Mosaic human preimplantation embryos and their developmental potential in a prospective, non-selection clinical trial.

Chromosome imbalance (aneuploidy) is the major cause of pregnancy loss and congenital disorders in humans. Analyses of small biopsies from human embryos suggest that aneuploidy commonly originates during early divisions, resulting in mosaicism. However, the developmental potential of mosaic embryos remains unclear. We followed the distribution of aneuploid chromosomes across 73 unselected preimplantation embryos and 365 biopsies, sampled from four multifocal trophectoderm (TE) samples and the inner cell mass (ICM). When mosaicism impacted fewer than 50% of cells in one TE biopsy (low-medium mosaicism), only 1% of aneuploidies affected other portions of the embryo. A double-blinded prospective non-selection trial (NCT03673592) showed equivalent live-birth rates and miscarriage rates across 484 euploid, 282 low-grade mosaic, and 131 medium-grade mosaic embryos. No instances of mosaicism or uniparental disomy were detected in the ensuing pregnancies or newborns, and obstetrical and neonatal outcomes were similar between the study groups. Thus, low-medium mosaicism in the trophectoderm mostly arises after TE and ICM differentiation, and such embryos have equivalent developmental potential as fully euploid ones.

Subcutaneous progesterone administration provides a similar ongoing pregnancy rate compared with intramuscular progesterone administration in hormone replacement therapy frozen embryo transfer cycles.

Objective: To compare the ongoing pregnancy rates (OPRs) for subcutaneous progesterone (SC-P) to intramuscular progesterone (IM-P) in hormone replacement therapy used in frozen embryo transfer (FET) cycles. Design: Prospective nonrandomized cohort study. Setting: Private fertility clinic. Patients: The study enrolled 224 patients scheduled for hormone replacement therapy (HRT)-FET cycles with SC-P (n = 133) or IM-P (n = 91). The route of P administration was decided according to the patient's preference and accessibility to the hospital. In the first FET cycle of a freeze-all cycle using single blastocyst transfers, a woman aged ≤35 was included. Main Outcomes: Ongoing pregnancy (OP). Results: The demographic, cycle, and embryologic characteristics were similar between groups. The clinical pregnancy rates (86/133[64.7%] vs. 57/91[62.6%]); miscarriage rates (21/86 [24.4%] vs. 10/57 [17.5%]), and OPR (65/133 [48.9%] vs. 47/91 [51.6%]) were comparable between the SC-P and IM-P groups. Binary logistic regression for OP as the dependent factor revealed that blastocyst morphology was found to be a significant independent prognosticator (for poor quality embryos adjusted odds ratio, 0.11; 95% confidence interval, 0.029-0.427) and progesterone route (SC-P vs. IM-P) was an insignificant prognosticator (adjusted odds ratio, 0.694; 95% confidence interval, 0.354-1.358). Conclusions: The OPR for SC-P administration was similar to that for IM-P in HRT-FET cycles. The effect of ET-day P levels may vary regarding the administration route. Randomized controlled trials comparing different P administration routes are needed, and large-scale prospective trials are warranted to evaluate the ET-day P levels on pregnancy outcome.