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Human Reproduction Update Jun 2024Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects of anticancer treatment in premenopausal women. Accumulating...
BACKGROUND
Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects of anticancer treatment in premenopausal women. Accumulating detailed data show that different chemotherapy regimens can lead to disturbance of ovarian hormone levels, reduced or lost fertility, and an increased risk of early menopause. Previous studies have often focused on the direct effects of chemotherapeutic drugs on ovarian follicles, such as direct DNA damage-mediated apoptotic death and primordial follicle burnout. Emerging evidence has revealed an imbalance in the ovarian microenvironment during chemotherapy. The ovarian microenvironment provides nutritional support and transportation of signals that stimulate the growth and development of follicles, ovulation, and corpus luteum formation. The close interaction between the ovarian microenvironment and follicles can determine ovarian function. Therefore, designing novel and precise strategies to manipulate the ovarian microenvironment may be a new strategy to protect ovarian function during chemotherapy.
OBJECTIVE AND RATIONALE
This review details the changes that occur in the ovarian microenvironment during chemotherapy and emphasizes the importance of developing new therapeutics that protect ovarian function by targeting the ovarian microenvironment during chemotherapy.
SEARCH METHODS
A comprehensive review of the literature was performed by searching PubMed up to April 2024. Search terms included 'ovarian microenvironment' (ovarian extracellular matrix, ovarian stromal cells, ovarian interstitial, ovarian blood vessels, ovarian lymphatic vessels, ovarian macrophages, ovarian lymphocytes, ovarian immune cytokines, ovarian oxidative stress, ovarian reactive oxygen species, ovarian senescence cells, ovarian senescence-associated secretory phenotypes, ovarian oogonial stem cells, ovarian stem cells), terms related to ovarian function (reproductive health, fertility, infertility, fecundity, ovarian reserve, ovarian function, menopause, decreased ovarian reserve, premature ovarian insufficiency/failure), and terms related to chemotherapy (cyclophosphamide, lfosfamide, chlormethine, chlorambucil, busulfan, melphalan, procarbazine, cisplatin, doxorubicin, carboplatin, taxane, paclitaxel, docetaxel, 5-fluorouraci, vincristine, methotrexate, dactinomycin, bleomycin, mercaptopurine).
OUTCOMES
The ovarian microenvironment shows great changes during chemotherapy, inducing extracellular matrix deposition and stromal fibrosis, angiogenesis disorders, immune microenvironment disturbance, oxidative stress imbalances, ovarian stem cell exhaustion, and cell senescence, thereby lowering the quantity and quality of ovarian follicles. Several methods targeting the ovarian microenvironment have been adopted to prevent and treat CAOD, such as stem cell therapy and the use of free radical scavengers, senolytherapies, immunomodulators, and proangiogenic factors.
WIDER IMPLICATIONS
Ovarian function is determined by its 'seeds' (follicles) and 'soil' (ovarian microenvironment). The ovarian microenvironment has been reported to play a vital role in CAOD and targeting the ovarian microenvironment may present potential therapeutic approaches for CAOD. However, the relation between the ovarian microenvironment, its regulatory networks, and CAOD needs to be further studied. A better understanding of these issues could be helpful in explaining the pathogenesis of CAOD and creating innovative strategies for counteracting the effects exerted on ovarian function. Our aim is that this narrative review of CAOD will stimulate more research in this important field.
REGISTRATION NUMBER
Not applicable.
PubMed: 38942605
DOI: 10.1093/humupd/dmae020 -
Hydroxychloroquine in recurrent pregnancy loss: data from a French prospective multicenter registry.Human Reproduction (Oxford, England) Jun 2024What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course...
STUDY QUESTION
What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course of these pregnancies beyond the first trimester?
SUMMARY ANSWER
In our cohort of pregnancies in women with a history of RPL exposed to HCQ early in pregnancy, we found that the only factor determining the success of these pregnancies was the number of previous miscarriages.
WHAT IS KNOWN ALREADY
Dysregulation of the maternal immune system plays a role in RPL. HCQ, with its dual immunomodulating and vascular protective effects, is a potential treatment for unexplained RPL.
