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Reproductive Sciences (Thousand Oaks,... Oct 2022Oocyte morphology assessment is easy to implement in any laboratory with possible quality grading prior to fertilization. At present, comprehensive oocyte morphology... (Review)
Review
Oocyte morphology assessment is easy to implement in any laboratory with possible quality grading prior to fertilization. At present, comprehensive oocyte morphology scoring is not performed as a routine procedure. However, it may augment chances for successful treatment outcomes if a correlation with certain dysmorphisms can be proven. In order to determine a correlation between oocyte morphology and treatment outcome, we performed a systematic search in PubMed and Cochrane Controlled Trials Register following PRISMA guidelines. A total of 52 articles out of 6,755 search results met the inclusion criteria. Dark colour of the cytoplasm (observed with an incidence rate of 7%), homogeneous granularity of the cytoplasm (19%) and ovoid shape of oocytes (7%) appeared to have no influence on treatment outcome. Abnormalities such as refractile bodies (10%), fragmented first polar body (37%), dark zona pellucida (9%), enlarged perivitelline space (18%) and debris in it (21%) are likely to affect the treatment outcome to some extent. Finally, cytoplasmic vacuoles (4%), centrally located cytoplasmic granularity (12%) and clusters of smooth endoplasmic reticulum (4%) negatively impact infertility treatment outcomes. Nonetheless, morphological assessment is informative rather than predictive. Adding oocyte morphology to the artificial intelligence (AI)-driven selection process may improve the precision of the algorithms. Oocyte morphology assessment can be especially useful in oocyte donation cycles, during oocyte freezing for fertility preservation and finally, objective oocyte scoring can be important in cases of very poor treatment outcome as a tool for explanation of results to the patient.
Topics: Artificial Intelligence; Humans; Infertility; Oocyte Donation; Oocytes; Zona Pellucida
PubMed: 34816375
DOI: 10.1007/s43032-021-00723-y -
Human Reproduction Update Mar 2017Successful cryopreservation of oocytes and embryos is essential not only to maximize the safety and efficacy of ovarian stimulation cycles in an IVF treatment, but also... (Meta-Analysis)
Meta-Analysis Review
Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance.
BACKGROUND
Successful cryopreservation of oocytes and embryos is essential not only to maximize the safety and efficacy of ovarian stimulation cycles in an IVF treatment, but also to enable fertility preservation. Two cryopreservation methods are routinely used: slow-freezing or vitrification. Slow-freezing allows for freezing to occur at a sufficiently slow rate to permit adequate cellular dehydration while minimizing intracellular ice formation. Vitrification allows the solidification of the cell(s) and of the extracellular milieu into a glass-like state without the formation of ice.
OBJECTIVE AND RATIONALE
The objective of our study was to provide a systematic review and meta-analysis of clinical outcomes following slow-freezing/thawing versus vitrification/warming of oocytes and embryos and to inform the development of World Health Organization guidance on the most effective cryopreservation method.
SEARCH METHODS
A Medline search was performed from 1966 to 1 August 2016 using the following search terms: (Oocyte(s) [tiab] OR (Pronuclear[tiab] OR Embryo[tiab] OR Blastocyst[tiab]) AND (vitrification[tiab] OR freezing[tiab] OR freeze[tiab]) AND (pregnancy[tiab] OR birth[tiab] OR clinical[tiab]). Queries were limited to those involving humans. RCTs and cohort studies that were published in full-length were considered eligible. Each reference was reviewed for relevance and only primary evidence and relevant articles from the bibliographies of included articles were considered. References were included if they reported cryosurvival rate, clinical pregnancy rate (CPR), live-birth rate (LBR) or delivery rate for slow-frozen or vitrified human oocytes or embryos. A meta-analysis was performed using a random effects model to calculate relative risk ratios (RR) and 95% CI.
