ImportanceThe safety of exogenous gonadotropin treatment, based on its effect on embryos and pregnancy outcomes, remains inconclusive.ObjectiveTo evaluate the associations of different doses and durations of gonadotropins with embryonic genetic status and pregnancy outcomes after euploid embryo transfer in couples with infertility.Design, Setting, and ParticipantsThis study was a post hoc analysis of a multicenter randomized clinical trial (RCT) conducted at 14 reproductive centers throughout China from July 2017 to June 2018 that evaluated the cumulative live birth rate with or without preimplantation genetic testing for aneuploidy (PGT-A) among couples with infertility and good prognosis. The PGT-A group from the original RCT was selected for secondary analysis. Patients were divided into 4 groups according to the total dosage of exogenous gonadotropins and treatment duration: group 1 (≤1500 IU and <10 days), group 2 (≤1500 IU and ≥10 days), group 3 (>1500 IU and <10 days), and group 4 (>1 500 IU and ≥10 days). Group 1 served as the control group. Data were analyzed from June through August 2023.InterventionsBlastocyst biopsy and PGT-A.Main outcomes and measuresThe primary outcomes were embryonic aneuploidy, embryonic mosaicism, and cumulative live birth rates after euploid embryo transfer.ResultsA total of 603 couples (mean [SD] age of prospective mothers, 29.13 [3.61] years) who underwent PGT-A were included, and 1809 embryos were screened using next-generation sequencing. The embryo mosaicism rate was significantly higher in groups 2 (44 of 339 embryos [13.0%]; adjusted odds ratio [aOR], 1.69 [95% CI, 1.09-2.64]), 3 (27 of 186 embryos [14.5%]; aOR, 1.98 [95% CI, 1.15-3.40]), and 4 (82 of 651 embryos [12.6%]; aOR, 1.60 [95% CI, 1.07-2.38]) than in group 1 (56 of 633 embryos [8.8%]). There were no associations between gonadotropin dosage or duration and the embryo aneuploidy rate. The cumulative live birth rate was significantly lower in groups 2 (83 of 113 couples [73.5%]; aOR, 0.49 [95% CI, 0.27-0.88]), 3 (42 of 62 couples [67.7%]; aOR, 0.41 [95% CI, 0.21-0.82]), and 4 (161 of 217 couples [74.2%]; aOR, 0.53 [95% CI, 0.31-0.89]) than in group 1 (180 of 211 couples [85.3%]).Conclusions and relevanceIn this study, excessive exogenous gonadotropin administration was associated with increased embryonic mosaicism and decreased cumulative live birth rate after euploid embryo transfer in couples with a good prognosis. These findings suggest that consideration should be given to minimizing exogenous gonadotropin dosage and limiting treatment duration to improve embryo outcomes and increase the live birth rate.Trial RegistrationClinicalTrials.gov Identifier: NCT03118141

Objective: Although consensus on the optimal endometrial preparation protocol for frozen-thawed embryo transfer (FET) is lacking, this is particularly true for patients with infertility and a history of endometrial polyps (EPs). In this study, we aimed to investigate whether a gonadotropin-releasing hormone agonist combined with hormone replacement therapy (GnRHa-HRT) could improve pregnancy outcomes in single euploid FET for patients with a history of EPs.Methods: In this retrospective cohort study, 395 women who underwent their first single euploid FET cycle were divided into groups according to endometrial preparation protocols as follows: natural cycle (NC) (n = 220), hormone replacement therapy (HRT) (n = 122), and GnRHa-HRT groups (n = 53). Subsequently, the FET cycles in the three groups were subdivided according to maternal age. All patients underwent hysteroscopic polypectomy before FET, and their EPs were confirmed by pathology.Results: No statistically significant differences were observed in live birth rates among the three groups (58.64%vs. 58.20%vs. 56.60%,P = 0.964). Furthermore, the rates of miscarriage, ectopic pregnancy, premature live birth, and pregnancy complications were comparable among the three groups (P >0.05). After adjusting for potential confounding factors, no significant differences in pregnancy outcomes were reported between the groups (adjusted odds ratios [OR] and 95% credible intervals [CI] for live birth rate, HRTvs. NC: 1.119, 0.660–1.896,P = 0.677; GnRHa-HRTvs. NC: 1.165, 0.610–2.226,P = 0.643). Additionally, the pregnancy outcomes of the FET cycle were not influenced by the endometrial preparation protocols in the subgroups when stratified by maternal age (P >0.05).Conclusion: GnRHa-HRT did not improve the pregnancy outcomes of the single euploid FET in patients with a history of EPs.

