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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 good-quality 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. RESULTS A total of 1212 patients underwent randomization, and 606 were assigned to each trial group. Live births occurred in 468 women (77.2%) in the PGT-A group and in 496 (81.8%) in the conventional-IVF group (absolute difference, -4.6 percentage points; 95% confidence interval [CI], -9.2 to -0.0; P

Background This study aimed to analyze the clinical outcomes of blastocyst which undergo the preimplantation genetic testing (PGT) transplantation from frozen-thawed D5 and D6. In addition, the effect of blastocyst grade on clinical and neonatal outcomes was also investigated in this study. Methods The pregnancy and miscarriage rates of 1130 cycles of frozen embryo transfer, including 784 D5 frozen embryos and 346 D6 frozen embryos in the Reproductive Hospital of Shandong University from January to December 2020 were analyzed. Gardner blastocyst scoring was used for blastocyst evaluation. Results The pregnancy rate of D5 blastocyst was significantly higher, whereas the miscarriage rate of D5 blastocyst was lower, than that of D6 blastocyst tissue biopsy. No significant difference was observed in birth weight and low birth weight of D5 blastocyst and D6 blastocyst, preterm birth, gestational age, and neonatal sex. Frozen-thawed D5 blastocysts have higher pregnancy success rates and lower miscarriage rates compared to D6 blastocysts. Conclusion Therefore, both blastocyst grade and embryo biopsy date must be considered when transferring frozen embryos.

Epimedium has gained widespread clinical application in Traditional Chinese Medicine, with the functions of promoting bone reproduction, regulating cell cycle and inhibiting osteoclastic activity. However, its precise cellular pharmacological therapeutic mechanism on osteoporosis (OP) remains elusive. This study aims to elucidate the molecular mechanism of epimedium in the treatment of OP based on system bioinformatic approach. Predicted targets of epimedium were collected from TCMSP, BATMAN-TCM and ETCM databases. Differentially expressed mRNAs of OP patients were obtained from Gene Expression Omnibus database by performing Limma package of R software. Epimedium-OP common targets were obtained by Venn diagram package for further analysis. The protein-protein interaction network was constructed using Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were carried out by using clusterProfiler package. Molecular docking analysis was conducted by AutoDock 4.2 software to validate the binding affinity between epimedium and top 3 proteins based on the result of protein-protein interaction. A total of 241 unique identified epimedium targets were screened from databases, of which 62 overlapped with the targets of OP and were considered potential therapeutic targets. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that these targets were positive regulation of cell cycle, cellular response to oxidative stress and positive regulation of cell cycle process as well as cellular senescence, FoxO, PI3K-Akt, and NF-kappa B signaling pathways. Molecular docking showed that epimedium have a good binding activity with key targets. Our study demonstrated the multitarget and multi-pathway characteristics of epimedium on OP, which elucidates the potential mechanisms of epimedium against OP and provides theoretical basis for further drug development.

IntroductionExisting randomised controlled trials (RCTs) comparing a freeze-all embryo transfer strategy and a fresh embryo transfer strategy have shown conflicting results. A freeze-all or a fresh transfer policy may be preferable for some couples undergoing in-vitro fertilisation (IVF), but it is unclear which couples would benefit most from each policy, how and under which protocols. Therefore, we plan a systematic review and individual participant data meta-analysis of RCTs comparing a freeze-all and a fresh transfer policy.Methods and analysisWe will search electronic databases (Medline, Embase, PsycINFO and CENTRAL) and trial registries (ClinicalTrials.gov and the International Clinical Trials Registry Platform) from their inception to present to identify eligible RCTs. We will also check reference lists of relevant papers. The search was performed on 23 September 2020 and will be updated. We will include RCTs comparing a freeze-all embryo transfer strategy and a fresh embryo transfer strategy in couples undergoing IVF. The primary outcome will be live birth resulting from the first embryo transfer. All outcomes listed in the core outcome set for infertility research will be reported. We will invite the lead investigators of eligible trials to join the Individual participant data meta-analysis of trials comparing frozen versus fresh embryo transfer strategy (INFORM) collaboration and share the deidentified individual participant data (IPD) of their trials. We will harmonise the IPD and perform a two-stage meta-analysis and examine treatment–covariate interactions for important baseline characteristics.Ethics and disseminationThe study ethics have been granted by the Monash University Human Research Ethics Committee (Project ID: 30391). The findings will be disseminated via presentations at international conferences and publication in peer-reviewed journals.PROSPERO registration numberCRD42021296566.

