Study question: What is the evidence available concerning gut and reproductive tract microbiomes in patients with endometriosis and what are the methodological approaches employed in microbiome studies on endometriosis?
Summary answer: The taxonomic profiles exhibited pronounced heterogeneity within women with and also within women without endometriosis across reviewed studies for all the anatomical districts evaluated.
What is known already: Both human and animal studies support differences in the microbiome composition of individuals with and without endometriosis. Endometriosis onset occurs with variable symptoms and manifestations. The microbiome composition at different sites may contribute to this variability.
Study design size duration: We used the scoping review methodology. Systematic searches of studies from the PubMed, EMBASE, and Web of Science databases published between 1 January 2016 and 1 November 2024 addressing endometriosis microbiome characterization in: (i) gut, (ii) vaginal fluid, (iii) cervical fluid, (iv) peritoneal fluid, (v) uterine fluid, (vi) ovarian cyst fluid, (vii) oropharyngeal fluid, and (viii) eutopic and (ix) ectopic tissues were performed using a combination of MeSH terms. References from relevant publications were systematically screened.
Participants/materials setting methods: Results were reported in accordance with the PRISMA-ScR guidelines. Studies that did not report original data, not written in English or providing a review of the field were excluded. From the 2182 publications retrieved, 36 papers were selected and analyzed, focusing on sample characterization (patients, controls, tissues, and fluids) and methodologies used.
Main results and the role of chance: Sound evidence is lacking to support a specific gut dysbiosis profile in women with endometriosis. The largest metagenome study performed using shotgun sequencing and controlling for multiple hypotheses testing did not detect significant differences between women with and without the disease. For eutopic and ectopic tissue microbiomes, the literature is too scant to draw any conclusion. Some data suggest a possible enrichment of Streptococcus sp. in cervical fluid and of Pseudomonas sp. in peritoneal fluid and a depletion of Lachnospira sp. in stool/anal fluid of endometriosis patients. However, these findings may be explained by confounders or by intrinsic patient or population characteristics. We appraised the limitations of the studies and proposed suggestions for optimizing sequencing techniques and experimental designs.
Limitations reasons for caution: The number of participants per study greatly varied and, with few exceptions, was typically low. Incomplete information on methodological approaches was broadly observed. The impact of participants' menstrual cycle p
Study question: Is Life's Essential 8 (LE8) score associated with sperm quality parameters in healthy reproductive-aged men?
Summary answer: Higher LE8 score adherence is positively associated with total sperm count, sperm concentration, total motility, and progressive motility.
What is known already: Several lifestyle and cardiovascular risk factors may affect sperm quality, but there is limited scientific evidence in men.
Study design size duration: A cross-sectional analysis in the context of the Led-Fertyl (Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters) study was conducted.
Participants/materials setting methods: A total of 223 young men aged 18-40 years were recruited between February 2021 and December 2024 in Reus (Catalonia, Spain). The AHA-LE8 ideal cardiovascular health (CVH) score (ranging from 0 to 100) was calculated as the means of eight CVH metrics and was considered as exposure. This score is based on four health behaviors (healthy diet, adequate physical activity, avoidance of nicotine, and healthy sleep) and four health factors (healthy weight, and healthy levels of blood lipids, blood glucose, and blood pressure). Conventional sperm quality parameters (count, concentration, vitality, total and progressive motility, and normal sperm morphology) were considered the main outcomes. Adherence to the LE8 score was categorized into tertiles using the lowest tertile as the reference (T1). All regression models were adjusted for several potential confounders: age (years), education (high school or less, college or higher education), monthly income (<2000 euros and ≥2000 euros), and sexual abstinence (days).
Main results and the role of chance: Compared with those in the lowest tertile, men in the highest tertile of the LE8 score had higher sperm concentration (β = 1.11; 95% CI: 0.12, 2.09), total motility (β = 6.05; 95% CI: 0.44, 11.65), and progressive motility (β = 5.84; 95% CI: 0.19, 11.48). In the continuous analysis, each 10-point increase in the LE8 score was positively associated with total sperm count (β = 0.88; 95% CI: 0.13, 1.63), sperm concentration (β = 0.45; 95% CI: 0.03, 0.86), total (β = 2.91; 95% CI: 0.56, 5.26), and progressive motility (β = 3.00; 95% CI: 0.63, 5.36). Compared with participants in the lowest tertile of the LE8 score, those in the highest tertile were 68% less likely to have an abnormal seminogram, according to the World Health Organization (2010) thresholds (OR: 0.32; 95% CI: 0.15, 0.67).
Limitations reasons for caution: Due to the cross-sectional design, a cause-effect relationship cannot be established. It is also not possible to generalize these results to other populations.
Wider implications of the findings: Our findings
Study question: What are the effects of three-times-a-day 10 mg oral dydrogesterone (DYD), initiated in the late follicular phase of natural menstrual cycles to induce endometrial receptivity for frozen-thawed embryo transfer (FET), on progesterone levels, indicative of ovulation on the day of FET, and how are levels of DYD, 20α-dihydrodydrogesterone (DHD), progesterone (P), and estradiol (E2) on the day of FET associated with clinical outcomes?
Summary answer: Late follicular phase initiation of oral 30 mg DYD is compatible with progesterone levels indicative of ovulation in 98% of cases, and DYD, DHD, P, and E2 blood levels on the day of FET do not show a consistent relationship with live birth achievement, whether evaluated in isolation or interaction.
What is known already: HRT regimens for FET have come under scrutiny due to: (i) the risk of insufficient progesterone exposure with conventional dosing schemes, and (ii) maternal and fetal risks associated with the iatrogenic absence of a corpus luteum. Oral DYD 10 mg three-times-a-day (tid) is considered unlikely to interfere with ovulation or corpus luteum formation and does not exhibit cross-reactivity with progesterone in ELISA. Therefore, it can be used to induce endometrial receptivity (i.e. to schedule the timing of FET in a natural cycle) and provide luteal phase support (LPS) while allowing ovulation to occur independently of the implantation window and enabling the monitoring of endogenous progesterone serum levels.
Study design size duration: Nested within a multi-centric, prospective, clinical cohort study (NCT03507673), 559 normally cycling women from the routine care population who underwent FET in a spontaneous menstrual cycle (12/2021-8/2023) had DYD, DHD, P, and E2 levels on day of FET measured by high-performance liquid chromatography/tandem mass spectroscopy (HPLC/MS/MS) or commercially available electrochemiluminescence immunoassay (ECLIA).
Participants/materials setting methods: Starting from cycle day 10, women underwent endocrine (E2, LH, and P) and sonographic monitoring until the following criteria were ideally met: a leading follicle ≥16 mm, endometrial thickness ≥6 mm, and E2 ≥ 180 pg/ml. At this point, physicians could initiate oral DYD 10 mg (tid) or, if there was no LH rise in serum, postpone initiation within 2 days of monitoring to align with patient and/or centre preferences (e.g. avoiding weekends). FET for Day 2-Day 5 embryos was performed on Day 3-6 of DYD intake.
Main results and the role of chance: DYD and DHD plasma levels on Day 3-6 of intake replicate previous findings. In FET with Day 4 or 5 embryos, serum P levels indicated ovulation in 98.1% (>1.5 ng/ml) and 95.4% (>3.0 ng/ml) of cases and levels were higher (ratio of geometric means 2.88, 95% CI 2.48-3.35) than in FET with Day 2 or 3 embryos. Progesterone levels on da

