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.
Background,Pregnanediol glucuronide (PdG), the principal urinary metabolite of progesterone, can assess luteal progesterone exposure, but interpretation depends on appropriate timing relative to ovulation. We evaluated whether urinary luteinizing hormone (LH)-based reference points could standardize luteal urinary PdG assessment compared with ultrasound-determined ovulation (USDO).,Methods,This retrospective secondary analysis included 216 ovulatory cycles from 95 women from an original cohort of 107 women (326 cycles). Eligible cycles had ultrasound-confirmed ovulation and an LH peak before USDO+3. The retrospectively identified LH peak and first urinary LH concentrations ≥10, ≥15, ≥20, ≥25, and ≥30 mIU/mL were evaluated for timing urinary PdG measurement 6–9 days later, using a prespecified threshold of ≥15 µg/mL. PdG classifications were compared with USDO-timed classifications using area under the receiver operating characteristic curve, sensitivity, specificity, predictive values, and likelihood ratios.,Results,Agreement remained high across assessment days. The LH peak showed the highest overall agreement. Among prospectively applicable strategies, first urinary LH ≥15 mIU/mL provided the best balance between agreement and cycle availability. Positive predictive values were consistently high (98–100%), whereas negative predictive values were modest. No assessment day consistently outperformed the others.,Conclusions,Urinary LH-based timing closely reproduced USDO-guided urinary PdG classification. The LH peak showed the highest agreement, whereas first urinary LH ≥15 mIU/mL was the most practical prospective reference point. PdG ≥15 µg/mL classifications showed near-universal agreement with ultrasound-guided timing. These findings support standardized PdG timing when ultrasound is unavailable but do not establish diagnostic criteria or predict reproductive outcomes.
Several studies have evaluated the reliability of using temperature sensors placed in different locations on the body to identify the day of ovulation. However, such demonstrations are lacking for axillary temperature wearable devices. This study aimed to evaluate the accuracy with which an axillary temperature armband sensor (Tempdrop) identifies the day of ovulation and the fertile window, using the Clearblue Connected Ovulation Test System as the reference method. A total of 194 cycles were analyzed from 125 women that participated in the study between April 2023 and June 2024. The performance parameters were high: the sensitivity (96.8% (95% CI 95.6; 97.7)), specificity (99.1% (98.8; 99.4)), accuracy (98.6% (98.2; 98.9)), positive predictive value (96.8% (95.6; 97.7)) and negative predictive value (99.1% (98.8; 99.4)). Furthermore, the results revealed a remarkably clear and better-than-expected change in temperature around the time of ovulation. This axillary temperature wearable sensor is an effective alternative to urine ovulation tests for determining the timing of ovulation. Another advantage is that it provides a clear temperature curve that can be used to evaluate the quality of the luteal phase.
Bernot G et al., 2025·European Journal of Obstetrics & Gynecology and Reproductive Biology
Fertility treatment pathways are complex and lengthy. The current prevalence of infertility makes it a public health issue. The involvement of general practitioners and the training of fertility instructors to provide therapeutic education have been suggested as ways of involving patients in the process and improving the therapeutic trajectory of these patients, who often have co-morbidities. To describe the activity of trained fertility instructors; to assess the interest of doctors in the fertility chart provided by women; and to describe the outcomes of their fertility care pathway. 66 French fertility instructors were interviewed in June 2024. The 15 general practitioners who had received additional training were also interviewed. The records of all couples who received fertility counselling and treatment between 1 January 2022 and 31 December 2023, the study cut-off date, were analysed. Doctors declared that the women had gained a clear understanding of their menstrual cycle, which was useful for diagnosis and treatment follow-up. The chart was particularly useful for diagnosing the causes of infertility and identifying when in the cycle to take medication. Only 4 of the 551 women were lost to follow-up. Of the remaining 547 women, 204 (37%) became pregnant. Of these, 75% had a live birth or an ongoing pregnancy at study cut-off. The involvement of fertility instructors and general practitioners improved the couple s ability to interact with doctors and to adhere to infertility treatment. The fertility chart provided by the women proved to be useful in the diagnosis and treatment process.
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.
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.
