58 research outputs found
Does maternal age affect assisted reproduction technology success rates after euploid embryo transfer? A systematic review and meta-analysis
No full textImportance: Maternal age-related embryo aneuploidy is considered the most significant limiting factor for a favorable outcome after assisted reproduction technology (ART) procedures. Thus, preimplantation genetic testing for aneuploidies has been proposed as a strategy to genetically evaluate embryos before transfer to the uterus. However, whether embryo ploidy justifies all the aspects of age-related fertility decline remains controversial. Objective: To investigate the effect of different maternal ages on ART success rates after transfer of euploid embryos. Data Sources: ScienceDirect, PubMed, Scopus, Embase, the Cochrane library, Clinicaltrials.gov, EU Clinical Trials Register, and World Health Organization International Clinical Trials Registry were searched from inception until November 2021 using combinations of relevant keywords. Study Selection and Synthesis: Observational and randomized controlled studies were included if they investigated the impact of maternal age on ART outcomes after the transfer of euploid embryos and reported frequencies of women achieving ongoing pregnancy or live birth. Main Outcomes: The ongoing pregnancy rate or live birth rate (OPR/LBR) after euploid embryo transfer comparing women <35 vs. women ≥35 years old was the primary outcome. Secondary outcomes included implantation rate and miscarriage rate. Subgroup and sensitivity analyses were also planned to explore the sources of inconsistency among studies. The quality of studies was assessed using a modified version of the Newcastle-Ottawa Scale, and body of evidence was evaluated using the Grading of Recommendations Assessment Development and Evaluation working group methodology. Results: A total of 7 studies were included (n = 11,335 ART embryo transfers of euploid embryos). A higher OPR/LBR (odds ratio, 1.29; 95% confidence interval [CI], 1.07–1.54; I2 = 40%) in women aged <35 years than in women ≥35 with a risk difference equal to 0.06 (95% CI, 0.02–0.09) was found. In line, implantation rate was higher in the youngest group (odds ratio, 1.22; 95% CI, 1.12–1.32; I2 = 0%). A statistically significant higher OPR/LBR was also found comparing women aged <35 to women 35–37, 38–40, or 41–42. A gradient relationship between age and OPR/LBR could be observed in proportion meta-analysis, especially if restricted to studies with low risk of bias. Conclusion and Relevance: Increasing maternal age is associated with a decline in ART success rates independent of embryo ploidy. This message contributes to an appropriate patient's counseling before starting preimplantation genetic testing for aneuploidies procedures. PROSPERO Registration Number: CRD42021289760. © 2023 American Society for Reproductive Medicin
Does Maternal Age Affect Assisted Reproduction Technology Success Rates After Euploid Embryo Transfer? A Systematic Review and Meta-analysis
No full textDespite recent advancements in assisted reproductive technology (ART), the rate of live birth in advanced-age women remains suboptimal. Although many factors likely contribute, age-related embryo aneuploidy is considered the most significant determinant of cycle outcomes and has the lowest rate among women in their middle to late 20s but rises steadily from age 31 through 43 years. Preimplantation genetic testing for aneuploidies is routinely conducted to genetically evaluate embryos before transfer; however, the benefits are uncertain, and it has become a contested procedure in the field of reproductive medicine. Research on factors other than embryo chromosome segregation errors that may affect reproductive outcomes is needed.This systematic review and meta-analysis aimed to investigate whether increasing maternal age may limit ART success independent of ploidy status. Studies that evaluated the impact of maternal age on ART outcomes after the transfer of euploid embryos and included assessment of ongoing pregnancy rate (OPR) or live birth rate (LBR) were included. Ongoing pregnancy was defined as pregnancy beyond 12 weeks' gestation. The primary study outcome was comparison of OPR or LBR in women younger than 35 years compared with those 35 years or older. Additional analyses included evaluation of