Cumulative live birth rates of in vitro fertilization/intracytoplasmic sperm injection after multiple complete cycles in China

There were few studies of cumulative live birth rates(CLBRs) based on multicenter reproductive clinical data from the general Chinese population.Here we report a retrospective cohort study,including 14 311 women with17 315 cycles,in three reproductive centers to evaluate two estimated parameters of CLBRs with multiple transfer cycles of in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI) in a Chinese population.We found that CLBRs were related to female age and endometrial thickness.By the fourth transfer cycle,the conservative and optimal estimates of CLBRs were 52.95% and 77.30% in women under 30 years of age,and 18.17% and26.51% in those 37 years of age or older,respectively.The two estimates were 44.70% and 63.15% in women with endometrial thickness more than 7 mm,and 32.05% and 46.18% in those with less than 7 mm,respectively.In addition,body mass index(BMI),duration of infertility,and infertility diagnoses may also be related to CLBRs on certain conditions.The findings from this study on CLBRs after multiple transfer cycles of IVF/ICSI treatment on different conditions in the Chinese population should be beneficial to both infertile couples and clinicians.

Effect of Dual Trigger In Vitro Fertilization and Intracytoplasmic Sperm Injection During the Gonadotropin-releasing Hormone-Antagonist Cycle on Final Oocyte Maturation and Cumulative Live Birth Rate in Women with Diminished Ovarian Reserve

Objective It is well known that a dual trigger treatment can improve clinical outcomes of in vitro fertilization(IVF)in high or normal ovarian responders.However,it is not clear whether dual triggering also benefits patients with diminished ovarian reserve(DOR).The aim of this study was to investigate whether a dual trigger treatment of gonadotropin-releasing hormone(GnRH)agonist combined with human chorionic gonadotropin(hCG)for final follicular maturation improves the cumulative live birth rate(CLBR)during the GnRH-antagonist cycle in patients with DOR.Methods This retrospective study included patients with DOR who received a GnRH-antagonist protocol during IVF and intracytoplasmic sperm injection(IVF-ICSI)cycles at Peking University People’s Hospital from January 1,2017 through December 31,2017.Oocyte maturation was triggered by GnRH combined with hCG(n=110)or hCG alone(n=71).Embryos were transferred on the third day after oocyte retrieval or during a subsequent freeze-thaw cycle.Patients were followed up for 3 years.Results The dual trigger treatment did not affect CLBR,which is an overall determinant of the success rate of assisted reproductive technology(ART).Women in the dual trigger group had significantly higher rates of fertilization than those in the hCG group(90.1%vs.83.9%,P=0.040).Conclusion Dual trigger with GnRH agonist and hCG did not improve CLBR in patients with DOR,but did slightly improve fertilization rate,oocyte count,and embryo quality.

Fatigue Crack Propagation Law of Corroded Steel Box Girders in Long Span Bridges

In order to investigate the fatigue performance of orthotropic anisotropic steel bridge decks,this study realizes the simulation of the welding process through elastic-plastic finite element theory,thermal-structural sequential coupling,and the birth-death element method.The simulated welding residual stresses are introduced into the multiscale finite element model of the bridge as the initial stress.Furthermore,the study explores the impact of residual stress on crack propagation in the fatigue-vulnerable components of the corroded steel box girder.The results indicate that fatigue cracks at the weld toe of the top deck,the weld root of the top deck,and the opening of the transverse diaphragm will not propagate under the action of a standard vehicle load.However,the inclusion of residual stress leads to the propagation of these cracks.When considering residual stress,the fatigue crack propagation paths at the weld toe of the transverse diaphragm and the U-rib weld toe align with those observed in actual bridges.In the absence of residual stress,the cracks at the toe of the transverse diaphragm with a 15%mass loss rate are categorized as type I cracks.Conversely,when residual stress is considered,these cracks become I-II composite cracks.Residual stress significantly alters the cumulative energy release rate of the three fracturemodes.Therefore,incorporating the influence of residual stress is essential when assessing the fatigue performance of corroded steel box girders in long-span bridges.

