Background Currently, there is no universal criteria for the trigger time of controlled ovarian hyperstimulation (COH), especially with the emerging depot GnRH agonist protocol. It is challenging to explore an indicator that is representative of target follicle cohort development as an alternative to the conventional approach of determining the trigger time based on a few leading follicles. Methods This was a large-sample retrospective analysis. Between January 2016 and January 2020, 1,925 young normal ovarian responders who underwent their first in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycle using the depot GnRH agonist protocol were included. They were divided into three groups based on the dominant follicular proportion (DFP, defined as the ratio of ≥ 18 mm dominant follicles/ ≥ 14 mm large follicles on the human chorionic gonadotropin (HCG) day; Group A: < 30%; Group B: 30%−60%; and Group C: ≥ 60%). The binary logistic regression and multivariate linear regression were used to assess whether the DFP was associated with clinical pregnancy, the number of frozen blastocysts, the blastocyst formation rate, and the low number of frozen blastocysts. Results The logistic regression analysis showed that compared with Group A, the odds ratio (OR) for clinical pregnancy was 1.345 in Group B (P = 0.023), and there was no statistical difference between Group C and Group A (P = 0.216). The multivariate linear regression analysis showed that DFP was negatively associated with the number of frozen blastocysts (β ± SE: Group B vs. Group A = − 0.319 ± 0.115, P = 0.006; Group C vs. Group A = − 0.432 ± 0.154, P = 0.005) as well as the blastocyst formation rate (β ± SE: Group B vs. Group A = − 0.035 ± 0.016, P = 0.031; Group C vs. Group A = − 0.039 ± 0.021, P = 0.067). Furthermore, the OR for the low number of frozen blastocysts was 1.312 in Group B (P = 0.039) and 1.417 in Group C (P = 0.041) compared to Group A. Conclusions For young normal ovarian responders using the depot GnRH agonist protocol, increasing DFP might reduce the developmental potential of oocytes and reduce the number of available blastocysts, and this might result in a lower cumulative pregnancy rate. However, further confirmation using strict prospective randomised controlled studies is required.
Purpose To explore the relationship between mitochondrial DNA quantity and heteroplasmy and early embryonic loss. Methods A total of 150 villous samples from patients with spontaneous abortion (SA, n = 75) or induced abortion (IA, n = 75) were collected. qPCR and next-generation sequencing (NGS) were used to test mitochondrial DNA quantity and heteroplasmy. Missense mutations with a CADD score > 15 and heteroplasmy ≥ 70% were defined as potentially pathogenic mutations. Results With respect to mitochondrial DNA copy numbers, there was no significant difference between the SA and IA groups (median (IQR), 566 (397–791) vs. 614 (457–739); P = 0.768) or between the euploid and aneuploid groups (median (IQR), 516 (345–730) vs. 599 (423–839); P = 0.107). mtDNA copy numbers were not associated with spontaneous abortion using logistic regression analysis (P = 0.196, 95% CI 1.000–1.001). In addition, more patients harbored possibly pathogenic mtDNA mutations in their chorionic villi in the SA group (70.7%, 53/75) compared with the IA group (54.7%, 41/75; P < 0.05). However, there was no statistical difference between the euploid (80%, 24/30) and aneuploid groups (64.4%, 29/45; p = 0.147). Conclusion Early embryonic loss and the formation of aneuploidy were not related to mtDNA copy number. Patients with spontaneous abortion were more likely to have possibly pathogenic mutations in their mtDNA, and this may assist in purifying pathogenic mtDNA. However, whether the accumulation of these potentially morbific mtDNA mutations caused early embryonic loss requires further investigation.
Purpose To explore the effect of different concentrations of peak serum estradiol levels on endometrial receptivity quantitatively. Methods In our reproductive medicine center, two best quality of day 3 (D3) embryos were transferred or frozen according to E 2 and progesterone levels on the day of human chorionic gonadotropin (hCG) administration and the number of oocytes retrieved. The remaining embryos were cultured to blastocyst stage and frozen. The patients were then categorized into three groups. The patients with frozen-thawed D3 embryo transfer in artificial cycles without blastocyst frozen served as group 1, those with fresh D3 embryo transfer without blastocyst frozen as group 2, and those with fresh D3 embryo transfer with blastocyst frozen as group 3. Each group was further stratified into 4 sub-groups according to E 2 levels on the day of hCG administration. Clinical pregnancy rate, implantation rate and abortion rate of frozen-thawed and fresh D3 embryo transfer were compared among the three groups in the same stratified E 2 levels. Results For E 2 <7,000 pg/mL, group 1 and group 2 had similar clinical pregnancy rate and implantation rate. But for E 2 ≥7,000 pg/mL, the clinical pregnancy rate in group 1 was significantly higher than in group 2 (p<0.05). For E 2 <7,000 pg/mL, pregnancy rate and implantation rate in group 1 were significantly lower than those in group 3 (P<0.05). But for E 2 ≥7,000 pg/mL, the pregnancy rate in group 1 was significantly higher than in group 3 (P<0.05). There was no significant difference in the abortion rate between group 1 and group 2, or between group 1 and group 3. Conclusions High serum E 2 concentration does not impair implantation and pregnancy rates unless exceeding a certain limit (e.g. 7,000 pg/mL) on the day of hCG administration. Since peak E 2 level was related to OHSS and adverse pregnancy outcomes, further study is needed to set a threshold peak E 2 level for fresh embryo transfer.
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