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Cell-free mitochondrial DNA in human follicular fluid: a promising bio-marker of blastocyst developmental potential in women undergoing assisted reproductive technology.

ABSTRACT: BACKGROUND:Cell-free mitochondrial DNA (cf-mtDNA) in body fluids has attracted much attention for the purpose of monitoring disease because of the clinical advantages. This study investigated whether the cf-mtDNA content in human follicular fluid samples was associated with oocyte and embryo developmental competence. METHODS:We collected 225 individual follicular fluid samples from 92 patients undergoing conventional in vitro fertilization (n?=?53) or intracytoplasmic sperm injection (n?=?39). cf-mtDNA and cell-free nuclear DNA (cf-nDNA) were measured using real-time quantitative PCR for the ND1 and ?-globin genes. Multivariate logistic regression and linear regression were used to analyze data. RESULTS:The relative cf-mtDNA content (cf-ND1/cf-?-globin ratio) in follicular fluid was significantly lower in the group showing blastocyst development than in the non-blastocyst group (P?=?0.030). Additionally, the relative cf-mtDNA content was significantly and positively correlated with the age of the female patient (P?=?0.009), while the relative cf-mtDNA content for older women (?38?years old) with anti-Müllerian hormone (AMH) ?1.1?ng/ml was significantly higher than in those with AMH >?1.1?ng/ml (P?<0.05). The cf-nDNA content was significantly positively correlated with the antral follicle count (P?=?0.012), and significantly negatively correlated with both the number of days of stimulation and the total dose of gonadotropin administration (P?=?0.039 and P?=?0.015, respectively). Neither cf-mtDNA nor cf-nDNA levels in follicular fluid were associated with oocyte maturation, fertilization, or Day 3 embryo morphological scoring. CONCLUSIONS:The relative cf-mtDNA content in human follicular fluid was negatively correlated with blastulation and positively correlated with the patient age, indicating that it is a promising bio-marker to evaluate oocyte developmental competence.

SUBMITTER: Liu Y

PROVIDER: S-EPMC6621940 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Cell-free mitochondrial DNA in human follicular fluid: a promising bio-marker of blastocyst developmental potential in women undergoing assisted reproductive technology.

Liu Yu Y Shen Qiuzi Q Zhao Xue X Zou Min M Shao Shumin S Li Jiao J Ren Xinling X Zhang Ling L

Reproductive biology and endocrinology : RB&E 20190710 1

<h4>Background</h4>Cell-free mitochondrial DNA (cf-mtDNA) in body fluids has attracted much attention for the purpose of monitoring disease because of the clinical advantages. This study investigated whether the cf-mtDNA content in human follicular fluid samples was associated with oocyte and embryo developmental competence.<h4>Methods</h4>We collected 225 individual follicular fluid samples from 92 patients undergoing conventional in vitro fertilization (n = 53) or intracytoplasmic sperm inject ...[more]

