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Article ; Online: Evidence that the woman's ovarian cycle is driven by an internal circamonthly timing system.

Ecochard, René / Stanford, Joseph B / Fehring, Richard J / Schneider, Marie / Najmabadi, Shahpar / Gronfier, Claude

2024 Volume 10, Issue 15, Page(s) eadg9646

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Female ; Humans ; Menstrual Cycle
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adg9646
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Article ; Online: Clustering of trajectories with mixed effects classification model: Inference taking into account classification uncertainties.

Dugourd, Charlotte / Abichou-Klich, Amna / Ecochard, René / Subtil, Fabien

Statistics in medicine

2023 Volume 42, Issue 25, Page(s) 4570–4581

Abstract: Classifying patient biomarker trajectories into groups has become frequent in clinical research. Mixed effects classification models can be used to model the heterogeneity of longitudinal data. The estimated parameters of typical trajectories and the ... ...

Abstract	Classifying patient biomarker trajectories into groups has become frequent in clinical research. Mixed effects classification models can be used to model the heterogeneity of longitudinal data. The estimated parameters of typical trajectories and the partition can be provided by the classification version of the expectation maximization algorithm, named CEM. However, the variance of the parameter estimates obtained underestimates the true variance because classification uncertainties are not taken into account. This article takes into account these uncertainties by using the stochastic EM algorithm (SEM), a stochastic version of the CEM algorithm, after convergence of the CEM algorithm. The simulations showed correct coverage probabilities of the 95% confidence intervals (close to 95% except for scenarios with high bias in typical trajectories). The method was applied on a trial, called low-cyclo, that compared the effects of low vs standard cyclosporine A doses on creatinine levels after cardiac transplantation. It identified groups of patients for whom low-dose cyclosporine may be relevant, but with high uncertainty on the dose-effect estimate.
Language	English
Publishing date	2023-08-14
Publishing country	England
Document type	Journal Article
ZDB-ID	843037-8
ISSN	1097-0258 ; 0277-6715
ISSN (online)	1097-0258
ISSN	0277-6715
DOI	10.1002/sim.9876
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Zs.A 1756: Show issues

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Article ; Online: Trajectory clustering using mixed classification models.

Klich, Amna / Ecochard, René / Subtil, Fabien

Statistics in medicine

2021 Volume 40, Issue 15, Page(s) 3425–3439

Abstract: Trajectory classification has become frequent in clinical research to understand the heterogeneity of individual trajectories. The standard classification model for trajectories assumes no between-individual variance within groups. However, this ... ...

Abstract	Trajectory classification has become frequent in clinical research to understand the heterogeneity of individual trajectories. The standard classification model for trajectories assumes no between-individual variance within groups. However, this assumption is often not appropriate, which may overestimate the error variance of the model, leading to a biased classification. Hence, two extensions of the standard classification model were developed through a mixed model. The first one considers an equal between-individual variance across groups, and the second one considers unequal between-individual variance. Simulations were performed to evaluate the impact of these considerations on the classification. The simulation results showed that the first extended model gives a lower misclassification percentage (with differences up to 50%) than the standard one in case of presence of a true variance between individuals inside groups. The second model decreases the misclassification percentage compared with the first one (up to 11%) when the between-individual variance is unequal between groups. However, these two extensions require high number of repeated measurements to be adjusted correctly. Using human chorionic gonadotropin trajectories after curettage for hydatidiform mole, the standard classification model classified trajectories mainly according to their levels whereas the two extended models classified them according to their patterns, which provided more clinically relevant groups. In conclusion, for studies with a nonnegligible number of repeated measurements, the use, in first instance, of a classification model that considers equal between-individual variance across groups rather than a standard classification model, appears more appropriate. A model that considers unequal between-individual variance may find its place thereafter.
MeSH term(s)	Cluster Analysis ; Computer Simulation ; Female ; Humans ; Pregnancy
Language	English
Publishing date	2021-04-07
Publishing country	England
Document type	Journal Article
ZDB-ID	843037-8
ISSN	1097-0258 ; 0277-6715
ISSN (online)	1097-0258
ISSN	0277-6715
DOI	10.1002/sim.8975
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Article ; Online: Relationship Between Steroid Hormone Profile and Premenstrual Syndrome in Women Consulting for Infertility or Recurrent Miscarriage.

Turner, Joseph V / McLindon, Lucas A / Turner, Damien V / Alefsen, Yolaine / Ecochard, René

Reproductive sciences (Thousand Oaks, Calif.)

2023 Volume 31, Issue 3, Page(s) 736–745

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Female ; Humans ; Progesterone ; Cross-Sectional Studies ; Retrospective Studies ; Premenstrual Syndrome/diagnosis ; Luteal Phase ; Infertility ; Abortion, Habitual/diagnosis
Chemical Substances	Progesterone (4G7DS2Q64Y)
Language	English
Publishing date	2023-10-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2276411-2
ISSN	1933-7205 ; 1933-7191
ISSN (online)	1933-7205
ISSN	1933-7191
DOI	10.1007/s43032-023-01375-w
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Article ; Online: The menstrual cycle is influenced by weekly and lunar rhythms.