Zona pellucida-free (ZP-free) embryos often fail to achieve good developmental outcomes and are routinely discarded in assisted reproductive laboratories. Existing attempts to rescue ZP-free embryos are not widely used due to operational complexity and high technical requirements. To handle cases with missing ZP, we applied modified sodium hyaluronate gel (MSHG) to embryo culture to determine if it can function as a substitute for human zona pellucida.The developmental process and the blastocyst formation rate of embryos were analyzed in both mouse and human. The first clinical application of MSHG was reported, and the pregnancy outcome was continuously followed up.Human and mouse ZP-free embryos cultured with MSHG showed a blastocyst formation rate similar to ZP-intact embryos. MSHG improves blastocysts formation rate by maintaining blastomere spatial arrangement at early stages. Compared to ZP-free embryos, the proportion of tetrahedrally arranged blastomeres at the 4-cell stage increased significantly in embryos cultured with MSHG in humans. A ZP-free blastocyst cultured in MSHG with the highest score was successfully implanted after day 5 transplantation and developed normally.These data demonstrate that MSHG can substitute the function of zona pellucida and rescue human ZP-free embryos during assisted reproductive technology.

PURPOSE: To evaluate clinical outcomes after frozen-thawed blastocyst transfer (TBT) with blastocysts which were derived from different cell numbers on day 3. METHODS: The study included 1444 patients undergoing single autologous frozen-thawed blastocyst transfer cycles, which were allocated to five groups according to the cell numbers on day 3 of the transferred blastocysts: ≤ 6-cell (n = 109), 7-cell (n = 169), 8-cell (n = 811), 9-cell (n = 136), and ≥ 10-cell (n = 219). RESULTS: The LBR of the ≤ 6-cell group was found to be statistically lower than that of the 8-cell group in single TBT cycles which had been transferred with fair quality blastocysts (defined as 4BB according to Gardner’s grading scale) (41.28% vs 55.73%, P = 0.004), while the miscarriage rate was significantly higher for the ≤ 6-cell group compared with the 8-cell group (25.00% vs 13.74%, P = 0.02). No differences were found between the two groups in terms of cPR (P = 0.06). However, for blastocysts categorized as high quality according to Gardner’s classification (defined as 4AA/4AB/4BA), cPR, LBR, and early miscarriage rates did not differ between the two groups (P = 0.76, P = 0.44, P = 0.40, respectively). CONCLUSIONS: When transferring blastocysts, an evaluation of the cleavage stage should be performed along with blastocyst morphology to shorten the time of conceiving. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10815-019-01664-x) contains supplementary material, which is available to authorized users.

A xylanase from Talaromyces thermophiles F1208 (T-Xyn) was used specifically to explore the effects of disulfide bond on hydrolytic activity. The T-Xyn-C122S-C166S mutant does not have the C122-C166 disulfide bond present in wild-type T-Xyn, whereas T-Xyn-T38C-S50C and T-Xyn-T38C-S50C-C122S-C166S mutants have an introduced disulfide bond, C38-C50, to T-Xyn and T-Xyn-C122S-C166S, respectively. The optimum pH of T-Xyn-T38C-S50C and T-Xyn-T38C-S50C-C122S-C166S was lower than that of T-Xyn and T-Xyn-C122S-C166S. The introduction of a disulfide bond caused a decrease in the optimum temperature and thermal stability of T-Xyn. The existence of a disulfide bond has a strong influence on the hydrolysis characteristics of T-Xyn, which caused changes in the composition and proportion of the hydrolysate products. T-Xyn-T38C-S50C produces the highest level of xylose when using beechwood xylan as the substrate, whereas T-Xyn produces the highest level of xylobiose and T-Xyn-T38C-S50C-C122S-C166S produces the largest amount of xylotriose. When birchwood xylan was used as the substrate, the introduction of a disulfide bond increased the content of xylose, decreased the content of xylotriose and a high degree of polymerization (DP ≥ 5) was observed. The hydrolysis of oat-spelt xylan is more complex with the introduction of the disulfide bond causing an increase in the degradation rate of xylotriose.

