Bouchard TP et al., 2026·Journal of ovarian research·
Open Access
Reproductive hormones of the fertile window are often referenced to women in regular cycles, but this may not be representative of the hormonal profiles of women in different circumstances like polycystic ovarian syndrome, the postpartum period, and the perimenopause transition. This observational cohort study sought to identify the variability in the reproductive hormones in various clinical circumstances and to establish potential thresholds for each category based on hormone measurements with the Mira urinary hormone monitor. A total of 57 women (ages 22-51) in various circumstances (regular cycles, polycystic ovarian syndrome, postpartum and perimenopause) tracked Mira urine hormone measurements (estrone-3-glucuronide, luteinizing hormone, pregnanediol glucuronide), contributing 444 cycles of data. Using additive mixed models, hormone values were stratified by the four different reproductive categories. The perimenopause and polycystic ovarian syndrome groups demonstrated relative hypoestrogenic states, while the perimenopause group showed low luteal pregnanediol glucuronide and the polycystic ovarian syndrome/polyendocrine metabolic ovarian syndrome (PCOS/PMOS) group showed high luteal pregnanediol glucuronide. The perimenopause group had significantly higher luteinizing hormone values throughout the whole cycle. The fertile window hormone thresholds vary depending on a woman's specific reproductive category. Women in different circumstances should not necessarily use the same hormonal thresholds for the fertile window and ovulation. A larger dataset with ultrasound correlation to ovulation is required to delineate the fertile window with more precision. Hormone differences across the menstrual cycle could be used for targeted treatments in polycystic ovarian syndrome and perimenopause women.
Bouchard TP et al., 2026·Reproductive biomedicine online
Does formation of the corpus luteum help to identify the day of ovulation on ultrasound when follicular collapse is missed, and how reliable are sonographers versus a review panel in identifying the day of ovulation on ultrasound? Sonographers in a clinic in Canada performed serial endovaginal ultrasound scans (six to eight per cycle) to identify the day of ovulation in regularly cycling women (n = 40) who were followed for one to five cycles (n = 85). The day of ovulation was identified by: (i) identification of the dominant follicle; (ii) disappearance of the dominant follicle; and (iii) identification and dating of the corpus luteum. The main outcome measures were inter-rater reliability between two sonographers, and Bland-Altman agreement between the supervising sonographer and a panel that reviewed each scan to identify the day of ovulation. Of the 85 menstrual cycles reviewed, two cycles did not have sufficient data to date ovulation, one cycle showed an incidental dermoid cyst, and 11 cycles showed anovulatory patterns. This left a total of 71 cycles (84%) for which intra-rater reliability between two sonographers for identifying the day of ovulation was high (intraclass correlation coefficient = 0.99, P < 0.0001), and Bland-Altman agreement showed no significant difference in the estimated day of ovulation between the supervising sonographer and the panel (t = -0.28, P = 0.78). Corpus luteum criteria were necessary to help identify the day of ovulation in 14 of 71 cycles (20%). The estimated day of ovulation can be determined reliably on ultrasound by trained sonographers using collapse of the dominant follicle and formation of the corpus luteum based on six to eight scans per cycle.
Bouchard TP et al., 2025·Preprints.org·
Open Access
Background/Objectives: Quantitative urine monitors are increasingly being used for a personalized approach to improve menstrual cycle knowledge and to manage fertility. Although several studies have evaluated urine fertility monitors in regular cycles, there is limited research in the use of quantitative monitors in reproductive disorders, such as polycystic ovarian syndrome (PCOS). Urine hormone data was collected with the Mira monitor from 20 participants, 10 of whom had PCOS and a matched group who had regular cycles. The main aim of this study was to evaluate the levels of luteinizing hormone (LH), estrone-3-glucuronide (E13G), and pregnanediol glucuronide (PDG) in PCOS menstrual cycles compared to regular cycles. Women with PCOS had higher BMI than regular cycling women (p=0.02). PCOS cycles were longer (p<0.05), peak day was later in the menstrual cycle (p<0.001), and luteal length was shorter (p < 0.01) compared to regular cycles. In whole cycle comparisons, E13G was found to be lower in PCOS cycles (p<0.01) and PDG was found to be higher in PCOS cycles (p<0.05). E13G was also lower in the follicular phase of and late luteal phase of PCOS cycles (p<0.00001). The results of this study demonstrate the feasibility of detecting hormonal differences in PCOS compared to regular cycles with at-home measurements with the Mira monitor. The metabolic dysregulation of PCOS is a possible factor in these hormone changes. Larger studies with different sub-types of PCOS will be needed to further clarify these changes and to understand the pathophysiology behind these hormonal changes.
