Day-specific Probabilities Of Conception Research Articles

Cervical-Vaginal Mucin in Fertility Assessment: CA125 as a Predictor of the Fertile Phase of the Normal Menstrual Cycle.

Background and objectives: To evaluate the cervical-vaginal mucin, CA125, as a measure of fertility and possible method for natural family planning (NFP). Materials and Methods: Cervical-vaginal fluid (CVF) swab samples have been previously used to measure CA125, ‘Qvaginal CA125 levels’, as a function of time of cycle relative to Day 0, the first day of positive urine LH (luteinizing hormone). Data from 15 women, 20 cycles were used with an algorithm to establish the Fertile Start Day (FSD) for the cycles. The FSD was determined as either the second consecutive day of ≥20% Qvaginal CA125 rise or the first day of ≥400% rise. The interval, (FSD to Day +3), was used as the theoretical window of fertility, and conception rates assuming abstinence during this predicted period of fertility were computed using published day-specific probabilities of conception (PoC). Results: The mean FSD was Day −4.8 ± 0.5 (SE), 95% CI (−5.9, −3.7). The estimated pregnancy failure rate (PFR) with abstinence during [FSD, +3] was 10.7% ± 2.0% (SE), 95% CI (6.9%, 14.8%); with exclusion of one cycle with very low levels of Qvaginal CA125, the estimated PFR was 9.8% ± 1.9%, 95% CI (6.3%, 13.8%). Furthermore, the day-specific Qvaginal CA125 values were normalized to the respective peak Qvaginal CA125 for each cycle, and a mean normalized day-specific Qvaginal CA125 plot was generated. The first derivative of the mean normalized day-specific Qvaginal CA125 plot showed a significant increase between Day −4.5 and Day −3.5, which correlated with the mean FSD. Conclusions: A Qvaginal CA125-based method holds promise as a means to identify the start of the fertile window and may prove useful in NFP, especially when combined with available home hormonal fertility awareness kits.

Anti-Müllerian hormone as a predictor of reproductive potential.

Anti-Müllerian hormone (AMH), a marker of ovarian reserve, declines over a woman's reproductive lifespan. AMH is highly correlated with a woman's age and number of primordial ovarian follicles, and has been shown to predict time to menopause in women in their 40s. For these reasons, it was assumed that AMH levels could predict a woman's reproductive potential or serve as a 'fertility test'. Recently, studies have sought to determine the association between AMH and fertility. Although a small, prospective, time-to-pregnancy study of 98 women suggested that an AMH level less than 0.7 ng/ml was associated with lower day-specific probabilities of conception, the follow-up, larger cohort did not identify an association with AMH and fecundability. Women with AMH values less than 0.7 ng/ml had similar pregnancy rates after 12 cycles of attempting to conceive as women with normal AMH values after adjusting for age. Four additional studies, including a secondary analysis of the NICHD EAGER trial including over 1200 women confirmed these findings. Although AMH is a marker of ovarian reserve, existing literature does not support the use of AMH as a marker of reproductive potential in the general population.

Estimation of Day-Specific Probabilities of Conception during Natural Cycle in Women from Babylon.

Background:Identifying predictors of the probabilities of conception related to the timing and frequency of intercourse in the menstrual cycle is essential for couples attempting pregnancy, users of natural family planning methods, and clinicians diagnosing for possible causes of infertility. The aim of this study is to estimate the days in which the likelihood of conception happened by using first trimester ultrasound fetal biometry in natural cycles and spontaneous pregnancy, and to explore some factors that may affect them.Materials and Methods:This study is retrospective cohort study, with random sampling. It involved 60 pregnant ladies at first trimester; the date of conception was estimated using: i. Crown-rump length biometry (routine ultrasound examinations were performed at a median of 70 days following Last menstrual period or equivalently 10 weeks), ii. Date of last menstrual cycle. Only women with previous infertility and now conceiving naturally with a certain date of Last menstrual period were selected.Results:The distribution of conception showed a sharp rise from day 8 onwards, reaching its maximum at day 13 and decreasing to zero by day 30 of Last menstrual period. The older and obese women had conceive earlier than younger women but there was insignificants difference between the two groups (P>0.05). According to the type of infertility, the women with secondary infertility had conceived earlier than those with primary infertility. There was a significant difference between the two groups (P<0.05).Conclusion:Day specific of conception may be affected by factors such as age, BMI, and type of infertility. This may be confirmed by larger sample size in metacentric study.

