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PubMed2003

Age-related decline in fertility.

A progressive decline in fecundity with advancing age is a reality, attributed primarily to the detrimental impact of various aging processes on female gametes. Despite medical advances that have dramatically prolonged the female life span, declining numbers and deteriorating quality of oocytes, and an increasing incidence of meiotic errors and aneuploidy of gametes and embryos, reduce clinical pregnancy rates and escalate pregnancy wastage. Increased fetal aneuploidies in ongoing pregnancies and an increased predisposition to obstetric morbidities further contribute to the diminishing reproductive successes associated with advancing age. The age of male partners, despite the decline in semen parameters and sexual performance with aging, does not appear to have a major impact on the eventual fertility of the aging couple. The contributions of age-related impaired sexuality and ejaculatory problems, although slight albeit significant, to declining fertility in the aging should be appreciated in appropriate cases. With the realization of the age-related detriment on fertility potential and the limitations of available therapeutic interventions, management of subfecundity in women beyond their mid-30s should be approached aggressively. Success of ovulation induction with clomiphine citrate or gonadotropins is marginal in women aged older than 40 years; a case can be made to proceed directly with ART in women in this age group, especially when there is coexisting male factor or pelvic disease. Except for the use of donor oocytes, the outcome of various therapeutic interventions to optimize reproductive performance in women aged older than 44 years remains dismal. A broader application of PGD techniques may contribute to improved live birth rates in reproductively aging women. The greater likelihood of obstetric complications in pregnancies resulting from donor oocytes and an increased prevalence of age-related medical problems complicating pregnancy should prompt a thorough medical evaluation before proceeding with ART.

Aging↗
PubMed1999

Nutrition, fertility and steady-state population dynamics in a pre-industrial community in Penrith, northern England.

The effect of nutrition on fertility and its contribution thereby to population dynamics are assessed in three social groups (elite, tradesmen and subsistence) in a marginal, pre-industrial population in northern England. This community was particularly susceptible to fluctuations in the price of grains, which formed their basic foodstuff. The subsistence class, who formed the largest part of the population, had low levels of fertility and small family sizes, but women from all social groups had a characteristic and marked subfecundity in the early part of their reproductive lives. The health and nutrition of the mother during pregnancy was the most important factor in determining fertility and neonatal mortality. Inadequate nutrition had many subtle effects on reproduction which interacted to produce a complex web of events. A population boom occurred during the second half of the 18th century; fertility did not change but there was a marked improvement in infant mortality and it is suggested that the steadily improving nutritional standards of the population, particularly during crucial periods in pregnancy (i.e. the last trimester), probably made the biggest contribution to the improvement in infant mortality and so was probably the major factor in triggering the boom.

Adolescent↗
PubMed2003

Maternal atopy and the number of offspring: is there an association?

We investigated the association between maternal atopy and the number of offspring. In a population- and pregnancy-based survey (part of the European Studies on Infertility and Subfecundity), we obtained information on the number of offspring, adverse pregnancy outcomes, age at pregnancy, and waiting time to pregnancy. The German portion of these surveys also included information on physician-diagnosis of asthma, atopic eczema, or hay fever. The odds ratio (OR) adjusted for age showed that the number of children was reduced among women with atopy (OR = 0.75, 95% CI: 0.57-0.98 in the pregnancy-based sample; OR = 0.79, 95% CI: 0.63-0.99 in the population-based sample). We did not identify other signs of reduced reproductive ability in atopic women. The results provide support for two assumptions: (i) either a lower number of offspring in atopic mothers combined with an increased risk of atopy in offspring of atopic mothers may explain the protective effect of a higher number of siblings on atopy in offspring; or (ii) successive pregnancies may decrease the atopic response of the mother and thus the risk of developing atopy in subsequent offspring.

Adult↗
PubMed2003

Does an effect of marriage duration on pre-transition fertility signal parity-dependent control? An empirical test in nineteenth-century Leuven, Belgium.