OUTCOMES
One RCT study comparing slow-freezing versus vitrification of oocytes was included. Vitrification was associated with increased ongoing CPR per cycle (RR = 2.81, 95% CI: 1.05-7.51; P = 0.039; 48 and 30 cycles, respectively, per transfer (RR = 1.81, 95% CI 0.71-4.67; P = 0.214; 47 and 19 transfers) and per warmed/thawed oocyte (RR = 1.14, 95% CI: 1.02-1.28; P = 0.018; 260 and 238 oocytes). One RCT comparing vitrification versus fresh oocytes was analysed. In vitrification and fresh cycles, respectively, no evidence for a difference in ongoing CPR per randomized woman (RR = 1.03, 95% CI: 0.87-1.21; P = 0.744, 300 women in each group), per cycle (RR = 1.01, 95% CI: 0.86-1.18; P = 0.934; 267 versus 259 cycles) and per oocyte utilized (RR = 1.02, 95% CI: 0.82-1.26; P = 0.873; 3286 versus 3185 oocytes) was reported. Findings were consistent with relevant cohort studies. Of the seven RCTs on embryo cryopreservation identified, three met the inclusion criteria (638 warming/thawing cycles at cleavage and blastocyst stage), none of which involved pronuclear-stage embryos. A higher CPR per cycle was noted with embryo vitrification compared with slow-freezing, though this was of borderline statistical significance (RR = 1.89, 95% CI: 1.00-3.59; P = 0.051; three RCTs; I2 = 71.9%). LBR per cycle was reported by one RCT performed with cleavage-stage embryos and was higher for vitrification (RR = 2.28; 95% CI: 1.17-4.44; P = 0.016; 216 cycles; one RCT). A secondary analysis was performed focusing on embryo cryosurvival rate. Pooled data from seven RCTs (3615 embryos) revealed a significant improvement in embryo cryosurvival following vitrification as compared with slow-freezing (RR = 1.59, 95% CI: 1.30-1.93; P < 0.001; I2 = 93%).
WIDER IMPLICATIONS
Data from available RCTs suggest that vitrification/warming is superior to slow-freezing/thawing with regard to clinical outcomes (low quality of the evidence) and cryosurvival rates (moderate quality of the evidence) for oocytes, cleavage-stage embryos and blastocysts. The results were confirmed by cohort studies. The improvements obtained with the introduction of vitrification have several important clinical implications in ART. Based on this evidence, in particular regarding cryosurvival rates, laboratories that continue to use slow-freezing should consider transitioning to the use of vitrification for cryopreservation.
Topics: Birth Rate; Blastocyst; Cohort Studies; Cryopreservation; Embryo Culture Techniques; Embryo Transfer; Female; Humans; Odds Ratio; Oocytes; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic
PubMed: 27827818
DOI: 10.1093/humupd/dmw038 -
International Journal of Environmental... Jul 2021Increasing numbers of women are undergoing oocyte or tissue cryopreservation for medical or social reasons to increase their chances of having genetic children. Social... (Review)
Review
Increasing numbers of women are undergoing oocyte or tissue cryopreservation for medical or social reasons to increase their chances of having genetic children. Social egg freezing (SEF) allows women to preserve their fertility in anticipation of age-related fertility decline and ineffective fertility treatments at older ages. The purpose of this study was to summarize recent findings focusing on the challenges of elective egg freezing. We performed a systematic literature review on social egg freezing published during the last ten years. From the systematically screened literature, we identified and analyzed five main topics of interest during the last decade: (a) different fertility preservation techniques, (b) safety of freezing, (c) usage rate of frozen oocytes, (d) ethical considerations, and (e) cost-effectiveness of SEF. Fertility can be preserved for non-medical reasons through oocyte, embryos, or ovarian tissue cryopreservation, with oocyte vitrification being a new and optimal approach. Elective oocyte cryopreservation is better accepted, supports social gender equality, and enhances women's reproductive autonomy. Despite controversies, planned oocyte cryopreservation appears as a chosen strategy against age-related infertility and may allow women to feel that they are more socially, psychologically, and financially stable before motherhood.
Topics: Aged; Child; Cryopreservation; Female; Fertility; Fertility Preservation; Humans; Middle Aged; Oocytes; Reproductive Techniques, Assisted
PubMed: 34360381
DOI: 10.3390/ijerph18158088 -
Human Reproduction (Oxford, England) Mar 2023What are the chances of achieving a live birth after embryo, oocyte and ovarian tissue cryopreservation (OTC) in female cancer survivors? (Meta-Analysis)
Meta-Analysis
Live birth rate after female fertility preservation for cancer or haematopoietic stem cell transplantation: a systematic review and meta-analysis of the three main techniques; embryo, oocyte and ovarian tissue cryopreservation.
STUDY QUESTION
What are the chances of achieving a live birth after embryo, oocyte and ovarian tissue cryopreservation (OTC) in female cancer survivors?
