Omega-3 fatty acid supplementation and fecundability.

Study Question: Is self-reported use of omega-3 fatty acid supplements associated with fecundability, the probability of natural conception, in a given menstrual cycle?

Summary Answer: Prospectively recorded omega-3 supplement use was associated with an increased probability of conceiving.

What Is Known Already: In infertile women, omega-3 fatty acid intake has been associated with increased probability of pregnancy following IVF. In natural fertility, studies are conflicting, and no study of natural fertility has evaluated omega-3 fatty acid supplementation and fecundity.

The limits of small-for-gestational-age as a high-risk category.

SGA (small for gestational age) is widely used to identify high-risk infants, although with inconsistent definitions. Cut points range from 2.5th to 10th percentile of birthweight-for-gestational age.

Pre-conception 25-hydroxyvitamin D (25(OH)D) and fecundability.

Study Question: Is pre-conception 25(OH)D associated with the per cycle probability of conception, i.e fecundability, in a prospective cohort study?

Summary Answer: There are suggestive associations of high 25(OH)D (at least 50 ng/ml) with increased fecundability and low 25(OH)D (<20 ng/ml) with reduced fecundability, but the estimates were imprecise.

What Is Known Already: Vitamin D has been associated with reproductive function and fertility in animal studies, but few human studies exist.

Association of urinary concentrations of early pregnancy phthalate metabolites and bisphenol A with length of gestation.

Background: Environmental exposure to phthalates and bisphenol A (BPA) may have endocrine disrupting effects that alter length of gestation. We assessed the association between the urinary concentrations of 11 phthalate metabolites and BPA with length of gestation in a cohort of women followed from before conception with daily 1st-morning urinary hormone measures that identified day of implantation.

Methods: Pre-implantation and post-implantation urinary phthalate metabolites and BPA concentrations were measured in pooled urine samples designed to limit single-measure variability due to the likely episodic nature of these exposures and the short half-life of these compounds.

Association of urinary concentrations of phthalate metabolites and bisphenol A with early pregnancy endpoints.

Background: Phthalates and bisphenol A (BPA) are environmental contaminants that may affect early embryonic development.

Objective: To assess the association between phthalate metabolites and BPA with early pregnancy endpoints in a cohort of women followed from before conception.

Methods: We quantified 11 phthalate metabolites and BPA in 137 conception cycles from naturally conceived clinical pregnancies.

25-Hydroxyvitamin D and Long Menstrual Cycles in a Prospective Cohort Study.

Background: Vitamin D insufficiency is associated with subfertility and prolonged estrus cycles in animals, but humans have not been well studied.

Methods: A prospective time-to-pregnancy study, Time to Conceive (2010-2015), collected up to 4 months of daily diary data. Participants were healthy, late reproductive-aged women in North Carolina who were attempting pregnancy.

Long-term Recall of Pregnancy-related Events.

Background: Early-life factors can be associated with future health outcomes and are often measured by maternal recall.

Methods: We used data from the North Carolina Early Pregnancy Study and Follow-up to characterize long-term maternal recall. We used data from the Early Pregnancy Study as the gold standard to evaluate the accuracy of prepregnancy weight, early pregnancy behaviors, symptoms and duration of pregnancy, and child's birthweight reported at follow-up, for 109 women whose study pregnancies had resulted in a live birth.

Long-term Recall of Time to Pregnancy.

Background: Despite the widespread use of retrospectively reported time to pregnancy to evaluate fertility either as an outcome or as a risk factor for chronic disease, only two small studies have directly compared prospective data with later recall.

Methods: The North Carolina Early Pregnancy Study (1982-1986) collected prospective time-to-pregnancy data from the beginning of participants' pregnancy attempt. In 2010, (24-28 years later) women were sent a questionnaire including lifetime reproductive history that asked about all prior times to pregnancy.

Urinary Concentrations of Phthalate Metabolites and Bisphenol A and Associations with Follicular-Phase Length, Luteal-Phase Length, Fecundability, and Early Pregnancy Loss.

Background: Certain phthalates and bisphenol A (BPA) show reproductive effects in animal studies and potentially affect human ovulation, conception, and pregnancy loss.

Objectives: We investigated these chemicals in relation to follicular- and luteal-phase lengths, time to pregnancy, and early pregnancy loss (within 6 weeks of the last menstrual period) among women attempting pregnancy.

Methods: Women discontinuing contraception provided daily first-morning urine specimens and recorded days with vaginal bleeding for up to 6 months.

Length of human pregnancy and contributors to its natural variation.

Study Question: How variable is the length of human pregnancy, and are early hormonal events related to gestational length?

Summary Answer: Among natural conceptions where the date of conception (ovulation) is known, the variation in pregnancy length spanned 37 days, even after excluding women with complications or preterm births.

What Is Known Already: Previous studies of length of gestation have either estimated gestational age by last menstrual period (LMP) or ultrasound (both imperfect measures) or included pregnancies conceived through assisted reproductive technology.

Study Design, Size, Duration: The Early Pregnancy Study was a prospective cohort study (1982-85) that followed 130 singleton pregnancies from unassisted conception to birth, with detailed hormonal measurements through the conception cycle; 125 of these pregnancies were included in this analysis.

Association between inhibited binding of folic acid to folate receptor alpha in maternal serum and folate-related birth defects in Norway.