Cycle Across the Lifespan · Cycle and General Health
Background Reproductive hormones of the fertile window are often referenced to women in regular cycles, but this may not be representative of the hormonal profiles of women in different circumstances like polycystic ovarian syndrome, the postpartum period, and the perimenopause transition. This observational cohort study sought to identify the variability in the hormones of the fertile window in various reproductive categories and to establish potential thresholds for each category based on hormone measurements with the Mira urinary hormone monitor. Results A total of 57 women (ages 22–51) in various circumstances (regular cycles, polycystic ovarian syndrome, postpartum and perimenopause) tracked Mira urine hormone measurements (estrone-3-glucuronide, luteinizing hormone, pregnanediol glucuronide), contributing 444 cycles of data. Using additive mixed models, hormone values were stratified by the four different reproductive categories. The perimenopause and polycystic ovararian syndrome groups demonstrated relative hypoestrogenic states, while the perimenopause group showed low luteal pregnanediol glucuronide and the polycystic ovarian syndrome group showed high luteal pregnanediol glucuronide. The perimenopause group had higher luteinizing hormone values throughout the whole cycle. Conclusion The fertile window hormone thresholds vary depending on a woman’s specific reproductive category. Women in different circumstances should not necessarily use the same hormonal thresholds for the fertile window and ovulation. A larger dataset with ultrasound correlation to ovulation is required to delineate the fertile window with more precision. Hormone differences across the menstrual cycle could be used for targeted treatments in polycystic ovarian syndrome and perimenopause women.
Bouchard T et al., 2025·J Restorative Reprod Med·
Open Access
There is considerable individual day-to-day variation within the menstrual cycle and between cycles in women. Average hormone curves inadequately describe the individual hormone patterns experienced by women. The present study applies a novel application of a statistical array (heat map) to demonstrate both individual and group menstrual cycle hormone variability.
Using pre-existing datasets, two cohorts of women were analysed using a statistical method to visualise quantitative hormonal variation. In one cohort, 107 women contributed a total of 283 menstrual cycles and in the second cohort, 21 women contributed a total of 62 menstrual cycles. Exposure: Women collected first morning urine samples for analysis of estrone-3-glucuronide (E1G) and luteinizing hormone (LH) in both datasets. In the larger dataset, pregnanediol-3-alpha-glucuronide (PDG) and follicle-stimulating hormone (FSH) were also collected. Serial ultrasounds identified the precise day of ovulation in the larger dataset. In the smaller dataset, peak LH was used to identify the estimated day of ovulation.
The main outcome measure was identifying hormonal variability using hormone array heat maps. Heat maps were able to quickly show clustering of hormone patterns in the fertile window and on the day of ovulation. Individual differences were identified in rows on the heat map relative to the day of ovulation. This new tool to visually represent hormonal changes with heat maps identifies both individual and group variability of menstrual cycle hormones.
Measurement and Statistics · Instrument Development and Validation
Bouchard TP et al., 2025·Womens Health Rep (New Rochelle)·
Open Access
Measuring quantitative menstrual cycle hormones at home may help women better understand their postpartum and perimenopause fertility transitions, but these quantitative fertility monitors require validation. This study included 16 North American women, aged 28-51, during either the postpartum (n = 8, cycles = 18) or perimenopause (n = 8, cycles = 35) fertility transitions testing daily first-morning urine testing with both the Mira Monitor and ClearBlue Fertility Monitor (CBFM) along with menstrual cycle parameter tracking. The main outcome measures were a rise in estrone-3-glucuronide (E13G) and luteinizing hormone (LH) urine hormone values from the Mira monitor correlated to low, high, or peak values on the CBFM. Both in the postpartum and perimenopause transitions, the identification of the day of ovulation based on the LH surge on the Mira and CBFM monitors was highly correlated (R = 0.94 and 0.83, p < 0.001). The E13G levels on the Mira monitor were significantly higher for a CBFM reading of "High" compared with "Low" for both the postpartum and perimenopausal cycles (all p < 0.001). Similarly, the LH levels on the Mira monitor were significantly higher for a CBFM reading of "Peak" (LH surge) compared with "High" for both the postpartum and perimenopausal cycles (all p < 0.001). The LH surge and levels of E13G in urine identified on the quantitative Mira fertility monitor strongly correlate to the LH surge and the shift from low to high on the CBFM during the postpartum and perimenopause transitions.
Ecochard R et al., 2024·Human reproduction (Oxford, England)
What is the effect of oestrogen and progesterone at the beginning of the menstrual cycle in delaying entry into the fertile window? Both oestrogen and progesterone contribute to a delay in the onset of the fertile window. Oestrogen enhances cervical mucus secretion while progesterone inhibits it. STUDY DESIGN, SIZE, Observational study. Daily observation of 220 menstrual cycles contributed by 88 women with no known menstrual cycle disorder. PARTICIPANTS/MATERIALS, SETTING, 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 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, 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. 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. N/A.
