No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Mucus observations in the fertile window: A better predictor of conception than timing of intercourse
Abstract
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.
... Billings [15] first proposed a now commonly used method to assess the progress of the biophysical properties of cervical secretion: to infer form the analysis of the cervical secretion at the vulva, fertile or infertile conditions according to its type, as a function of its physical touch sensation, visual appearance and consistency. Many similarly observational methods have appeared in the literature, including those by Hilgers, Ferning and others [11,[16][17][18][19][20]. Cervical discharge is a hydrogel where the liquid component is an aqueous solution of various biochemical compounds (e.g., salts, minerals, sugars, amino acids, lipids, protein chains, enzymes, etc.) and the solid component mainly glycoproteins. ...
... The secretion type G (gestagen) is scarce, thick, opaque, and cellular which blocks sperm penetration. Since stretching and transparency in an estrogenic cervical secretion increases in the preovulatory phase their measurement and characterization can be used as basic indicators of FW [14][15][16][17][18][19][20]24]. The internal structure of cervical secretion varies depending on the glycoprotein net that retains a liquid medium in its meshes. ...
... Most studies attempting to determine the FW using observations of the cervical secretion utilize similar intervals -6 days EDO [14][15][16][17][18][19][20][26][27][28]. Currently, most studies comparing FW with cervical discharge include the biophysical fertile window (BFW) [14,28]. ...
Background
Cervical discharge is considered a hydrogel, which is part liquid and part solid. Under physiological conditions, the characteristic “fern-leaf” arborization is proportional to the circulating estradiol concentration and maximal in the preovulatory phase. Crystallization of the cervical secretion is a process of dehydration with the arrangement of sodium and potassium chloride crystals around a main axis composed of mucin. L-type (Loaf) (L) is proportional to the circulating estradiol concentration and is higher in the Fertile Window (FW). Currently, most studies comparing the FW with cervical discharge include the biophysical fertile window (BFW) which is 6 days before the estimated day of ovulation (EDO).
Methods
Samples were taken from the vulvovaginal region within the FW using the Creighton Model System for Fertility Care (CrMS). Optical images of the samples were digitized to perform a binarization, skeletonization, and crystallization directionality study of the scanned branches. These samples taken from the vulvovaginal secretion were not collected from the endocervix. They were recorded by the Vaginal Secretion Recording System (VDRS) using CrMS. The FW was taken into account from 6 days before the peak (P) day according to CrMS. A statistical study was performed by comparing vulvovaginal crystallization samples including –6 day EDO in FW.
Results
Out of 29 samples, 58.6% deemed true positives, 34% were true negatives, 6.8% represented 2 false positives, and no cases were false negatives (p < 0.001).
Conclusions
Our analysis of the statistical distribution of the branching angles of the crystallization of cervical secretions allowed us to detect a significant contribution of 90-degree frecuencies, indicating, the existence of an L-type pattern in the FW samples that we studied. The skeletonization of the studied images together with a FW indicator allowed us to identify this crystallization pattern. We therefore propose this feature detection mechanism as a novel biomarker of fertility.
... Under these conditions, sperm must migrate from the seminal fluid and transit the high viscosity medium to reach the site of fertilization near the oviduct and standby for ovulation (the period of 24-48 h where the ovum is ready for fertilization) 56,57 . At ovulation, the secretions within the female tract increase, by upwards of two-to three-fold 19 , and viscosity decreases, to as low as 2 cP in the oviduct 19 , to promote passage of sperm to the ovum and sperm-ovum engagement 52,58,59 . An ability to overcome the high-viscosity medium presented earlier in the cycle would improve the chances of fertilization. ...
... At the start of the fertilization journey and during non-ovulatory periods, sperm with high DNA integrity and decapacitation factors engage in cooperation that enables faster migration through the high-viscosity secretions leading to the oviduct. Upon reaching the oviduct, and at the onset of ovulation (characterized by an increase in capacitation-promoting factors 83,86 and a decrease in secretion viscosity 52,58,59 ), sperm undergo capacitation, cease cooperation, and swim individually in competition through a low-viscosity medium to engage with the ovum. ...
... Sperm cease cooperative behavior upon entering a lowerviscosity medium. Ovulation involves an increase of secretions with capacitation-promoting factors that induce sperm capacitation 83,86 -a potential trigger to cease cooperative behavior-and a decrease in secretion viscosity 52,58,59 . We investigated whether the decrease in viscosity associated with ovulation could additionally prompt sperm to cease cooperative behavior. ...
Human sperm compete for fertilization. Here, we find that human sperm, unexpectedly, cooperate under conditions mimicking the viscosity contrasts in the female reproductive tract. Sperm attach at the head region to migrate as a cooperative group upon transit into and through a high viscosity medium (15-100 cP) from low viscosity seminal fluid. Sperm groups benefit from higher swimming velocity, exceeding that of individual sperm by over 50%. We find that sperm associated with a group possess high DNA integrity (7% fragmentation index) – a stark contrast to individual sperm exhibiting low DNA integrity (> 50% fragmentation index) – and feature membrane decapacitation factors that mediate sperm attachment to form the group. Cooperative behaviour becomes less prevalent upon capacitation and groups tend to disband as the surrounding viscosity reduces. When sperm from different male sources are present, related sperm preferentially form groups and achieve greater swimming velocity, while unrelated sperm are slowed by their involvement in a group. These findings reveal cooperation as a selective mode of human sperm motion – sperm with high DNA integrity cooperate to transit the highly viscous regions in the female tract and outcompete rival sperm for fertilization – and provide insight into cooperation-based sperm selection strategies for assisted reproduction.
... Previous studies that have used ultrasound, serum or urine hormones to assess cyclic changes in mucus quantity and quality have demonstrated the accuracy of observing changes in cervical mucus for identifying ovulation and the fertile window (fecund window), based on recognizing the appearance and disappearance of estrogenic quality mucus (World Health Organization, 1983b;Leader et al., 1985;Ecochard et al., 2001;Fehring, 2002;Stanford et al., 2003;Bigelow et al., 2004;Fehring et al., 2004;Alliende et al., 2005;Zinaman, 2006). In particular, the rise in estrogen before ovulation supports the secretion of estrogenic cervical mucus, which is observed by the woman as a discharge that is clear, stretchy, and or slippery (lubricative), known as peak type mucus (Billings et al., 1972;Hilgers and Prebil, 1979;Ecochard et al., 2015). ...
... In particular, the rise in estrogen before ovulation supports the secretion of estrogenic cervical mucus, which is observed by the woman as a discharge that is clear, stretchy, and or slippery (lubricative), known as peak type mucus (Billings et al., 1972;Hilgers and Prebil, 1979;Ecochard et al., 2015). The estrogenic quality of mucus is a strong indicator of the day-specific probability of pregnancy for intercourse on a specific day (Bigelow et al., 2004), and the overall mucus score for a menstrual cycle correlates strongly with cycle fecundability, for women without subfertility (Stanford et al., 2003). Clinically, women's observations have been used successfully to aid in avoiding pregnancy (Peragallo Urrutia et al., 2018) or achieving pregnancy (Mu and Fehring, 2014;Stanford, 2015). ...
... When a woman observed any mucus discharge that stretched over approximately 1 inch, was clear or partially clear in color, and/or had a sensation of lubrication, peak type mucus was considered to be present on that day. These qualities of mucus are associated with estrogen stimulation, in the absence of progesterone; i.e. estrogenic mucus (Hilgers and Prebil, 1979;Fehring, 2002;Bigelow et al., 2004;Ecochard et al., 2015). ...
STUDY QUESTION
What is the normal range of cervical mucus patterns and number of days with high or moderate day-specific probability of pregnancy (if intercourse occurs on a specific day) based on cervical mucus secretion, in women without known subfertility, and how are these patterns related to parity and age?
SUMMARY ANSWER
The mean days of peak type (estrogenic) mucus per cycle was 6.4, the mean number of potentially fertile days was 12.1; parous versus nulliparous, and younger nulliparous (<30 years) versus older nulliparous women had more days of peak type mucus, and more potentially fertile days in each cycle.
WHAT IS KNOWN ALREADY
The rise in estrogen prior to ovulation supports the secretion of increasing quantity and estrogenic quality of cervical mucus, and the subsequent rise in progesterone after ovulation causes an abrupt decrease in mucus secretion. Cervical mucus secretion on each day correlates highly with the probability of pregnancy if intercourse occurs on that day, and overall cervical mucus quality for the cycle correlates with cycle fecundability. No prior studies have described parity and age jointly in relation to cervical mucus patterns.
STUDY DESIGN, SIZE, DURATION
This study is a secondary data analysis, combining data from three cohorts of women: ‘Creighton Model MultiCenter Fecundability Study’ (CMFS: retrospective cohort, 1990–1996), ‘Time to Pregnancy in Normal Fertility’ (TTP: randomized trial, 2003–2006), and ‘Creighton Model Effectiveness, Intentions, and Behaviors Assessment’ (CEIBA: prospective cohort, 2009–2013). We evaluated cervical mucus patterns and estimated fertile window in 2488 ovulatory cycles of 528 women, followed for up to 1 year.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Participants were US or Canadian women age 18–40 years, not pregnant, and without any known subfertility. Women were trained to use a standardized protocol (the Creighton Model) for daily vulvar observation, description, and recording of cervical mucus. The mucus peak day (the last day of estrogenic quality mucus) was used as the estimated day of ovulation. We conducted dichotomous stratified analyses for cervical mucus patterns by age, parity, race, recent oral contraceptive use (within 60 days), partial breast feeding, alcohol, and smoking. Focusing on the clinical characteristics most correlated to cervical mucus patterns, linear mixed models were used to assess continuous cervical mucus parameters and generalized linear models using Poisson regression with robust variance were used to assess dichotomous outcomes, stratifying by women’s parity and age, while adjusting for recent oral contraceptive use and breast feeding.
MAIN RESULTS AND THE ROLE OF CHANCE
The majority of women were <30 years of age (75.4%) (median 27; IQR 24–29), non-Hispanic white (88.1%), with high socioeconomic indicators, and nulliparous (70.8%). The mean (SD) days of estrogenic (peak type) mucus per cycle (a conservative indicator of the fertile window) was 6.4 (4.2) days (median 6; IQR 4–8). The mean (SD) number of any potentially fertile days (a broader clinical indicator of the fertile window) was 12.1 (5.4) days (median 11; IQR 9–14). Taking into account recent oral contraceptive use and breastfeeding, nulliparous women age ≥30 years compared to nulliparous women age <30 years had fewer mean days of peak type mucus per cycle (5.3 versus 6.4 days, P = 0.02), and fewer potentially fertile days (11.8 versus 13.9 days, P < 0.01). Compared to nulliparous women age <30 years, the likelihood of cycles with peak type mucus ≤2 days, potentially fertile days ≤9, and cervical mucus cycle score (for estrogenic quality of mucus) ≤5.0 were significantly higher among nulliparous women age ≥30 years, 1.90 (95% confidence interval (CI) 1.18, 3.06); 1.46 (95% CI 1.12, 1.91); and 1.45 (95% CI 1.03, 2.05), respectively. Between parous women, there was little difference in mucus parameters by age. Thresholds set a priori for within-woman variability of cervical mucus parameters by cycle were examined as follows: most minus fewest days of peak type mucus >3 days (exceeded by 72% of women), most minus fewest days of non-peak type mucus >4 days (exceeded by 54% of women), greatest minus least cervical mucus cycle score >4.0 (exceeded by 73% of women), and most minus fewest potentially fertile days >8 days (found in 50% of women). Race did not have any association with cervical mucus parameters. Recent oral contraceptive use was associated with reduced cervical mucus cycle score and partial breast feeding was associated with a higher number of days of mucus (both peak type and non-peak type), consistent with prior research. Among the women for whom data were available (CEIBA and TTP), alcohol and tobacco use had minimal impact on cervical mucus parameters.
LIMITATIONS, REASONS FOR CAUTION
We did not have data on some factors that may impact ovulation, hormone levels, and mucus secretion, such as physical activity and body mass index. We cannot exclude the possibility that some women had unknown subfertility or undiagnosed gynecologic disorders. Only 27 women were age 35 or older. Our study participants were geographically dispersed but relatively homogeneous with regard to race, ethnicity, income, and educational level, which may limit the generalizability of the findings.
WIDER IMPLICATIONS OF THE FINDINGS
Patterns of cervical mucus secretion observed by women are an indicator of fecundity and the fertile window that are consistent with the known associations of age and parity with fecundity. The number of potentially fertile days (12 days) is likely greater than commonly assumed, while the number of days of highly estrogenic mucus (and higher probability of pregnancy) correlates with prior identifications of the fertile window (6 days). There may be substantial variability in fecundability between cycles for the same woman. Future work can use cervical mucus secretion as an indicator of fecundity and should investigate the distribution of similar cycle parameters in women with various reproductive or gynecologic pathologies.