Leiva R et al., 2024·Seminars in reproductive medicine
Smartphone-based fertility awareness methods with home-based urinary hormonal testing are gaining popularity for fertility tracking. In our university-affiliated family practice, we integrated a previously developed ovulation tracking application into a protocol for monitoring urinary sex hormones and cervical secretions. Serum progesterone was used to confirm the luteal phase, with levels ≥ 15.9 nmol/L ensuring confirmation. Data from 110 women seen for infertility treatment (n = 95) or family planning advice (n = 15) and using our ovulation prediction protocol showed that most opted for a combination of cervical mucus and luteinizing hormone testing (n = 86). Among those using it for family planning, the median usage among women spanned 56 cycles, and 13 cycles per woman required progesterone testing for confirmation. Thirteen patients are still using the method without unintended pregnancies. No unintended pregnancies occurred. Confidence in tests based on serum progesterone was high (93%). For infertility, the method helped in the identification of anovulation, evaluating treatment response, and in diagnosing subfertility causes. This proof-of-concept retrospective descriptive case series suggests the potential for smartphone-based monitoring in fertility management, urging further studies for application enhancements and prospective validation.
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.
Turner JV et al., 2024·Reproductive sciences (Thousand Oaks, Calif.)
To determine the relationships between luteal-phase steroidal hormonal profile and PMS for a large number of women attending a dedicated fertility clinic. This was a retrospective cross-sectional study on women attending a hospital-based clinic for fertility concerns and/or recurrent miscarriage. All participants were assessed with a women's health questionnaire which also included evaluation of premenstrual symptoms. Day of ovulation was identified based on the peak mucus symptom assessed by the woman after instruction in a fertility awareness-based method (FABM). This enabled reliable timing of luteal-phase serum hormone levels to be taken and analysed. Between 2011 and 2021, 894 of the 2666 women undertaking the women's health assessment had at least one evaluable serum luteal hormone test. Serum progesterone levels were up to 10 nmol/L lower for symptomatic women compared with asymptomatic women. This difference was statistically significant (p < 0.05) for the majority of PMS symptoms at ≥ 9 days after the peak mucus symptom. A similar trend was observed for oestradiol but differences were generally not statistically significant. ROC curves demonstrated that steroid levels during the luteal phase were not discriminating in identifying the presence of PMS symptoms. Blood levels for progesterone were lower throughout the luteal phase in women with PMS, with the greatest effect seen late in the luteal phase.
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.
Intrauterine insemination with ovarian stimulation (IUI-OS) is a first-line treatment for couples with unexplained infertility. Individual participant data meta-analysis (IPD-MA) is the gold standard for evidence synthesis. To compare the effectiveness and safety of ovarian stimulation with gonadotrophin, Letrozole and clomiphene citrate (CC) and to explore treatment-covariate interactions for important baseline characteristics in women undergoing IUI. We searched electronic databases including PubMed, MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL). We included randomised controlled trials (RCTs) comparing IUI-OS with gonadotropins, Letrozole or CC among couples with unexplained infertility. We excluded dose comparing studies of the same drug. We contacted the authors of eligible RCTs to share the IPD and established the IUI IPD-MA collaboration. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. We used a one-stage approach using a random effects model. Six RCTs (n= 2299) provided IPD. Gonadotropins increased the chance of a live birth compared to both CC (5 RCTs, 1946 women, RR 1.28, 95%CI 1.10 to 1.49, I2 = 25%, moderate-quality evidence) whereas there was insufficient evidence of a difference between Letrozole and CC (1 RCT, 599 women, RR 0.77 95%CI 0.58 to 1.03). Gonadotropins increased the risk of a multiple pregnancy compared to both CC (4 RCTs, 1696 women, RR 2.17, 95%CI 1.33 to 3.55, I2 = 69%, low-quality evidence) whereas there was insufficient evidence of a difference between Letrozole and CC (1 RCT, 599 women, RR 0.71, 95%CI 0.33 to 1.56). No strong evidence on the treatment-covariate interactions (female age, BMI or primary versus secondary infertility) was found. Gonadotropins increased the chance of a live birth compared to both CC and Letrozole but also increased the chance of a multiple pregnancy. Further RCTs comparing Letrozole and other interventions in couples with unexplained infertility are needed.
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.
We are seeing now a renewed interest in female physiology; particularly, in the female menstrual cycle. This desire has not been overridden, however, by the widespread use of hormonal contraception. Cycle monitoring applications for smart phones have now millions of users.
