Comparison of woman‐picked, expert‐picked, and computer‐picked Peak Day of cervical mucus with blinded urine luteinising hormone surge for concurrent identification of ovulation

Stanford, Joseph B.; Schliep, Karen C.; Chang, Chun‐Pin; O’Sullivan, J.A.M; Porucznik, Christina A.

doi:10.1111/ppe.12642

Cited by 11 publications

(7 citation statements)

References 38 publications

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“…Although the cervical mucus peak day is a reliable marker of ovulation, it is not as precise as serial follicular ultrasound, or some hormonal measures, which introduces imprecision in the outcome measures ( Ecochard et al , 2001 ; Stanford et al , 2020 ). 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 generalizability of our findings.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of menstrual cycles with or without intercourse in women with no known subfertility

Najmabadi

Schliep

Simonsen

et al. 2022

Human Reproduction Open

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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 two days of cervical fluid with estrogen-stimulated qualities. WHAT IS KNOWN ALREADY Human females are spontaneous ovulators, experiencing a luteinizing hormone 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-days 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 centres 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 2,564 cycles of 530 women, followed for up to one 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 one year, yielding 2,564 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 one day of sexual intercourse were shorter (29.1 days (95% confidence interval 27.6, 30.7) versus 30.1 days (95% confidence interval 28.7, 31.4)), had shorter luteal phases (10.8 days (95% confidence interval 10.2, 11.5) versus 11.4 days (95% confidence interval 10.9, 12.0)), had a higher probability of luteal phase deficiency (<10 days) (adjusted probability ratio 1.31 (95% confidence interval 1.00, 1.71)), had a higher probability of two days of premenstrual spotting (adjusted probability ratio 2.15 (95% confidence interval 1.09, 4.24)), and a higher probability of having two or fewer days of peak-type (estrogenic) cervical fluid (adjusted probability ratio 1.49 (95% confidence interval 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 gynaecologic 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 towards 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 (Creighton Model MultiCenter Fecundability Study), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Time to Pregnancy in Normal Fertility), and the Office of Family Planning, Office of Population Affairs, Health and Human Services (Creighton Model Effectiveness, Intentions, and Behaviors Assessment). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER N/A

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Section: Discussionmentioning

confidence: 99%

Characteristics of menstrual cycles with or without intercourse in women with no known subfertility

Najmabadi

Schliep

Simonsen

et al. 2022

Human Reproduction Open

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“…Third, we did not train participants on how to identify different vaginal sensations and discharge. It is possible that this training may further increase the accuracy of MPIQ in identifying FP, OW, and LP (Stanford et al, 2020). Fourth, while we excluded participants in the parent studies for the use of hormonal contraceptives within the last 3 months, it is possible that hormonal contraceptive use more than 3 months ago may have influenced our results (Nassaralla et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Menstrual Phase Identification Questionnaire (MPIQ): Development and validation of a cross-sectional survey to identify follicular and luteal phases.

Allen

Valenti

Linde-Krieger

et al. 2024

Experimental and Clinical Psychopharmacology

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Evidence continues to accumulate on the influence of the menstrual phase on several biobehavioral outcomes (e.g., substance misuse). Expansion of this knowledge is limited due to the burdensomeness of accurate menstrual phase assessment. Thus, we sought to create and validate a questionnaire that can be used as a stand-alone item within low-resource settings and numerous study designs (e.g., cross-sectional) to accurately identify both the follicular phase (FP) and the luteal phase (LP). Participants completed the selfadministered four-item Menstrual Phase Identification Questionnaire (MPIQ) in two recently completed clinical trials. We assessed the accuracy of two MPIQ scoring criteria (less restrictive and more restrictive), as compared to self-report of onset of menses alone, with progesterone confirmation via dried blood spots. Participants (n = 59) were, on average, 33.7 (standard deviation [SD]: ±4.3) years old and provided a total of 83 responses. Assessing FP and LP using the self-reported onset of menses alone classified 65.1% of the responses with an overall phase identification accuracy of 60.2%. While the more restrictive MPIQ scoring classified 100% of the responses, it yielded a similar accuracy (68.4%). In contrast, the less restrictive MPIQ scoring classified 100% of the responses and also significantly improved phase identification accuracy to 92.1% ( p < .001). The MPIQ, as a stand-alone item, allows all cross-sectional responses to be classified with a high level of accuracy. This low-burden questionnaire can be used alone to identify FP and LP in studies that may be otherwise limited by study design, finances, and/or participant burden. Public Health SignificanceSelf-report of vaginal sensations and discharge plus the onset of menses improves the identification of follicular and luteal menstrual phases as compared to the self-reported onset of menses alone (60.2% accuracy vs. 92.1% accuracy; p < .001). The use of the Menstrual Phase Identification Questionnaire (MPIQ) alone will allow more biobehavioral research to identify follicular and luteal menstrual phases, especially research that may be limited by study design (e.g., cross-sectional), finances (e.g., unable to include hormonal biomarkers), and/or participant burden.

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“…Prior research has established a high correlation of the peak day of cervical mucus in relation to the urinary surge of luteinizing hormone (Fehring, 2002), as well as ultrasound or other hormonal markers (Hilgers et al, 1978;Ecochard et al, 2001;Fehring, 2002;Porucznik et al, 2014;Ecochard et al, 2015;Stanford, 2015). We have also validated the expert-picked CrM mucus peak day in relation to urinary LH surge within one of the source cohorts for this study (TTP) (Stanford et al, 2020). In our study, all peak days were reviewed by at least two experts in the interpretation of CrM mucus records, including reference to information on the resulting luteal phase length and the consistency with other cycles from the same woman.…”

Section: Estimated Day Of Ovulation (Mucus Peak Day)mentioning

confidence: 92%

Cervical mucus patterns and the fertile window in women without known subfertility: a pooled analysis of three cohorts

et al. 2021

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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

show abstract

Comparison of woman‐picked, expert‐picked, and computer‐picked Peak Day of cervical mucus with blinded urine luteinising hormone surge for concurrent identification of ovulation

Cited by 11 publications

References 38 publications

Characteristics of menstrual cycles with or without intercourse in women with no known subfertility

Characteristics of menstrual cycles with or without intercourse in women with no known subfertility

Menstrual Phase Identification Questionnaire (MPIQ): Development and validation of a cross-sectional survey to identify follicular and luteal phases.

Cervical mucus patterns and the fertile window in women without known subfertility: a pooled analysis of three cohorts

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