Ecochard R et al., 2024·Fertil Steril·
Open Access
To study whether the menstrual cycle has a circaseptan (7 days) rhythm and whether it is associated with the lunar cycle (also defined as the synodic month, it is the cycle of the phases of the Moon as seen from Earth, averaging 29.5 days in length).
Cross-sectional study. A total of 35,940 European and North American women aged 18-40 years. Exposure: Data were collected in real-life conditions. No intervention was performed. The onset of menstruation was assessed in prospectively measured menstrual cycles (311,064 cycles) over 3 full years (2019-2021). Associations were calculated between the onset of menstruation and the day of the week, and between the onset of menstruation and the lunar phase. In this large data set, a circaseptan (7-day) rhythmicity of menstruation was observed, with a peak (acrophase) of menstrual onset on Thursdays and Fridays. This circaseptan rhythm was observed in every age group, in every phase of the lunar cycle, and in all seasons. This feature was most pronounced for cycle durations between 27 and 29 days. In winter, the circaseptan rhythm was found in cycles of 27-29 days, but not in other cycle lengths. A circalunar rhythm was also statistically significant, but not as clearly defined as the circaseptan rhythm. The peak (acrophase) of the circalunar rhythm of menstrual onset varied according to the season. In addition, there was a small but statistically significant interaction between the circaseptan rhythm and the lunar cycle. Although relatively small in amplitude, the weekly rhythm of menstruation was statistically significant. Menstruation occurs more often on Thursdays and Fridays than on other days of the week. This is particularly true for women whose cycles last between 27 and 29 days. Circalunar rhythmicity was also statistically significant. However, it is less pronounced than the weekly rhythm.
Abdullah S et al., 2023·Hormone molecular biology and clinical investigation
During normal menstrual cycles, serum levels of progesterone vary widely between cycles of same woman and between women. This study investigated the profiles of pregnanediol during the luteal phase. Data stemmed from a previous multicenter prospective observational study and concerned 107 women (who contributed 326 menstrual cycles). The study analyzed changes in observed cervical mucus discharge, various hormones in first morning urine, and serum progesterone. Transvaginal ultrasonography and cervical mucus helped identifying the day of ovulation. Changes in pregnanediol glucuronide levels during the luteal phase were examined and classified according to the length of that phase, a location parameter, and a scale parameter. Associations between nine pregnanediol glucuronide profiles and other hormone profiles were examined. Low periovulatory pregnanediol glucuronide levels and low periovulatory luteinizing hormone levels were associated with delayed increases in pregnanediol glucuronide after ovulation. That 'delayed increase profile' was more frequently associated with cycles with prolonged high LH levels than in cycles with rapid pregnanediol glucuronide increases. A 'plateau-like profile' during the luteal phase was associated with longer cycles, cycles with higher estrone-3-glucuronide and pregnanediol glucuronide during the preovulatory phase, and cycles with higher periovulatory pregnanediol glucuronide levels. Distinct profiles of urinary progesterone levels are displayed during the luteal phase. These profiles relate to early hormone changes during the menstrual cycle. In everyday clinical practice, these findings provide further evidence for recommending progesterone test seven days after the mucus peak day. The search for other correlations and associations is underway.
The uses of cervical mucus and basal body temperature as indicators of return to fertility postpartum have resulted in high unintended pregnancy rates. In 2013, a study found that when women used urine hormone signs in a postpartum/breastfeeding protocol this resulted in fewer pregnancies. To improve the original protocol's effectiveness, three revisions were made: (1) women were to increase the number of days tested with the Clearblue Fertility Monitor, (2) an optional second luteinizing hormone test could be done in the evening, and (3) instructions were given to manage the beginning of the fertile window for the first six cycles postpartum. The purpose of this study was to determine the correct and typical use effectiveness rates to avoid pregnancy in women who used a revised postpartum/breastfeeding protocol. A cohort review of an established data set from 207 postpartum breastfeeding women who used the protocol to avoid pregnancy was completed using Kaplan-Meier survival analysis. Total pregnancy rates that included correct and incorrect use pregnancies were eighteen per one hundred women over twelve cycles of use. For the pregnancies that met a priori criteria, the correct use pregnancy rates were two per one hundred over twelve months and twelve cycles of use and typical use rates were four per one hundred women at twelve cycles of use. The protocol had fewer unplanned pregnancies than the original, however, the cost of the method increased.
