Endometriosis is defined as the presence of endometrial-type mucosa outside the uterine cavity. Of the proposed pathogenic theories (retrograde menstruation, coelomic metaplasia and Müllerian ...remnants), none explain all the different types of endometriosis. According to the most convincing model, the retrograde menstruation hypothesis, endometrial fragments reaching the pelvis via transtubal retrograde flow, implant onto the peritoneum and abdominal organs, proliferate and cause chronic inflammation with formation of adhesions. The number and amount of menstrual flows together with genetic and environmental factors determines the degree of phenotypic expression of the disease. Endometriosis is estrogen-dependent, manifests during reproductive years and is associated with pain and infertility. Dysmenorrhoea, deep dyspareunia, dyschezia and dysuria are the most frequently reported symptoms. Standard diagnosis is carried out by direct visualization and histologic examination of lesions. Pain can be treated by excising peritoneal implants, deep nodules and ovarian cysts, or inducing lesion suppression by abolishing ovulation and menstruation through hormonal manipulation with progestins, oral contraceptives and gonadotropin-releasing hormone agonists. Medical therapy is symptomatic, not cytoreductive; surgery is associated with high recurrence rates. Although lesion eradication is considered a fertility-enhancing procedure, the benefit on reproductive performance is moderate. Assisted reproductive technologies constitute a valid alternative. Endometriosis is associated with a 50% increase in the risk of epithelial ovarian cancer, but preventive interventions are feasible.
ICSI is currently the most commonly used assisted reproductive technology, accounting for 70-80% of the cycles performed. This extensive use, even excessive, is partly due to the high level of ...standardization reached by the procedure. There are, however, some aspects that deserve attention and can still be ameliorated. The aim of this systematic review was to evaluate the results of available publications dealing with the management of specific situations during ICSI in order to support embryologists in trying to offer the best laboratory individualized treatment.
This systematic review is based on material obtained by searching PUBMED between January 1996 and March 2015. We included peer-reviewed, English-language journal articles that have evaluated ICSI outcomes in the case of (i) immature oocytes, (ii) oocyte degeneration, (iii) timing of the various phases, (iv) polar body position during injection, (v) zona-free oocytes, (vi) fertilization deficiency, (vii) round-headed sperm, (viii) immotile sperm and (ix) semen samples with high DNA fragmentation.
More than 1770 articles were obtained, from which only 90 were specifically related to the issues developed for female gametes and 55 for the issues developed for male gametes. The studies selected for this review were organized in order to provide a guide to overcome roadblocks. According to these studies, the injection of rescue metaphase I oocytes should be discouraged due to poor clinical outcomes and a high aneuploidy rates; laser-assisted ICSI represents an efficient method to solve the high oocyte degeneration rate; the optimal ICSI timing and the best polar body position during the injection have not been clarified; injected zona-free oocytes, if handled carefully, can develop up to blastocyst stage and implant; efficient options can be offered to patients who suffered fertilization failure in previous conventional ICSI cycles. Most controversial and inconclusive are data on the best method to select a viable spermatozoa when only immotile spermatozoa are available for ICSI and, to date, there is no reliable approach to completely filter out spermatozoa with fragmented DNA from an ejaculate. However, most of the studies do not report essential clinical outcomes, such as live birth, miscarriage and fetal abnormality rate, which are essential to establish the safety of a procedure.
This review provides the current knowledge on some controversial technical aspects of the ICSI procedures in order to improve its efficacy in specific contexts. Notwithstanding that embryologists might benefit from the approaches presented herein in order to improve ICSI outcomes, this area of expertise still demands a greater number of well-designed studies, especially in order to solve open issues about the safety of these procedures.
Objective To evaluate serum antimüllerian hormone (AMH) level modification after surgical excision of ovarian endometriomas. Design Systematic review. MEDLINE search from January 1990 to April 2012 ...using the combination of medical terms endometriosis, endometrioma, endometriotic cyst, and AMH or antimüllerian hormone, MIF or müllerian inhibiting factor. Reference lists of selected studies were checked for additional potential contributions. Setting Not applicable. Patient(s) Women with ovarian endometriomas requiring surgery. Intervention(s) Serum AMH level assessment. Main Outcome Measure(s) Serum AMH level modifications. Result(s) Eleven articles satisfied our selection criteria. Data pooling were deemed inopportune owing to the heterogeneity of the study designs and of the reported parameters. Nine of 11 studies documented a statistically significant reduction of serum AMH level after surgery. The two studies failing to document this decrease were published by the same study group and partly overlapped. The magnitude of the decline was more evident in women operated on for bilateral endometriomas. Conclusion(s) Evidence deriving from the evaluation of serum AMH level modifications after surgical excision of endometriomas supports a surgery-related damage to ovarian reserve.
