The London Women's Clinic is a private healthcare centre situated in London's Harley Street. Owned by Dr Kamal Ahuja, and founded in 1992, the centre has a reputation for helping single women and lesbian couples conceive. The clinic is closely associated with the London Sperm Bank and the London Egg Bank.
Introduction A balanced endometrial immune profile is considered to be the ideal environment for a successful implantation, as opposed to endometrial immune dysregulation. However, the embryo quality may be the pivotal 'immune' factor compared to the uterine immune environment.Study method After providing informed consent, young infertile patients involved in ART underwent an analysis of their endometrial immune profile before their embryo transfer (ET). Each ET was classified as a Top transfer if the used embryos were of Top morphology; all other transfers were classified as non-Top. The live birth rate (LBR) after ET was compared between patients with a balanced endometrial immune profile and patients with a dysregulated endometrial immune profile, with no intervention to regulate the endometrial environment (conventional care).Results Overall, the LBR did not differ significantly between patients with balanced and dysregulated endometrial profile receiving conventional care (39.5% vs 29.7%; OR: 1.55 [0.66-2.72]). However, among patients with a non-Top transfer, the LBR was higher in the balanced group (38.4% vs 21.2%; OR: 2.11 [1.02-4.37]). In contrast, no difference was observed in the case of a Top transfer (46.3% vs 45.8%; OR: 0.99 [0.38-2,55]).Conclusion These preliminary results suggest that a balanced endometrial immune environment may favour the implantation in patients using morphologically suboptimal embryos. In contrast, an endometrial immune dysregulation negatively impacts the implantation of morphologically suboptimal embryos.Trial registration NCT02262117Trial registration date October, 7th, 2014Date of the first patient's enrolment October, 30th, 2015
RESEARCH QUESTION:Does the use of embryo warming with an ultrafast protocol influence clinical and perinatal health outcomes when compared with conventional warming protocols? DESIGN:A retrospective cohort study was conducted at a single IVF centre evaluating frozen embryo transfer cycles performed between November 2023 and December 2024. Traditionally vitrified embryos were subsequently warmed using either traditional or ultrafast protocols. Live birth rate and perinatal outcomes including gestational age, neonatal birthweight and twin rates were calculated. RESULTS:A total of 4061 blastocyst warming events in 3657 embryo transfer cycles were analysed, of which 2761 involved warming using an ultrafast protocol and 1300 warming using a traditional protocol. Embryo survival was 99% following both methods. Live birth rates were comparable (37% versus 35.4%). No significant differences were observed in perinatal health outcomes. CONCLUSIONS:Warming with an ultrafast protocol provides excellent embryological and clinical outcomes equivalent to those achieved with traditional warming, without evident adverse effects on perinatal health outcomes. These findings support the efficiency of the ultrafast protocol as a routine approach in assisted reproduction and its potential to maintain optimal patient outcomes.
Research question is a fresh embryo transfer cycle or a frozen embryo transfer after a freeze-all approach superior in achieving a live birth in IVF cycles? Design This is a retrospective matched analysis of 9923 autologous oocyte collections and 9,716 embryo transfers performed between 2016-2023 at a single UK centre. Patients underwent either fresh transfer, or a decision was made to freeze all embryos. First embryo transfer outcomes from each cycle were assessed, and a separate analysis assessing the hazard ratio of live birth across multiple embryo transfers arising from a single oocyte retrieval, of which 1664 cumulative live births after 4202 fresh transfer cycles and 1354 cumulative live births after 2312 freeze all embryo cycles. Results No differences were seen in live birth odds when stratifying by age. Among low responders (<6 oocytes) fresh and first frozen embryo transfers demonstrated comparable live birth rates (aOR 1 [0.7-1.5]; 26% vs 27% respectively, P = 1). In high responders (16 +oocytes) and high embryo yield cycles (5+), higher outcomes in fresh transfers were observed but was non-significant. Low embryo yield cycles (<3) were associated with significantly improved outcomes after a freeze-all approach controlled for embryo quality (aOR 1.6 [1.2-2.1]; 38% vs 29%, P = 0.02), with potential greater benefit to patients 38 or older. In sub-optimal grade embryo transfers, freeze-all was associated with 2-fold increase in live birth odds in under 38s, yet lost significance post-correction. Cumulatively, while greater rates of achieving a LB were observed for fresh cycles in patients under 38 than FAE, overall there were no significant differences in LBs per cycle. Conclusions To conclude, findings suggest a freeze-all approach may improve outcomes in low embryo yield cycles and younger patients with suboptimal graded embryos but requires further confirmatory analyses.
