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Is paternal age associated with transfer day, developmental stage, morphology, and initial hCG-rise of the competent blastocyst leading to live birth? A multicenter cohort study.

ABSTRACT: In this study we investigated whether age of men undergoing assisted reproductive technology (ART) treatment was associated with day of transfer, stage, morphology, and initial hCG-rise of the competent blastocyst leading to a live birth? The design was a multicenter historical cohort study based on exposure (age) and outcome data (blastocyst stage and morphology and initial hCG-rise) from men whose partner underwent single blastocyst transfer resulting in singleton pregnancy/birth. The ART treatments were carried out at sixteen private and university-based public fertility clinics. We included 7246 men and women, who between 2014 and 2018 underwent controlled ovarian stimulation (COS) or Frozen-thawed Embryo Transfer (FET) with a single blastocyst transfer resulting in singleton pregnancy were identified. 4842 men with a partner giving birth were included, by linking data to the Danish Medical Birth Registry. We showed that the adjusted association between paternal age and transfer day in COS treatments was OR 1.06, 95% CI (1.00;1.13). Meaning that for every increase of one year, men had a 6% increased probability that the competent blastocyst was transferred on day 6 compared to day 5. Further we showed that the mean difference in hCG values when comparing paternal age group 30-34, 35-39 and 40-45 with the age group 25-29 in those receiving COS treatment, all showed significantly lower adjusted values for older men. In conclusion we hypothesize that the later transfer (day 6) in female partners of older men may be due to longer time spent by the oocyte to repair fragmented DNA of the sperm cells, which should be a focus of future research in men.

SUBMITTER: Borgstrom MB

PROVIDER: S-EPMC9333207 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundLuteinizing hormone (LH) and progesterone (PROG) on human chorionic gonadotropin (hCG) trigger day are significantly correlated with assisted reproductive technology (ART) outcome. Moreover, LH and PROG are also involved in the functional preparation of the endometrium during the implantation window; however, whether they are related to endometrial thickness (EMT) is still unknown. The aim of the present study was to assess whether EMT has a positive correlation on the live birth rate following fresh embryo transfer (ET), and whether LH and PROG have an impact on EMT.MethodsA total of 2,260 normogonadotrophic women were treated with a GnRH agonist for in vitro fertilization (IVF)/intracytoplasmic sperm injection. Patients with advanced age and poor ovarian reserve were excluded. The levels of LH, PROG, and EMT on the hCG trigger day were divided into binary variables, respectively, by the cutoff values, and which were obtained based on receiver operating characteristic curve analysis of live birth among LH, PROG and EMT levels on the hCG trigger day, respectively. Multivariate binary logistic regression was used to confirm the role of LH, PROG, and EMT on the live birth, and stratified analysis was used to determine whether LH and PROG have an impact on EMT.ResultsEMT and LH were protective factors for live births, with odds ratios (OR) of 1.11 [95% confidence interval (CI): 1.066-1.157] and 1.696 (95% CI: 1.345-2.139), respectively. However, PROG was a risk factor for live birth, with an OR of 0.635 (95% CI: 0.526-0.766). The hierarchical cross-table analysis indicated that EMT had no significant difference for live birth in the combination of low LH and high PROG group. In the other subgroups, thick EMT was associated with a higher live birth rate (P<0.05).ConclusionsOn hCG trigger day, EMT, LH, and PROG all were independent factors that affected the live birth of fresh ETs. Thick EMT can significantly increase the live birth rate. However, multivariate logistic regression analysis showed that EMT does not affect the live birth rate in combination of low LH and high PROG environment.