The etiopathogenesis of endometriosis is a multifactorial process resulting in a heterogeneous disease. Considering that endometriosis etiology and pathogenesis are still far from being fully ...elucidated, the current review aims to offer a comprehensive summary of the available evidence. We performed a narrative review synthesizing the findings of the English literature retrieved from computerized databases from inception to June 2019, using the Medical Subject Headings (MeSH) unique ID term "Endometriosis" (ID:D004715) with "Etiology" (ID:Q000209), "Immunology" (ID:Q000276), "Genetics" (ID:D005823) and "Epigenesis, Genetic" (ID:D044127). Endometriosis may origin from Müllerian or non-Müllerian stem cells including those from the endometrial basal layer, Müllerian remnants, bone marrow, or the peritoneum. The innate ability of endometrial stem cells to regenerate cyclically seems to play a key role, as well as the dysregulated hormonal pathways. The presence of such cells in the peritoneal cavity and what leads to the development of endometriosis is a complex process with a large number of interconnected factors, potentially both inherited and acquired. Genetic predisposition is complex and related to the combined action of several genes with limited influence. The epigenetic mechanisms control many of the processes involved in the immunologic, immunohistochemical, histological, and biological aberrations that characterize the eutopic and ectopic endometrium in affected patients. However, what triggers such alterations is not clear and may be both genetically and epigenetically inherited, or it may be acquired by the particular combination of several elements such as the persistent peritoneal menstrual reflux as well as exogenous factors. The heterogeneity of endometriosis and the different contexts in which it develops suggest that a single etiopathogenetic model is not sufficient to explain its complex pathobiology.
We performed a comprehensive narrative synthesis of systematic reviews with meta-analysis published in the last 5 years on the association of endometriosis and adenomyosis with reproductive and ...obstetric outcomes. This review aimed to define the information on which to base preconceptional counseling and clarify whether and in which cases pregnant women with endometriosis and adenomyosis should be referred to tertiary care centers and followed as high-risk obstetric patients.
Reduced pregnancy and live birth rates and an increased miscarriage rate were observed in women with endometriosis and adenomyosis. The effect was larger in women with adenomyosis than in those with endometriosis. Women with superficial peritoneal and ovarian endometriosis do not appear to be at considerably increased risk of major obstetric and neonatal complications, whereas women with severe endometriosis, whether operated or not, are at several-fold increased risk of placenta previa. Moreover, deep infiltrating endometriosis is a risk factor for spontaneous hemoperitoneum in pregnancy and is associated with surgical complications at cesarean section. Overall, women with adenomyosis are at increased risk of various adverse obstetric outcomes, including preeclampsia, preterm delivery, fetal malpresentation, postpartum hemorrhage, low birth weight, and small for gestational age.
Most studies included in the considered systematic reviews are characterized by substantial qualitative and quantitative heterogeneity. This makes a reliable assessment of the available evidence difficult, and caution should be exercised when attempting to derive clinical indications.
Nevertheless, women with deep infiltrating endometriosis and severe adenomyosis should be considered at high obstetric risk and can benefit from referral to tertiary care centers where they can be safely followed through pregnancy and delivery. Whether the same should apply also to pregnant women with minimal endometriosis and adenomyosis forms is currently uncertain.
Emerging evidence suggests that some adverse reproductive and obstetric outcomes observed in women with endometriosis are, in fact, associated with coexisting adenomyosis.
