterone levels were found compared with children with a normal birth weight, indicating an overactive adrenal gland in children with low birth weight. These data indicate that impaired fetal growth may have long-lasting effects on pubertal development. The fact that results of human studies on the relationship between fetal growth and the onset of puberty are often controversial may be explained by the heterogeneity of children born small for gestational age with respect to the intrauterine insult that they experience. From rat studies, it is clear that a serious intrauterine insult associated with growth failure can lead to dysregulation of puberty and gonadal function.     

Selection intensities in menopausal and permanent contraceptor women of a rural population in India

Changing fertility and mortality patterns due to socioeconomic forces have a profound effect on natural selection in human populations. The opportunity for selection was estimated in the rural population of Visakhapatnam District, Andra Pradesh, India, in 1979. A total of 1570 women were interviewed, 1544 among them had ever been pregnant. Data were analyzed to compute fertility and mortality components of the population. The index of total selection was found to be low. Selection in relation to birth control reveals that opportunity for selection is lower among women who completed their fertility by family planning methods than in women who completed their fertility by attaining menopause. Further, the results showed that differential fertility and mortality make equal contributions to the total measure of selection in both groups, whereas in developed countries like the US the mortality component contributes only a small fraction to the total index, due to improved health conditions.     

Oocyte pick-up in juvenile lambs affects neither onset of puberty nor their future fertility

A study was designed to evaluate whether the time of onset of puberty and fertility of young ewe lambs would be affected by oocyte pick-up conducted in single or repeated sessions during the first months of lambs' live. Five groups of lambs from the Karagouniko breed were used (A-E each n=12). In group A no treatments were applied (control group) while, laparoscopical follicular aspiration (OPU) was performed early in the third, fourth and fifth month of lambs age (groups C-E, respectively). From the second to fifth month of their age, group B lambs were aspirated four times in monthly intervals. All lambs were weighed at birth, weaning, at second month and monthly thereafter until the eighth month of age. Progesterone priming and ovarian stimulation by serial FSH administrations proceeded each OPU session. To determine onset of puberty blood progesterone concentration was assayed in samples collected initially every week and after the seventh month of age twice weekly. From the seventh month a fertile ram was introduced in each group and oestrous behavior/mating was daily monitored and recorded. Pregnancy diagnosis was carried out by transabdominal ultrasound scanning 55 days after rams' removal. At the fourth and fifth month of age group B lambs were lighter (p<0.05) than controls, but this difference was later equalized. The time of onset of puberty did not differ between groups (p=0.069) and ranged between 224 and 270 days. Some animals (n=15) entered puberty with a full-length luteal phase having progesterone concentration greater than 1ng/ml, while others (n=32) exhibited one or two short luteal phases before luteal length restoration. During the first breeding season 41 animals were fertilized and maintained pregnancy to term, without noticeable differences between groups (p=0.555). During the second breeding season, all ewes were naturally served and lambed at the expected time. It is concluded that OPU in young dairy lambs does not affect the time of onset of puberty, the endocrine profile of the lambs and it does not compromise their future fertility even if it is applied at four successive months.     

Optimal timing of operation for bleeding peptic ulcer: prospective randomised trial.

From October 1980 to September 1983 all patients with upper gastrointestinal bleeding were admitted to a centralised unit and investigated by early endoscopy. A total of 142 patients with a proved duodenal or gastric ulcer were randomised after stratification for age and site of ulcer to early (aggressive) surgical management or a delayed (conservative) policy. Significantly more operations (n = 42; 60%) were performed in the early than in the delayed (n = 9; 20%) groups (p less than 0.01). There were no deaths among the 42 patients under 60. The overall mortality in the 100 patients aged over 60 was 10% and when analysed on an "intention to treat" basis there was no difference between early and delayed surgery. When, however, an unrelated death from a bleeding colonic polyp was excluded and the data analysed on "treatment received" the mortality was only 2% in the early group compared with 13% in the delayed group (p less than 0.05). When analysis was confined to gastric ulcer the difference between early (0%) and delayed (24%) treatment was even greater. The results of this trial indicate that for patients over 60 an aggressive surgical policy is associated with a significant reduction in mortality.     