Environmental Exposures · Radiation and Electromagnetic Exposure
Garmier-Billard M et al., 2019·Trends Med·
Open Access
Assess quantitatively the impact of nocturnal light pollution on the menstrual cycle. Cross-sectional observational study. Single French institute from November 2017 to March 2018. Nineteen ostensibly healthy menstruating women aged 19 to 45, inclusive. Intervention(s): None. Assessment of nocturnal light pollution (questionnaire and lux meter) and 22 clinical signs of ovulation disorder. Wilcoxon tests were used to quantify the abilities of nocturnal light pollution factors to predict clinical signs of ovulation disorders. Nearly half of the 94 daily observations made by questionnaire and measurements made by lux meter indicated light pollution due to light flooding into the bedroom from indoor or outdoor sources. Nearly more than half of the 56 menstrual cycles presented at least mild abnormalities. The data showed that some clinical signs of ovulation disorders may be significantly predicted by factors of light pollution but a lack of power prevented reaching Bonferroni criterion. The indications of negative impact of dim light at night on some menstrual cycle characteristics call for a randomized study to quantify improvements of menstrual cycle characteristics brought by suppressing nocturnal light pollution. This will pave the way for new therapeutic perspectives for some difficult cases of ovulation disorders.
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.
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.
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.
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.
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.
To describe the LH surge variants in ovulating women and analyze their relationship with the day of ovulation and other hormone levels. Secondary analysis of a prospective cohort observational study. Eight natural family planning clinics. Normally fertile women (n = 107) over 283 cycles. INTERVENTION(S): Women collected daily first morning urine, charted basal body temperature and cervical mucus discharge, and underwent serial ovarian ultrasound. MAIN OUTCOME MEASURE(S): Urinary LH, FSH, estrone-3-glucuronide (E3G), pregnanediol-3α-glucuronide (PDG), and day of ovulation by ultrasound (US-DO). RESULT(S): Individual LH surges were extremely variable in configuration, amplitude, and duration. The study also showed that LH surges marked by several peaks were associated with statistically significant smaller follicle sizes before rupture and lower LH level on the day of ovulation. LH surges lasting >3 days after ovulation were associated with a lower E3G before ovulation, a smaller corpus luteum 2 days after ovulation, and a lower PDG value during the first 4 days after ovulation. CONCLUSION(S): In clinical practice, LH profiles should be compared with the range of profiles observed in normally fertile cycles, not with the mean profile.
Ecochard R et al., 2008·Reprod Biol Endocrinol·
Open Access
To assess the amount of variability in ovarian follicular growth rate and maximum follicular diameter related to different centers, women and cycles of the same women in a multicenter observational study of follicular growth. Secondary analysis of a prospective cohort study from eight centers in Europe. There were 533 ultrasound examinations in 282 cycles of 107 women with normal fertility. A random effects model with center, woman and cycle as hierarchical units of variation was used to analyze mean follicular diameter on days preceding ovulation. Follicular growth did not differ by center. There was homogenous growth across women and cycles, and the maximum follicular diameter before ovulation varied substantially across cycles but not across women. Many (about 40%) women had small maximum follicular diameter on the day before ovulation (<19 mm). Pre-ovulatory cycle length was not related to maximum follicular diameter. In normal fecundity, there is a substantial variation in maximum follicular diameter from cycle to cycle based on variation in the duration of follicular development, but the variation could not be explained by different characteristics of different women. Explanation of variation in follicular growth has to be found on the cycle level.
Ecochard R, 2006·Statistical methods in medical research
Modelization of fecundability stepped recently from demography and population-based contexts to reproductive biology and treatment of infertility. This created a strong call for flexibility and robustness. Indeed, explained and unexplained heterogeneities are non-negligible sources of bias that result in false conclusions as to the determinants of fertility or to the success rates of reproductive techniques, among other examples. There are two main sources of heterogeneity: biological heterogeneity and heterogeneity of sexual behaviour. A uniform presentation of time-to-pregnancy and Barrett-Marshall models is proposed to enlighten their similarities and differences in modelling heterogeneity of fecundability. Mixed models for fecundability studies are presented as tools to allow for unexplained heterogeneity and to quantify heterogeneity of the effect of observed factors and variability of size of this unexplained heterogeneity between subpopulations. Some criteria for the modelling strategy in fecundability studies are suggested with emphasis on the unit-treatment additivity criterion. The strong and complex selection process resulting from heterogeneity is described as well as the selection and cross-selection processes of observed and unobserved fecundability factors. Consequences regarding data collection and statistical inference are discussed. In the current context, a consensus setting general rules for data collection and statistical analysis would be useful to compare the results and increase the reliability of these results in medical practice.