Project description:PURPOSE:The objective of our study is to assess the relationship of embryo ploidy status in relation to embryo sex, morphological characteristics, and transfer parameters. METHODS:This is a retrospective cohort study at an academic medical center of patients who underwent in vitro fertilization with preimplantation genetic screening (PGS) from 2010 to 2015. Embryos were screened with 24-chromosome preimplantation genetic screening with day 5/6 trophectoderm biopsy. We investigated embryo euploidy in relation to morphology (expansion, inner cell mass, trophectoderm), embryo sex, biopsy day, and blastocyst cohort size. We used multivariate logistic regression to calculate odds ratios of euploidy in relation to these parameters. RESULTS:A total of 1559 embryos from 316 cycles and 233 patients (mean maternal age = 37.8 ± 4.2 years) were included in the analysis. Six hundred and twenty-eight blastocysts (40.3%) were found to be euploid. Expansion (p < 0.001), inner cell mass (ICM) (p < 0.01), and trophectoderm grade (p < 0.001) were significantly associated with embryo ploidy in bivariate models controlling for maternal age, while embryo sex, biopsy day, and blastocyst cohort size were not associated with embryo ploidy. In a multivariate model, we found that maternal age (p < 0.001), higher grade of expansion (p < 0.01), and better quality trophectoderm (p < 0.001 for A compared to C grade) remained significantly associated with increased embryo euploidy, but ICM grade was no longer significant. Embryo sex was not associated with ploidy status, though male embryos were found to be associated with higher trophectoderm scores (p < 0.02). CONCLUSIONS:This is the largest study to date to investigate PGS-tested embryo sex and ploidy status. While maternal age and some morphological parameters (expansion, trophectoderm grade) are associated with euploidy in our cohort, other parameters such as embryo sex, biopsy day, and cohort size are not. Though embryo sex was not associated with euploidy, male embryos were found to be associated with higher trophectoderm grades. Additional investigation in larger studies is warranted.

Project description:BackgroundIn an in vitro fertilization (IVF) cycle, the embryo ends its wandering time and begins the process of implantation into the uterine cavity on the seventh day after oocyte pick-up (OPU + 7), which is closer than OPU + 5 to the time of nidation. Therefore, measuring the oestradiol (E2)/progesterone (P) ratio on OPU + 7 may be helpful for predicting pregnancy outcomes.MethodsThis is a retrospective cohort study of 2,257 women undergoing a follicular-phase depot gonadotropin-releasing hormone agonist (GnRH-a) protocol for in vitro fertilization /intracytoplasmic sperm injection (IVF/ICSI) treatment and fresh blastocyst embryo transfer cycles at a university-affiliated fertility center between January 2016 and April 2021. First, 2,257 women were split into two groups based on clinical pregnancy for analyzing the levels of E2 and P and the E2/P ratio on the day of OPU + 2, OPU + 5 and OPU + 7. And then 2,257 cycles were stratified into three groups based on E2/P ratio tertiles on OPU + 7: the low group (1.3-15.7 pg/ng), middle group (15.7-28.8 pg/ng), and high group (28.8-487.2 pg/ng). The threshold effect of the E2/P ratio on OPU + 7 on live birth was investigated using a two-piecewise linear regression model and a smoothing function curve.ResultsThe level of P in the clinical pregnancy group were lower than that in the nonclinical pregnancy group on both OPU + 2 and OPU + 7 (201.9 ± 71.6 ng/ml vs 213.1 ± 77.6 ng/ml, 89.5 ± 88.5 ng/ml vs 99.5 ± 94.9 ng/ml, P < 0.05). The E2/P ratio in the clinical pregnancy group were higher than that in the nonclinical pregnancy group on both OPU + 2 and OPU + 7 (8.4 ± 6.5 pg/ng vs 8.0 ± 6.8 pg/ng, 32.3 ± 38.5 pg/ng vs 25.2 ± 31.0 pg/ng, P < 0.01). The E2/P ratio on OPU + 7 was positively associated with positive hCG (adjusted OR = 1.01; 95% CI, 1.01-1.02; P < 0.0001), clinical pregnancy (adjusted OR = 1.01; 95% CI, 1.00-1.01; P = 0.0067) and live birth (adjusted OR = 1.01; 95% CI, 1.00-1.01; P < 0.001), and a nonlinear correlation was observed between the E2/P ratio and LBR on OPU + 7.ConclusionsA higher E2/P ratio is associated with a higher LBR, but the E2/P ratio should be maintained within a suitable range.

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Is paternal age associated with transfer day, developmental stage, morphology, and initial hCG-rise of the competent blastocyst leading to live birth? A multicenter cohort study.

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