Developmental order, fibre caliber, and vascularization predict tract-wise declines: Testing retrogenesis and physiological predictions in white matter aging.

To understand the consistently observed spatial distribution of white-matter (WM) aging, developmentally driven theories of retrogenesis have gained traction, positing that the order WM development predicts declines. Regions that develop first are often expected to deteriorate the last, i.e. "last-in-first-out". Alternatively, regions which develop most rapidly may also decline most rapidly in aging, or the "gains-predict-loss" model. The validity of such theories remains uncertain, in part due to lack of clarity on the definition of developmental order. Our recent findings also suggest that WM degeneration may vary by physiological parameters such as perfusion. Furthermore, it is informative to link perfusion to fibre metabolic need, which varies with fibre size. Here we address the question of whether WM degeneration is determined by development trajectory or physiological state across both microstructural and perfusion measures using data drawn from the Human Connectome Project in Aging (HCP-A). Our results indicate that developmental order of tract myelination provides the strongest support for the retrogenesis hypothesis, with the last to complete myelination the first to decline. Moreover, higher mean axon diameter and lower macrovascular density are associated with lower degrees of WM degeneration across measures. Tract perfusion, in turn also tends to be higher and the arterial transit time longer for tracts that appear first. These findings suggest that WM degeneration in different tracts may be governed by their developmental trajectories and physiology, and ultimately influenced by each tract's metabolic demand.

Preimplantation genetic testing for aneuploidy in patients with low embryo numbers: benefit or harm?

PURPOSE: We sought to explore the utility of preimplantation genetic testing for aneuploidy (PGT-A) in a poor prognosis group of women with few embryos available for transfer. METHODS: This was a retrospective matched cohort study examining records for first or second-cycle IVF patients with 1 to 3 blastocysts. The study group comprised 130 patients who underwent PGT-A on all embryos. The control group included 130 patients matched by age, BMI, and blastocyst number and quality who did not undergo PGT-A during the same time period. RESULTS: The live birth rate (LBR) per embryo transfer (ET) were similar in the PGT-A and control groups, and the spontaneous abortion (SAB) rate was the same (23%). However, we found a significantly higher LBR per oocyte retrieval in the control group vs the PGT-A group (43% vs 20%, respectively) likely due to the many no-euploid cycles in the PGT-A group. In a subgroup analysis for age, the similar LBR per ET persisted in women < 38. However, in older women, there was a trend to a higher LBR per ET in the PGT-A group (43%) vs the control group (22%) but a higher LBR per oocyte retrieval in the control group (31%) vs the PGT-A group (13%). CONCLUSIONS: Overall, we observed a significant increase in LBR per oocyte retrieval in women in the control group compared to women undergoing PGT-A, and no difference in SAB rate. Our data suggests that PGT-A has no benefit in a subpopulation of women with few embryos and may cause harm.

Effect of long-term combined oral contraceptive pill use on endometrial thickness.

OBJECTIVE: To estimate whether there is any association of long-term use of combined oral contraceptive pills (OCP) with adverse endometrial growth. METHODS: We reviewed the charts of 137 patients with history of OCP use undergoing endometrial preparation with estrogen for frozen embryo transfer. Endometrial thickness was measured by transvaginal ultrasonography on day 10 after menses and patients were divided into two groups (less than 7 mm and 7 mm or more). RESULTS: Thirty patients had endometrial thickness less than 7 mm and 107 had thickness of 7 mm or more. Mean years of combined OCP use in each group were 9.8±4.54 and 5.8±4.52, respectively (P<.001). With 10 years of combined OCP use as the threshold, the difference between the two groups (63.35% users in less than 7 mm group compared with 28.04% in the 7 mm or more thickness group) was highly significant (P<.001 by Fisher exact test), with an odds ratio of 4.43 (95% confidence interval 1.89-10.41). Past use of 5 years of OCPs was also associated with a significant (P=.002) difference in endometrial thickness. The mean endometrial thicknesses on cycle day 10 in patients using combined OCP for less than 10 years and 10 years or more were 9.54±1.88 mm and 8.48±2.33 mm, respectively, with P=.007. The mean endometrial thickness was 9.72±1.69 mm in less than 5 years and 8.81±2.23 mm in 5 or more years of use, respectively (P=.008). Cycle cancellation rates in the less than 7 mm group and 7 mm or greater endometrial thickness group were 23% and 4%, respectively (P=.002), but there was no difference in the clinical pregnancy rates between the two groups (13% compared with 27%, respectively; P=.15). CONCLUSION: Long-term combined OCP use (5 years or more) can potentially affect optimal endometrial growth, leading to a higher cancellation rate and longer stimulation in frozen embryo transfer cycles. These findings suggest a previously unidentified adverse effect of long-term combined OCP use in women who are anticipating future fertility. LEVEL OF EVIDENCE: II.

Comparison of clinical outcomes with low-voltage (cut) versus high-voltage (coag) waveforms during hysteroscopic endometrial ablation with the rollerball: a pilot study.

STUDY OBJECTIVE: To compare efficacy of rollerball endometrial ablation with low-voltage (cut) versus high-voltage (coag) waveforms. DESIGN: Pilot comparative clinical study (Canadian Task Force Classification II-1). SETTING: University-affiliated teaching hospital. PATIENTS: Fifty premenopausal women with menorrhagia. INTERVENTION: Women with menorrhagia were allocated randomly to thermal destruction of the endometrium by a 5-mm rollerball with unmodulated cutting current or modulated coagulating current. Complication rate, clinical outcomes, and need for reintervention were evaluated. MEASUREMENTS AND MAIN RESULTS: At 2 years of follow-up, the reintervention rate was 26.3% in the cutting waveform group versus 31.4% in the coagulating waveform group. This difference was not statistically significant. Hysterectomy was performed in 3 (14%) women in the cutting waveform group and 5 (20%) women in the coagulating waveform group. There were no complications in either group. CONCLUSION: Both cutting and coagulating waveforms are equally effective for hysteroscopic endometrial ablation with the rollerball.