Effect of CD74 on the prognosis of patients with resectable pancreatic cancer

BACKGROUND: CD74 is known as a type II transmembrane glycoprotein that is associated with the major histocompatibility complex class II α and β chains. Recent studies have demonstrated that the expression of CD74 is also linked to some forms of tumors. The present study was to assess the effect of CD74 expression on the prognosis of resectable pancreatic ductal adenocarcinoma(PDAC). METHODS: Forty-six patients who had received a curative resection of primary PDAC and postoperative chemotherapy were included in this study. Immunohistochemical staining was conducted of CD74 on paraffin-embedded tumor sample slices. The patients were grouped according to CD74 staining: CD74(-): CD74 positive tumor cells 【25%; and CD74(+): CD74 positive tumor cells ≥25%. The correlation of CD74 expression level with clinicopathological features and cumulative survival rate was calculated. RESULTS: The numbers of CD74(+) and(-) patients were 32 and 14, respectively. CD74(+) patients showed a high rate of perineural invasion(P=0.007). The 3- and 5-year cumulative survival rates of CD74(-) patients were significantly higher than those of CD74(+) patients(62% and 41% vs 9% and 0%, P=0.000). Multivariate analysis showed that CD74 expression and lymphatic permeation were the independent prognostic indicators. CONCLUSIONS: The overexpression of CD74 is a key factor associated with perineural invasion. Lower-stage(I and II) PDAC patients with CD74 overexpression have a poor prognosis even if they receive a curative resection. CD74 can be used as a prognostic indicator for resectable PDAC.

Enhanced resistance of Portunus trituberculatus to Vibrio alginolyticus by selective breeding

We established a line (screened) of Portunus trituberculatus by selectively breeding individuals that survived from challenge with Vibrio alginolyticus, and compared the response of screened and unscreened (control) P. trituberculatus challenged with V. alginolyticus. We measured superoxide dismutase, catalase, acid phosphatase, alkaline phosphatase, and peroxidase activity and the content of hemocyanin in the plasma and phenoloxidase activity in serum. The cumulative survival rate after 24-h challenge with V. alginolyticus was significantly higher in the screened crabs than in the unscreened crabs (P<0.05). T-SOD and PO activity were significantly lower in the screened stock than in the unscreened stock (P<0.05). POD, CAT, and ACP activity and hemocyanin content were significantly higher in the screened stock than in the unscreened stock. Our results suggest that the screened stock was more resistant to infection. Furthermore, the indices we measured may be used to evaluate the health state of P. trituberculatus.

Role of ICSI in Non-male Factor Cycles as the Number of Oocytes Retrieved Decreases from Four to One

This study aimed to investigate whether intracytoplasmic sperm injection（ICSI） shows an advantage over in vitro fertilization（IVF） in non-male factor cycles as the number of oocytes retrieved decreases from four to one.We undertook a retrospective analysis of 1305 IVF/ICSI cycles of non-male factor in which four or fewer oocytes were retrieved.Comparisons were made between conventional IVF（CI） and ICSI when one,two,three or four oocyte（s） were retrieved.Primary outcomes including normal fertilization rate,proportion of embryos per obtained oocyte,cycle cancellation rate,implantation rate,clinical pregnancy rate（PR）,live birth rate（LBR）,cumulative PR and cumulative LBR were evaluated.The results showed that the normal fertilization rate（72.5% vs.50.0%） and the proportion of embryos per obtained oocyte（72.5% vs.55.0%） were significantly increased in one oocyte retrieved cycles in ICSI group as compared with CI group.However,the proportion of embryos per obtained oocyte was markedly decreased in ICSI group when three（52.3% vs.61.3%） or four（56.9% vs.64.0%） oocytes were retrieved.The implantation rates,clinical PRs,LBRs,cumulative PRs and cumulative LBRs in CI group were comparable to those in ICSI group when one,two,three or four oocyte（s） were retrieved.In conclusion,ICSI doesn＇t show advantages over IVF in low oocyte yield cycles of non-male factors,even when only one oocyte was retrieved.Key words

Analysis of related factors affecting cumulative live birth rates of the first ovarian hyperstimulation in vitro fertilization or intracytoplasmic sperm injection cycle: a population-based study from 17,978 women in China