To investigate the occurrence and development state of embryo vacuoles between the 8-cell and morula stages, and to explore how vacuoles affected the development of embryos. A retrospective study of a cohort of 422 patients undergoing conventional in vitro fertilization or intracytoplasmic sperm injection. With the help of time-lapse imaging, the development processes and outcomes of good quality embryos with or without vacuoles were analyzed. Vacuole positive embryos had significantly lower blastulation rate and good quality blastulation rate than vacuole negative embryos, p

It is known that the male hypogonadism plays an important role in regulating adipose metabolism. In the present study, fifteen pairs of full male sibs were divided into a castrated group and an intact group with a paired experiment design. The pigs were slaughtered at an age of 175days. The carcass characteristics and fat deposit of the studied animal were measured, and the hormone and serum lipid levels of the peripheral blood samples were determined, and the differentially expressed genes of the back fat between the two groups were screened with porcine genome array. Our results showed that the absence of male gonadal steroids attributed to castration significantly raised the serum lipid levels and increased fat accumulation in the pigs. A total of 225 differentially expressed genes were identified between the boars and barrows and 135 of them were upregulated. The analysis of Gene Ontology categories and KEGG pathway indicated that these differentially expressed genes were mainly involved in metabolism of lipid, carbohydrate, amino acid, xenobiotics biodegradation, and immune diseases pathways. Our results indicated that there were higher capacity of fatty acid of synthesis, enhanced uptaking capacity of fatty acids and cholesterol, inhibited lipolysis, and enhanced carbohydrate metabolism in the adipose tissue of barrows compared to boars. The findings of the present study provide new insight into the mechanisms of adipose metabolism induced by hormone deficiency.

To investigate the clinical outcomes of conventional IVF and ICSI in female patients aged 40 years and over with no more than five oocytes retrieved and non-male factor infertility. A retrospective study of a cohort of 644 patients undergoing IVF/ICSI treatment. The 534 female patients aged ≧ 40 years with no more than five oocytes retrieved and non-male factor infertility undergoing their first conventional IVF cycles were assigned in IVF group. The rest of 110 patients aged 40 years and over with no more than five oocytes retrieved and non-male factor infertility undergoing first ICSI cycles were recruited in ICSI group. Our results showed the clinical pregnancy, live birth and miscarriage rates were similar between the IVF and ICSI groups (21.59% vs. 13.25%, P > 0.05; 12.16% vs. 6.02%, P > 0.05; 43.68% vs. 54.55%, P > 0.05; respectively), however, the implantation and cumulative live-birth rates were significantly higher in the IVF compared to the ICSI group (15.11% vs. 7.75%, 14.59% vs. 5.56%, P

PURPOSE: The etiology of fertilization failure and polyspermy during assisted reproductive technology (ART) remains elusive. The aim of this study was to determine whether mutations in the IZUMO1 receptor (IZUMO1R) gene, which is essential for mammalian fertilization, contribute to the pathogenesis of fertilization failure or polyspermy in humans. METHODS: We recruited 215 female subjects with fertilization failure/poor fertilization, 330 females with polyspermy, and 300 matched controls. All subjects underwent IVF treatment. Peripheral blood DNA of cases was extracted and screened for mutations in IZUMO1R gene. RESULTS: Four rare single nucleotide polymorphisms (SNPs) of the IZUMO1R were identified among specimens from patients with fertilization failure and polyspermy but were absent in the 300 control subjects. These included a missense SNP (rs76779571 in exon 4), which was found in two fertilization failure patients, and a nonsynonymous SNP (rs61742524 in exon 1) and two synonymous SNPs (rs76781645 in exon 1 and rs377369966 in intron 2), which were found among three polyspermy cases. CONCLUSIONS: The variations in IZUMO1R might play a role in the pathogenesis of fertilization failure and polyspermy, and the putative functions and effects of these rare variants require further studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10815-017-1101-5) contains supplementary material, which is available to authorized users.