It has been demonstrated for many pre-industrial populations that the age at marriage, or marriage duration, influences age-specific marital fertility but the reason for this remains unclear. Among the several mechanisms that may be responsible, the following are often cited: secondary sterility or increased subfecundity associated with parity; declining coital frequency; the age difference between the spouses; and, importantly, parity-dependent fertility control. If the latter mechanism were partly responsible for the marriage-duration effect in pre-transition populations, it would contradict the concept of the modern fertility transition as the evolution (or revolution) from parity-independent to parity-dependent fertility. The study presented in this paper investigates the relative importance of these alternative explanations. The application of multivariate Poisson regression to the fertility data from two birth cohorts in the Belgian city of Leuven shows that a linearly declining or even concave age-specific fertility pattern, disaggregated by age at marriage, does not imply parity-dependent fertility limitation.

Belgium↗
PubMedDate not supplied

Menstrual disorders and month of birth.

Menstrual characteristics in a population of 23,227 women who participated in a breast cancer screening programme were considered with respect to month of birth. High and low risk months of birth were defined according to the seasonal preovulatory overripeness ovopathy (SPrOO) hypothesis. Positive associations were found in 11 out of the 14 relations studied. The results were significant for early menarche (< or = 11 years), long menstrual cycles (> or = 5 weeks), menorrhagia (> or = 7 days and profuse blood loss), and early (< or = 40 years) or late (> or = 56 years) menopause. The results not only confirm the birth excess of these women in specific months, as has been found by others. They apparently agree with the SPrOO hypothesis and with a transgenerational concept of familial subfecundability along matrilineal lines and hence, familial clustering of pathological progeny, independent of Mendelian rules.

Adult↗
PubMed2004

Childbearing and the risk of scleroderma: a population-based study in Sweden.

This study examined associations between childbearing and risk of scleroderma by using national population-based registry data from Sweden. Women with a discharge diagnosis of scleroderma from 1964 to 1999 (n = 2,149) were identified in the Swedish Inpatient Register. These cases were matched by year and month of birth and region of residence to as many as five controls obtained from the Multi-Generation Register. Pregnancy history (number of births, age at each birth) was restricted to births before the first scleroderma-related hospitalization for cases and the corresponding age for their matched controls. Risk estimates, measured by the odds ratio and 95% confidence interval, were obtained by using conditional logistic regression. Nulliparity was associated with an increased risk of scleroderma (odds ratio = 1.37, 95% confidence interval: 1.22, 1.55). Risk decreased with increasing number of births. Similar results were found when analyses were limited to births up to 2 years or up to 5 years before hospitalization. Among parous women, younger age at first birth was associated with an increased risk of scleroderma. The association between lower parity and increased risk of scleroderma could reflect subfecundity caused by scleroderma before disease became clinically evident, possible common causes of infertility and scleroderma, or a protective effect of pregnancy through an unknown mechanism.

Adolescent↗
PubMed2003

Intake of wine, beer and spirits and waiting time to pregnancy.

BACKGROUND: A high intake of alcohol may prolong waiting time to pregnancy, whereas a moderate intake may have no or perhaps even a positive effect on fecundity. In previous studies on fecundity, different types of beverages have not been taken into consideration, although moderate wine drinkers appear to have fewer strokes, lung and digestive tract cancers, and overall mortality than both abstainers and moderate drinkers of beer or spirits. We examined the association between different types of alcoholic beverages and waiting time to pregnancy. METHODS: Self-reported data were used for 29,844 pregnant women, recruited to the Danish National Birth Cohort in 1997-2000. Main outcome measures were odds ratios for a prolonged waiting time to pregnancy according to consumption of wine, beer and spirits. RESULTS: All levels of wine intake compared with non-wine drinking or with consumption of beer or spirits had subfecundity odds ratios between 0.7 and 0.9. No association was seen regarding beer drinking, while the association with spirits was J-shaped. CONCLUSION: Our findings suggest that wine drinkers have slightly shorter waiting times to pregnancy than both non-wine drinkers and consumers of other alcoholic beverages. Whether this is an effect of wine itself or the characteristics of the wine drinker is not known.

Alcohol Drinking↗
PubMed2005

Time trends in waiting time to pregnancy among Danish twins.

