Modeling Fertile Window Differences Across the Reproductive Lifespan with Quantitative Urine Hormone Monitoring of the Menstrual Cycle

Maria Meyers

Western Health Center, Midfield, AL, USA

Abstract: 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.


O-014 Unraveling the interplay of gut microbiota, metabolic alterations, and endometrial senescence in polycystic ovary syndrome and its implications for adverse pregnancy outcomes

Abstract:
Abstract

Study question
What gut microbiota and metabolic alterations are associated with Polycystic ovary syndrome (PCOS) and linked to adverse pregnancy outcomes (APOs)?

Summary answer
In PCOS, P. merdae decreases, BCAAs increase, raising the risk of APOs. Meanwhile, endometrial senescence and decidualization impairment are found, worsening with higher Ile concentration.

What is known already
PCOS, a prevalent and complex endocrine disorder, stands as the primary cause of anovulatory infertility. The rising prevalence of PCOS in China over the past decade has led to a substantial increase in disease burden. Our previous ten-year retrospective analysis revealed that PCOS patients undergoing their first fresh embryo transfer faced a heightened risk of APOs, such as miscarriage. However, the factors influencing disease progression and future obstetric outcomes in PCOS remain elusive.

Study design, size, duration
This prospective cohort study encompassed a diverse cohort of 220 women (110 with PCOS and 110 controls) from 44 cities across China, with a median follow-up duration of 16.6 months.

Participants/materials, setting, methods
Women aged < 35 years with PCOS (Rotterdam criteria) and age-/BMI-matched controls were recruited. Fecal microbiomes were analyzed using 16S rRNA sequencing and metagenomics, while serum metabolites were assessed through both untargeted and targeted metabolomics. Endometrial stromal cell senescence was evaluated based on a constellation of markers, including cell proliferation, senescence-associated secretory phenotype factors, cell cycle, ROS levels, and SA-β-Gal activity. Endometrial decidualization was gauged by measuring prolactin and IGFBP-1 levels using ELISA.

Main results and the role of chance
Our study revealed significant gut microbiota alterations, including reduced α-diversity and a notable decline in Parabacteroides merdae (P. merdae), a key species differentiating PCOS from controls. Serum metabolomics identified 45 differential metabolites, with branched-chain amino acids (BCAAs), especially isoleucine (Ile), exhibiting strong diagnostic potential. Targeted metabolomics further validated BCAAs’ (Valine, Leucine, and Ile) upregulation and short-chain fatty acids’ downregulation in PCOS.
During follow - up, PCOS patients had a higher cumulative incidence of APOs despite similar pregnancy rates. And the adjustment for potential confounders did not substantially change the estimates. Intriguingly, individuals who experienced APOs showed a reduction in gut P. merdae levels and an elevation in serum BCAAs, suggesting their potential association with APOs occurrence.
Further analysis revealed increased Ile levels in the endometrial tissue of PCOS (P < 0.05) and higher proportions of cells positive for senescence markers (P21, P16, IL6, and IL1β), indicating aggravated cellular senescence, particularly in endometrial stromal cells (ESCs). ESCs from PCOS patients displayed classical senescence features, including proliferation loss, increased SA-β-Gal activity, cell cycle arrest, and elevated ROS levels. The accumulation of senescent ESCs in PCOS endometrium ultimately resulted in a disrupted decidualization process, which was exacerbated by increasing concentrations of Ile supplementation.

Limitations, reasons for caution
However, we must acknowledge certain limitations of this study. While our study makes a significant contribution to existing scientific knowledge, it is crucial to validate these findings in diverse populations. In addition, clinical translatability of biomarkers needs further exploration.

Wider implications of the findings
This study highlights gut microbiota-metabolite crosstalk as a novel axis influencing reproductive health in PCOS. Moreover, the identification of P. merdae and BCAAs as potential biomarkers for PCOS patients and the associated APOs risk opens up new avenues for risk stratification and personalized interventions.

Trial registration number
No


Participation of general practitioners and therapeutic patient education in the care of infertile couples

Abstract: BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

European Journal of Obstetrics & Gynecology and Reproductive Biology


Correction to "Time to Diagnose Endometriosis: Current Status, Challenges and Regional Characteristics-A Systematic Literature Review"

BJOG : an international journal of obstetrics and gynaecology


Per- and Polyfluoroalkyl Substances in Eutopic Endometrium Tissue and Risk of Endometriosis: Findings from the Investigating Mixtures of Pollutants and Endometriosis in Tissue (IMPLANT) Study

Leslie V Farland

Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona; Department of Obstetrics and Gynecology, College of Medicine -...

Abstract:
Background: Perand polyfluoroalkyl substances (PFAS) exposure is widespread and has been linked with gynecologic disease. To our knowledge, no study has measured PFAS in endometrial tissue.

Methods: Eutopic endometrial tissue specimens (n=434) were collected from Investigating Mixtures of Pollutants and Endometriosis in Tissue (IMPLANT) study participants undergoing laparoscopy or laparotomy for any indication (2007-2009). Nine PFAS were measured by high-performance liquid chromatography-tandem mass spectrometry [perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorododecanoic acid (PFDoDA), perfluoroheptanoic acid (PFHpA), perfluorooctanesulfonamide (PFOSA), and perfluoroundecanoic acid (PFUnDA)]. Surgeons diagnosed endometriosis by gold-standard visualization and evaluated the endometriosis staging as moderate and severe (stages 3 and 4) compared to minimal and mild (stages 1 and 2) using American Society of Reproductive Medicine (ASRM) classification. We used modified Poisson regression models adjusted for age (continuous), race (white, all other race/ethnicities), smoking status (serum cotinine >10 ng/mL), study site (Utah, California), and body mass index (continuous) to obtain relative risks (RR) of endometriosis diagnosis and 95% confidence intervals (CIs) for each PFAS. PFAS mixtures were evaluated using Bayesian kernel machine regression.

Results: Participants were, on average, 33±7 years old, and 75% of participants were non-Hispanic white. Of the 181 participants with an incident endometriosis diagnosis, 73% had ASRM stage 1 or 2, while 27% had stage 3 or 4. Median [interquartile range (IQR)] eutopic endometrium tissue levels, in nanograms per gram, were 6.58 (6.44) for PFOS, 1.93 (1.71) for PFOA, 0.65 (0.75) for PFHxS, 0.58 (0.52) for PFNA, and 0.12 (0.18) for PFOSA. PFAS in the endometrial tissue was not associated with endometriosis. However, select PFAS in the eutopic tissue were associated with a risk of more advanced (stage 3 or 4 vs. 1 or 2) endometriosis [PFOSA RR=1.25 (95% CI: 1.10, 1.43), PFHxS RR=1.37 (95% CI: 1.12, 1.68), PFOS RR=1.36 (95% CI: 1.02, 1.81)].

Conclusion: PFAS were widely detected in eutopic endometrial tissue. There was no evidence that PFAS in endometrial tissue were associated with a higher risk of endometriosis diagnosis. However, PFOS, PFOSA, and PFHxS in the endometrial tissue were associated with risk of more severe stage of endometriosis. https://doi.org/10.1289/EHP15852.


Fertility Treatment 2023: Trends and Figures

Human Fertilisation and Embryology Authority

Abstract:
# Fertility treatment 2023: trends and figures
Preliminary UK statistics for IVF and DI treatment, storage, and donation
Published: June 2025
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[Download the underlying dataset as Excel Worksheet](https://www.hfea.gov.uk/media/3qip3kon/fertility-treatment-2023-trends-and-figures-underlying-dataset.xlsx "Download the underlying dataset for the ‘Fertility treatment 2023: trends and figures’ report")
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2023-trends-and-figures/#main-points)
- [Note on preliminary data](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2023-trends-and-figures/#note-on-preliminary-data)
- [Section 1: More babies born from IVF in the UK](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2023-trends-and-figures/#section-1)
- [Section 2: IVF pregnancy and birth rates using fresh embryo transfers increased over the years, though lower for Black patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2023-trends-and-figures/#section-2)
- [Section 3: Average pregnancy and birth rates using frozen embryo transfers increased in 2023](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2023-trends-and-figures/#section-3)
- [Section 4: Multiple births rate from IVF is one of the lowest in the world](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2023-trends-and-figures/#section-4)
- [Section 5: Most treatment types have increased across the UK since 2019](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertili...


The Menstrual Cycle as a Vital Sign: a comprehensive review

Shruthi Mahalingaiah

Department of Obstetrics & Gynecology, Boston University Medical Center, Boston, MA.

Anne Marie Z. Jukic

National Institute of Environmental Health Sciences

Abstract: Some medical professional organizations have advocated for including the menstrual cycle as a vital sign in adolescence, but not in adulthood. However, documenting menstrual cycle patterns is not routine clinical or research practice. Vital signs are used to predict health outcomes, indicate needed treatment, and monitor a clinical course. They can help identify pathologies, affirm wellness, and are responsive to exposures. Here we review the scientific evidence showing how the menstrual cycle meets these criteria and should therefore be treated as a vital sign. Using key words and controlled vocabulary terms, we carried out multiple literature searches, prioritizing the inclusion of systematic reviews, meta-analyses, and clinical practice guidelines. This review describes how the menstrual cycle is a health indicator, can cyclically impact health conditions, and its associations with long-term post-menopausal health outcomes. We review exposures influencing the menstrual cycle, evidence underlying its use to optimize wellness, and available tools for documenting cycles. Supplementary materials include patient handouts on menstrual cycle tracking, and an index of related clinical practice guidelines and reviews by subject. The menstrual cycle is a vital sign from menarche through menopause, an underutilized but powerful tool for understanding gynecological and general health.