STUDY FUNDING/COMPETING INTEREST(S)
Funding for the three cohorts analyzed was provided by the Robert Wood Johnson Foundation (CMFS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (TTP), and the Office of Family Planning, Office of Population Affairs, Health and Human Services (CEIBA). The authors declare that they have no conflict of interest.
TRIAL REGISTRATION NUMBER
N/A
... Cervicovaginal mucus properties also change over the estrus cycle. It is well described that at the luteal phase, cervical mucus is less hydrated and more viscous [10], which is also accompanied by an increase in protein production [11e13], which results in cloudier mucus than that at the follicular phase [11]. ...
... In the current study, there was a significant effect of phase of the cycle on mucus production, with more mucus at the follicular than at the luteal phase. The production of cervical mucus has been shown to increase under the influence of oestrogen in the lead up to ovulation [10,21]. This explains the higher mucus production at the follicular than at the luteal phase in our study. ...
... These differences in mucus colour between high and low fertility ewe breeds could be key to elucidate molecular components in the cervical mucus related to impaired sperm transport in some ewe breeds. It has been previously reported that mucus colour is affected by mucus volume, hydration and protein concentration [10,11]. As outlined earlier, mucus structure changes by varying the molecular configuration and cross linkages between mucin proteins, which allow sperm migration through the mucus mesh [27,28]. ...
In sheep, cervical artificial insemination (AI) involves depositing semen at the cervical opening, as it is not possible to traverse the cervix due to its complex anatomy. However, internationally this method yields low pregnancy rates when frozen-thawed semen is used. An exception to this is in Norway, in which vaginal deposition of frozen-thawed semen to a natural estrus yields pregnancy rates around 70%. As the cervix and its secretions are the principal factors influencing sperm transport to the site of fertilization the aim of this study was to characterise the differences in the cervical anatomy as well as the cervicovaginal mucus properties of six European ewe breeds across three countries known to have differences in pregnancy rates following cervical AI with frozen-thawed semen. These were Suffolk and Belclare in Ireland, Fur and Norwegian White Sheep (NWS) in Norway and Ile de France and Romanov in France (n ¼ 28e30 ewes/breed). Cervicovaginal mucus was collected at the follicular and luteal phases of both a synchronized and natural cycle and assessed for mucus weight, viscosity and colour. The anatomical characteristics of the cervix (length of the cervix, number of cervical rings and the appearance of the external os) were assessed post-mortem. There was a type of the cycle by ewe breed interaction represented by no differences in mucus production between ewe breeds at the natural cycle for both the follicular and luteal phases of the cycle. However, there were differences between ewe breeds at the synchronized cycle (P < 0.05). Belclare had the lowest mucus production at the follicular phase while NWS had the lowest amount of mucus at the luteal phase of the synchronized cycle. Overall, across all ewe breeds, mucus production was higher at the follicular than at the luteal phase (P < 0.05). Despite reports of Suffolk and NWS having the most divergent pregnancy rates following cervical AI with frozen-thawed semen, both breeds had the lowest overall mucus viscosity at the follicular phase of both types of cycle with no differences between both ewe breeds (P > 0.05). The length of the cervix, number of cervical rings and the external os type were affected by ewe breed (P < 0.05). Suffolk ewes had longer cervices but lower number of cervical rings than NWS and Fur ewes (both with higher pregnancy rates). In conclusion, while mucus production and mucus viscosity was affected by breed, these changes are not consistent with the known differences between ewe breeds in their pregnancy rates following cervical AI with frozen-thawed semen.
... The accuracy of the self-identified fertile peak relative to ultrasonography-confirmed ovulation varies among methods, 4 with urinary hormonal arrays and cervical fluid monitoring consistently found to be the most accurate. [5][6][7][8][9][10] Calendar methods are based on statistical averages and do not necessarily reflect the current menstrual cycle. 3 BBT measurements are difficult to interpret prospectively since the temperature rise is an event that indicates retrospectively when ovulation has occurred. ...
... The potential increase in fecundability from monitoring cervical fluid is physiologically plausible, and has been supported in several observational studies. 6,[8][9][10]41,42 However, a prior small randomised trial failed to confirm the impact of monitoring cervical fluid on time-topregnancy, suggesting that additional research may still be needed. 43 Feeling ovulation was associated with increased fecundability after adjustment for some potential confounders, but not after additional adjustment for reproductive history and gynaecological factors. ...
Background
The use of fertility indicators to predict ovulation has largely been studied for contraceptive purposes, while less so as fertility‐promoting tools.
Objective
To investigate the association between fertility indicators and fecundability in Danish women trying to conceive.
Methods
Web‐based preconception cohort study. We analysed data from 11,328 females aged 18–49 years trying to conceive without fertility treatment for ≤6 menstrual cycles, from the Danish SnartGravid.dk and SnartForældre.dk cohorts (2007–2023). Participants reported the use of fertility indicators (counting days since the last menstrual period, cervical fluid monitoring, urinary ovulation testing, feeling ovulation, using a smartphone fertility app and measuring basal body temperature [BBT] ). Time to pregnancy was measured in menstrual cycles ascertained by self‐reported pregnancy status. We estimated fecundability ratios (FR) and 95% confidence intervals (CIs) using proportional probabilities regression models adjusted for age, socio‐economic position, health indicators, reproductive history and gynaecological factors.
Results
Fertility indicators were used by 63.3% of participants at study entry. Counting days was the most common (46.9%), while measuring BBT was the least (3.0%). Other indicators ranged from 17.0% to 23.6%, with 69.7% using more than one indicator. Compared with non‐use, use of any fertility indicator was associated with greater fecundability (adjusted FR 1.14, 95% CI 1.08, 1.19). Cervical fluid monitoring showed the strongest association (aFR 1.46, 95% CI 1.03, 2.07), followed by urinary ovulation testing (aFR 1.35, 95% CI 1.16, 1.58) and counting days (aFR 1.18, 95% CI 1.09, 1.29). Feeling ovulation and fertility apps were modestly associated with fecundability, while measuring BBT was not associated. Sensitivity analysis restricting to ≤2 cycles of attempt time and two cycles of follow‐up showed an aFR for any indicator use of 1.21 (95% CI 1.13, 1.31).
Conclusion
In this Danish preconception cohort, use of fertility indicators was associated with a higher fecundability, varying by type of indicator.
... 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]. ...
There is an increasing number of couples interested in identifying the fertile window
for the purpose of conceiving. From what has been published so far, it can be concluded that there are no reliable methods to predict ovulation, and, therefore, to predict the fertile window. Proteins of the cervical mucus (CM) could behave as biomarkers to allow the early and precise identification of ovulation. CM samples were collected from the lumen of the cervical canal from women of reproductive age, on three different days of the same menstrual cycle. Samples were first analyzed and classified by light microscopy. High-resolution mass spectrometry and bioinformatic analysis were performed afterwards to determine the in vivo changes of CM protein composition. CM underwent cyclical changes in its biophysical composition, which were evidenced by changes in the crystallographic patterns observed under the light microscope. The proteomic analysis revealed changes in the protein composition of CM along the cycle. Twenty-five out of the forty-eight total proteins identified could become potential biomarkers of ovulation. The coordinated changes in the composition of the CM around the time of ovulation could be happening to specifically grant access to a foreign body, such as the sperm might be.
... All days with mucus that was clear, stretchy or lubricative (estrogen-stimulated qualities) were considered days of peak-type mucus (Hilgers and Prebil, 1979;Fehring, 2002;Bigelow et al., 2004;Ecochard et al., 2015;Najmabadi et al., 2021). Days with any mucus discharge that had none of the characteristics of peak-type mucus were considered days with non-peak mucus (Najmabadi et al., 2021). ...
... Like other investigators, we found a substantial variability of the luteal phase length overall (Blaicher et al., 1999;Duijkers et al., 2005;Jones and Lopez, 2006;Fritz and Speroff, 2011). Cycles with fewer days of peak-type mucus have lower potential fecundability (Stanford et al., 2003;Bigelow et al., 2004). We cannot exclude entirely the possibility that seminal fluid or arousal fluid Generalized linear mixed models were used to generate risk ratios and 95% confidence intervals. ...
STUDY QUESTION
Does sexual intercourse enhance the cycle fecundability in women without known subfertility?
SUMMARY ANSWER
Sexual intercourse (regardless of timing during the cycle) was associated with cycle characteristics suggesting higher fecundability, including longer luteal phase, less premenstrual spotting and more than 2 days of cervical fluid with estrogen-stimulated qualities.
WHAT IS KNOWN ALREADY
Human females are spontaneous ovulators, experiencing an LH surge and ovulation cyclically, independent of copulation. Natural conception requires intercourse to occur during the fertile window of a woman’s menstrual cycle, i.e. the 6-day interval ending on the day of ovulation. However, most women with normal fecundity do not ovulate on Day 14, thus the timing of the hypothetical fertile window varies within and between women. This variability is influenced by age and parity and other known or unknown elements. While the impact of sexual intercourse around the time of implantation on the probability of achieving a pregnancy has been discussed by some researchers, there are limited data regarding how sexual intercourse may influence ovulation occurrence and menstrual cycle characteristics in humans.
STUDY DESIGN, SIZE, DURATION
This study is a pooled analysis of three cohorts of women, enrolled at Creighton Model FertilityCare centers in the USA and Canada: ‘Creighton Model MultiCenter Fecundability Study’ (CMFS: retrospective cohort, 1990–1996), ‘Time to Pregnancy in Normal Fertility’ (TTP: randomized trial, 2003–2006) and ‘Creighton Model Effectiveness, Intentions, and Behaviors Assessment’ (CEIBA: prospective cohort, 2009–2013). We evaluated cycle phase lengths, bleeding and cervical mucus patterns and estimated the fertile window in 2564 cycles of 530 women, followed for up to 1 year.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Participants were US or Canadian women aged 18–40 and not pregnant, who were heterosexually active, without known subfertility and not taking exogenous hormones. Most of the women were intending to avoid pregnancy at the start of follow-up. Women recorded daily vaginal bleeding, mucus discharge and sexual intercourse using a standardized protocol and recording system for up to 1 year, yielding 2564 cycles available for analysis. The peak day of mucus discharge (generally the last day of cervical fluid with estrogen-stimulated qualities of being clear, stretchy or slippery) was used to identify the estimated day of ovulation, which we considered the last day of the follicular phase in ovulatory cycles. We used linear mixed models to assess continuous cycle parameters including cycle, menses and cycle phase lengths, and generalized linear models using Poisson regression with robust variance to assess dichotomous outcomes such as ovulatory function, short luteal phases and presence or absence of follicular or luteal bleeding. Cycles were stratified by the presence or absence of any sexual intercourse, while adjusting for women’s parity, age, recent oral contraceptive use and breast feeding.
MAIN RESULTS AND THE ROLE OF CHANCE
Most women were <30 years of age (75.5%; median 27, interquartile range 24–29), non-Hispanic white (88.1%), with high socioeconomic indicators and nulliparous (70.9%). Cycles with no sexual intercourse compared to cycles with at least 1 day of sexual intercourse were shorter (29.1 days (95% CI 27.6, 30.7) versus 30.1 days (95% CI 28.7, 31.4)), had shorter luteal phases (10.8 days (95% CI 10.2, 11.5) versus 11.4 days (95% CI 10.9, 12.0)), had a higher probability of luteal phase deficiency (<10 days; adjusted probability ratio (PR) 1.31 (95% CI 1.00, 1.71)), had a higher probability of 2 days of premenstrual spotting (adjusted PR 2.15 (95% CI 1.09, 4.24)) and a higher probability of having two or fewer days of peak-type (estrogenic) cervical fluid (adjusted PR 1.49 (95% CI 1.03, 2.15)).
LIMITATIONS, REASONS FOR CAUTION
Our study participants were geographically dispersed but relatively homogeneous in regard to race, ethnicity, income and educational levels, and all had male partners, which may limit the generalizability of the findings. We cannot exclude the possibility of undetected subfertility or related gynecologic disorders among some of the women, such as undetected endometriosis or polycystic ovary syndrome, which would impact the generalizability of our findings. Acute illness or stressful events might have reduced the likelihood of any intercourse during a cycle, while also altering cycle characteristics. Some cycles in the no intercourse group may have actually had undocumented intercourse or other sexual activity, but this would bias our results toward the null. The Creighton Model FertilityCare System (CrM) discourages use of barrier methods, so we believe that most instances of intercourse involved exposure to semen; however, condoms may have been used in some cycles. Our dataset lacks any information about the occurrence of female orgasm, precluding our ability to evaluate the independent or combined impact of female orgasm on cycle characteristics.