Abstract Context The bladder is the most common site affected in urinary tract endometriosis. There is controversy regarding the pathogenesis, clinical management (diagnosis and treatment), impact on ...fertility, and risk of malignant transformation of bladder endometriosis (BE). Objective To systematically evaluate evidence regarding the pathogenesis, diagnosis, medical and surgical treatment, impact on female fertility, and risk of malignant transformation of BE. Evidence acquisition A systematic review of PubMed/Medline from inception until October 2016 was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and was registered in the PROSPERO registry ( www.crd.york.ac.uk/prospero; CRD42016039281). Eighty-seven articles were selected for inclusion in this analysis. Evidence synthesis BE is defined as the presence of endometrial glands and stroma in the detrusor muscle. Ultrasonography is the first-line technique for assessment of BE owing to its accuracy, safety, and cost. Clinical management can be conservative, using hormonal therapies, or surgical. When conservative treatment is preferred, estrogen-progestogen combinations and progestogens should be chosen because of their favorable profile that allows long-term therapy. Surgery should guarantee complete removal of the bladder nodule to minimize recurrence, so transurethral surgery alone should be avoided in favor of segmental bladder resection. There is not a strong rationale for hypothesizing a detrimental impact of BE per se on fertility. Furthermore, current evidence does not support the removal of bladder endometriotic lesions because of the potential risk of malignant transformation since this phenomenon is exceedingly rare. Conclusions BE is a challenging condition, and the common coexistence of other types of endometriosis means that clinical management of BE should involve collaboration between gynecologists and urologists. Patient summary In this article we review available knowledge on bladder endometriosis. The review provides a useful tool to guide physicians in the management of this complex condition.
ABSTRACT
Cryopreservation of reproductive cells and tissues represents an essential aspect of ART practices that might be particularly strategic and helpful during severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2) emergency. However, recommendations on how and when to preserve reproductive tissues and cells during a novel severe pandemic are scanty. This article uses a SWOT (strengths, weaknesses, opportunities and threats) analysis to identify favourable and unfavourable factors and to recognize challenges and obstacles related to the use of cryopreservation procedures during the spreading of a new virus. One of the strengths associated with the cryopreservation is represented by the availability of robust European guidelines on storage safety to prevent sample contamination or cross-contamination by pathogens. These recommendations should be deep-rooted in all ART laboratories. Weaknesses include uncertainties regarding the management of COVID-19 affected asymptomatic patients, the suboptimal accuracy of diagnostic tests for the disease, the nebulous prospective regarding the duration of the pandemic and the additional costs. The application of the strategy represents an opportunity to postpone pregnancy in order to avoid a severe infectious disease during gestation while concomitantly counteracting the possible detrimental effect of time. Critical threats, at present still undefined, are represented by potential adverse events for the mother and offspring due to infected gametes or embryos after thawing and, subsequently, the re-spreading of the virus.
Abstract
In the most recent version of the ‘WHO Laboratory Manual For The Examination And Processing Of Human Semen’, the updated target population used to infer reference values included 3589 ...fertile subjects, representative of 12 countries and 5 continents, and 10 studies. We have critically evaluated the newly proposed distribution of semen examination results using an approach borrowed from clinical chemistry laboratories and based on the recommendations of the International Federation of Clinical Chemistry for estimation of reference intervals. Surprisingly, most prerequisites to produce common reference intervals through multicentric data were not met. Moreover, when we assessed with the bootstrap method the descriptive reference values obtained from raw data of the 10 individual studies for sperm concentration, sperm number, motility and normal forms, we found that none of the populations was completely correctly described by the reference centiles. We concluded that aggregated data used to build the reference distribution cannot be considered to originate from the same population, and this can result from real differences among individuals or different methodological approaches used in the various studies. Transferability conditions across studies did not seem to have been met. Our findings strengthen the relevance of concerns regarding the use of reference populations in the World Health Organization manual to discriminate between fertile and infertile men.
Communication between embryo and maternal endometrium occurs during a specific time frame in which implantation is possible. Here we demonstrate for the first time that conditioned media from ...non-manipulated human embryos cultured in vitro for 3 days or up to the blastocyst stage contain extracellular vesicles (EVs) with a diameter of 50 to 200 nm and bearing the traditional microvesicle and exosome marker proteins CD63, CD9 and ALIX. The embryonic origin of these EVs has been confirmed by the presence of stemness gene transcripts and their enrichment in the non-classical HLA-G protein. NANOG and POU5F1 transcripts were shown to be contained in vesicles deriving from embryos at different stages of development. In line with a higher detection rate of the HLA-G protein in blastocysts compared to cleavage stage embryos, a significantly higher amount of HLA-G was found in vesicles accumulated in spent media from day 3 to day 5 of development compared to those isolated from the earlier stage. Uptake of dye-labeled embryo-derived EVs by human primary endometrial epithelial and stromal cells was also demonstrated with a fluorescence intensity signal significantly higher for cells treated with vesicles derived from blastocysts. Based on these findings, EV exchange may be suggested as an emerging way of communication at the maternal-fetal interface.
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