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European Journal of Obstetrics,... Dec 2021To compare the available evidence of the effectiveness of single blastocyst stage transfer against the effectiveness of single cleavage stage embryo transfer. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To compare the available evidence of the effectiveness of single blastocyst stage transfer against the effectiveness of single cleavage stage embryo transfer.
STUDY DESIGN
A systematic research based on Pubmed, Embase and the Cochrane Library was performed until May 2, 2020 to identify all relevant studies. The Cochrane Collaboration's Review Manager (RevMan) 5.0.2 software was used for statistical analysis.
RESULTS
Five randomized controlled trials (RCTs) were included in analysis, involving 1784 patients in total, who were divided into 2 groups, which were the single blastocyst stage transfer (SBT) group of 932, and the single cleavage stage transfer (SCT) group of 852. Our meta-analysis concluded that SBT group had a significantly higher clinical pregnancy rate (RR 1.26; 95%CI: 1.14-1.39), ongoing pregnancy rate (RR 1.19; 95%CI: 1.05-1.35) and delivery rate (RR 1.4; 95%CI: 1.13-1.75) than SCT group during the fresh transfer. While miscarriage rate (RR 0.93; 95% CI: 0.66-1.33), multiple pregnancy rate (RR, 1.12; 95% CI, 0.51-2.45) and ectopic pregnancy rate (RR, 0.5; 95% CI: 0.13-1.90) between two groups showed no significant difference. However, the SCT group contained notably more cryopreserved embryos than the SBT group. (RR -0.68, 95% CI: -0.95 to -0.41).
CONCLUSIONS
Our results indicate that single blastocyst stage transfer is associated with higher ongoing pregnancy rate and delivery rate comparing to single cleavage stage transfer in the clinical practice. Due to the low quality of the evidence of the primary outcomes, other higher-quality lager RCTs are necessary before a fully informed decision is made.
Topics: Blastocyst; Cleavage Stage, Ovum; Embryo Transfer; Female; Fertilization in Vitro; Humans; Live Birth; Pregnancy; Pregnancy Rate; Single Embryo Transfer
PubMed: 34689021
DOI: 10.1016/j.ejogrb.2021.10.004 -
Reproductive Biomedicine Online Feb 2022The preservation of fertility in women of childbearing age with breast cancer is challenging because the time for ovarian stimulation is restricted and only a limited... (Meta-Analysis)
Meta-Analysis Review
The preservation of fertility in women of childbearing age with breast cancer is challenging because the time for ovarian stimulation is restricted and only a limited number of oocytes can be retrieved before gonadotoxic therapies. The aim of this meta-analysis was to evaluate the fertility preservation outcomes after ovarian stimulation with various protocols in women with breast cancer. PubMed, Embase and the Cochrane Library were searched. Twenty-two studies comparing the outcomes of women with breast cancer receiving random-start ovarian stimulation or conventional protocol; single or double ovarian stimulation cycles; and coadministration of aromatase inhibitors or tamoxifen were included. Random-start ovarian stimulation resulted in a comparable number of retrieved oocytes to the conventional protocol. Two ovarian stimulation cycles had significantly higher numbers of total retrieved oocytes than one cycle (mean difference 7.91, 95% confidence interval [CI] 3.42 to 12.40). Coadministration of letrozole and tamoxifen showed similar results for retrieved oocytes to those without. A significantly lower peak serum oestradiol concentration was observed in letrozole-based groups than in letrozole-free groups (mean difference -1.22; 95% CI -1.42 to -1.02). In conclusion, this study indicated that implementing random-start protocols to shorten the duration of waiting for ovarian stimulation, applying two ovarian stimulation cycles, and coadministration of letrozole can lead to more desirable outcomes.
Topics: Breast Neoplasms; Cryopreservation; Female; Fertility Preservation; Humans; Letrozole; Oocytes; Ovulation Induction; Tamoxifen
PubMed: 34656436
DOI: 10.1016/j.rbmo.2021.08.003 -
Reproductive Biology and Endocrinology... Sep 2021Sequential embryo transfer has been proposed as a way to improve embryo implantation in women for in vitro fertilization (IVF), but the effect on pregnancy outcomes...
