Project description:This study aimed to compare the clinical outcomes between in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in sibling oocytes. Additionally, we evaluated whether the implementation of split insemination contributed to an increase in the number of ICSI procedures.A total of 571 cycles in 555 couples undergoing split insemination cycles were included in this study. Among them, 512 cycles (89.7%) were a couple's first IVF cycle. The patients were under 40 years of age and at least 10 oocytes were retrieved in all cycles. Sibling oocytes were randomly allocated to IVF or ICSI.Total fertilization failure was significantly more common in IVF cycles than in ICSI cycles (4.0% vs. 1.4%, p<0.05), but the low fertilization rate among retrieved oocytes (as defined by fertilization rates greater than 0% but <30%) was significantly higher in ICSI cycles than in IVF cycles (17.2% vs. 11.4%, p<0.05). The fertilization rate of ICSI among injected oocytes was significantly higher than for IVF (72.3%±24.3% vs. 59.2%±25.9%, p<0.001), but the fertilization rate among retrieved oocytes was significantly higher in IVF than in ICSI (59.2%±25.9% vs. 52.1%±22.5%, p<0.001). Embryo quality before embryo transfer was not different between IVF and ICSI. Although the sperm parameters were not different between the first cycle and the second cycle, split insemination or ICSI was performed in 18 of the 95 cycles in which a second IVF cycle was performed.The clinical outcomes did not differ between IVF and ICSI in split insemination cycles. Split insemination can decrease the risk of total fertilization failure. However, unnecessary ICSI is carried out in most split insemination cycles and the use of split insemination might make ICSI more common.
Project description:In order to find out to what extent ovarian aging could be compensated by the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatments, a total of 4102 women above the age of 35 undergoing 6489 complete cycles from 2009 to 2015 with follow-up visits until 2017 were retrospectively analyzed. Cumulative live birth rates (CLBRs) across multiple IVF/ICSI cycles were compared in the study population stratified by age and ovarian reserve (classified by the POSEIDON criteria). Younger patients (aged between 35 and 40) could well benefit from repeat IVF treatments, with the optimal CLBRs ranging from 62%-72% for up to four complete cycles. However, the CLBRs sharply declined to 7.7%-40% in older patients (>40yrs). In light of ovarian reserve, the optimal-estimated-four-cycle CLBR of younger patients (35-40yrs) in POSEIDON group 2 could approached to those with normal ovarian response (non-POSEIDON), with 57.3%-70% versus 74.5%-81% respectively. However, the CLBR of older patients (>40yrs) in POSEIDON group 2 only reached 50% of their counterparts. Extending the number of IVF cycles beyond three or four is effective for advanced-aged women, especially in younger normal responders (non-POSEIDON) and unexpected poor/suboptimal responders (POSEIDON group 2). The real turning point at which female fecundity dropped after multiple IVF cycles is at the age of 40.
Project description:Study questionDoes the duration of embryo exposure to hyaluronic acid (HA) enriched medium improve the rate of live birth events (LBEs)?Summary answerThe use of embryo transfer (ET) medium rich in HA improves LBE (a singleton or twin live birth) regardless of the duration of exposure evaluated in this study, but does not alter gestation or birthweight (BW).What is known alreadyHA-enriched medium is routinely used for ET in ART to facilitate implantation, despite inconclusive evidence on safety and efficacy.Study design size durationA cohort study was performed evaluating clinical treatment outcomes before and after HA-enriched ET medium was introduced into routine clinical practice. In total, 3391 fresh ET procedures were performed using low HA and HA-rich medium in women undergoing publicly funded IVF/ICSI treatment cycles between May 2011 and April 2015 were included in this cohort study.Participants/materials setting methodsA total of 1018 ET performed using low HA medium were compared with 1198, and 1175 ET following exposure to HA-rich medium for 2-4 h (long HA exposure) or for 10-30 min (short HA exposure), respectively. A multiple logistic regression analysis was used to compare clinical outcomes including BW, gestational age and sex ratios between groups, whilst adjusting for patient age, previous attempt, incubator type and the number of embryos transferred.Main results and the role of chanceThe use of HA-rich medium for ET was positively and significantly associated with improved clinical pregnancy rate and LBE, for both exposure durations: long HA (odds ratio (OR) = 1.21, 95% CI: 0.99-1.48), short HA (OR = 1.32, 95% CI: 1.02-1.72) and pooled OR = 1.26, 95% CI: 1.03-1.54, relative to the use of low HA medium. A comparative analysis