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Mucus observations in the fertile window: A better predictor of conception than timing of intercourse

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Intercourse results in a pregnancy essentially only if it occurs during the 6-day fertile interval ending on the day of ovulation. The strong association between timing of intercourse within this interval and the probability of conception typically is attributed to limited sperm and egg life times. A total of 782 women recruited from natural family planning centres in Europe contributed prospective data on 7288 menstrual cycles. Daily records of intercourse, basal body temperature and vaginal discharge of cervical mucus were collected. Probabilities of conception were estimated according to the timing of intercourse relative to ovulation and a 1-4 score of mucus quality. There was a strong increasing trend in the day-specific probabilities of pregnancy with increases in the mucus score. Adjusting for the mucus score, the day-specific probabilities had limited variability across the fertile interval. Changes in mucus quality across the fertile interval predict the observed pattern in the day-specific probabilities of conception. To maximize the likelihood of conception, intercourse should occur on days with optimal mucus quality, as observed in vaginal discharge, regardless of the exact timing relative to ovulation.
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Advance Access publication February 27, 2004
Mucus observations in the fertile window: a better
predictor of conception than timing of intercourse
Jamie L.Bigelow
1
, David B.Dunson
2
,
7
, Joseph B.Stanford
3
, Rene
Â
Ecochard
4
,
Christian Gnoth
5
and Bernardo Colombo
6
1
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC,
2
Biostatistics Branch, National Institute
of Environmental Health Sciences, Research Triangle Park, NC,
3
Department of Family and Preventive Medicine, University of
Utah, USA,
4
Service de Biostatistiques, Centre Hospitalo-Universitaire, Lyon, France,
5
Department of Gynecological Endocrinology
and Reproductive Medicine, Staedtische, Kliniken Duesseldorf gGmbH, Frauenklinik Benrath, Duesseldorf, Germany and
6
Department of Statistics, University of Padua, Padua, Italy
7
To whom correspondence should be addressed. E-mail: dunson1@niehs.nih.gov
BACKGROUND: Intercourse results in a pregnancy essentially only if it occurs during the 6-day fertile interval
ending on the day of ovulation. The strong association between timing of intercourse within this interval and the
probability of conception typically is attributed to limited sperm and egg life times. METHODS: A total of 782
women recruited from natural family planning centres in Europe contributed prospective data on 7288 menstrual
cycles. Daily records of intercourse, basal body temperature and vaginal discharge of cervical mucus were collected.
Probabilities of conception were estimated according to the timing of intercourse relative to ovulation and a 1±4
score of mucus quality. RESULTS: There was a strong increasing trend in the day-speci®c probabilities of preg-
nancy with increases in the mucus score. Adjusting for the mucus score, the day-speci®c probabilities had limited
variability across the fertile interval. CONCLUSIONS: Changes in mucus quality across the fertile interval predict
the observed pattern in the day-speci®c probabilities of conception. To maximize the likelihood of conception, inter-
course should occur on days with optimal mucus quality, as observed in vaginal discharge, regardless of the exact
timing relative to ovulation.
Key words: Bayesian analysis/cervical mucus/day-speci®c pregnancy probabilities/menstrual cycle/ovulation
Introduction
Intercourse is unlikely to result in a conception unless it
occurs during the 6-day fertile interval ending on the day
of ovulation (Wilcox et al., 1995; Dunson et al., 1999).
The start of the fertile interval generally corresponds to a
signi®cant rise in estrogen levels, which results in the
secretion of estrogenic cervical mucus and characteristic
changes in vaginal discharge (Billings et al., 1972; Insler
et al., 1972; Katz et al., 1997). Although monitoring of
these changes has long been used as a marker of the fertile
interval (Billings et al., 1989; World Health Organization,
1983; Dorairaj, 1991; Hilgers and Stanford, 1998; Sinai
et al., 1999), the extent to which mucus characteristics
predict the day-speci®c probabilities of conception within
the fertile interval is not known.
Because properties of cervical mucus determine whether
sperm will be capable of survival and transport to the ovum
(Moghissi, 1973; Yudin et al., 1989; Katz, 1991; Kunz et al.,
1997), we hypothesize that mucus characteristics on the day of
intercourse provide a clinically important predictor of the
probability of conception independent of the timing relative to
ovulation. In particular, consistent with the well known role of
estrogenic mucus in enhancing progressive sperm motility
(Eriksen et al., 1998) and allowing for penetration, storage and
transport of normal spermatozoa (Odeblad, 1968, 1997;
Menarguez et al., 2003), we anticipate that the day-speci®c
probabilities of conception will increase progressively with a
ranking of the fertility of the mucus.