Outcomes and Effectiveness · Cumulative Versus Per Cycle Reporting
Ecochard R, 2005·Revue d'epidemiologie et de sante publique
Heterogeneity in women and men's fecundity is a well-established fact. The selection process of men and women treated for infertility might bias the success rates of reproductive technology. Bias may also arise from frequency and timing of intercourse with respect to the day of ovulation. Several datasets were collected and analysed. They concern normally fertile couples who used natural family planning methods and infertile couples treated by artificial insemination with husband or donor's spermatozoa. The effects of heterogeneity on the success rates of treatment cycles are described and solutions are proposed as to data collection and statistical analysis in this specific field. The decrease in the success rates along successive cycles of assisted reproduction is a consequence of heterogeneity. The probability of conception varies among women and among men. After a first success, the probability of another success is higher. After a failure, the probability of success is lower. The most specialised centres treat the less fecund couples. There is a negative correlation between men and women's fertility in case of oligo/azoospermia. The fecund window cannot be correctly located by calendar calculations, but more appropriately by assessment of cervical mucus at the vulva. The variability of this location is wide. The decrease in the success rate with men and women's age results from a complex mixture of an increase in the proportion of sterile patients and a decrease in fecund patients' fecundity. Care should be taken to limit the bias due to patient selection and specific statistical methods should be used to allow for the progressive selection of patients during fertility studies and for the variability of the frequency and the timing of intercourse or insemination relative to ovulation.
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.
To monitor gonadotropin and ovarian hormone levels in relation to sleep duration in normally cycling women. Observational and cross-sectional study. Multicentric collaborative study. PATIENT(S): One hundred six healthy and normally cycling women, aged 19 to 44 years, with cycle lengths of 24 to 34 days. INTERVENTION(S): Follow-up during one to four consecutive cycles with daily urine collection. MAIN OUTCOME MEASURE(S): Urine concentrations of LH, FSH, estrone-3-glucuronide (E1-3-G), and pregnanediol-3-alpha-glucuronide (Pd-3alpha-G). Ultrasound determination of day of ovulation and estimation of sleep duration. RESULT(S): We found a significant association between FSH levels and sleep duration (P=.008). Follicle-stimulating hormone levels were 20% higher in long-time sleepers than in short-time sleepers. This association persisted whatever the age or the body mass index. There was no significant association between belonging to any group and LH, E1-3-G, or Pd-3alpha-G levels. CONCLUSION(S): Our results suggest that sleep duration could be related to FSH levels, although the study design did not allow us to establish a causal relationship nor to explain the physiological basis of the observed relationship.
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.
Ecochard R et al., 2001·European journal of obstetrics, gynecology, and reproductive biology
Women with cyclic mastalgia seem to be at risk of fibrocystic breast disease and/or breast cancer. We studied the relationships between mastalgia and hormone levels throughout the menstrual cycle. Ostensibly healthy women were monitored during a sum of 326 cycles. A case-control study compared personal and hormonal variables of 30 women experiencing cyclic mastalgia with those of 77 women without this symptom. Except sleeping times, no significant differences were found in personal variables. Cyclic mastalgia and symptoms of fluid retention were slightly associated. Menses and the luteal phase were significantly longer in cases than in controls. Gonadotropin but not ovarian hormone levels were also significantly higher in cases throughout the cycle. Cyclic mastalgia is less related to symptoms of fluid retention or to ovarian hormone levels than to regularly high gonadotropin levels, specific inhibitors might thus be used to alleviate the symptom.
Delay until conception is generally described by a mixture of geometric distributions. Weinberg and Gladen (1986, Biometrics 42, 547-560) proposed a regression generalization of the beta-geometric mixture model where covariates effects were expressed in terms of contrasts of marginal hazards. Scheike and Jensen (1997, Biometrics 53, 318-329) developed a frailty model for discrete event times data based on discrete-time analogues of Hougaard's results (1984, Biometrika 71, 75-83). This paper is on a generalization to a three-parameter family distribution and an extension to multivariate cases. The model allows the introduction of explanatory variables, including time-dependent variables at the subject-specific level, together with a choice from a flexible family of random effect distributions. This makes it possible, in the context of medically assisted conception, to include data sources with multiple pregnancies (or attempts at pregnancy) per couple.
