Environmental Effects On Fertility

环境对生育力的影响

• 批准号: 6672941
• 负责人: DONNA D. BAIRD
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6672941
• 关键词: caffeine; clinical research; corpus luteum; data collection methodology /evaluation; environmental contamination; environmental exposure; epidemiology; estrogens; fertility; health surveys; hormone metabolism; human subject; in vitro fertilization; interview; menstrual cycle; obesity; ovary disorder; ovulation detection /prediction; ovulation time; pregnancy loss; progesterone; questionnaires; smoking

Most people take their ability to reproduce for granted, but when couples can't have a baby they want, it can be devastating. Fecundability, defined as the per cycle probability of conceiving, involves a series of complex biological processes in both male and female partners. Environmental factors that interfere with any of these can result in reproductive failure in any given menstrual cycle. Identifying such factors has become an active area of research internationally, and the biological processes involved are studied both clinically and as subjects of basic research. I am particularly interested in using time-to-pregnancy data to evaluate fecundability, and in the biological processes involved in achieving a viable pregnancy. I contribute to the field through consulting, collaborations, reviews, commentaries, and continuing analysis of data from the North Carolina Early Pregnancy Study. The aim of this project is to learn more about environmental effects on fertility by developing methods for studying fertility in human populations, and analyzing data that describe aspects of human fertility and factors affecting it. Assessing human fertility. For identifying the day of ovulation, we proposed a semi-parametric mixture model that uses multiple independent markers of ovulation to account for measurement error. The model assigns each method of assessing ovulation a distinct non-parametric error distribution, and corrects bias in estimates of day-specific fecundability. We used a Monte Carlo EM algorithm for joint estimation of (i) the error distribution for the markers, (ii) the error-corrected fertility parameters, and (iii) the couple-specific random effects. We appied the methods to data from a North Carolina fertility study to assess the magnitude of error in measures of ovulation based on urinary luteinizing hormone and metabolites of ovarian hormones, and estimated the corrected day-specific probabilities of clinical pregnancy. Menopause status. We assessed associations with menopausal status based on either menstrual cycle or elevated (more than 20+ IU/L) FSH. Higher body mass index was associated with a lower likelihood of elevated FSH, but not with menstrual-based menopause. Exercise (3 times per week) was associated with a lower likelihood of being postmenopausal. Alcohol use also tended to be moderately associated with postmenopausal status by either measure. There was little evidence of associations with ethnicity, education, age at menarche, number of live births, and oral contraceptive use. Menstrual-based definitions of menopause can be misclassified for women with menstrual irregularity. Conception. Emergency post-coital contraceptives effectively reduce the risk of pregnancy, but their degree of efficacy depends on the pregnancy rate without treatment, which cannot be measured directly. We provided indirect estimates of such pregnancy rates. We estimated the probability of pregnancy relative to intercourse on a given cycle day. We found that the possibility of late ovulation produces a persistent risk of pregnancy even into the sixth week of the cycle. Post-coital contraceptives may be indicated even when intercourse has occurred late in the cycle. Pregnancy Testing. We estimated the maximum screening sensitivity of pregnancy tests when used on the first day of the expected period, taking into account the natural variability of ovulation and implantation. We conducted a community-based prospective cohort study of women who were planning to conceive. Main outcome measures were day of implantation, defined by the serial assay of first morning urine samples using an extremely sensitive immunoradiometric assay for hCG, relative to the first day of the missed period, based on self-reported usual cycle length. Data were available for 136 clinical pregnancies conceived during the study, 14 (10%) of which had not yet implanted by the first day of the missed period. The highest possible screening sensitivity for an hCG-based pregnancy test therefore is estimated to be 90% on the first day of the missed period. By 1 week after the first day of the missed period, the highest possible screening sensitivity is estimated to be 97%. In this study, using an extremely sensitive assay for hCG, 10% of clinical pregnancies were undetectable on the first day of missed menses. In practice, an even larger percentage of clinical pregnancies may be undetected by current test kits on this day, given their reported assay properties and other practical limitations. Onset of symptoms of pregnancy. 221 women attempting pregnancy made daily records of the presence or absence of symptoms of pregnancy during cycles of attempting pregnancy and during the 8 weeks following the LMP. Among 136 women delivering live infants, 89% had onset of symptoms by the end of the 8th week (median day 36). Women who smoked tobacco or marijuana, or who had clinical miscarriages had later onset of symptoms. Among 48 who lost their pregnancies before 6 weeks LMP, 21% reported symptom onset. Nearly 90% of women with successful pregnancies experience symptoms within 8 weeks LMP. Very early losses (before 6 weeks) are unlikely to be confirmed clinically, but they are sometimes recognized as symptomatic by women themselves. Age and fertility. Most analyses of age-related changes in fertility cannot separate effects due to reduced frequency of sexual intercourse v. those related to ageing. Information on intercourse collected daily through each menstrual cycle provides the data for estimating day-specific probabilities of pregnancy for specific days relative to ovulation, and these estimates allow unconfounded analysis of ageing effects. 782 healthy couples using natural family planning methods contributed prospective data on 5 860 menstrual cycles. Day of ovulation was based on basal body temperature measurements. Estimates of day-specific probabilities of pregnancy and the length of the fertile window were compared across age groups. Nearly all pregnancies occurred within a 6 day fertile window. There was no evidence for a shorter fertile window in older men or women. On average, the day-specific probabilities of pregnancy declined with age for women from the late 20s onward. Controlling for age of the woman, fertility was significantly reduced for men aged 35+ years. Women's fertility begins to decline in the late 20s with substantial decreases by the late 30s. Fertility for men is less affected by age, but shows significant decline by the late 30s.

大多数人都认为自己有生育能力是理所当然的，但当一对夫妇生不出他们想要的孩子时，这可能是毁灭性的。生育能力，定义为每个周期受孕的概率，涉及男性和女性伴侣的一系列复杂的生物过程。干扰这些因素的环境因素可能导致在任何给定的月经周期内生殖失败。识别这些因素已成为国际上一个活跃的研究领域，所涉及的生物学过程在临床和基础研究中都得到了研究。我特别感兴趣的是使用怀孕时间数据来评估生育能力，以及在实现可行怀孕所涉及的生物学过程。我通过咨询、合作、评论、评论和对北卡罗来纳早孕研究数据的持续分析，为该领域做出了贡献。该项目的目的是通过发展研究人口生育率的方法和分析描述人类生育率各方面及其影响因素的数据，更多地了解环境对生育率的影响。