Methods for obtaining valid data on time to pregnancy among men and women.
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Biomedical subjects
Publications and source records attributed to M Joffe.
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The main objective of the Asclepios program was to examine occupational risk factors for the male reproductive system. The program focused on occupational exposure to fungicides (farmers, greenhouse workers, and vineyard workers), styrene (laminators in the reinforced plastics industry) and inorganic lead (battery workers, foundry workers, and lead smelters). Questionnaire studies of time to pregnancy were combined with longitudinal and cross-sectional studies of semen quality. The 8 data-collecting centers addressed 6553 male workers and contributed time-to-pregnancy values on the 3077 most recent pregnancies. Data collection was by interview or self-collection. The average response rate across all exposures and centers was 69.8%. The Asclepios project is the first international multicenter research project on environmental risks to male reproductive function. A protocol for epidemiologic research on occupational risk factors to the male reproductive system was developed, and links between epidemiologic and experimental units were established. The majority, but not all, of the studies was completed within the given time frame.
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OBJECTIVE: Circumstantial evidence suggests that organic farmers may have higher sperm count than other men, but comprehensive epidemiological studies of male fecundity among farmers have never been carried out. A substantial increase of sperm count is expected to translate into a shorter time to pregnancy--the number of menstrual cycles or months it takes a couple to get pregnant from discontinuation of birth control. Toxicological effects on spermatogenesis in humans and animals have been described after exposure to several pesticides. The aim of this study was to examine time to pregnancy among farmers who used pesticides (traditional farmers) and farmers who did not (organic farmers). METHODS: A total of 904 (84%) men, selected from the Danish Ministry of Agriculture lists of traditional and organic farmers, participated in telephone interviews. Information was collected on time to pregnancy for the youngest child, exposure to pesticides, and potential confounders. RESULTS: With the discrete analogue of the Cox regression model (including potential confounders: male and female smoking, female age, parity, and contraceptive method), the fecundability ratio between traditional farmers who used pesticides and organic farmers was 1.03 (95% confidence interval (95% CI) 0.75 to 1.40). In the group of farmers who sprayed with pesticides, none of the characteristics related to the use of pesticides could account for the variation in time to pregnancy. CONCLUSIONS: No overall effect of pesticides on male fecundability was found in this retrospective study among Danish farmers. Also, we found no evidence of higher male fecundability in organic farmers.
OBJECTIVES: To develop a polymerase chain reaction (PCR) method to detect Haemophilus ducreyi DNA in cultured isolates and clinical material. METHODS: Primers specific to the H ducreyi 16s rRNA gene were synthesised. PCR conditions were optimised and products were verified by restriction endonuclease digestion and agarose gel electrophoresis. RESULTS: The method was able to detect all 28 H ducreyi strains tested; specificity was demonstrated using lysates of 12 related organisms. Applied to clinical samples from genital ulcer swabs obtained in Harare, Zimbabwe, H ducreyi DNA was detected in repeated assays in 35 clinical samples. CONCLUSION: PCR amplification using primers from the 16s rRNA gene may be a useful alternative to culture for the detection of H ducreyi and the diagnosis of chancroid.
Infertility is an increasing problem for both individuals and societies. The number of couples seeking treatment for infertility is increasing each year, and public interest seems to be rising along with the new treatment methods and the improving results. Male infertility is also of great interest now that several studies suggest a deterioration in the quality of semen in many countries, Finland being an exception. The assisted reproductive technologies have improved tremendously since the first child conceived by in vitro fertilization was born in 1978. The new techniques include e.g. intrauterine insemination (IUI), gamete intrafallopian transfer (GIFT), in vitro fertilization (IVF), intracellular sperm injection (ICSI) and various combination treatments. These treatments are costly and both physically and emotionally stressful, and the success rate varies according to the aetiology of infertility, the age of the woman treated and the method used. More information is needed about the aetiology and incidence of fertility disorders as well as about the availability of treatment in the circumpolar areas and the couples' opinions of treatment. Our own study population, which was drawn form the northern Finland birth cohort for 1966, provides an outstanding opportunity to study these issues, since data are available for the whole life course of the individuals, dating back to prenatal life.