implantation rate and miscarriage rate (MR), as well as comparison between different age groups (ie, <35 vs 35-37, 38-40, 41-42, >42 years; <38 vs >= 38 years). The body of evidence was assessed by 2 investigators using the GRADE methodology. Meta-analysis of binary outcomes was performed with a random-effects model, and study outcomes were expressed using odds ratio (OR) with 95% confidence intervals (CIs).A total of 7 studies were included in this meta-analysis including 2 multicenter randomized controlled trials and 5 retrospective trials comprising a total of 11,335 embryo transfer cycles. Aneuploidy rate in biopsied blastocysts was reported in 4 studies and ranged between 28.9% and 54.2%. Meta-analysis revealed a significantly higher OPR/LBR (OR, 1.29; 95% CI, 1.07-1.54; P = 0.006; RD, 0.06; 95% CI, 0.02-0.09) among women younger than 35 years compared with those 35 years or older. In addition, the implantation rate was significantly higher in the youngest group (OR, 1.22; 95% CI, 1.12-1.32; P < 0.00001; RD, 0.04; 95% CI, 0.02-0.06), and there was a trend toward a lower MR (OR, 0.084; 95% CI, 0.71-1.00; P = 0.05; RD, -0.02; 95% CI, -0.03 to 0.00).The results of this study suggest that the increase in maternal age is associated with a lower OPR/LBR even after the transfer of euploid blastocysts. Notably, this gradient relationship between age and OPR/LBR remained when sensitivity analysis was conducted restricting analysis to only studies with low risk of bias
Intracytoplasmic sperm injection versus conventional in vitro insemination in couples with non-male infertility factor in the ‘real-world’ setting: analysis of the HFEA registry
No full textAbstract Background In assisted reproductive technology (ART), the choice between intracytoplasmic sperm injection (ICSI) and conventional in vitro insemination (IVF) remains a pivotal decision for couples with female or unexplained infertility. The hypothesis that ICSI may not confer significant improvements in live birth rates in the absence of a male infertility factor was explored in this study. Methods This was a retrospective collection of data recorded by the Human Fertilisation and Embryology Authority (HFEA) in the UK from 2005 to 2018 and analysed through regression analysis models on both the entire dataset and a matched-pair subset. First fresh ART cycles were analysed according to the insemination technique in order to compare live birth as the main outcome. Cycles were included if complete information regarding infertility cause, female age, number of oocytes retrieved, allocation to ICSI or IVF, and treatment outcome in terms of live birth was available. Matching was performed at a 1:1 ratio between IVF and ICSI cycles according to the cause of infertility, female age, number of oocytes, and year of treatment. Results This study, based on 275,825 first cycles, revealed that, compared with IVF, ICSI was associated with higher fertilization rates and lower cycle cancellations rates. However, ICSI was associated with a lower chance of implantation and live birth than IVF in cycles with female-only infertility: in the entire dataset, the adjusted odds of having a live birth decreased by a factor of 0.95 (95% CI 0.91–0.99, p = 0.011), while in the matched-pair analyses it decreased by a factor of 0.91 (95% CI 0.86–0.96, p = 0.003) using ICSI compared to IVF. For unexplained infertility cycles, the adjusted odds ratios for live birth in ICSI compared to IVF cycles were 0.98 (95% CI 0.95–1.01) in the entire dataset and 0.97 (95% CI 0.93–1.01) in the matched-pair analysis. Conclusions Compared with IVF, ICSI was associated with a reduction in live births when ART was indicated due to female-only factors. Additionally, no significant improvements were associated with the use of ICSI in cycles with unexplained infertility. Our findings impose a critical reevaluation regarding the use of ICSI over IVF for cases with female-only factors and unexplained infertility
Live Birth After Oocyte Donation In Vitro Fertilization Cycles in Women With Endometriosis
No full textImportance
Although multiple mechanisms have been proposed to explain the infertility related to endometriosis, there are no conclusive data on the association of endometriosis with endometrial receptivity. The oocyte donation model in assisted reproduction technology (ART) cycles can clarify this issue.