A composite likelihood approach to predict the sex of the baby.

Couples with diseases associated with the sexual chromosomes, as well as families in countries where the desire for a male is extreme, are interested in influencing the sex of the baby. We propose an original composite likelihood approach to analyse the relation between sex of the newborn and timing of the intercourse which leads to conception. Although there exist numerous works on this relation, only few studies have been carried out on independent datasets to validate the existing theories. Since the sex of the newborn is only known in case of conception, the full likelihood of the data is not easily defined without strong assumptions. A composite likelihood is a pseudo likelihood defined as the product of likelihood functions relative to subsets of the data. In particular, we consider two such likelihoods, one modelling the day-specific probabilities of conception and the other modelling the sex of the newborn given a conception has occurred. The methodology is applied to a dataset from a European fecundability study. The results show no significant dependence of the sex of the newborn on the time of intercourse. The method developed may be applied to other situations when data are affected by selective sampling.

Day-specific probabilities of conception in fertile cycles resulting in spontaneous pregnancies

When, within the female cycle, does conception occur in spontaneously fertile cycles? This study provides reference values of day-specific probabilities of date of conception in ongoing pregnancies. The maximum probability of being within a 5-day fertile window was reached on Day 12 following the last menstrual period (LMP). The true date of conception is not observable and may only be estimated. Accuracy of these estimates impacts on obstetric management of ongoing pregnancies. Timing of ovulation and fertility has been extensively studied in prospective studies of non-pregnant fertile women using error-prone proxies, such as hormonal changes, body-basal temperature and ultrasound, yielding day-specific probabilities of conception and fertile windows. In pregnant women, date of conception may be retrospectively estimated from early pregnancy fetal measurement by ultrasound. Retrospective analysis of consecutive pregnancies in women referred for routine first-trimester screening, over a 3-year period (2009-2011) in a single ultrasound center (n = 6323). Within the overall population, 5830 cases with a certain date of last menses were selected for analysis. The date of conception was estimated using a crown-rump length biometry and an equation derived from IVF/ICSI pregnancies. Day-specific probabilities of conception were estimated across several covariates, including age, cycle characteristics and ethnicity, using deconvolution methods to account for measurement error. Overall, the day-specific probability of conception sharply rises at 7 days after the LMP, reaching its maximum at 15 days and returning to zero by 25 days. Older women tend to conceive earlier within their cycle, as did women with regular cycles and white and black women compared with Asian ethnicity. The probability of being within the fertile window was 2% probability at Day 4, a maximum probability of 58% at Day 12 and a 5% probability by Day 21 of the cycle. Although conception is believed to occur within hours following ovulation, a discrepancy is theoretically possible. However, when comparing our results to those of prospective studies, no such difference was found. The equation used for estimating the date of pregnancy was estimated in IVF/ICSI pregnancies, which could lead to potential bias in spontaneous pregnancies. However, in our population, the observed bias was negligible. Non-fertile cycles and early pregnancy losses are necessarily overlooked because of the nature of our data. Because of the wider access to retrospective data and the potential bias in prospective studies of ovulation monitoring, this study should broaden the perspectives of future epidemiologic research in fertility and pregnancy monitoring. None.