Prenatal ambient air pollution associations with DNA methylation in asthma- and allergy-relevant genes: findings from ECHO

Palmore M, Thompson EE, Fang F, Bastain TM, Breton C, Collingwood S, Gilliland FD, Gold DR, Habre R, Hartert T, Khurana Hershey GK, Jackson DJ, Miller R, Ryan P, Shorey-Kendrick L, Spindel ER, Stanford J, Gern J, McKennan C, Ober C, Ladd-Acosta C

Abstract: Prenatal exposure to air pollution is an important risk factor for child health outcomes, including asthma. Identification of DNA methylation changes associated with air pollutant exposure can provide new intervention targets to improve children's health. The aim of this study is to test the association between prenatal air pollutant exposure and DNA methylation in developmental and asthma-/allergy-relevant biospecimens (placenta, buccal, cord blood, nasal mucosa, and lavage). A subset of 2294 biospecimens collected from 1906 child participants enrolled in the Environmental Influences on Child Health Outcomes program with prenatal air pollutant and high-quality Illumina Asthma&Allergy DNA methylation array measures (n = 37 197 probes) were included. Prenatal ozone, nitrogen dioxide, and fine particulate matter were derived using residential history during pregnancy and spatiotemporal models. For each pollutant, biospecimen type, and prenatal exposure window, we estimated the effects of air pollution on gene DNA methylation levels. We compared results across pollutants, biospecimen types, and trimesters and tested for critical months of exposure using distributed lag models. DNA methylation levels at 154 out of 4746 tested genes were associated with air pollution; over 95% were exposure window, pollutant, and biospecimen-type specific. The fewest gene associations were detected in trimester 2, relative to other exposure windows. A variety of trends in methylation patterns were observed in response to lagged monthly pollution levels. Child DNA methylation changes at specific respiratoryand immune-relevant genes are associated with prenatal air pollutant exposures. Future studies should examine the relationship between these pollution-sensitive genes and child health.


Early-Life Factors and Body Mass Index Trajectories Among Children in the ECHO Cohort

Liu C, Chow SM, Aris IM, Dabelea D, Neiderhiser JM, Leve LD, Blair C, Catellier DJ, Couzens L, Braun JM, Ferrara A, Aschner JL, Deoni SCL, Dunlop AL, Gern JE, Rivera-Spoljaric K, Hartert TV, Hershey GKK, Karagas MR, Kennedy EM, Karr CJ, Barrett ES, Zhao Q, Lester BM, Check JF, Helderman JB, O'Connor TG, Rasmussen JM, Stanford JB, Mihalopoulos NL, Wright RJ, Wright RO, Carroll KN, McEvoy CT, Breton CV, Trasande L, Weiss ST, Elliott AJ, Hockett CW, Ganiban JM, Environmental influences on Child Health Outcomes (ECHO)

Abstract:
Importance: Identifying atypical body mass index (BMI) trajectories in children and understanding associated, modifiable early-life factors may help prevent childhood obesity.

Objective: To characterize multiphase BMI trajectories in children and identify associated modifiable early-life factors.Design, Setting, and ParticipantsThis cohort study included longitudinal data obtained from January 1997 to June 2024, from the Environmental influences on Child Health Outcomes (ECHO) cohort, which included children aged 1 to 9 years with 4 or more weight and height assessments. Analyses were conducted from January to June 2024.

Exposure: sPrenatal exposure to substances and stress (smoking, alcohol, depression, anxiety), maternal characteristics (prepregnancy BMI, gestational weight gain), child characteristics (preterm birth, birth weight, breastfeeding), and demographic covariates.Main Outcomes and MeasuresBMI (calculated as weight in kilograms divided by length in meters squared for children aged 1 and 2 years and as weight in kilograms divided by height in meters squared for children older than 2 years) obtained using medical records, staff measurements, caregiver reports, or remote study measures. The analysis was conducted using a multiphase latent growth mixture model.

Results: This study included 9483 children (4925 boys [51.9%]). Two distinct 2-phase BMI patterns were identified: typical and atypical. The typical group (n = 8477 [89.4%]) showed linear decreases in BMI (b2, −0.23 [95% CI, −0.24 to −0.22]), with the lowest BMI at age 6 years (95% CI, 5.94-6.11), followed by linear increases from 6 to 9 years (slope difference [b4 − b2], 0.81 [95% CI, 0.76-0.86]; mean BMI at 9 years: 17.33). The atypical group (n = 1006 [10.6%]) showed a stable BMI from ages 1 to 3.5 years (b6, 0.06 [95% CI, −0.04 to 0.15]), followed by rapid linear increases from ages 3.5 to 9 years (slope difference [b8 − b6], 1.44 [95% CI, 1.34-1.55]). At age 9 years, this group reached a mean BMI (26.2) that exceeded the 99th percentile. Prenatal smoking, high prepregnancy BMI, high gestational weight gain, and high birth weight were key risk factors for the atypical trajectory.

Conclusions and RelevanceIn this cohort study of children in the ECHO cohort, analyses identified children on the path to obesity as early as age 3.5 years. Modifiable factors could be targeted for early prevention and intervention programs aimed at reducing childhood obesity.


Exploring the link between periodontal disease and sperm quality: a comprehensive systematic review study

Abstract: Background: Periodontal diseases are among the most prevalent oral health conditions globally, with evidence suggesting their systemic effects, including potential impacts on male reproductive health. Inflammation associated with periodontitis might interfere with spermatogenesis and alter sperm parameters such as count, motility, morphology, and DNA integrity. This systematic review aims to critically assess existing studies on the relationship between periodontal disease and sperm quality to delineate its clinical implications for male infertility. Methods: The research was registered in the International Prospective Register of Systematic Reviews (PROSPERO) at the National Institute for Health Research (PROSPERO code: CRD420251005800). A comprehensive literature search was conducted across multiple databases, including PubMed, EMBASE, ProQuest, Scopus, Web of Science (WOS), and Google Scholar, up to September 2024. Inclusion criteria targeted human studies reporting associations between periodontal health and sperm quality parameters. To assess the quality of the included studies, the Newcastle-Ottawa Scale (NOS) was used. Data were synthesized qualitatively and analyzed for trends. Results: Nine studies encompassing 1,386 participants were included. Evidence suggests a significant association between periodontitis and decreased sperm motility, abnormal morphology, and increased DNA fragmentation. However, findings on sperm count and concentration were inconsistent. Mechanistic pathways suggest that inflammatory cytokines and oxidative stress contribute to these disruptions. Conclusion: This review highlights the systemic implications of periodontal disease on male reproductive health. Given the global decline in male fertility, maintaining oral health may serve as an adjunct strategy in managing infertility. Future research should prioritize large-scale, longitudinal studies to establish causality and explore preventive interventions.


Ovulatory and anovulatory cycle phase influences on QT interval dynamics during the menstrual cycle

Sonia Shirin

University of British Columbia, Vancouver, BC, Canada

Christopher Cheung

Heart Rhythm Services, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract:
Background: Ovarian hormones affect cardiovascular health yet few sufficient-sized studies with reliable ovulatory documentation have assessed the QTc-hormonal relationship. This study investigated QTc changes across ovulatory and anovulatory menstrual cycle phases.

Methods: This prospective cohort investigation, a cardiac sub-study of the Menstruation and Ovulation Study 2 (MOS2), involved 62 healthy, regularly menstruating community-dwelling women during spontaneous menstrual cycles. Electrocardiographic recordings were obtained within-woman during different cycle phases: mid-follicular for all, and luteal (ovulatory) or premenstrual (anovulatory), documented by the validated Quantitative Basal Temperature© method. Fridericia's formula rate-corrected the QT interval (QTc). A subsequent meta-analysis was conducted, pooling data from three additional studies to evaluate ovulatory follicular-luteal phase QTc changes.

Results: In the 26 ovulatory cycles, QTc minimally decreased from the mid-follicular to the luteal phases (383.0 ± 12.8 vs 382.6 ± 12.8 msec, P = .859). QTc in the 36 anovulatory cycles tended to increase from mid-follicular to premenstrual phases (381.7 ± 13.1 vs 385.0 ± 16.1 msec, P = .166). The meta-analysis in ovulatory cycles yielded a random-effects weighted mean QTc shortening of 1.67 msec (P = .53) in the luteal vs the follicular phase, aligning with our cohort data.

Conclusion: In confirmed ovulatory cycles, QTc changes were minimal, showing no meaningful luteal phase QTc shortening. QTc changes in anovulatory cycles were also insignificant, with a small QTc prolongation likely due to longer estradiol exposure not counterbalanced by progesterone. Under normal physiological conditions, QTc changes during the menstrual cycle are trivial, and menstrual status does not need to be considered when interpreting the QT interval.


Breast tenderness and swelling experiences related to menstrual cycles and ovulation in healthy premenopausal women: Secondary analysis of the 1-year "Prospective Ovulation Cohort"

Abstract: Breast tenderness and swelling are associated with premenstrual symptoms but are not well described in healthy women. In this 1-year prospective observational study, we examined daily breast tenderness and swelling to determine whether differences existed between normally ovulatory and ovulatory disturbed (short luteal phase and anovulatory) cycles in a cohort of community dwelling, non-smoking, healthy premenopausal women. Enrolment required two consecutive normal-length and normally ovulatory cycles by Quantitative Basal Temperature© analysis. Women (n = 53) ages 20-41 recorded their daily breast experiences in the Menstrual Cycle Diary© across an average of 13.6 cycles. In all 720 cycles, the median breast tenderness was 1.4 (on a 0-4 scale, range 0.0-3.0), in cycles with a mean length of 28.1 days (95% CI 27.5-28.8). Comparison of breast tenderness and breast size (changes from usual) parameters between all normally ovulatory cycles and all ovulatory disturbed cycles in the whole cohort showed significantly higher levels in normally ovulatory (luteal length ≥10 days) in both Breast Tenderness Score [intensity X duration in days; 6.0 (range 1.0-14.0) vs. 3.0 (0.0-11.0) (P=.005)] and breast size [4.0 (2.0-4.0) vs. 4.0 (0.0-4.0) (P=.034]). However, within-woman in the forty-seven women with both normally ovulatory and ovulatory disturbed cycles, breast tenderness (intensity, duration, and Breast Tenderness Score), did not differ between normally ovulatory cycles and cycles with ovulatory disturbances. This study also demonstrated that in all ovulatory cycles, the timing of breast tenderness increased in parallel with breast swelling; the maximum for both was in the late luteal phase.