BACKGROUND: Little is known about time trends in fecundity because few population-based data are available. In a survey among female twins born from 1953 to 1976, their time to pregnancy did not differ from singletons and can be considered to represent the fecundity of the general population. METHODS: Information was collected by interview about waiting time to first pregnancy (TTP) and any periods of subfecundity among both male and female twins born between 1931 and 1952. Trends were analysed by considering the year of birth of the index person (birth cohort effect) or year at which the first attempt started (period effect). RESULTS: Eighty-five percent of male and 81.3% of female eligible twins participated. A total of 1598 male twins and 1653 female twins reported a TTP value and 1671 men and 1715 women had a value for their first attempt to conceive including unsuccessful attempts. No overall trends in either male or female TTP were observed with increasing year of birth or of starting time, after adjustment for confounders, but for attempts fecundity increased among female twins by year of birth or of starting the attempt. A decreasing risk of severe infertility with increasing year of birth or year for start of the attempt was observed among male twins, but this observation was based on only 81 men and was not seen among female twins. CONCLUSION: No decreasing trend in fecundity was observed among Danish twins born between 1931 and 1952 who had completed their reproduction. Female twins had a slight increase in fecundity, and men a decrease in severe infertility. In addition, TTP was apparently well reported and recalled for up to 50 years among both male and female twins.

Adult↗
PubMed2006

Epilepsy and febrile seizures in children of treated and untreated subfertile couples.

BACKGROUND: Only few studies have addressed the long-term neurological outcomes of children born by subfertile couples. We studied the risk of epilepsy and febrile seizures in children of treated and untreated subfertile couples. METHODS: The study included 83 194 live singletons born by mothers who took part in the Danish National Birth Cohort (DNBC). Information on time to pregnancy (TTP) and infertility treatment was reported by the mothers in computer-assisted telephone interviews. Data on epilepsy and febrile seizures were extracted from the Danish National Hospital Register. RESULTS: Overall, children of subfertile couples (TTP > 12 months) had a 51% higher risk of epilepsy [incidence rate ratio (IRR): 1.51; 95% confidence interval (95% CI): 1.17-1.94] compared with children of couples with a TTP of 0-5 months. The corresponding estimates were 1.71 (95% CI: 1.21-2.42) if the couples had received infertility treatment and 1.38 (95% CI: 1.00-1.89) if they conceived spontaneously. Children of subfertile couples did not have a higher risk of febrile seizures except for those who received hormonal treatment (HT) with or without intrauterine insemination (IRR = 1.37; 95% CI: 1.14-1.66). CONCLUSIONS: Children of subfertile couples had a slightly increased risk of epilepsy, and the risk tended to be higher for children of couples who received infertility treatment. Whether this reflects side effects of treatment or severity of subfecundity is not known.

Child↗
PubMed1987

Body fat, menarche, fitness and fertility.

Many well-trained athletes, ballet dancers and women who diet excessively have secondary or primary amenorrhoea. Less extensive training or weight loss may result in anovulatory menstrual cycles, or a shortened luteal phase. These disruptions of reproductive ability are due to hypothalamic dysfunction, which is correlated with weight loss or excessive leanness. It is proposed that these associations are causal and that the high percentage of body fat (26-28%) in the mature human female may influence reproduction directly. Four mechanisms are known: (i) adipose tissue converts androgens to oestrogen by aromatization. Body fat is thus a significant extragonadal source of oestrogen; (ii) body weight, hence fatness, influences the direction of oestrogen metabolism to more potent or less potent forms; leaner women make more catechol oestrogens, the less potent form; (iii) obese women and young, fat girls have a diminished capacity for oestrogen to bind sex-hormone-binding-globulin; (iv) adipose tissue can store steroid hormones. An indirect mechanism may be signals of abnormal control of temperature and changes in energy metabolism, which accompany excessive leanness. The hypothalamic reproductive dysfunction results in abnormal gonadotrophin secretion: there is an age inappropriate secretory pattern of luteinizing hormone (LH) and follicle stimulating hormone (FSH), resembling that of prepubertal children. The secretion of LH and the responses to LHRH are reduced in direct correlation with the amount of weight loss. Other evidence from non-athletic and athletic women and mammals is presented in support of the hypothesis that a particular, minimum ratio of fat to lean mass is normally necessary for menarche (approximately 17% fat/body wt) and the maintenance of female reproductive ability (approximately 22% fat/body wt). Nomograms are given for the prediction of these critical weights for height from a fatness index; these weights are useful clinically in the evaluation of nutritional amenorrhoea and the restoration of fertility in underweight women. Evidence is presented that undernutrition and hard physical work can affect the natural fertility of populations, by the delay of menarche, a longer period of adolescent subfecundity, a longer birth interval and an earlier age of menopause. Data from a study of the long-term reproductive health of 2622 former college athletes compared with 2766 non-athletes show that the former college athletes had a significantly lower lifetime occurrence of breast cancer and cancers of the reproductive system, and a lower lifetime occurrence of benign tumours of these tissues, compared with the non-athletes.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗
PubMed2000

The genetics of obesity. Lessons for polycystic ovary syndrome.