Ecochard R et al., 2000·European journal of obstetrics, gynecology, and reproductive biology
Evaluation of sensitivity and specificity of 4 ultrasound indices of ovulation. Multicenter collaborative study of 794 abdominal and transvaginal ultrasound scanning of ovaries performed during 271 cycles in 107 normally fertile women. Comparison of sensitivities and specificities of indices using McNemar test. The sensitivity and specificity of the indices were 84 and 89.2, respectively, for disappearance or sudden decrease in follicle size; 38.4 and 79.7 for appearance of ultrasonic echoes in the follicle; 61.6 and 87.1 for irregularity of follicular walls; 71.0 and 88.2 for appearance of free fluid in the cul-de-sac of Douglas. Ultrasonic echoes had a significantly lower sensitivity (P<0.001) and specificity (P<0.01) than other indices.
To characterize the relationships between body mass index (BMI) and LH or FSH levels over the cycle in normally cycling women. We compared baseline characteristics, cycle characteristics, follicle sizes, and daily hormone levels among women with low (n = 22), normal (n = 63), or high (n = 22) BMIs over 326 cycles. There were no significant differences in age or other lifestyle characteristics between groups. High BMI was significantly associated with younger age at menarche and less sleeping time. No differences were observed between high- and low-BMI groups in cycle length or diameter of the dominant follicle. Luteinizing hormone levels were significantly higher only in the beginning of the cycle in women with low BMIs than in those with high BMIs. Follicle-stimulating hormone levels were also significantly higher but were high during all three phases of the cycle (early follicular, periovulatory, and luteal phases). Mean levels were approximately 1. 9, 1.8, and 1.2 times higher, respectively, in the low-BMI group than the high-BMI group. Luteinizing hormone levels and BMI were inversely associated in normally cycling women during the early follicular phase. Follicule-stimulating hormone levels and BMI were inversely associated during the whole cycle, independent of age.
Ecochard R et al., 2000·Human reproduction (Oxford, England)
This study was undertaken to establish whether ovulation in humans alternates consistently from right to left ovary in successive cycles and whether the site of ovulation affects the next cycle length or the hormonal profiles. A total of 199 cycles in 80 normally fertile women were studied. The volunteers were monitored with ultrasonography to determine the day and side of ovulation and to calculate follicular and luteal phase lengths. Urinary hormone concentrations were also assayed. Right-sided ovulations occurred in 104 of the 199 cycles (52.3%; not significantly different from 50%). Alternate ovulations occurred in 61 of the 119 pairs of succeeding cycles (51.3%, not significant). The follicular phase length in contralateral ovulation (14.59 +/- 0.33 days; mean +/- SEM) did not differ significantly from that of ipsilateral ovulation (14.59 +/- 0. 37 days). There were also no significant differences in urinary concentrations of oestrone-3-glucuronide, pregnanediol-3alpha glucuronide, follicle stimulating hormone, and luteinizing hormone between ipsilateral and contralateral ovulation in either early follicular, peri-ovulatory or luteal phase of the cycle. It is concluded that in normally fertile women, the cycle length and the hormonal profile are independent of the, most probably random, site of ovulation.
To determine whether hMG offers an advantage over clomiphene citrate (CC) in achieving pregnancy after IUI with husband's sperm. Randomized prospective trial. Infertility patients in a university teaching hospital. PATIENT(S): Fifty-eight women under 39 years old undergoing ovulation induction before IUI. INTERVENTION(S): The women were assigned randomly to one of two treatment groups. Patients in group I (CCHH) received CC for the first two cycles and hMG for the last two cycles. Patients in group II (HHCC) received hMG for the first two cycles and CC for the last two cycles. MAIN OUTCOME MEASURE(S): Cycle fecundity rates for the two treatment modalities were compared statistically with use of life-table analysis. RESULT(S): Of the 174 cycles studied, overall cycle fecundity rate was 11.11 (9 of 81 cycles) in the CCHH group and 10.75 (10 of 93 cycles) in the HHCC group. The difference was not statistically significant. The cycle fecundity rate was 14.44% (13 of 90 cycles) for cycles with CC and 7.14% (6 of 84) with hMG. The difference was not statistically significant. CONCLUSION(S): These data suggest that CC is an effective alternative to hMG in the population examined.