WIDER IMPLICATIONS OF THE FINDINGS
Sexual activity may change reproductive hormonal patterns, and/or levels of reproductive hormones may influence the likelihood of sexual activity. Future work may help with understanding the extent to which exposure to seminal fluid, and/or female orgasm and/or timing of intercourse could impact menstrual cycle function. In theory, large data sets from women using menstrual and fertility tracking apps could be informative if women can be appropriately incentivized to record intercourse completely. It is also of interest to understand how cycle characteristics may differ in women with gynecological problems or subfertility.
STUDY FUNDING/COMPETING INTEREST(S)
Funding for the research on the three cohorts analyzed in this study was provided by the Robert Wood Johnson Foundation #029258 (Creighton Model MultiCenter Fecundability Study), the Eunice Kennedy Shriver National Institute of Child Health and Human Development 1K23 HD0147901-01A1 (Time to Pregnancy in Normal Fertility) and the Office of Family Planning, Office of Population Affairs, Health and Human Services 1FPRPA006035 (Creighton Model Effectiveness, Intentions, and Behaviors Assessment). The authors declare that they have no conflict of interest.
TRIAL REGISTRATION NUMBER
N/A.
... The cervix plays a dynamic role in fertility, which is regulated by endogenous hormones (mainly estrogen and progesterone) across the follicular and luteal phases of the estrous cycle. At the follicular phase, there is an increase in mucus production [11,12] to allow sperm with normal morphology and motility to traverse the cervix [13]. At the luteal phase, mucus production and hydration decrease [14] resulting in more viscous and cloudier mucus than that at the follicular phase [6], thereby providing an effective barrier against pathogens [11,15]. ...
... At the follicular phase, there is an increase in mucus production [11,12] to allow sperm with normal morphology and motility to traverse the cervix [13]. At the luteal phase, mucus production and hydration decrease [14] resulting in more viscous and cloudier mucus than that at the follicular phase [6], thereby providing an effective barrier against pathogens [11,15]. These cyclic changes in mucus properties are also accompanied by changes in cervical gene expression. ...
Worldwide, cervical artificial insemination (AI) using frozen–thawed semen yields low pregnancy rates. The only exception to this is in Norway, where vaginal insemination with frozen–thawed semen yields pregnancy rates in excess of 60% and which has been attributed to the specific ewe breed used. Our previous work demonstrated differences in cervical gene expression at the follicular phase of the oestrous cycle in ewe breeds with known differences in pregnancy rates. In this study, we characterised the cervical transcriptome of the same ewe breeds (Suffolk, Belclare, Fur and Norwegian White Sheep (NWS)) during the luteal phase, as an optimal environment at the luteal phase could better prepare the cervix for sperm migration through the cervix at the subsequent follicular phase. High-quality-RNA extracted from post-mortem cervical tissue was analysed by RNA-sequencing. After stringent filtering, 1051, 1924 and 611 differentially expressed genes (DEGs) were detected in the low fertility Suffolk breed compared to Belclare, Fur and NWS, respectively. Gene ontology analysis identified increased humoral adaptive immune response pathways in Suffolk. Increased expression of multiple immune genes supports the presence of an active immune response in the cervix of Suffolk ewes which differentiates them significantly from the other three ewe breeds. Inflammatory pathways were up-regulated in the Suffolk, resulting in higher expression of the potent pro-inflammatory cytokines. Therefore, higher levels of pro-inflammatory cytokines indicate unresolved inflammation in the cervix of the low fertility Suffolk breed that could contribute to reduced cervical sperm transport in the next follicular phase.
... The majority of fertility awareness/natural family planning (NFP) methods encompass subjective observations of cervical mucus/cervical-vaginal fluid (CVF) [1][2][3]. The physical properties of cervical mucus/CVF that lend themselves to female self-observation can be even more accurate in assessing the fertile time than timing relative to the point of ovulation [4]. Given the importance of the physical cervical mucus/CVF paradigm in natural family planning methods, one can hypothesize that there are biochemical and molecular factors that could serve to objectify assessment of the fertile and infertile phases and prove useful to women practicing NFP. ...
... This is the first report of a cervical mucus and vaginal fluid macromolecule that has been considered for a practical method for fertility awareness and natural family planning. The theoretical probabilities of pregnancy-that is, the pregnancy failure rates with the Qvaginal CA125 methodwere calculated using day-specific pregnancy probabilities indexed to the first day of positive urine LH, Day 0. It should be noted that the theoretical pregnancy failure rate, 10.7% ± 2.0%(SE), because of the index based on the urine LH signal, may have a high bias, since there are clinical trials which indicate that cervical mucus/CVF physical parameters can be a better predictor of the fertile window than timing with hormonal values [4,28,29]. Assuming that CA125 (the MUC16 mucin) tracks fertile cervical mucus, a day of low Qvaginal CA125 and low rate of change even in the fertile window of Day −4 to Day +1, would putatively indicate less fertility than that solely considered by reference to urine LH signal. ...
: To evaluate the cervical-vaginal mucin, CA125, as a measure of fertility and possible method for natural family planning (NFP). 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). 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. 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.
... As long as the model adequately distinguishes the follicular and luteal phases, the conditional probabilities for a subject being in the first or second stages of the menstrual cycle could be used for a model-based judgement for the day of ovulation. Several methods have been proposed to objectively identify the day of ovulation based on the BBT, which include a widely used rule of thumb called the three over six rule (Bortot et al. 2010, Colombo and Masarotto 2000, Bigelow et al. 2004), a method based on the cumulative sum test (Royston and Abrams 1980), and a stopping rule based on a change-point model (Carter and Blight 1981). A limitation shared among these methods is that they may be difficult to apply, or less effective even if used (Carter and Blight 1981), when observations in the BBT time series are missing. ...
The menstrual cycle is composed of the follicular phase and subsequent luteal phase based on events occurring in the ovary. Basal body temperature (BBT) reflects this biphasic aspect of menstrual cycle and tends to be relatively low during the follicular phase. In the present study, we proposed a state-space model that explicitly incorporates the biphasic nature of the menstrual cycle, in which the probability density distributions for the advancement of the menstrual phase and that for BBT switch depend on a latent state variable. Our model derives the predictive distribution of the day of the next menstruation onset that is adaptively adjusted by accommodating new observations of BBT sequentially. It also enables us to obtain conditional probabilities of the woman being in the early or late stages of the cycle, which can be used to identify the duration of follicular and luteal phases, as well as to estimate the day of ovulation. By applying the model to real BBT and menstruation data, we show that the proposed model can properly capture the biphasic characteristics of menstrual cycles, providing a good prediction of the menstruation onset in a wide range of age groups. An application to a large data set containing 25,622 cycles provided by 3,533 woman subjects further highlighted the between-age differences in the population characteristics of menstrual cycles, suggesting wide applicability of the proposed model.
... Az egészséges pároknál a terhesség legnagyobb valószínűsége ciklusonként ~20-40%, a populáció jellemzőitől függően, beleértve az életkort és a paritást. Ez akkor következik be, ha a párok az ovuláció előtt 1-2 nappal házaséletet élnek, különösen azokon a napokon, amikor a méhnyaknyák ösztrogéntulajdonságai a legnagyobbak (áttetsző, nyúlós, csúszós folyadék), ami optimalizálja a spermiumok túlélését és továbbhaladását [24,39]. Számos tanulmány vizsgálta a termékenység elérését célzó időzített együttlétet több különböző termékenységtudatossági módszer esetében [11,[40][41][42][43]. Összességében ezek a vizsgálatok azt sugallják, hogy az egészséges párok 85-90%-ában 6 hónapon belül megfoganhat a várandósság termékenységre összpontosító együttléttel [28,44]. ...
The so-called restorative reproductive medicine (RRM) tries to help and support infertility couples who want to
avoid the assisted reproductive technologies or they are after failed in vitro fertilization. This approach supports the
spontaneous fertilization. Fertility awareness methods of natural family planning teach couples about reproductive
health. They allow daily monitoring and interpretation of certain physical signs, such as cervical mucus. These
changes can reflect hormonal changes in the female fertility cycle, helping to identify the ovulation in paper or electronic
cycle calendars (Creighton, Fertility Education and Medical Management, Billings, Sensiplan). Fertility awareness
methods can be important not only for those with religious beliefs, but can also be recommended for all motivated, healthy couples, as they can effectively help them conceive. The information obtained from the cycle charts
can be used in the work of restorative reproductive medicine to complement the diagnosis of infertility, which is
considered a chronic condition, and also to monitor the treatment of each individual. The methods can also be used
independently by couples with infertility to determine timed intercourse to achieve pregnancy. To be effective, it is
recommended that they are used with the guidance of trained educators. A common aspect of the methods is that
they make childbearing a shared responsibility of the couple, emphasizing understanding and communication between
husband and wife. Unfortunately, little information is available on the various fertility awareness-based methods
in medical education. Restorative reproductive medicine aims to restore normal physiological fertility, using
fertility awareness methods in combination with medical and surgical treatments. Cycle charts allow women to track
their ovulation cycle by monitoring hormonal-based physical changes, identifying the fertile period. This allows the
couple to understand, maintain and improve the woman’s reproductive health and increase their self-awareness.
Specialized restorative reproductive medicine clinics are located at the Assisted Reproduction Center of the Department
of Obstetrics and Gynecology of Semmelweis University and at the Christian Family Center of the Irgalmasrendi
Hospital of Buda.
Keywords: fertility awareness, women’s health, natural family planning, infertility, restorative reproductive medicine
... This database contains information on 51,013 cycles from 3296 women from Great Britain, Italy, France, Germany, and Belgium and includes five sets of data, as shown in Fig. 1. The database has undergone consistency checks and has been used for several studies on the menstrual cycle (72,73), fecundity (71,(74)(75)(76), and the evolution of the menstrual cycle with age (77,78). The data were obtained from women with no known cycle disorders. ...
The ovarian cycle has a well-established circa-monthly rhythm, but the mechanisms involved in its regularity are unknown. Is the rhythmicity driven by an endogenous clock-like timer or by other internal or external processes? Here, using two large epidemiological datasets (26,912 cycles from 2303 European women and 4786 cycles from 721 North American women), analyzed with time series and circular statistics, we find evidence that the rhythmic characteristics of the menstrual cycle are more likely to be explained by an endogenous clock-like driving mechanism than by any other internal or external process. We also show that the menstrual cycle is weakly but significantly influenced by the 29.5-day lunar cycle and that the phase alignment between the two cycles differs between the European and the North American populations. Given the need to find efficient treatments of subfertility in women, our results should be confirmed in larger populations, and chronobiological approaches to optimize the ovulatory cycle should be evaluated.
... Blood, mucus, and saliva are among the biological fluids that display viscoelastic behavior (Chhabra R. P. & Richardson J F., 2010). Cervical mucus is a vital fluid that fills the female reproductive tract in the context of human fertility, and its viscoelastic nature is critical in determining the fertile phase of a woman's hormonal cycle (Bigelow et al., 2004). Viscoelastic fluids do not follow the linear relationship between shear stress ( ) and shear rate ( ), in contrast to Newtonian fluids, in which the shear stress ( ) is linearly proportional to the shear rate ( ), with viscosity ( ) being the proportional constant or with a constitutive relation of = . ...
Mammalian sperm need to travel a long distance of the complicated female reproductive tract in order to fertilize the egg. Meanwhile, the fertility assessment of a male is primarily based on analysis that is performed with semen diluted in a simple lab medium, sandwiched between glass surfaces. It is not surprising that the existing semen analysis does not have the best predictive power of the fertility potential of the male, while a large portion of infertility remains unexplained. To help address this deficiency, it is important to develop a better understanding of how sperm move in a physical environment that better assembles the natural environment they will encounter in females. This study aims to shine a light on the propulsion mechanism experimentally. Sperm swim in highly viscoelastic mucus in females, therefore we focus on sperm motility within a polymeric viscoelastic fluid. High-speed microscopy and particle image are used to visualize and analyze the motion of bovine sperm as well as the fluid in a viscoelastic fluid.
A previous theoretical study has shown that polar-ordered suspensions are unstable for low-Reynolds number systems such as swimming sperm, yet here we show that sperm can form a polar-ordered flock stable for at least 13 minutes, suggesting a propulsion mechanism that does not require pushing of the surrounding fluid.
We also aim to understand the flow generation through sperm flagellum beating, and we made progress on two fronts in this direction. First, in theoretical or numerical models that explain swimming through flagellum beating, it is often assumed that the velocity of the fluid is the same as the velocity of the solid/flagellum, which is also called a no-slip boundary condition. Here, we experimentally show that our viscoelastic fluid has a highly slippery boundary condition at a solid surface. Second, by measuring the flow field generated by sperm motility, we found that very limited flow was actually generated, while not observing the typical flow field expected from a pusher microswimmer.
The findings of this study provide new insights into the mechanisms of sperm motility and could inform the design of new strategies for controlling and manipulating the propulsion of sperm in complex fluids.