Bayesian selection of optimal rules for timing intercourse to conceive by using calendar and mucus

To find optimal clinical rules that maximize the probability of conception while limiting the number of intercourse days required. Multicenter prospective study. Women were followed prospectively while they kept daily records of menstrual bleeding, intercourse, and mucus symptom characteristics. In some cycles, women sought to conceive, whereas in other cycles, they sought to avoid pregnancy. Four centers providing services on fertility awareness. One hundred ninety-one healthy women using the Billings Ovulation Method. Women were invited to enroll by their instructors if they satisfied the entry criteria. We excluded cycles in which mucus was not recorded on a day with intercourse. None. Clinically identified pregnancies. There were 161 clinically identified pregnancies in 2,536 menstrual cycles from 191 women. Our approach relies on a statistical model that relates daily predictors, such as type of mucus symptom, to the day-specific probabilities of conception. By using Bayesian methods to search over a large set of possible clinical rules, focusing on rules based on calendar and mucus, we found that simple rules that are based on days within the midcycle calendar interval that also have the most fertile-type mucus symptom present have high utility. Couples can shorten their time to pregnancy efficiently by timing intercourse on days that the most fertile-type mucus symptom is observed at the vulva.

Levonorgestrel emergency contraception: a joint analysis of effectiveness and mechanism of action

To model the effectiveness that can be obtained if levonorgestrel-only emergency contraception (EC) acts only through disrupting ovulation, in relation to other effects that may occur before or after fertilization and accounting for delays in administration. We modeled follicular growth as a function of follicular size, using known day-specific probabilities of conception and known disruption of ovulation by levonorgestrel-only EC, to estimate the expected effectiveness of EC. Combined data from multiple clinical studies. Simulation models. Disruption of ovulation. Effectiveness in the form of proportion of pregnancies prevented. With disruption of ovulation alone, the potential effectiveness of levonorgestrel EC ranged from 49% (no delay) to 8% (72-hour delay). With complete inhibition of fertilization before the day of ovulation, the potential effectiveness of levonorgestrel EC ranged from 90% (no delay) to 16% (72-hour delay). The gap between effectiveness of levonorgestrel EC estimated from clinical studies and what can be attributed to disruption of ovulation may be explained by overestimation of actual effectiveness and supplementary mechanisms of action, including postfertilization effects. Additional data with follicular ultrasound and precise measures of delay between intercourse and EC administration would yield greater insight into effectiveness and mechanisms of action.

Estimation of the day‐specific probabilities of conception: current state of the knowledge and the relevance for epidemiological research

Conception, as defined by the fertilisation of an ovum by a sperm, marks the beginning of human development. Currently, a biomarker of conception is not available; as conception occurs shortly after ovulation, the latter can be used as a proxy for the time of conception. In the absence of serial ultrasound examinations, ovulation cannot be readily visualised leaving researchers to rely on proxy measures of ovulation that are subject to error. The most commonly used proxy measures include: charting basal body temperature, monitoring cervical mucus, and measuring urinary metabolites of oestradiol and luteinising hormone. Establishing the timing of the ovulation and the fertile window has practical utility in that it will assist couples in appropriately timing intercourse to achieve or avoid pregnancy. Identifying the likely day of conception is clinically relevant because it has the potential to facilitate more accurate pregnancy dating, thereby reducing the iatrogenic risks associated with uncertain gestation. Using data from prospective studies of couples attempting to conceive, several researchers have developed models for estimating the day-specific probabilities of conception. Elucidating these will allow researchers to more accurately estimate the day of conception, thus spawning research initiatives that will expand our current limited knowledge about the effect of exposures at critical periconceptional windows. While basal body temperature charting and cervical mucus monitoring have been used with success in field-based studies for many years, recent advances in science and technology have made it possible for women to get instant feedback regarding their daily fertility status by monitoring urinary metabolites of reproductive hormones in the privacy of their own homes. Not only are innovations such as luteinising hormone test kits and digital fertility monitors likely to increase study compliance and participation rates, they provide valuable prospective data that can be used in epidemiological research. Although we have made great strides in estimating the timing and length of the fertile window, more work is needed to elucidate the day-specific probabilities of conception using proxy measures of ovulation that are inherently subject to error. Modelling approaches that incorporate the use of multiple markers of ovulation offer great promise to fill these important data gaps.