Objective: To evaluate the effect of SARS-CoV-2 infection and vaccination on ovarian reserve. Methods: Relevant articles were identified in the EMBASE, PubMed, and Web of Science databases from January 2020 to May 2023. Available clinical indicators of ovarian reserve, such as anti-M & uuml;llerian hormone (AMH), antral follicle count (AFC), follicle-stimulating hormone (FSH), and estradiol (E2), as well as the time interval from infection or vaccination to measurements, were assessed. Results: Only 2 studies provided evidence that SARS-CoV-2 infection could damage ovarian function. In a comparison of the vaccinated and unvaccinated groups, although 1 prospective cohort study observed the transient statistically significant decrease on serum AMH levels at 3 or 6 months of follow-up, serum AMH levels remained within the normal reserve range (>1.1 ng/dl) throughout the study period. Conclusion: Overall, whether ovarian reserve may be affected by SARS-CoV-2 infection remains controversial and further investigations are warranted to clarify this issue. Based on the current evidence, it is safe to assume that COVID-19 vaccination does not exert any adverse effect on ovarian reserve parameters such as AMH, AFC, FSH, and E2, which will provide reassurance for women attempting to fall pregnant.

Background The aim of the retrospective cohort study was to investigate the prognostic effect of subchorionic hematomas (SCH) in the first trimester on pregnancy outcomes after euploid embryo transfer. Methods We retrospectively analyzed women achieving singleton pregnancy by PGT-A or PGT-SR from January 2017 to January 2022. Patients were enrolled in the study if they had a viable intrauterine pregnancy at ultrasound between 6 0/7 and 8 0/7 weeks of gestation. Pregnancy outcomes as well as the incidence of maternal complications were compared between patients with and without SCH. Logistic regression was used for adjusting for potential confounding factors. Results A total of 1539 women were included, of which 298 with SCH and 1241 with non-SCH. The early miscarriage rate in SCH group was significantly higher than that in the non-SCH group (10.1% vs. 5.6%, adjusted odds ratio [aOR] 1.99, 95% confidence interval [CI] 1.25–3.16, P = 0.003). The live birth rate in SCH group was significantly lower than that in the non-SCH group. (85.6% vs. 91.2%, aOR 0.57, 95% CI 0.39–0.84, P = 0.005). In addition, SCH group had an increased risk of hypertensive disorder of pregnancy (HDP) (8.9% vs. 5.2%, P = 0.022), especially in hematoma with bleeding (19.3% vs. 6.0%, P = 0.002). The incidence of gestational diabetes mellitus (GDM), major congenital abnormalities rate, normal birth weight rate and low birth weight rate were similar between the two groups. Conclusions The presence of SCH in the first trimester was associated with worse pregnancy outcomes after euploid embryo transfer, including an increased risk of early miscarriage and hypertensive disorder of pregnancy, along with a reduced live birth rate.

Background During human early placentation, a proportion of extravillous trophoblasts (EVTs) migrate to the maternal decidua, differentiating into endovascular EVTs to remodel spiral arteries and ensure the establishment of blood circulation at the maternal-fetal interface. Inadequate EVT migration and endovascular differentiation are closely associated with adverse pregnancy outcomes such as miscarriage. Activin A and fibronectin are both secretory molecules abundantly expressed at the maternal-fetal interface. Activin A has been reported to regulate EVT biological functions. However, whether fibronectin mediates activin A-promoted EVT migration and acquisition of endothelial-like phenotype as well as the underlying molecular mechanisms remain unknown. Additionally, the role of fibronectin in pregnancy establishment and maintenance warrants further investigation. Methods Primary and immortalized (HTR8/SVneo) human EVTs were used as in vitro study models. Cultured human first-trimester chorionic villous explants were utilized for ex vivo validation. A local fibronectin knockdown model in ICR mouse uteri, achieved by nonviral in vivo transfection with small interfering RNA (siRNA) targeting fibronectin 1 (si- Fn1 ), was employed to explore the roles of fibronectin in the establishment and maintenance of early pregnancy. Results Our results showed that activin A treatment significantly induced fibronectin 1 ( FN1 ) mRNA expression and fibronectin protein production, which is essential for human trophoblast migration and endothelial-like tube formation. Both basal and activin A-upregulated fibronectin expression were abolished by the TGF-β type I receptor inhibitor SB431542 or siRNA-mediated knockdown of activin receptor-like kinase ( ALK4 ) or SMAD4 . Moreover, activin A-increased trophoblast migration and endothelial-like tube formation were attenuated following the depletion of fibronectin. Fibronectin knockdown via intrauterine siRNA administration reduced CD31 and cytokeratin 8 (CK8) expression at the maternal-fetal interface, resulting in a decrease in the number of implantation sites and embryos. Conclusions Our study demonstrates that activin A promotes trophoblast cell migration and acquisition of endothelial-like phenotype via ALK4-SMAD2/3-SMAD4-mediated fibronectin upregulation. Furthermore, through a local fibronectin knockdown model in mouse uteri, we found that the absence of fibronectin at the maternal-fetal interface impedes endovascular migration of trophoblasts and decidual vascularization, thereby interfering with early embryo implantation and the maintenance of pregnancy. These findings provide novel insights into placental development during early pregnancy establishment and contribute to the advancement of therapeutic approaches for managing pregnancy complications related to trophoblast dysfunction.