Ecochard, René / Leiva, Rene / Bouchard, Thomas P / Van Lamsweerde, Agathe / Pearson, Jack T / Stanford, Joseph B / Gronfier, Claude

Fertility and sterility

2024 Volume 121, Issue 4, Page(s) 651–659

Abstract: Objective: 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 ... ...

Abstract	Objective: 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). Design: Cross-sectional study. Subjects: A total of 35,940 European and North American women aged 18-40 years. Exposure: Data were collected in real-life conditions. Intervention: No intervention was performed. Main outcome measure: 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. Results: 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. Conclusion: 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.
MeSH term(s)	Female ; Humans ; Moon ; Cross-Sectional Studies ; Menstrual Cycle ; Menstruation ; Seasons ; Circadian Rhythm
Language	English
Publishing date	2024-01-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	80133-1
ISSN	1556-5653 ; 0015-0282
ISSN (online)	1556-5653
ISSN	0015-0282
DOI	10.1016/j.fertnstert.2023.12.009
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Zs.A 73: Show issues

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Article ; Online: Drug prescription goals in primary care: a cross-sectional study.

Bernard, Louis / Ecochard, René / Gueyffier, François / Letrilliart, Laurent

BMC health services research

2020 Volume 20, Issue 1, Page(s) 6

Abstract: Background: Care goals are often implicit, although their identification is a key element of any prescription process. This study aimed to describe the clinical goals of drug prescriptions in general practice, their determinants and the agreement ... ...

Abstract	Background: Care goals are often implicit, although their identification is a key element of any prescription process. This study aimed to describe the clinical goals of drug prescriptions in general practice, their determinants and the agreement between physicians and patients. Methods: This was a cross-sectional study conducted by 11 resident trainees acting as observers in 23 general practices. The residents recorded the indication and main physician's goal for all drugs prescribed during five consultation days in each practice in December 2015, and the main patient's goal for a sub-sample of consultations. We used an eight-category generic classification of prescription goals, including three specific (mortality, morbidity and cure), three non-specific (symptoms, quality of life, functioning) and two non-specified (other goal, no goal) categories. Analyses were based on a multivariable, multilevel model and on the kappa statistic applied to the sub-sample of consultations. Results: The sample encompassed 2141 consultations and 5036 drugs. The main physicians' goal of drug prescriptions was to relieve symptoms (43.3%). The other goals were to decrease the risk of morbidity (22.4%), to cure disease (11.7%), to improve quality of life (10.6%), to decrease the risk of mortality (8.5%) and to improve functioning (1.8%). The choice of a specific goal was more frequent in patients with the following characteristics: over 50 (OR [1.09;1.15]), of male gender (OR [1.09;1.39]), with full financial coverage for a long-term condition (OR [1.47;1.97]), known by the physician (OR [1.19;2.23]), or with a somatic health problem (OR [2.56;4.17]). Cohen's kappa for drug prescription goals between the patients and the physicians was 0.26 (0.23-0.30). Conclusions: Physicians' goals are poorly shared with patients. It remains to be assessed whether it is possible to collect and discuss information on prescription goals on a daily basis.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Drug Prescriptions ; Female ; France ; General Practice ; General Practitioners/psychology ; General Practitioners/statistics & numerical data ; Goals ; Humans ; Male ; Middle Aged ; Physician-Patient Relations ; Practice Patterns, Physicians' ; Primary Health Care ; Young Adult
Language	English
Publishing date	2020-01-02
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Observational Study
ISSN	1472-6963
ISSN (online)	1472-6963
DOI	10.1186/s12913-019-4870-y
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Article ; Online: Functional representation of the network organisation of dialysis activities in France: A novel level for assessing quality of care.

Couchoud, Cécile / Ecochard, René / Prezelin-Reydit, Mathilde / Lobbedez, Thierry / Bayer, Florian

PloS one

2022 Volume 17, Issue 10, Page(s) e0276068

Abstract: To assess quality of care, groups of care units that cared for the same patients at various stages of end-stage renal disease, might be more appropriate than the centre level. These groups constitute "communities" that need to be delineated to evaluate ... ...

