Summary 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.

Despite next-generation sequencing, which now allows for the accurate detection of segmental aneuploidies from in vitro fertilization embryo biopsies, the origin and characteristics of these aneuploidies are still relatively unknown. Using a multifocal biopsy approach (four trophectoderms [TEs] and one inner cell mass [ICM] analyzed per blastocyst; n ¼ 390), we determine the origin of the aneuploidy and the diagnostic predictive value of segmental aneuploidy detection in TE biopsies toward the ICM's chromosomal constitution. Contrary to the prevalent meiotic origin of whole-chromosome aneuploidies, we show that sub-chromosomal abnormalities in human blastocysts arise from mitotic errors in around 70% of cases. As a consequence, the positive-predictive value toward ICM configuration was significantly lower for segmental as compared to whole-chromosome aneuploidies (70.8% versus 97.18%, respectively). In order to enhance the clinical utility of reporting segmental findings in clinical TE biopsies, we have developed and clinically verified a risk stratification model based on a second TE biopsy confirmation and segmental length; this model can significantly improve the prediction of aneuploidy risk in the ICM in over 86% of clinical cases enrolled. In conclusion, we provide evidence of the predominant mitotic origin of segmental aneuploidies in preimplantation embryos and develop a risk stratification model that can help post-test genetic counseling and that facilitates the decision-making process on clinical utilization of these embryos.

BackgroundEndometrial preparation with hormone replacement therapy (HRT) is the preferred regimen for clinicians due to the opportunity to schedule the day of embryo transfer and for patients due to the requirement of fewer visits for frozen-warmed embryo transfers (FET). The increasing number of FETs raises the question of the serum P levels required to optimize the pregnancy outcome on the embryo transfer day.MethodsThis prospective cohort study includes patients who underwent single euploid FET. All patients received HRT with oestradiol valerate (EV) and 100 mg of intramuscular (IM) progesterone (P). FET was scheduled 117–120 h after the first IM administration of 100 mg P. The serum P level was analyzed 1 h before the embryo transfer (ET). In all cycles, only embryos that were biopsied on day 5 were utilized for FET. Next generation sequencing (NGS) was used for comprehensive chromosomal analysis.ResultsOverall, the ongoing pregnancy rate (OPR) was 58.9% (99/168). Data were then categorized according to the presence (Group I; n = 99) or the absence (Group II; n = 69) of an ongoing pregnancy. No significant differences regarding, female age, body mass index (BMI), number of previous miscarriages, number of previous live birth, sperm concentration, number of oocytes retrieved, number of mature oocytes (MII), rate of fertilized oocytes with two pronuclei (2PN), trophectoderm score, inner cell mass (ICM) score, endometrial thickness (mm), oestrodiol (E2) and P levels prior to IM P administration were found between two groups. The P levels on the day of ET (ng/ml) were significantly higher in Group I (28 (5.6–76.4) vs 16.4 (7.4–60) p = 0.039). The P level on the day of ET was a predictor of a higher OPR (p < 0.001 OR: 1.033 95%CI [1.009–1.056]) after multivariate analysis. The ROC curve showed a significant predictive value of serum P levels on the day of ET for OPR, with an AUC (95%CI) = 0.716 (0.637–0.795). The optimal cut-off value for prediction of the OPR was a P level of 20.6 ng/ml (71.7% sensitivity, 56.5% specificity).ConclusionsThe present study suggests a minimum threshold of the serum P value on the day of ET that needs to be reached in HRT cycles to optimize the clinical outcome. Individualization of the P dosage should be evaluated in further studies.

Background To assess the predictive value of patient characteristics, controlled ovarian stimulation and embryological parameters on the live birth outcome of single euploid frozen-warmed blastocyst transfer (FBT). Methods This was a retrospective cohort study including 707 single FBTs after preimplantation genetic testing for aneuploidy (PGT-A) that were performed from October 1, 2015, to January 1, 2018. The effects of patient-, cycle-and embryology-related parameters on the live birth outcome after FBT were assessed.

Repeat LEEP conization can reveal undiagnosed microinvasive cervical carcinoma in women with positive ectocervical margins.

The aim of this study was to evaluate the possible effects of endometriosis on early embryo development, by comparing the morphokinetic development of embryos obtained from women with clinically confirmed endometriosis with the ones obtained from tubal factor infertility cases. A total of 82 cycles/patients including 53 cycles with endometriosis and 29 cycles with tubal factor infertility were evaluated. A total of 439 embryos were scored for embryo morphokinetics. Age, body mass index, fertilization rates were similar within the groups. However, the number of previous ART trials was found to be higher (p < 0.05) in the study group. Also, the number of retrieved oocytes and M2 oocytes were found to be significantly lower in patients with endometriosis (p < 0.01). The duration of the first cell cycle (ECC1) and S2 (the time between t3 and t4) displayed significant distortions compared with embryos in the control group. All other analyzed early morphokinetic parameters (t2, t3, t4, t5, t6, t7, t8) and duration of events (VP, cc2a, ECC2, ECC3, S3) showed similar values between study and control groups, respectively. In the light of these findings, it is apparent that endometriosis predominantly affects the duration of the early morphokinetic events and cell cycles.

CPA: concentrated cryoprotective agent; COH: controlled ovarian stimulation; FET: frozen embryo transfer; HSG: hysterosalpingogram; mHTF: modified human tubal medium; SSM: single step media; SSS: synthetic serum substitute; TV-USG: transvaginal ultrasound.

Background Is freeze-all strategy effective in terms of cumulative live birth rates (CLBRs) in all patients? Methods This retrospective single-center study analyzed the CLBRs of 2523 patients undergoing fresh or electively frozen blastocyst transfer cycles. In 1047, cycles, the fresh embryo transfer (ET) strategy was applied for the 1 st ET, whereas electively frozen ET (e-FET) was performed in 1476 cycles. Female age � 37 and blastocysts frozen via vitrification were included. The patients in each arm were further stratified into four subgroups according to the number of oocytes retrieved as follows: Group A: 1-5, group B: 6-10, group C: 11-15 and group D: 16-25 oocytes retrieved. The primary endpoint was the CLBR. The secondary endpoints were the ovarian hyperstimulation syndrome (OHSS) rate and the live birth rates (LBRs) following fresh ETs and e-FETs for the first transfers. Result(s) The CLBR was similar between the fresh ET and e-FET arms in group A (35/76 (46.1%) vs 29/67 (43.3%), p = 0.74) and group B (165/275 (60%) vs 216/324 (66.7%), p = 0.091), whereas significantly higher rates were detected in favor of the e-FET arm within group C (328/460 (71.3%) vs 201/348 (57.8%), p<0.001) and group D (227/348 (65.2%), vs 446/625 (71.5%), p<0.001). The OHSS rate was also found to be higher in the fresh ET arm among group C (12/348 (3.4%) vs 0/460 (0%), p<0.001) and group D (38/348 (10.9%) vs 3/625 (0.5%), p<0.001) patients than e-FET arm. Perinatal and obstetrical outcomes were nonsignificantly different between fresh and e-FET arms. However, the birth weights were significantly lower for fresh ET, 3064 versus 3201 g for singletons (p<0.001)