This study aimed to test whether there is an association between embryo morphokinetic parameters and ploidy status.Patients with high risk of aneuploidy were analyzed by time-lapse microscopy combined with preimplantation genetic screening (PGS). Accordingly, 256 blastocysts from 75 patients were subjected to trophectoderm biopsy and microarray comparative genomic hybridization (array-CGH). Blastocyst development process was analyzed using time-lapse images.Morphokinetic parameters: tPNf, t2, t3, t4, t5, t8, t9, tcom, tM, tSB, tB, tEB, CC1, CC2, CC3, S2, S3, t5-t2, and tB-tSB showed no significant difference in euploid embryos compared to aneuploid counterparts. In addition, two risk models based on previously published morphokinetic parameters failed to segregate euploid from aneuploid embryos.Morphokinetic parameters subjected to investigation in the present study failed to improve the chance of selecting euploid embryos.

To compare the effectiveness of two protocols of blastocyst biopsy submitted to preimplantation genetic testing for aneuploidies (PGT-A). This is a randomized controlled trial of a cohort of 221 patients undergoing PGT-A. 106 female patients aged ≤ 40 years with no less than 8 mature oocytes retrieved and ≥ 3 good-quality embryos on day 3 were randomly assigned to the day-3 hatching-based TE biopsy. The remaining 115 females aged ≤ 40 years with ≥ 8 MII oocytes obtained and no less than 3 high-quality embryos on day 3 were assigned to the TE biopsy without hatching group (also called the new biopsy group). The primary outcome was measured by a live birth after the first embryo transfer. The live birth rate did not differ significantly between the two groups (50.00% vs. 59.26%, P > 0.05, OR 1.46; 95% CI 0.78–2.70). There was no significant between-group difference in the rates of implantation, clinical pregnancy, and miscarriage. However, the frozen blastocyst rate was significantly lower in the day-3 hatching-based TE biopsy compared with the new biopsy group (47.54% vs. 53.96%, P

Background: Oocyte vitrification is widely used throughout the world, but its clinical efficacy is inconsistent and depends on the vitrification media. This study compared the developmental potential and clinical results of in vivo matured oocytes cryopreserved with different vitrification media. Methods: This retrospective study involved vitrified-warmed oocytes at one in vitro fertilization laboratory. Vitrification media kits comprised the MC kit (ethylene glycol [EG] plus 1,2-propanediol [PROH]), the KT kit (EG plus dimethyl sulphoxide [DMSO]), and the Modified kit (EG plus DMSO and PROH kit). Rates of oocyte survival and subsequent developmental potential were recorded and analyzed. The t-test and the Chi-square test were used to evaluate each method′s efficacy. Results: Oocyte survival rate was significantly higher for the Modified kit (92.0%) than for the MC kit (88.2%) (P < 0.05) and the KT kit (77.3%) (P < 0.001). The rate of high-quality embryo development in the Modified kit group (35.8%) was significantly higher than in the MC kit group (29.0%) and the KT kit group (28.3%) (P < 0.001). No significant differences were observed in the clinical pregnancy and implantation rates among the MC, KT, and Modified kit groups (37.2% vs. 30.2% vs. 39.6%; 21.9% vs. 18.8% vs. 27.4%, respectively) (P > 0.05). The high-quality embryo rate per warmed oocyte was significantly higher (23.4%) in the Modified kit group than in the other groups (P < 0.001). The embryo utilization and live birth rates per warmed oocyte were the highest in the Modified kit group, but not significantly (P > 0.05). Conclusions: Modified vitrification media are efficient for oocyte vitrification and, with further verification, may be able to replace commercially available media in future clinical applications.

OBJECTIVE To evaluate the efficiency of spermatozoa cryopreservation and to compare the clinical pregnancy outcomes in intracytoplasmic sperm injection (ICSI) using fresh versus cryopreserved spermatozoa collected by testicular sperm aspiration (TESA). METHODS A retrospective study was performed to compare the outcomes of men who accepted frozen-spermatozoa-based TESA-ICSI with those of men who underwent TESA-ICSI using fresh spermatozoa between January 1, 2015, and December 30, 2016. The groups were matched for age. The rates of fertilization, good-quality embryos, blastocyst formation, and clinical pregnancy outcomes were obtained from clinical records and were compared between the groups. RESULTS There were no significant differences between the frozen TESA group (n=79) and the fresh TESA group (n=194) in the rates of fertilization (71.4% vs 73.4%), good-quality embryos (55.3% vs 54.5%), blastocyst formation (60.9% vs 60.1%), clinical pregnancy (61.7% vs 55.1%), and live delivery (51.1% vs 45.7%) (P>0.05 for all comparisons). CONCLUSION Freezing low-count sperm collected by TESA with a cryoprotectant was an efficient method in the treatment of male factor infertility.

