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Human Reproduction Update Jul 2023Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as... (Review)
Review
BACKGROUND
Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as well as the elimination of infected or damaged cells throughout life. Quality control through regulation of cell death pathways is particularly important in the germline, which is responsible for the generation of offspring. Women are born with their entire supply of germ cells, housed in functional units known as follicles. Follicles contain an oocyte, as well as specialized somatic granulosa cells essential for oocyte survival. Follicle loss-via regulated cell death-occurs throughout follicle development and life, and can be accelerated following exposure to various environmental and lifestyle factors. It is thought that the elimination of damaged follicles is necessary to ensure that only the best quality oocytes are available for reproduction.
OBJECTIVE AND RATIONALE
Understanding the precise factors involved in triggering and executing follicle death is crucial to uncovering how follicle endowment is initially determined, as well as how follicle number is maintained throughout puberty, reproductive life, and ovarian ageing in women. Apoptosis is established as essential for ovarian homeostasis at all stages of development and life. However, involvement of other cell death pathways in the ovary is less established. This review aims to summarize the most recent literature on cell death regulators in the ovary, with a particular focus on non-apoptotic pathways and their functions throughout the discrete stages of ovarian development and reproductive life.
SEARCH METHODS
Comprehensive literature searches were carried out using PubMed and Google Scholar for human, animal, and cellular studies published until August 2022 using the following search terms: oogenesis, follicle formation, follicle atresia, oocyte loss, oocyte apoptosis, regulated cell death in the ovary, non-apoptotic cell death in the ovary, premature ovarian insufficiency, primordial follicles, oocyte quality control, granulosa cell death, autophagy in the ovary, autophagy in oocytes, necroptosis in the ovary, necroptosis in oocytes, pyroptosis in the ovary, pyroptosis in oocytes, parthanatos in the ovary, and parthanatos in oocytes.
OUTCOMES
Numerous regulated cell death pathways operate in mammalian cells, including apoptosis, autophagic cell death, necroptosis, and pyroptosis. However, our understanding of the distinct cell death mediators in each ovarian cell type and follicle class across the different stages of life remains the source of ongoing investigation. Here, we highlight recent evidence for the contribution of non-apoptotic pathways to ovarian development and function. In particular, we discuss the involvement of autophagy during follicle formation and the role of autophagic cell death, necroptosis, pyroptosis, and parthanatos during follicle atresia, particularly in response to physiological stressors (e.g. oxidative stress).
WIDER IMPLICATIONS
Improved knowledge of the roles of each regulated cell death pathway in the ovary is vital for understanding ovarian development, as well as maintenance of ovarian function throughout the lifespan. This information is pertinent not only to our understanding of endocrine health, reproductive health, and fertility in women but also to enable identification of novel fertility preservation targets.
Topics: Adult; Animals; Female; Humans; Apoptosis; Granulosa Cells; Mammals; Oocytes; Ovarian Follicle; Ovary; Regulated Cell Death; Homeostasis
PubMed: 36857094
DOI: 10.1093/humupd/dmad005 -
American Journal of Obstetrics &... Jul 2022Pelvic inflammatory disease during pregnancy is a rare and an understudied occurrence with potential negative outcomes. (Review)
Review
BACKGROUND
Pelvic inflammatory disease during pregnancy is a rare and an understudied occurrence with potential negative outcomes.
OBJECTIVE
This study aimed to evaluate the outcomes of pregnant women with pelvic inflammatory disease with or without pelvic abscesses.
DATA SOURCES
We performed a systematic review of the literature using Ovid MEDLINE, Scopus, CINAHL, and PubMed (including Cochrane) with no time limitations.
STUDY ELIGIBILITY CRITERIA
Relevant studies on pelvic inflammatory disease during pregnancy were identified and considered eligible if they described at least 1 case of pelvic inflammatory disease after conception, defined as infection in one or more of the following: uterus, fallopian tubes, and ovaries; based on clinical findings, physical examination, and imaging with or without pelvic abscesses present. Only studies on pelvic inflammatory disease with or without tubo-ovarian abscesses during pregnancy that evaluated perinatal outcomes were included. Data on the risk factors, delivery methods, and maternal, fetal, and neonatal outcomes were collected.
METHODS
Reviewers screened all relevant titles using the inclusion/exclusion criteria and selected relevant articles for appraisal. A total of 49 cases with reported pelvic inflammatory disease, pelvic abscesses, or both were included.
