Live Birth with or without Preimplantation Genetic Testing for Aneuploidy

Background:Embryo selection with preimplantation genetic testing for aneuploidy(PGT-A)may improve pregnancy outcomes after initial embryo transfer.However,it remains uncertain whether PGT-A improves the cumulative live-birth rate as compared with conventional in vitro fertilization(IVF).Methods:In this multicenter,randomized,controlled trial,we randomly assigned subfertile women with three or more goodquality blastocysts to undergo either PGT-A or conventional IVF;all the women were between 20 and 37 years of age.Three blastocysts were screened by next-generation sequencing in the PGT-A group or were chosen by morphologic criteria in the conventional-IVF group and then were successively transferred one by one.The primary outcome was the cumulative live-birth rate after up to three embryo-transfer procedures within 1 year after randomization.We hypothesized that the use of PGT-A would result in a cumulative live-birth rate that was no more than 7 percentage points higher than the rate after conventional IVF,which would constitute the noninferiority margin for conventional IVF as compared with PGT-A.

The effect of SARS-CoV-2 infection on human embryo early development:a multicenter prospective cohort study

Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection has swept the globe for 3 years(Zhou et al.,2020).With the nationwide relaxation of controls on the coronavirus disease 2019(COVID-19)epidemic since December 2022 in China,fertility and in vitro fertilization(IVF)centers are receiving increasing numbers of infected patients.

Early changes to the extracellular space in the hippocampus under simulated microgravity conditions

The smooth transportation of substances through the brain extracellular space(ECS)is crucial to maintaining brain function;however,the way this occurs under simulated microgravity remains unclear.In this study,tracer-based magnetic resonance imaging(MRI)and DECS-mapping techniques were used to image the drainage of brain interstitial fluid(ISF)from the ECS of the hippocampus in a tail-suspended hindlimb-unloading rat model at day 3(HU-3)and 7(HU-7).The results indicated that drainage of the ISF was accelerated in the HU-3 group but slowed markedly in the HU-7 group.The tortuosity of the ECS decreased in the HU-3 group but increased in the HU-7 group,while the volume fraction of the ECS increased in both groups.The diffusion rate within the ECS increased in the HU-3 group and decreased in the HU-7 group.The alterations to ISF drainage and diffusion in the ECS were recoverable in the HU-3 group,but neither parameter was restored in the HU-7 group.Our findings suggest that early changes to the hippocampal ECS and ISF drainage under simulated microgravity can be detected by tracer-based MRI,providing a new perspective for studying microgravity-induced nano-scale structure abnormities and developing neuroprotective approaches involving the brain ECS.

The interaction effect between advanced paternal age and paternal obesity is associated with the low implantation rate in couples with unexplained recurrent pregnancy loss

Objective:To explore the roles of advanced paternal age(APA)and abnormal paternal weight on embryo quality and pregnancy outcomes for unexplained recurrent pregnancy loss(uRPL)couples who underwent preimplantation genetic testing for aneuploidies(PGT-A).Methods:This study included 779 uRPL couples who underwent their first PGT-A cycles between 2014 and 2018.Male patients’aging and nutritional status were quantified by paternal age and body mass index(BMI).Routine semen parameters and sperm DNA fragmentation index(DFI)were used to reflect the seminal quality.Blastocyst formation rate and aneuploidy rate were used to reflect the embryo quality.Cycle cancellation rate,implantation rate,pregnancy loss rate,and live birth rate were measured to evaluate the treatment efficiency from IVF.To remove the interference of maternal age,only the women younger than 38 years old were included.After univariate screening,interaction tests were performed in a generalized linear model(GLM)to further examine the effects of paternal age and BMI on each outcome indicator.Results:In the total population(779 cycles),there were no statistical differences in aneuploidy rate,cycle cancellation rate,implantation rate,pregnancy loss rate,and live birth rate,whether stratified by paternal age or paternal BMI.Similar results occurred in the younger men(<40 y.o.,633 cycles).Conversely,among the men with advanced age(≥40 y.o.,146 cycles),there were statistical differences between the three BMI groups in four semen parameters(total sperm number,total motility,progressive motility,and total motile sperm count),implantation rate,and live birth rate.After interaction testing,the results of GLM suggested that the interaction effect between APA and paternal obesity was associated with the low implantation rate of uRPL couples.Conclusions:For the uRPL couples seeking for PGT-A treatment,if the male patients have both advanced age and obesity,their spouses are at higher risks for embryo implantation failure.