Both polycystic ovary syndrome (PCOS) and obesity are common disorders with a complex phenotype. Both are presumably heterogeneous in etiology. Understanding the genetics of obesity, which has a longer and richer history, may therefore illuminate the genetics of PCOS, where major projects are now underway. Obesity may be the penultimate condition in which the effects of heredity and environment will forever mingle. Most obesity mutations identified to date (with the exception of the Agouti mutation) are inherited in an autosomal recessive manner. Therefore, it is unlikely that such mutations, even when identified in a human population, could explain only a fraction of the cases that make up the high prevalence of both of these disorders. Although the mouse models of single gene defects causing obesity contain many similar aspects of the PCOS phenotype such as obesity and subfecundity, there is no mouse model that mimics all aspects of the syndrome, especially the circulating androgen excess. This elevation in circulating androgens may be the sine qua non of the syndrome as indicated by our findings in sisters of PCOS probands that hyperandrogenemia may be the distintinctive reproductive phenotype. Isolation of PCOS and obesity genes may allow the development of targeted interventions that will lead to effective and safe treatment of both obesity and PCOS.

Adipocytes↗
PubMed1985

Female reproductive health in two lamp factories: effects of exposure to inorganic mercury vapour and stress factors.

To evaluate the possible influence of mercury vapour on female reproduction, 153 women working in a mercury vapour lamp factory have been compared with 193 women employed in another factory of the same company, where mercury was not used. Both groups of subjects were exposed to stress factors (noise, rhythms of production, and shift work). The production process has been analysed by inspection of the plants and by collective discussions with "homogeneous groups" of workers; a retrospective inquiry into work history and reproductive health events has been subsequently performed by an individual interview. Women exposed to mercury vapour currently not exceeding the time weighted average air concentration of 0.01 mg/m3 declared higher prevalence and incidence rates of menstrual disorders, primary subfecundity, and adverse pregnancy outcome; however, the progression of these problems with the level of exposure to mercury inside the same factory was not always clear. The results of this study neither prove nor exclude the possibility that occupational exposure to this concentration of mercury has a negative effect on female reproduction.

Adult↗
PubMed2001

Solvent use and time to pregnancy among female personnel in biomedical laboratories in Sweden.

OBJECTIVES: To elucidate possible effects on fecundability from chemical, biological, and physical agents in laboratories, a retrospective study based on a questionnaire was conducted among female personnel who worked in Swedish biomedical research laboratories. Female personnel in non-laboratory departments were used as a reference group. The maximum number of women included in the analyses was 560. This corresponded to 2519 menstrual cycles. These women had given birth at least once during the period 1990-4. METHODS: Time to pregnancy was used to estimate the fecundability-that is, probability of conception of a clinically detectable pregnancy per cycle. The fecundability ratio (FR) between exposed and unexposed cycles was calculated with a discrete time analogue of the Cox's proportional-hazards model. The FR estimates below unity indicate subfecundity. RESULTS: Work with organic solvents in general in laboratory work, gave a decreased adjusted fecundability ratio (FR) of 0.79 (95% confidence interval (95 % CI) 0.68 to 0.93). Moreover, work with acetone and use of viruses also showed decreased FRs, 0.72 (0.53 to 0.97) and 0.66 (0.49 to 0.90), respectively. CONCLUSIONS: The results of the present study give some indications of reduced fecundability for work with specific agents in laboratories, and support previously reported findings of a negative influence of organic solvents on fecundity among female laboratory personnel.

Adult↗
PubMed1993

Design options and methodological fallacies in the studies of reproductive failures.

Reproductive failures are at first sight well suited for epidemiologic research. The time of pregnancy is closely monitored, and failures such as spontaneous abortions and subfecundity are rather frequent. Although epidemiologists' interest in the field has been growing, there is still disappointingly little new information of relevance for prevention. A number of methodologic shortcomings may explain this. A large part of disease classification is not well suited for etiologic research, reduced fertility has diminished the populations at risk, close medical monitoring tends to mask causal links, and many scientific problems related to this area bring limitations to the research field. Still, much more could be learned from a systematic use of epidemiologic knowledge, existing registers, and the joint effort between different research groups.