Marital fertility in polygynous unions in Nigeria

The effect of polygyny on fertility, by age cohort, was examined in 4 regions of Nigeria through use of data from the 1981-82 Nigerian Fertility Survey. Simple tabulation of numbers of live births by maternal age and type of marriage union indicated that, with the exception of the 30-39-year age group, fertility in polygynous unions tends to be higher than that in monogamous marriages. Overall, such tabulations reveal an average of 3.90 births among polygynous women and 3.47 births among monogamous women. However, when age-specific fertility rates were compared, except for women under 20 and over 40 years of age, rates were higher in monogamous unions (7.286 overall) than for women in polygynous households (7.200 overall). Mean completed fertility, taking into account marriage duration as well, shows a tendency for women in polygynous unions to be more fertile (with the exception of women aged 25-44 years who had been married 10-19 years). The absolute difference in fertility between the 2 types of marital unions ranged from 0.32 children in the northwest to 0.64 in the southeast. With adjustment for independent variables such as education, the absolute mean differences were reduced, from between 0.28 children in the southeast to 0.42 in the northeast, but the direction of high fertility was still in favor of women in polygynous unions. But when the covariates (e.g., age at marriage) were taken into account as well as the independent variables, there was a dramatic reduction in the mean difference between the fertility of these 2 groups of women. These findings suggest that some changes in reproductive behavior are taking place in Nigeria that are restricting the fertility of women in polygynous unions. These changes are hypothesized to reflect the spread of formal education in Nigeria, with the expectation that women will contribute to the costs involved in educating their children.     

The delineation of fertility strategies in a tribal population of India: the Koyas of Koraput District,Orissa

Demographic data collected for a tribal population of India, the Koyas of Koraput District, Orissa, were examined in light of 2 models of reproductive behavior associated with the economic value of children: the replacement effect and son survivorship motivation. Both models are united in the concept that infant/child mortality affects subsequent fertility. The database consists of retrospective fertility histories of Koya women who had completed their reproductive period. The total number was 260, with the total offspring numbering 1407. 2 distinct cohorts of women were formed for the purpose of analysis, separated only by the criterion of offspring survival: women who had experienced infant child mortality (129 women with 739 children); and women who completed their reproductive period without suffering offspring loss of this nature (132 women with 668 children). The cohort without child loss had a mean parity of 5.10, lower than the average parity of 5.73 recorded for the cohort whose reproductive histories included at least 1 infant/child death. Age specific marital fertility and birth interval analyses indicated that this differential was because of biological, not behavioral, factors. The age pattern of fertility of females suffering offspring mortality failed to demonstrate a high rate of childbearing in the later age intervals of the reproductive period, a characteristic pattern of couples attempting to "replace" lost offspring. Birth interval analysis pointed to biological "interval effect," whereby infant/child mortality caused a cessation of lactation and hence a shortening of postpartum amenorrhea. Computer simulation further indicated that the higher fertility differential of the cohort experiencing offspring loss still did not result in high son survivorship values. The findings agree with earlier studies indicating that for predemographic transitional populations, economically motivated fertility strategies are ineffectual.     