Objective:We evaluate whether next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) improves the cumulative pregnancy outcomes of patients with unexplained recurrent implantation failure (uRIF) as compared to conventional in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI).Patients and Methods:This was a retrospective cohort study (2015-2022). A total of 705 couples diagnosed with uRIF were included in the study. 229 women transferred blastocysts based on morphological grading (IVF/ICSI) and 476 couples opted for PGT-A to screen blastocysts by NGS. Women were further stratified according to age at retrieval (<38 years and ≥38 years). The primary outcome was the cumulative live-birth rate after all the embryos were transferred in a single oocyte retrieval or until achieving a live birth. Confounders were adjusted using binary logistic regression models.Results:Cumulative live-birth rate was similar between the IVF/ICSI group and the PGT-A group after stratified by age: IVF/ICSI vs PGT-A in the <38 years subgroup (49.7% vs 57.7%, adjusted OR (95% CI) = 1.25 (0.84-1.84), P = 0.270) and in the ≥38 years subgroup (14.0% vs 19.5%, adjusted OR (95% CI) = 1.09 (0.41-2.92), P = 0.866), respectively. Nonetheless, the PGT group had a lower first-time biochemical pregnancy loss rate (17.0% vs 8.7%, P = 0.034) and a higher cumulative good birth outcome rate (35.2% vs 46.4%, P = 0.014) than the IVF/ICSI group in the <38 years subgroup. Other pregnancy outcomes after the initial embryo transfer and multiple transfers following a single oocyte retrieval were all similar between groups.Conclusion:Our results showed no evidence of favorable effects of PGT-A treatment on improving the cumulative live birth rate in uRIF couples regardless of maternal age. Use of PGT-A in the <38 years uRIF patients would help to decrease the first-time biochemical pregnancy loss and increase the cumulative good birth outcome.

Objective: To evaluate whether prolonged storage of vitrified blastocysts negatively impacts pregnancy and neonatal outcomes. Design: A retrospective cohort study.Setting: University hospital.Patient(s): A total of 6,900 patients who desired to transfer vitrified blastocysts from the same oocyte retrieval cycle as their last live birth met the inclusion criteria and were grouped according to the storage duration (1,890 patients in group 1 with storage duration < 3 years, 2,693 patients in group 2 with storage duration between 3 and 4 years, 1,344 patients in group 3 with storage duration between 4 and 5 years, 578 patients in group 4 with storage duration between 5 and 6 years and 395 patients in group 5 with storage duration R 6 years but % 10.5 years).Intervention(s): None.Main Outcome Measure(s): Rates of blastocyst survival, biochemical pregnancy, clinical pregnancy, miscarriage, ectopic pregnancy, and live birth and neonatal outcomes.Result(s): The survival rates of the vitrified blastocysts significantly decreased with prolonged storage from group 1 to the subsequent groups 2, 3, 4, and 5. After adjusting for potential confounding factors, the rates of biochemical pregnancy, clinical pregnancy, and live birth were significantly decreased when the vitrified blastocysts were stored for more than 6 years (group 5) compared with these for less than 3 years (group 1) but no distinct differences were found in these above-mentioned indicators among group 1, 2, 3, and group 4 (group 1 as reference). However, no significant differences were noted in the rates of miscarriage and ectopic pregnancy and neonatal outcomes on prolonged storage of vitrified blastocysts. Conclusion(s): Long-term blastocyst vitrification for more than 6 years can negatively affect the rates of biochemical pregnancy, clinical pregnancy, and live birth but does not impact neonatal outcomes. (Fertil Sterile 2023;119:36-44. (c) 2022 by American Society for Reproductive Medicine.)El resumen esta disponible en Espanol al final del articulo.