Abortion, Spontaneous↗
PubMed1999

Environmental fertility research at the turn of the century.

Research into environmental causes of impaired human fertility is still immature. Knowledge on the strengths and limitations of several research options, the main sources of bias, the occurrence of infertility and subfecundity in several countries, the patterns of contraceptive behavior, and the distribution of sperm counts at the population level has advanced, but the much-debated questions about temporal and regional trends in fertility and semen quality remain unsettled. Refined biological markers of male fecundity and markers feasible for large-scale studies of female fecundity are needed. The effects of several life-style factors have been characterized successfully, but the detrimental effects of environmental exposures have not. Most studies are either inconclusive or fail to demonstrate any important risks. If comprehensive knowledge on biological mechanisms is a criterion of maturity, epidemiologic and toxicologic fertility research is young. The new millennium will be challenged to determine the role played by the environment in developed countries, wrong exposure time windows, too crude or inappropriate measures of fertility, and overlooked critical exposures.

Epidemiologic Methods↗
PubMed2005

Age and male fertility: biological factors.

Although the effect of maternal age on fertility is well known, whether paternal age also affects fertility remains unclear. If there is an effect, the biological causes and consequences, especially for the offspring, are unclear. We present a short review of the data and various studies on this subject. Data on young men or fathers are not considered here. Advanced male age has been associated with: Increased time-to-pregnancy (TTP) and subfecundity; low semen volume, total sperm count, sperm motility and normal sperm morphology; gradual modification of testicular vascularisation and regular decrease in the number of Sertoli and Leydig cells, with an associated decrease in serum testosterone. There are wide interindividual variations of these modifications, with some elderly men having a reproductive function similar to young men. Whether there is an increase in levels of qualitative and or quantitative alterations of the sperm chromosomes with advancing age remains controversial. It can be suggested that there is an increased risk of developmental defects in the offspring of older men, as the spontaneous mutation rate is closely related to the age of the man. An increasing rate of miscarriages has been related to older fathers and several studies suggest older fathers are at the origin of several diseases in the new-born. In conclusion, further studies are needed due to the increasing number of older men wishing to become a father.

Adult↗
PubMed1994

[The impact of reproductive loss for human fertility. Results of the German part of a European study of the epidemiology of infertility and subfertility].

Within the German part of an European Community study of the epidemiology of infertility and subfecundity we analysed the fetal loss (i.e. spontaneous abortions, artificial abortions, ectopic pregnancies, stillbirth, early neonatal death and all babies who died after the 7th day within the first year of life). For this investigation women from 5 urban and rural regions in Germany in the age group 25-45 years were selected in five districts from random samples of the local registers. 1531 interviews were conducted in 1992 by trained female interviewers in the same way as in the other participating European countries. 1248 of the women had a positive reproductive anamnesis with 3018 pregnancies. 565 (= 45.3% of women who were pregnant at any time) had fetal loss. In East Germany as well as in West Germany we found a positive age and pregnancy association. The main loss we observed in the age group under 20 and over 35 years. In all groups artificial abortion was the most important part of fetal loss (rural region of East Germany: 15.5% and West Germany: 13.1% of all registered pregnancies). The time to pregnancy (TTP) was prolonged in women over 30 years of age. Here we also found an increasing rate of spontaneous abortions. Smokers are more prevalent in women with ectopic pregnancies, spontaneous abortions and live born babies who died within the first 7 days after delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗
PubMed1993

Absolute male factor infertility. A useful model for evaluating the efficacy of cryopreserved semen.

Cryopreserved semen generally results in diminished pregnancy rates when used for donor insemination. However, coexisting female subfecundity may significantly confound the pregnancy outcome. Therefore, in order to determine the efficacy of cryopreserved semen, 43 consecutive women with absolute male factor infertility (single women or wives of azoospermic men) were inseminated with cryopreserved spermatozoa using cervical caps. Life table analysis of the results revealed a cumulative probability of conception of 84% with a monthly fecundability rate of 19% after eight insemination cycles. These results are similar to those reported using fresh semen, suggesting that the efficacy of cryopreserved semen may be higher than previously believed.

Confounding Factors, Epidemiologic↗