Abstract	To assess quality of care, groups of care units that cared for the same patients at various stages of end-stage renal disease, might be more appropriate than the centre level. These groups constitute "communities" that need to be delineated to evaluate their practices and outcomes. In this article, we describe the use of an agglomerative (Fast Greedy) and a divisive (Edge Betweenness) method to describe dialysis activities in France. The validation was based on the opinion of the field actors at the regional level of the REIN registry. At the end of 2018, ESRD care in France took place in 1,166 dialysis units. During 2016-2018, 32 965 transfers occurred between dialysis units. With the Edge Betweenness method, the 1,114 French dialysis units in metropolitan France were classified into 156 networks and with the Fast Greedy algorithm, 167 networks. Among the 32 965 transfers, 23 168 (70%) were defined in the same cluster by the Edge Betweenness algorithm and 26 016 (79%) in the same cluster by the Fast Greedy method. According to the Fast Greedy method, during the study period, 95% of patients received treatment in only one network. According to the opinion of the actors in the field, the Fast Greedy algorithm seemed to be the best method in the context of dialysis activity modelling. The Edge Betweenness classification was not retained because it seemed too sensitive to the volume of links between dialysis units.
MeSH term(s)	Humans ; Renal Dialysis ; Kidney Failure, Chronic/therapy ; Registries ; Organizations ; France
Language	English
Publishing date	2022-10-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0276068
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Article ; Online: Distinct urinary progesterone metabolite profiles during the luteal phase.

Abdullah, Saman / Bouchard, Thomas / Leiva, René / Boehringer, Hans / Iwaz, Jean / Ecochard, René

Hormone molecular biology and clinical investigation

2022 Volume 44, Issue 2, Page(s) 137–144

Abstract: Objectives: 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.: Methods: Data stemmed from a previous ... ...

Abstract	Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.
MeSH term(s)	Female ; Humans ; Progesterone ; Luteal Phase ; Pregnanediol/urine ; Luteinizing Hormone ; Glucuronides ; Menstrual Cycle
Chemical Substances	Progesterone (4G7DS2Q64Y) ; Pregnanediol (JR3JD1Y22C) ; Luteinizing Hormone (9002-67-9) ; Glucuronides
Language	English
Publishing date	2022-12-30
Publishing country	Germany
Document type	Observational Study ; Journal Article
ZDB-ID	2536635-X
ISSN	1868-1891 ; 1868-1883
ISSN (online)	1868-1891
ISSN	1868-1883
DOI	10.1515/hmbci-2022-0065
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Article ; Online: Descriptive analysis of the relationship between progesterone and basal body temperature across the menstrual cycle.

Écochard, René / Leiva, René / Bouchard, Thomas / Boehringer, Hans / Iwaz, Jean / Plotton, Ingrid

Steroids

2022 Volume 178, Page(s) 108964

Abstract: Objective: Describe the relationship between basal body temperature (BBT) and pregnanediol-3 alpha-glucuronide (PDG, the urine metabolite of progesterone) across the menstrual cycle.: Design: Observational study.: Setting: Study carried out from ... ...

Abstract	Objective: Describe the relationship between basal body temperature (BBT) and pregnanediol-3 alpha-glucuronide (PDG, the urine metabolite of progesterone) across the menstrual cycle. Design: Observational study. Setting: 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. Result: (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. Conclusion: (s): PDG and BBT had parallel increases at low PDG rates but diverged at higher rates.
MeSH term(s)	Body Temperature ; Female ; Humans ; Menstrual Cycle/urine ; Ovulation ; Pregnanediol/urine ; Progesterone
Chemical Substances	Progesterone (4G7DS2Q64Y) ; Pregnanediol (JR3JD1Y22C)
Language	English
Publishing date	2022-01-20
Publishing country	United States
Document type	Journal Article ; Observational Study
ZDB-ID	80312-1
ISSN	1878-5867 ; 0039-128X
ISSN (online)	1878-5867
ISSN	0039-128X
DOI	10.1016/j.steroids.2022.108964
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Article ; Online: Diversity of the quality of data collection in a registry: proposal of an analysis approach and application to the REIN register

Couchoud, Cécile / Duthe, Fabien / Boyer, Sylvie / Mercadal, Lucile / Lassalle, Mathilde / Riche, Benjamin / Rabilloud, Muriel / Ecochard, René

Nephrologie & therapeutique

2023 Volume 19, Issue 3, Page(s) 155–170

Abstract: Missing data may lead to bias and loss of information in epidemiological research. In this article, we propose an approach to analyze missing data on comorbidity variables in a register with consideration of the territorialized organization of the ... ...

Title translation	Diversité de la qualité de recueil des données dans un registre : proposition d’une démarche d’analyse et application au registre REIN
Abstract	Missing data may lead to bias and loss of information in epidemiological research. In this article, we propose an approach to analyze missing data on comorbidity variables in a register with consideration of the territorialized organization of the collection. To illustrate this approach, we used the national REIN registry as an application case.
MeSH term(s)	Humans ; Data Collection ; Registries ; Comorbidity ; Bias
Language	French
Publishing date	2023-04-04
Publishing country	France
Document type	Journal Article
ZDB-ID	2229575-6
ISSN	1872-9177 ; 1769-7255
ISSN (online)	1872-9177
ISSN	1769-7255
DOI	10.1684/ndt.2023.16
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