Risk of endometriosis progression in infertile women trying to conceive naturally or using IVF

Edgardo Somigliana

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Abstract: The use of hormonal treatments for endometriosis has increased in recent years. Their effectiveness lies in creating a stable hormonal environment, reducing peripheral estrogen levels, and suppressing ovulation and menstruation. Although these agents do not cure endometriosis and symptoms often return after discontinuation, they effectively relieve pain in most cases and help prevent disease progression or recurrence. Women are therefore typically managed with long-term hormonal treatments, with or without surgery. However, this approach is unsuitable for those seeking natural pregnancy or undergoing IVF, as all hormonal treatments hinder conception. For women pursuing natural pregnancy, these treatments should be discontinued for about 1 year, the time needed to diagnose infertility. However, this suspension exposes women to the risk of recurrence or progression and is therefore clinically acceptable only if the woman has a reasonable likelihood of achieving pregnancy naturally. In women with endometriosis who are infertile and therefore require IVF, ovarian stimulation significantly raises estrogen levels-up to 10 times those of a natural cycle-potentially boosting the risk of endometriosis relapse. Evidence is reassuring on this issue even if some limited data suggest that ovarian stimulation may promote deep invasive endometriosis progression. Overall, physicians and patients must balance the chances of natural or ART-assisted pregnancy against the risk of disease recurrence or progression during treatment discontinuation or IVF. This choice is also complicated by the increased risk of severe pregnancy complications in women with endometriosis, possibly depending on the conception method. This review discusses the available evidence that can be helpful in guiding the decision-making process.


Characterisation and comparison of semen microbiota and bacterial load in men with infertility, recurrent miscarriage, or proven fertility

Phil Bennett

Tommy's National Centre for Miscarriage Research, Imperial College London, South Kensington, London, United Kingdom.

Abstract: Several studies have associated seminal microbiota abnormalities with male infertility but have yielded differing results owing to their limited sizes or depths of analyses. The semen microbiota during recurrent pregnancy loss (RPL) has not been investigated. Comprehensively assessing the seminal microbiota in men with reproductive disorders could elucidate its potential role in clinical management. We used semen analysis, terminal-deoxynucleotidyl-transferase-mediated-deoxyuridine-triphosphate-nick-end-labelling, Comet DNA fragmentation, luminol reactive oxidative species (ROS) chemiluminescence, and metataxonomic profiling of semen microbiota by 16S rRNA amplicon sequencing in this prospective, cross-sectional study to investigate composition and bacterial load of seminal bacterial genera and species, semen parameters, ROS, and sperm DNA fragmentation in men with reproductive disorders and proven fathers. 223 men were enrolled, including healthy men with proven paternity (n=63), the male partners in a couple encountering RPL (n=46), men with male factor infertility (n=58), and the male partners of couples with unexplained infertility (n=56). Rates of high sperm DNA fragmentation, elevated ROS, and oligospermia were more prevalent in the study group compared with control. In all groups, semen microbiota clustered into three major genera-dominant groups (1, Streptococcus; 2, Prevotella; 3, Lactobacillus and Gardnerella); no species clusters were identified. Group 2 had the highest microbial richness (p<0.001), alpha-diversity (p<0.001), and bacterial load (p<0.0001). Overall bacterial composition or load has not been found to associate with semen analysis, ROS, or DNA fragmentation. Whilst global perturbation of the seminal microbiota is not associated with male reproductive disorders, men with unidentified seminal Flavobacterium are more likely to have abnormal seminal analysis. Future studies may elucidate if Flavobacterium reduction has therapeutic potential.


Experiences of Care and Gaslighting in Patients With Vulvovaginal Disorders

Abstract:
Importance: Medical gaslighting, in which a patient's concerns are dismissed without proper evaluation, has been described anecdotally in vulvovaginal patient care, but has not been quantified.

Objective: To use a patient-centered instrument to measure adverse experiences in vulvovaginal care. DESIGN, SETTING, AND

Participants: Common themes from National Vulvodynia Association patient testimonials were used to design a mixed-methods measure of patient experience that included both quantitative and qualitative questions. An instrument was created and submitted to officers from the National Vulvodynia Association and Tight-Lipped, another patient advocacy organization, for feedback. The measure was then completed by patients before their first appointment at a vulvovaginal disorder referral clinic from August 2023 to February 2024.

Exposure: Participation in the survey.

Main Outcomes and Measures: The primary outcome was the incidence of reported clinician behavior and consequent distress as reported on the survey instrument. Quantitative data were analyzed using simple descriptive statistics (mean [SD], median [IQR], and percentage). Narrative responses provided by patients were analyzed using the clinical-qualitative method for content analysis.

Results: A total of 520 patients completed surveys; 5 were eliminated because the patient was younger than 18 years, 6 were eliminated for duplication, 6 were eliminated because they had no past clinician, and 56 were eliminated for completely blank responses. Thus, surveys of 447 patients (mean [SD] age, 41.7 [15.2] years) were analyzed (86% response rate). Patients had a mean (SD) of 5.50 (4.53) past clinicians. Patients reported that a mean (SD) of 43.5% (33.9%) of past practitioners were supportive, 26.6% (31.7%) were belittling, and 20.5% (30.9%) did not believe the patient. In total, 186 patients (41.6%) were told they just needed to relax more, 92 (20.6%) were recommended to drink alcohol, 236 (52.8%) considered ceasing care because their concerns were not addressed, 92 (20.6%) were referred to psychiatry without medical treatment, 72 (16.8%) felt unsafe during a medical encounter, and 176 (39.4%) said they were made to feel crazy, the most distressing surveyed behavior (rated at a mean [SD] of 7.39 [3.06] of 10 on a numerical rating scale of distress). A total of 1150 quotations were analyzed qualitatively; common themes included lack of clinician knowledge (247 quotations) and dismissive behaviors (211 quotations).

Conclusions and Relevance: In this cross-sectional study, a patient-centered measure of adverse experiences in vulvovaginal care was developed. Participants reported common past experiences with gaslighting and substantial distress; they frequently considered ceasing care. There is an urgent need for education supporting a biopsychosocial, trauma-informed approach to vulvovaginal pain and continued development of validated instruments to quantify patient experiences.


Impact of mRNA and Inactivated COVID-19 Vaccines on Ovarian Reserve

Esra Balcioglu

Department of Histology and Embryology, Faculty of Medicine, Erciyes University, 38030 Kayseri, Turkey

Busra Karaca

Hakan Cetinsaya Good Clinical Practice and Research Center, 38030 Kayseri, Turkey.

Hande Doganay

Obsterics annd Gynecology Clinic, Nigde Omer Halisdemir University Training and Research Hospital, 51100 Nigde, Turkey

Orhan Yildiz

Deparment of Clinical Microbiology and Infectious Disease, Faculty of Medicine, Erciyes University, 38030 Kayseri, Turkey

Erol Karakas

Op. Dr. Erol Karakas Gynecology-Obstetrics-Genital Aesthetics and Sexual Health Clinic, 38140 Kayseri, Turkey

Abstract:
Objectives: This study aimed to elucidate the effects of messenger RNA (mRNA) and inactivated coronavirus disease 2019 (COVID-19) vaccines on ovarian histology and reserve in rats.

Methods: Thirty female Wistar albino rats, aged 16-24 weeks, were randomly divided into three groups (n = 10): control, mRNA vaccine, and inactivated vaccine groups. Each vaccine group received two doses (on day 0 and day 28) at human-equivalent doses. Four weeks post-second vaccination, ovarian tissues were harvested for analysis.

Results: Immunohistochemical analysis was performed to evaluate the expression of transforming growth factor beta-1 (TGF-β1), vascular endothelial growth factor (VEGF), caspase-3, and anti-Müllerian hormone (AMH) in ovarian follicles. Both vaccines induced significant increases in TGF-β1, VEGF, and caspase-3 expression, with more pronounced effects in the mRNA vaccine group. Conversely, AMH expression in the granulosa cells of primary, secondary, and antral follicles showed marked reductions (p < 0.001). The counts of primordial, primary, and secondary follicles decreased significantly in the inactivated vaccine group relative to controls and further in the mRNA vaccine group compared to the inactivated group (p < 0.001). Additionally, the mRNA vaccine group exhibited a decrease in antral and preovulatory follicles and an increase in atretic follicles compared to the other groups (p < 0.05). The serum AMH level was diminished with the mRNA vaccination in comparison with the control and inactivated groups.

Conclusions: Our findings suggest that both mRNA and inactivated COVID-19 vaccines may detrimentally impact ovarian reserve in rats, primarily through accelerated follicular loss and alterations in apoptotic pathways during folliculogenesis. Given these observations in a rat model, further investigations into the vaccines' effects on human ovarian reserve are needed.


Dietary patterns and age at menarche in a prospective study of girls in the USA

K Cushing-Haugen

Public Health Sciences Division, Fred Hutchinson Cancer Center , Seattle, WA,

Abstract:
STUDY Question: Are dietary patterns associated with age at menarche after accounting for BMI-for-age (BMIz) and height?

SUMMARY ANSWER: We observed associations between both the Alternative Healthy Eating Index (AHEI) and the Empirical Dietary Inflammatory Pattern (EDIP) and age at menarche.

WHAT IS KNOWN ALREADY: Dietary patterns have been sparsely examined in relation to age at menarche and no studies have examined the association between the AHEI, a healthier diet, and EDIP, a pro-inflammatory diet, and menarche.

STUDY DESIGN, SIZE, DURATION: The Growing Up Today Study (GUTS) is a prospective cohort of children ages 9-14 years at study enrollment. GUTS enrolled in two waves with enrollment beginning in 1996 (GUTS1) and 2004 (GUTS2). For this analysis, GUTS1 and GUTS2 participants were followed through 2001 and 2008, respectively.

PARTICIPANTS/MATERIALS, SETTING, Methods: We included 7530 participants who completed food frequency questionnaire(s) (FFQ) prior to menarche who then self-reported age at menarche during study follow-up. Cox proportional hazard models were used to calculate multivariable hazard ratios (HRs) and 95% CIs for the associations between two dietary patterns, the AHEI and EDIP, and age at menarche, with and without adjustment for time-varying BMIz and height.

