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.

大多数人都认为重复理所当然，但是当夫妻无法生育自己想要的孩子时，这可能是毁灭性的。定义为受想的每周循环概率的繁殖力涉及男性和女性伴侣的一系列复杂生物学过程。干扰任何这些的环境因素在任何给定的月经周期中都可能导致生殖失败。确定此类因素已成为国际研究的活跃领域，并且在临床和基础研究的主题上都研究了所涉及的生物学过程。我特别有兴趣使用期待时间数据来评估屈光度，以及在实现可行妊娠的生物学过程中。我通过咨询，合作，评论，评论以及对北卡罗来纳州早期怀孕研究的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开发研究人群中生育能力的方法，并分析描述人类生育能力方面的数据以及影响其影响的因素，以了解有关生育能力的环境影响的更多信息。 评估人类的生育能力。为了识别排卵的一天，我们提出了一种半参数混合模型，该模型使用多个独立的排卵标记来说明测量误差。该模型为评估排卵的每种方法分配了一个独特的非参数误差分布，并在估计日期特异性的繁殖性估计中纠正了偏差。我们使用蒙特卡洛EM算法进行（i）标记的误差分布，（ii）误差校正的生育参数以及（iii）夫妇特定的随机效应。我们将方法附加到了北卡罗来纳州生育研究的数据中，以评估基于尿叶叶霉激素和卵巢激素代谢产物的排卵量量的幅度，并估计了临床妊娠的校正日期特异性概率。更年期状态。我们根据月经周期或升高（超过20+ IU/L）FSH评估了与更年期状态的关联。较高的体重指数与FSH升高的可能性较低，但与月经更年期无关。运动（每周3次）与绝经后的可能性较低有关。饮酒也往往通过两种措施中适度地与绝经后状态相关。几乎没有证据表明与种族，教育，初潮的年龄，活产数和口服避孕药的使用相关。对于月经不规则的女性，基于月经的定义可能会被错误分类。 概念。急诊后避孕药有效地降低了怀孕的风险，但是它们的疗效程度取决于未经治疗的怀孕率，这无法直接衡量。我们提供了这种怀孕率的间接估计。我们估计了在给定的周期日相对于性交的妊娠概率。我们发现，晚期排卵的可能性即使在周期的第六周也会产生持续的怀孕风险。即使在周期后期发生性交，也可以指示后毛状避孕药。 怀孕测试。考虑到排卵和植入的自然变异性，我们估计妊娠试验的最大筛查敏感性。我们对计划怀孕的妇女进行了一项基于社区的前瞻性队列研究。主要结果度量是植入日，这是由第一个早晨尿液样品的串行测定，使用非常敏感的HCG免疫放射测定法，相对于错过期的第一天，基于自我报告的通常的通常循环长度。在研究期间构思的136例临床妊娠的数据可获得，其中14例（10％）尚未在错过的第一天植入。因此，基于HCG的妊娠试验的最高筛查敏感性估计在错过的第一天，估计为90％。在错过期的第一天之后的1周之后，可能的最高筛查灵敏度估计为97％。在这项研究中，使用对HCG的极敏感测定法，在错过月经的第一天无法检测到10％的临床妊娠。实际上，鉴于其报道的测定属性和其他实际限制，当前的测试套件可能未发现临床妊娠的比例更大。 怀孕症状的发作。 221名企图怀孕的妇女每天记录在尝试怀孕的周期以及LMP后的8周内存在怀孕症状的记录。在136名妇女分娩活婴儿中，有89％的症状在第8周结束时出现了症状（中间第36天）。吸烟或大麻或临床流产的妇女以后发作。在48名LMP之前失去怀孕的人中，有21％的人报告了症状发作。在8周内，近90％的成功怀孕女性经历了症状。临床上不太可能在6周之前（6周之前）损失（6周之前），但有时她们会被女性视为症状。 年龄和生育能力。大多数与年龄相关的生育能力变化的分析无法分离性交的频率降低，因此与衰老有关的频率降低。每天通过每个月经周期收集的有关性交的信息提供了用于估计特定天数相对于排卵的日期特异性概率的数据，而这些估计值允许对衰老效应的不符分析。 782种使用自然计划生育方法的健康夫妇在5 860个月经周期上贡献了前瞻性数据。排卵天基于基础体温测量。比较了年龄组的妊娠日期特异性概率和肥沃窗口长度的估计。几乎所有怀孕都发生在一个6天的肥沃窗口中。没有证据表明在老年男女中较短的肥沃窗户。平均而言，从20多岁开始，孕妇的妊娠概率随着年龄的增长而下降。控制女性的年龄，35岁以上男性的生育能力大大降低。在20年代后期，妇女的生育能力开始下降，到30年代后期大幅下降。男性的生育能力受年龄影响较小，但在30年代后期显示出显着下降。