Changes in pig fertility have occurred as a result of domestication, but are not understood at the level of genetic variation. To identify variations potentially responsible for prolificacy, we sequenced the genomes of the highly prolific Taihu pig breed and four control breeds. Genes involved in embryogenesis and morphogenesis were targeted in the Taihu pig, consistent with the morphological differences observed between the Taihu pig and others during pregnancy. Additionally, excessive functional non-coding mutations have been specifically fixed or nearly fixed in the Taihu pig. We focused attention on an oestrogen response element (ERE) within the first intron of the bone morphogenetic protein receptor type-1B gene ( BMPR1B ) that overlaps with a known quantitative trait locus (QTL) for pig fecundity. Using 242 pigs from 30 different breeds, we confirmed that the genotype of the ERE was nearly fixed in the Taihu pig. ERE function was assessed by luciferase assays, examination of histological sections, chromatin immunoprecipitation, quantitative polymerase chain reactions, and western blots. The results suggest that the ERE may control pig prolificacy via the cis-regulation of BMPR1B expression. This study provides new insight into changes in reproductive performance and highlights the role of non-coding mutations in generating phenotypic diversity between breeds.

To evaluate the relationship between day 3 embryo quality and nucleus spreading rate/signal resolution rate in Fluorescence in situ hybridization (FISH) during the PGD procedure.This study was a retrospective data analysis. 367 day-3 embryos were classified based on morphological scoring: grade 1 to grade 4 were defined from worse to better embryo quality. Day 3 embryos were classified as good quality when the number of blastomeres was between 6 and 10 and grade better than 2'. Nucleus spreading rate, signal rate and the full signal rate were compared between embryos with different morphological scoring.Nucleus spreading rate of blastomeres from morphological high-quality embryos was significantly higher (86.25 %) than from poor-quality embryos (76.53 %) (p0.05). The rate of blastomeres with full signals was significantly higher (79.32 %) in the morphological high-quality group than in poor-quality group (64.54 %) (p0.05). Similar results were found from day 3 embryos with cell number between 6 cells and 10 cells (nucleus spreading rate 86.01 vs. 76.34 %, p0.05; full signal rate 78.72 vs. 62.71 %, p0.05). Both have no significant difference in the signal rate (82.67 vs. 89.66 %; 83.10 vs. 89.95 %).Blastomeres from day 3 embryos with better morphological quality had higher nucleus spreading rate and higher full signal rate during FISH. Through this study, we speculate on whether it should reconsider the necessity of FISH application in embryos with poor quality.

This retrospective study analyzed fertilization protocols and pregnancy outcomes for oocytes with with narrow perivitelline space and heterogeneous zona pellucid (NPVS/HZP).In 63 in-vitro fertilization cycles filled with NPVS/HZP oocytes (abnormal oocytes group) and 521 cycles with normal oocytes (normal oocytes group), major clinical and laboratory parameters were recorded and compared in different fertilization cycles (conventional IVF cycles, rescue ICSI cycles, and traditional ICSI cycles).NPVS/HZP oocytes meant lower MIIoocytes rates in both IVF and ICSI cycles compared with normal oocytes (p0.05). The 2PN rates for abnormal oocytes were significantly lower than those for normal oocytes in both conventional IVF cycles (58.8% VS 71.3%, P0.05) and rescue ICSI cycles (58.0% VS 78.0%, P = 0.0000). The high-quality embryo rates in normal oocytes groups were significantly higher than those in abnormal oocytes groups in different fertilization cycles (52.2% VS 35.0%, P0.01; 42.9% VS 23.9%, P0.001; 50.6% VS 31.0%, P = 0.0000, respectively). No clinical pregnancy was obtained from abnormal oocytes in 11 conventional IVF cycles. The clinical pregnancy rates in rescue ICSI and traditional ICSI cycles were comparatively lower in abnormal oocytes groups, but there was no significant difference as compared with normal oocytes groups (35.0% VS 48.1% and 26.7% VS 50.7%, P0.05, respectively).Retrieval of oocytes characterized by NPVS/PZP from cycle to cycle was one of the reasons for obscure infertility. ICSI may be the right way to avoid fertilization failure and get pregnancy in women with NPVS/HZP oocytes.