Bouchard TP et al., 2022·J Womens Health (Larchmt)·
Some studies have suggested minor changes in the menstrual cycle after COVID-19 vaccination, but more detailed analyses of the menstrual cycle are needed to evaluate more specific changes in the menstrual cycle that are not affected by survey-based recall bias. Using a pretest-post-test quasi-experimental evaluation of menstrual cycle parameters before and after COVID-19 vaccination, we conducted an anonymous online survey of two groups of North American women who prospectively monitor their menstrual cycle parameters daily including bleeding patterns, urinary hormone levels using the ClearBlue Fertility Monitor, or cervical mucus observations. The primary outcome measures were cycle length, length of menses, menstrual volume, estimated day of ovulation (EDO), luteal phase length, and signs of ovulation. Perceived (subjective) menstrual cycle changes and stressors were also evaluated in this study as secondary outcome measures. Of the 279 women who initiated the survey, 76 met the inclusion criteria and provided 588 cycles for analysis (227 pre-vaccine cycles, 145 vaccine cycles, 216 post-vaccine cycles). Although 22% of women subjectively identified changes in their menstrual cycle, there were no significant differences in menstrual cycle parameters (cycle length, length of menses, EOD, and luteal phase length) between the pre-vaccine, vaccine, and post-vaccine cycles. COVID-19 vaccines were not associated with significant changes in menstrual cycle parameters. Perceived changes by an individual woman must be compared with statistical changes to avoid confirmation bias.
Describe the relationship between basal body temperature (BBT) and pregnanediol-3 alpha-glucuronide (PDG, the urine metabolite of progesterone) across the menstrual cycle. Observational study. Study carried out from 1996 to 1997 in eight European family planning clinics. PARTICIPANT(S): One hundred and seven normally fertile and cycling women. MAIN OUTCOME MEASURE(S): BBT and PDG level on each day of 283 cycles and ultrasound determination of the day of ovulation. (s): In comparison with previous end-of-cycle levels, decreases in PDG and BBT on the first day of menses were seen in nearly 90% and 80% of cycles, respectively. In a non-negligible percentage of cycles, luteolysis would continue during menses: between the second and the third day after menses, small but significant decreases in PDG and BBT were seen in 76% and 48% of cycles, respectively. During the peri-ovulatory phase, between the third and the second day before ovulation, PDG and BBT began to rise in 56% and 41% of cycles, respectively. There was a medium degree of correlation between PDG levels and BBT (r = 0.53; 7,279 days with available measurements). The relationship between PDG levels and BBT was linear at low PDG levels but BBT increased no longer when PDG levels continued to rise above a threshold of nearly 10 mcg/mg Cr. (s): PDG and BBT had parallel increases at low PDG rates but diverged at higher rates.
Women of reproductive age need reliable and effective family planning methods to manage their fertility. Natural family planning (NFP) methods or fertility awareness-based methods (FABMs) have been increasingly used by women due to their health benefits. Nevertheless, effectiveness of these natural methods remains inconsistent, and these methods are difficult for healthcare providers to implement in their clinical practice. The purpose of this study is to evaluate the effectiveness of the Marquette Model NFP system to avoid pregnancy for women at multiple teaching sites using twelve months of retrospectively collected teaching data. Survival analysis (Kaplan-Meier) was used to determine typical unintended pregnancy rates for a total of 1,221 women. There were forty-two unintended pregnancies which provided a typical use unintended pregnancy rate of 6.7 per 100 women over twelve months of use. Eleven of the forty-two unintended pregnancies were associated with correct use of the method. The total unintended pregnancy rate over twelve months of use was 2.8 per 100 for women with regular cycles, 8.0 per 100 women for the postpartum and breastfeeding women, and 4.3 per 100 for women with irregular menstrual cycles. The Marquette Model system of NFP was effective when provided by health professionals who completed the Marquette Model NFP teacher training program.
This study involved determining whether healthcare professionals at ten sites across the United States and Canada trained to provide the Marquette Method NFP services can replicate the effectiveness demonstrated in previous studies of the method. We found a high level of effectiveness (i.e., very low pregnancy rates) in using the Marquette Method among women from various regions across North America with diverse reproductive backgrounds and in particular when using hormonal fertility marker. Healthcare providers who have been trained to teach NFP can successfully incorporate NFP services in their practice and assist their clients in choosing appropriate family planning methods.
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. 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. Women were aged 33.4 ± 5.5 years and had menstrual cycles ranging between 23 and 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. 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.
Bouchard TP et al., 2019·Front Public Health·
Open Access
Progesterone rises \~24-36 h after ovulation. Past studies using ultrasound-confirmed ovulation have shown that three consecutive tests with a threshold of 5μg/mL of urine progesterone (pregnanediol-3-glucuronide, PDG), taken after the luteinizing hormone (LH) surge, confirmed ovulation with 100% specificity. The purpose of this study was to a evaluate a new urine PDG self-test to retrospectively confirm ovulation in women who were monitoring ovulation using a hormonal fertility monitor. Thirteen women of reproductive age were recruited to test urine PDG while using their home hormonal fertility monitor. The monitor measured the rise in estrogen (estrone-3-glucuronide, E3G) and LH to estimate the fertile phase of the menstrual cycle. The women used an online menstrual cycle charting system to track E3G, LH and PDG levels for four menstrual cycles. The participants (Mean age 33.6) produced 34 menstrual cycles of data (Mean length 28.4 days), 17 of which used a PDG test with a threshold of 7μg/mL and 17 with a threshold of 5μg/mL. In the cycles that used the 7μg/mL test strips, 59% had a positive confirmation of ovulation, and with the 5μg/mL test strips, 82% of them had a positive confirmation of ovulation. The 5μg/mL PDG test confirmed ovulation in 82% of cycles and could assist women in the evaluation of the luteal progesterone rise of their menstrual cycle.