... Indeed, in biological systems microorganisms such as sperm cells navigate in a non-Newtonian fluid. The nonlinearity of the dispersing medium may affect the sperm transport [33] apart from being important in several other processes including biofilm formation [34,35] or fertilization [36]. As previously reported, a viscoelastic medium may even induce propulsion to a reciprocal swimmer which performs periodic, timereversible, body-shape deformations [37]. ...
Driven or self-propelling particles moving in viscoelastic fluids recently emerged as a novel class of active systems showing a complex yet rich set of phenomena due to the non-Newtonian nature of the dispersing medium. Here we investigate the one-dimensional growth of clusters made of active colloidal shakers, which are realized by oscillating magnetic rotors dispersed within a viscoelastic fluid and at different concentrations of the dissolved polymer. These magnetic particles when actuated by an oscillating field display a flow profile similar to that of a shaker force dipole, i.e., without any net propulsion. We design a protocol to assemble clusters of colloidal shakers and induce their controlled expansion into elongated zigzag structures. We observe a power law growth of the mean chain length and use theoretical arguments to explain the measured 1 / 3 exponent. These arguments agree well with both experiments and particle based numerical simulations.
Published by the American Physical Society 2024
... The composition of cervical mucus changes immediately after ovulation when the corpus luteum of the ovary begins synthesizing progesterone. Progesterone reduces the quantity and composition of cervical mucus, making it thicker and stickier [4]. The biochemical processes underlying these changes are poorly understood, but it is known that changes in the number and types of polysaccharide chains (glycans) attached to proteins during post-translational modification can drastically increase the proteins' molecular weights and thereby alter their solubility, solution viscosity, and biological function. ...
Cervical mucus (CM) is a viscous fluid that is produced by the cervical glands and functions as a uterine cervix plug. Its viscosity decreases during ovulation, providing a window for non-invasive sampling. This study focuses on proteomic characterization of CM to evaluate its potential as a non-invasively acquired source of biomarkers and in understanding of molecular (patho)physiology of the female genital tract. The first objective of this work was to optimize experimental workflow for CM processing and the second was to assess differences in the proteomic composition of CM during natural ovulatory cycles obtained from intrauterine insemination (IUI) cycles and in vitro fertilization (IVF) cycles with controlled ovarian hyperstimulation. Proteomic analysis of CM samples revealed 4370 proteins involved in processes including neutrophil degranulation, cellular stress responses, and hemostasis. Differential expression analysis revealed 199 proteins enriched in IUI samples and 422 enriched in IVF. The proteins enriched in IUI were involved in phosphatidic acid synthesis, responses to external stimulus, and neutrophil degranulation, while those enriched in IVF samples were linked to neutrophil degranulation, formation of a cornified envelope and hemostasis. Subsequent analyses clarified the protein composition of the CM and how it is altered by hormonal stimulation of the uterus.
... The Digitrapper reflux testing system, a commercial product from Medtronic, can quantify acid reflux symptoms with catheter based impedance testing 20 . In the reproductive tract, the medical grade kegg fertility tracker device helps to more accurately predict a woman's fertile window by measuring electrolyte levels through cervical fluid impedance 21 . ...
The surface mucosa that lines many of our organs houses myriad biometric signals and, therefore, has great potential as a sensor–tissue interface for high-fidelity and long-term biosensing. However, progress is still nascent for mucosa-interfacing electronics owing to challenges with establishing robust sensor–tissue interfaces; device localization, retention and removal; and power and data transfer. This is in sharp contrast to the rapidly advancing field of skin-interfacing electronics, which are replacing traditional hospital visits with minimally invasive, real-time, continuous and untethered biosensing. This Review aims to bridge the gap between skin-interfacing electronics and mucosa-interfacing electronics systems through a comparison of the properties and functions of the skin and internal mucosal surfaces. The major physiological signals accessible through mucosa-lined organs are surveyed and design considerations for the next generation of mucosa-interfacing electronics are outlined based on state-of-the-art developments in bio-integrated electronics. With this Review, we aim to inspire hardware solutions that can serve as a foundation for developing personalized biosensing from the mucosa, a relatively uncharted field with great scientific and clinical potential. The surface mucosa that lines many of our organs hosts a diverse set of biometric signals. This Review compares present skin-interfacing and mucosa-interfacing electronics to inspire hardware solutions for developing devices for personalized biosensing from the mucosa.
... In couples without subfertility, the highest probability of pregnancy per cycle is ∼20-40%, depending on the characteristics of the population, including age and parity. It occurs when couples have intercourse 1-2 days before ovulation, particularly on days with the greatest estrogenic qualities of cervical fluid (clear, stretchy, slippery fluid), which optimizes sperm survival and transport (28,64,66). Data are sparse and mixed as to whether frequent intercourse decreases or actually increases overall sperm motility and concentration, and how this may impact the probability of pregnancy (67)(68)(69). ...
Background:
Fertility awareness-based methods (FABMs) educate about reproductive health and enable tracking and interpretation of physical signs, such as cervical fluid secretions and basal body temperature, which reflect the hormonal changes women experience on a cyclical basis during the years of ovarian activity. Some methods measure relevant hormone levels directly. Most FABMs allow women to identify ovulation and track this "vital sign" of the menstrual or female reproductive cycle, through daily observations recorded on cycle charts (paper or electronic).
Applications:
Physicians can use the information from FABM charts to guide the diagnosis and management of medical conditions and to support or restore healthy function of the reproductive and endocrine systems, using a restorative reproductive medical (RRM) approach. FABMs can also be used by couples to achieve or avoid pregnancy and may be most effective when taught by a trained instructor.
Challenges:
Information about individual FABMs is rarely provided in medical education. Outdated information is widespread both in training programs and in the public sphere. Obtaining accurate information about FABMs is further complicated by the numerous period tracking or fertility apps available, because very few of these apps have evidence to support their effectiveness for identifying the fertile window, for achieving or preventing pregnancy.
Conclusions:
This article provides an overview of different types of FABMs with a published evidence base, apps and resources for learning and using FABMs, the role FABMs can play in medical evaluation and management, and the effectiveness of FABMs for family planning, both to achieve or to avoid pregnancy.
... These results are similar to those described by Hilgers [25] in 1978 where he shows evidences a peak day between (-3 and +3) in relation to the peak day of ovulation. Bigelow describes the characteristics of cervical discharge on a fourth scales [26]. He found a relationship between the quality of cervical mucus and the probability of pregnancy, being the day -3 OED higher for a type 4 mucus, which decreased as he moved away from OED. ...
Background
The principal objective of this study was to correlate biophysical properties of vaginal discharge present in the cervical mucus with the timing of the fertile window. In particular, we produce measures of the viscoelasticity of the cervical secretion using two methods. The first uses only the elasticity extracted from the Creighton Model Fertility Care System (CrMs) scale, calculated P-6 ovulation estimated day (OED) with respect to the peak day of the CrMs. The second uses a numerical method that takes into account the changes in viscoelasticity, but without reference to the peak day calculated using the CrMs model. Using both methods, twelve records were obtained from a single female subject.
Methods
The methodology used to evaluate the viscoelasticity factor was by measuring the approximate length in centimeters (cm) of the vaginal discharge of cervical discharge. For this, the scale of the stretching graph established by observing the stretching of CrMS was used, taking into account the previous 6 days at peak day P-6. The first method, which we termed CFW (Clinical Fertile Window), uses a measure based on the approximate length (cm) of the maximal stretchiness of the vaginal discharge. The second method we termed SFW (Software-CrMS/strectching) (Software-based Fertile Window).
Results
The fertile window was detected correctly in 100% of the cases using either method, and a correlation value of 0.71 was observed between the two methods.
Conclusions
We conclude that the assessment of viscoelasticity using SFW algorithm allowed in this pilot study to detect the fertile window and to describe the evolution pattern of cervical discharge throughout the fertile window. Our study provides support for the use of computational methods in detecting the fertile window, taking only into account the time evolution of the cervical discharge throughout the menstrual cycle.
... These findings have been corroborated with the Creighton Model Fertility Care System. In this way, it has been possible through cervical secretion to identify and describe cervical secretion from the early follicular phase to the peak day of cervical mucus (16). Through these studies and others, the detection of the peak day has been determined as a biomarker of maximum characteristics and has been contrasted using different modalities. ...
Today it is possible to detect the fertile window about six days before ovulation and two daysafter ovulation. The estimated day of ovulation (EDO) has been used as a strategy and testing tool to determine intervals that detect changes from infertile to fertile phase.This methodology has enabled the clinical fertile window approach in several performances in clinical practice. Some intervals and methodologies related to practical applications in the diagnosis of the fertile window are discussed. - (CFW): Clinical Fertile Window
- (BFW): Physiological fertile window defned by (ASRM) as the frst day whenestrone-3-glucuronide (E3G) is detected in the urine, until the second day afterthe peak of luteinizing hormone (LH), which usually ranges from <1 to > 7 days. - (CFW): (mucus-mucus): Starts on the frst day of any cervical mucus andends on the fourth day after peak mucus. - (CFW-BBT): Beginning on the frst day of any cervical mucus and ending onthe third day of high BBT. - (CFW-peak mucus): Beginning on the frst day of peak mucus and ending onthe last day of this type of mucus. - Ovulation window (OW): The last 2 days of BFW.
... In this regard, it is possible by self-observation of cervical secretion to evaluate cervical mucus objectively. This is possible, for example, by recording and characterizing the evolution of cervical mucus using different globally recognized scales such as, for example, the Creighton Modeling System (CrMs) (52)(53)(54)(55)(56)(57). The predictive evaluation of cervical secretion in the fertile window, excluding inflammatory or infectious pathology, or causes of cervical mucus hostility, allows prediction of the fertile window where ovulation occurs. ...
The objective of this analysis is to evaluate the different tests that investigate tubal patency, along with the microenvironments of the female reproductive tract that can affect gamete transport. The female menstrual cycle is determined by the interaction between the regulatory systems of the hypothalamic-pituitary-gonadal axis at three main levels: at the gonadotropin-releasing hormone (GnRH) pulse, at the pituitary level and at the ovarian hormone level. The physiological variability of estrogen and progesterone concentrations throughout the men-strual cycle determines in an orderly fashion the outcome of a chain of events that follow one after the other. The integral evaluation between cervical flow and sperm swimming is one of the current challenges in the approach to infertility.
... For example, it has been well documented that cervical mucus properties and quantities are controlled by cycling reproductive hormones [14]- [16] and that these changes can be observed and reported by app users [3], [5]. Body temperature at wake-up has been shown to increase after ovulation and in early pregnancy [15], [17]. ...
Globally, millions of women track their menstrual cycle and fertility via smartphone-based health apps, generating multivariate time series with frequent missing data. To leverage this type of data for studies of fertility or studies of the effect of the menstrual cycle on symptoms and diseases, it is critical to have methods for identifying reproductive events, such as ovulation, pregnancy losses or births. Here, we present a hierarchical approach relying on hidden semi-Markov models that adapts to changes in tracking behavior, explicitly captures variable and state dependent missingness, allows for variables of different type, and quantifies uncertainty. The accuracy on simulated data reaches 98% with no missing data and 90% with realistic missingness. On our partially labeled real-world time series, the accuracy reaches 93%. Our method also accurately predicts cycle length by learning user characteristics. Its implementation is publicly available (HiddenSemiMarkov R package) and transferable to any health time series, including self-reported symptoms and occasional tests.
... The aim of these methods is to determine the timing of the fertile window and to predict the occurrence of ovulation. Sexual intercourse during the fertile window may result in pregnancy, with increasing chance of conception as the day of ovulation approaches then occurs (Bigelow et al. 2004). For contraceptive purposes, therefore, intercourse during the fertile window should be avoided until such time as there is confidence that ovulation has occurred and the ovum is no longer ...
Alzheimer`s disease (AD) is the most common and incurable form of dementia. The present AD treatments produce only an uncertain amelioration of symptoms. Research on AD has particularly focused on the central nervous system. Though, some systemic and peripheral abnormalities are now clearly understood that are associated to AD. Current research on these alterations that leads to AD are becoming further defined more evidently. Two microscopic features contribute for the depiction of the disease, the amyloid plaques and neurofibrillary tangles. All these aspects are accountable for the deliberate and gradual weakening of memory that disturb the cognitive control, language, thinking and personality. For the diagnosis of AD, some neuropsychological tests are being performed in various spheres of cognitive functions. To date, cholinesterase inhibitors are used as a drug for the treatment of AD, because these are the individual drugs that have depicted substantial enhancements in the cognitive functions of AD patients. Despite the efficacy of cholinesterase inhibitors, the degeneration of neurons is continuing even while being treated an AD patient. For this cause, further biochemical pathways related to pathophysiology of AD have been revealed as an alternative for the treatment of these conditions such as hindrance of glycogen synthase kinase-3β and β-secretase. The present chapter aims to conduct a review of the pathophysiology, symptoms, epidemiology, analysis and treatment of AD.
