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Mitochondrial DNA Content May Not Be a Reliable Screening Biomarker for Live Birth After Single Euploid Blastocyst Transfer.

ABSTRACT: An increasing number of studies have related the mitochondrial DNA (mtDNA) content to embryo viability and transfer outcomes. However, previous studies have focused more on the relationship between mtDNA and embryo implantation, few studies have studied the effect of the mtDNA content on live birth. In the study, we investigated whether mtDNA content is a reliable screening biomarker for live birth after single blastocyst transfer. A total of 233 couples with 316 blastocyst stage embryos undergoing in vitro fertilization treatment and pre-implantation genetic testing analysis were included in the study. All embryos were chromosomally normal and had undergone single-embryo transfers. There was no significant difference observed in the blastocyst mtDNA content among the live birth, miscarriage and non-implanted groups (p=0.999), and the mtDNA content in blastocysts from the miscarriage and live birth groups was similar [median (interquartile range), 1.00*10⁸(7.59*10⁷- 1.39*10⁸) vs 1.01*10⁸ (7.37*10⁷- 1.32*10⁸)]. Similarly, no significant association was observed between mtDNA content and embryo implantation potential (p=0.965). After adjusting for multiple confounders in a logistic regression analysis with generalized estimating equations, no associations between mtDNA content and live birth were observed in all blastocysts, Day-5 and Day-6 blastocysts (p=0.567, p=0.673, p=0.165, respectively). The live birth rate was not significantly different between blastocysts with an elevated mtDNA content and blastocysts with a normal mtDNA content (26.7% vs 33.6% p=0.780). Additionally, there was no linear correlation between the mtDNA content and maternal age (p=0.570). In conclusion, the mtDNA content does not seem to be a potential biomarker for embryo transfer outcomes (i.e., implantation and live birth) based on the existing testing tools. Embryos with an elevated mtDNA content also have development potential for successful live birth.

SUBMITTER: Zhou X

PROVIDER: S-EPMC8637898 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundA number of studies have compared the clinical outcomes between the two endometrial preparation methods: natural cycles (NCs) and hormone replacement treatment (HRT) before frozen embryo transfer, but the results were conflicting. In order to mitigate the potential effect of embryos per se, several researchers have worked on this subject for euploid blastocyst transfer, but the results were still inconsistent. Therefore, the present study was aimed to investigate the clinical outcomes between HRT and NC for autologous single vitrified-warmed euploid blastocyst transfer based on our data.MethodsA total of 598 frozen-thawed single euploid blastocyst transfer cycles in the assisted reproductive center of Northwest Women's and Children's Hospital from January 2014 to May 2021 were retrospectively analyzed. Women were stratified into the NC (n = 125) or HRT (n = 473) group according to the patient's preference and the physician's guidance. Multivariate regression models and subgroup analysis were constructed to analyze the association between endometrial preparation and live birth.ResultsWomen in the NC group had a higher live birth rate (68.80% versus 58.35%, P = 0.034) and a lower risk of total pregnancy loss (8.51% versus 21.14%, P = 0.005) when compared with women in the HRT group. The biochemical pregnancy rate (75.20% versus 74.00%, P = 0.784) and clinical pregnancy rate (74.40% versus 69.98%, P = 0.334) were similar between the two groups (NC versus HRT). NC was associated with an increased odds of live birth compared with HRT by different multivariable analysis models (Model 1: adjusted odds ratio [aOR], 95% confidence interval [CI]: 0.57, 0.36 - 0.90; Model 2: aOR, 95%CI: 0.57, 0.35 - 0.92). In addition, the increased chance of live birth in the NC group was found in all subgroups. No major obstetrical complications and two malformation livebirths were reported.ConclusionsIn women undergoing single euploid frozen blastocyst transfers, the NC group was associated with a lower pregnancy loss rate and an ultimately higher live birth rate than the HRT group. Although HRT is convenient for both clinicians and patients, the lower live birth rate should be taken into account and NC might be the first choice of endometrial preparation method.

Project description:Study questionHas cumulative live birth rate (CLBR) improved over time and which factors are associated with such an improvement?Summary answerDuring an 11-year period, 2007-2017, CLBR per oocyte aspiration increased significantly, from 27.0% to 36.3%, in parallel with an increase in blastocyst transfer and cryopreservation by vitrification.What is known alreadyWhile it has been shown that live birth rate (LBR) per embryo transfer (ET) is higher for fresh blastocyst than for fresh cleavage stage embryo transfer, CLBR per oocyte aspiration, including one fresh ET and all subsequent frozen embryo transfers (FET), does not seem to differ between the two culture strategies.Study design size durationA national register study including all oocyte aspirations performed in Sweden from 2007 to 2017 (n = 124 700 complete IVF treatment cycles) was carried out. Oocyte donation cycles were excluded.Participants/materials setting methodsData were retrieved from the Swedish National Registry of Assisted Reproduction (Q-IVF) on all oocyte aspirations during the study period where autologous oocytes were used. CLBR was defined as the proportion of deliveries with at least one live birth per oocyte aspiration, including all fresh and/or frozen embryo transfers within 1 year, until one delivery with a live birth or until all embryos were used, whichever occurred first. The delivery of a singleton, twin, or other multiples was registered as one delivery. Cryopreservation of cleavage stage embryos was performed by slow freezing and of blastocyst by vitrification.Main results and the role of chanceIn total, 124 700 oocyte aspirations were performed (in 61 313 women), with 65 304 aspirations in women <35 years and 59 396 in women ≥ 35 years, resulting in 38 403 deliveries with live born children. Overall, the CLBR per oocyte aspiration increased significantly during the study period, from 27.0% to 36.3% (odds ratio (OR) 1.039, 95% CI 1.035-1.043) and from 30.0% to 43.3% if at least one ET was performed (adjusted OR 1.055, 95% CI 1.050-1.059). The increase in CLBR was independent of maternal age, number of oocytes retrieved and number of previous IVF live births. The CLBR for women <35 and ≥35 years both increased significantly, following the same pattern. During the study period, a substantially increasing number of blastocyst transfers was performed, both in fresh and in FET cycles. Other important predicting factors for live birth, such as number of embryos transferred, could not explain the improvement. An increased single embryo transfer rate was observed with time.Limitations reasons for cautionThe retrospective design implicates that other confounders of importance for CLBR cannot be ruled out. In addition, some FET cycles might be performed later than 1 year post oocyte aspiration for the last year (2017) and are, thus, not included in this study. In addition, no data on 'dropouts', i.e. patients that do not continue their treatment despite having cryopreserved embryos, are available, or if this drop-out rate has changed over time.Wider implications of the findingsThe results suggest that blastocyst transfer, particularly when used in FET cycles and in combination with vitrification, is an important contributor to the improved live birth rates over time. This gives a possibility for a lower number of oocyte aspirations needed to achieve a live birth and a shortened time to live birth.Study funding/competing interestsThe study was financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-70940) and by Hjalmar Svensson's research foundation. None of the authors declares any conflict of interest.

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Mitochondrial DNA Content May Not Be a Reliable Screening Biomarker for Live Birth After Single Euploid Blastocyst Transfer.

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