Clinical outcomes of sildenafil application in patients of poor endometrial development

Objective:To determine whether sildenafil has an efect on pregnancy outcomes in patients with poor endometrial development.Mathods:This study included 472 infertility patients who underwent in viro fer tilization/intracytoplasmadc spemm injection and frozen-thawed embryo tr ansfer(IVF/ICSI-FET)and subsequently sufered from poor endo-metral dewelopment during homnone replacement cycle(HRC)from April 2017 to July 2019.The patients were divided into two groups:the sildenafl group(n=88)and the control group(n=384).We analyzed endometrial thicknuess and types on endometrial transformation day,as well as pregnancy outcomes after FET(biochemical pregnancy,clinical pregnancy,early abortion,late abortion,and live birth rates)between the two groups.Results:After adjusting for confounding factors,we found no significant differences in endometrial thicknesses and types on endometrial transfomation day between the sildenafil group and the control group(0.79±0.08 vs 0.81±0.09,P=0.144;79.76%vs83.87%,P=0.402).There were also no statistcally significant differences in biochemical pregnancy rate(75.0%vs76.8%,P=0.892),clinical pregnancy rate(59.09%vs 69.53%,P=0.087),early abortion rate(17.31%vs 14.61%,P=0.557),late abortion rate(3.85%vs 4.49%,P=0.859),or live birth rate(45.45%vs 55.47%,P=0.101)between the two groups.In subgroup analysis,the application of sildenafil was unable to improve endometrial thickness(group one:0.80±0.08 cm vs 0.82±0.08 cm;group two:0.78±0.08 cm vs 0.80±0.10 cm;group three:0.75±0.11 cm vs 0.77±0.08 cm,p>0.05)and type endometrium on transfomation day(group one:78.57%vs 86.78%;group two:80.65%vs 77.78%;group three:81.82%ws.83.78%,p>0.05).Moreover,sildenafil use was not closely associated with clinical pregnancy outcomes,clinical pregnancy rate,early abortion rate,late abortion rate,and live birth rate(p>0.05).Conclusions:Sildenafl did not benefit endometrial development and pregnancy outcomes in patients with poor endometr:ial development during the hormone replacement cycle.

Pharmacogenetic study of Asn680Ser and-29A>G in FSHR gene in Chinese women undergoing controlled ovarian hyperstimulation

The outcome of controlled ovarian hyperstimulation(COH)is various and unpredictable.According to previous studies,2 single nucleotide polymorphisms,Asn680Ser and-29A/G,have a pharmacogenetic association with ovarian response to COH.However,studies on the Asn680Ser polymorphism have yielded inconsistent conclusions and only a few studies with small sample sizes have been performed on-29A/G.The association of these 2 polymorphisms with ovarian response remains unclear.The present study evaluated the association of Asn680Ser and-29A/G genotypes with COH.A total of 414 Chinese women undergoing in vitro fertilization-embryo transfer were included.Genotypes for these single nucleotide polymorphisms were identified by high-resolution melting-curve analysis.The value of exogenous follicle-stimulating hormone dosage per oocyte divided by the body surface area(Dosage/Oocyte
Surface)was calculated for each patient as an indicator of ovarian response.The results of statistical analyses showed no association between Asn680Ser genotype and ovarian response.As for-29A/G,heterozygote individuals had more oocytes retrieved(P=0.034).Combinatorial analysis of these 2 single nucleotide polymorphisms showed that genotype A/G-Asn/Asn had lower basal-follicle-stimulating hormone and more oocytes retrieved.Analysis of genotype association with ovarian response also revealed this genotype had a significantly higher risk of developing hyper response(OR=7.86;95%CI:1.31-9.43).To some extent,there were associations between the studied polymorphisms and ovarian response;however,the power of this link is weak and has limited value for clinical prediction.