MAIN RESULTS AND THE ROLE OF CHANCE: Six thousand nine hundred ninety-two participants (93%) reported menarche during the study period. On average, participants completed the baseline FFQ 1.75 years prior to menarche. Participants in the highest quintile of AHEI diet score (indicating a healthier diet) were 8% less likely to attain menarche within the next month compared to those in the lowest quintile (95% CI = 0.85-0.99; Ptrend = 0.03). This association remained after adjustment for BMIz and height (corresponding HR = 0.93; 95% CI = 0.86-1.00; Ptrend = 0.04). Participants in the highest quintile of the EDIP score (i.e. most inflammatory diet), were 15% more likely to attain menarche in the next month relative to those in the lowest quintile (95% CI = 1.06-1.25; Ptrend = 0.0004), and the association remained following adjustment for BMIz and height (corresponding HR = 1.15; 95% CI = 1.06-1.25; Ptrend = 0.0004).

LIMITATIONS, REASONS FOR CAUTION: Self-reported questionnaires are subject to some error; however, given our prospective study design it is likely this error is non-differential with respect to the outcome.

WIDER IMPLICATIONS OF THE Findings: Our findings of an association between both the AHEI and EDIP and age at menarche indicate that diet quality may play a role in age at menarche independent of BMI or height. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Breast Cancer Research Foundation. The GUTS is supported by the National Institutes of Health U01 HL145386. C.P.D. was supported by National Institutes of Health T32 CA094880. The authors have no conflicts of interest to disclose.

TRIAL REGISTRATION NUMBER: N/A.


Menstrual Cycle Heat Maps: Visualising menstrual cycle variability using hormone heat map arrays referenced to the ultrasound day of ovulation

Abstract:
Objective: 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.
Design: Using pre-existing datasets, two cohorts of women were analysed using a statistical method to visualise quantitative hormonal variation.

Subjects: 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.
Outcome measure: The main outcome measure was identifying hormonal variability using hormone array heat maps.

Conclusion: 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.

Journal of Restorative Reproductive Medicine


The association between preconception polycystic ovary syndrome and gestational diabetes mellitus among women with and without pre-pregnancy hypertension: a cross-sectional study from Utah's Pregnancy Risk Assessment Monitoring System Survey (2016-2021)

Abstract:
Objectives: The objective of this study is to test the association between preconception polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) using Utah's Pregnancy Risk Assessment Monitoring System (2016-2021). In addition, pre-pregnancy hypertension will be tested as a potential effect moderator.

Methods: This cross-sectional study utilizes data from Phase 8 of the Utah Pregnancy Risk Assessment Monitoring System (PRAMS) survey (2016-2021). The association between PCOS and GDM was tested using Poisson regression to generate adjusted prevalence ratios and 95% confidence intervals.

Results: PCOS was associated with higher prevalence of GDM in all models, regardless of whether the outcome data (GDM) came from the infant's birth certificate, the PRAMS survey, or the combined measure. When adjusting for sociodemographic characteristics, lifestyle factors, reproductive history, and comorbidities, women with PCOS were 1.50 (1.16-1.95) times as likely to have GDM (reported on birth certificate and/or survey) compared to women without PCOS. Pre-pregnancy hypertension was not found to be a statistically significant effect moderator.

Conclusions: The findings from this study were consistent with the majority of research indicating that women with PCOS have increased risk for GDM. This is also the first known study to test pre-pregnancy hypertension as an effect moderator between PCOS and GDM. More research is needed on the role of comorbidities such as chronic hypertension as effect modifiers between PCOS and GDM.
Implications: These findings show that women with PCOS are at high risk for GDM, among a population-based sample of mothers. Interventions to reduce the risk of GDM among women with PCOS need to be developed and evaluated.


"Nettle (Urtica dioica) leaves as a novel food: Nutritional, phytochemical profiles, and bioactivities"

Abstract: Urtica dioica is widely distributed across temperate regions of the world and is highly beneficial and packed with nutritional value including a rich profile of phytochemicals, amino acids, and essential minerals. Due to abundance of these attributes, the nutritional, antioxidant, and antimicrobial properties of Urtica dioica were assessed systematically. Additionally, proximate, functional, antinutrient, mineral, polyphenolic compounds, FRAP, and DPPH assays were also examined. The findings revealed that Urtica dioica contains high Mg, Ca, Fe, and Zn. The examined values of DPPH and FRAP showed high antioxidant potential of Urtica dioica. UHPLC and GC-MS analysis confirmed Urtica dioica as an excellent source of phenolic and bioactive compounds. In view of these experimental findings, Urtica dioica can be incorporated into edible coatings and functional foods. Its excellent antimicrobial properties against Gram +ve and Gram -ve bacteria underscore its viability as an excellent source of functional ingredients in edible coatings.


Unleashing the pharmacological potential of taste receptors in reproductive processes beyond their gustatory role

Abstract: Traditionally, taste receptors (TRs) have been understood to reside within the taste buds on the tongue, serving as initiators for different taste perceptions. However, recent research has expanded our understanding, revealing that TRs are found throughout the body and perform a wide range of functions beyond taste perception as non-tasting functions. These receptors, along with their genetic variations, have been linked to various human health conditions. They are activated by an array of substances, including hormones, nutrients, and toxins, indicating their involvement in numerous biological processes. Specifically, in males, TRs are notably present in the testes and epididymis, where they contribute to the hormonal production, spermatogenesis, and sperm maturation. In females, these receptors are found in the ovaries, uterus, and myometrium, playing crucial roles in ovulation, menstrual cycle regulation, and embryo implantation. There are a lot of missed areas regarding TRs research that imposes to fulfill the gaps in the current understanding of their role in reproduction. This review aims to provide a comprehensive overview of the emerging roles of extraoral TRs in reproductive health, highlighting their physiological and pathophysiological significance in various reproductive processes. As well, grabbing the attention towards the release of new pharmacological interventions to manage conception and contraception in male and female was considered.


Association between endometriosis and type and age of menopause: a pooled  analysis of 279 948 women from five cohort studies

Gita D Mishra

School of Public Health University of Queensland Herston QLD Australia

Abstract:
STUDY Question: What is the association between endometriosis and the type and age of menopause?

SUMMARY ANSWER: Women with endometriosis had a 7-fold increased risk of undergoing surgical menopause rather than natural menopause and were more likely to experience premature or early menopause, both surgically and naturally.

WHAT IS KNOWN ALREADY: Endometriosis is associated with reduced ovarian reserve, but evidence on its relationship with the type of menopause (surgical vs natural) and timing (especially premature and early menopause) is limited. Women with endometriosis are more likely to undergo hysterectomy and/or oophorectomy (either unilateral or bilateral), but the average age of these surgeries remains unclear.

STUDY DESIGN, SIZE, DURATION: The study analysed individual-level data from 279 948 women in five cohort studies conducted in the UK, Australia, Sweden, and Japan between 1996 and 2022.

PARTICIPANTS/MATERIALS, SETTING, Methods: Women whose menopause type and age could not be determined due to premenopausal hysterectomy with ovarian preservation or use of menopausal hormone therapy were excluded. Endometriosis was identified through self-reports and administrative data. Surgical menopause was defined as premenopausal bilateral oophorectomy. Fine-Gray subdistribution hazard models estimated hazard ratios (HRs) for surgical and natural menopause. Age at menopause was determined by the ages at the final menstrual period or bilateral oophorectomy. Linear regression assessed mean differences in menopause age, while multinomial logistic regression estimated odds ratios (ORs) for categorical menopause age: <40 (premature), 40-44 (early), 45-49, 50-51 (reference), 52-54, and ≥55 years. Spontaneous premature ovarian insufficiency (POI) was defined as natural menopause before age 40 years.

MAIN RESULTS AND THE ROLE OF CHANCE: Endometriosis was identified in 3.7% of women. By the end of follow-up, 7.9% had surgical menopause and 58.2% experienced natural menopause. Using a competing risk model, women with endometriosis had a 7-fold increased risk of surgical menopause (HR: 7.54, 95% CI 6.84, 8.32) and were less likely to experience natural menopause (HR: 0.40, 95% CI 0.33, 0.49). On average, surgical menopause occurred 1.6 years (19 months) earlier (β: -1.59, 95% CI -1.77, -1.42) in women with endometriosis. Among women who experienced natural menopause, it was 0.4 years (5 months) earlier (β: -0.37, 95% CI -0.46, -0.28) for those with endometriosis. Women with endometriosis were twice as likely to experience premature surgical menopause (<40 years) (OR: 2.11, 95% CI 2.02, 2.20) or 1.4 times more likely to develop spontaneous POI (OR: 1.36, 95% CI 1.17, 1.59). They were also at increased odds of early surgical and natural menopause (40-44 years).

LIMITATIONS, REASONS FOR CAUTION: This study could not differentiate between subtypes and stages of endometriosis or assess treatments for ovarian endometrioma, which may impact ovarian reserve. Self-reported menopause type and age could introduce recall bias.

WIDER IMPLICATIONS OF THE Findings: Given the consistent findings across individual studies, our results are likely to be generalizable to different populations, highlighting the need for tailored management of endometriosis to prevent medically induced or premature menopause. Long-term monitoring of women with endometriosis is recommended, given their elevated risk of surgical menopause and premature or early menopause, which are associated with adverse health outcomes in later life. STUDY FUNDING/COMPETING INTEREST(S): The InterLACE Consortium is funded by the Australian National Health and Medical Research Council project grant (APP1027196) and Centres of Research Excellence (APP1153420). G.D.M. is funded by the Australian National Health and Medical Research Council Leadership Fellowship (APP2009577). This research is funded in part by the Japan Society for the Promotion of Science (JSPS KAKENHI: 19KK0235, 23KK0167). The authors have no conflict of interest. Where authors are identified as personnel of the International Agency for Research on Cancer or WHO, the authors alone are responsible for the views expressed in this article, and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer or WHO.

TRIAL REGISTRATION NUMBER: N/A.