BACKGROUND
Sequential embryo transfer has been proposed as a way to improve embryo implantation in women for in vitro fertilization (IVF), but the effect on pregnancy outcomes remains ambiguous. This systematic review was conducted to investigate the efficacy of sequential embryo transfer on IVF outcomes.
METHODS
A literature search was performed in the PubMed, Web of Science, Cochrane Library, ScienceDirect and Wanfang databases. Data were pooled using a random- or fixed-effects model according to study heterogeneity. The results are expressed as relative risks (RRs) with 95% confidence intervals (CIs). Heterogeneity was evaluated by the I statistic. The study protocol was registered prospectively on INPLASY, ID: INPLASY202180019.
RESULTS
Ten eligible studies with 2658 participants compared sequential embryo transfer and cleavage transfer, while four studies with 513 participants compared sequential embryo transfer and blastocyst transfer. The synthesis results showed that the clinical pregnancy rate was higher in the sequential embryo transfer group than in the cleavage embryo transfer group (RR 1.42, 95% CI 1.26-1.60, P< 0.01) for both women who did experience repeated implantation failure (RIF) (RR 1.58, 95% CI 1.17-2.13, P< 0.01) and did not experience RIF (Non-RIF) (RR 1.44, 95% CI 1.20-1.66, P< 0.01). However, sequential embryo transfer showed no significant benefit over blastocyst embryo transfer.
CONCLUSION
The current systematic review demonstrates that sequential cleavage and blastocyst embryo transfer improve the clinical pregnancy rate over conventional cleavage embryo transfer. For women with adequate embryos, sequential transfer could be attempted following careful consideration. More high-grade evidence from prospective randomized studies is warranted.
Topics: Blastocyst; Cleavage Stage, Ovum; Embryo Transfer; Embryo, Mammalian; Female; Fertilization in Vitro; Humans; Infertility; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Treatment Outcome
PubMed: 34521412
DOI: 10.1186/s12958-021-00824-y -
Fertility and Sterility Dec 2021To examine the disposition outcomes and disposition intentions of elective egg freezers (EEFs) toward their surplus frozen oocytes and the psychosocial determinants... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine the disposition outcomes and disposition intentions of elective egg freezers (EEFs) toward their surplus frozen oocytes and the psychosocial determinants underlying these.
DESIGN
A systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Actual EEFs (women with oocytes in storage), potential EEFs (women investigating elective oocyte cryopreservation or about to freeze their oocytes), and women of reproductive age (women in the community aged ≥18 years).
INTERVENTION(S)
A systematic review was undertaken and electronically searched MEDLINE, Embase, and PsycINFO on the Ovid platform for conference abstracts and peer-reviewed articles, published in English after January 1, 2010. A search strategy combined synonyms for oocyte, cryopreservation, donation, disposition, elective, and attitude. Eligible studies assessed disposition outcomes (how an oocyte was disposed of) and disposition intentions (how women intend to dispose of an oocyte) and/or the psychosocial determinants underlying disposition outcomes and intentions. The Joanna Briggs Institute Prevalence Tool was used to assess the risk of bias. A meta-analysis using random effects was applied to pool proportions of women with similar disposition intentions toward their oocytes.
MAIN OUTCOME MEASURE(S)
Disposition outcomes and intentions toward surplus frozen oocytes: donate to research; donate to others; discard; unsure. Psychosocial determinants (beliefs, attitudes, barriers, and facilitators) of disposition outcomes and intentions.