... Cervical mucus will also change shortly after ovulation, lessening in quantity and becoming thicker, thus inhibiting the survival of sperm (Bigelow et al., 2004). ...
Objectives: Infertility has been disproportionately associated with distress in women, yet, there has been limited research focusing on the influence of coping strategies and fertility-monitoring techniques (e.g., ovulation predictor tests) in women attempting to conceive naturally.
Methods: Fifty-eight women were recruited for a study, via social media, examining the daily coping strategies and fertility monitoring methods (e.g., use of ovulation predictor tests), in relation to daily infertility distress among women with infertility. Over the course of one menstrual cycle, daily coping strategies, use of fertility monitoring methods, quality of life, and mood was assessed in the morning and evening of every second day.
Results: A number of influential coping strategies were identified impacting women’s psychological outcomes. Participants who had sought emotional support from professionals and reported focusing on other life goals were more likely to report improved psychological outcomes, while those who reported avoidance of infertility reminders, using food, drugs, or alcohol to cope, and seeking social support on the internet (e.g. chatrooms) were more likely to report worsened psychological outcomes. When the outcome of a pregnancy test was negative, there was an associated increase in depression but also a decrease in anxiety compared to days where no test was taken. A positive test, in contrast, was associated with less depressive mood but also increased anxiety.
Conclusion: These findings highlight a number of potential areas for clinical targets for future infertility specific interventions.
... During ovulation, if sampled and allowed to dry on glass slides, cervical mucus and saliva will form fern-like patterns observable under a microscope [31,38,42]. The instructions prompt users to observe the changes in these fluids with the curious eye, as well as to observe changes in the texture of cervical mucus by stretching it between their fingers, as this is also an indicator of ovulation [13]. The poster prompts the repetition of these experiments in different stages of the cycle. ...
... The cycles are evaluated according to the so-called "double-check" principle: two parameters each secure both the beginning and the end of the fertile window [2]. There is a high correlation between the cycle parameters used (cervical mucus, temperature rise and calculation rules) with objective ovulation [3,4]. Ovulation in cycles in which Sensiplan is applied is in 81% about 1-2 days before the temperature rise (mean of 0.92 ± 1.17 days before temperature rise) or 0.11 ± 1.31 days after the day of peak cervical mucus. ...
Purpose:
Many physicians and other healthcare professionals are often asked questions on interfering factors for conception by couples with a desire for children. Such possible disturbances include, for example, the very common minor diseases, stress and also sexual intercourse during the suspected implantation period. Non-scientifically based statements about disturbances in conception cycles, as found in many layman publications and on the internet, can strongly unsettle couples with a desire for children and force them into corset of rules of conduct. Therefore, a systematic scientific evaluation of the impact of disturbances on conception is urgently needed.
Methods:
A search for possible disturbances in natural conception cycles together with up to three of the respective pre-cycles in a large cycle database from users of the symptothermal method of natural family planning in Germany was performed. Disturbances were qualified by scientific panel decision and analysed statistically with their effects on the chances of spontaneous conception. Mixed logistical regression models and survival time analyses were used.
Results:
A total of 237 women with a total of 747 cycles could be included in the analysis. In 61% of all 237 conception cycles, disturbances occurred. The statistical analysis shows that disturbances in natural conception cycles unexpectedly increase the likelihood of pregnancy by an overall factor of 1.32 (95% CI 1.04-1.70). Sexual intercourse in the window of implantation does not decrease the chances of conception. Relaxation states at the time of ovulation and/or during the implantation period have no representable effect and do not increase the chance of pregnancy.
Conclusions:
Couples trying to conceive should at least be informed that disturbances in conception cycles, such as minor diseases, stress or sexual intercourse during the implantation period do not interfere with conception. Relaxation has no effect in favour of success. This takes away the guilty feeling of couples, fearing that they possibly did something wrong in cycles without the desired pregnancy.
Study question:
What is the effect of oestrogen and progesterone at the beginning of the menstrual cycle in delaying entry into the fertile window?
Summary answer:
Both oestrogen and progesterone contribute to a delay in the onset of the fertile window.
What is known already:
Oestrogen enhances cervical mucus secretion while progesterone inhibits it.
Study design, size, duration:
Observational study. Daily observation of 220 menstrual cycles contributed by 88 women with no known menstrual cycle disorder.
Participants/materials, setting, methods:
Women recorded cervical mucus daily and collected first-morning urine samples for analysis of oestrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FHS, and LH. They underwent serial ovarian ultrasound examinations. The main outcome measure was the timing within the cycle of the onset of the fertile window, as identified by the appearance of mucus felt or seen at the vulva.
Main results and the role of chance:
Low oestrogen secretion and persistent progesterone secretion during the first week of the menstrual cycle both negatively affect mucus secretion. Doubling oestrogen approximately doubled the odds of entering the fertile window (OR: 1.82 95% CI=1.23; 2.69). Increasing PDG from below 1.5 to 4 µg/mg creatinine was associated with a 2-fold decrease in the odds of entering the fertile window (OR: 0.51 95% CI=0.31; 0.82). Prolonged progesterone secretion during the first week of the menstrual cycle was also statistically significantly associated with higher LH secretion. Finally, the later onset of the fertile window was associated with statistically significant persistently elevated LH secretion during the luteal phase of the previous menstrual cycle.
Limitations, reasons for caution:
This post hoc study was conducted to assess the potential impact of residual progesterone secretion at the beginning of the menstrual cycle. It was conducted on an existing data set because of the scarcity of data available to answer the question. Analysis with other datasets with similar hormone results would be useful to confirm these findings.
Wider implications of the findings:
This study provides evidence for residual progesterone secretion in the early latency phase of some menstrual cycles, which may delay the onset of the fertile window. This progesterone secretion may be supported by subtly increased LH secretion during the few days before and after the onset of menses, which may relate to follicular waves in the luteal phase. Persistent progesterone secretion should be considered in predicting the onset of the fertile window and in assessing ovulatory dysfunction.
Study funding/competing interest(s):
The authors declare no conflicts of interest. No funding was provided for this secondary data analysis.
Trial registration number:
N/A.
Ovulation is critical for both conception and overall health, but many people who may ovulate are not tracking ovulation or any other part of their menstrual cycle. Failure to track ovulation, especially in those trying to conceive, can lead to fertility challenges due to absent ovulation, mistiming intercourse, or an undetected luteal phase defect. Ovulatory disorders and mistiming intercourse are both primary causes of infertility, and tracking ovulation is shown to decrease the average time to conception. While there are many tracking methods and apps available, the majority are predictive apps or ovulation predictor kits and do not test or track both successful ovulation and the health of the luteal phase, leading to missing information that could contribute to diagnosis or successful conception. Here, we review why ovulation tracking and a healthy luteal phase are important for those trying to conceive. We present currently available ovulation tracking methods that detect both ovulation and the luteal phase, including cervical mucus, urinary hormone testing, and basal body temperature, and discuss the use, advantages, and disadvantages of each. Finally, we consider the role of digital applications and tracking technologies in ovulation tracking.
Gebelikte Radyasyon Maruziyeti Ahmet Eren ŞEN Mustafa EROL Gebelikte Üriner Sistem Hastalıkları İhsan ŞAFAK Endometriyum ve Serviks Malignitelerinde Fertilite Koruyucu Yaklaşım Mürşide ÇEVİKOĞLU KILLI Gebelik ve Gastointestinal Sistem Hastalıkları İhsan ŞAFAK Gebelikte Antifosfolipid Sendromunun Etkileri ve Yönetimi Yusuf DAL Kadın İnfertilitesine Yaklaşım Feden Kübra ÖZDİLEK KIRÇİÇEĞİ Hipertansif Gebeliklerde Umblikal Doppler Rezistans İndeksinin Önemi Gülay BALKAŞ Gebelik ve Migren Utku AKGÖR Nonimmun Hidrops Fetalis Serdar AYKUT Teratojenler Mesut AVAN
The self-monitoring of the menstrual cycle enables women to track their cycle, to determine the time of ovulation and the fertile window and to identify possible cycle disorders. It is known as natural family planning (NFP). The principles of self-observation include changes in cervical mucus and the basal body temperature. The cervical mucus is found externally on the vulva and serves as an indicator for the fertile window. Together with the temperature rise it indicates the time of ovulation. Cycle monitoring does not require regular cycles or a specific lifestyle. There are different approaches and methods of NFP, the quality and effectiveness of which vary. Cycle apps and new measurement systems have increased the use of cycle monitoring but are very often unreliable. Furthermore, luteinizing hormone (LH) kits are often overestimated and can lead to incorrect results. Gynecologists can refer women to qualified counsellors to learn the Sensiplan method, which is recommended by the German Society for Gynecological Endocrinology and Fertility Medicine (DGGEF). This has become established due to its contraceptive safety, the clearly defined methodology and the continuous scientific evaluation.
Background:
Many factors influence fertility, one being the timing of intercourse. The 'fertile window' describes a stage in the cycle when conception can occur and is approximately five days before to several hours after ovulation. 'Timed intercourse' is the practice of prospectively identifying ovulation and, thus, the fertile window to increase the likelihood of conception. Methods of predicting ovulation include urinary hormone measurement (luteinising hormone (LH) and oestrogen), fertility awareness-based methods (FABM) (including tracking basal body temperatures, cervical mucus monitoring, calendar charting/tracking apps), and ultrasonography. However, there are potentially negative aspects associated with ovulation prediction, including stress, time consumption, and cost implications of purchasing ovulation kits and app subscriptions. This review considered the evidence from randomised controlled trials (RCTs) evaluating the use of timed intercourse (using ovulation prediction) on pregnancy outcomes.
Objectives:
To evaluate the benefits and risks of ovulation prediction methods for timing intercourse on conception in couples trying to conceive.
Search methods:
We searched the Cochrane Gynaecology and Fertility (CGF) Group Specialised Register, CENTRAL, MEDLINE, and Embase in January 2023. We also checked the reference lists of relevant studies and searched trial registries for any additional trials.
Selection criteria:
We included RCTs that compared methods of timed intercourse using ovulation prediction to other forms of ovulation prediction or intercourse without ovulation prediction in couples trying to conceive.
Data collection and analysis:
We used standard methodological procedures recommended by Cochrane to select and analyse studies in this review. The primary review outcomes were live birth and adverse events (such as depression and stress). Secondary outcomes were clinical pregnancy, pregnancy (clinical or positive urinary pregnancy test not yet confirmed by ultrasound), time to pregnancy, and quality of life. We assessed the overall quality of the evidence for the main comparisons using GRADE methods.
Main results:
This review update included seven RCTs involving 2464 women or couples. Four of the five studies from the previous review were included in this update, and three new studies were added. We assessed the quality of the evidence as moderate to very low, the main limitations being imprecision, indirectness, and risk of bias. Urinary ovulation tests versus intercourse without ovulation prediction Compared to intercourse without ovulation prediction, urinary ovulation detection probably increases the chance of live birth in couples trying to conceive (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.02 to 1.81, 1 RCT, n = 844, moderate-quality evidence). This suggests that if the chance of a live birth without urine ovulation prediction is 16%, the chance of a live birth with urine ovulation prediction is 16% to 28%. However, we are uncertain whether timed intercourse using urinary ovulation detection resulted in a difference in stress (mean difference (MD) 1.98, 95% CI -0.87 to 4.83, I² = 0%, P = 0.17, 1 RCT, n = 77, very low-quality evidence) or clinical pregnancy (RR 1.09, 95% CI 0.51 to 2.31, I² = 0%, 1 RCT, n = 148, low-quality evidence). Similar to the live birth result, timed intercourse using urinary ovulation detection probably increases the chances of clinical pregnancy or positive urine pregnancy test (RR 1.28, 95% CI 1.09 to 1.50, I² = 0, 4 RCTs, n = 2202, moderate-quality evidence). This suggests that if the chance of a clinical pregnancy or positive urine pregnancy test without ovulation prediction is assumed to be 18%, the chance following timed intercourse with urinary ovulation detection would be 20% to 28%. Evidence was insufficient to determine the effect of urine ovulation tests on time to pregnancy or quality of life. Fertility awareness-based methods (FABM) versus intercourse without ovulation prediction Due to insufficient evidence, we are uncertain whether timed intercourse using FABM resulted in a difference in live birth rate compared to intercourse without ovulation prediction (RR 0.95, 95% CI 0.76 to 1.20, I² = 0%, 2 RCTs, n = 157, low-quality evidence). We are also uncertain whether FABM affects stress (MD -1.10, 95% CI -3.88 to 1.68, 1 RCT, n = 183, very low-quality evidence). Similarly, we are uncertain of the effect of timed intercourse using FABM on anxiety (MD 0.5, 95% CI -0.52 to 1.52, P = 0.33, 1 RCT, n = 183, very low-quality evidence); depression (MD 0.4, 95% CI -0.28 to 1.08, P = 0.25, 1 RCT, n = 183, very low-quality evidence); or erectile dysfunction (MD 1.2, 95% CI -0.38 to 2.78, P = 0.14, 1 RCT, n = 183, very low-quality evidence). Evidence was insufficient to detect a benefit of timed intercourse using FABM on clinical pregnancy (RR 1.13, 95% CI 0.31 to 4.07, 1 RCT, n = 17, very low-quality evidence) or clinical or positive pregnancy test rates (RR 1.08, 95% CI 0.89 to 1.30, 3 RCTs, n = 262, very low-quality evidence). Finally, we are uncertain whether timed intercourse using FABM affects the time to pregnancy (hazard ratio 0.86, 95% CI 0.53 to 1.38, 1 RCT, n = 140, low-quality evidence) or quality of life. No studies assessed the use of timed intercourse with pelvic ultrasonography.