Background:More and more scholars have called for the cumulative live birth rate(CLBR)of a complete ovarian stimulation cycle as a key indicator for assisted reproductive technology.This research aims to study the CLBR of the first ovarian hyperstimulation cycles and analyze the related prognosis factors that might affect the CLBR.Methods:Our retrospective study included first in vitro fertilization or intracytoplasmic sperm injection(IVF/ICSI)cycles performed between January 2013 to December 2014.A total of 17,978 couples of first ovarian hyperstimulation IVF/ICSI cycles were included.The study was followed up for 4 years to observe the CLBR.The multivariable logistic regression model was used to analyze the prognosis factor,P value of<0.05 was considered statistically significant.Results:The cumulative pregnancy rate was 58.14%(10,452/17,978),and the CLBR was 49.66%(8928/17,978).The female age was younger in the live birth group when compared with the non-live birth group(30.81±4.05 vs.33.09±5.13,P<0.001).The average duration of infertility was shorter than the non-live birth cohort(4.22±3.11 vs.5.06±4.08,P<0.001).The preliminary gonadotropin used and the total number of gonadotropin used were lower in the live birth group when compared with the non-live birth group(both P<0.001).Meanwhile,the number of oocytes retrieved and transferrable embryos were both significantly higher in the live birth group(15.35±7.98 vs.11.35±7.60,P<0.001;6.66±5.19 vs.3.62±3.51,P<0.001,respectively).Conclusions:The women's age,body mass index,duration of infertility years,infertility factors,controlled ovarian hyperstimulation protocol,the number of acquired oocytes,and number of transferrable embryos are the prognosis factors that significantly affected the CLBR.

Prediction of Cumulative Live Birth Rate in Women Aged 40 Years and Over Undergoing In vitro Fertilization/Intracytoplasmic Sperm Injection

Objective:To investigate cumulative live birth rate (cLBR) per oocyte retrieval in infertile patients aged 40 years and over undergoing their first in vitro fertilization/intracytoplasmic sperm injection cycles and to identify the possible predictors.Methods:A total of 1,613 patients at a university hospital in China from January 2013 to May 2017 were enrolled in this retrospective study.All data for fresh and subsequent frozen-thawed cycles were analyzed.Multivariate logistic regression analysis with stepwise selection of possible predictors for cLBR was performed,and Loess curve was constructed to determine the association between cLBR and the number of oocytes retrieved.Results:cLBR significantly increased with the number of oocytes retrieved and reached up to 75% when > 20 oocytes were retrieved (P<0.001).Variables of antral follicle count (AFC) and the number of oocytes retrieved were selected using multiple logistic regression analysis with stepwise selection to predict the significance of cLBR.cLBR demonstrated an obvious upward trend as the number of oocytes retrieval increased in the Loess curve.Conclusions:For patients aged 40 years and over,AFC and the number of oocytes retrieved were two key predictors for cLBR and maximization of ovarian reserve exploitation was pivotal to increase the chance of live birth.

The Multi-Center Comparative Clinical Trial of the Second Generation of Indomethacin VCu and TCu380A

Objective To study the effectiveness and side effects of the modified new indomethacin VCu IUD Material & methods It is a randomized multi-center clinical trial. Indomethacin VCu and TCu380A were inserted in 2 000 healthy women in 6 clinical units including urban and rural area from May 1997 to Feb 1998, with 1 000 cases in each group. Follow up time were 6, 12, and 24 month after insertion. Results The clinical characteristics of subjects in two groups were similar. Follow up was completed in 98.25% of cases. The net cumulative continuous rate at 6 month was 95.5% in TCu380A group and 97.5% in Indomethacin VCu group (P<0.05); at 12 month it was 93.79% and 94.78% respectively; at 24 month it was 88.23% and 89.77% respectively. The expulsion rate was higher in T group than in V group during 24 months. Termination due to pregnancy and bleeding or pain was similar in two groups. The occurrence of menorrahgia, prolonged bleeding and abdominal pain was also higher in T group than that in V group during 24 months after insertion. Spotting was more often in T group in 12 month. On the other hand, more subjects complained hypomenorrhea in V group. The total B/S period, average B/S period and the longest B/S period were all longer in T group during 4～6 month after IUD insertion (P< 0.01). The amount of hemoglobin was similar in two groups before IUD insertion. At the end of study, the amount of hemoglobin in T group decreased compared with baseline (P<0.001), and was lower than V group at the same time (P<0.001), while no change was observed in V group. Conclusion Compared with TCu380A, the second generation of indomethacin VCu possess the same contraceptive effect and cumulative continuous rate and lower side effects such as bleeding and abdominal pain. VCu is more beneficial to reproductive health of women, therefore, is worth of clinical application.