Background and Aims: Hereditary nephropathy, including monogenic nephropathy, is an important cause of renal insufficiency and end-stage renal disease. Therefore, genetic blockade is necessary for couples with monogenic nephropathy. Following routine application of prenatal diagnosis, preimplantation genetic testing for monogenic disorders (PGT-M) has been applied to the genetic blockade of monogenic disease patients. The purpose of this study is to retrospectively analyze genetic counseling process for patients with nephropathy-related disease and provide clinical overviews of patients with monogenic nephropathy who underwent PGT-M. Method: A single-center retrospective cohort study was conducted at Center for Reproductive Medicine, Shandong University from January 2014 to December 2022. 352 couples with nephropathy-related disease were included in the cohort totally. Statistical analysis was performed using Statistical Package for Social Science software 26.0. Results: Of the 352 couples with nephropathy-related disease, 291 underwent genetic counseling, followed by 180 accepting genetic screening. 104 couples with monogenic nephropathy indications proceeded with PGT-M, including 91 of autosomal dominant inheritance, 9 of autosomal recessive inheritance, 3 of X-linked dominant inheritance, and one of X-linked recessive inheritance. 498 blastocysts were tested by PGT-M combined with preimplantation genetic testing for aneuploidy (PGT-A), making 72 transferable embryos, 249 non-transferable embryos, 72 genetic counseling embryos and 7 amplification failedembryos. Finally, 80 vitrified-thawed single blastocyst transfer cycles were performed. Live births occurred in 38 women, of which 37 transferred embryos with non-pathogenic genotypes. The results of prenatal diagnosis of all newborns were consistent with the testing results for embryos transferred. The cumulative live birth, biochemical pregnancy, clinical pregnancy, ongoing pregnancy and pregnancy loss rates were 36.54%, 56.73%, 49.04%, 7.69%, and 22.03% respectively. Conclusion: PGT-M is an effective means of genetic blockade for couples with monogenic nephropathy. The absence of genetic abnormalities detected by prenatal diagnosis in healthy newborns without monogenic nephropathy also underscore its validity.

Background and Aims: Cesarean delivery (CD) rates continue to rise worldwide. Prior studies have indicated that CD is associated with not only various gynaecological symptoms and obstetric complications but also lower probability of subsequent fertility. However, the recognition about impact of CD on clinical outcomes in subsequent IVF/ICSI-FET is very limited. The purpose was to investigate the effects of previous CD on pregnancy and neonatal outcomes in single frozen-thawed embryo transfer (FET) cycles so that women with a previous cesarean delivery can be given detailed fertility counseling during the ART process. Methods: This is a large retrospective cohort study including a total of 5,750 patients who desired to transfer single vitrified-thawed blastocyst from the same oocyte retrieval cycle as their last live birth between January 2011 and January 2021 in a center for reproductive medicine in Shandong, China, comprising FET cycles of 3,853 previous single CD and 1,897 previous single vaginal delivery (VD). Results: Women with a previous CD had significantly lower rates of biochemical pregnancy (64.52% vs. 71.48% before propensity score matching (PSM), P<0.001; and 65.58% vs. 71.49% after PSM, P<0.001), clinical pregnancy (58.16% vs. 65.79% before PSM, P<0.001; and 59.22% vs. 66.17% after PSM, P<0.001) and live birth (48.17% vs. 55.82% before PSM, P<0.001; and 49.29% vs. 56.10% after PSM, P<0.001) than those with a previous VD. Meanwhile, the CD rate was significantly higher in the CD group (97.85% vs. 18.53% before PSM, P<0.001; and 98.02% vs. 20.51% after PSM, P<0.001). The rates of multiple pregnancy, miscarriage, ectopic pregnancy, multiple live birth, labor complications and preterm and neonatal outcomes were comparable between the two groups. Conclusion: Compared to VD, a previous CD is associated with a significant reduction in the rates of biochemical pregnancy, clinical pregnancy and live birth in patients undergoing subsequent single frozen-thawed blastocyst transfer.

This retrospective cohort study aimed to assess the effect of chromosomal reciprocal translocation on meiotic segregation products of non-translocation chromosomes. A total of 744 reciprocal translocation carriers and 875 non-carriers were included in this study. A total of 6,832 blastocysts were biopsied and tested by next-generation sequencing. Blastocysts from the carrier group were classified into five subgroups according to the theoretical segregation pattern of quadrivalent structure. For carrier patients, normal meiotic segregation products of the non-translocation chromosome were classified after excluding the segregation modes of the quadrivalent structure. The proportion of normal non-translocation chromosome meiotic segregation products was similar between the carrier and noncarrier groups (p = 0.69). The generalized Estimation Equation revealed that there was no correlation between reciprocal translocation and meiotic segregation products of non-translocation chromosomes. Moreover, subgroup analyses showed that the segregation modes of quadrivalent structure (p = 0.00) and carrier's gender (p = 0.00) may affect the meiotic segregation products of non-translocation chromosomes. In conclusion, reciprocal translocation does not directly reduce the proportion of normal segregation products of non-translocation chromosomes. The difference among subgroups of different quadrivalent segregation patterns implied that interchromosomal effect may exist but the high incidence of chromosomal abnormalities for reciprocal translocation carriers should not be attributed to interchromosomal effect.