Ecochard R et al., 1999·International journal of andrology
We analysed 12,100 consecutive cycles of artificial insemination by donor spermatozoa in 1901 infertile couples. In our analysis, particular attention was given to finding an appropriate way of taking into account the respective effects of female and male factors on the pregnancy success rate and the level at which these factors act (cycle vs. woman and donation vs. donor). A total of 1213 pregnancies occurred. The pregnancy rate per cycle was lower as the age of the woman increased (p < 0.0001) and varied with the type of infertility: fecundity was higher (p = 0.03) in the case of azoospermia than of severe oligozoospermia. After taking into account these factors, significant unexplained variation in likelihood to conceive remained. A part of this heterogeneity was shown to be due to variation in fecundability between semen donors. In order to explain this heterogeneity between donors, compositional covariates were used, particularly the mean of results of the semen analysis performed for donations from the same donor. For each semen characteristic, the overall mean of the different donations of a donor was an important predictive factor of successful insemination: after taking into account all of the other factors, the odds ratios for an increase of 50 x 10(6)/mL spermatozoa, of a 20% increase in sperm motility and of a 2 point increase in the post-thaw quality index, were, respectively, 1.13, 1.37 and 1.56. After adjustment for these factors, the specific characteristics of each semen donation were no longer significantly predictive of successful insemination. This observation has a biological interpretation: sperm with low parameters but produced by a normally fertile man can have a satisfactory success rate.
Ecochard R et al., 1998·Contraception, fertilite, sexualite (1992)
The analysis concerned 626 users using NFP in order to avoid a conception during a total of 6740 cycles. Participation in the study did not interfere with their plan of conception, and they were invited to behave, as far as possible, as though they ignored the study. Of these 626 couples, 530 were french, 61 belgian and 35 swiss. On the whole, 39.3% used birth control to limit births and 60.7% to space them. The observed pregnancy rates are 1.13, 6.47 and 17.58 for one year in actuarial method respectively for method, method + user and total pregnancy rate. The pregnancy rate was higher for women before 35 years (RR: 3.8; 95 p100 confidence interval: 1.4-10.3), during the six months after delivery (RR: 2.5; 1.0-4.6) and, of course, for couples with inprotected sexual intercourse in fertile phase (RR: 4.8; 2.1-11.2). NFP can be placed among methods of great theorical effectiveness. But pregnancies as a result of intercourses during the fertile phase despite its identification are frequent: couples have to be informed.
Ecochard R, 1997·Open Research Online (The Open University)
The main aim of this dissertation is to explore methodological approaches to correlated binary data and to assess their suitability for the analysis of data on human fertility. The dataset concerns a study of Artificial Insemination by Donor (AID). AID represents an unusual research opportunity to study both male and female fecundability simultaneously. In each attempt to conceive, artificial insemination is carried out in consecutive ovulatory cycles until conception or change of treatment. The probability of conception may differ between women, so that the data are discrete time survival data with censoring and between-subject heterogeneity. There is also potential heterogeneity between donors. Non-systematic allocation of the donor to recipient ensures that the same woman receives semen from several donors, This added heterogeneity as well as other cycle dependent covariates have to be taken into account. The analysis must also take account of covariates, most of them time-varying. Our dataset have a crossed hierarchical structure due to the presence of both, female and male factors. The rather complicated "design" calls for unit specific regression models. These models are presented as well as their lack of tractability except in some rather specific cases. The motivation for choosing Gaussian random effects in unit specific regression models is discussed. We demonstrate the use of an approximate inference method (Penalized Quasi Likelihood). This method is shown to be a useful and practical way of carrying out preliminary data analysis. Finally a Bayesian procedure (Gibbs sampling) provides validation and more accurate results despite the intensive computation it needs. The main substantive finding of the analysis is the unexpectedly pronounced heterogeneity of donor fecundability, even after inclusion of conventional measures of sperm quality into the model. These measures were shown to be predictive at the donor level but not at the level of individual donation.
Outcomes and Effectiveness · Cumulative Versus Per Cycle Reporting
Mathieu C et al., 1995·Human reproduction (Oxford, England)
This paper presents the analysis of 901 cycles of intrauterine artificial insemination with the husband's spermatozoa (AIHIU) in 274 couples who obtained 80 pregnancies. The cumulative pregnancy rate after three cycles of AIHIU was 22% and reached 39% after six cycles. Univariate analysis disclosed two factors of poor prognosis: duration of infertility > 3 years (P = 0.01) and husband's age (P = 0.03). Multivariate analysis revealed that the most significant factor contributing to a decreased likelihood of pregnancy was the age of the husband (P = 0.01), then duration of infertility and dysovulation. The wife's age > or = 35 years did not appear to be of poor prognostic value when taking into consideration the three other factors.