Propensity score-matched study and meta-analysis of cumulative outcomes of day 2/3 versus day 5/6 embryo transfers

The superiority of the cumulative outcomes of day 5/6 embryo transfer to those of day 2/3 embryo transfer in infertile couples has been debated. This retrospective study included data collected from 1051 patients from July 2011 to June 2014. Multiple maternal baseline covariates were subjected to propensity score matching analysis, and each day 5/6 group woman was matched to one day 2/3 group woman. A systematic meta-analysis was conducted to vaUdate the results. After matching was completed, 217 patients on the day 2/3 group were matched with those on the day 5/6 group, and no significant differences in the baseline characteristics were observed between the two groups. The cumulative pregnancy rate （57.14% vs. 53.46%, OR 1.16, 95% CI 0.79-1.70） and cumulative live birth rate （53.00% vs. 49.77%, OR 1.14, 95% CI 0.78-1.66） of day 5/6 embryo transfers were higher than those of day 2/3 embryo transfers, but this difference was not significant. The mean cycles per live birth and mean days per live birth in the day 5/6 group were significantly lower than those in the day 2/3 group. This study demonstrated that day 5/6 embryo transfer is a more cost-effective and time-efficient policy than day 2/3 embryo transfer to produce a live baby.

Magnetic-activated cell sorting of nonapoptotic spermatozoa with a high DNA fragmentation index improves the live birth rate and decreases transfer cycles of IVF/ICSI

The present study aimed to evaluate the clinical outcomes of magnetic-activated cell sorting(MACS)in sperm preparation for male subjects with a sperm DNA fragmentation index(DFI)≥30%.A total of 86 patients who had undergone their first long-term long protocol were selected.The protocol involved in vitro fertilization(IVF)and intracytoplasmic sperm injection(ICSI)cycles,and the patients were divided into the MACS or control groups.The MACS group included sperm samples analyzed with MACS that were combined with density gradient centrifugation(DGC)and the swim-up(SU)technique(n=39),and the control group included sperm samples prepared using standard techniques(DGC and SU;n=41).No differences were noted with regard to basic clinical characteristics,number of oocytes retrieved,normal fertilization rate,cleavage rate,or transplantable embryo rate between the two groups in IVF/ICSI.In addition,the clinical pregnancy and implantation rates of the first embryo transfer cycles indicated no significant differences between the two groups.However,there was a tendency to improve the live birth rate(LBR)of the first embryo transfer cycle(63.2%vs 53.9%)and the cumulative LBR(79.5%vs 70.7%)in the MACS group compared with the control group.Moreover,the number of transferred embryos(mean±standard deviation[s.d.]:1.7±0.7 vs 2.3±1.6)and the transfer number of each retrieved cycle(mean±s.d.:1.2±0.5 vs 1.6±0.8)were significantly lower in the MACS group than those in the control group.Thus,the selection of nonapoptotic spermatozoa by MACS for higher sperm DFI could improve assisted reproductive clinical outcomes.

In vitro fertilization-embryo transfer in patients with unexplained recurrent pregnancy loss

Background:Empiric therapy for patients with unexplained recurrent pregnancy loss(URPL)is not precise.Some patients will ask for assisted reproductive technology due to secondary infertility or advanced maternal age.The clinical outcomes of URPL patients who have undergonein vitro fertilization-embryo transfer(IVF-ET)require elucidation.The IVF outcome and influencing factors of URPL patients need further study.Methods:A retrospective cohort study was designed,and 312 infertile patients with URPL who had been treated during January 2012 to December 2015 in the Reproduction Center of Peking University Third Hospital were included.By comparing clinical outcomes between these patients and those with tubal factor infertility(TFI),the factors affecting the clinical outcomes of URPL patients were analyzed.Results:The clinical pregnancy rate(35.18%vs.34.52%in fresh ET cycles,P=0.877;34.48%vs.40.27%in frozen-thawed ET cycles,P=0.283)and live birth rate(LBR)in fresh ET cycles(27.67%vs.26.59%,P=0.785)were not significantly different between URPL group and TFI group.URPL group had lower LBR in frozen-thawed ET cycles than that of TFI group(23.56%vs.33.56%,P=0.047),but the cumulative LBRs(34.69%vs.38.26%,P=0.368)were not significantly different between the two groups.The increased endometrial thickness(EMT)on the human chorionic gonadotropin day(odds ratio[OR]:0.848,95%confidence interval[CI]:0.748-0.962,P=0.010)and the increased number of eggs retrieved(OR:0.928,95%CI:0.887-0.970,P=0.001)were protective factors for clinical pregnancy in stimulated cycles.The increased number of eggs retrieved(OR:0.875,95%CI:0.846-0.906,P<0.001),the increased two-pronucleus rate(OR:0.151,95%CI:0.052-0.437,P<0.001),and increased EMT(OR:0.876,95%CI:0.770-0.997,P=0.045)in ET day were protective factors for the cumulative live birth outcome.Conclusion:After matching ages,no significant differences in clinical outcomes were found between the patients with URPL and the patients with TFI.A thicker endometrium and more retrieved oocytes increase the probability of pregnancy in fresh transfer cycles,but a better normal fertilization potential will increase the possibility of a live birth.