Using data from the European Study of Daily Fecundability
(Colombo and Masarotto, 2000), we estimate the day-speci®c
probabilities of conception according to both the timing of
sexual intercourse relative to ovulation and a 1±4 ranking of the
fertility of the mucus. Our data provide additional information
not available in the World Heath Organization (1983) study
evaluating the use of vulvar mucus observations in estimating
the fertile interval. Because the WHO study did not have a
mucus-independent marker of ovulation day, the data cannot be
used to address our hypotheses. In addition, the WHO study
had problems with under-reporting of intercourse (Trussell and
Grummer-Strawn, 1991).
Human Reproduction Vol.19, No.4 pp. 889±892, 2004 DOI: 10.1093/humrep/deh173
Human Reproduction vol. 19 no. 4
ã
European Society of Human Reproduction and Embryology 2004; all rights reserved 889
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Materials and methods
Description of study design and data
The European Study of Daily Fecundability is a prospective cohort
study conducted to determine the daily probability of conception on
each cycle day relative to ovulation for healthy women in their
reproductive years. From 1992 to 1996, 782 women were recruited
from seven European centres providing services in fertility awareness
and natural family planning (NFP). Women enrolled were experienced
in NFP, married or in a stable heterosexual relationship, 18±40 years
of age, had at least one menses after cessation of breastfeeding or
delivery (if applicable), and were not currently taking hormonal
medication or drugs affecting fertility. In addition, neither partner
could have a history of fertility problems, and couples were required
not to use barriers or spermicide generally. Additional details on the
inclusion and exclusion criteria, the demographics of the cohort, and
other study methods and initial results have been published elsewhere
(Colombo and Masarotto, 2000).
Women kept daily records of basal body temperature (BBT),
cervical mucus symptoms and intercourse. The daily mucus observa-
tions were classi®ed according to Table I, ranging from a score of 1
(no discharge and dry) to 4 (transparent, stretchy, slippery). This 1±4
mucus scoring system is designed to summarize a wide variety of
different mucus characteristics in a way that is predictive of the
presence of fertile-type estrogenic mucus, which is characterized by a
high score. If a discharge exhibited mixed characteristics, or if a
woman observed multiple types of mucus through the course of the
day, the highest matching category was chosen to assign the score. A
primary goal of this study is to assess directly the extent to which the
different levels of the mucus score predict a real difference in the
conception probability.
The BBT data are used as a mucus-independent marker to estimate
the day of ovulation within each menstrual cycle using the three over
six rule (Marshall, 1968) to identify the last day of hypothermia as
described by Colombo and Masarotto (2000). Previous research
suggested that a BBT-based estimate of the ovulation day has a high
probability of being within 1 day of the true ovulation day, and that
estimates of day-speci®c conception probabilities based on BBT are
very similar to those based on estimating ovulation through urinary
hormonal assays (Dunson et al., 1999) or ultrasound (Gnoth et al.,
1996). A comparison of multiple markers of ovulation with the
ultrasound-determined day of ovulation indicated that the last day of
hypothermia, while not perfect, is an accurate marker of ovulation day
(Ecochard et al., 2001).
In a previous analysis of these data, Dunson et al. (2002) found that
nearly all pregnancies occurred from intercourse that took place in the
6-day window ending with the BBT-determined day of ovulation. This
6-day period was considered to be the fertile interval, and days outside
this period were not taken into consideration. Cycles were excluded
from the analysis if there were insuf®cient BBT data to determine the
ovulation day, if there were no reported intercourse acts during the
fertile interval, or if there was a day within the fertile interval on which
intercourse occurred but mucus information was missing. Out of 6724
menstrual cycles of data with 487 pregnancies, 1473 cycles remained
in the analysis, with 353 pregnancies. For the purposes of this study,
pregnancy is de®ned as either an ongoing pregnancy of at least 60 days
from the last menses or a clinically identi®ed spontaneous abortion
within 60 days of the last menses.
Bayesian statistical analysis approach
Modelling and estimation of pregnancy probabilities were carried out
using a Bayesian hierarchical modelling approach (Dunson, 2001).
This involves choosing prior distributions for unknown parameters in
a statistical model based on previous information and updating this
information with the data in the study to obtain posterior distributions,
which represent the current state of knowledge about the unknown
parameters. We base our inferences on summaries of the posterior
distribution, including posterior means, 95% credible intervals and
posterior probabilities.