RESULT(S)
A total of 3,560 records were identified, of which 22 (17 studies) met the inclusion criteria (8 studies from Europe, 7 from North America, and 2 from Asia). No studies reported on past oocyte disposition outcomes. Seventeen studies reported on the future disposition intentions of 5,446 women. Only 2 of the 17 studies reported on the psychosocial determinants of oocyte disposition intentions. There was substantial heterogeneity in the pooled results, which was likely a result of the significant variation in methodology. Actual EEFs were included in eight studies (n = 873), of whom 53% (95% confidence interval [CI], 44-63; I, 87%) would donate surplus oocytes to research, 31% (95% CI, 23-40; I, 72%) were unsure, 26% (95% CI, 17-38; I, 92%) would donate to others, and 12% (95% CI, 6-21; I, 88%) would discard their eggs. Psychosocial determinants: One study reported that 50% of these women were aware of friends and/or family having difficulty conceiving, which may have contributed to their willingness to donate to others. Potential EEFs were included in 4 studies (n = 645), of whom 38% (95% CI, 28-50; I, 84%) would donate to research, 32% (95% CI, 17-51; I, 91%) would donate to others, 29% (95% CI, 17-44; I, 89%) would discard, and 7% (95% CI, 1-27; I, 77%) were unsure. Psychosocial determinants: No studies. Women of reproductive age were included in 5 studies (n = 3,933), of whom 59% (95% CI, 48-70; I, 97%) would donate to research and 46% (95% CI, 35-57; I, 98%) would donate to others. "Unsure" and "discard" were not provided as response options. Psychosocial determinants: One study reported that the facilitators for donation to others included a family member or friend in need, to help others create a family, financial gain, to further science, and control or input over the selection of recipients. Barriers for donation included fear of having a biological child they do not know or who is raised by someone they know.
CONCLUSION(S)
No studies reported on the disposition outcomes of past EEFs. Disposition intentions varied across the three groups; however, "donating to research" was the most common disposition preference. Notably, the second disposition preference for one-third of actual EEFs was "unsure" and for one-third of potential EEFs was "donate to others." There were limited studies for actual and potential EEFs, and only two studies that explored the psychosocial determinants of oocyte disposition intentions. Additionally, these data suggest that disposition decisions change as women progress on their egg freezing journey, highlighting the importance of ongoing contact with the fertility team as intentions may change over time. More research is needed to understand the psychosocial determinants of oocyte disposition decisions so fertility clinics can provide EEFs with the support and information they need to make informed decisions about their stored eggs and reduce the level of uncertainty reported among EEFs and the potential risk of psychological distress and regret.
CLINICAL TRIAL REGISTRATION NUMBER
PROSPERO 2020: CRD42020202733.
Topics: Adult; Embryo Disposition; Female; Fertility Preservation; Health Knowledge, Attitudes, Practice; Humans; Intention; Oocytes
PubMed: 34452749
DOI: 10.1016/j.fertnstert.2021.07.1195 -
Archives of Toxicology Oct 2021In the female reproductive tract, oocytes and embryos are in a dark environment, while during the in vitro fertilization (IVF) they are exposed to various visible and...
In the female reproductive tract, oocytes and embryos are in a dark environment, while during the in vitro fertilization (IVF) they are exposed to various visible and invisible lights such as daylight, microscope, and laminar hood fluorescent lights. Studies have shown that light could damage cellular compartments of oocytes and embryos and consequently decrease rates of fertilization, development, and blastocyst formation. However, due to the lack of consensus about the effects of light on the embryos, and subsequently the inability to make definitive decisions regarding the light exposure management to improve IVF results, in the present study, we systematically reviewed the effect of light with different wavelengths and intensities on pre-implantation embryos. The toxic impact of light depends on the wavelength, intensity, and duration of light exposure and also the stage of embryo. Therefore, reducing the observation time of embryos out of the incubator and also using light filters can alleviate the detrimental effect of light in IVF labs.