An Extended Weibull Model with Variable Periodicity

A new distribution for the fluctuation of materials＇ lifetime cumulative hazard rate is firstly proposed. The new distribution is extended from the Weibull distribution by adding a sine function. After that, the properties of its hazard rate function, cumulative hazard rate function, probability density function and cumulative distribution function are studied. The analysis result shows this distribution can well model the lifetime with variable and periodic hazard rate. Finally, the new distribution is verified with two real data sets as examples to demonstrate its capability.

Clinical Results of In Vitro Fertilization or Intracytoplasmic Sperm Injection Treatments in Women Aged 40 Years and above

Objective:The study was designed to estimate the live birth rate(LBR)and cumulative LBR(CLBR)in patients aged≥40 years undergoing in vitro fertilization or intracytoplasmic sperm injection treatments during their first and multiple ovarian stimulation cycle(s).Methods:A total of 697 advanced women underwent 1,293 treatment cycles,and 973 fresh embryo transfers were performed.The LBR and CLBR were analyzed with respect to an increase in the maternal age by every year.Results:A declining trend in LBR and CLBR of the first cycle was seen with an increase in maternal age.The LBR in women aged 40 years was significantly higher than that in women aged≥44 years(18.39%and 4.39%,respectively);the CLBR in women aged 40 years was also significantly higher than that in women aged 42,43,and≥44 years(22.40%,9.09%,9.09%,and 4.80%,respectively).However,there was no significant difference(P>0.05)in the rate of miscarriage among all groups.For those who underwent multiple cycles,the number of live-born babies decreased rapidly after three ovarian stimulation cycles;the LBR in patients aged 40 years was significantly higher than that in patients aged 42 years and≥44 years(15.24%,5.20%,and 4.49%,respectively),and the CLBR in patients aged 40-41 years was significantly higher than that in patients aged≥42 years.The CLBR in all groups gradually plateaued after three cycles;women aged 40-41 years achieved relatively reasonable CLBR,while the CLBR was<10%in women aged≥42 years.Conclusions:Women aged 40-41 years had a low but acceptable outcome in the first three ovarian stimulation cycles.The success rate quickly decreased,and for women aged≥42 years,the decision to continue after three ovarian stimulation cycles should be made cautiously.

Reducing the Trigger Dose of Human Chorionic Gonadotrophin Does Not Affect Final Oocyte Maturation and Subsequently Pregnancy Outcome of Frozen-thawed Embryo Transfer

To compare the efficacy of human chorionic gonadotrophin （hCG） at reduced doses of 2 000 IU and 3 000 IU for moderate or high responders with the dose of 5 000 IU in term of inducing final oocyte maturation for IVF/ICSI and the subsequent pregnancy outcome in frozen-thawed embryo transfer （FET）. Methods In the retrospective cohort study, 2 166patients undergoing IVF/ICSI with moderate or high response were recruited and classified into three groups according to the trigger dose of hCG： 2 000 IU （group A, n=722）, 3 000 IU （group B, n=722） and 5 000 IU （group C, n= 722）. The main outcome was the proportion of mature oocytes retrieved, fertilization rates, clinical pregnancy rates, cumulative pregnancy rates and incidence of ovarian hyperstimulation syndrome （OHSS）. Results No evidence of statistically difference was found in the proportion of mature oocytes retrieved （89.92%, 91.40%, 90.20%, respectively） and fertilization rate （79.8%, 80.07%, 80.51%, respectively） among groups A, B and C. Serum E2 level on the day of hCG injection, the number of mature oocytes retrieved and good-quality embryos in group A were significantly higher than those in group B and group C. Clinical pregnancy rates per transfer cycle （45.95%, 43.97% and 44.25%）, ongoing pregnancy rates （43.17%, 40.91% and 42,53%）, implantation rates （30, 74%, 2Z 78% and 29.86%） and cumulative pregnancy rates per patient （58.31%, 53.6% and 54.85%）A reduced hCG dose of 2 000 IUfor moderate or high responders leads