RESULTS
After exclusion of articles that did not meet the inclusion criteria, 34 manuscripts describing the occurrence of pelvic inflammatory disease in 49 pregnancies were analyzed, focusing primarily on cases reported after 1971. The mean age of patients was 25±6.3 years, the mean gestational age at diagnosis was 19.0±10.3 weeks, and 67.6% of patients were multiparous. Of all included patients, 27 (62.8%) underwent exploratory laparotomies, 14 (32.6%) underwent unilateral salpingo-oophorectomies, and 11 (25.6%) underwent appendectomies. Of all the deliveries, 13 (50%) pregnancies were full term, 14 (53.8%) were cesarean deliveries, 10 (38.5%) were spontaneous vaginal deliveries, and 2 (7.7%) were cesarean hysterectomies. There were 26 (60.5%) cases of viable births (mean gestational age at delivery, 33.8±5.1 weeks) and 17 (39.5%) cases of nonviable births. Sepsis was a complication in 3 (7.0%) cases and caused 3 neonatal deaths.
CONCLUSION
Although rare, pelvic inflammatory disease can have severe health consequences. Risk factors for pelvic inflammatory disease development include maternal pelvic structural anomalies, a history of sexually transmitted infections, recent pelvic surgery, and in vitro fertilization or oocyte retrieval. Pelvic inflammatory disease can coincide with pregnancy and can occur in the second trimester. Making a prompt diagnosis can help to improve the outcomes; therefore, if a high enough suspicion exists, treatment should not be delayed.
Topics: Abscess; Cesarean Section; Female; Gestational Age; Humans; Parturition; Pelvic Inflammatory Disease; Pregnancy
PubMed: 35405372
DOI: 10.1016/j.ajogmf.2022.100643 -
Climacteric : the Journal of the... Apr 2023The objective of this review was to answer the global prevalence of premature ovarian insufficiency (POI), and explore the associated factors including etiopathology and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objective of this review was to answer the global prevalence of premature ovarian insufficiency (POI), and explore the associated factors including etiopathology and regions with POI.
METHODS
The search was conducted on reports from a total of eight databases that comprised Chinese National Knowledge Infrastructure (CNKI), Wanfang, China BioMedical Literature Database (CBM), PubMed, the Cochrane Library, Embase, Web of Science and Ovid MEDLINE between 1946 and 2021. To analyze the source of heterogeneity, we performed subgroup analysis based on different etiologies and regions. Meta-analysis was carried out by Stata14.0 software.
RESULTS
The results showed that the global overall prevalence of POI among women was 3.5%. By subgroup analysis, the prevalence of POI among women with iatrogenic etiology was 11.2%, followed by autoimmunity (10.5%); the prevalence of POI by region was 11.3% at the highest in North America followed by South America (5.4%); and the prevalence of POI was 5.3% in a developing country, higher than 3.1% in a developed country. The trend of prevalence of POI over the past 20 years was on the rise (although > 0.05).
CONCLUSION
We recommend that health and medical institutions strengthen public health awareness, achieve health-education goals related to POI and increase women's awareness of and attention to POI.
Topics: Female; Humans; Prevalence; Primary Ovarian Insufficiency; Menopause, Premature; China
PubMed: 36519275
DOI: 10.1080/13697137.2022.2153033 -
Clinical Drug Investigation May 2020The levonorgestrel oral emergency contraceptive is well tolerated and effective, however its use is still limited, mainly due to safety concerns. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The levonorgestrel oral emergency contraceptive is well tolerated and effective, however its use is still limited, mainly due to safety concerns.
OBJECTIVE
This systematic review and meta-analysis aimed to summarize current evidence regarding the adverse events, and their prevalence, reported during the use of oral levonorgestrel emergency contraceptives.
METHODS
Four electronic databases and the US FDA Adverse Event Reporting System (FAERS) Public Dashboard were searched. Studies that reported or investigated safety outcomes or adverse reactions during the use of levonorgestrel as an emergency oral contraceptive were included. Data on study design, demographics of levonorgestrel and the control cohort, and reported adverse effects were extracted.