of the risks of early pregnancy loss following long HA exposure (OR = 0.76, 95% CI: 0.54-1.06), short HA exposure (OR = 0.84, 95% CI: 0.54-1.30) and late miscarriage (OR = 0.88, 95% CI: 0.51-1.53) (OR = 1.41, 95% CI 0.72-2.77), were lower and not statistically significant. Similarly, ordinary regression analysis of the differences in BW at both HA exposures; pooled OR = -0.9 (-117.1 to 115.3), and adjusted BW between both HA cohorts; pooled OR = -13.8 (-106.1 to 78.6) did not show any differences. However, a difference in gestational age (pooled OR -0.3 (-3.4 to 2.9)) and sex ratio (pooled OR 1.43 (0.95-2.15)) were observed but these were not statistically significant relative to low HA medium.Limitations reasons for cautionThe strength of a randomized treatment allocation was not available in this evaluation study, therefore effects of unmeasured or unknown confounding variables cannot be ruled out.Wider implications of the findingsThe result of this large cohort study strengthens the case for using HA-rich medium routinely at transfer, while adding the important clinical information that duration of exposure may not be critical. The composition and effects of commercial IVF culture media on success rate and safety remains a major controversy despite increasing calls for transparency and evidence-based practice in ART. Nonetheless, the lack of differences in BW and gestational age observed in this study were reassuring. However, an appraisal of clinical outcomes and appropriate research investigations are required for the continuous evaluation of efficacy and safety of HA.Study funding/competing interestsT.A. is funded by a Clinical Doctoral Research Fellowship (CDRF) grant (reference: ICA-CDRF-2015-01-068) from the National Institute for Health Research (NIHR). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. The authors declare no conflict of interest.
Project description:It has been widely acknowledged that anti-Müllerian hormone (AMH) is a golden marker of ovarian reserve. Declined ovarian reserve (DOR), based on experience from reproductive-aged women, refers to both the quantitative and qualitative reduction in oocytes. This view is challenged by a recent study clearly showing that the quality of oocytes is similar in young women undergoing IVF cycles irrespective of the level of AMH. However, it remains elusive whether AMH indicates oocyte quality in women with advanced age (WAA). The aim of this study was to investigate this issue. In the present study, we retrospectively analysed the data generated from a total of 492 IVF/ICSI cycles (from January 2017 to July 2020), and these IVF/ICSI cycles contributed 292 embryo transfer (ET) cycles (from June 2017 to September 2019, data of day 3 ET were included for analysis) in our reproductive centre. Based on the level of AMH, all patients (= > 37 years old) were divided into 2 groups: the AMH high (H) group and the AMH low (L) group. The parameters of in vitro embryo development and clinical outcomes were compared between the two groups. The results showed that women in the L group experienced severe DOR, as demonstrated by a higher rate of primary diagnosis of DOR, lower antral follicle count (AFC), higher level of basal follicle stimulating hormone (FSH) and cancelation cycles, lower level of E2 production on the day of surge, and fewer oocytes and MII oocytes retrieved. Compared with women in the H group, women in the L group showed slightly reduced top embryo formation rate but a similar normal fertilization rate and blastocyst formation rate. More importantly, we found that the rates of implantation, spontaneous miscarriage and livebirth were similar between the two groups, while the pregnancy rate was significantly reduced in the L group compared with the H group. Further analysis indicated that the higher pregnancy rate of women in the H group may be due to more top embryos transferred per cycle. Due to an extremely low implantation potential for transfer of non-top embryos from WAA (= > 37 years old) in our reproductive centre, we assumed that all the embryos that implanted may result from the transfer of top embryos. Based on this observation, we found that the ratio of embryos that successfully implanted or eventually led to a livebirth to top embryos transferred was similar between the H and the L groups. Furthermore, women with clinical pregnancy or livebirth in the H or L group did not show a higher level of serum AMH but were younger than women with non-pregnancy or non-livebirth. Taken together, this study showed that AMH had a limited role in predicting in vitro embryo developmental potential and had no role in predicting the in vivo embryo developmental potential, suggesting that in WAA, AMH should not be used as a marker of oocyte quality. This study supports the view that the accumulation of top embryos via multiple oocyte retrieval times is a good strategy for the treatment of WAA.
