The Incidence of Mosaicism for Individual Chromosome in Human Blastocysts Is Correlated With Chromosome Length.

Mosaicism, known as partial aneuploidies, mostly originates from mitotic errors during the post-zygotic stage; it consists of different cell lineages within a human embryo. The incidence of mosaicism has not been shown to correlate with maternal age, and its correlation with individual chromosome characteristics has not been well investigated. In this study, the results of preimplantation genetic testing for aneuploidy (PGT-A) derived from 4,036 blastocysts (930 IVF couples) were collected from 2015 to 2017. Via next-generation sequencing for comprehensive chromosome screening, embryo ploidy was identified as aneuploid, mosaic, and euploid. Total mosaicism was classified into two categories: "mosaic euploid/aneuploidy" (with mosaic aneuploidy between 20 and 80%) and "mosaic and aneuploidy" (a uniformly abnormal embryo superimposed with mosaic aneuploidies). Frequency of mosaicism was analyzed according to the function of chromosomal lengths, which divides involved chromosomes into three groups: group A (156-249 Mb), group B (102-145 Mb), and group C (51-90 Mb). The results show that the aneuploidy was more frequent in group C than in group A and group B (A: 23.7%, B: 35.1, 41.2%, p < 0.0001), while the mosaicism was more frequent in group A and group B than in group C [(Mosaic euploid/aneuploid) A: 14.6%, B: 12.4%, C: 9.9%, p < 0.0001; (mosaic and aneuploid) A: 21.3%, B: 22.9%, C: 18.9%, p < 0.0001; (Total mosaicism) A: 35.9%, B: 35.3%, C: 28.8%, p < 0.0001]. The significantly higher frequency of aneuploidy was on the shorter chromosome (< 90 Mb), and that of mosaicism was on the longer chromosomes (> 100 Mb). The length association did not reach significance in the patients with advanced age (≥ 36 years), and of the chromosome-specific mosaicism rate, the highest prevalence was on chromosome 14 (5.8%), 1 (5.7%), and 9 (5.6%). Although the length association was observed via group comparison, there may be affecting mechanisms other than chromosomes length. Eventually, twenty patients with mosaic embryo cryotransfers resulted in six live births. No significant correlation was observed between the transfer outcomes and chromosome length; however, the analysis was limited by small sample size.

A Patient Friendly Corifollitropin Alfa Protocol without Routine Pituitary Suppression in Normal Responders.

The release of corifollitropin alfa simplifies daily injections of short-acting recombinant follicular stimulating hormone (rFSH), and its widely-used protocol involves short-acting gonadotropins supplements and a fixed GnRH antagonist regimen, largely based on follicle size. In this study, the feasibility of corifollitropin alfa without routine pituitary suppression was evaluated. A total of 288 patients were stimulated by corifollitropin alfa on cycle day 3 following with routine serum hormone monitoring and follicle scanning every other day after 5 days of initial stimulation, and a GnRH antagonist (0.25 mg) was only used prophylactically when the luteinizing hormone (LH) was ≧ 6 IU/L (over half of the definitive LH surge). The incidence of premature LH surge (≧ 10 IU/L) was 2.4% (7/288) before the timely injection of a single GnRH antagonist, and the elevated LH level was dropped down from 11.9 IU/L to 2.2 IU/L after the suppression. Two hundred fifty-one patients did not need any antagonist (87.2% [251/288]) throughout the whole stimulation. No adverse effects were observed regarding oocyte competency (fertilization rate: 78%; blastocyst formation rate: 64%). The live birth rate per OPU cycle after the first cryotransfer was 56.3% (161/286), and the cumulative live birth rate per OPU cycle after cyrotransfers was 69.6% (199/286). Of patients who did and did not receive GnRH antagonist during stimulation, no significant difference existed in the cumulative live birth rates (78.4% vs. 68.3%, p = 0.25). The results demonstrated that the routine GnRH antagonist administration is not required in the corifollitropin-alfa cycles using a flexible and hormone-depended antagonist regimen, while the clinical outcome is not compromised. This finding reveals that the use of a GnRH antagonist only occasionally may be needed.

Effect of continuous administration of conjugated estrogen plus medroxyprogesterone acetate (Premelle) in postmenopausal women in Taiwan.

BACKGROUND: To compare the metabolic effects on lipids and acceptability and safety of, and compliance with, a continuous administration of conjugated estrogen plus medroxyprogesterone acetate (Premelle) versus a placebo in non-hysterectomized postmenopausal women. METHODS: Sixty-six generally healthy, female, early post-menopausal women, from 45-60 years of age, were randomized for an administration of conjugated estrogen plus medroxyprogesterone acetate (Premelle, Premarin 0.625 mg plus medroxyprogesterone acetate 2.5 mg/tablet orally) or a placebo for 6 months. The changes in each patient's lipid profiles from baseline, the frequency of hot flushes, bleeding occurrences, and climacteric symptoms, were evaluated. Safety was monitored by means of physical examination, Papanicolau smear, transvaginal ultrasonography, and laboratory check-up. Adverse events were also recorded. RESULTS: The difference before and after treatment in serum LDL-C and total cholesterol (TC) was statistically significant in the Premelle group (LDL-C, p = 0.006, TC, p = 0.040). No statistically significant difference in the change from baseline was observed in the levels of LDL-C and TC in the placebo treatment group. There was a statistically significant change from baseline in menopausal symptoms, which were evaluated by the Greene Climacteric Scales in the Premelle group. There was no clinically significant finding in the physical examination, vital signs, laboratory data, or endometrial thickness in either treatment group. The difference in the number of patients who reported an adverse event was not statistically significant between the 2 treatment groups. CONCLUSIONS: This study demonstrated that Premelle was effective in decreasing LDL-C and total cholesterol levels, and also showed an improvement in some menopausal symptoms, such as vasomotor and sexual dysfunction symptoms. No significant bleeding was observed with Premelle, which was well tolerated in this study. The results of this study could support the use of Premelle tablets as a convenient alternative hormone therapy.