SUMMARY ANSWER
The live birth rates (LBRs) following embryo and oocyte cryopreservation are 41% and 32%, respectively, while for IVF and spontaneous LBR after tissue cryopreservation and transplantation, these rates are 21% and 33%, respectively.
WHAT IS KNOWN ALREADY
Currently, fertility preservation (FP) has become a major public health issue as diagnostic and therapeutic progress has made it possible to achieve an 80% survival rate in children, adolescents and young adults with cancer. In the latest ESHRE guidelines, only oocyte and embryo cryopreservation are considered as established options for FP. OTC is still considered to be an innovative method, while it is an acceptable FP technique in the American Society for Reproductive Medicine guidelines. However, given the lack of studies on long-term outcomes after FP, it is still unclear which technique offers the best chance to achieve a live birth.
STUDY DESIGN, SIZE, DURATION
We performed a systematic review and meta-analysis of published controlled studies. Searches were conducted from January 2004 to May 2021 in Medline, Embase and the Cochrane Library using the following search terms: cancer, stem cell transplantation, FP, embryo cryopreservation, oocyte vitrification, OTC and reproductive outcome.
PARTICIPANTS/MATERIALS, SETTING, METHODS
A total of 126 full-text articles were preselected from 1436 references based on the title and abstract and assessed via the Newcastle-Ottawa Quality Assessment Scale. The studies were selected, and their data were extracted by two independent reviewers according to the Cochrane methods. A fixed-effect meta-analysis was performed for outcomes with high heterogeneity.
MAIN RESULTS AND THE ROLE OF CHANCE
Data from 34 studies were used for this meta-analysis. Regarding cryopreserved embryos, the LBR after IVF was 41% (95% CI: 34-48, I2: 0%, fixed effect). Concerning vitrified oocytes, the LBR was 32% (95% CI: 26-39, I2: 0%, fixed effect). Finally, the LBR after IVF and the spontaneous LBR after ovarian tissue transplantation were 21% (95% CI: 15-26, I2: 0%, fixed-effect) and 33% (95% CI: 25-42, I2: 46.1%, random-effect), respectively. For all outcomes, in the sensitivity analyses, the maximum variation in the estimated percentage was 1%.
LIMITATIONS, REASONS FOR CAUTION
The heterogeneity of the literature prevents us from comparing these three techniques. This meta-analysis provides limited data which may help clinicians when counselling patients.
WIDER IMPLICATIONS OF THE FINDINGS
This study highlights the need for long-term follow-up registries to assess return rates, as well as spontaneous pregnancy rates and birth rates after FP.
STUDY FUNDING/COMPETING INTEREST(S)
This work was sponsored by an unrestricted grant from GEDEON RICHTER France. The authors have no competing interests to declare.
REGISTRATION NUMBER
CRD42021264042.
Topics: Pregnancy; Female; Humans; Fertility Preservation; Birth Rate; Cryopreservation; Oocytes; Pregnancy Rate; Live Birth; Neoplasms; Hematopoietic Stem Cell Transplantation; Retrospective Studies
PubMed: 36421038
DOI: 10.1093/humrep/deac249 -
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 -
Journal of Ovarian Research Jul 2017Endometriosis is an estrogen-dependent chronic inflammatory condition that affects women in their reproductive period causing infertility and pelvic pain. The disease,... (Meta-Analysis)
Meta-Analysis Review
Endometriosis is an estrogen-dependent chronic inflammatory condition that affects women in their reproductive period causing infertility and pelvic pain. The disease, especially at the ovarian site has been shown to have a detrimental impact on ovarian physiology. Indeed, sonographic and histologic data tend to support the idea that ovarian follicles of endometriosis patients are decreased in number and more atretic. Moreover, the local intrafollicular environment of patients affected is characterized by alterations of the granulosa cell compartment including reduced P450 aromatase expression and increased intracellular reactive oxygen species generation. However, no comprehensive evaluation of the literature addressing the effect of endometriosis on oocyte quality from both a clinical and a biological perspective has so far been conducted. Based on this systematic review of the literature, oocytes retrieved from women affected by endometriosis are more likely to fail in vitro maturation and to show altered morphology and lower cytoplasmic mitochondrial content compared to women with other causes of infertility. Results from meta-analyses addressing IVF outcomes in women affected would indicate that a reduction in the number of mature oocytes retrieved is associated with endometriosis while a reduction in fertilization rates is more likely to be associated with minimal/mild rather than with moderate/severe disease. However, evidence in this field is still far to be conclusive, especially with regards to the effects of different stages of the disease and to the impact of patients' previous medical/surgical treatment(s).