Maternal vaginal and fecal microbiota in later pregnancy contribute to child fecal microbiota development in the ECHO cohort

Liu T, Kress AM, Debelius J, Zhao N, Smirnova E, Bandyopadhyay S, Bonham K, Comstock SS, Gill S, Gern JE, Koinis-Mitchell D, Klepac-Ceraj V, Lee-Sarwar K, Litonjua AA, McKee K, McCauley K, O'Connor TG, Rosas-Salazar C, Scheible K, Stanford JB, Moore B, Jacobson LP, Mueller NT, program collaborators for Environmental Influences on Child Health Outcomes

Abstract: There is growing interest in the use of microbial-seeding interventions to mitigate the impacts of prenatal antibiotics, C-section, and lack of breastfeeding on mother-child microbe sharing. However, the relative importance of maternal vaginal vs. fecal microbiota in this process is unclear. Analyzing 16S rRNA sequences from five US birth cohorts, we found that maternal vaginal and fecal microbiota became more similar as pregnancy progressed, and both niches influenced the child's fecal microbiota. The relative contribution of maternal vaginal microbiota increased when vaginal sampling occurred later in gestation. As children aged from birth to 5 years, their fecal microbiota increasingly resembled their mother's fecal microbiota as compared to vaginal microbiota. Patterns of sharing appeared to differ by prenatal antibiotic use, birth mode (C-section vs. vaginal), and breastfeeding. Our findings enhance understanding of niche-specific mother-child microbe sharing and may inform microbial-seeding interventions. Metagenomic studies are needed to identify specific shared strains.


Surgery in Restorative Reproductive Medicine

Abstract:
Restorative reproductive surgery has emerged to become an exciting and promising field of surgery that can transform the way that we treat patients, especially regarding fertility. As a prime example of this type of surgery, restorative reproductive surgery for endometriosis, a common and debilitating disease that can lead to infertility and pelvic pain, offers a root cause treatment to remove the actual disease and to optimize the reproductive anatomy, for best patient outcomes. Optimal excision of endometriosis and prevention of pelvic adhesions has been shown to lead to reduce symptoms, to lead to high natural fertility rates, and to lead to very low rates of the need for repeat surgery. Patients have improved symptoms and quality of life, in addition to improved fertility chances for one and subsequent pregnancies (if desired), demonstrating the link between wellness and fertility.
There is an urgent need for more resources, training, advocacy, research and publication for this exciting area of restorative reproductive surgery. Its time has come.


Ibuprofen for menstrual cramps

Ibuprofen for menstrual cramps

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre


Energy Intake and Appetite in Laboratory and Free-Living Conditions are Consistent Across Menstrual Cycle Phases

Jonathan Little

Faculty of Medicine, Department of Medicine, Southern Medical Program, Centre for Chronic Disease Prevention and Management, Kelowna, BC, V1V 1V7, Canada; Faculty of Health and Social Development, ...

Miranda Smith

Department of Pathology, Southern Regional Area Health Education Center, Fayetteville, North Carolina, USA.

Zoë Soon

University of British Columbia, Okanagan Campus


Potential relationship of the gut microbiome with testosterone level in men: a systematic review

Abstract: The gut microbiome influences the metabolism and health of several organs beyond the gut and has recently gained considerable attention. The gut plays a central role in food digestion, absorption, nutrition, and general health. Hence, the gut microbiome has become a research subject for almost all health conditions. Imbalance or dysbiosis in the gut microbiome can cause different health issues in men, including reproductive and sexual health issues associated with testosterone levels. Several studies have investigated the relationship between the gut microbiome and testosterone levels. In this systematic review, we aimed to examine the relationship between the gut microbiome and testosterone levels in men. Literature searches were conducted by scanning PubMed, ProQuest, EBSCO, Taylor & Francis Online, Wiley Online, Springer Link, Web of Science, Google Scholar, and Science Direct databases for relevant keywords following the preferred reporting items for the systematic review guidelines. This review included cross-sectional, case-control, retrospective, and prospective cohort studies. Quality assessment was conducted using the Newcastle-Ottawa Scale. We found a significant positive correlation between the gut microbiome and testosterone levels in men. Several microbes play substantial roles in testosterone production. Mechanisms have been proposed as factors that contribute to testosterone levels, namely the hypothalamus-pituitary-gonad axis modulation, androgen metabolism, and intestinal homeostasis, by balancing the bone morphogenic protein (BMP) and the Wnt diverse microbiome. Ruminococcus showed a stronger correlation with testosterone levels than other microorganisms. The gut microbiome has complex correlations with testosterone metabolism. However, the microbiome with the most significant influence on testosterone levels cannot be easily identified and requires further research.


Gut microbiota: a hidden player in polycystic ovary syndrome

Abstract: Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects reproductive-aged women worldwide, causing hormonal imbalances and ovarian dysfunction. PCOS affects metabolic health and increases the risk of obesity, insulin resistance, and cardiovascular disease, in addition to infertility. This review delves deeper into the connections of gut microbiota with PCOS pathophysiology, particularly into its impact on hormone metabolism, obesity, inflammation, and insulin resistance by way of short-chain fatty acids, lipopolysaccharides, and gut-brain axis. Studies also show that changes in the metabolic processes and immune responses are seen in changes in the gut microbiota in PCOS subjects, such as changes in the Bacteroidetes and Firmicutes groups. Some bacteria, like Escherichia and Shigella, have been associated with dysbiosis in patients with PCOS, leading to systemic inflammation and changed hormone levels, which further worsen the clinical symptoms. Therapeutic interventions targeting the gut microbiota comprise probiotics, prebiotics, and fecal microbiota transplantation; these have potential to alleviate the symptoms of PCOS. Other precision microbiome-based therapies include postbiotics, and CRISPR-Cas9 genome editing, which are relatively new avenues toward precision treatment. This complex interlink of gut microbiota and PCOS pathophysiology will open the avenues for possible treatments for hormonal imbalances and metabolic problems that characterize these complex disorders. The review here focuses on the requirement of further studies to be able to elucidate the specific pathways relating gut microbiota dysregulation to PCOS and, thus, improve microbiome-based therapies for better clinical outcomes in affected individuals.


Endometriosis and Cancer: What is the Connection?

Pierlorenzo Pallante

Institute for Experimental Endocrinology and Oncology


Commentary On Infertility and Restorative Reproductive Medicine

Abstract:
In 1972, a seminal article was published demonstrating that women, adequately trained, could detect the approach of ovulation in the fertile window of their menstrual cycle. It was demonstrated that the symptoms perceived by women at the vulva correlate closely with changes in steroid hormone levels associated with folliculogenesis and the luteal phase. The fertility charting performed by women trained to recognize vulvar symptoms associated with hormonal changes serves as an instrument for detecting potential pathologies and monitoring the effects of treatment These findings established the biological foundations of a tool of fertility awareness tracking that has facilitated the development of restorative reproductive medicine (RRM): an approach that can be applied to identify and treat the underlying causes of infertility/subfertility.
Several core characteristics—or foundational pillars—of the RRM approach to fertility can be identified. These include: a commitment to respecting healthy physiological processes, comprehensive health care for both the couple and the potential embryo, and the provision of education and continuous support throughout the therapeutic process.
This commentary aims to elucidate the interplay of these foundational pillars by drawing upon evidence from peer-reviewed biomedical literature. Finally, the challenges faced by RRM in strengthening its scientific foundations, engaging with the broader scientific community, and promoting the dissemination of this approach are described.

Journal of Restorative Reproductive Medicine


Identification of an aryl hydrocarbon receptor agonistic disperse dye in commercially available textile products by effect-directed analysis

Abstract: Textile products contain various chemicals, making safety evaluation complex. We conducted an exploratory investigation of aryl hydrocarbon receptor (AhR) agonists in textile products using effect-directed analysis (EDA), which combines biological assays and chemical analysis. A cell-based assay was employed to detect the activation of the AhR, using a cell line that expresses the AhR-responsive luciferase gene. Testing the extracts of 10 commercially available textile products revealed high AhR agonistic activities in two of them. To identify the specific AhR agonist in one product, the sample was fractionated using chemical techniques. The active fractions were further separated using liquid chromatography. Confirmation of the active component was achieved through Orbitrap-liquid chromatography/mass spectrometry (MS), which matched the retention time and tandem MS spectrum with the standard for Disperse Violet 93:1. It has also been confirmed that Disperse Violet 93:1 activates the AhR in a dose-dependent manner. Additionally, the AhR agonistic properties of other disperse dyes were examined, leading to the discovery of Disperse Blue 291 and Disperse Blue 373 as AhR agonists. These disperse dyes had not been previously recognized as AhR agonists. Textile products have received little attention as potential sources of exposure to AhR agonists. Activation of the AhR has both positive and negative effects on human health. Therefore, conducting detailed exposure assessments and toxicity evaluations is crucial to comprehensively assess the health risks associated with these substances. The identification of disperse dyes that activate the AhR suggests that it is now possible to conduct these detailed assessments in the future.


Spermatozoa as harbingers of mortality: the curious link between semen quality and life expectancy


Children’s executive functioning and health behaviors across pediatric life stages and ecological contexts

Kelly NR, Kosty D, Bodovski Y, Blackwell CK, Ganiban JM, Neiderhiser JM, Dabelea D, Gilbert-Diamond D, Aschner JL, Bastain TM, Breton CV, Bush NR, Calub CA, Camargo CA, Camerota M, Croen LA, Elliott AJ, Enlow MB, Ferrara A, Hartert T, Joseph RM, Karagas MR, Kelly RS, Lyall K, Magee KE, McEvoy CT, Merced-Nieves FM, O’Connor TG, Santarossa S, Schantz SL, Schmidt RJ, Stanford JB, Straughen JK, Stroustrup A, Talge NM, Wright RJ, Zhao Q, Leve LD, Smith PB, Newby KL, Adair L, Catellier D, Jacobson L, Cella D, Gershon R, Teitelbaum SL, Merhar S, Lampland A, Reynolds A, Hudak M, Pryhuber G, Moore P, Washburn L, Trasande L, Gatzke-Kopp L, Swingler M, Mansbach JM, Spergel JM, Samuels-Kalow ME, Stevenson MD, Bauer CS, Mitchell DK, Deoni S, D’Sa V, Duarte CS, Monk C, Posner J, Canino G, Gern J, Zoratti E, Johnson C, Farzan S, Habre R, Hertz-Picciotto I, Hipwell A, Keenan K, Karr C, Tylavsky F, Mason A, Sathyanarayana S, Lester B, Carter B, Pastyrnak S, Neal C, Smith L, Helderman J, Leve L, Weiss ST, Litonjua A, O’Connor G, Zeiger R, Bacharier L, Tepper R, Volk H, Landa R, Ozonoff S, Miller RK, Simhan H, Buss C, Wadhwa P, Huff K, O’Shea M, Vaidya R, Obeid R, Rollins C, Bear K, Lenski M, Singh R, Msall M, Frazier J, Gogcu S, Montgomery A, Kuban K, Douglass L, Jara H, Kerver JM, Barone C, Fussman C, Paneth N, Elliott M, Ruden D, Woodruff T, Porucznik C, Giardino A, Huddleston K, Nguyen R, Barrett E, LeWinn KZ, Swan S


Association of Polycystic Ovary Syndrome With Sensorineural Hearing Loss: A Systematic Review and Meta-analysis

Abstract:
OBJECTIVE: Despite certain studies indicating hearing impairments in individuals with polycystic ovary syndrome (PCOS), the correlation between PCOS and sensorineural hearing loss (SNHL) remains inconclusive. This study aimed to investigate the association between PCOS and SNHL.