STUDY DESIGN, SIZE, DURATION
The FALCO (Facteurs de récidive précoce des fausses couches) registry is an ongoing French multicenter infertility registry established in 2017 that includes women (aged from 18 to 49 years) with a history of spontaneous RPL (at least three early miscarriages (≤12 weeks of gestation (WG)) recruited from several university hospitals.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Spontaneous pregnancies enrolled in the FALCO registry with an exposure to HCQ (before conception or at the start of pregnancy) were included. Pregnancies concomitantly exposed to tumor necrosis factor inhibitors, interleukin-1 and -2 inhibitors, intravenous immunoglobulin, and/or intravenous intralipid infusion, were excluded. Concomitant treatment with low-dose aspirin (LDA), low-molecular weight heparin (LMWH), progesterone, and/or prednisone was allowed. All patients underwent the recommended evaluations for investigating RPL. Those who became pregnant received obstetric care in accordance with French recommendations and were followed prospectively. The main endpoint was the occurrence of a pregnancy continuing beyond 12 WG, and the secondary endpoint was the occurrence of a live birth.
MAIN RESULTS AND THE ROLE OF CHANCE
One hundred pregnancies with HCQ exposure in 74 women were assessed. The mean age of the women was 34.2 years, and the median number of previous miscarriages was 5. Concomitant exposure was reported in 78 (78%) pregnancies for prednisone, 56 (56%) pregnancies for LDA, and 41 (41%) pregnancies for LMWH. Sixty-two (62%) pregnancies ended within 12 WG, the other 38 (38%) continuing beyond 12 WG. The risk of experiencing an additional early spontaneous miscarriage increased with the number of previous miscarriages, but not with age. The distributions of anomalies identified in RPL investigations and of exposure to other drugs were similar between pregnancies lasting ≤12 WG and those continuing beyond 12WG. The incidence of pregnancies progressing beyond 12 WG was not higher among pregnancies with at least one positive autoantibody (Ab) (i.e. antinuclear Ab titer ≥1:160, ≥1 positive conventional and/or non-conventional antiphospholipid Ab, and/or positive results for ≥1 antithyroid Ab) without diminished ovarian reserve (18/51, 35.3%) than among those without such autoantibody (18/45, 40.0%) (P = 0.63). Multivariate analysis showed that having ≤4 prior miscarriages was the only factor significantly predictive for achieving a pregnancy > 12 WG, after adjustment for age and duration of HCQ use prior to conception (adjusted odds ratio (OR) = 3.13 [1.31-7.83], P = 0.01).
LIMITATIONS, REASONS FOR CAUTION
Our study has limitations, including the absence of a control group, incomplete data for the diagnostic procedure for RPL in some patients, and the unavailability of results from endometrial biopsies, as well as information about paternal age and behavioral factors. Consequently, not all potential confounding factors could be considered.
WIDER IMPLICATIONS OF THE FINDINGS
Exposure to HCQ in early pregnancy for women with a history of RPL does not seem to prevent further miscarriages, suggesting limited impact on mechanisms related to the maternal immune system.
STUDY FUNDING/COMPETING INTEREST(S)
The research received no specific funding, and the authors declare no competing interests.
TRIAL REGISTRATION NUMBER
clinicaltrial.gov NCT05557201.
PubMed: 38942601
DOI: 10.1093/humrep/deae146 -
BMJ Paediatrics Open Jun 2024Raised intracranial pressure (ICP) contributes to approximately 20% of the admissions in the paediatric intensive care unit (PICU) in our setting. Timely identification... (Observational Study)
Observational Study
BACKGROUND
Raised intracranial pressure (ICP) contributes to approximately 20% of the admissions in the paediatric intensive care unit (PICU) in our setting. Timely identification and treatment of raised ICP is important to prevent brain herniation and death in such cases. The objective of this study was to examine the role of optic nerve sheath diameter (ONSD) in detecting clinically relevant raised ICP in children.
METHODS
A hospital-based observational analytical study in a PICU of a tertiary care institute in India on children aged 2-14 years. ONSD was measured in all children on three time points that is, day 1, day 2 and between day 4 and 7 of admission. ONSD values were compared between children with and without clinical signs of raised ICP.