IntroductionUltrasound (US) has gained popularity in the evaluation of haemophilic joint diseases because it enables the imaging of soft-tissue lesions in the joints and bone-cartilage lesions. We aimed to determine the correlation between US evaluations and clinical assessments performed using HJHS 2.1 and to evaluate their respective characteristics in assessing early haemophilic arthropathy.MethodsA total of 178 joints (32 knees, 85 elbows, and 61 ankles) in 45 haemophilia A patients (median age, 10 years; range, 6–15) were assessed using US and HJHS 2.1. Ultrasonographic scoring was performed in consensus assessments by one imager by using the US scores.ResultsThe total HJHS 2.1 and US scores showed a strong correlation (rS=0.651, P=0.000, CI: 0.553–0.763), with an excellent correlation for the elbows (rS=0.867, P=0.000, CI: 0.709–0.941) and a substantial correlation for the knees (rS=0.681, P=0.000, CI: 0.527–0.797). The correlation for the ankles was relatively moderate (rS=0.518, P=0.000, CI: 0.308–0.705). Nine subjects (15.5%) without abnormalities, as indicated by HJHS 2.1, showed haemophilic arthropathy in US scoring. All nine joints showed moderate (1/9) to severe (8/9) synovial thickening in the ankle (5/9) and elbow joints (4/9). In contrast, 50 joints (50.5%) showed normal US scores and abnormal changes as indicated by HJHS 2.1. S scores correlated well with HJHS 2.1 for overall and individual joints.DiscussionUS could identify some early pathological changes in joints showing normal clinical findings, but still cannot replace the HJHS; however, it can serve as an imaging examination complementing HJHS 2.

Objectives: To evaluate whether preimplantation genetic testing for aneuploidy (PGT-A) can improve pregnancy and neonatal outcomes for patients with limited good-quality embryos. Design: Retrospective cohort study. Setting: University hospital. Population: A total of 1,553 patients who intended to pursue PGT-A for the first time but obtained only two or less good-quality embryos on day 3 after oocyte retrieval were divided into two groups: 997 in the PGT-A group and 556 in the drop-out group of withdrawing PGT-A due to poor embryological outcome. Results: After adjusting for potential confounding factors, PGT-A group exhibited significantly lower cumulative rates of biochemical pregnancy (19.96% vs. 30.22%, P-adj < 0.001), clinical pregnancy (17.55% vs. 23.38%, P-adj < 0.001) and live birth (14.14% vs. 16.19%, P-adj = 0.005) per oocyte retrieval and longer median time to pregnancy and live birth compared with drop-out group. However, significant increases in rates of biochemical pregnancy (72.16% vs. 35.50%, P-adj < 0.001), clinical pregnancy (61.86% vs. 26.98%, P-adj < 0.001), and live birth (48.45 vs. 18.26%, P-adj < 0.001) per transfer were found in the PGT-A group. No significant differences were observed in cumulative miscarriage and ectopic pregnancy rates, number of ETs needed per live birth and neonatal outcomes. Conclusion: PGT-A failed to improve cumulative live birth rate or shorten time to pregnancy, but optimized pregnancy outcomes per transfer for patients with limited good-quality embryos. Keywords: preimplantation genetic testing for aneuploidy, cumulative live birth rate, live birth rate per transfer, neonatal outcomes

Abstract Background PGT-A has been widely used for RPL couples to help improve pregnancy outcomes by selecting euploid embryos. However, there is still insufficient evidence to determine the effectiveness of PGT-A in RPL couples, especially on the cumulative live birth rate. This study aims to investigate whether preimplantation genetic testing for aneuploidy (PGT-A) could improve the cumulative live birth rate in patients with recurrent pregnancy loss (RPL). Methods A retrospective large cohort study with 1003 RPL couples (799 in the PGT-A group, and 204 in the conventional IVF/ICSI group) was conducted in a university-affiliated reproductive center. Stratified analysis was performed according to female age (< 35 years and ≥ 35 years). The associations between embryo selection with PGT-A and cumulative pregnancy outcomes were further analyzed by a binary logistic regression model. Results The cumulative live birth rates were similar between the PGT-A group and the conventional IVF/ICSI group both in women under 35 years old [53.32% vs. 61.97%, adjusted OR (95%CI): 0.853(0.547–1.330), P = 0.483] and in women aged ≥ 35 years [28.75% vs. 30.65%, adjusted OR (95%CI): 1.314(0.671–2.574), P = 0.426]. Whereas, a significantly lower cumulative rates of biochemical pregnancy loss (10.13% vs. 32.56%, P < 0.05) and clinical pregnancy loss [20.89% vs. 37.21%, adjusted OR (95%CI): 0.408(0.173–0.966), P = 0.042] were found in the PGT-A group compared with the control group, only among women aged ≥ 35 years. The numbers of embryo transfers were significant less in PGT-A women with < 35 years old [1(1;2) vs. 1(1;2), P < 0.05] and with ≥ 35 years old [1(1;1) vs. 1(1;2), P < 0.05]. Conclusions PGT-A could not improve cumulative live birth rate in RPL couples regardless maternal age.