Measuring fecundity with standardised estimates of expected pregnancies

Approaches to measuring fecundity include the assessment of time to pregnancy and day-specific probabilities of conception (daily fecundities) indexed to a day of ovulation. In this paper, we develop an additional approach of calculating expected pregnancies based on daily fecundities indexed to the last day of the menstrual cycle. Expected pregnancies can thus be calculated while controlling for frequency and timing of coitus. Comparing observed pregnancies with expected pregnancies allows for a standardised comparison of fecundity between studies or groups within studies, and can be used to assess the effects of categorical covariates on the woman or couple level, and also on the cycle level. This can be accomplished in a minimal data set that does not necessarily require hormonal measurement or the explicit identification of ovulation. We demonstrate this approach by examining the effects of age and parity on fecundity in a data set from women monitoring their fertility cycles with the Creighton Model FertilityCare System.

Workshop recommendations for the preconception cohort of the National Children’s Study

This paper summarises discussions on incorporating preconception recruitment in the National Children's Study (NCS); these were part of the workshop on Expanding Methodologies for Capturing Day-Specific Probabilities of Conception. Four key issues were discussed in relation to the NCS: (1) differences between pregnancy 'planners' and 'non-planners'; (2) a tiered approach to preconception data collection; (3) data gaps in preconception studies; and (4) assessment of early pregnancy in subsequent pregnancies for women with a child already in the study. Practical recommendations were developed for each theme, which have relevance for other prospective studies of conception, pregnancy and human development.

Bayesian Inferences on Predictors of Conception Probabilities

Reproductive scientists and couples attempting pregnancy are interested in identifying predictors of the day-specific probabilities of conception in relation to the timing of a single intercourse act. Because most menstrual cycles have multiple days of intercourse, the occurrence of conception represents the aggregation across Bernoulli trials for each intercourse day. Because of this data structure and dependency among the multiple cycles from a woman, implementing analyses has proven challenging. This article proposes a Bayesian approach based on a generalization of the Barrett and Marshall model to incorporate a woman-specific frailty and day-specific covariates. The model results in a simple closed form expression for the marginal probability of conception, and has an auxiliary variables formulation that facilitates efficient posterior computation. Although motivated by fecundability studies, the approach can be used for efficient variable selection and model averaging in general applications with categorical or discrete event time data.

Methodologic and statistical approaches to studying human fertility and environmental exposure.

Although there has been growing concern about the effects of environmental exposures on human fertility, standard epidemiologic study designs may not collect sufficient data to identify subtle effects while properly adjusting for confounding. In particular, results from conventional time to pregnancy studies can be driven by the many sources of bias inherent in these studies. By prospectively collecting detailed records of menstrual bleeding, occurrences of intercourse, and a marker of ovulation day in each menstrual cycle, precise information on exposure effects can be obtained, adjusting for many of the primary sources of bias. This article provides an overview of the different types of study designs, focusing on the data required, the practical advantages and disadvantages of each design, and the statistical methods required to take full advantage of the available data. We conclude that detailed prospective studies allowing inferences on day-specific probabilities of conception should be considered as the gold standard for studying the effects of environmental exposures on fertility.

Bayesian modeling of the level and duration of fertility in the menstrual cycle.

Time to pregnancy studies that identify ovulation days and collect daily intercourse data can be used to estimate the day-specific probabilities of conception given intercourse on a single day relative to ovulation. In this article, a Bayesian semiparametric model is described for flexibly characterizing covariate effects and heterogeneity among couples in daily fecundability. The proposed model is characterized by the timing of the most fertile day of the cycle relative to ovulation, by the probability of conception due to intercourse on the most fertile day, and by the ratios of the daily conception probabilities for other days of the cycle relative to this peak probability. The ratios are assumed to be increasing in time to the peak and decreasing thereafter. Generalized linear mixed models are used to incorporate covariate and couple-specific effects on the peak probability and on the day-specific ratios. A Markov chain Monte Carlo algorithm is described for posterior estimation, and the methods are illustrated through application to caffeine data from a North Carolina pregnancy study.