Authors' conclusions:
The new evidence presented in this review update shows that timed intercourse using urine ovulation tests probably improves live birth and pregnancy rates (clinical or positive urine pregnancy tests but not yet confirmed by ultrasound) in women under 40, trying to conceive for less than 12 months, compared to intercourse without ovulation prediction. However, there are insufficient data to determine the effects of urine ovulation tests on adverse events, clinical pregnancy, time to pregnancy, and quality of life. Similarly, due to limited data, we are uncertain of the effect of FABM on pregnancy outcomes, adverse effects, and quality of life. Further research is therefore required to fully understand the safety and effectiveness of timed intercourse for couples trying to conceive. This research should include studies reporting clinically relevant outcomes such as live birth and adverse effects in fertile and infertile couples and utilise various methods to determine ovulation. Only with a comprehensive understanding of the risks and benefits of timed intercourse can recommendations be made for all couples trying to conceive.
Objective:
To assess the effect of randomization to FertilityFriend.com (FF), a mobile computing fertility-tracking app, on fecundability.
Design:
Parallel non-blinded randomized controlled trial nested within Pregnancy Study Online (PRESTO), a North American preconception cohort.
Subjects:
Female participants aged 21-45 years attempting conception for ≤6 menstrual cycles at enrollment (2013-2019).
Intervention:
Randomization (1:1) of 5,532 participants to receive a premium FF subscription.
Main outcome measures:
Fecundability (per-cycle probability of conception). Participants completed bimonthly follow-up questionnaires until pregnancy or a censoring event, whichever came first. We first performed an intent-to-treat analysis of the effect of FF randomization on fecundability. In secondary analyses, we used a per-protocol approach that accounted for adherence in each trial arm. In both analyses, we used proportional probabilities regression models to estimate fecundability ratios (FR) and 95% confidence intervals (CI) comparing those randomized vs. not randomized, and applied inverse probability weights to account for loss-to-follow-up (intent-to-treat and per-protocol analyses) and adherence (per-protocol analyses only).
Results:
Using life-table methods, 64% of the 2,775 participants randomized to FF and 63% of the 2,767 participants not randomized to FF conceived during 12 cycles; these respective percentages were each 70% among those with 0-1 cycles of attempt time at enrollment. Of those randomized to FF, 72% were defined as adherent (68% of observed menstrual cycles). In intent-to-treat analyses, there was no appreciable association overall (FR=0.97, 95% CI: 0.90-1.04) or within strata of pregnancy attempt time at enrollment, age, education, or other characteristics. In per-protocol analyses, we observed little association overall (FR=1.06, 95% CI: 0.99-1.14), but weak-to-moderate positive associations among participants who had longer attempt times at enrollment (FR=1.15, 95% CI: 0.98-1.35 for 3-4 cycles; 1.14, 95% CI: 0.87-1.48 for 5-6 cycles), were aged <25 years (FR=1.29, 95% CI: 1.01-1.66), had ≤12 years of education (FR=1.32, 95% CI: 0.92-1.89), or were non-users of hormonal contraception within 3 months before enrollment (FR=1.10, 95% CI: 1.02-1.19).
Conclusion:
No appreciable associations were observed in intent-to-treat analyses. In secondary per-protocol analyses that accounted for adherence, randomization to FF was associated with slightly greater fecundability among selected subgroups of participants; however, these results are susceptible to unmeasured confounding.
In the space of one generation major changes have begun to take place in the field of human reproduction. A rapid increase in the control of fertility and the understanding and treatment of sexual health issues have been accompanied by an emerging threat to reproductive function linked to increasing environmental pollution and dramatic changes in lifestyle. Organised around four key themes, this book provides a valuable review of some of the most important recent findings in human reproductive ecology. Major topics include the impact of the environment on reproduction, the role of physical activity and energetics in regulating reproduction, sexual maturation and ovulation assessment and demographic, health and family planning issues. Both theoretical and practical issues are covered, including the evolution and importance of the menopause and the various statistical methods by which researchers can analyse characteristics of the menstrual cycle in field studies.
In the space of one generation major changes have begun to take place in the field of human reproduction. A rapid increase in the control of fertility and the understanding and treatment of sexual health issues have been accompanied by an emerging threat to reproductive function linked to increasing environmental pollution and dramatic changes in lifestyle. Organised around four key themes, this book provides a valuable review of some of the most important recent findings in human reproductive ecology. Major topics include the impact of the environment on reproduction, the role of physical activity and energetics in regulating reproduction, sexual maturation and ovulation assessment and demographic, health and family planning issues. Both theoretical and practical issues are covered, including the evolution and importance of the menopause and the various statistical methods by which researchers can analyse characteristics of the menstrual cycle in field studies.
In the space of one generation major changes have begun to take place in the field of human reproduction. A rapid increase in the control of fertility and the understanding and treatment of sexual health issues have been accompanied by an emerging threat to reproductive function linked to increasing environmental pollution and dramatic changes in lifestyle. Organised around four key themes, this book provides a valuable review of some of the most important recent findings in human reproductive ecology. Major topics include the impact of the environment on reproduction, the role of physical activity and energetics in regulating reproduction, sexual maturation and ovulation assessment and demographic, health and family planning issues. Both theoretical and practical issues are covered, including the evolution and importance of the menopause and the various statistical methods by which researchers can analyse characteristics of the menstrual cycle in field studies.
In the space of one generation major changes have begun to take place in the field of human reproduction. A rapid increase in the control of fertility and the understanding and treatment of sexual health issues have been accompanied by an emerging threat to reproductive function linked to increasing environmental pollution and dramatic changes in lifestyle. Organised around four key themes, this book provides a valuable review of some of the most important recent findings in human reproductive ecology. Major topics include the impact of the environment on reproduction, the role of physical activity and energetics in regulating reproduction, sexual maturation and ovulation assessment and demographic, health and family planning issues. Both theoretical and practical issues are covered, including the evolution and importance of the menopause and the various statistical methods by which researchers can analyse characteristics of the menstrual cycle in field studies.
In the space of one generation major changes have begun to take place in the field of human reproduction. A rapid increase in the control of fertility and the understanding and treatment of sexual health issues have been accompanied by an emerging threat to reproductive function linked to increasing environmental pollution and dramatic changes in lifestyle. Organised around four key themes, this book provides a valuable review of some of the most important recent findings in human reproductive ecology. Major topics include the impact of the environment on reproduction, the role of physical activity and energetics in regulating reproduction, sexual maturation and ovulation assessment and demographic, health and family planning issues. Both theoretical and practical issues are covered, including the evolution and importance of the menopause and the various statistical methods by which researchers can analyse characteristics of the menstrual cycle in field studies.
In the space of one generation major changes have begun to take place in the field of human reproduction. A rapid increase in the control of fertility and the understanding and treatment of sexual health issues have been accompanied by an emerging threat to reproductive function linked to increasing environmental pollution and dramatic changes in lifestyle. Organised around four key themes, this book provides a valuable review of some of the most important recent findings in human reproductive ecology. Major topics include the impact of the environment on reproduction, the role of physical activity and energetics in regulating reproduction, sexual maturation and ovulation assessment and demographic, health and family planning issues. Both theoretical and practical issues are covered, including the evolution and importance of the menopause and the various statistical methods by which researchers can analyse characteristics of the menstrual cycle in field studies.
In the space of one generation major changes have begun to take place in the field of human reproduction. A rapid increase in the control of fertility and the understanding and treatment of sexual health issues have been accompanied by an emerging threat to reproductive function linked to increasing environmental pollution and dramatic changes in lifestyle. Organised around four key themes, this book provides a valuable review of some of the most important recent findings in human reproductive ecology. Major topics include the impact of the environment on reproduction, the role of physical activity and energetics in regulating reproduction, sexual maturation and ovulation assessment and demographic, health and family planning issues. Both theoretical and practical issues are covered, including the evolution and importance of the menopause and the various statistical methods by which researchers can analyse characteristics of the menstrual cycle in field studies.
In the space of one generation major changes have begun to take place in the field of human reproduction. A rapid increase in the control of fertility and the understanding and treatment of sexual health issues have been accompanied by an emerging threat to reproductive function linked to increasing environmental pollution and dramatic changes in lifestyle. Organised around four key themes, this book provides a valuable review of some of the most important recent findings in human reproductive ecology. Major topics include the impact of the environment on reproduction, the role of physical activity and energetics in regulating reproduction, sexual maturation and ovulation assessment and demographic, health and family planning issues. Both theoretical and practical issues are covered, including the evolution and importance of the menopause and the various statistical methods by which researchers can analyse characteristics of the menstrual cycle in field studies.
In the space of one generation major changes have begun to take place in the field of human reproduction. A rapid increase in the control of fertility and the understanding and treatment of sexual health issues have been accompanied by an emerging threat to reproductive function linked to increasing environmental pollution and dramatic changes in lifestyle. Organised around four key themes, this book provides a valuable review of some of the most important recent findings in human reproductive ecology. Major topics include the impact of the environment on reproduction, the role of physical activity and energetics in regulating reproduction, sexual maturation and ovulation assessment and demographic, health and family planning issues. Both theoretical and practical issues are covered, including the evolution and importance of the menopause and the various statistical methods by which researchers can analyse characteristics of the menstrual cycle in field studies.
Knowledge of fertilization and implantation is essential for understanding both normal reproduction and the pathological basis of infertility. The purpose of this chapter is to discuss our current understanding of normal fertilization and implantation. A healthy spermatozoon is essential for reproduction and must undergo a variety of changes in order to fertilize an oocyte. Spermatogenesis occurs in the seminiferous tubules of the testes and is controlled by the effect of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) on testicular Sertoli and Leydig cells. Mature spermatozoa are then transported through the epididymis, combined with seminal vesicle and prostatic secretions, and ultimately transported into the vaginal vault with ejaculation. Through a calcium-mediated process called capacitation, the spermatozoon develops hypermotile flagella and an activated acrosome, eventually resulting in penetration of an oocyte. Normal oogenesis and folliculogenesis are crucial in order to produce a healthy oocyte for fertilization. Following menarche, release of FSH and LH stimulates development of antral follicles, completion of meiosis, and subsequent ovulation of a dominant follicle. An activated spermatozoon binds to the outer layer of the oocyte, the zona pellucida, and fertilization by a single spermatozoon ensues. With completion of a second meiotic division, and genomic union of the sperm and oocyte, a zygote forms. Approximately day 6 or 7 post-ovulation, the trophoectoderm of the blastocyst implants into the endometrial epithelium. Many factors are required for successful implantation. In addition to proper trophoblast development and invasion, endometrial receptivity has been shown to be crucial for normal implantation, and disruption of it is a major cause of abnormal placentation and infertility. Due to the complexity of fertilization and implantation, it is not surprising that two of the most common mechanisms of infertility are failure of fertilization and failure of implantation.KeywordsGranulosa cellZona pellucidaCumulus cellAcrosomal reactionPrimordial follicle
Background
A new fertility monitor is now available that provides quantitative measurement of urinary hormones, but clinical use requires validation against an established fertility monitor that provides only qualitative results.
Research design and methods
Two fertility monitors were compared using daily first morning urine samples over 3 cycles of use in 21 women users with experience using a fertility monitor with the Marquette Method of Natural Family Planning.
Results
Women were aged 33.4 ± 5.5 years and had menstrual cycles ranging between 23-41 days. The quantitative Mira Monitor estimates of ovulation were highly correlated with the qualitative ClearBlue Fertility Monitor (CBFM) estimates of ovulation. Both monitors provided an accurate estimate of the fertile window.