Abstract Study question To evaluate whether preimplantation genetic testing for aneuploidy (PGT-A) can improve pregnancy and neonatal outcomes for patients with limited good-quality embryos. Summary answer PGT-A failed to improve cumulative live birth rate or shorten time to pregnancy, but optimized pregnancy outcomes per transfer for patients with limited good-quality embryos. What is known already PGT-A is currently widely used to screen for aneuploidy with the goal of improving live birth rates. Remarkably, previous studies have focused on the effect of PGT-A on cumulative clinical outcomes in women with good pregnancy prognosis. However, it is still unclear whether PGT-A can improve the cumulative pregnancy outcomes in patients with limited good-quality embryos. Study design, size, duration A retrospective cohort study was performed among 1553 women who intended PGT-A for the first time but obtained only two or less good-quality embryos on day 3 after oocyte retrieval from March 2017 to June 2021. Participants/materials, setting, methods A total of 1553 patients were divided into two groups: 997 in the PGT-A group and 556 in the drop-out group of withdrawing PGT-A due to poor embryological outcome. Multivariable logistic regression was performed to adjust for potential confounders when comparing the clinical outcomes between two groups. Main results and the role of chance After adjusting for potential confounding factors, PGT-A group exhibited significantly lower cumulative rates of biochemical pregnancy (19.96% vs. 30.22%, P-adj < 0.001), clinical pregnancy (17.55% vs. 23.38%, P-adj < 0.001) and live birth (14.14% vs. 16.19%, P-adj = 0.005) per oocyte retrieval and longer median time to pregnancy and live birth compared with drop-out group. However, significant increases in rates of biochemical pregnancy (72.16% vs. 35.50%, P-adj < 0.001), clinical pregnancy (61.86% vs. 26.98%, P-adj < 0.001), and live birth (48.45 vs. 18.26%, P-adj < 0.001) per transfer were found in the PGT-A group. No significant differences were observed in cumulative miscarriage and ectopic pregnancy rates, number of ETs needed per live birth and neonatal outcomes. Limitations, reasons for caution This study was limited by the inherent potential bias of retrospective studies and small sample size. Thus, additional studies with larger sample sizes are needed to confirm our findings. Wider implications of the findings PGT-A failed to improve cumulative live birth rate or shorten time to pregnancy, but optimized pregnancy outcomes per transfer for patients with limited good-quality embryos. Trial registration number Not applicable

Background and Aims: The association of dyslipidemia with reproductive outcomes is largely unknown, especially in recurrent implantation failure (RIF) patients. This study aimed to explore the impact of abnormal blood lipid levels on embryo genetic status and pregnancy outcomes in unexplained RIF (uRIF) patients after preimplantation genetic testing for aneuploidy (PGT-A). Method: In this retrospective study, they were divided into 4 groups according to the levels of cholesterol and triglyceride: non-hyperlipidemia group (NonH group), simple hypercholesterolemia group (SHC group), simple hypertriglyceridemia group (SHC group) and mixed hyperlipidemia group (MixH group). Additionally, patients were divided into 2 groups according to their HDL-C level. Embryos’ genetic status and pregnancy outcomes after transfer of euploid embryos were analyzed. Binary logistic regression and/or generalized estimating equation model were conducted to investigate the association of different types of dyslipidemia with aneuploid embryo rate and cumulative live-birth rate. Results: A total of 474 women were divided into four groups: NonH group (N=349), SHC group (N=55), SHT group (N=52) and MixH group (N=18). Compared with the NonH group, SHC group had a significantly increased aneuploid embryo rate [48.3% vs. 36.7%, P=0.006; adjusted OR (95% CI) = 1.52(1.04-2.22)], as well as a reduced number of good-quality blastocysts [3.00±2.29 vs. 3.74±2.77, P=0.033]. The SHC group showed a lower cumulative live-birth rate (47.0% vs. 40.0%), good birth outcome (37.2% vs. 34.5%) and a higher risk of clinical pregnancy loss (11.1% vs. 17.9%) but did not reach statistical significance. The incidences of obstetric or neonatal complications and other adverse events were similar in the four groups. Conclusion: We found that uRIF women with hypercholesterolemia had an increased proportion of aneuploid embryos and a reduced number of high-quality embryos, while different types of hyperlipidemias had no correlation with cumulative live birth rate as well as pregnancy and neonatal outcomes.

