Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryos.

BACKGROUND: To preclude transfer of aneuploid embryos, current preimplantation genetic screening (PGS) usually involves one trophectoderm biopsy at blastocyst stage, assumed to represent embryo ploidy. Whether one such biopsy can correctly assess embryo ploidy has recently, however, been questioned. METHODS: This descriptive study investigated accuracy of PGS in two ways. Part I: Two infertile couples donated 11 embryos, previously diagnosed as aneuploid and, therefore, destined to be discarded. They were dissected into 37 anonymized specimens, and sent to another national laboratory for repeat analyses to assess (i) inter-laboratory congruity and (ii) intra-embryo congruity of multiple embryo biopsies in a single laboratory. Part II: Reports on human IVF cycle outcomes after transfer of allegedly aneuploid embryos into 8 infertile patients. RESULTS: Only 2/11 (18.2 %) embryos were identically assessed at two PGS laboratories; 4/11 (36.4 %), on repeat analysis were chromosomally normal, 2 mosaic normal/abnormal, and 5/11 (45.5 %) completely differed in reported aneuploidies. In intra-embryo analyses, 5/10 (50 %) differed between biopsy sites. Eight transfers of previously reported aneuploid embryos resulted in 5 chromosomally normal pregnancies, 4 delivered and 1 ongoing. Three patients did not conceive, though 1 among them experienced a chemical pregnancy. CONCLUSIONS: Though populations of both study parts are too small to draw statistically adequately powered conclusions on specific degrees of inaccuracy of PGS, here presented results do raise concerns especially about false-positive diagnoses. While inter-laboratory variations may at least partially be explained by different diagnostic platforms utilized, they cannot explain observed intra-embryo variations, suggesting more frequent trophectoderm mosiaicsm than previously reported. Together with recentl published mouse studies of lineages-specific degrees of survival of aneuploid cells in early stage embryos, these results call into question the biological basis of PGS, based on the assumption that a single trophectoderm biopsy can reliably determine embryo ploidy.

Atraumatic segmental atypical femur fracture secondary to bisphosphonate use: A case report.

Atypical femur fractures as a result of long term bisphosphonate use are characterized by several unique radiographic features. We describe an atypical femur fracture treated by cephalomedullary nail with a previously undescribed segmental fracture pattern. Other than 1.5 years of bisphosphonate use the patient did not have any other risk factors known to cause atypical femur fractures. Judicious bisphosphonate use as well as increased awareness of the associated complications may help reduce the rate of bisphosphonate associated atypical femur fractures.

Intramedullary Nail Fixation of Atypical Femur Fractures With Bone Marrow Aspirate Concentrate Leads to Faster Union: A Case-Control Study.

OBJECTIVES: To evaluate bone marrow aspirate concentrate (BMAC) use in the treatment of AFF. DESIGN: Retrospective case control. SETTING: Level 1 trauma center. PATIENTS: Complete AFF, defined according to American Society of Bone and Mineral Research (ASBMR) criteria, from September 2009 to April 2015 with minimum 1-year follow-up. INTERVENTION: Operative treatment with antegrade intramedullary nails. Beginning June 2014, BMAC from the ipsilateral iliac crest was added to all AFFs. MAIN OUTCOME MEASUREMENTS: Time to union as determined by a blinded panel of 3 attending orthopaedic surgeons, union rates, complications. RESULTS: Thirty-five patients with 36 AFFs were reviewed, of which 33 AFFs were included and 11 received BMAC. Alendronate was the most commonly prescribed bisphosphonate, with a similar mean duration of use in controls and BMAC cases (5.6 versus 6 years, P = 0.79). BMAC use significantly decreased time to union (3.5 versus 6.8 months, P = 0.004). Varus malreduction was associated with a significant delay in union (9.7 versus 4.7 months, P = 0.04). Overall, 1 year union rate was 86.2% and nonsignificantly higher in BMAC compared with controls (100.0% versus 77.3%, P = 0.11). Multivariate analysis revealed BMAC and varus malreduction as independent predictors of time to union. There were no complications related to BMAC use. CONCLUSION: Our findings support intramedullary nailing of AFFs as an effective treatment option with a low surgical complication rate and highlight the importance of avoiding varus malreduction. BMAC use significantly reduced time to fracture union without an increase in surgical complication rates. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Surgical versus nonsurgical treatment of the SE4-equivalent ankle fracture: a retrospective functional outcome study.

Treatment of Lauge-Hansen supination-eversion (SE)4-equivalent ankle fractures is controversial. This retrospective study conducted at a level-I trauma center compared the clinical outcome of nonsurgical vs open management of these fractures. One thousand eight ankle fractures treated between 1998 and 2003 were reviewed. Forty-three patients who met the criteria for a SE4-equivalent ankle fracture were identified. Average patient age of 23 men and 20 women was 42 years (range, 18-84 years). Olerud Molander ankle scores were recorded. Medical records and radiographs of all patients were reviewed. Average follow-up was 20 months.Twenty-six patients were treated nonsurgically, with an average ankle score of 84 ± 4. Seventeen patients treated surgically had an average ankle score of 63 ± 5. The difference is statistically significant (unpaired t test, P=.0035). There was no difference between open vs closed treatment in maintaining a reduction. To investigate the reason for poor results in the surgical group, we sought an association between functional ankle score and common covariables and found that age and preoperative radiographic grading were important variables for ankle score. Patients younger than 30 years had an average ankle score of 85, whereas those older than 50 years had an average score of 61 (P<.001). Type 1 fractures (medial clear space >5 mm in stress view only) had an average ankle score of 89, type 2 (medial clear space >5 mm but <10 mm) an average score of 76, and type 3 (medial clear space >10 mm or presented with fracture dislocation and/or syndesmosis injury) an average score of 61. Our data support that type 1 and 2 fractures can effectively be treated nonsurgically.