RESULTS
A total of 47 articles were included in this systematic review, from which it was shown that most of the adverse reactions were common and not serious. Uncommon adverse reactions identified included anorexia, ectopic pregnancy, exanthema, chloasma, miscarriage, and weight gain. Multiple serious adverse events, including convulsion, ectopic pregnancy, febrile neutropenia, stroke, abdominal hernia, anaphylaxis, cancer, ovarian cyst rupture, serious infections, and suicidal ideation, were reported. In addition, the prevalence of adverse events after a levonorgestrel 0.75 mg two-dose regimen and a levonorgestrel 1.5 mg single-dose regimen were not statistically different (p > 0.05).
CONCLUSIONS
The most common adverse effects of levonorgestrel were not serious. This systematic review shows that data regarding the adverse reactions of repeated use of levonorgestrel are scarce. Studies on the multiple uses of levonorgestrel emergency contraception are still required to ensure its safety.
Topics: Contraceptive Agents, Hormonal; Contraceptives, Postcoital; Female; Humans; Levonorgestrel; Pregnancy
PubMed: 32162237
DOI: 10.1007/s40261-020-00901-x -
European Journal of Obstetrics,... Jan 2024To evaluate the effect of SARS-CoV-2 infection and vaccination on ovarian reserve. (Review)
Review
OBJECTIVE
To evaluate the effect of SARS-CoV-2 infection and vaccination on ovarian reserve.
METHODS
Relevant articles were identified in the EMBASE, PubMed, and Web of Science databases from January 2020 to May 2023. Available clinical indicators of ovarian reserve, such as anti-Müllerian hormone (AMH), antral follicle count (AFC), follicle-stimulating hormone (FSH), and estradiol (E2), as well as the time interval from infection or vaccination to measurements, were assessed.
RESULTS
Only 2 studies provided evidence that SARS-CoV-2 infection could damage ovarian function. In a comparison of the vaccinated and unvaccinated groups, although 1 prospective cohort study observed the transient statistically significant decrease on serum AMH levels at 3 or 6 months of follow-up, serum AMH levels remained within the normal reserve range (>1.1 ng/dl) throughout the study period.
CONCLUSION
Overall, whether ovarian reserve may be affected by SARS-CoV-2 infection remains controversial and further investigations are warranted to clarify this issue. Based on the current evidence, it is safe to assume that COVID-19 vaccination does not exert any adverse effect on ovarian reserve parameters such as AMH, AFC, FSH, and E2, which will provide reassurance for women attempting to fall pregnant.
Topics: Pregnancy; Female; Humans; Ovarian Reserve; Ovarian Follicle; Prospective Studies; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Follicle Stimulating Hormone; Anti-Mullerian Hormone
PubMed: 37976767
DOI: 10.1016/j.ejogrb.2023.10.029 -
Frontiers in Immunology 2023Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of immunosuppressive regimens in adults with LN.
METHODS
We systematically searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases, including conference proceedings, trial registries, and reference lists, from inception until July 10, 2022. The effects of treatment were compared and ranked using the surface under the cumulative ranking curve (SUCRA). The primary endpoint was total remission. The secondary endpoints were complete remission, systemic lupus erythematosus disease activity index (SLEDAI), relapse, all-cause mortality, end-stage renal disease (ESRD), infection, herpes zoster, ovarian failure, myelosuppression, and cancer.
RESULTS
Sixty-two trials reported in 172 studies involving 6,936 patients were included in the network meta-analysis. The combination of tacrolimus (TAC), mycophenolate mofetil (MMF), and glucocorticoid (GC) provided the best result for the total remission rate (SUCRA, 86.63%) and SLEDAI (SUCRA, 91.00%), while the combination of voclosporin (VCS) , MMF and GC gave the best improvement in the complete remission rate (SUCRA, 90.71%). The combination of cyclophosphamide (CYC), MMF and GC was associated with the lowest risk of relapse (SUCRA, 85.57%) and cancer (SUCRA, 85.14%), while the combination of obinutuzumab (OTB), MMF and GC was associated with the lowest risk of all-cause mortality (SUCRA, 84.07%). Rituximab (RTX) plus MMF plus GC was associated with the lowest risk of ESRD (SUCRA, 83.11%), while the risk of infection was lowest in patients treated with azathioprine (AZA) plus CYC plus GC (SUCRA, 68.59%). TAC plus GC was associated with the lowest risk of herpes zoster (SUCRA, 87.67%) and ovarian failure (SUCRA, 73.60%). Cyclosporine (CsA) plus GC was associated with the lowest risk of myelosuppression (SUCRA, 79.50%), while AZA plus GC was associated with the highest risk of myelosuppression (SUCRA, 16.25%).