The uterine epithelium undergoes a dramatic spatiotemporal transformation to enter a receptive state, involving a complex interaction between ovarian hormones and signals from stromal and epithelial cells. Redox homeostasis is critical for cellular physiological steady state; emerging evidence reveals that excessive lipid peroxides derail redox homeostasis, causing various diseases. However, the role of redox homeostasis in early pregnancy remains largely unknown. It is found that uterine deletion of Glutathione peroxidase 4 (GPX4), a key factor in repairing oxidative damage to lipids, confers defective implantation, leading to infertility. To further pinpoint Gpx4's role in different cell types, uterine epithelial-specific Gpx4 is deleted by a lactotransferrin (Ltf)-Cre driver; the resultant females are infertile, suggesting increased lipid peroxidation levels in uterine epithelium compromises receptivity and implantation. Lipid peroxidation inhibitor administration failed to rescue implantation due to carbonylation of major receptive-related proteins underlying high lipid reactive oxygen species. Intriguingly, superimposition of Acyl-CoA synthetase long-chain family member 4 (ACSL4), an enzyme that promotes biosynthesis of phospholipid hydroperoxides, along with uterine epithelial GPX4 deletion, preserves reproductive capacity. This study reveals the pernicious impact of unbalanced redox signaling on embryo implantation and suggests the obliteration of lipid peroxides as a possible therapeutic approach to prevent implantation defects.

Background and Aims: Maternal age has been reported to impact on embryo genetic status. However, current data on the association between maternal age and early embryo development are limited and inconclusive, especially among good-prognosis women. This study aims to determine the association between female age and embryonic aneuploidy based on next generation sequencing (NGS), as well as morphological score among women aged 20-37 years with a good prognosis. Method: This is a secondary analysis of a multi-center, randomized controlled trial conducted from July 2017 through June 2018, which investigated the efficacy of preimplantation genetic testing for aneuploidy (PGT-A) in good-prognosis infertile population. The women with PGT-A treatment were divided into three groups (20-24 yrs, 25-30 yrs, 31-37 yrs) according to maternal age. The diversity of embryo testing results based on NGS and morphological score were compared between three groups. Results: A total of 1809 embryos were analyzed in this study. The rates of embryonic overall aneuploidy (14.5%) and monosomy (3.0%) among females in the 25-30 age group were lower than those (aneuploidy 21.3%, monosomy 6.9%) in the 31-37 age group (adjusted P= 0.009, 0.004, respectively). However, the rates of embryonic aneuploidy (18.9%) and monosomy (3.9%) of females in the 20-24 age group did not differ from other two age groups. Although there was no significant difference in subsegmental aneuploidy rate among the three groups (P=0.215), the variation trend with age was consistent with that of embryonic aneuploidy. There was no significant difference in embryo morphological scores between the three groups. Conclusion: For young infertile women with a good prognosis, embryonic aneuploidy and monosomy are more likely to occur in advanced age more than 30 years. And embryonic development scores do not change significantly with increasing age.

Context Some studies have reported the early miscarriage rate is higher in polycystic ovary syndrome (PCOS) women. However, there is a lack of evidence as to whether the risk of embryo abnormalities increases in PCOS women. Objective This work aimed to evaluate the association between PCOS and embryo ploidy. Methods A secondary analysis of a multicenter, randomized controlled trial was conducted from July 2017 to June 2018. The original intent was to identify whether preimplantation genetic test for aneuploidy (PGT-A) improves the live birth rate as compared with in vitro fertilization (IVF). From 14 reproductive centers, 190 patients diagnosed with PCOS and 1:1 age-matched non-PCOS patients were chosen from a PGT-A group. A total of 380 patients with 1118 embryos were included in our study. Intervention included women diagnosed with PCOS, and the main outcome measures were embryonic aneuploidy and embryonic mosaic. Results After adjusting for potential confounders, the rate of embryonic aneuploidy and embryonic mosaic in the PCOS group were comparable with the control group (embryonic aneuploid rate PCOS group: 14.0% vs control group: 18.3%, adjusted OR [95% CI]: 0.78 [0.54, 1.12]; P = .19; embryonic mosaic rate 10.9% vs 10.1%, adjusted OR [95% CI]: 0.91 [0.59, 1.40]; P = .66). We further stratified PCOS women into 4 groups according to phenotype. The rate of aneuploid and mosaic embryos was comparable between each PCOS phenotype and control group. There was still no significant difference of embryonic aneuploid and embryo mosaic rates among the 4 phenotypes. Conclusion The risk of aneuploid and mosaic embryos did not increase in PCOS women. Thus, we suggest that the miscarriage rate arising from abnormal embryonic chromosomes could be similar between PCOS and non-PCOS women.

