Dataset Information

Associations of sperm mitochondrial DNA copy number and deletion rate with fertilization and embryo development in a clinical setting.

ABSTRACT:

Study question

Are sperm mitochondrial DNA copy number (mtDNAcn) and deletion rate (mtDNAdel) associated with odds of fertilization and high embryo quality at Days 3 and 5?

Summary answer

Higher sperm mtDNAcn and mtDNAdel were associated with lower odds of high quality Day 3 embryos and transfer quality Day 5 embryos, both of which were primarily driven by lowered odds of fertilization.

What is known already

Sperm mtDNAcn and mtDNAdel have been previously associated with poor semen parameters and clinical male infertility. One prior study has shown that mtDNAdel is associated with lower fertilization rates. However, it is unknown whether these characteristics are linked with ART outcomes.

Study design, size, duration

This prospective observational study included 119 sperm samples collected from men undergoing ART in Western Massachusetts. ART outcomes were observed through to Day 5 post-insemination.

Participants/materials, settings, methods

As part of the Sperm Environmental Epigenetics and Development Study (SEEDS), 119 sperm samples were collected from men undergoing ART in Western Massachusetts. Sperm mtDNAcn and mtDNAdel were measured via triplex probe-based qPCR. Fertilization, Day 3 embryo quality and Day 5 embryo quality measures were fitted with mtDNAcn and mtDNAdel using generalized estimating equations.

Main results and the role of chance

After adjusting for male age and measurement batches, higher sperm mtDNAcn and mtDNAdel were associated with lower odds of fertilization (P = 0.01 and P < 0.01), high quality Day 3 embryos (P = 0.02 for both) and transfer quality Day 5 embryos (P = 0.01 and P = 0.09). However, the associations of mtDNAcn and mtDNAdel with Day 3 high quality status and Day 5 transfer quality status were attenuated in models restricted to fertilized oocytes. Sperm mtDNAcn and mtDNAdel remained statistically significant in models adjusted for both male age and semen parameters, although models including both mtDNA markers generally favoured mtDNAdel.

Limitations, reasons for caution

Our sample only included oocytes and embryos from 119 couples and thus large diverse cohorts are necessary to confirm the association of sperm mtDNA biomarkers with embryo development.

Wider implications of the findings

To our knowledge, our study is the first to assess the associations of sperm mtDNAcn and mtDNAdel with fertilization and embryo quality. The biological mechanism(s) underlying these associations are unknown. Multivariable models suggest that sperm mtDNAcn and mtDNAdel provide discrimination independent of age and semen parameters; therefore, future investigation of the utility of sperm mtDNA as a biomarker for ART outcomes is warranted.

Study funding/competing interest(s)

This work was supported by Grant (K22-ES023085) from the National Institute of Environmental Health Sciences. The authors declare no competing interests.

Trial registration number

N/A.

SUBMITTER: Wu H

PROVIDER: S-EPMC6295960 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionSpermatozoa motility is the critical parameter to affect the treatment outcomes during assisted reproductive technologies (ART), but its reproductive capability remains a little informed in condition of severe male factor infertility. This retrospective cohort study aimed to evaluate the effects of reduced sperm motility on the embryological and clinical outcomes in intra-cytoplasmic sperm injection (ICSI) treatment of severe oligozoospermia.Patients and methods966 cycles (812 couples) of severe oligozoospermia diagnosed by spermatozoa count ? 5 × 106/mL and motile spermatozoa ? 2 × 106/mL were divided into four groups in according to the number of motile spermatozoa in one ejaculate on the day of oocyte retrieval (Group B-E). The control (Group A) was 188 cycles of moderate oligozoospermia with spermatozoa count > 5 × 106/mL and motile spermatozoa > 2 × 106/mL. All female partners were younger than 35 years of age. Logistic regression analyzed embryological outcomes (the rates of fertilization, cleavage and good-quality embryo) and clinical outcomes (the rates of pregnancy, implantation, early miscarriage and live birth). Quality of embryo transfer (ET) was divided into three classes as continuous factor to test the effects of embryo quality on clinical outcomes.ResultsThe reduction in the number of motile sperm in four groups of severe oligozoospermia gave rise to comparable inability of the fertilization (p < 0.001) and a decreased rate of good-quality embryo at Day 3 (p < 0.001) by compared to the control. The cleavage rate of the derived zygotes was similar to the control. ET classes significantly affected the clinical outcomes (p < 0.001). Class I ET gave rise to similar rates of clinical outcomes between five groups, but Class II and Class III ET retarded the rates of pregnancy, implantation and live birth and this particularly occurred in Group C, D and E. The rate of early miscarriage was not comparably different between groups. Overall rates in all groups were 41.26% clinical pregnancy, 25.74% implantation and 36.32% live birth, which gave live birth to 252 girls and 252 boys.ConclusionsThe reduction of motile spermatozoa in severe oligozoospermia decreased the rates of fertilization and good-quality embryo. Obtaining and transfer of good-quality embryos was the good prognostic to achieve prospective clinical outcomes regardless of the severity of oligozoospermia.