Topics: Biomarkers; Cellular Microenvironment; Endometriosis; Female; Fertilization in Vitro; Granulosa Cells; Humans; Infertility, Female; Oocytes; Ovarian Follicle; Ovary; Pregnancy
PubMed: 28701212
DOI: 10.1186/s13048-017-0341-4 -
Journal of Clinical Oncology : Official... Jul 2013To update guidance for health care providers about fertility preservation for adults and children with cancer. (Review)
Review
PURPOSE
To update guidance for health care providers about fertility preservation for adults and children with cancer.
METHODS
A systematic review of the literature published from March 2006 through January 2013 was completed using MEDLINE and the Cochrane Collaboration Library. An Update Panel reviewed the evidence and updated the recommendation language.
RESULTS
There were 222 new publications that met inclusion criteria. A majority were observational studies, cohort studies, and case series or reports, with few randomized clinical trials. After review of the new evidence, the Update Panel concluded that no major, substantive revisions to the 2006 American Society of Clinical Oncology recommendations were warranted, but clarifications were added.
RECOMMENDATIONS
As part of education and informed consent before cancer therapy, health care providers (including medical oncologists, radiation oncologists, gynecologic oncologists, urologists, hematologists, pediatric oncologists, and surgeons) should address the possibility of infertility with patients treated during their reproductive years (or with parents or guardians of children) and be prepared to discuss fertility preservation options and/or to refer all potential patients to appropriate reproductive specialists. Although patients may be focused initially on their cancer diagnosis, the Update Panel encourages providers to advise patients regarding potential threats to fertility as early as possible in the treatment process so as to allow for the widest array of options for fertility preservation. The discussion should be documented. Sperm and embryo cryopreservation as well as oocyte cryopreservation are considered standard practice and are widely available. Other fertility preservation methods should be considered investigational and should be performed by providers with the necessary expertise.
Topics: Adolescent; Adult; Child; Communication; Cryopreservation; Decision Making; Embryo, Mammalian; Evidence-Based Medicine; Female; Fertility; Health Services Accessibility; Healthcare Disparities; Humans; Infertility; Infertility, Female; Infertility, Male; Interdisciplinary Communication; Male; Neoplasms; Oocytes; Ovary; Patient Care Team; Patient Education as Topic; Referral and Consultation; United States
PubMed: 23715580
DOI: 10.1200/JCO.2013.49.2678 -
Journal of Assisted Reproduction and... Jul 2018Mammalian oogenesis and folliculogenesis share a dynamic connection that is critical for gamete development. For maintenance of quiescence or follicular activation,... (Review)
Review
PURPOSE
Mammalian oogenesis and folliculogenesis share a dynamic connection that is critical for gamete development. For maintenance of quiescence or follicular activation, follicles must respond to soluble signals (growth factors and hormones) and physical stresses, including mechanical forces and osmotic shifts. Likewise, mechanical processes are involved in cortical tension and cell polarity in oocytes. Our objective was to examine the contribution and influence of biomechanical signaling in female mammalian gametogenesis.
METHODS
We performed a systematic review to assess and summarize the effects of mechanical signaling and mechanotransduction in oocyte maturation and folliculogenesis and to explore possible clinical applications. The review identified 2568 publications of which 122 met the inclusion criteria.
RESULTS
The integration of mechanical and cell signaling pathways in gametogenesis is complex. Follicular activation or quiescence are influenced by mechanical signaling through the Hippo and Akt pathways involving the yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), phosphatase and tensin homolog deleted from chromosome 10 (PTEN) gene, the mammalian target of rapamycin (mTOR), and forkhead box O3 (FOXO3) gene.
CONCLUSIONS
There is overwhelming evidence that mechanical signaling plays a crucial role in development of the ovary, follicle, and oocyte throughout gametogenesis. Emerging data suggest the complexities of mechanotransduction and the biomechanics of oocytes and follicles are integral to understanding of primary ovarian insufficiency, ovarian aging, polycystic ovary syndrome, and applications of fertility preservation.