This study was to determine whether multiple vitrification-warming procedures and insemination method are associated with pregnancy and neonatal outcomes in preimplantation genetic testing for aneuploidy (PGT-A). This was a retrospective, single-center, observational study of 112 patients who underwent standard PGT-A practice and 154 patients who desired PGT-A for their vitrified unbiopsied blastocysts. A total of 97 euploid blastocysts biopsied and vitrified-warmed once and 117 euploid blastocysts biopsied once but vitrified-warmed twice (83 in vitro fertilization [IVF]–derived and 34 intracytoplasmic sperm injection [ICSI]–derived euploid blastocysts) were transferred. The primary outcome was the blastocyst survival rate for transfer, live birth rate, and neonatal outcomes. The results showed that an additional vitrification-warming procedure on blastocysts resulted in a lower but not statistically different survival rate for transfer. Compared with euploid blastocysts vitrified-warmed once, those vitrified-warmed twice provided statistically similar live birth rate. Neonatal outcomes, including the sex ratio, gestational age, birthweight, preterm birth rate, and low birthweight rate, did not differ between single and double vitrification. No significant differences were observed in rates of blastocyst survival, blastocyst euploid and live birth, and neonatal outcomes resulting from either conventional IVF or ICSI. The neonatal follow-up of babies live-born so far did not report any congenital malformations. In conclusion, an additional vitrification-warming on blastocysts had no detectable adverse impact on clinical outcomes after frozen-thawed single euploid blastocyst transfer in PGT-A cases; and ICSI did not confer any benefit in improving clinical outcomes compared with conventional IVF in cases requiring PGT-A on already vitrified nonbiopsied blastocysts.

Background and Aims: The safety of exogenous gonadotropins regarding its impact on embryos as well as pregnancy outcomes is still inconclusive. This study aimed to evaluate the effects of different doses and duration of gonadotropins on embryonic genetic status, pregnancy outcomes in infertile women with a good prognosis. Method: This is a secondary analysis of a multi-center, randomized controlled trial conducted from July 2017 through June 2018, which investigated the efficacy of preimplantation genetic testing for aneuploidy (PGT-A) in good-prognosis infertile population. Couples with PGT-A treatment were included in this study, and were divided into four groups according to the total dosage of exogenous gonadotropins and the duration of stimulation: Group1,2,3,4 with gonadotropins doses and stimulation duration [Formula: see text]1500 IU, <10 days; [Formula: see text]1500 IU, [Formula: see text]10 days; >1500 IU, <10 days; >1500 IU, [Formula: see text]10 days, respectively. Group 1 served as the control group. The main outcome measures were the rates of embryonic aneuploidy, mosaicism and cumulative live birth after transfers of euploid embryos. Results: A total of 579 couples were included, with 1737 embryos being genetically screened using NGS. After adjusting for confounding factors, embryo mosaicism rate was significantly increased in Group 2, 3, 4 in comparison with Group 1 (Group 2,3,4: 13.4%, 14.8%, 12.4%, respectively, vs. Group1: 8.9%; adjusted OR [95% CI]: 1.65[1.07, 2.54], [Formula: see text]=0.024; 1.76[1.02, 3.30], [Formula: see text]=0.041; 1.50[1.01, 2.22], [Formula: see text]=0.043; respectively). There was no association between gonadotropins dose or duration and embryo aneuploidy rate. The cumulative live-birth rate was significantly lower in Group 2, 3 and 4 than that in Group 1 (Group 2,3,4: 73.2%, 64.8%, 75.2%, respectively, vs. Group 1: 85.0%; adjusted OR [95% CI]: 0.50 0.28, 0.89], [Formula: see text]=0.019; 0.34[0.17, 0.68], [Formula: see text]=0.002; 0.59[0.35, 0.98], [Formula: see text]=0.043; respectively). Conclusions: High dose, prolonged ovarian stimulation may increase mosaic embryo rate and decrease cumulative live-birth rate after transfers of euploid embryos.in infertile women with a good prognosis.