RESULTS
Out of 137 paediatric patients recruited, 34 had signs of raised ICP. Mean ONSD on day 1 was higher in children with signs of raised ICP (4.99±0.57 vs 4.06±0.40; p<0.01). Mean ONSD on day 2 also was higher in raised ICP patients (4.94±0.55 vs 4.04±0.40; p<0.01). The third reading between days 4 and 7 of admission was less than the first 2 values but still higher in raised ICP patients (4.48±1.26 vs 3.99±0.57; p<0.001). The cut-off ONSD value for detecting raised ICP was 4.46 mm on the ROC curve with an area under curve 0.906 (95% CI 0.844 to 0.968), 85.3% sensitivity and 86.4% specificity. There was no difference in ONSD between the right and the left eyes at any time point irrespective of signs of raised ICP.
CONCLUSION
We found that measurement of ONSD by transorbital ultrasound was able to detect clinically relevant raised ICP with an excellent discriminatory performance at the cut-off value of 4.46 mm.
Topics: Humans; Child; Optic Nerve; Intracranial Hypertension; Child, Preschool; Female; Male; Adolescent; Intensive Care Units, Pediatric; India; Ultrasonography; Intracranial Pressure; ROC Curve; Sensitivity and Specificity
PubMed: 38942587
DOI: 10.1136/bmjpo-2023-002353 -
Evidence-based Nursing Jun 2024
PubMed: 38942467
DOI: 10.1136/ebnurs-2023-103888 -
Identification of Rare Genetic Variants in the PCDH Genetic Family in a Cohort of Transgender Women.F&S Science Jun 2024To study the identification of rare genetic variants in the PCDH genetic family in a cohort of transgender women and their potential role in gender identity.
OBJECTIVE
To study the identification of rare genetic variants in the PCDH genetic family in a cohort of transgender women and their potential role in gender identity.
DESIGN
Exome sequencing and functional ontology analysis.
SETTING
Augusta University, including the Equality Clinic of Augusta and the Reproductive Medicine and Infertility Associates Clinic.
PATIENTS
24 transgender women and 22 cisgender men.
INTERVENTIONS
Exome sequencing followed by variant confirmation through Sanger sequencing and functional classification analysis using the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool.
MAIN OUTCOME MEASURES
Identification of rare, functionally significant genetic variants in the PCDH gene family and their prevalence in transgender women compared to cisgender men.
RESULTS
Exome sequencing revealed 38,524 genetic variants, of which 2441 were rare and predicted to be functionally significant. DAVID analysis demonstrated a statistically enriched functional group, "homophilic cell adhesion via plasma membrane adhesion molecules" (Benjamini corrected p-value 1.5 x 10-11), containing 55 genes, including 18 PCDH gene family members. A total of 37 rare variants in 21 PCDH genes were identified, with 36 confirmed by Sanger sequencing. A statistically significant increase in these variants was observed in transgender women compared to cisgender men (Z = 2.08905, p= 0.037).
CONCLUSIONS
Transgender women exhibited a greater than 3-fold increase in functionally significant PCDH gene variants compared to cisgender men. These findings suggest that the PCDH family may play a role in the genetic pathways associated with gender identity in transgender women.
PubMed: 38942387
DOI: 10.1016/j.xfss.2024.06.005 -
Cells & Development Jun 2024Trophoblasts play a crucial role in embryo implantation and in interacting with the maternal uterus. The trophoblast lineage develops into a substantial part of the... (Review)
Review
Trophoblasts play a crucial role in embryo implantation and in interacting with the maternal uterus. The trophoblast lineage develops into a substantial part of the placenta, a temporary extra-embryonic organ, capable of undergoing distinctive epigenetic events during development. The critical role of trophoblast-specific epigenetic signatures in regulating placental development has become known, significantly advancing our understanding of trophoblast identity and lineage development. Scientific efforts are revealing how trophoblast-specific epigenetic signatures mediate stage-specific gene regulatory programming during the development of the trophoblast lineage. These epigenetic signatures have a significant impact on blastocyst formation, placental development, as well as the growth and survival of embryos and fetuses. In evolution, DNA hypomethylation in the trophoblast lineage is conserved, and there is a significant disparity in the control of epigenetic dynamics and the landscape of genomic imprinting. Scientists have used murine and human multipotent trophoblast cells as in vitro models to recapitulate the essential epigenetic processes of placental development. Here, we review the epigenetic signatures of the trophoblast lineage and their biological functions to enhance our understanding of placental evolution, development, and function.