Topics: Animals; Blastocyst; Embryo Culture Techniques; Embryonic Development; Female; Fertilization in Vitro; Humans; Light; Oocytes; Time Factors
PubMed: 34448882
DOI: 10.1007/s00204-021-03139-4 -
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 -
FASEB Journal : Official Publication of... Jul 2021During the in vitro fertilization treatment, human chorionic gonadotrophin (hCG) is routinely used as a substitute for the natural endogenous LH surge during the final... (Meta-Analysis)
Meta-Analysis
During the in vitro fertilization treatment, human chorionic gonadotrophin (hCG) is routinely used as a substitute for the natural endogenous LH surge during the final stage of oocyte maturation. However, it does not provide the FSH surge observed in the mid-cycle of the natural cycle. To date, whether the FSH surge can improve oocyte quality and pregnancy outcomes remains unknown. Randomized controlled trials comparing the following four trigger methods to conventional hCG were examined: GnRH agonist (GnRHa), kisspeptin, GnRHa plus hCG (dual trigger), and FSH plus hCG (FSH co-trigger). The results showed that the use of dual triggers was associated with a significantly higher number of retrieved cumulus-oocyte complexes (COCs) (weighted mean difference [WMD] 1.625, 95% CI 0.684-2.565), retrieved mature oocytes (WMD 0.986, 95% CI 0.426-1.545) and fertilized (2PN) oocytes (WMD 0.792, 95% CI 0.083-1.501), compared with the use of hCG. However, there was no significant difference between the two groups in terms of pregnancy rate. The FSH co-trigger resulted in significantly higher rates of 2PN oocytes retrieved than the hCG trigger (WMD 0.077, 95% CI 0.028-0.126). Notably, the risk of OHSS did not differ among the three treatment groups compared to that of the hCG group. This review protocol was registered with PROSPERO (CRD 42020194201).
Topics: Female; Fertilization in Vitro; Humans; In Vitro Oocyte Maturation Techniques; Oocytes; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Sperm Injections, Intracytoplasmic
PubMed: 34085322
DOI: 10.1096/fj.202100406R -
Human Reproduction Update Aug 2021Miscarriage describes the spontaneous loss of pregnancy before the threshold of viability; the vast majority occur before 12 weeks of gestation. Miscarriage affects...
BACKGROUND
Miscarriage describes the spontaneous loss of pregnancy before the threshold of viability; the vast majority occur before 12 weeks of gestation. Miscarriage affects one in four couples and is the most common complication of pregnancy. Chromosomal abnormalities of the embryo are identified in ∼50% of first trimester miscarriages; aneuploidy accounts for 86% of these cases. The majority of trisomic miscarriages are of maternal origin with errors occurring during meiotic division of the oocytes. Chromosome segregation errors in oocytes may be sporadic events secondary to advancing maternal age; however, there is increasing evidence to suggest possible maternal germline contributions to this.
OBJECTIVE AND RATIONALE
The objective of this review was to appraise critically the existing evidence relating to maternal germline factors associated with pregnancy loss secondary to embryo aneuploidy, identify limitations in the current evidence base and establish areas requiring further research.
SEARCH METHODS
The initial literature search was performed in September 2019 and updated in January 2021 using the electronic databases OVID MEDLINE, EMBASE and the Cochrane Library. No time or language restrictions were applied to the searches and only primary research was included. Participants were women who had suffered pregnancy loss secondary to numerical chromosomal abnormalities of the embryo. Study identification and subsequent data extraction were performed by two authors independently. The Newcastle-Ottawa Scale was used to judge the quality of the included studies. The results were synthesized narratively.
OUTCOMES
The literature search identified 2198 titles once duplicates were removed, of which 21 were eligible for inclusion in this systematic review. They reported on maternal germline factors having variable degrees of association with pregnancy loss of aneuploid origin. The Online Mendelian Inheritance in Man (OMIM) gene ontology database was used as a reference to establish the functional role currently attributed to the genes reported. The majority of the cases reported and included were secondary to the inheritance of maternal structural factors such as Robertsonian translocations, deletions and insertions. Germline factors with a plausible role in aneuploid pregnancy loss of maternal origin included skewed X-inactivation and CGG repeats in the fragile X mental retardation (FMR1) gene. Studies that reported the association of single gene mutations with aneuploid pregnancy loss were conflicting. Single gene mutations with an uncertain or no role in aneuploid pregnancy loss included mutations in synaptonemal complex protein 3 (SYCP3), mitotic polo-like kinase 4 (PLK4) and meiotic stromal antigen 3 (STAG3) spindle integrity variants and 5,10-methylenetetrahydrofolate reductase (MTHFR).
WIDER IMPLICATIONS
Identifying maternal genetic factors associated with an increased risk of aneuploidy will expand our understanding of cell division, non-disjunction and miscarriage secondary to embryo aneuploidy. The candidate germline factors identified may be incorporated in a screening panel for women suffering miscarriage of aneuploidy aetiology to facilitate counselling for subsequent pregnancies.