Hemoglobin genotype, fertility, and the malaria hypothesis

Epidemiological and clinical studies (Fleming et al. 1985; Perrin et al. 1982) indicate that hemoglobin (Hb) AS individuals have a selective advantage in malarial environments. Thus the high frequency of Hb S in human populations has been attributed to the decreased malarial morbidity and mortality experienced by Hb AS heterozygotes. It has also been suggested that Hb AS women have a higher fertility than that of Hb AA women, thus contributing to the elevated frequency of Hb S in malarial environments (Livingstone 1957). Firschein (1961) demonstrated a significantly greater fertility among Hb AS females, whereas Custodio and Huntsman (1984) documented no fertility differential between Hb AS and Hb AA women. Here I examine the reproductive careers of Hb AA and Hb AS subjects 40 years of age and older from Limon, Costa Rica. The purpose is to determine whether normal homozygotes and heterozygotes have significantly different fertilities. The research shows that these groups do not have significantly different completed family sizes (t = 0.38, ns) or significantly different numbers of pregnancies (t = 0.34, ns), live births (t = 0.36, ns), or abortions (t = 0.20, ns). My results support previous suggestions that differential fertility does not contribute to the maintenance of the Hb S polymorphism.     

The effects of high altitude on age at menarche and menopause

The age at menarche and menopause of three groups of Bhotia females living at high altitude, Himalayan region — Uttar Pradesh, North India, were studied. The Johari Bhotia women had earliest menarche (¯X=15.1±1.1 years) as compared to Rang Bhotias, settled (¯X=15.6±0.9 years) and Rang Bhotias, migratory (¯X=16.0±1.0 years). The differences between all these three groups for age at menarche were significant. A trend towards increase in age at menarche with an increase in altitude has been observed, but the total fertility period in the three groups remained similar as early menarche has been found to be associated with early onset of menopause and late menarche with late menopause.     

Selection intensities in menopausal and permanent contraceptor women of a rural population in India

Abstract

The opportunity for selection was estimated in the rural population of Visakhapat‐nam District, Andhra Pradesh, India. The index of total selection was found to be low. Selection in relation to birth control reveals that opportunity for selection is lower among the women who completed their fertility by family planning methods than in women who completed their fertility by attaining menopause. Further, the results showed that differential fertility and mortality make equal contributions to the total measure of selection in both groups.     

Effects of age, photoperiod and follicle-stimulating hormone on lactate production by cultured Sertoli cells from prepubertal Siberian hamsters (Phodopus sungorus).

To define a functional difference in Sertoli cells of animals exposed to different photoperiodic conditions, we isolated Sertoli cells from the testes of juvenile Siberian hamsters and cultured them in serum-free medium. In all age groups studied, Sertoli cells isolated from hamsters with delayed and normal puberty responded to follicle-stimulating hormone (FSH) with an increase in lactate production. The increase in lactate production induced by 1000 ng FSH ml-1 was significantly greater in Sertoli cells isolated from hamsters with delayed puberty than in those with normal puberty. These results suggest that Sertoli cells of Siberian hamsters exposed to short photoperiod in vivo may respond to increases in plasma FSH concentrations associated with photostimulation or spontaneous sexual maturation by an increase in secretory activity that may be critical for the initiation of spermatogenesis.     

Population genetics study of the differential fertility in urban populations

In an urban population with widespread birth control practice the distribution of the number of pregnancies, births and abortions was studied in a cohort of women of completed fertility. The mean number of pregnancies per woman was 4.03 +/- 0.08 (sigma = = 2.98); the mean number of births - 1.12 +/- 0.02 (sigma = 0.77). 7.4% of women which had completed their reproductive performance had no pregnancies and 19.5% - no births. The Crow's Index of the Opportunity for Selection and its components connected with differential fertility and differential mortality were estimated. In the population under study two components of selection - selection at the prenatal stages and selection associated with infertility - are shown to be still significant. Such type of selection is exemplified by investigation of couples suffering from repeated spontaneous abortions.     