PubMed: 38942294
DOI: 10.1016/j.cdev.2024.203934 -
Environmental Pollution (Barking, Essex... Jun 2024Increased systemic oxidative stress, implicated in adverse pregnancy outcomes for both mothers and fetuses, has been associated with gestational exposure to air...
Increased systemic oxidative stress, implicated in adverse pregnancy outcomes for both mothers and fetuses, has been associated with gestational exposure to air pollutants such as polycyclic aromatic hydrocarbons (PAHs), fine particulate matter (PM), and nitrogen dioxide (NO). However, it is unclear whether exposure to pollutants at levels below the current air quality standards can increase oxidative stress in pregnant women. In a cohort of 305 pregnant persons residing in western New York, we examined the association between exposure to PM, NO, and PAHs (measured as urinary 1-hydroxypyrene) and urinary biomarkers of oxidative stress (malondialdehyde [MDA] and 8-hydroxy-2'-deoxyguanosine [8-OHdG]) measured in each trimester. After controlling for gestational stage, maternal age, lifestyles, and socioeconomic factors, each interquartile range (IQR) increase in 1-hydroxypyrene concentration (65.8 pg/ml) was associated with a 7.73% (95%CI: 3.18%,12.3%) higher in MDA levels throughout the pregnancy and in the first and second trimester. An IQR increase in PM concentration (3.20 μg/m) was associated with increased MDA levels in the first trimester (8.19%, 95%CI: 0.28%,16.1%), but not the 2 (-7.99%, 95% CI: -13.8%, -2.23%) or 3 trimester (-2.81%, 95% CI: -10.0%, 4.38%). The average cumulative PM exposures in the 3-7 days before urine collection were associated with increased 8-OHdG levels during the second trimester, with the largest difference (22.6%; 95% CI: 3.46%, 41.7%) observed in relation to a one IQR increase in PM concentration in the previous 7 days. In contrast, neither oxidative stress biomarker was associated with NO exposure. Observed in pregnant women exposed to low-level air pollution, these findings expanded previously reported associations between systemic oxidative stress and high-level PM and PAH concentrations. Further, the first and second trimesters may be a susceptible window during pregnancy for oxidative stress responses to air pollution exposure.
PubMed: 38942277
DOI: 10.1016/j.envpol.2024.124463 -
Environmental Research Jun 2024The ongoing increase in the global mean temperature will increase around the globe, indicating that women and infants will have higher exposure to heat events leading to...
BACKGROUND
The ongoing increase in the global mean temperature will increase around the globe, indicating that women and infants will have higher exposure to heat events leading to adverse outcomes. The study investigates the effect of non-optimal ambient temperature on the risk of preterm birth stratified by social position in Nepal.
METHOD
This is a space-time-stratified case-crossover design, based on hospital-registered perinatal data between 2017 and 2021 (n=47,807). A daily count of pregnant women residing in seven heat-prone districts was extracted together with their social status (ethnicity), obstetric complication and gestation of birth. The daily count of events was matched with the daily ambient temperature of their residence using the NASA spatial temperature recording. Ambient temperature exposure was analysed using conditional Poisson regression and distributed lag non-linear models.
FINDINGS
In the general population, with exposure to ambient temperature at the 75 centile (28 °C) the cumulative risk of preterm birth over 28 days was 1·29 times higher (RR, 1·29; 95% CI; 1·09, 1·54) than at median temperature (24.1 °C), and even higher among the socially disadvantaged population. Cumulative risk of preterm birth to cold ambient temperature at the 1 centile is high but not significant. Exposure to ambient temperature at the 90 centile (32·5 °C) has the highest cumulative risk of preterm birth for pregnant women from socially disadvantaged populations (RR 1·81; 95% CI; 1·28, 2·55). The delayed effect after exposure to temperatures above the 75 percentile seems to be more prolonged in the disadvantaged than the advantaged social group.