DATA SOURCES: A systematic literature search was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Library from inception to June 24, 2024.

REVIEW METHODS: This meta-analysis included cross-sectional, case-control, or cohort studies examining the association between PCOS and SNHL without language or regional restrictions. Case reports, case series, animal studies, and in vitro studies were excluded. We adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and utilized the Newcastle-Ottawa Scale to assess the risk of bias in the included studies.

RESULTS: After performing the systematic review, we conducted a meta-analysis that included 489 patients from 5 studies: 349 patients with PCOS and 140 age- and sex-matched controls without PCOS. The meta-analysis compared the mean differences in frequency-specific pure-tone thresholds between patients with PCOS and matched controls, providing 95% confidence intervals for these differences. Given the expected clinical heterogeneity, we employed the DerSimonian and Laird random-effects model. Our results revealed significant hearing loss at specific frequencies (1000, 4000, 8000, 10,000, 12,000, 14,000, 16,000, 18,000, and 20,000 Hz) in the PCOS group compared to the control group (P < .05). Furthermore, the degree of hearing loss is greater at higher frequencies.

CONCLUSION: This meta-analysis demonstrated an association between PCOS and SNHL, particularly at higher frequencies.

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery


Optimizing Air Quality Monitoring: Comparative Analysis of Linear Regression and Machine Learning in Low-Cost Sensor Calibration

Abstract: Background Low-cost sensors (LCS) are widely used for air quality monitoring, but their accuracy depends on proper calibration. This study compares linear regression (LR) and machine learning (ML) techniques, particularly random forest (RF), to determine optimal calibration strategies. Objectives This study aims to compare the effectiveness of LR and RF models in calibrating the Plantower PMS 3003 sensor under different environmental conditions. It also explores ways to streamline calibration efforts while maintaining accuracy. Methods Sensor data were collected in a controlled laboratory setting, with measurements compared against a reference monitor. LR and RF models were developed to calibrate the sensor, and their performance was evaluated based on RMSE, R2, and bias. Additionally, the study examined whether using fewer sensors for training could still produce reliable calibration models. Results Both LR and RF models demonstrated strong calibration performance. LR models were effective for low to moderate PM2.5 concentrations and required fewer computational resources, making them suitable for large-scale monitoring with limited resources. RF models captured nonlinear relationships, showing superior accuracy at high PM concentrations and in conditions with high relative humidity. The findings suggest that LR models trained on smaller datasets can achieve practical accuracy, reducing the need for extensive individual sensor calibration. Conclusions The selection of a calibration model should be guided by study-specific requirements, including environmental conditions and resource availability. LR models are recommended for large-scale studies with constrained resources, while RF models may offer advantages in high-exposure environments due to their ability to model complex interactions. This study is the first to explore reducing sensor calibration efforts while maintaining accuracy, highlighting the potential for optimized strategies in resource-limited settings. Future research should validate these findings in real-world deployments to further refine calibration models for LCS applications. Graphical Abstract


Validating At-Home Urinary Hormone Measurements in Postpartum and Perimenopause Fertility Transitions

Abstract:
Background: 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.

Materials and Methods: 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.

Results: 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).

Conclusions: 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.

Women's health reports (New Rochelle, N.Y.)


Ectopic Pregnancy

Ectopic Pregnancy

Abstract: Ectopic pregnancy occurs when a fertilized egg implants outside the uterine cavity, a condition that affects approximately 1% to 2% of pregnancies in the United States. Ectopic pregnancy is a potentially life-threatening condition and accounts for 2.7% of pregnancy-related deaths. Most ectopic pregnancies (approximately 97%) occur within the fallopian tube, commonly linked to underlying fallopian tube abnormalities. Such abnormalities may result from prior infections (eg, gonorrhea or chlamydia), tubal surgeries (including sterilization), prior ectopic pregnancies, or exposure to diethylstilbestrol in utero. Additional risk factors include conception while using intrauterine devices (IUDs) or progesterone-only contraceptives. Although rare, ectopic pregnancies can also occur outside the fallopian tube, such as in the cervix, ovary, abdomen, uterine cornua, or cesarean scars. These extratubal ectopic pregnancies are less likely to be associated with the typical risk factors or tubal pathology, making their diagnosis and management particularly challenging. Regardless of the location, early detection is critical for conservative treatment and improving outcomes. Ectopic pregnancy often causes lower abdominal pain, typically on one side, along with vaginal bleeding. Symptoms like dizziness, fainting, shoulder pain, or severe pelvic pain may indicate a ruptured ectopic pregnancy. However, these signs can mimic other conditions, eg, early normal intrauterine pregnancy, miscarriage, ovarian cyst rupture, or appendicitis. Therefore, differentiating ectopic pregnancy from conditions with similar clinical features can be difficult, making prompt medical evaluation crucial for accurate diagnosis and treatment. Management primarily aims to preserve fertility, improve diagnostic accuracy, and provide psychological support. Treatment varies, depending on clinical stability, ectopic location, beta-human chorionic gonadotropin (β-hCG) levels, and ultrasound findings ranging from expectant management to surgical interventions. In select cases, nonsurgical treatment with methotrexate may be effective, especially when pregnancies are diagnosed early and meet specific criteria. However, medical treatment is less likely to succeed in cases involving larger masses, high β-hCG levels, or visible embryos. Advanced or ruptured cases typically require urgent surgical intervention.


Efficacy of open-label placebos for premenstrual syndrome: a randomised  controlled trial

Abstract:
Objective: To investigate the efficacy and safety of open-label placebos (OLP) in premenstrual syndrome (PMS).
Design: Randomised controlled trial.
Setting: Switzerland, 2018-2020.

Participants: 150 women (18-45 years of age) with PMS or premenstrual dysphoric disorder.

Intervention: Random assignment (1:1:1) to treatment as usual (TAU), OLP without treatment rationale (OLP-), or OLP with treatment rationale (OLP+). OLP consisted of two placebo pills per day for 6 weeks.

Main Outcome Measures: Primary outcomes were PMS symptom intensity and interference between groups across three menstrual cycles (MC1-MC3); adverse events (ie, safety) were measured at weeks 3 and 6 after the start of the intervention. Secondary outcomes were psychological and somatic subscales of PMS symptom intensity, and adherence.

Results: From 2 August 2018 to 3 December 2020,


2025 Canadian guideline for physical activity, sedentary behaviour and sleep throughout the first year post partum

Abstract: This consensus aims to provide guidance for postpartum women and people, healthcare providers and exercise professionals on physical activity, sedentary behaviour and sleep throughout the first year postpartum. The development of this guideline followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and the Appraisal of Guidelines for Research and Evaluation II instrument. The Guideline Consensus Panel consisted of representatives from key professional groups, researchers and methodological experts. Literature was retrieved through searches of 12 online databases, and articles on maternal physical activity, sedentary behaviour or sleep in the first year after childbirth were eligible for inclusion if they reported on any of 21 maternal or infant health outcomes, which were prioritised considering the preferences and values of postpartum individuals. There was no restriction on language, and all study designs were eligible except for case studies. The certainty of evidence was rated using GRADE. This evidence review produced seven systematic reviews, which informed this consensus statement. A Delphi process was conducted to identify relative contraindications to postpartum moderate-intensity to vigorous-intensity physical activity, which informed the development of the Get Active Questionnaire for Postpartum. Evidence to decision tables were developed, and feedback on the recommendations was solicited from end users (healthcare providers, exercise professionals, researchers, policy organisations and postpartum women and people). Adhering to these consensus recommendations for postpartum women and people is likely to result in large improvements in psychological well-being, as well as pelvic, musculoskeletal and cardiometabolic health, and reduced fatigue, while not experiencing adverse events (moderate certainty evidence). Most end users indicated that following these recommendations would be feasible, acceptable and equitable, and likely to require minimal resources from individual and health systems perspectives. PROSPERO registration number CRD42022359282.


Higher Pregnancy Success Rates in Patients with Diminished Ovarian Reserve < 40 Years When Initially Treated by Intrauterine Insemination with Mild Ovarian Stimulation Compared to In Vitro Fertilization Alone: A Pilot Study

Abstract: For women with idiopathic diminished ovarian reserve (DOR), direct start with IVF has been suggested to potentially shorten the time to pregnancy. Others however prefer intra-uterine insemination with ovarian stimulation (IUI + OS) due to the expected low response in IVF. In this pilot study, we determined the effect of these two strategies in women with DOR < 40 years. From a retrospective cohort, we included 135 women that met the diagnostic criteria of DOR. Patients were randomly referred to two different outpatient clinics in the Netherlands between 2012-2018 because of subfertility. Primary outcome was clinical pregnancy; secondary outcomes included ongoing pregnancies, live births, time to pregnancy and pregnancy-related complications. An instrumental variable analysis was used to assess the average effect of treatment with IUI + OS followed by IVF (protocol A) compared to IVF alone (protocol B) and correct for (unknown) confounders. Treatment protocol A was performed in 72.6% patients in Centre 1 and 30.6% in Centre 2. In Centre 1 61.6% (45/73) women had a clinical pregnancy compared to 41.9% (26/62) in Centre 2 (difference 19.7% (95% CI 3.1%-36.3%), p = 0.02). Early miscarriage occurred in 24% of the women in Centre 1 in comparison to 45% of the women in Centre 2. There were no significant differences in pregnancy-related complications. This pilot study suggests that women < 40 with DOR, if treated with IUI + OS followed by IVF, have higher estimated cumulative clinical pregnancy success, with a trend towards higher ongoing pregnancies and live births, in comparison to women treated with IVF alone.