Topics: Abortion, Spontaneous; Aneuploidy; Cell Cycle Proteins; Chromosome Segregation; Female; Fragile X Mental Retardation Protein; Humans; Maternal Age; Oocytes; Pregnancy; Protein Serine-Threonine Kinases
PubMed: 33969392
DOI: 10.1093/humupd/dmab010 -
Andrologia Jul 2021Zona pellucida (ZP)-bound spermatozoa have normal morphology and motility and can enhance the ICSI outcomes. Selection of zona pellucida-bound spermatozoa is recently... (Meta-Analysis)
Meta-Analysis Review
Zona pellucida (ZP)-bound spermatozoa have normal morphology and motility and can enhance the ICSI outcomes. Selection of zona pellucida-bound spermatozoa is recently considered to find functional spermatozoa for ICSI. This study reviewed the efficacy of ZP-bound sperm selection on the ICSI outcomes includes fertilisation rate, embryo quality, embryo transfer rate and clinical pregnancy rate. The databases searched include PubMed, Scopus and Cochrane databases up to January 2019. All research reports with full text and in English language that addressing the relation between ZP-sperm selection and ICSI outcomes were included. Fifty studies were suitable after screening of the 845 identified articles. After exclusions, five of these studies were included. Meta-analytic pooling of data indicated no association between the ICSI outcomes and ZP-bound sperm selection except a marginal effect on implantation rate. Eliminating one study indicated that ZP-bound sperm selection technique improves embryo quality, implantation rate and clinical pregnancy rate. This study revealed that ZP-bound sperm selection produces only a slight improvement in implantation rate. However, further studies with a large number of couples must be done to clarify the potential beneficial effect of ZP-bound spermatozoa on ICSI outcomes.
Topics: Female; Humans; Male; Pregnancy; Selection, Genetic; Sperm Injections, Intracytoplasmic; Sperm-Ovum Interactions; Spermatozoa; Zona Pellucida
PubMed: 33942906
DOI: 10.1111/and.14022 -
Journal of Obstetrics and Gynaecology :... Feb 2022The removal of cumulus cells in a process called oocyte denudation is required in order to visualise, grade and manipulate the oocytes before injection. The objective of... (Meta-Analysis)
Meta-Analysis
The removal of cumulus cells in a process called oocyte denudation is required in order to visualise, grade and manipulate the oocytes before injection. The objective of this study was to appraise critically the published randomised controlled trials (RCTs) comparing recombinant hyaluronidase with bovine hyaluronidase for oocyte denudation before intracytoplasmic sperm injection (ICSI). We performed a comprehensive literature search of the standard medical databases in order to identify the RCTs comparing oocyte denudation with recombinant hyaluronidase or bovine hyaluronidase before ICSI. Three RCTs involving 2445 oocytes collected from 200 women were analysed. There was substantial heterogeneity among the included RCTs. A meta-analysis from the available moderate to high quality trials found no statistical difference in terms of fertilisation rate, embryo quality and live birth rate between the use of recombinant or bovine hyaluronidase for oocyte denudation before ICSI.IMPACT STATEMENT The removal of cumulus cells in a process called oocyte denudation is required in order to visualise, grade and manipulate the oocytes before injection. The long-established source of hyaluronidase has been represented by bovine testes, but concern has been raised regarding the possible negative effects over the fragile oocytes by mechanisms involving low enzyme purity, variable concentrations, trauma, prolonged exposure and integration of external DNA in the oocyte. Recombinant human hyaluronidase has been proposed as an alternative in order to counteract the possible negative effects of using animal derived products. A meta-analysis from the available moderate to high quality trials found no statistical difference in fertilisation rate, embryo quality and live birth rate between the use of recombinant or bovine hyaluronidase for oocyte denudation before ICSI. Future trials should be powered adequately in order to be able to identify the possible small differences between the study groups and they should be conducted according to the CONSORT guidelines as the absence of blinding for outcome assessors can induce detection bias.
Topics: Animals; Birth Rate; Cattle; Female; Fertilization in Vitro; Humans; Hyaluronoglucosaminidase; Oocytes; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic
PubMed: 33938350
DOI: 10.1080/01443615.2021.1893670