Topics: Animals; Female; Humans; Mechanotransduction, Cellular; Oocytes; Oogenesis; Ovarian Follicle; Ovary; Signal Transduction
PubMed: 29691711
DOI: 10.1007/s10815-018-1180-y -
Biology of Reproduction Feb 2022The ovary is the first organ to age in humans with functional decline evident already in women in their early 30s. Reproductive aging is characterized by a decrease in...
The ovary is the first organ to age in humans with functional decline evident already in women in their early 30s. Reproductive aging is characterized by a decrease in oocyte quantity and quality, which is associated with an increase in infertility, spontaneous abortions, and birth defects. Reproductive aging also has implications for overall health due to decreased endocrinological output. Understanding the mechanisms underlying reproductive aging has significant societal implications as women globally are delaying childbearing and medical interventions have greatly increased the interval between menopause and total lifespan. Age-related changes inherent to the female gamete are well-characterized and include defects in chromosome and mitochondria structure, function, and regulation. More recently, it has been appreciated that the extra-follicular ovarian environment may have important direct or indirect impacts on the developing gamete, and age-dependent changes include increased fibrosis, inflammation, stiffness, and oxidative damage. The cumulus cells and follicular fluid that directly surround the oocyte during its final growth phase within the antral follicle represent additional critical local microenvironments. Here we systematically review the literature and evaluate the studies that investigated the age-related changes in cumulus cells and follicular fluid. Our findings demonstrate unique genetic, epigenetic, transcriptomic, and proteomic changes with associated metabolomic alterations, redox status imbalance, and increased apoptosis in the local oocyte microenvironment. We propose a model of how these changes interact, which may explain the rapid decline in gamete quality with age. We also review the limitations of published studies and highlight future research frontiers.
Topics: Cumulus Cells; Female; Follicular Fluid; Humans; Oocytes; Ovarian Follicle; Pregnancy; Proteomics
PubMed: 34982142
DOI: 10.1093/biolre/ioab241 -
Reproductive Biology and Endocrinology... Jul 2023To explore whether prolonged hCG-ovum pickup interval improves assisted reproductive technology outcomes. (Meta-Analysis)
Meta-Analysis Review
RESEARCH QUESTION
To explore whether prolonged hCG-ovum pickup interval improves assisted reproductive technology outcomes.
DESIGN
CENTRAL, CNKI, Cochrane Systematic Reviews, EMBASE, MEDLINE, PUBMED, and Web of Science up to May 13 2023 were searched for studies reporting associations between hCG-ovum pickup intervals and assisted reproductive technology outcomes. Intervention types included short (≤ 36 h) and long (> 36 h) hCG-ovum pickup intervals in assisted reproductive technology cycles. All outcomes were based upon only fresh embryo transfers. Primary outcome is defined as the clinical pregnancy rate. Data were pooled using random-effects models. Heterogeneity was assessed using the I 2 statistics.
RESULTS
Twelve studies were included in the meta-analysis, including five retrospective cohort studies, one prospective cohort study, and six randomized or quasi-randomized controlled trials. The short and long interval groups had similar oocyte maturation rates, fertilization rate and high-quality embryo rate (OR, 0.69; 95% CI, 0.45-1.06; I 2 = 91.1%, OR, 0.88; 95% CI, 0.77-1.0; I 2 = 44.4% and OR, 1.05; 95% CI, 0.95-1.17; I 2 = 8.6%, respectively). The clinical pregnancy rates in the long retrieval group were significantly higher than in the short retrieval group (OR, 0.66; 95% CI, 0.45-0.95; I 2 = 35.4%). The groups had similar miscarriage and live birth rates (OR, 1.92; 95% CI, 0.66-5.60; I 2 = 0.0% and OR, 0.50; 95% CI, 0.24-1.04; I 2 = 0.0%, respectively).
CONCLUSIONS
The clinical pregnancy rates can be increased by prolonging the hCG-ovum pickup interval, which would help us develop more reasonable time schedules for fertility centers and patients.
META-ANALYSIS REGISTRATION
PROSPERO CRD42022310006 (28 Apr 2022).
Topics: Pregnancy; Female; Humans; Oocyte Retrieval; Retrospective Studies; Prospective Studies; Pregnancy Rate; Chorionic Gonadotropin; Live Birth; Fertilization in Vitro
PubMed: 37400840
DOI: 10.1186/s12958-023-01110-9