CONCLUSION
Although exposure to cold with certain effect on preterm births, heat (increase in ambient temperature) carries a risk of preterm birth in Nepal, and is more profound among socially disadvantaged populations.
PubMed: 38942260
DOI: 10.1016/j.envres.2024.119501 -
Environmental Research Jun 2024Microplastics (MPs) can enter the reproductive system and can be potentially harmful to human reproductive health. In this study, 13 types of microplastics (MPs) were...
Microplastics (MPs) can enter the reproductive system and can be potentially harmful to human reproductive health. In this study, 13 types of microplastics (MPs) were identified in patient blood, cancer samples, and paracarcinoma samples using Raman spectroscopy, with polyethylene, polypropylene and polyethylene-co-polypropylene being the most abundant polymer types. Futher, cotton was also found in our study. The diversity and abundance of MPs were higher in blood samples than in cancerous tissues, and there was a significant positive correlation between diversity (p < 0.05). Furthermore, the diversity and abundance of MPs in cancerous tissues were higher than in paracancerous tissues. The dimensional sizes of MPs in these samples were also very similar, with the majority of detected MPs being smaller in size. Correlation analysis showed that patient's age correlated with the abundance of MPs in blood samples, body mass index (BMI) correlated with the abundance of MPs in cancerous tissues. Notably, the frequency with which patients consume bottled water and beverages may also increase the abundance of MPs. This study identifies for the first time the presence of MPs and cotton in cancerous and paracancerous tissues of human cervical cancer patients. This provides new ideas and basic data to study the risk relationship between MP exposure and human health.
PubMed: 38942254
DOI: 10.1016/j.envres.2024.119498 -
Journal of Minimally Invasive Gynecology Jun 2024To estimate the risk of bowel obstruction after hysterectomy for benign indications depending on the surgical method (abdominal, vaginal, or laparoscopic) and identify...
STUDY OBJECTIVE
To estimate the risk of bowel obstruction after hysterectomy for benign indications depending on the surgical method (abdominal, vaginal, or laparoscopic) and identify risk factors for adhesive bowel obstruction.
DESIGN
A national registry-based cohort.
SETTING
Danish hospitals during the period 1984-2013.
PATIENTS
Danish women who underwent hysterectomy for benign indications (N=125,568).
INTERVENTIONS
Abdominal hysterectomies were compared with vaginal hysterectomies, laparoscopic hysterectomies, and minimally invasive (vaginal and laparoscopic) hysterectomies.
MEASUREMENTS AND MAIN RESULTS
The incidence of bowel obstruction according to the surgical method was compared using Cox proportional hazard regression. The covariates included were the time period, age, concomitant operations, prior abdominal surgery or disease, and socioeconomic factors. In a sub-analysis (n=35,712 women) of the period 2004-2013, detailed information from the Danish Hysterectomy Database enabled the inclusion of patient-related, surgery-related, and complication-related covariates. The overall crude incidence of bowel obstruction was 17.4/1000 hysterectomies (2196 incident cases). The 10-year cumulative incidence of bowel obstruction differed between the surgical routes (abdominal, 1.7%; laparoscopic, 1.4%; and vaginal, 0.9%). In multiple adjusted analyses, the risk of bowel obstruction was higher after abdominal hysterectomy than after vaginal (HR 1.64 [95% CI 1.39-1.93]) and minimally invasive (vaginal or laparoscopic) hysterectomy (HR 1.54 [1.33-1.79]). Additional pre-existing risk factors for bowel obstruction at the time of hysterectomy were increased age, low education, low income, smoking, high ASA comorbidity score, history of infertility, abdominal infection, and prior abdominal surgery (apart from cesarean section),penetrating lesions in abdominal organs, or operative adhesiolysis. Perioperative risk factors at the time of hysterectomy included concomitant removal of the ovaries, adhesiolysis, blood transfusion, readmission, and overall presence of perioperative complications.
CONCLUSION
Abdominal hysterectomy is associated with a 54% higher risk of bowel obstruction than minimally invasive (laparoscopic or vaginal) hysterectomy.
PubMed: 38942232
DOI: 10.1016/j.jmig.2024.06.010