The effects of type of female circumcision on infertility and fertility in Sudan

This study explores the association between type of female circumcision and infertility and fertility in Sudan using the 1989-90 Demographic and Health Survey. It is hypothesized that women with either Pharaonic or Intermediate circumcision would have higher infertility and lower fertility compared with women with Sunna circumcision, and that uncircumcised women would have the lowest infertility and highest fertility of the three groups. This hypothesis, a widely held assumption, proved to be largely incorrect. Though women with Pharaonic or Intermediate circumcision did have a higher prevalence of primary infertility than uncircumcised women, women with Sunna circumcision had even lower rates of primary infertility compared with uncircumcised women. This pattern prevailed in multivariate models controlling for confounding variables, where women with Pharaonic or Intermediate circumcision had significantly higher primary infertility. Moreover, though women with Pharaonic or Intermediate circumcision also had the highest prevalence of secondary infertility, once confounding covariates were controlled in multivariate models, there was no significant difference among the three groups of women. With respect to fertility, the total fertility rate was 7.6 for women with Pharaonic or Intermediate circumcision, 8.1 for women with Sunna circumcision and 8.3 for uncircumcised women. Differences in fertility were found to be insignificant when covariates were controlled. The multivariate models were estimated using logistic regression. In conclusion, Pharaonic or Intermediate circumcision may be associated with higher primary infertility while there was no evidence suggesting that either secondary infertility or fertility was associated with a woman's circumcision status.     

Variability of selection opportunities with changing socio-cultural environments

Opportunity for selection has been studied against their contrasting socioeconomic and cultural backgrounds in two endogamous populations, namely, Brahmins and Jalaris of Visakhapatnam, India. Total selection was slightly higher among the better off Brahmins than in Jalaris. But a marked qualitative and quantitative variation was found in the contributing components; the fertility differential was circa 60% in Brahmins while the mortality differential was circa 60% in Jalaris according to the Crow Index. The decreased mortality differential in Brahmins suggests that this component was directly affected by the better socio-economic level and reflects on the population's transitional phase. Further, the If value fell to a half in women who completed their fertility by family planning when compared to women who completed their fertility by menopause, thus reducing the variance in fertility component in the family planning group.     

Physiological changes in successive pregnancies and birth‐order effects

Abstract

An analysis of mortality rates documents that the well‐established female advantage in mortality continues to increase. Data from the U.S. census show that the sex differential in mortality has increased from 1.69 in 1963 to 1.82 in 1976. The age groups which show the most pronounced changes are youth (15–24), young adults (25–34), and old persons (75–84). Following Enterline (1961), we assess the major causes of death within each of these age groups in terms of their relative contributions to changing sex ratios. The major factors among young persons, apart from declining maternal mortality, are found to involve violent deaths, especially traffic accidents and suicide. Among old persons, death rates in general have declined, but advances in medical technology appear to have been more beneficial for older women than for older men, supporting the hypothesis of a biological superiority among women. However, death rates for malignant neoplasms have increased for older women as well as older men, suggesting that changing life styles may eventually have an impact on female mortality. The data suggest a need for additional research concerning the increase in violent deaths among young women and the potential increase in cancer deaths among older women.     

Influence of season of birth on onset of gonadotrophic and ovarian functions in young doe hares (Lepus europaeus).

The pituitary and ovarian responses to a monthly i.v. injection of 5 micrograms luteinizing-hormone-releasing hormone (LHRH) were studied in three groups of young doe hares, born in January-February (group I), in April (group II) or at the end of the breeding season (August-September, group III). The LHRH injection was always followed by a release of LH and progesterone, which did not differ among the three groups at 3 months of age. The pituitary and ovarian responses to LHRH increased gradually from the age of 3 months in groups I and III and from the age of 9 months in group II. One female of the ten born in January-February ovulated and reached puberty in June, at the age of 4 months, but with a weak pituitary response. The females born in April displayed a seasonally delayed puberty, at 9 months of age (two of five females ovulated in the next January). Four of the five females born at the end of the breeding season ovulated after LHRH when 5 months old (in February), with a full pituitary-ovarian response. The low pituitary response of group I in June-August, even if 10-20% of females ovulated after LHRH, suggests a need for a period of short days. Then, the most favourable conditions for the hare to reach puberty would be a period of short decreasing daylengths during the fall, followed by increasing daylengths after the winter solstice.     

Sex related differences in short and long-term prognosis after acute myocardial infarction: 10 year follow up of 3073 patients in database of first Danish Verapamil Infarction Trial.