Project description:PurposeTo investigate whether personalized embryo transfer (pET) protocol guided by an endometrial receptivity array (ERA) can improve clinical outcomes of assisted reproduction.MethodsWe searched PubMed, Embase, Web of Science, and the Cochrane library for studies in which analytical comparisons of outcomes of pET and standard embryo transfer (sET) groups were undertaken. The references to the included studies were also manually searched. The primary outcome was clinical pregnancy rate (CPR), and the secondary outcomes were live birth rate (LBR), human chorionic gonadotropin (HCG) positivity, biochemical pregnancy rate (BPR), miscarriage rate (MR), implantation rate (IR), and ongoing pregnancy rate (OPR).ResultsTen studies were included in the meta-analysis, including one randomized controlled trial (RCT) and nine cohort studies. We observed no significant difference in the primary outcome of CPR between the pET and sET groups in unselected patients (RR = 1.07; 95% confidence interval [CI], 0.87-1.30; P = 0.53; I2 = 89%). In terms of secondary outcomes, we likewise noted no significant differences between the groups. Further subgroup analyses indicated that the pET protocol not only significantly reduced the MR for poor-prognosis patients, but it also reduced the CPR in donor cycles, elevated the BPR for good-prognosis patients, non-preimplantation genetic testing (PGT), and programmed cycles, and decreased the proportion of women showing HCG positivity in non-PGT cycles.ConclusionsThis meta-analysis revealed that ERA appears to possess limited guidance in embryo transfer. More high-quality RCTs are therefore needed to investigate the clinical validity and feasibility of ERA in the future.
Project description:PurposeChromosomal polymorphisms (CPs) have been reported to be associated with infertility; however, their effects on the outcomes of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) are still controversial. In this retrospective study, we aimed to evaluate the effect of CPs on IVF/ICSI-ET outcomes.MethodsTo investigate whether CPs affected the outcomes of fresh IVF/ICSI-ET cycles in a Chinese population, we evaluated infertile couples with male carriers of CPs (n?=?348), infertile couples with female carriers (n?=?99), and unaffected couples (n?=?400) who had received their first treatment cycles in our hospital between January 2013 and March 2015.ResultsCPs in either male or female carriers seemed to have adverse effects on IVF/ICSI-ET outcomes. CPs in male carriers affected outcomes mainly by decreasing the rates of fertilization, embryo cleavage, good quality embryos, clinical pregnancies, ongoing pregnancies, and deliveries as well as increasing the biochemical pregnancy rate (P?<?0.05); CPs in female carriers affected outcomes only by lowering the embryo cleavage rate (P?<?0.05). The mean fertilization rate of couples with male CP carriers undergoing IVF was significantly lower than that in those undergoing ICSI (61.1 versus 66.5 %, respectively; P?=?0.0004).ConclusionsOur data provide evidence for the involvement of CPs in the poor outcomes of fresh IVF/ICSI-ET cycles in a Chinese population. The use of ICSI might improve outcomes by increasing the fertilization rate for men with CPs.
Project description:The morphological assessment of oocytes is important for embryologists to identify and select MII oocytes in IVF/ICSI cycles. Dysmorphism of oocytes decreases viability and the developmental potential of oocytes as well as the clinical pregnancy rate. Several reports have suggested that oocytes with a dark zona pellucida (DZP) correlate with the outcome of IVF treatment. However, the effect of DZP on oocyte quality, fertilization, implantation, and pregnancy outcome were not investigated in detail. In this study, a retrospective analysis was performed in 268 infertile patients with fallopian tube obstruction and/or male factor infertility. In 204 of these patients, all oocytes were surrounded by a normal zona pellucida (NZP, control group), whereas 46 patients were found to have part of their retrieved oocytes enclosed by NZP and the other by DZP (Group A). In addition, all oocytes enclosed by DZP were retrieved from 18 patients (Group B). No differences were detected between the control and group A. Compared to the control group, the rates of fertilization, good quality embryos, implantation and clinical pregnancy were significantly decreased in group B. Furthermore, mitochondria in oocytes with a DZP in both of the two study groups (A and B) were severely damaged with several ultrastructural alterations, which were associated with an increased density of the zona pellucida and vacuolization. Briefly, oocytes with a DZP affected the clinical outcome in IVF/ICSI cycles and appeared to contain more ultrastructural alterations. Thus, DZP could be used as a potential selective marker for embryologists during daily laboratory work.