Objective
To explore the association of a history of endometriosis with ART outcomes in recipients of oocyte donation.
Data Sources
In this systematic review and meta-analysis, electronic databases were searched from inception until August 31, 2023, using combinations of relevant keywords. Moreover, we retrieved data from the databases of the Society for Assisted Reproductive Technology (SART) in the US and the Human Fertilization and Embryology Authority (HFEA) in the United Kingdom.
Study Selection
Observational studies were included if they investigated the impact of endometriosis on ART outcomes with donor oocytes.
Data Extraction and Synthesis
Publicly available data related to ART from various sources were gathered, and a retrospective aggregate and nonaggregate analysis using registries of in vitro fertilization cycles with oocyte or embryo donation was conducted.
Main Outcomes and Measures
The primary outcome was live birth rate (LBR) following oocyte donor cycles. The effect measures of comparisons between groups are presented as odds ratios (ORs) with a 95% CI.
Results
This study analyzed 7212 oocyte donation cycles from 4 studies for the meta-analysis, along with 162 082 cycles from 2 registries (137 182 from SART and 24 900 from HFEA). No significant differences between the groups were observed in the meta-analysis of published data after adjusting for confounding factors (OR, 0.54; 95% CI, 0.19-1.57). A statistically significant lower LBR was identified in women with endometriosis when analyzing the aggregate data from SART and HFEA databases (OR, 0.89; 95% CI, 0.81-0.97).
Conclusions and Relevance
This study found a modest decrease in LBR among women with a history of endometriosis, although only results from the pooled analysis of registry data and not those from the meta-analysis reached statistical significance. These findings suggest that a marginal impairment of uterine receptivity may contribute to infertility mechanisms in women affected by endometriosis
Long-acting recombinant follicle-stimulating hormone in random-start ovarian stimulation protocols for fertility preservation in women with cancer
No full textIntroduction: The objective of this study was to assess the effectiveness and potential benefits of the use of long-acting recombinant follicle-stimulating hormone (FSH) in a random-start protocol for fertility preservation in women with cancer. Material and methods: This is a retrospective before-and-after study performed between February 2013 and December 2015 in women who underwent ovarian hyperstimulation for oocyte cryobanking using a random-start approach. In the first part of the study period, the women were treated with daily recombinant FSH whereas in the second part the stimulation was initiated with long-acting recombinant FSH. The primary aim of the study was to compare the number of oocytes stored in the two study periods. In all, 140 women were ultimately selected. Results: Compared with daily recombinant FSH, the use of the long-acting compound was associated with a reduced number of injections (12.5 ± 3.5 vs. 16.4 ± 0.3; p < 0.001) and a longer duration of stimulation (11.4 ± 1.9 vs. 10.6 ± 1.9, p = 0.01). Conversely, the number of oocytes collected (13.7 ± 9.5 vs. 11.3 ± 7.0, p = 0.10) as well as those cryopreserved (11.0 ± 8.0 vs. 9.5 ± 5.8, p = 0.21) did not differ. Conclusions: The use of long-acting recombinant FSH in random-start protocols for fertility preservation appears to be a valuable option
The statistical foundation of the reference population for semen analysis included in the sixth edition of the WHO manual: a critical reappraisal of the evidence
No full textIn 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
Parthenogenesis in mammals: pros and cons in pluripotent cell derivation
No full textEmbryonic stem cells (ESCs) represent a useful tool for cell therapy studies, however the use of embryos for their derivation give rise to ethical, religious and legal problems when applied to the human. During the last years parthenogenesis has been proposed as an alternative source to obtain ESCs. Based on the fact that parthenotes avoid many concerns surrounding the "ad hoc" in vitro production and following destruction of viable human embryos. Unfortunately many aspects related to parthenogenetic cell biology are not fully understood and still need to be elucidated. In this review we describe advantages and limits of these cells. We discuss their typical ESC morphology and high telomerase activity, which disappears after differentiation. We examine the pluripotency signature that they share with bi-parental ESCs. We review their high differentiation plasticity that allow for the derivation of several mature cell type populations when we expose these cells to adequate conditions. On the other hand, in-depth analysis demonstrated chromosome mal-segregation and altered mechanisms controlling centriole arrangement and mitotic spindle formation in these cells. We hypothesize their monoparental origin as one of the possible cause of these anomalies and suggest a great caution if a therapeutic use is considered