Conclusions
In this preliminary trial, the Mira monitor was shown to be effective at delineating the fertile window and ovulation. We demonstrated the feasibility of applying the Marquette Method algorithm with the use of the Mira monitor. Satisfaction differences between the two monitors did not reach statistical significance. We anticipate that quantitative fertility monitoring will give couples and health care providers new and unprecedented insights into the menstrual cycle and fertility.
Cycle apps indicate the fertile window by tracking menstrual cycle parameters. Thus, women use them for both avoiding and achieving pregnancy. The apps vary according to their underlying scientific quality and can be divided into three categories: (1) Forecast apps: these predict the fertile window based on data of previous cycles (e.g. cycle lengths, previous temperature rises). In view of the natural variability of the day of ovulation and the fertile window even in women with comparatively regular cycles, these apps are not sufficiently precise. (2) NFP apps: these apps work on the basis of evidence-based methods of natural family planning (NFP) (see guidelines of the “Section Natural Fertility” of the German Society of Gynecological Endocrinology and Reproductive Medicine, DGGEF). They determine the fertile window based on parameters of the current cycle. (3) Apps associated with measuring systems: these systems measure hormones in urine or saliva, as well as other new parameters such as end-tidal CO2 pressure, nocturnal pulse rate and peripheral body temperature. Most apps are still at the experimental stage.
Globally, millions of women track their menstrual cycle and fertility via smartphone-based health apps, generating multivariate time series with frequent missing data. To leverage data from self-tracking tools in epidemiological studies on fertility or the menstrual cycle's effects on diseases and symptoms, it is critical to have methods for identifying reproductive events, e.g. ovulation, pregnancy losses or births. We present two coupled hidden semi-Markov models that adapt to changes in tracking behavior, explicitly capture variable-- and state-- dependent missingness, allow for variables of different type, and quantify uncertainty. The accuracy on synthetic data reaches 98% with no missing data, 90% with realistic missingness, and 94% accuracy on our partially labeled real-world time series. Our method also accurately predicts cycle length by learning user characteristics. It is publicly available (HiddenSemiMarkov R package) and transferable to any health time series, including self-reported symptoms and occasional tests.
Objective
To explore use of fertility awareness–based methods (FABMs) and factors that influence their use.
Design
Secondary data analysis of the National Survey of Family Growth, 2015 to 2017.
Setting
Surveys were conducted in the homes of a national sample of women in the civilian, noninstitutionalized population of the United States.
Participants
A subset of women (N = 423) ages 19 to 49 years who sought advice about becoming pregnant.
Intervention/Measurements
Descriptive statistics and multivariate logistic regression were used to describe sample characteristics and to examine predictors for FABM use.
Results
The sample was primarily married (70%), non-Hispanic women age 35 years or older (M = 37.4 years, SD = 7.3). Most were college educated (n = 253, 74.4%), were employed (n = 317, 74.9%), and had health insurance (n = 392, 92.7%). Only 113 women (27%) used one of three FABMs. The most frequent FABM was calendar rhythm (n = 103, 24.6%). Few used temperature/cervical mucus (n = 33, 7.9%) or Standard Days/Cycle Beads (n = 25, 6%). Catholic religion and age were not significant factors in FABM use. There was no significant difference among women with and without college degrees in FABM use: χ²(1, N = 423) = .27, p = .60. The model containing all predictors was not statistically significant: χ²(6, N = 423) = 5.686, p < .459; this indicates that the model was unable to distinguish differences in predictors between respondents who had or had not used an FABM. The model explained 1.7% (Cox and Snell R²) and 2.5% (Nagelkerke R²) of the variance in FABM use.
Conclusion
The most effective FABM (temperature/cervical mucus) was used infrequently among women who sought advice to achieve pregnancy. Although the effects were insignificant in predicting which women used an FABM, descriptive findings on FABM use were clinically informative. Considering the cost, emotional strain, and potential complications of infertility treatment, clinicians should consider initially recommending a fertility awareness–based method to women seeking advice about achieving pregnancy.
A review of 23 research articles to examine fertility awareness-based methods revealed biologic indicators and tracking methods to identify the fertile window in reproductive-aged women. This literature review indicated that a woman's cycle regularity is a major determinant of which method is best. Additionally, the woman's desire to achieve a pregnancy and her preference regarding the intensity of training are factors in method choice. Some evidence suggests that use of at least two biologic indicators is most effective for determining the fertility window. Recommended web and mobile applications also are discussed.
Natural family planning (NFP) is a type of family planning that is based on fertility awareness and its application in achieving the couple's goal of either having or preventing pregnancy. Any of the natural methods either independently or combined is a great alternative to other forms of alternative contraception. The general objective of this scoping review was to identify research gaps and clarify key concepts in existing literature with regards to NFP and to examine the extent, range, and nature of research activity about NFP. The scop-ing review was underpinned by the five-stage framework Arksey and O'Malley and one hundred ninety nine articles were included in the study. The results indicate that use of natural family planning involves an interplay of factors that influence either the user or the provider. Common goals for use are achieving or preventing preventing pregnancy. No adverse pregnancy outcomes were found. There is an increasing and evolving trend of research activity across all natural family planning methods.
Cervical mucus is a glycoprotein gel whose biological functions depend upon its macromolecular architecture. Using freeze-substitution fixation techniques, we have used transmission electron microscopy to examine the fine structural aspects of mucus, before and after unidirectional physical shearing, and during its interaction with sperm. The microstructure of mucus that has not been directionally stretched consists of a homogenous pattern of interconnecting electron-dense elements. The thickness of the primary structural elements varies from 0.04 to 0.5 microns, giving the impression that the elements have fibrillar but also ribbon-like properties. This dimension is smaller than the sizes depicted by prior studies using scanning electron microscopy. Within the mucus interior, the interstitial distance between adjacent primary elements ranges from 0.5 to 0.8 microns, and is filled with a fibrous network of secondary structural elements. This interstitial dimension is also significantly smaller than that suggested by prior electron microscopic work. At the exterior borders of the mucus, the interstitial sizes are reduced. After physical stretching by forceps, the mucus microstructure undergoes a radical deformation. In some specimens, the primary structural elements become longitudinally aligned and are less interconnected, with compaction at the exterior mucus borders. In other specimens, the primary structural elements become laterally compressed along the longitudinal axis; within the regions of compression, the intrapore diameter is reduced to less than 0.1 microns. These compressed regions will often exclude spermatozoa. Individual sperm deform the local mucus microstructure. The mucus directly anterior to the sperm head is stretched, and the mucus adjacent to the bending flagellum is compressed on the forward side and stretched on the opposite side.
The symptoms of self-observation of the menstrual cycle (basal body temperature, mucus symptom, autopalpation of the cervix) are often regarded as not reliable for ovulation detection. In a prospective study 87 NFP cycles are monitored additionally with ultrasound and LH tests to calculate the correlation of the ovulation-time with the symptoms of self-observation. Our results show that the symptoms of self-observation allow a reliable detection of the time of ovulation. Only a short introduction into the method of self-observation is a necessary precondition. The reliable detection of ovulation gives the opportunity of cycle analysis of large groups especially in long time investigations. In this way a large set of valuable and reliable data on normal and disturbed menstrual cycles will be available.
To evaluate the use effectiveness of Creighton Model (CrM) NaProEducation Technology for avoiding pregnancy.
CrM is a medical model of natural procreation education that is a fully standardized modification of the Billings ovulation method. This system has been used as a means to avoid pregnancy and has been prospectively evaluated in five use effectiveness studies. A prospective life-table analysis of the five studies (meta-analysis) was undertaken, yielding both net and gross rates. Discontinuation rates were also calculated. These studies were conducted at CrM centers in Omaha, St. Louis, Wichita, Houston, and Milwaukee.
A total of 1,876 couples used CrM NET for a total of 17,130.0 couple months of use. The method and use effectiveness rates for avoiding pregnancy were 99.5 and 96.8 at the 12th ordinal month and 99.5 and 96.4 at the 18th ordinal month, respectively. The discontinuation rate was 11.3% at the 12th ordinal month and 12.1% at the 18th ordinal month.
CrM is highly effective as a means of avoiding pregnancy in both its method and use effectiveness. The method effectiveness has remained stable over the years of the studies, but the use effectiveness for avoiding pregnancy appears to have improved over the study period.
Women who monitor their fertility signs and recognize when they are fertile can use this knowledge to conceive or to avoid pregnancy. Studies have shown that there is a rather small fertile window of several days during each menstrual cycle. Established methods of identifying the fertile window, such as the Ovulation and the Symptothermal methods of Natural Family Planning, can be very effective in helping couples avoid pregnancy. A new algorithm for identifying the fertile window has been developed, based on monitoring and recording of cervical secretions. The TwoDay Algorithm appears to be simpler to teach, learn, and use than current natural methods. A large existing data set from a World Health Organization study of the Ovulation Method, along with Natural Family Planning charts from women using the Ovulation Method and the Symptothermal Method, were used to determine the potential effectiveness of the TwoDay Algorithm in identifying the fertile window. Results suggest that the algorithm can be an effective alternative for low literacy populations or for programs that find current Natural Family Planning methods too time consuming or otherwise not feasible to incorporate into their services. Further studies are needed to determine the efficacy of the TwoDay Algorithm in avoiding pregnancy and to assess its acceptability to users and providers.
Reproductive behaviour in modern western society has changed dramatically in the last two decades. Parenthood is now well planned. If planned pregnancies do not occur as expected, early infertility care is often demanded with the risk of over-treatment. Live birth rates in untreated subfertile couples reach nearly 55% in 36 months. During this period, self-monitoring with natural family planning (NFP) methods may be all that is necessary, especially in couples with unexplained infertility.
Abstract Data on 1898 menstrual cycles, for 241 married women, were analysed by means of a quantal regression programme. The locations of the day of ovulation was determined by the basal body temperature method. Estimates were obtained of the risk of conception from an act of coitus on each day, as measured from the day of ovulation. The relationship between fecundability and coital frequency was also examined.
To determine whether normal women could predict and identify symptomatically the occurrence of ovulation, twenty-two volunteers were instructed in a pattern of vaginal "mucus symptoms " which had been established previously. Plasma luteinising hormone and urinary oestrogens and pregnanediol were measured to provide a "hormonal estimate" of the day of ovulation. A characteristic "lubricative" mucus identified by all the women occurred on the day of ovulation in five, 1 day before in nine, and 2 days before in four. The onset of mucus symptoms occurred 6·2 days (mean) before ovulation. It is concluded that the time of ovulation can be identified clinically, without recourse to temperature measurement or more specialised tests.
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.
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.
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.
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.
The timing of sexual intercourse in relation to ovulation strongly influences the chance of conception, although the actual number of fertile days in a woman's menstrual cycle is uncertain. The timing of intercourse may also be associated with the sex of the baby.
We recruited 221 healthy women who were planning to become pregnant. At the same time the women stopped using birth-control methods, they began collecting daily urine specimens and keeping daily records of whether they had sexual intercourse. We measured estrogen and progesterone metabolites in urine to estimate the day of ovulation.
In a total of 625 menstrual cycles for which the dates of ovulation could be estimated, 192 pregnancies were initiated, as indicated by increases in the urinary concentration of human chorionic gonadotropin around the expected time of implantation. Two thirds (n = 129) ended in live births. Conception occurred only when intercourse took place during a six-day period that ended on the estimated day of ovulation. The probability of conception ranged from 0.10 when intercourse occurred five days before ovulation to 0.33 when it occurred on the day of ovulation itself. There was no evident relation between the age of sperm and the viability of the conceptus, although only 6 percent of the pregnancies could be firmly attributed to sperm that were three or more days old. Cycles producing male and female babies had similar patterns of intercourse in relation to ovulation.
Among healthy women trying to conceive, nearly all pregnancies can be attributed to intercourse during a six-day period ending on the day of ovulation. For practical purposes, the timing of sexual intercourse in relation to ovulation has no influence on the sex of the baby.
Changes in cervical mucus occur during the proliferative phase of the menstrual cycle and are known to correlate with receptivity to sperm and to the endocrine milieu. Prior studies, however, have often lacked biological incisiveness and technical objectivity and precision. This study analyzed daily changes in mucus water content (hydration) prior to the LH surge (LH+0) in normal women, in relation to daily levels of serum LH, FSH, estradiol and progesterone, and to daily tests of sperm penetration of the mucus. Cervical mucus was studied for 12 cycles in 10 ovulating women. Three to ten mucus specimens were collected per cycle, over the days LH-8 to LH+0. Each specimen was subjected to measurement of both water content (hydration) and penetration by spermatozoa from fresh specimens of normal human semen. For the latter, a new microscale assay was developed and applied, which was amenable to very small volumes of mucus. The new technique determines objective measures of both the numbers of penetrating sperm (motile and non-motile) and the distance penetrated by the forwardmost vanguard sperm. In these experiments, variations in semen quality were controlled by performing a companion penetration assay in an artificial 1.5% polyacrylamide gel.