OBJECTIVE:To study the parental origin, timing, and within-embryo distribution of unbalanced structural chromosomal abnormalities (segmental aneuploidy) in human blastocysts initially classified as nonmosaic by single trophectoderm biopsy (TE1) during clinical preimplantation genetic testing for aneuploidy (PGT-A). DESIGN:Retrospective cohort study. SUBJECTS:Human blastocysts donated for research after clinical PGT-A cycles. EXPOSURE:Clinical PGT-A followed by multisample embryo analysis using an independent second trophectoderm biopsy (TE2), microdissected inner cell mass (ICM) sampling, and low-pass whole-genome sequencing with single-nucleotide polymorphism-informed haplotyping. MAIN OUTCOME MEASURES:Concordance of segmental aneuploidy across three embryonic samples, mosaicism, parental origin, inferred timing of origin, and evidence of secondary intrachromosomal events. RESULTS:A total of 105 blastocysts with at least one nonmosaic segmental aneuploidy identified by TE1 were analyzed using low-pass whole-genome sequencing with single-nucleotide polymorphism-informed haplotyping. For each embryo, an independent TE2 and a microdissected ICM were analyzed. Despite nonmosaic classification at TE1, 81% (85/105) of embryos demonstrated discordant findings across samples, consistent with mosaicism, whereas only 19% (20/105) were concordant across TE1, TE2, and ICM. Multisample analysis altered the inferred chromosomal status in 37.1% of embryos initially flagged by single-biopsy PGT-A. Fifty-two embryos (49.5%) had >1 paternally derived error, compared with 40 (38%) >1 maternal, contrasting with the predominantly maternal origin of whole-chromosome aneuploidy. Reciprocal gain-loss patterns with shared breakpoints, and other patterns consistent with isochromosomes or ring chromosomes, were identified in 22.9%. Evidence suggested that segmental errors may undergo postzygotic rescue or be followed by additional structural abnormalities affecting the same chromosome, i.e., an "intrachromosomal effect." CONCLUSIONS:Segmental aneuploidy in human blastocysts is frequently mosaic at the embryo level despite nonmosaic classification by TE1. It is meiotically derived in over 50% of cases, is often paternal in origin, and is commonly associated with secondary intrachromosomal structural changes. These findings highlight fundamental biological differences between segmental and whole-chromosome aneuploidy and have implications for the interpretation of segmental abnormalities detected during clinical PGT-A.
Direct evidence from live cell imaging and single-cell sequencing of disaggregated cells that mitotic abnormalities continue to occur in the trophectoderm at the blastocyst stage, resulting in clones of aneuploid cells, has important implications for preimplantation genetic testing (PGT) for aneuploidies. Here we argue that, to improve accuracy and minimize the deselection of potentially viable embryos with only mitotic aneuploidies of unknown clinical significance, the use of methods that, up until now, have only been used for PGT for monogenic/single-gene defects could provide the answer. Genome-wide single-nucleotide polymorphism parental haplotyping (karyomapping) is a universal linkage-based method for tracking the inheritance of disease genes. However, the same method can be used for molecular karyotyping to identify meiotic trisomies and monosomies or segmental deletions by the presence of dual parental haplotypes, or absence of parental haplotypes, respectively. Combined with parental intensity analysis to detect mitotic aneuploidies with normal biparental inheritance, this allows meiotic and mitotic, whole and segmental chromosome aneuploidies to be identified. This provides the opportunity to prioritize the deselection of embryos with meiotic aneuploidies affecting the whole embryo while considering those with only mitotic aneuploidies for transfer, with appropriate genetic counselling.