Ovulation confirmation is a fundamental component of the evaluation of infertility. To inform the design of a larger clinical trial to determine the effectiveness of a new home-based pregnanediol glucuronide (PDG) urine test to confirm ovulation when compared with the standard of serum progesterone. In this observational prospective cohort study (single group assignment) in an urban setting (stage 1), a convenience sample of 25 women (aged 18-42 years) collected daily first morning urine for luteinisinghormone (LH), PDG and kept a daily record of their cervical mucus for one menstrual cycle. Serum progesterone levels were measured to confirm ovulation. Sensitivity and specificity were used as the main outcome measures. Estimation of number of ultrasound (US)-monitored cycles needed for a future study was done using an exact binomial CI approach. Recruitment over 3 months was achieved (n=28) primarily via natural fertility regulation social groups. With an attrition rate of 22%, specificity of the test was 100% for confirming ovulation. Sensitivity varied depending on whether a peak-fertility mucus day or a positive LH test was observed during the cycle (85%-88%). Fifty per cent of participants found the test results easy to determine. A total of 73 US-monitored cycles would be needed to offer a narrow CI between 95% and 100%. This is first study to clinically evaluate this test when used as adjunct to the fertility awareness methods. While this pilot study was not powered to validate or test efficacy, it helped to provide information on power, recruitment and retention, acceptability of the procedures and ease of its use by the participants. Given this test had a preliminary result of 100% specificity, further research with a larger clinical trial (stage 2) is recommended to both improve this technology and incorporate additional approaches to confirm ovulation. NCT03230084.
Identifying the return of fertility with cervical mucus observations is challenging during the postpartum period. Use of urinary measurements of estrogen and progesterone can assist in understanding the return to fertility during this period. The purposes of this study were to describe the postpartum return of fertility by an analysis of total estrogen (TE) and pregnanediol glucuronide (PDG) profiles and to correlate these profiles with cervical mucus observations. Twenty-six participants collected urine samples during the postpartum period and recorded mucus scores. TE and PDG hormones were analyzed and compared with mucus scores. During amenorrhea, mucus reflected TE changes in only 35 percent of women; after amenorrhea, typical mucus patterns were seen in 33 percent of cycles. We concluded that postpartum mucus and hormone profiles are significantly dissociated but that monitoring urinary hormones may assist in identifying the return of fertility. We also identified different hormonal patterns in the return to fertility. The postpartum period is a challenging time for identifying the return of fertility. The purposes of this study were to describe the hormonal patterns during the return of fertility and to correlate these patterns with cervical mucus observations. Twenty-six postpartum women collected urine samples and recorded mucus scores. Urinary estrogen and progesterone hormones were analyzed and compared with mucus scores. Before the return of menses, mucus reflected hormonal changes in only 35 percent women and after first menses in 33 percent of cycles. We found that hormone profiles do not correlate well with mucus observations during the postpartum return of fertility.
Abdulla SH et al., 2018·Front Public Health·
Open Access
Explore potential relationships between preovulatory, periovulatory, and luteal-phase characteristics in normally cycling women.
Observational study.
Eight European natural family planning clinics. Patient(s): Ninety-nine women contributing 266 menstrual cycles. Intervention(s): The participants collected first morning urine samples that were analyzed for estrone-3 glucuronide (E1G), pregnanediol-3alpha-glucuronide (PDG), follicle stimulating hormone (FSH), and luteinizing hormone (LH). The participants underwent serial ovarian ultrasound examinations. Main Outcome Measure(s): Four outcome measures were analyzed: short luteal phase, low mid-luteal phase PDG level (mPDG), normal then low luteal PDG level, low then normal luteal PDG level. A long preovulatory phase was a predictor of short luteal phase, with or without adjustment for other variables. A high periovulatory PDG level was a predictor for short luteal phase as well as normal then low luteal PDG level. A low periovulatory PDG level predicted low mPDG and low then normal luteal PDG level, with or without adjustment for other variables. A small maximum follicle predicted normal then low luteal PDG level, with or without adjustment for other variables. The relationship between small maximum follicle size and short luteal phase or small maximum follicle size and low mPDG was no longer present when the regression was adjusted for certain characteristics. A younger age at menarche and a high body mass index were both predictors of low mPDG. Luteal phase abnormalities exist over a spectrum where some ovulation disorders may exist as deviations from the normal ovulatory process.This study confirms the negative impact of a small follicle size on the quality of the luteal phase. The occurrence of normal then low luteal PDG level is confirmed as a potential sign of luteal phase abnormality.
