Which factors affect the likelihood of miscarriage after single euploid blastocyst transfer?

Research questionWhich parameters affect the likelihood of miscarriage after single euploid frozen–thawed blastocyst transfer (FBT)?DesignIn this retrospective study, clinical and laboratory data from 1051 single euploid FBTs were evaluated. Exclusion criteria were endocrine or systemic pathologies, uterine anomalies or pathologies, unilateral or bilateral hydrosalpinx, karyotypic abnormalities (either maternal or paternal) or thrombophilia. Patients were divided into two groups according to pregnancy outcome: live birth and miscarriage.ResultsBody mass index (BMI) (25.98 ± 0.5 versus 24.36 ± 0.21, P = 0.019), duration of infertility (6.62 ± 0.54 versus 4.92 ± 0.18, P = 0.006) and number of previous miscarriages (1.36 ± 0.13 versus 0.79 ± 0.05, P < 0.001) were significantly higher in the miscarriage group (n = 100) than in the live birth group (n = 589). Although the trophectoderm and inner cell mass (ICM) percentage scores were not statistically different among the miscarriage and live birth groups, the percentage of day-6 biopsied embryos was significantly higher in the miscarriage group. Binary logistic regression analysis revealed that BMI (OR 1.083, 95% CI 1.013 to 1.158, P = 0.02) and number of previous miscarriages (OR 1.279, 95% CI 1.013 to 1.158, P = 0.038) were independent factors for miscarriage. Patients with elevated BMI and a higher number of miscarriages were at increased risk of miscarriage.ConclusionAfter a single euploid FBT, BMI and number of previous miscarriages are predictors of miscarriage. Lifestyle interventions before FBT may decrease miscarriage rates.     

The impact of patient,embryo, and translocation characteristics on the ploidy status of young couples undergoing preimplantation genetic testing for structural rearrangements (PGT-SR) by next generation sequencing (NGS)

PurposeTo evaluate the factors that affect the incidence of euploid balanced embryos and interchromosomal effect (ICE) in carriers of different structural rearrangements.MethodsThis retrospective study includes 95 couples with reciprocal translocations (RecT) and 36 couples with Robertsonian translocations (RobT) undergoing Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR) between March 2016 and July 2019. Next-generation sequencing (NGS) was the technique used coupled with trophectoderm (TE) biopsy. Only cases with females under 38 years were included. A total of 532 blastocysts were evaluated.ResultsThe euploidy rate was similar in RobT when compared with RecT carriers [57/156 (36.5%) vs. 112/376 (29.8%), p = 0.127]. The pure ICE rate was significantly higher in RobT carriers [48/156 (30.8%) vs. 53/376 (14.1%), p < 0.001] than it was in RecT carriers. Female age was the independent factor for the probability of obtaining a euploid embryo in RecT and RobT carriers, and increasing female age decreases the probability of obtaining a euploid embryo. In RecT carriers, no significant differences were observed in euploidy rates, pure ICE, or combined ICE according to the length of the translocated fragment and the chromosome group. However, total ICE was significantly lower when there was a breakpoint in the short chromosome arm together with a breakpoint in the long arm [(44/158 (27.8%) for pq or qp, 51/155 (32.9%) for pp and 30/63 (47.6%) for qq; p = 0.02].ConclusionThe incidence of euploid/balanced blastocysts was similar in both types of translocations. However, there was a significant increase in pure ICE in RobT compared to RecT carriers. In RecT carriers, the presence of the breakpoints in the long arm of the chromosomes involved in the rearrangement resulted in a higher total ICE.     

Structural and mechanistic insight into N-glycan processing by endo-α-mannosidase

N-linked glycans play key roles in protein folding, stability, and function. Biosynthetic modification of N-linked glycans, within the endoplasmic reticulum, features sequential trimming and readornment steps. One unusual enzyme, endo-α-mannosidase, cleaves mannoside linkages internally within an N-linked glycan chain, short circuiting the classical N-glycan biosynthetic pathway. Here, using two bacterial orthologs, we present the first structural and mechanistic dissection of endo-α-mannosidase. Structures solved at resolutions 1.7–2.1 Å reveal a (β/α)₈ barrel fold in which the catalytic center is present in a long substrate-binding groove, consistent with cleavage within the N-glycan chain. Enzymatic cleavage of authentic Glc_1/3Man₉GlcNAc₂ yields Glc_1/3-Man. Using the bespoke substrate α-Glc-1,3-α-Man fluoride, the enzyme was shown to act with retention of anomeric configuration. Complexes with the established endo-α-mannosidase inhibitor α-Glc-1,3-deoxymannonojirimycin and a newly developed inhibitor, α-Glc-1,3-isofagomine, and with the reducing-end product α-1,2-mannobiose structurally define the -2 to +2 subsites of the enzyme. These structural and mechanistic data provide a foundation upon which to develop new enzyme inhibitors targeting the hijacking of N-glycan synthesis in viral disease and cancer.     

Euploidy rates of embryos in young patients with good and low prognosis according to the POSEIDON criteria

Research questionDoes an association exist between ovarian reserve, ovarian response and embryonic euploidy in female patients under age 35 years?DesignThis was a retrospective analysis of intracytoplasmic sperm injection and preimplantation genetic testing for aneuploidies cycles among patients enrolled at Bahceci Fulya IVF Center between January 2016 and August 2019. A total of 133 patients in POSEIDON group 1 (suboptimal responder; female age <35 years, antral follicle count [AFC] ≥5, number of oocytes retrieved <10) (group A), 133 patients in POSEIDON group 3 (expected low responder; female age <35 years, AFC <5) (group B) and 323 in the non-low-prognosis group (female age <35 years, AFC ≥5 and number of oocytes retrieved >9) (group C) were included.ResultsThere was no significant difference in euploidy rate per embryo among the three groups (61.7% [145/235] for group A versus 53.5% [68/127] for group B versus 62% [625/1008] for group C; P = 0.13). The cancellation rate in cycles without a euploid blastocyst was significantly lower in group C than groups A and B (8.4% versus 12.8% and 16.5%; P = 0.034). Multivariate regression analysis indicated that the ovarian response group did not significantly affect the probability of obtaining a euploid embryo. Trophectoderm score ‘C’ (odds ratio 0.520, P = 0.007) and inner cell mass score ‘C’ (odds ratio 0.480, P < 0.001) were associated with a decreased probability of obtaining a euploid embryo.ConclusionsThese results confirm that POSEIDON group 1 and group 3 and non-low-prognosis patients have different probabilities of euploid embryos being obtained per cycle. However, euploidy rates per embryo are not affected by the patient’s ovarian reserve and response.