Folate, homocysteine and selected vitamins and minerals status in infertile women
No full textDiet has been recognised as a crucial factor influencing fetal and maternal health. Adequate levels of substances such as homocysteine, folate and vitamin B12 have been associated with a higher rate of success in infertility treatments. Few data, however, are available on the average levels of micronutrients in the blood of reproductive-aged women, and specific values for adequate levels are not available. The aim of this cross-sectional study was to measure levels of folate, homocysteine and selected vitamins and minerals in women attending the infertility unit of an academic hospital for in vitro fertilisation (IVF)
The Gametotoxic Effects of the Endometrioma Content: Insights from a Parthenogenetic Human Model
No full textThe present randomized controlled in vitro study was designed to evaluate the effects of the exposure of human cryopreserved oocytes to endometriotic fluid. Twenty-three women aged 36 (4) years donated a total of 147 vitrified supernumerary metaphase II oocytes. Warmed oocytes were randomly assigned to exposure to endometriotic fluid or unexposed control. Thereafter, oocytes were parthenogenetically activated and cultured for up to 5 days. The rate of activation on day 1 and the developmental rates on days 3 and 5 did not significantly differ between the 2 groups. The rate of day 3 good quality parthenotes per oocyte was lower in exposed compared to unexposed oocytes, being 22% (13/60) and 41% (25/61), respectively. Moreover, in the exposed parthenotes, a significantly higher proportion of parthenotes failing to develop to the blastocyst stage showed cellular fragmentation (relative risk: 0.64, 95% confidence interval: 1.04-2.57). Exposure of human oocytes to endometriotic fluid has a negative effect on the morphology of deriving embryos/parthenotes mainly due to an excess of cellular fragmentation
Presence of antiphospholipid antibodies is associated with increased implantation failure following in vitro fertilization technique and embryo transfer: A systematic review and meta-analysis
No full textPurposeA systematic review and meta-analysis was conducted comparing the presence of anti-phospholipid (anti-PL) antibodies between women of reproductive age, without diagnosis of antiphospholipid syndrome, who experienced at least two implantation failures following in vitro fertilization and embryo transfer (IVF-ET), and either women who had a successful implantation after IVF-ET or women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET.MethodsSystematic search of the literature and meta-analysis of the relevant studies studying presence of antiphospholipid antibodies in women experiencing at least two implantation failures in IVF-ET as compared to either women who had a successful implantation after IVF-ET or/and women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET. Six hundred ninety-four published reports were retrieved; 17 of them fulfilled the inclusion criteria set.ResultsPresence of either any type of anti-phospholipid or anticardiolipin antibodies or lupus-anticoagulant in women experiencing at least two implantation failures in IVF-ET was associated with increased implantation failure compared to women who had a successful implantation after IVF-ET (relative risk, RR: 3.06, 5.06 and 5.81, respectively). Presence of either anticardiolipin or lupus-anticoagulant or anti-beta2 glycoprotein-I or anti-phosphatidylserine antibodies in women experiencing at least two implantation failures in IVF-EΤ was associated with increased implantation failure compared to unselected healthy fertile women with no history of IVF-ET (RR:13.92, 6.37, 15.04 and 164.58, respectively).ConclusionThe prevalence of antiphospholipid antibodies, particularly that of anti-beta2 glycoprotein-I and anti-phosphatidylserine antibodies, in women experiencing at least two implantation failures in IVF-ET without diagnosis of antiphospholipid syndrome is significantly greater than either in women who had a successful implantation after IVF-ET or women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET
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