To compare the clinical outcomes after day 3 embryo transfer, day 5 single blastocyst transfer (SBT) and frozen-thawed embryo transfer (FET) in high responder patients (15 retrieved oocytes) undergoing IVF/ICSI treatment.A retrospective analysis of three embryo transfer strategies for the high responder patients in IVF/ICSI cycles. The 1041 high responder patients diagnosed as primary infertility with more than 15 oocytes retrieved were recruited in Day 3 ET group, 308 patients with more than 15 oocytes retrieved first transferred with one blastocyst in SBT group and 425 patients with more than 15 oocytes retrieved in fresh cycle, first transferred with one frozen-thawed blastocyst were assigned in FET group.In the high responder patients, the clinical pregnancy rate after day 5 SBT was significantly lower than that of day 3 ET (43.18% VS 57.16%, p0.05). In addition, the clinical pregnant rate and implantation rate of FET cycles were significantly higher than SBT cycles (59.06% vs. 43.18% and 64.70% vs. 47.40%, p0.05). The multiple pregnancy rate in FET cycles was markedly lower than that of day 3 ET (2.35% VS 34.97%, p0.05).FET was the preferable strategy for the high responder patients in IVF/ICSI cycles to obtain both desirable clinical outcome and lower multiple pregnancy rates.

Chinese domestic chickens have been routinely subjected to artificial selection for the production of meats and eggs. Selection results in distinctive signatures in the genome that can reveal the genes underlying phenotypes of interest to breeders. In this study, we used the Chicken60K SNP chip to analyze DNA from Dwarf Brown-egg Layers (DB, n = 203) and Silky Fowls (SF, n = 181) and then examined the relative extended haplotype homozygosity (REHH) and fixation index (FST) to detect selection signatures. Since population structure analysis showed that SF was stratified into 2 subpopulations (SF1 and SF2), we removed the 20 SF1 chickens, and the remaining individuals (DB and SF2) were scanned for genome-wide selection signatures. A total of 939 selection signatures, including 446 candidate genes, were found to be potential selection targets using the FST test. REHH analysis identified 93 and 128 core regions, including 112 and 181 genes, in DB and SF2, respectively. Among the candidate genes, domestication-related genes such as NELL1 were found. After comparing the candidate genes with the Animal QTL database, we identified additional genes possibly associated with growth, reproduction, egg laying, and immune response, including GRHL3, CDK1, AKT1, and KMD3A. Functional enrichment analysis suggests that genes associated with muscle development have undergone positive selection. Our findings provide a genome-wide selection signature draft for DB and SF, and establish a resource that can be exploited in chicken breeding programs to manipulate the genes that underlie desired phenotypes.

Funder: Open Philanthropy Project; FundRef: http://dx.doi.org/10.13039/100014895, Funder: Curci and Weston Heavens Foundations, Funder: European molecular biology organisation; FundRef: http://dx.doi.org/10.13039/100004410, Apico-basal polarization of cells within the embryo is critical for the segregation of distinct lineages during mammalian development. Polarized cells become the trophectoderm (TE), which forms the placenta, and apolar cells become the inner cell mass (ICM), the founding population of the fetus. The cellular and molecular mechanisms leading to polarization of the human embryo and its timing during embryogenesis have remained unknown. Here, we show that human embryo polarization occurs in two steps: it begins with the apical enrichment of F-actin and is followed by the apical accumulation of the PAR complex. This two-step polarization process leads to the formation of an apical domain at the 8–16 cell stage. Using RNA interference, we show that apical domain formation requires Phospholipase C (PLC) signaling, specifically the enzymes PLCB1 and PLCE1, from the eight-cell stage onwards. Finally, we show that although expression of the critical TE differentiation marker GATA3 can be initiated independently of embryo polarization, downregulation of PLCB1 and PLCE1 decreases GATA3 expression through a reduction in the number of polarized cells. Therefore, apical domain formation reinforces a TE fate. The results we present here demonstrate how polarization is triggered to regulate the first lineage segregation in human embryos.