Oral contraceptives (OCs) are often prescribed to adolescents and young adults for the treatment of health problems and to avoid unwanted pregnancies. We hypothesized that the use of OCs, among adolescents and young adults, is associated with a greater likelihood of pregnancy, abortion, sexually transmitted diseases (STDs), pelvic inflammatory disease (PID), and sexual behaviors that will enhance those problems (i.e., earlier sexual debut and more sexual partners) than adolescents and young adults not using OCs. To test this hypothesis, data from 1,365 adolescents and young adults in the 2011-2013 National Survey of Family Growth (NSFG) were used to describe the influence of ever use of OCs on ever having sex, sexual debut, multiple sexual partners, STDs, PID, pregnancy, and abortion. A secondary purpose was to evaluate protective factors from unhealthy sexual practices like religiosity, church attendance, and intact families. We found that the "ever use" of OCs by US adolescents and young adults results in a greater likelihood of ever having sex, STDs, PID, pregnancy, and abortion compared with those adolescents and young adults who never used OCs. Furthermore, those adolescents who ever used OCs had significantly more male sexual partners than those who never used OCs, and they also had an earlier sexual debut by almost two years. Conversely, we found that frequent church attendance, identification of the importance of religion, and having an intact family among adolescents were associated with less likelihood of unsafe sexual practices. We concluded that the use of OCs by adolescents and young adults might be considered a health risk. Further research is recommended to confirm these associations.
The purpose of this article was to show the correlation between contraceptive use in adolescents and negative sexual outcomes. We used data from the 2011-2013 NSFG and demonstrated that never married adolescents who used oral hormonal contraception were three times more likely to have an STD, have PID, and to become pregnant, and, surprisingly, ten times more likely of having an abortion compared to noncontracepting adolescents. These are outcomes that contraception is intended to prevent. These data also showed that the contraceptors had significantly more male partners than their contraceptive counterparts. Protective factors such as church attendance and family cohesiveness were associated with a decreased likelihood of sexual activity.
Abdullah S et al., 2018·Methods of information in medicine
Even in normally cycling women, hormone level shapes may widely vary between cycles and between women. Over decades, finding ways to characterize and compare cycle hormone waves was difficult and most solutions, in particular polynomials or splines, do not correspond to physiologically meaningful parameters. We present an original concept to characterize most hormone waves with only two parameters. The modelling attempt considered pregnanediol-3-alpha-glucuronide (PDG) and luteinising hormone (LH) levels in 266 cycles (with ultrasound-identified ovulation day) in 99 normally fertile women aged 18 to 45. The study searched for a convenient wave description process and carried out an extended search for the best fitting density distribution. The highly flexible beta-binomial distribution offered the best fit of most hormone waves and required only two readily available and understandable wave parameters: location and scale. In bell-shaped waves (e.g., PDG curves), early peaks may be fitted with a low location parameter and a low scale parameter; plateau shapes are obtained with higher scale parameters. I-shaped, J-shaped, and U-shaped waves (sometimes the shapes of LH curves) may be fitted with high scale parameter and, respectively, low, high, and medium location parameter. These location and scale parameters will be later correlated with feminine physiological events. Our results demonstrate that, with unimodal waves, complex methods (e.g., functional mixed effects models using smoothing splines, second-order growth mixture models, or functional principal-component- based methods) may be avoided. The use, application, and, especially, result interpretation of four-parameter analyses might be advantageous within the context of feminine physiological events.
Bouchard TP et al., 2018·Front Med (Lausanne)·
Open Access
To determine the effectiveness of achieving pregnancy with focused intercourse in the fertile window identified using natural fertility indicators. 24-cycle prospective effectiveness study.
A North American web-based fertility monitoring service. 256 North American women aged 20-43 (mean age 29.2 years) seeking to achieve pregnancy. Participants identified their fertile window with either electronic hormonal fertility monitoring or cervical mucus monitoring, or both, and recorded their observations on an online fertility tracking system. Pregnancies were validated by nurses with an online self-assessed pregnancy evaluation form. Survival analysis was used to determine pregnancy rates. There were 150 pregnancies among the 256 participants with an overall pregnancy rate of 78 per 100 women over 12 menstrual cycles. There were 54 pregnancies (68%) among the 80 women using the fertility monitor, 11 pregnancies (46%) among the 24 women using mucus monitoring, and 90 (63%) among the 143 women using both mucus and monitor. The 12-cycle pregnancy rates per 100 women were 83 (monitor group), 72 (mucus group), and 75 (mucus and monitor group). Pregnancy rates reached 100% at 24 cycles of use for those women using the hormonal fertility monitor. Use of the hormonal fertility monitor alone seems to offer the best natural estimate of the fertile phase of the menstrual cycle for women wishing to achieve a pregnancy. Focusing intercourse through 24 menstrual cycles can be beneficial for achieving pregnancy.