DISCUSSION
This study showed that a combination of TAC, MMF and GC was the best regimen for improving the total remission rate. The optimal regimen for specific outcomes should be highlighted for high-risk patients.
Topics: Humans; Adult; Immunosuppressive Agents; Lupus Nephritis; Network Meta-Analysis; Treatment Outcome; Cyclophosphamide; Tacrolimus; Azathioprine; Mycophenolic Acid; Glucocorticoids; Bone Marrow Diseases; Kidney Failure, Chronic; Recurrence; Herpes Zoster; Neoplasms
PubMed: 37901212
DOI: 10.3389/fimmu.2023.1232244 -
The Australasian Journal of Dermatology Feb 2020Hidradenitis suppurativa has been associated with a number of pathologies, including various endocrine and autoimmune disorders. Although signs of hyperandrogenism are... (Meta-Analysis)
Meta-Analysis
BACKGROUND/OBJECTIVES
Hidradenitis suppurativa has been associated with a number of pathologies, including various endocrine and autoimmune disorders. Although signs of hyperandrogenism are common in hidradenitis suppurativa, few formal studies have assessed the relationship between hidradenitis suppurativa and polycystic ovarian syndrome. Therefore, we performed a systematic review and meta-analysis to assess the association between hidradenitis suppurativa and polycystic ovarian syndrome.
METHODS
We performed a systematic review and meta-analysis according to PRISMA guidelines. Odds ratio was used as the effect size, with random-effects meta-analysis.
RESULTS
We identified five case-control studies for inclusion. From pooled data, we found a significantly higher proportion of polycystic ovarian syndrome in hidradenitis suppurativa cases compared with controls (OR 2.64; 95% CI 1.69-4.11; P < 0.00001). There was significant heterogeneity noted (I = 88%, P < 0.00001). Limitations included that studies reviewed were observational by design which are susceptible to bias, and lack of randomisation.
CONCLUSIONS
In summary, pooled analysis of existing case-control studies supports a significant association between hidradenitis suppurativa and polycystic ovarian syndrome. Our results imply that hidradenitis suppurativa patients with signs of hyperandrogenism may benefit from screening for polycystic ovarian syndrome, and may potentially benefit from anti-androgen therapy.
Topics: Female; Hidradenitis Suppurativa; Humans; Polycystic Ovary Syndrome
PubMed: 31261440
DOI: 10.1111/ajd.13110 -
Biomedicines May 2023Anti-NMDAR encephalitis has been associated with multiple antigenic triggers (i.e., ovarian teratomas, prodromal viral infections) but whether geographic, climatic, and... (Review)
Review
Anti-NMDAR encephalitis has been associated with multiple antigenic triggers (i.e., ovarian teratomas, prodromal viral infections) but whether geographic, climatic, and environmental factors might influence disease risk has not been explored yet. We performed a systematic review and a meta-analysis of all published papers reporting the incidence of anti-NMDAR encephalitis in a definite country or region. We performed several multivariate spatial autocorrelation analyses to analyze the spatial variations in the incidence of anti-NMDA encephalitis depending on its geographical localization and temperature. Finally, we performed seasonal analyses in two original datasets from France and Greece and assessed the impact of temperature using an exposure-lag-response model in the French dataset. The reported incidence of anti-NMDAR encephalitis varied considerably among studies and countries, being higher in Oceania and South America (0.2 and 0.16 per 100,000 persons-year, respectively) compared to Europe and North America (0.06 per 100,000 persons-year) ( < 0.01). Different regression models confirmed a strong negative correlation with latitude (Pearson's R = -0.88, < 0.00001), with higher incidence in southern hemisphere countries far from the equator. Seasonal analyses showed a peak of cases during warm months. Exposure-lag-response models confirmed a positive correlation between extreme hot temperatures and the incidence of anti-NMDAR encephalitis in France ( = 0.03). Temperature analyses showed a significant association with higher mean temperatures and positive correlation with higher ultraviolet exposure worldwide. This study provides the first evidence that geographic and climatic factors including latitude, mean annual temperature, and ultraviolet exposure, might modify disease risk.
PubMed: 37371620
DOI: 10.3390/biomedicines11061525 -
European Journal of Surgical Oncology :... Sep 2023Patients with ovarian metastasis of colorectal cancer (CROM) usually have poor prognosis. Metastasectomy is controversial in patients with CROM. This study aims to... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Patients with ovarian metastasis of colorectal cancer (CROM) usually have poor prognosis. Metastasectomy is controversial in patients with CROM. This study aims to evaluate the prognostic value of ovarian metastasectomy and other factors in CROM patients.