We estimated the probability that intercourse would result in
pregnancy on each of the days in the 6-day interval ending on the day
of ovulation. In a cycle where intercourse occurred on more than one
day during the fertile period, it is impossible to determine which act
resulted in the pregnancy. Following Barrett and Marshall (1969),
Wilcox et al. (1995), Dunson et al. (2002) and Stanford et al. (2003)
among others, we use a statistical model that allows for the
incorporation of information from cycles where multiple intercourse
acts occurred. Since most women contributed more than one cycle to
the data, the model was also designed to account for within-woman
dependency. The analyses presented in this article are based on the
methods of Dunson and Stanford (2003).
Results
There was clear evidence of an increasing trend in the
pregnancy probability with increases in the mucus score after
adjusting for the timing and frequency of intercourse relative to
Table I. Classi®cation of mucus symptoms from vaginal discharge
Mucus score Feeling Appearance
1 Dry, rough and itchy or nothing felt Nothing seen
2 Damp Nothing seen
3 Damp Mucus is thick, creamy, whitish, yellowish, or sticky
4 Wet, slippery, smooth Mucus is transparent, like raw egg white, Stretchy/elastic, liquid, watery, or reddish
Figure 1. Estimated probability of pregnancy with a single act of
intercourse in the fertile interval conditional on mucus observations.
J.L.Bigelow et al.
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the BBT-identi®ed ovulation day. In particular, the posterior
probability of no effect of mucus on the pregnancy probability
was <0.01. The signi®cant trend was attributable to a steady
increase in the pregnancy probability with each unit increase in
the mucus score. Speci®cally, the posterior probability of an
increase in the pregnancy probability in going from a mucus
score of 1 to 2 was 0.95, while the corresponding probabilities
in going from scores of 2 to 3 and from 3 to 4 were 0.97 and
>0.99, respectively.
This relationship is demonstrated in Figure 1, which shows
the estimated day-speci®c pregnancy probabilities for the four
mucus types. The day of lowest fertility was 5 days before
ovulation, and the day of highest fertility was 3 days before
ovulation. The difference in pregnancy probability between
these two days ranged from 0.06 to 0.14, depending on mucus
quality, while the difference in pregnancy probability attrib-
utable to increasing the mucus score from 1 to 4 ranged from
0.1 to 0.18. Thus the gain in pregnancy probability attributable
to an increase from the lowest to highest mucus score is
generally higher than the gain attributable to having intercourse
3 days before ovulation instead of 5 days before ovulation.
Intercourse on any day in the 6-day window where the mucus is
type 4 has a pregnancy probability that is >0.17, while the
pregnancy probability does not exceed 0.13 on days with no
secretions (mucus score = 1). Within the fertile window, the
type of mucus observed on the day of intercourse is more
predictive of conception than the timing relative to ovulation.
Figure 2 shows the distribution of the reported mucus scores
according to timing within the fertile interval. On each day,
type 4 mucus is the most common, with the largest proportion
occurring 2 days before ovulation, which is also the day on
which the smallest proportion of cycles had no vaginal
discharge (type 1 mucus). It is important to note that each of
the days had a substantial proportion of women in each of the
mucus categories. Although fewer women reported type 2
mucus and that proportion remained essentially constant across
the fertile window, there was a signi®cant difference in the
pregnancy probabilities between type 2 mucus and the other
categories.
Discussion
Regardless of the timing of intercourse relative to ovulation,
pregnancy probabilities are highest when observations indicate
the presence of the most fertile-type estrogenic mucus. In
particular, the highest conception probability when there is no
observed discharge, occurring 2 days before ovulation, is lower
than the conception probability on any day in the 6-day interval
when most fertile-type mucus is present. These results provide
direct evidence that mucus plays a role in fertility that is more
important than its previously identi®ed role as a marker of the
fertile window of the menstrual cycle. Observations of the most
fertile-type mucus are probable throughout the fertile window,
but are most prevalent 2 days before the estimated ovulation
day.
Previous estimates of pregnancy probabilities on days
relative to ovulation did not account for daily observations of
the quality of mucus, though researchers have identi®ed
increased conception probabilities on days when secretions
were observed compared with no secretions (Dunson et al.,
2001) and in cycles with high mucus scores averaged over the
fertile window (Stanford et al., 2003). Our study demonstrates
that the quality of mucus explains most of the relationship
between the pregnancy probability and the timing of inter-
course relative to ovulation. It is remarkable that even a rough
categorization of mucus on a scale of 1±4, based on a woman's
own observations (Table I), explained more of the variability in
the day-speci®c probabilities of pregnancy than could be
attributed to timing of intercourse relative to ovulation.