To study the best possible luteinizing hormone (LH) threshold to predict ovulation within the 24, 48, and 72 h. Observational study. Multicenter collaborative study. A total of 107 women. Women collected daily first morning urine for hormonal assessment and underwent serial ovarian ultrasound. This is a secondary analysis of 283 cycles. The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were estimated for varying ranges of LH thresholds. Receiver operating characteristic curves and cost-benefit ratios were used to estimate the best thresholds to predict ovulation. The best scenario to predict ovulation at random was within 24 h after the first single positive test. The false-positive rate was found to increase as (1) the cycle progressed or (2) two or three consecutive tests were used, or (3) ovulation was predicted within 48 or 72 h. Testing earlier in the cycle increases the predictive value of the test. The ideal thresholds to predict ovulation ranged between 25 and 30 mIU/ml with a PPV (50-60%), NPV (98%), LR+ (20-30), and LR- (0.5). At least, one day with LH ≥25 mIU/ml followed by three negatives (LH <25) occurred before ovulation in 31% of all cycles. When used throughout the cycle and evaluated together, peak-fertility type mucus with a positive LH test ≥25 mIU/ml provides a higher specificity than either mucus or LH testing alone (97-99 vs. 77-95 vs. 91%, respectively). We identified that beginning LH testing earlier in the cycle (day 7) with a threshold of 25-30 mIU/ml may present the best predictive value for ovulation within 24 h. However, prediction by LH testing alone may be affected negatively by several confounding factors so LH testing alone should not be used to define the end of the fertile window. Complementary markers should be further investigated to predict ovulation and identify the fertile window. The use of the peak cervical mucus along with an LH test may provide a higher specificity and predictive value than either of them alone. We recommend that manufacturers disclose their tests' threshold to the public.
To characterize the variability of hormonal profiles during the luteal phase in normal cycles. Observational study. Not applicable. PATIENT(S): Ninety-nine women contributing 266 menstrual cycles. INTERVENTION(S): The women collected first morning urine samples that were analyzed for estrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FSH, and LH. The women had serum P tests (twice per cycle) and underwent ultrasonography to identify the day of ovulation. MAIN OUTCOME MEASURE(S): The luteal phase was divided into three parts: the early luteal phase with increasing PDG (luteinization), the midluteal phase with PDG ≥10 μg/mg Cr (progestation), and the late luteal phase (luteolysis) when PDG fell below 10 μg/mg Cr. RESULT(S): Long luteal phases begin with long luteinization processes. The early luteal phase is marked by low PDG and high LH levels. Long luteinization phases were correlated with low E1G and low PDG levels at day 3. The length of the early luteal phase is highly variable between cycles of the same woman. The duration and hormonal levels during the rest of the luteal phase were less correlated with other characteristics of the cycle. CONCLUSION(S): The study showed the presence of a prolonged pituitary activity during the luteinization process, which seems to be modulated by an interaction between P and LH. This supports a luteal phase model with three distinct processes: the first is a modulated luteinization process, whereas the second and the third are relatively less modulated processes of progestation and luteolysis.
Fehring RJ et al., 2017·J Obstet Gynecol Neonatal Nurs·
To analyze the effectiveness of an online, nurse-managed natural family planning (NFP) program among breastfeeding women and subgroups of these women.
Longitudinal comparative cohort study.
A university-based online NFP education program and menstrual cycle charting system. Women (N = 816) with a mean age of 30.3 years (standard deviation = 4.5) who registered to use the online NFP system and indicated they were breastfeeding. Participants tracked their fertile times with an electronic hormone fertility monitor (EHFM), cervical mucus monitoring, or both. All unintended pregnancies were evaluated by professional nurses. The correct use pregnancy rates were 3 per 100 users over 12 cycles of use, and typical rates were 14 per 100 at 12 cycles of use. At 12 cycles of use, total pregnancy rates were 16 per 100 for electronic hormone fertility monitor users (n = 380), 81 per 100 among mucus-only users (n = 45), and 14 per 100 for electronic hormone fertility monitor plus mucus users (n = 391). Use of a nurse-managed online NFP program for women can be effective to help women avoid pregnancy while breastfeeding, especially with correct and consistent use.
Serum progesterone (P) rises after ovulation in the luteinisation process. To identify an accurate progesterone threshold to confirm ovulation in the assessment of a woman's fertility. In a secondary analysis of an observational European multicentre study, this study included 107 women over 326 menstrual cycles and tracked daily first morning urine (FMU), changes in observed cervical mucus discharge, serum progesterone, and ultrasonography to identify the day of ovulation. A serum progesterone level was available for 102 women over a total 260 cycles with one or two P levels per cycle. It was found that a single serum P⩾5ng/ml is highly specific with a specificity of 98.4 (95% CI 96.0-99.5), with a sensitivity of 89.6 (95% CI 85.2-92.9). A random serum progesterone level ⩾5ng/ml confirms ovulation. This may be of use for clinicians wanting to confirm that ovulation has occurred.