Antiphospholipid syndrome in pregnancy: a comprehensive literature review

Abstract:
BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune disorder associated with thrombotic events and adverse obstetric outcomes, particularly in its obstetric form (OAPS). Affecting approximately 0.5% of the population, APS is a leading contributor to recurrent pregnancy loss (RPL), preeclampsia (PE), and fetal growth restriction ((FGR). Despite advancements in understanding its pathophysiology and management, optimal treatment strategies for APS in pregnancy remain challenging and require systematic evaluation. This review synthesizes current evidence on APS mechanisms, diagnostic criteria, and therapeutic interventions, with a focus on maternal and fetal outcomes in OAPS.

METHODS: A comprehensive search of PubMed, was conducted to identify studies exploring APS pathogenesis, diagnostic standards, and treatment efficacy in obstetric settings. Inclusion criteria prioritized randomized controlled trials, cohort studies, and systematic reviews with a clear focus on APS and pregnancy.

RESULTS: The review confirmed that APS current accepted pathogenesis is governed by a "two-hit" model, where antiphospholipid antibodies (aPLs) initiate endothelial damage, culminating in thrombosis and placental insufficiency. Epidemiological analysis underscores the prevalence and severity of APS in obstetric contexts, with lupus anticoagulant (LA) emerging as a significant predictor of adverse outcomes. Evidence supports the use of low-dose aspirin (LDA) and heparin to reduce miscarriage rates, while adjunctive treatments, such as hydroxychloroquine (HCQ), have shown promise in improving live birth rates and reducing preterm delivery in high-risk cases. Emerging therapies, including tumoral necrosis factor (TNF-alpha) inhibitors and nitric oxide modulators, may offer additional benefits in refractory cases.

CONCLUSION: APS remains a critical determinant of adverse pregnancy outcomes, necessitating precise diagnostic criteria and tailored management approaches. This systematic review emphasizes the importance of individualized therapeutic regimens to optimize maternal and fetal health in OAPS and highlights areas for future research, particularly regarding novel pharmacological approaches. Further studies are essential to refine treatment protocols and improve clinical guidelines for managing APS in pregnancy.


The association of prenatal dietary factors with child autism diagnosis and  autism-related traits using a mixtures approach: Results from the ECHO Cohort

Bragg MG, Rando J, Carroll KN, Eick SM, Karagas MR, Lin PI, Schmidt RJ, Lyall K

Abstract:
Background: Previous research on the role of maternal diet in relation to autism has focused on examining individual nutrient associations. Few studies have examined associations with multiple nutrients using mixtures approaches, which may better reflect true exposure scenarios.

Objective: To examine associations of nutrient mixtures with children's autism diagnosis and traits scores within a large, diverse population.

Methods: Participants were drawn from the US Environmental influences on Child Health Outcomes (ECHO) consortium. Maternal prenatal diet was reported via validated food frequency questionnaires. Children's autism-related traits were measured using the Social Responsiveness Scale (SRS) and autism diagnoses were from parent report of physician diagnosis. Bayesian kernel machine regression (BKMR) was used to examine the overall mixture effect and interactions between a set of 5 primary nutrients (folate, vitamin D, omega 3 and omega 6 fatty acids, and iron), adjusted for potential confounders, in relationship to child outcomes. Secondary analyses were conducted in a subset of cohorts with an expanded set of 14 nutrients. Traditional linear and logistic regression models were also run for comparison of results to mixture models.

Results: 2,614 participants drawn from 7 ECHO cohorts were included in primary analysis. Mixture analyses suggested that increasing the overall 5-nutrient mixture was associated with lower SRS scores. Individual U-shaped associations and bivariate interactions between folate and omega 3 fatty acids were suggested. In the subset included in the secondary analyses of the 14-nutrient mixture, a modest inverse trend remained, but individual nutrient associations were altered, with vitamin D demonstrating higher relative importance than other nutrients. Strong associations with autism diagnosis were not observed.

Conclusion: In this large sample, we found evidence for combined nutrient effects with broader autism-related traits. Because results for individual nutrients were sensitive to mixture components, replication of combined associations between nutrients and autism-related outcomes is needed.


A Remedy for the Injustice of IVF

A Remedy for the Injustice of IVF

Renee Mirkes

Pontifical John Paul II Institute for Studies on Marriage and Family


Abstract P1174: Endometriosis diagnosis, staging, and typology in relation to inflammatory cytokines

Leslie V Farland

Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona; Department of Obstetrics and Gynecology, College of Medicine -...

Abstract:
Introduction: Endometriosis, affecting 11% of reproductive-aged persons, is characterized by ectopic endometrial tissue and chronic inflammation. Prior research suggests those with endometriosis have higher cardiovascular disease risk, but mechanisms remain elusive. The objective of this study is to assess whether endometriosis diagnosis, staging, and typology (superficial endometriosis (SE), ovarian endometriomas (OE), and deep infiltrating endometriosis (DE)) are associated with serum interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-) concentrations.

Methods: The study analyzed data from 395 premenopausal persons in Utah undergoing gynecologic laparoscopy who participated in the NICHD ENDO study (2007–2009). Post-operative reports determined endometriosis typology (SE, OE, DE) and staging (minimal, mild, moderate, severe) using Revised American Society for Reproductive Medicine classification. Elevated serum cytokine concentrations were defined as IL-6 ≥2pg/mL, IL-8 ≥3pg/mL, and TNF- ≥7.5pg/mL. Generalized linear models generated adjusted prevalence ratios (aPR) 95% CI controlling for age, BMI, marital status, race/ethnicity, and serum cotinine.

Results: Participants were on average 32 years (SD=7) at time of gynecologic laparoscopy/laparotomy, non-Hispanic white (79%), married (71%), mean BMI 28 (SD=8) and non-smokers (83% serum cotinine <10ng/mL). Forty-two percent (n=166) were diagnosed with incident endometriosis. We found no differences among those with, compared to without, endometriosis and elevated IL-6, 12% vs 10%, aPR: 1.01 (0.97, 1.10), IL-8, 5% vs 8%, aPR: 0.99 (0.94, 1.04); and TNF, 16% vs 13%, aPR: 1.00 (0.96, 1.04). While there were no statistically significant associations between endometriosis staging or typology and cytokines, those with moderate to severe endometriosis had nonsignificant lower IL-6 and IL-8 (aPR: 0.61 [0.15, 2.52] and aPR: 0.74 [0.17, 3.20]) but higher TNF- (aPR: 1.27 [0.56, 2.84]), compared to no endometriosis. Individuals with OE and DE had nonsignificant trends of IL-6 and Il-8 (aPR: 0.86 [0.11, 2.52] and aPR: 0.93 [0.14, 6.43]) but higher TNF- (aPR: 1.93 [0.77, 4.84]).

Conclusions: In summary, this study found no clear correlation between endometriosis diagnosis, staging, typology and inflammatory markers IL-6, IL-8, and TNF-. Whether endometriosis severity or typology is associated with TNFshould be explored in future studies with adequate power and more representative samples.


Abstract P1175: Endometriosis diagnosis, staging, and typology in relation to dyslipidemia

Jessica Chan

UNIVERSITY UTAH, Salt Lake City, Utah, United States

Madeline Paulsen

Department of Family and Preventive Medicine, University of Utah, Salt Lake City, UT, USA.

Abstract:
Background:
Individuals with endometriosis, a gynecologic condition affecting approximately 11% of people with a uterus, may have an elevated risk for developing cardiovascular disease (CVD) later in life. However, the mechanisms underlying this association are not well understood.

Methods:
We investigated the association between incident endometriosis diagnosis, staging, and typology and lipid biomarkers measured at time of diagnostic surgery among women participating in the NICHD ENDO study (n=395). Endometriosis was categorized using the American Society for Reproductive Medicine staging (I−IV). Endometriosis typology was defined by lesion depth and location and categorized as superficial endometriosis (SE), ovarian endometrioma (OE), and deep infiltrating endometriosis (DE). With no endometriosis as our reference, we evaluated the associations between endometriosis diagnosis, stage (I/II vs III/IV), and typology (SE, OE, DE, OE+DE) and dyslipidemia using standard clinical thresholds (total cholesterol ≥200 mg/dL, high-density lipoprotein (HDL) <50 mg/dL, low-density lipoprotein (LDL) ≥100 mg/dL, triglycerides ≥175 mg/dL, non-HDL ≥130 mg/dL, VLDL ≥30 mg/dL, Apolipoprotein A-1 (APO-A1) <125 mg/dL, Apolipoprotein B (APOB) ≥120 mg/dL; APOB/APO-A1 ratio >0.78). We calculated adjusted prevalence ratios (aPR) and 95% CIs via generalized linear models, controlling for age, race/ethnicity, marital status, BMI, income (poverty level), and serum cotinine as a marker of smoking.

Results:
At the time of gynecologic surgery, individuals were mean 32 years (SD: 7 years), non-Hispanic white (79%), married (71%), and mean BMI 28 (SD=8). While we found no differences in endometriosis diagnosis or endometriosis staging and dyslipidemia (
Figure 1; Table 1
), a pattern emerged regarding endometriosis typology (
Table 2
). Women with OE+DE, compared to no endometriosis, had increased prevalence of dyslipidemia: total cholesterol >200 mg/dL: 1.87 (0.99, 3.57); triglycerides
>
175 mg/dL: 2.48 (1.34, 4.57); VLDL ≥30 mg/dL: 2.08 (1.28, 3.38); and APOB mg/dL ≥120: 2.86 (1.22, 6.66). OE appeared to be driving this association. SE was not associated with dyslipidemia.