The patterns of change in mucus hydration varied quantitatively among women, with preovulatory baseline levels ranging from 93.8-96.5%. All normal cycles (as defined by endocrine profiles) displayed a significant increase in hydration over a one-day period occurring 3-4 days before the LH peak. The magnitude of this shift varied among women between 2 and 3% (absolute hydration), a distinction well within the precision of the hydration assay. This quantum increase in hydration was more pronounced than the corresponding increase in serum estradiol on the same day. The change in mucus hydration, and the associated increase in sperm penetrability, were more consistent among cycles than the changes in reproductive hormones.
There was a strong but non-linear correlation between mucus hydration and sperm penetrability. Once the value of hydration rose above approximately 97.5%, there was a substantial increase in penetrability. This 'cut-off point' in sperm penetrability was in the middle of the range of hydration values (across women) which preceded the quantum jump in hydration - which, itself, preceded the surge of L.H. Hydration began to increase approximately 2 days before measurable increases in sperm penetration of the mucus in vitro.
These results demonstrate that mucus hydration may be a valuable marker of the approach to ovulation and delineation of the fertile period. They also provide new methods for assessing sperm penetration into both large periovulatory and very small samples of collected mucus.
Rapid as well as sustained sperm transport from the cervical canal to the isthmical part of the fallopian tube is provided by cervico-fundal uterine peristaltic contractions that can be visualized by vaginal sonography. The peristaltic contractions increase in frequency and presumably also in intensity as the proliferative phase progresses. As shown by placement of labeled albumin macrospheres of sperm size at the external cervical os and serial hysterosalpingoscintigraphy (HSSG) sperm reach, following their vaginal deposition, the uterine cavity within minutes. In the early follicular phase a large proportion of the macrospheres remains at the site of application, while a smaller proportion enters the uterine cavity with even a smaller one reaching the isthmical part of the tubes. In the mid-follicular phase of the cycle with increased frequency and intensity of the uterine contractions the proportion of macrospheres entering the uterine cavity as well as the tubes has significantly increased. In the late follicular phase with maximum frequency and intensity of uterine peristalsis the proportion of macrospheres entering the tube increases further at the expense of those at the site of application as well as within the uterine cavity. The transport of the macrospheres into the tube is preferentially directed into the tube ipsilateral to the dominant follicle, which becomes apparent in the mid-follicular phase as soon as a dominant follicle can be identified by ultrasound. Since the macrosphere are inert particles the directed sperm transport into the tube ipsilateral to the dominant follicle is not functionally related to a mechanism such as chemotaxis but is rather provided by uterine contraction of which the direction may be controlled by a specific myometrial architecture in combination with an asymmetric distribution of myometrial oestradiol receptors.
To test the hypothesis that human cervical mucins affect the motility and hyperactivated motility of human spermatozoa.
University hospital.
Healthy donors.
Swim-up sperm fractions of normozoospermic semen samples were incubated in the presence of 0 (control) to 1.3 mg/mL of mucins purified from cervical mucus plugs released during labor. Motility analyses were performed at time 0, and after 0.5, 1, 3, and 7 hours.
Sperm kinematic variables recorded by computer-aided sperm analysis. Hyperactivation was defined as linearity <30%, amplitude of lateral head displacement >7.0 microm, and curvilinear velocity >70 microm/s.
A dose-related effect of cervical mucins on sperm motility was found. Mucins at a concentration of 1.3 mg/mL caused an immediate and significant increase in sperm linearity (27%) and straight-line velocity (16%) compared with control samples. During the first 3 hours of incubation, an approximately 25% increase in linearity and straight-line velocity was found; this increase was statistically significant. Effects on the hyperactivation pattern were found as incubation with mucins for 3 and 7 hours significantly reduced the percentage of hyperactivation from 18% to 9%.
Cervical mucins increase the percentage of progressively motile sperm and decrease the percentage of sperm that show hyperactivation.
Two studies have related the timing of sexual intercourse (relative to ovulation) to day-specific fecundability. The first
was a study of Catholic couples practising natural family planning in London in the 1950s and 1960s and the second was of
North Carolina couples attempting to become pregnant in the early 1980s. The former identified ovulation based on the ovulatory
shift in the basal body temperature, while the latter used urinary assays of hormones. We use a statistical model to correct
for error in identifying ovulation and to re-estimate the length of the fertile window and day-specific fecundabilities. We
estimate the same 6-day fertile interval in both studies after controlling for error. After adjusting for error both data
sets showed the highest estimate of the probability of pregnancy on the day prior to ovulation and both fell close to zero
after ovulation. Given that the fertile interval is before ovulation, methods that anticipate ovulation by several days (such
as the assessment of cervical mucus) would be particularly useful for couples who want to time their intercourse either to
avoid or facilitate conception.
In the past decade, there have been enormous advances in the use of Bayesian methodology for analysis of epidemiologic data, and there are now many practical advantages to the Bayesian approach. Bayesian models can easily accommodate unobserved variables such as an individual's true disease status in the presence of diagnostic error. The use of prior probability distributions represents a powerful mechanism for incorporating information from previous studies and for controlling confounding. Posterior probabilities can be used as easily interpretable alternatives to p values. Recent developments in Markov chain Monte Carlo methodology facilitate the implementation of Bayesian analyses of complex data sets containing missing observations and multidimensional outcomes. Tools are now available that allow epidemiologists to take advantage of this powerful approach to assessment of exposure-disease relations.
To improve prediction of ovulation in normal cycles.
Collection of women's characteristics and their menstrual cycles. Monitoring and analysis of time relationships between several indicators of ovulation: transvaginal ultrasonography, cervical mucus, basal body temperature, urinary luteinising hormone, and ratio of urinary oestrogen to progesterone metabolites.
Each of eight natural family planning clinics was to study 12 women for at least three cycles.
One hundred and seven normally fertile and cycling women aged 18 to 45.
Daily measurements of urinary luteinising hormone, follicle stimulating hormone, oestrone-3-glucuronide and pregnanediol-3alpha-glucuronide. Basal body temperature recording and cervical mucus checking. Transvaginal ultrasound examination of the ovaries.
Delays between the expected day of ovulation according to the luteinising hormone peak or to ultrasound evidence and the expected days according to the other indices of ovulation.
Ultrasonography was able to show evidence of ovulation in 283 out of 326 cycles. The average time lag between luteinising hormone peak and ultrasound evidence was less than one day (+0.46) but premature and late luteinising hormone-expected date of ovulation were observed in nearly 10% and 23% of cycles, respectively. Basal body temperature rise was observed in 98% of cycles. Cervical mucus peak symptom, rapid drop in the ratio of urinary metabolites, and luteinising hormone initial rise were all close to ultrasonographic evidence in more than 72% of cycles.
For accuracy and practical reasons, the cervical mucus peak symptom, the ratio of urinary metabolites and luteinising hormone initial rise might be better indices of ovulation than the luteinising hormone peak.
The TwoDay Algorithm is a simple method for identifying the fertile window. It classifies a day as fertile if cervical secretions are present on that day or were present on the day before. This approach may be an effective alternative to the ovulation and symptothermal methods for populations and programmes that find current natural family planning methods difficult to implement.
We used data on secretions from a large multinational European fecundability study to assess the relationship between the days predicted to be potentially fertile by the TwoDay Algorithm and the day-specific probabilities of pregnancy based on intercourse patterns in 434 conception cycles from the study.
The days around ovulation that had the highest fecundability were the days most likely to be classified as fertile by the TwoDay Algorithm. In addition, intercourse on a particular day in the fertile interval was twice as likely to result in a pregnancy if cervical secretions were present on that day or the day before.
The TwoDay Algorithm is effective, both in identifying the fertile days of the cycle and in predicting days within the fertile interval that have a high pregnancy rate. Our data provide the first direct evidence that cervical secretions are associated with higher fecundability within the fertile window.
Most analyses of age-related changes in fertility cannot separate effects due to reduced frequency of sexual intercourse from effects directly 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.
A total of 782 healthy couples using natural family planning methods contributed prospective data on 5860 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, with probabilities of pregnancy twice as high for women aged 19-26 years compared with women aged 35-39 years. 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.
This multicenter study has produced a database of 7017 menstrual cycles contributed by 881 women. It provides improved knowledge on length and location of the "fertile window" (identified as of up to 12 days duration) and the patterns and level of daily conception probability. The day of ovulation was identified in each cycle from records of basal body temperature and mucus symptoms. By referencing days of intercourse to the surrogate ovulation markers, estimates of daily fecundability were computed either directly or by the Scwartz model, both for single and multiple acts of intercourse in the fertile window. The relationship between coital pattern and fecundability has been explored. Univariate analysis underlines the significant link with fecundability only of the woman's reproductive history.
To assess the day-specific and cycle-specific probabilities of conception leading to clinical pregnancy, in relation to the timing of intercourse and vulvar mucus observations.
This was a retrospective cohort study of women beginning use of the Creighton Model Fertility Care System in Missouri, Nebraska, Kansas, and California. Data were abstracted from Creighton Model Fertility Care System records, including women's daily standardized vulvar observations of cervical mucus discharge, days of intercourse, and clinically evident pregnancy (conception). Established statistical models were used to estimate day-specific probabilities of conception.
Data were analyzed from 1681 cycles with 81 conceptions from 309 normally fertile couples (initially seeking to avoid pregnancy) and from 373 cycles with 30 conceptions from 117 subfertile couples (who were initially trying to achieve pregnancy). The highest probability of pregnancy occurred on the peak day of vulvar mucus observation (.38 for normally fertile couples and.14 for subfertile couples). The probability of pregnancy was greater than.05 for normally fertile couples from 3 days before to 2 days after the peak, and for subfertile couples from 1 day before to 1 day after the peak. The cycle-specific probability of conception correlated with the quality of mucus discharge in normally fertile couples but not in subfertile couples.
Standardized vulvar observations of vaginal mucus discharge identify the days with the greatest likelihood of conception from intercourse in normal fertility and subfertility and provide an indicator of the overall potential for conception in a given menstrual cycle in normal fertility.
This study was conducted on human cervical mucus using light microscopy (LM) and scanning electron microscopy (SEM). The objective was the morphological characterization of the different mucus types, with samples taken from the lumen of the cervix and from the different secretory zones of the cervical mucosa.
A total of 230 samples from 195 women were spread out on slides and air dried. The phenomenon of 'ferning' was observed and assessed in these samples using both LM and SEM. Further samples from the lumen of the cervix and the different secretory crypts were spread out on cover slips and fixed with glutaraldehyde (2.5%) to be studied by SEM.
The results show the presence of four different morphological mucus types, namely L, S, P and G, in both types of sample using dried and fixed techniques.
Mucus from the lumen of the cervix appears to be a morphologically heterogeneous entity. It contains different types of secretions, the proportions of which vary throughout the menstrual cycle. The different mucosal types show different types of crystallization, different patterns of ultrastructure (probably related to the arrangement of the glycoprotein network) and are produced in different secretory zones of the crypts in the cervix.
Bayesian Order Restricted Inference for Count and Binary Data. Discussion Paper Series: Institute of Statistics and Decision Sciences
- Dunson
- Db
- Stanford
Dunson DB and Stanford JB (2003) Bayesian Order Restricted Inference for Count and Binary Data. Discussion Paper Series: Institute of Statistics and Decision Sciences, Duke University, Durham, NC.
Symptoms and hormonal changes accompanying ovulation Billings Atlas of the Ovulation Method. Ovulation Method Research and Reference Centre of Australia Daily fecundability: ®rst results from a new data base The modi®ed mucus method in India
- Billings Jj Brown
- Burger
Billings EL, Billings JJ, Brown JB and Burger HG (1972) Symptoms and hormonal changes accompanying ovulation. Lancet 1,282±284. Billings EL, Billings JJ and Catarinich M (1989) Billings Atlas of the Ovulation Method. Ovulation Method Research and Reference Centre of Australia, Melbourne, Australia. Colombo B and Masarotto G (2000) Daily fecundability: ®rst results from a new data base. Demogr Res 3,5. Dorairaj K (1991) The modi®ed mucus method in India. Am J Obstet Gynecol 165,2066±2067.
Billings Atlas of the Ovulation Method. Ovulation Method Research and Reference Centre of Australia
- El Billings
- Jj Billings
- M Catarinich
Billings EL, Billings JJ and Catarinich M (1989) Billings Atlas of the
Ovulation Method. Ovulation Method Research and Reference Centre of
Australia, Melbourne, Australia.
A prospective multicentre trial of the ovulation method of natural family planning. III. Characteristics of the menstrual cycle and of the fertile phase
World Health Organization (1983) A prospective multicentre trial of the
ovulation method of natural family planning. III. Characteristics of the
menstrual cycle and of the fertile phase. Fertil Steril 40,773±778.