To assess the sensitivity and specificity of the self-identified fertile window. Observational study. Not applicable. PATIENT(S): A total of 107 women. INTERVENTION(S): Women recorded cervical mucus observation and basal body temperature daily while undergoing daily ovarian ultrasound. MAIN OUTCOME MEASURE(S): The biological fertile window, defined as the 6 days up to and including the day of ovulation; and the 2-day ovulation window, defined as the day before and the day of ovulation. RESULT(S): The self-identification of the biological fertile window by the observation of any type of cervical mucus provides 100% sensitivity but poor specificity, yielding a clinical fertile window of 11 days. However, the identification of the biological fertile window by peak mucus (defined as clear, slippery, or stretchy mucus related to estrogen) yielded 96% sensitivity and improved specificity. The appearance of the peak mucus preceded the biological fertile window in less than 10% of the cycles. Likewise, this type of mucus identified the ovulation window with 88% sensitivity. CONCLUSION(S): These results suggest that, when perceived accurately, more accurate clinical self-detection of the fertile window can be obtained by identification of peak mucus. This may improve efforts to focus intercourse in the fertile phase for couples with fertility concerns.
To describe FSH profile variants. Observational study. Multicenter collaborative study. PATIENT(S): A total of 107 women. INTERVENTION(S): Women collected daily first morning urine and underwent serial ovarian ultrasound. MAIN OUTCOME MEASURE(S) FSH RESULT(S): The individual FSH cyclic profiles demonstrated a significant departure from the currently accepted model. A decline in FSH levels at the end of the follicular phase was observed in only 42% of cycles. The absence of this decline was significantly associated with a shorter luteal phase and higher pregnanediol-3α-glucuronide, FSH, and LH levels at the time of ovulation. In 34% of the cycles, significant FSH variability was observed throughout the follicular phase; this variability was associated with higher body mass index and lower overall FSH and LH levels throughout the cycle. The FSH peak occurs on average 2 hours before ovulation. The FSH peak duration was shorter than the LH peak. CONCLUSION(S): These results suggest that average FSH profiles may not reflect the more complex dynamics of daily hormonal variations in the menstrual cycle. It is possible that discrepancies between the average normal FSH profile and the individual day-to-day variants can be used to detect abnormalities.
Urinary hormonal markers may assist in increasing the efficacy of Fertility Awareness Based Methods (FABM). This study uses urinary pregnanediol-3a-glucuronide (PDG) testing to more accurately identify the infertile phase of the menstrual cycle in the setting of FABM. Secondary analysis of an observational and simulation study, multicentre, European study. The study includes 107 women and tracks daily first morning urine (FMU), observed the changes in cervical mucus discharge, and ultrasonography to identify the day of ovulation over 326 menstrual cycles. The following three scenarios were tested: (A) use of the daily pregnandiol-3a-glucuronide (PDG) test alone; (B) use of the PDG test after the first positive urine luteinizing hormone (LH) kit result; (C) use of the PDG test after the disappearance of fertile type mucus. Two models were used: (1) one day of PDG positivity; or (2) waiting for three days of PDG positivity before declaring infertility. After the first positivity of a LH test or the end of fertile mucus, three consecutive days of PDG testing over a threshold of 5μg/mL resulted in a 100% specificity for ovulation confirmation. They were respectively associated an identification of an average of 6.1 and 7.6 recognized infertile days. The results demonstrate a clinical scenario with 100% specificity for ovulation confirmation and provide the theoretical background for a future development of a competitive lateral flow assay for the detection of PDG in the urine.
The postpartum period is a challenging time for family planning, especially for women who breastfeed. Breastfeeding delays the return of menses (lactational amenorrhea), but ovulation often occurs before first menses. For this reason, a protocol was developed to assist women in identifying their return of fertility postpartum to avoid pregnancy. In this prospective, 12-month, longitudinal cohort study, 198 postpartum women aged 20 to 45 years (mean age, 30.2 years) were taught a protocol for avoiding pregnancy with either online or in-person instruction. A hand-held fertility monitor was used to identify the fertile period by testing for urinary changes in estrogen and luteinizing hormone, and the results were tracked on a web site. During lactational amenorrhea, urine testing was done in 20-day intervals. When menses returned, the monitor was reset at the onset of each new menstrual cycle. Participants were instructed to avoid intercourse during the identified fertile period. Kaplan-Meier survival analysis was used to calculate unintentional pregnancy rates through the first 12 months postpartum. There were 8 unintended pregnancies per 100 women at 12 months postpartum. With correct use, there were 2 unintended pregnancies per 100 women at 12 months. The online postpartum protocol may effectively assist a select group of women in avoiding pregnancy during the transition to regular menstrual cycles.