Conclusions:
The association between endometriosis, especially of more severe typology, and subsequent CVD may be through dyslipidemia, which may be detectable at the time of endometriosis diagnosis. Further research in larger, more representative samples is needed before definitive conclusions can be made.


Vasectomy

Vasectomy

Abstract: Mayo Clinic patient overview of vasectomy, a permanent male contraceptive procedure that cuts and seals the vas deferens. Covers indications, the no-scalpel technique, risks, recovery, and semen testing. Notes vasectomy reversal and IVF are possible after vasectomy but are harder, costly, and not guaranteed, so vasectomy should be considered permanent. By Mayo Clinic Staff, updated March 7, 2025.


Progesterone supplementation after postovulatory mifepristone reduce changes in  human endometrial gene expression

Miguel Del Rio

Reproductive Health Research Institute, Santiago, Chile

Pilar Vigil

Pontificia Universidad Católica de Chile

Abstract: IN BRIEF: Progesterone supplementation reverses 83% of transcript changes in the secretory endometrium induced by postovulatory mifepristone, potentially mitigating its antiprogestogenic effects. ABSTRACT: Mifepristone (RU486) antagonizes progesterone signaling in human endometrium interfering in the secretory phenotype after estradiol priming. The objective of the present study was to determine effect in the endometrial transcript profile of progesterone supplementation after the administration of 200 mg of the antiprogestin mifepristone 48 h after the LH peak (LH+2, LH+0 = LH peak). Endometrial samples were obtained on LH+7 after vaginal administration of micronized progesterone 200 mg/day for 3 days in nine women of proven fertility, each one contributing with one cycle treated with progesterone and another with a placebo. In addition, endometrial samples were obtained in LH+7 from a subgroup of four women with no administration of mifepristone, with each one contributing with one cycle treated with vaginal progesterone supplementation or placebo as a reference. RNA-seq was used to identify transcripts significantly regulated under the administration of progesterone vs placebo with or without postovulatory mifepristone. We observed that 713 transcripts changed significantly in the endometrium under mifepristone after progesterone supplementation in group A. Of these, progesterone reversed approximately 83% of the transcripts affected by mifepristone in the secretory endometrium. Bioinformatic analyses revealed that these transcripts were enriched in genes associated with mitochondrial function, particularly oxidative phosphorylation. In addition, NR2C2 and DLX1 were identified as potential transcription factors that may mediate the effects of progesterone in the endometrium. We conclude that progesterone supplementation after postovulatory mifepristone administration can reverse the antiprogestogenic effects for most of the affected endometrial transcripts.


Appetite and Energy Intake in Laboratory and Free-Living Conditions Remain Consistent Across Menstrual Cycle Phases when Using Precise Measurement Methods

Jonathan Little

Faculty of Medicine, Department of Medicine, Southern Medical Program, Centre for Chronic Disease Prevention and Management, Kelowna, BC, V1V 1V7, Canada; Faculty of Health and Social Development, ...

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Miranda Smith

Department of Pathology, Southern Regional Area Health Education Center, Fayetteville, North Carolina, USA.

Zoë Soon

University of British Columbia, Okanagan Campus

Abstract: Self-reported dietary intake varies across menstrual cycle phases, but objective assessments of dietary intake together with appetite and resting metabolic rate (RMR) are limited. This study aimed to assess differences in appetite, dietary intake, and RMR during two hormonally-distinct menstrual cycle phases in laboratory and free-living settings. Healthy premenopausal females with predictable normal-length menstrual cycles completed two study visits: one in the late-follicular and one in the mid-luteal phase. Menstrual cycle phases were identified using urinary luteinizing hormone surge and cycle days. Participants consumed a 2-day energy- and macronutrient-balanced run-in diet prior to each visit. RMR was measured with indirect calorimetry, followed by appetite ratings before and after a standardized breakfast, and completed a food cravings questionnaire. Appetite was also tracked for 2.5 days post-visit in a free-living environment. Ad libitum energy and macronutrient intake were measured using pre-weighed plus weighing of uneaten food at an in-laboratory lunch meal, as well as during the 2.5-day free-living period. Eighteen participants were included (age: 21±4 years; body mass index: 21.2±1.5 kg/m 2 ). There were no differences between in-laboratory ad libitum energy or macronutrient intakes, appetite, or food cravings between phases. RMR did not differ between phases, although the mid-luteal phase RMR trended toward higher (104±218 kcal/day higher ; P =0.074). No main nor interaction effects for phase and time were observed for free-living dietary intake nor appetite ratings. Accurate measurements show no differences in appetite or energy intake between menstrual cycle phases, though RMR may be slightly elevated in the luteal phase.


Demographic Correlates of Autism: How Do Associations Compare Between Diagnosis and a Quantitative Trait Measure?

Lyall K, Dickerson AS, Green AM, Frndak S, Croen LA, Ames JL, Avalos LA, Aschner JL, Bush NR, Camargo CA, D'Sa V, Dager SR, Dunlop AL, Ferrara A, Ganiban JM, Gern JE, Gissandaner TD, Graff JC, Hertz-Picciotto I, Hipwell AE, Ma T, Miller M, Murphy L, Karagas MR, Kelly RS, Margolis A, Koinis-Mitchell D, McEvoy CT, Messinger D, Nguyen R, Oken E, Ozonoff S, Page GP, Schantz SL, Schmidt RJ, Shuster CL, Schweitzer JB, Sheinkopf SJ, Stanford JB, Trevino CO, Weiss ST, Volk HE, Joseph RM, program collaborators for Environmental Influences on Child Health Outcomes

Abstract: Prevalence of autism diagnosis has historically differed by demographic factors. Using data from 8224 participants drawn from the Environmental influences on Child Health Outcomes (ECHO) Program, we examined relationships between demographic factors and parent-reported autism-related traits as captured by the Social Responsiveness Scale (SRS; T score > 65) and compared these to relations with parent-reported clinician diagnosis of ASD, in generalized linear mixed effects regression analyses. Results suggested lower odds of autism diagnosis, but not of SRS T > 65, for non-Hispanic Black children (adjusted odds ratio [OR] = 0.76, 95% CI 0.55, 1.06) relative to non-Hispanic White children. Higher maternal education was associated with reduced odds of both outcomes (OR = 0.73, 95% CI 0.51, 1.05 for ASD autism diagnosis and 0.4, 95% CI 0.29, 0.55 for SRS score). In addition, results suggested a lower likelihood of autism diagnosis but a higher likelihood of an SRS score > 65 in Black girls. Findings suggest lower diagnostic recognition of autism in non-Hispanic Black children, despite a similar degree of SRS-assessed autism-related traits falling in the clinically elevated range. Further work is needed to address this disparity.

Autism research : official journal of the International Society for Autism Research


Estrogen-Gut-Brain Axis: Examining the Role of Combined Oral Contraceptives on Mental Health Through Their Impact on the Gut Microbiome

Abstract: Combined oral contraceptives (COCs) possess the ability to alter the normal composition of the gut microbiome and the permeability of the gastrointestinal (GI) tract, which may cause both gut-related and non-gut-related complications. The gut-estrogen axis examines the relationship between estrogens (particularly the active form, estradiol) and the gastrointestinal system and can be attributed to the maintenance of the estrobolome and circulating estradiol levels. The gut-brain axis involves the relationship between the brain and the gastrointestinal system and can be attributed to the gut microbiome in relation to the enteric nervous system (ENS) and serotonin levels. Overall, the introduction of exogenous hormones into an endogenous environment alters the normal balance of both hormones and bacteria. Currently, there is a gap in knowledge regarding the link between COCs and mental health complications such as anxiety and depression, and the diversity in these complications may be related to different types of COCs, their composition, and variations in study populations. This article reviews existing evidence from animal and human studies on the role of COCs in the development of mental health issues through their impact on the gut microbiome.


Hormonal birth control is associated with altered gut microbiota β-diversity in physically active females across the menstrual cycle: a pilot trial

Abstract: Understanding changes to gut microbiota composition in response to hormonal birth control (HBC) may provide insight into the microbial mechanisms underlying the metabolic effects of HBC, for example, altered short-chain fatty acid (SCFA) production. Athletes' unique physiological demands may interact with these microbial mechanisms in distinct ways; however, there is limited research on HBC and gut microbiota diversity and composition across different menstrual cycle phases in physically active females. A pilot cohort of physically active females using HBC (oral contraceptives, hormone-based intrauterine devices, or arm implants) and a control group not using HBC (n = 12 per group; 22 ± 2 yr, 24 ± 4 kg/m2 vs. 22 ± 4 yr, 23 ± 4 kg/m2; Ps ≥ 0.496) provided fecal samples alongside self-reported menstrual phase and circulating sex hormones. α-diversity (microbial richness and evenness) was assessed using the Shannon index whereas β-diversity (microbial composition differences) was analyzed using PERMANOVA based on Bray-Curtis dissimilarity. Circulating estrogen and luteinizing hormone increased from early (days 1-5) to mid-cycle (days 12-17) in both groups (time effect Ps ≤ 0.01), with greater changes in Control (Ps ≤ 0.046) than HBC (Ps ≥ 0.231). Although no menstrual phase effect was observed on either diversity measure (Ps ≥ 0.473), β-diversity differed between Control and HBC groups (P = 0.015), reflecting distinct gut microbiota profiles irrespective of menstrual phase. Seven taxa linked to SCFA production were less abundant in the HBC group (unadjusted Ps ≤ 0.046), though significance was lost after adjusting for multiple comparisons. These findings suggest that in physically active females, hormonal contraception influences gut microbial composition, which may have downstream effects on metabolism and performance.NEW & NOTEWORTHY This study is the first to investigate interactions between hormonal contraception and the gut microbiota in a cohort of physically active young females across the menstrual cycle. Our findings suggest that hormonal contraception may influence gut microbiota composition, potentially through a reduced relative abundance of short-chain fatty acid-producing taxa. Experimental studies are needed to confirm these associations and explore their potential implications for metabolism, health, and performance.

Journal of applied physiology (Bethesda, Md. : 1985)