BACKGROUND: Postmenopausal hormone therapy has both benefits and hazards, including decreased risks of osteoporosis and cardiovascular disease and an increased risk of breast cancer. METHODS: We examined the relation between the use of postmenopausal hormones and mortality among participants in the Nurses' Health Study, who were 30 to 55 years of age at base line in 1976. Data were collected by biennial questionnaires beginning in 1976 and continuing through 1992. We documented 3637 deaths from 1976 to 1994. Each participant who died was matched with 10 controls alive at the time of her death. For each death, we defined the subject's hormone status according to the last biennial questionnaire before her death or before the diagnosis of the fatal disease; this reduced bias caused by the discontinuation of hormone use between the time of diagnosis of a potentially fatal disease and death. RESULTS: After adjustment for confounding variables, current hormone users had a lower risk of death (relative risk, 0.63; 95 percent confidence interval, 0.56 to 0.70) than subjects who had never taken hormones; however, the apparent benefit decreased with long-term use (relative risk, 0.80; 0.67 to 0.96, after 10 or more years) because of an increase in mortality from breast cancer among long-term hormone users. Current hormone users with coronary risk factors (69 percent of the women) had the largest reduction in mortality (relative risk, 0.51; 95 percent confidence interval, 0.45 to 0.57), with substantially less benefit for those at low risk (13 percent of the women; relative risk, 0.89; 95 percent confidence interval, 0.62 to 1.28). CONCLUSIONS: On average, mortality among women who use postmenopausal hormones is lower than among nonusers; however, the survival benefit diminishes with longer duration of use and is lower for women at low risk for coronary disease.
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INTRODUCTION: Growing evidence of reproductive effects associated with occupational and environmental agents has created the need for research with sensitive and well validated methods. There is a complex relation between manifest effects and underlying pathogenic processes. Conceptions will on average tend to be delayed in a population exposed to an agent that causes embryonic damage, an increase in germ cell mutations, or decreased fertility. STUDYING TIME TO PREGNANCY: Time to pregnancy can be used to measure the degree of delay in conceiving, across the whole continuum of biological fertility, in either men or women. The distribution of time to pregnancy largely reflects a sorting process, as the more fertile couples become progressively less well represented with the passage of time. The basic research strategy is comparison of the time to pregnancy within groups defined by their exposures, allowing for potential confounding factors relating not only to the study subject but also to his or her partner. MEASUREMENT AND VALIDITY: Prospective and retrospective methods are available, and each has strengths and weaknesses. Prospective studies have some theoretical advantages, but have unrepresentative populations and problems of feasibility and cost. Retrospective assessment of time to pregnancy is feasible with a short questionnaire, without intruding into sensitive areas of respondents' lives, with good validity at the group level, and without the necessity of large populations. Potential biases have been identified that can be minimised by careful design and analysis; the principal remaining problem is difficulty in obtaining exposure data retrospectively.
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BACKGROUND: There has been much interest in the apparent decrease in semen quality. Because the evidence for such a decrease is open to criticism, a different type of evidence is needed. Finland seems to have escaped this decrease, as well as other disorders of the male reproductive tract, notably testicular cancer. If there has been a true decrease, the implications for fertility are unknown. METHODS: The most sensitive functional measure of fertility is time to pregnancy (TTP); this can be studied retrospectively at group level with a high degree of validity. To test the hypothesis that Finnish men are more fertile than British men, TTP distributions from published Finnish studies and data from Britain were compared. Two comparisons were made: a pair of antenatal studies, and a pair of cross-sectional studies. FINDINGS: In both comparisons, fertility was statistically significantly greater in Finland than in Britain. The findings did not seem to be due to methodological problems; in particular, the results could not be attributed to differences in frequency of intercourse, since this would have had the opposite effect on sperm concentration and on TTP. INTERPRETATION: The previously reported difference in sperm counts between Finland and elsewhere in northwest Europe (including Britain) is probably not artefactual, suggesting that the reported world-wide decline in semen quality is also real. Reasons for the "Finnish exception" may include maternal smoking, which used to be lower in Finnish women than elsewhere, and which might affect developing make offspring.