Background: Folic acid intake during pregnancy can reduce the risk of neural tube defects (NTDs) and perhaps also oral facial clefts. Maternal autoantibodies to folate receptors can impair folic acid binding. We explored the relationship of these birth defects to inhibition of folic acid binding to folate receptor α (FRα), as well as possible effects of parental demographics or prenatal exposures.

Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti-Mi-2 autoantibodies in women.

Objective: Because studies suggest that ultraviolet (UV) radiation modulates the myositis phenotype and Mi-2 autoantigen expression, we conducted a retrospective investigation to determine whether UV radiation may influence the relative prevalence of dermatomyositis and anti-Mi-2 autoantibodies in the US.

Methods: We assessed the relationship between surface UV radiation intensity in the state of residence at the time of onset with the relative prevalence of dermatomyositis and myositis autoantibodies in 380 patients with myositis from referral centers in the US. Myositis autoantibodies were detected by validated immunoprecipitation assays.

Accuracy of reporting of menstrual cycle length.

There are many studies based on self-reported menstrual cycle length, yet little is known about the validity of this measure. The authors used data collected in 1990 from 352 women born in Chicago, Illinois, aged 37-39 years. Women reported their usual cycle length and behavioral and reproductive characteristics at study enrollment and then completed daily menstrual diaries for up to 6 months.

Parent's occupation and isolated orofacial clefts in Norway: a population-based case-control study.

Purpose: Occupational factors have been associated with risk of orofacial clefts in offspring, although data are limited. We explored associations between parent's occupation and isolated orofacial clefts using a population-based case-control study.

Methods: Cases were restricted to infants born with an isolated orofacial cleft in Norway during the period 1996 to 2001 (314 with cleft lip with or without palate [CLP] and 118 with cleft palate only [CPO]).

Folic acid supplements and risk of facial clefts: national population based case-control study.

Objective: To explore the role of folic acid supplements, dietary folates, and multivitamins in the prevention of facial clefts.

Design: National population based case-control study.

Setting: Infants born 1996-2001 in Norway.

Intact HCG, free HCG beta subunit and HCG beta core fragment: longitudinal patterns in urine during early pregnancy.

Background: Detecting and monitoring early pregnancy depend on the measurement of HCG. Little is known about how production of various forms of HCG may evolve over the earliest weeks of pregnancy, particularly in naturally conceived pregnancies.

Methods: We describe the daily excretion of three urinary HCG analytes during the first 6 weeks post-conception in 37 naturally conceived pregnancies ending in singleton birth.

On the frequency of intercourse around ovulation: evidence for biological influences.

Background: Intercourse in mammals is often coordinated with ovulation, for example through fluctuations in libido or by the acceleration of ovulation with intercourse. Such coordination has not been established in humans. We explored this possibility by examining patterns of sexual intercourse in relation to ovulation.

Rescue of the corpus luteum in human pregnancy.

Rescue of the corpus luteum from its programmed senescence maintains progesterone production required for pregnancy. In primates, chorionic gonadotropin produced by the developing conceptus acts as the primary luteotrophic signal. The purpose of this research was to assess corpus luteum rescue by examining changes in daily urinary progesterone metabolite levels during the first week after implantation.

Preimplantation urinary hormone profiles and the probability of conception in healthy women.

Objective: To examine hormonal predictors of conception in menstrual cycles from normal women.

Design: Longitudinal study.

Setting: Community.

Preimplantation hormonal differences between the conception and non-conception menstrual cycles of 32 normal women.

We compared daily urinary concentrations of oestrogen and progesterone metabolites in paired menstrual cycles (conception and non-conception) from 32 women. Volunteers with no known fertility problems were enrolled in the study at the time they began trying to become pregnant. They collected first-morning urine specimens and kept daily records of menstrual bleeding and sexual intercourse for 6 months or until they became clinically pregnant.

Application of a method for estimating day of ovulation using urinary estrogen and progesterone metabolites.

Longitudinal epidemiologic studies of menstrual and reproductive function are more informative if one can identify day of ovulation. We previously developed a method for estimating day of ovulation that is feasible for epidemiologic studies. The method relies on the relative concentrations of estrogen and progesterone metabolites in daily first-morning urine specimens and does not require creatinine adjustment.

Hormonal profiles of natural conception cycles ending in early, unrecognized pregnancy loss.

Loss of a conceptus early in development can be detected by very sensitive assays specific for hCG. We examined 20 menstrual cycles ending in early loss of a conceptus in order to identify hormonal correlates of loss. Each loss cycle was compared to a successful conception cycle in the same woman, using daily concentration of urinary estrone-3-glucuronide and pregnanediol-3-glucuronide (PdG).

Using the ratio of urinary oestrogen and progesterone metabolites to estimate day of ovulation.

We have developed a method of estimating day of ovulation using urinary ovarian hormone data. The method identifies a day of luteal transition that occurs at the shift from production of follicular oestrogen to luteal progesterone. The algorithm for identifying this shift was evaluated and judged better than specified alternatives in that it resulted in (1) a high concordance between the day of luteal transition and peaks in urinary luteinizing hormone (LH) for cycles with well-defined peaks, (2) a low variance in the length of the luteal phase of the menstrual cycle, which presumably reflects a low measurement error in estimating day of ovulation, and (3) a high proportion of cycles for which an approximate day of ovulation could be determined.