Gallot-Lavallée P et al., 1995·Contraception, fertilite, sexualite (1992)
This meta-analysis compares different ovulation inductions before intrauterine insemination. Under hMG, the results seem to be better, but this has to be taken with caution as studies are seldom randomized.
The effect of aging on the number of non-growing follicles (NGF) and early-growing follicles (EGF) was studied in humans through use of a database obtained by pooling two subsets of ovarian pairs (2 x 43 pairs) collected in two distinct populations. A previously suggested model of exponential regression of NGF counts in relation to the subject's age was tested but did not adequately fit the observed data points. This lack of fit is attributable mainly to the existence of a significant relation between a woman's age and the corresponding NGF count decay rate. Consequently, various regression models were tested. Two different periods of decay rate were observed for each population of small follicles. The first corresponds to younger ages with a decay rate that is slow for both types of follicles, although faster for NGF than for EGF. The second period corresponds to older ages with an accelerated decay rate that appears similar for NGF and EGF. The changing points were found at 38.0 +/- 2.4 and 39.0 +/- 1.9 yr (mean +/- SD) for NGF and EGF, respectively. Extrapolation of the fitted model suggested the presence of approximately 402,000 healthy NGF per ovary at birth and a total exhaustion of the follicular stock at around 74 yr of age. These results support the view that depletion of the NGF pool is caused mainly by atresia in younger women but mainly by entrance of NGF into the growing pool in older women. The mechanisms triggering accelerated entrance into the growth phase of NGF are discussed in relation to the previously reported increase in FSH plasma levels that starts in the late thirties, approximately, and precedes the menopausal period by several years.
Frey R et al., 1989·Revue francaise de gynecologie et d'obstetrique
The authors have analyzed the characteristics of menstrual cycles during the post-partum without breastfeeding, according to the nature of the first period. 172 women gave the thermal curve from childbirth to the first period. Among them, 118, 111, 98 and 54 women gave the self-observation data concerning, respectively, the first, second, third and the fourth cycle after the first period. They have noticed more short luteal phases and delays in ovulation after an anovulatory first period than after an ovulatory first period. The hormonal studies in the post-partum without breastfeeding seem not to explain the whole of these anomalies ascertained beyond twelve post-partum weeks. Most authors admit that the gonadotropin axis returns to a normal state within the fifth post-partum week. Because of the peculiar kinetics of follicle development, the ovary could be an important component of the "remnant effect of gestation", that is to say, of the delay of return to post-partum ovulation following the gestation state.
Ecochard R et al., 1988·Revue francaise de gynecologie et d'obstetrique
Evaluation of self-observation signs noted during post-partum, enables to study the physiology of this period. The signs analyzed in this study are: discharge of vaginal secretions, temperature discrepancy and bleeding. The originality of the study lies in the comparison of successive post-partum periods: 2 to 6 post-partum periods were studied in 163 women; in addition, we studied 38 cases including breast feeding time details and children reactions. The authors described especially the retention effect of the pregnancy and the inhibiting effect of breast feeding on the return of the fertility, by progressively escaping these two effects, and the part of the woman's reaction.
Ecochard R et al., 1984·Contraception, fertilite, sexualite
24 women, of whom 2 each presented with primary and secondary infertility, were taught to observe their cervical mucus secretions outside the vulva. The correlation between the sensation, presence, and aspect of the mucus and the quantity of estrone and estradiol excreted in the urine were determined for each day of the cycle. The women were aged 24-39 years and had 0-7 children, with an average of 2.3. 2 women kept incomplete records and 2 had anovulatory cycles, leaving 20 in the sample. All 20 noted at least 1 day of fertile type mucus. 11 women noted 3 or fewer days which corresponded to the estrogenic peak. 4 of the women who noted more than 3 days of fertile type mucus identified 1-3 days of maximum wetness, bringing to 15 the number of favorable cases. In 4 cases the women observed fertile type mucus outside the estrogenic peak. In 14 cases the fertile type mucus was preceded by 1 or more days of thick mucus. It is hoped that this method will be of use in the treatment of infertility.