METHODS
We searched literature up to November 1, 2021 in MEDLINE (PubMed), Embase, Cochrane Library, and Clinicaltrials.gov. Retrospective studies were assessed if survival outcome of CROM patients was reported. Results were pooled in a random-effects model and reported as hazard ratios (HRs) with 95% confidence intervals (CI). Sensitivity was analyzed.
RESULTS
Among 2497 studies screened, 15 studies with 997 patients, published between 2000 and 2021, were included. Longer overall survival (OS) was correlated with ovarian metastasectomy (pooled HR = 0.44, 95% CI: 0.34-0.58, P < 0.05) and R0 resection (pooled HR = 0.26, 95% CI: 0.16-0.41, P < 0.05). Longer disease-specific survival (DSS) was associated with systematic chemotherapy (pooled HR = 0.26, 95% CI: 0.15-0.45, P < 0.0001). Shorter OS was associated with extraovarian metastases (pooled HR = 3.00, 95% CI 1.68-5.36, P < 0.05) and bilateral OM (pooled HR = 1.66, 95% CI: 1.09-2.51, P < 0.05). No significant difference in OS was observed among patients with systematic chemotherapy (pooled HR = 0.68, 95% CI: 0.35-1.31, P > 0.05).
CONCLUSION
Metastasectomy achieving R0 resection can significantly prolong OS and DSS of CROM patients as a reasonable treatment modality. Primary tumor resection and systematic chemotherapy can improve patients' outcomes.
REGISTRATION NUMBER
CRD42022299185 (http://www.crd.york.ac.uk/PROSPERO).
Topics: Humans; Female; Metastasectomy; Retrospective Studies; Prognosis; Ovarian Neoplasms; Colorectal Neoplasms
PubMed: 37355393
DOI: 10.1016/j.ejso.2023.06.013 -
Journal of Minimally Invasive Gynecology May 2021To review short- and long-term complications associated with intraoperative rupture of benign ovarian cysts. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To review short- and long-term complications associated with intraoperative rupture of benign ovarian cysts.
DATA SOURCES
The Cochrane Central Register of Controlled Trials, BIOSIS, Medline (Ovid), Web of Science, ClinicalTrials.gov, and Google Scholar were searched using the following terms and their combinations: "spillage," "rupture," "leakage," "ovarian cyst," "teratoma," "dermoid," "operative," "surgery," "outcome."
METHODS OF STUDY SELECTION
Randomized controlled and observational studies evaluating the operative outcomes of surgical treatment of ovarian cysts with intraoperative spillage compared with those of surgical treatment of ovarian cysts without spillage were included. A systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed.
TABULATION, INTEGRATION, AND RESULTS
A total of 28 studies were included in the qualitative analysis and 12 in the quantitative analysis. Ovarian cyst diameter was not found to be associated with the risk for spillage (relative risk [RR] 0.75; 95% confidence interval [CI], -0.33 to 1.82). Intraoperative benign ovarian cyst rupture was not associated with adverse short- and long-term outcomes such as reoperation (RR 1.16; 95% CI, 0.39-3.48), infertility (RR 0.73; 95% CI, 0.15-3.63), transient fever (RR 3.22; 95% CI, 0.83-12.51), and readmission (RR 1.00; 95% CI, 0.33-2.98). However, intraoperative spillage was found to be associated with increased risk for benign recurrence (RR 3.1; 95% CI, 1.05-9.14). A subgroup analysis of the studies that included only dermoid cysts showed an association between intraoperative cyst rupture and postoperative chemical peritonitis (RR 9.36; 95% CI, 1.20-73.28).
CONCLUSION
Intraoperative ovarian cyst spillage of a benign cyst is associated with limited adverse clinical outcomes. Although the surgical approach (minimally invasive vs open) should not be affected by the concern regarding an intraoperative cyst rupture, maximal efforts should be made to prevent intra-abdominal spillage.
Topics: Female; Humans; Laparoscopy; Neoplasm Recurrence, Local; Ovarian Cysts; Peritonitis; Postoperative Complications; Teratoma
PubMed: 33279627
DOI: 10.1016/j.jmig.2020.11.025