Our results have important clinical implications. Because
vulvar observations of cervical mucus predict not only the
fertile days of the cycle but also the probabilities of conception
within the fertile interval, monitoring of mucus provides
additional information not provided by other methods for
identifying the fertile interval. In particular, methods based on
cycle monitoring by daily vaginal ultrasound and/or urinary
LH detection are not informative about the probability of
conception at a particularly time in the fertile interval within an
ovulatory cycle. In addition, such monitoring is expensive and
inconvenient and can miss the beginning of the fertile interval
and even the most fertile days. Many women already rely on
their own calculations to predict ovulation, often obtaining
estimates different from results of ultrasound or LH detection
(Gnoth et al., 2002). Hence, monitoring of mucus provides a
useful clinical marker of days with high conception probabil-
ities.
Acknowledgements
The authors thank Guido Masarotto, Petra Frank-Herrmann and the
other principal investigators of the European Study of Daily
Fecundability for providing the data and for helpful discussions.
Thanks also to Allen Wilcox and Donna Baird for their insightful
comments.
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... This period is known as the "Fertile Window" and includes the days preceding ovulation and the day of ovulation itself [2][3][4]. Studies suggest that the "fertility window" begins 5-6 days before ovulation and ends on the day of ovulation [5]. ...
... Moreover, the spermatozoa, which, by themselves, would die in hours thanks to the changes in the protein composition of the CM around the ovulatory phase, survive, accommodated in the cervical crypts for up to 5 days, ready to go towards the most distal part of the fallopian tube when ovulation happens [5]. ...
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Evaluation of cervical mucus is a standard for determining the fertile period in natural family planning. Cervical mucus accepts, filters, prepares, and releases sperm for successful transport to the egg and fertilization. Recent scientific advances provide answers to how the mucus regulates fertility as its physical properties change during the menstrual cycle. Transmission electron microscopy reveals small interstices between mucus macromolecules relative to a sperm head. Thus advancing sperm must push aside or cut through the microstructure. The interstices are largest in the periovulatory phase of the cycle. Small magnetic spheres, comparable with the size of a sperm head, are now being used to study the physical properties of the mucus on the scale of individual sperm.
Article
The modified mucus method-Prajanan Jagriti (fertility awakening) is intended to serve the cultural needs of illiterate and semilliterate women. Over 10 months, 3003 women in northern India were taught the modified mucus method. There were a total of 42 pregnancies in 24,702 cycles for a Pearl index of 2.04. High effectiveness is attributed to the support that was provided to clients by the instructor. PIP Prajanan Jagriti, a modified mucus method designed to fit the cultural needs of illiterate and semiliterate women with low status within the family, has enabled poor Indian women who cannot be reached with other methods of fertility control to plan their families. Although based on the observation of cervical mucus, this simplified method does not require its user to chart her menstrual cycle and demands fewer days of abstinence than traditional natural family planning (NFP) methods. In a 10-month period, 3003 women from North India, Uttar Pradesh, and Madhya Pradesh received structured teaching of the application of Prajanan Jagriti and supportive counseling from female village leaders. To ensure a thorough grasp of NFP concepts, only 10 women were instructed per month by each of the 37 village woman leaders, who were in turn supervised by 12 cluster coordinators from the Training and Action Pilot Project for non-Catholics. All 3003 women completed the first 3 months of training, and there were no unplanned pregnancies in the first month. In the 10 month study period, there were 42 unplanned pregnancies, for a Pearl index of 2.04. The main risk factor associated with these pregnancies was having no living child. Also contributing to method failure were cultural pressures to produce children, poor intraspouse communication, difficulties abstaining from sexual relations on the part of husbands, and the longer fertile period among younger women. Overall, however, project staff reported a high level of motivation on the part of these acceptors and a responsiveness to the shorter period of abstinence required by this modified method.
Article
Reanalysis of data on the ovulation method of natural family planning collected by the World Health Organization yields the following conclusions. The method is effective during perfect (correct and consistent) use, with a first-year probability of failure of 3.4%. However, it is extremely unforgiving of imperfect use, with a first-year probability of failure of 84.2% if the method is not used correctly. During the initial year, 87% of the cycles were characterized by perfect use. Nevertheless, the 13% of cycles characterized by imperfect use had a tremendous impact on the overall failure rate. During the first year of typical use 22.5% of the women in the clinical trial became accidentally pregnant.
Article
502 couples used the basal-body-temperature method of regulating births through 8294 cycles. The overall failure-rate in those confining coitus to the postovulatory phase of the menstrual cycle was 6·6 pregnancies per 100 women-years, while in those having coitus in the preovulatory and postovulatory phases it was 19·3 pregnancies per 100 women-years. The biological effectiveness of the method was greater than this, and was achieved by certain subgroups in the survey.