OBJECTIVE--To re-examine the prevailing hypothesis that women fare worse than men after acute myocardial infarction. DESIGN--10 year follow up of all patients with confirmed acute myocardial infarction registered in the database of the Danish verapamil infarction trial in 1979-81. SETTING--16 coronary care units, covering a fifth of the total Danish population. PATIENTS--3073 consecutive patients with acute myocardial infarction, 738 (24%) women and 2335 (76%) men. MAIN OUTCOME MEASURES--Early mortality (before day 15). For patients alive on day 15: mortality, cause of death, admission with recurrent infarction, and mortality after reinfarction. RESULTS--Early mortality increased significantly with age (P < 0.0001) but was not significantly related to sex, with a 15 day mortality of 17% in women and 16% in men. Adjustment for age and sex simultaneously revealed a significant interaction (P = 0.02) between these variables, with a greater increase with age in early mortality for men than for women (early mortality was equal for the two sexes at age 64 years). Ten year mortality in patients alive on day 15 was 58.8%. The overall age adjusted hazard ratio (95% confidence interval) for women versus men was 0.90 (0.80 to 1.01); 0.90 (0.78 to 1.04) for 10 year reinfarction (48.8%); and 0.98 (0.82 to 1.16) for 10 year mortality after reinfarction (82.3%). No difference in cause of death was found between the sexes. With a follow up of up to 10 years for patients alive on day 15 mortality, rate of reinfarction, and mortality after reinfarction increased with increasing age (P < 0.0001). CONCLUSION--Sex by itself is not a risk factor after acute myocardial infarction.     

Pubertal growth as a determinant of adult height in boys with constitutional delay of growth and puberty

In boys with constitutional delay of growth and puberty, adult height may be inconsistent with parental (target) height. We aimed at studying which period of growth was important to account for adult height being above or below target height. In this retrospective study, adult height measured after 20 years in 39 patients was compared with target height and height data obtained at about 6 and 12 years of age and at diagnosis of delayed puberty (mean 14.6 years). Twenty-eight patients were untreated while 11 received testosterone enanthate (50 or 100 mg/month for 6 months). The growth data from both groups were pooled since they were not different. On average, the adult height standard deviation score (-0. 6 +/- 0.8, mean +/- SD) was similar to target height (-0.5 +/- 0.6). There were, however, marked individual differences since adult height varied between 1.7 SD (11 cm) below target height and 1.4 SD (9.5 cm) above target height. Multiple regression analysis showed that the most significant determinant of the difference between adult height and target height was height catch up during puberty (p < 0.002). We conclude that the magnitude of height catch up during puberty is a significant determinant of adult height in boys with constitutional delay of growth and puberty. Thus, optimizing pubertal growth may be a relevant therapeutic aim for adult height in boys with short stature and delayed puberty. Copyrightz1999S. KargerAG,Basel     

Progressive deceleration in growth as an early sign of delayed puberty in boys

OBJECTIVE: To describe the prepubertal growth pattern in boys with delayed puberty. METHODS: Growth curves for height and height velocity covering the age range 4-14 years were constructed on the basis of retrospectively obtained data in 85 boys with delayed puberty, who attained a normal final height. RESULTS: Between the age of 4 and 14 years the height in this cohort progressively deviated from the normal reference. At the age of 4 years, the height SDS was already significantly lower (median -0.8; p < 0.001) and progressively diminished during childhood, resulting in a median height SDS of -1.1 at the age of 12 years (p < 0.001). The median final height of this cohort (-0.4) was not different from their target height (-0.2). The degree of deceleration in growth during childhood was not determined by birth weight or birth height and did not influence final height. The decline of the height velocity with age in this group of boys with delayed puberty was significantly smaller (p < 0.001) than predicted by the model of Rikken and Wit. CONCLUSION: Late-maturing boys often show a prepubertal deceleration in growth that starts at an early age but that does not affect final height.