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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: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:To investigate hCG-? level on postovulatory day (POD) 12 and its fold increase as predictors for pregnancy outcome after in vitro fertilization (IVF) cycles.A retrospective cohort study was performed in total 1408 fresh and 598 frozen cycles between November 2008 and October 2011, which resulted in biochemical pregnancy, early pregnancy loss, or live birth of singleton pregnancy. The serum hCG-? levels of POD 12 and 14 were compared among biochemical pregnancy, early pregnancy loss, and live birth groups. The cutoff values of POD 12 and 14 hCG-? levels and the degree of hCG-? increase from POD 12 to 14 were determined for each pregnancy outcome.POD 12 and 14 hCG-? levels stratified based on pregnancy outcomes were significantly different among the biochemical pregnancy, early pregnancy loss, and live birth in both fresh and frozen cycles. Serum hCG-? levels of POD 12 and 14 and the fold increase of hCG-? levels from POD 12 to 14 significantly predict pregnancy outcomes after fresh and frozen cycles. Among these, the cutoff value of POD 14 hCG-? had the highest sensitivity and positive predictive value (PPV). In fresh cycles, the cutoff values of POD 12 and 14 serum hCG-? levels for clinical pregnancies were 30.2 mIU/mL (sensitivity 81.3 %, specificity 79.6 %, and PPV 92.3 %) and 70.5 mIU/mL (sensitivity 88.4 %, specificity 85.2 %, and PPV 94.7 %). In pregnancies with POD 12 serum hCG-? levels ?30.2 mIU/mL, the cutoff level of increase of hCG-? for clinical pregnancy was 2.56 (sensitivity 73.6 %, specificity 72.4 %, and PPV 97.8 %). Sequential application of cutoff values such as POD 12 hCG-? and fold increase of hCG-? improved predictability of pregnancy outcome as compared with that of POD 12 hCG-? alone. The cutoff values of POD 12 and 14 serum hCG-? levels for live birth were 40.5 mIU/mL (sensitivity 75.2 %, specificity 72.6 %, PPV 78.9 %) and 104.5 mIU/mL (sensitivity 80.3 %, specificity 74.1 %, PPV 80.8 %). In the frozen cycles, the cutoff values of POD 12 and 14 serum hCG-? level for clinical pregnancy were 31.5 IU/L (sensitivity 80.4 %, specificity 71.1 % and PPV 90 %) and 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %). In pregnancies with POD 12 serum hCG-? level ?31.5 mIU/mL, the cutoff value for fold increase of hCG-? was 2.38 for clinical pregnancy (sensitivity 81.6 %, specificity 71.4 % and PPV 87.9 %). The cutoff values of POD 12 and 14 for live birth were 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %) and 101.6 mIU/mL (sensitivity 79.6 %, specificity 71.1 %, PPV 78.4 %). Sequential application of cutoff values for POD 12 hCG-? level and fold increase of hCG-? significantly increased PPV for live birth but not clinical pregnancy in frozen cycles.Early prediction of pregnancy outcome by using POD 12 and 14 cutoff levels and sequential application of cutoff value of fold increase could provide appropriate reference to health care providers to initiate earlier management of high-risk pregnancies and precise follow-up of abnormal pregnancies.

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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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