Project description:Emotional states such as sadness, anger, and threat have been shown to play a critical role in decision-making processes. Here we addressed the question of whether risk preferences are influenced by postural threat and whether this influence generalizes across motor tasks. We examined risk attitudes in the context of arm-reaching (ARM) and whole-body (WB) leaning movements, expecting that increased postural threat would lead to proportionally similar changes in risk-sensitivity for each motor task. Healthy young adults were shown a series of two-alternative forced-choice lotteries, where they were asked to choose between a riskier lottery and a safer lottery on each trial. Our lotteries consisted of different monetary rewards and target sizes. Subjects performed each choice task at ground level and atop an elevated platform. In the presence of this postural threat, increased physiological arousal was correlated with decreased movement variability. To determine risk-sensitivity, we quantified the frequency with which a subject chose the riskier lottery and fit lottery responses to a choice model based on cumulative prospect theory (CPT). Subjects exhibited idiosyncratic changes in risk-sensitivity between motor tasks and between elevations. However, we found that overweighting of small probabilities increased with postural threat in the WB task, indicating a more cautious, risk-averse strategy is ascribed to the possibility of a fall. Subjects were also more risk-seeking in the WB movements than in ARM at low elevation; this behavior does not seem to derive from consistent distortions in utility or probability representations but may be explained by subjects' inaccurate estimation of their own motor variability. Overall, our findings suggest that implicit threat can modify risk attitudes in the motor domain, and the threat may induce risk-aversion in salient movement tasks.
Project description:To compare the two GnRH-a protocols (long GnRH-a protocol and short GnRH-a protocol) for ovarian stimulation in IVF/ICSI cycles in patients of various age ranges.A total of 5662 IVF-ET/ICSI cycles from 2010 to 2013 were retrospectively identified. The cycles were divided into two groups: a long protocol group and short protocol group. In each group, the patients were divided into four age ranges: <31 years, 31 to 35 years, 36 to 40 years, and >40 years. The duration of stimulation, total dose of Gn, implantation rate and pregnancy rate were compared.The total dose of Gn was significantly higher, and the duration of stimulation was significantly longer, in the long protocol group than in the short protocol group for all age ranges (P<0.05). If the patients were of the same age range, the number of oocytes retrieved, MII oocytes, and high-quality embryos in the long protocol group were all significantly greater than those in the short protocol group (P<0.05). In the long protocol group, the clinical pregnancy rates of the four age ranges were 52.76%, 44.33%, 36.15% and 13.33%, respectively, which were significantly higher than those in the short protocol group (33.33%, 24.58%, 22.49% and 8.72%, respectively; P<0.05). The same trend was also found in the implantation rates of the four age ranges. As the age increased, the clinical pregnancy and implantation rates, as well as the number of oocytes retrieved, MII oocytes, and high-quality embryos, of the long protocol group significantly decreased (P<0.05).Our study demonstrated that regardless of patient age, the long protocol was superior to the short protocol in terms of the number of retrieved oocytes, as well as the implantation and pregnancy rates.
Project description:OBJECTIVE:To compare success rates, associated risks and cost-effectiveness between intrauterine insemination (IUI) and in vitro fertilisation (IVF). DESIGN:Retrospective observational study. SETTING:The UK from 2012 to 2016. PARTICIPANTS:Data from Human Fertilisation and Embryology Authority's freedom of information request for 2012-2016 for IVF/ICSI (intracytoplasmic sperm injection)and IUI as practiced in 319 105 IVF/ICSI and 30 669 IUI cycles. Direct-cost calculations for maternal and neonatal expenditure per live birth (LB) was constructed using the cost of multiple birth model, with inflation-adjusted Bank of England index-linked data. A second direct-cost analysis evaluating the incremental cost-effective ratio (ICER) was modelled using the 2016 national mean (baseline) IVF and IUI success rates. OUTCOME MEASURES:LB, risks from IVF and IUI, and costs to gain 1 LB. RESULTS:This largest comprehensive analysis integrating success, risks and costs at a national level shows IUI is safer and more cost-effective than IVF treatment.IVF LB/cycle success was significantly better than IUI at 26.96% versus 11.49% (p<0.001) but the IUI success is much closer to IVF at 2.35:1, than previously considered. IVF remains a significant source of multiple gestation pregnancy (MGP) compared with IUI (RR (Relative Risk): 1.45 (1.31 to 1.60), p<0.001) as was the rate of twins (RR: 1.58, p<0.001).In 2016, IVF maternal and neonatal cost was £115 082 017 compared with £2 940 196 for IUI and this MGP-related perinatal cost is absorbed by the National Health Services. At baseline tariffs and success rates IUI was £42 558 cheaper than IVF to deliver 1LB with enhanced benefits with small improvements in IUI. Reliable levels of IVF-related MGP, OHSS (ovarian hyperstimulation syndrome), fetal reductions and terminations are revealed. CONCLUSION:IUI success rates are much closer to IVF than previously reported, more cost-effective in delivering 1 LB, and associated with lower risk of complications for maternal and neonatal complications. It is prudent to offer IUI before IVF nationally.