PMID: 31291946

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Project description:BackgroundApproximately 1 in 7 couples experience subfertility, many of whom have lifestyles that negatively affect fertility, such as poor nutrition, low physical activity, obesity, smoking, or alcohol consumption. Reducing lifestyle risk factors prior to pregnancy or assisted reproductive technology treatment contributes to the improvement of reproductive health, but cost-implications are unknown.ObjectiveThe goal of this study was to evaluate reproductive, maternal pregnancy, and birth outcomes, as well as the costs of pre-conception lifestyle intervention programs in subfertile couples and obese women undergoing assisted reproductive technology.MethodsUsing a hypothetical model based on quantitative parameters from published literature and expert opinion, we evaluated the following lifestyle intervention programs: (1) Smarter Pregnancy, an online tool; (2) LIFEstyle, which provides outpatient support for obese women; (3) concurrent use of both Smarter Pregnancy and LIFEstyle for obese women; (4) smoking cessation in men; and (5) a mindfulness mental health support program using group therapy sessions. The model population was based on data from the Netherlands.ResultsAll model-based analyses of the lifestyle interventions showed a reduction in the number of in vitro fertilization, intracytoplasmic sperm injection, or intrauterine insemination treatments required to achieve pregnancy and successful birth for couples in the Netherlands. Smarter Pregnancy was modeled to have the largest increase in spontaneous pregnancy rate (13.0%) and the largest absolute reduction in potential assisted reproductive technology treatments. Among obese subfertile women, LIFEstyle was modeled to show a reduction in the occurrence of gestational diabetes, maternal hypertensive pregnancy complications, and preterm births by 4.4%, 3.8%, and 3.0%, respectively, per couple. Modeled cost savings per couple per year were €41 (US $48.66), €360 (US $427.23), €513 (US $608.80), €586 (US $695.43), and €1163 (US $1380.18) for smoking cessation, mindfulness, Smarter Pregnancy, combined Smarter Pregnancy AND LIFEstyle, and LIFEstyle interventions, respectively.ConclusionsAlthough we modeled the potential impact on reproductive outcomes and costs of fertility treatment rather than collecting real-world data, our model suggests that of the lifestyle interventions for encouraging healthier behaviors, all are likely to be cost effective and appear to have positive effects on reproductive, maternal pregnancy, and birth outcomes. Further real-world data are required to determine the cost-effectiveness of pre-conception lifestyle interventions, including mobile apps and web-based tools that help improve lifestyle, and their effects on reproductive health. We believe that further implementation of the lifestyle app Smarter Pregnancy designed for subfertile couples seeking assistance to become pregnant is likely to be cost-effective and would allow reproductive health outcomes to be collected.

Project description:BackgroundA Delphi consensus was conducted to evaluate global expert opinions on key aspects of assisted reproductive technology (ART) treatment.MethodsTen experts plus the Scientific Coordinator discussed and amended statements plus supporting references proposed by the Scientific Coordinator. The statements were distributed via an online survey to 35 experts, who voted on their level of agreement or disagreement with each statement. Consensus was reached if the proportion of participants agreeing or disagreeing with a statement was >66%.ResultsEighteen statements were developed. All statements reached consensus and the most relevant are summarised here. (1) Follicular development and stimulation with gonadotropins (n = 9 statements): Recombinant human follicle stimulating hormone (r-hFSH) alone is sufficient for follicular development in normogonadotropic patients aged <35 years. Oocyte number and live birth rate are strongly correlated; there is a positive linear correlation with cumulative live birth rate. Different r-hFSH preparations have identical polypeptide chains but different glycosylation patterns, affecting the biospecific activity of r-hFSH. r-hFSH plus recombinant human LH (r-hFSH:r-hLH) demonstrates improved pregnancy rates and cost efficacy versus human menopausal gonadotropin (hMG) in patients with severe FSH and LH deficiency. (2) Pituitary suppression (n = 2 statements): Gonadotropin releasing hormone (GnRH) antagonists are associated with lower rates of any grade ovarian hyperstimulation syndrome (OHSS) and cycle cancellation versus GnRH agonists. (3) Final oocyte maturation triggering (n=4 statements): Human chorionic gonadotropin (hCG) represents the gold standard in fresh cycles. The efficacy of hCG triggering for frozen transfers in modified natural cycles is controversial compared with LH peak monitoring. Current evidence supports significantly higher pregnancy rates with hCG + GnRH agonist versus hCG alone, but further evidence is needed. GnRH agonist trigger, in GnRH antagonist protocol, is recommended for final oocyte maturation in women at risk of OHSS. (4) Luteal-phase support (n = 3 statements): Vaginal progesterone therapy represents the gold standard for luteal-phase support.ConclusionsThis Delphi consensus provides a real-world clinical perspective on the specific approaches during the key steps of ART treatment from a diverse group of international experts. Additional guidance from clinicians on ART strategies could complement guidelines and policies, and may help to further improve treatment outcomes.

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Cell-free mitochondrial DNA in human follicular fluid: a promising bio-marker of blastocyst developmental potential in women undergoing assisted reproductive technology.

Publications

Cell-free mitochondrial DNA in human follicular fluid: a promising bio-marker of blastocyst developmental potential in women undergoing assisted reproductive technology.

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