OBJECTIVE: To assess the suitability of the standard primipara (a subset of the obstetric population that has relatively low risk or intervention and of adverse outcome) for making inter-unit comparisons of indicators of the process and outcome of maternity care. DESIGN: Inter-unit comparison of 10 indicators of obstetric intervention and adverse outcome derived from routinely collected computerised data held on the St Mary's Maternity Information System. SETTING: Fifteen maternity units in the former North West Thames Region. PARTICIPANTS: 15,463 primiparae who were delivered in 1992. MAIN OUTCOME MEASURES: Proportion of primiparae within the standard definition; degree to which standard primiparae are associated with lower rates of intervention and adverse outcome, as compared to other primiparae. RESULTS: Within the database, 42.6% of all primiparae were found to be standard, with rates varying between units from 25.9% to 57.7%. As expected, the standard primiparous woman is at less risk of intervention or adverse outcome than other primiparae. All but one component variable of the standard definition is a significant risk factor for at least four of the 10 indicators. Statistically significant differences in indicator rates are seen between standard and nonstandard primiparae within units. Within the standard group, significant differences in rates of intervention and adverse outcome are seen between units. Units with relatively high levels of intervention within the higher risk nonstandard group also have relatively high levels of intervention within the standard group. CONCLUSIONS: Use of the standard primipara, rather than the whole obstetric population, as the basis for inter-unit comparisons of maternity care will control for the substantial difference in case mix seen in different units, thereby increasing the validity of those comparisons. The technique has the additional benefit of clarifying the relationship between everyday clinical decision making and a unit's performance in comparative indicator reports. The approach must be combined with a separate study of the other groups in the case mix, such as multiparae and high risk primiparae. Additional nonoverlapping groups, homogeneous in terms of risk factors, should be defined and used to extend the basis on which comparisons may be made.
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STUDY OBJECTIVE: To establish the degree of validity of data on time to pregnancy, derived retrospectively using a short questionnaire. DESIGN: Information from the questionnaire was compared with data that had been collected concurrently from the same individuals. SETTING AND PARTICIPANTS: Questionnaires were mailed to 1647 women who continue to be followed up by the Oxford Family Planning Association contraceptive study, and a further 424 were approached for personal interview. Response rates were 91% and 79% respectively. MAIN RESULTS: Matching was successful in 91% of pregnancies. Median recall time was 14 years (interquartile range, 11-16 years). At the group level, remarkably good agreement was found between the two sources of information, presented as cumulative percentage distributions of live births. The findings were at least as good with longer recall (> 14 years) as with shorter recall. Digit performance was present to a limited degree. At the individual level, some misclassification was evident, which has implications for statistical power. For detection of clinical infertility (no conception within 12 months), the sensitivity was in the range 67%-91%, and the specificity was 92%-96%. Variations with format, duration of recall, age at delivery, year of birth, parity, social class, smoking habit, last contraceptive method, and outcome (live birth or not) were generally small, and were not statistically significant. CONCLUSIONS: Time to pregnancy is a sensitive way of assessing reproductive function in either sex. Valid data at a group level can be derived retrospectively, with a long duration of recall, using a short questionnaire.
Fertility is affected by the age of the female partner, but not that of the male partner, in the age ranges within which most attempts at conception occur. However, the literature on the effect of the smoking status of each partner is inconclusive. As part of a longitudinal study representative of all people born in Britain in 1958, 11,407 people were interviewed in 1991, of whom 3,132 female and 2,576 male cohort members had had or fathered at least one pregnancy. The outcome measure was the time to pregnancy of the first pregnancy (live births only), and the antecedent variables were the cohort member's age at that time and both partner's smoking habits and educational levels. Unadjusted analysis demonstrated that both the time to pregnancy and clinical subfertility were associated with higher maternal but not paternal age and with the smoking habits and educational levels of both parents. Multivariate analysis showed that paternal smoking failed to enter the model if the educational variables were also included. Findings were similar in the two separate analyses on male and female cohort members. This study confirms previous findings on the relative importance of maternal and paternal age in this age range. Maternal smoking affects fertility, but earlier reports of an apparent effect of paternal smoking may be due to confounding with socioeconomic status.