Sex Ratio Outcomes in Assisted Reproductive Technologies
Summary
The secondary sex ratio (SSR) of live births following assisted reproductive technologies (ART) has emerged as a significant concern for clinicians, researchers and prospective parents. Typically around 1.05–1.07 males per female in natural conception, this ratio may shift under different ART protocols. Variations have been observed with in vitro fertilisation (IVF) versus intracytoplasmic sperm injection (ICSI), fresh versus frozen embryo transfers, and the timing and morphology of embryo development. Blastocyst transfers often yield a higher proportion of male infants compared with cleavage-stage transfers, while ICSI has been associated with a modest reduction in male births. Patient factors such as parental age, stimulation regimens and underlying infertility aetiology further modulate outcomes. This global body of work enhances understanding of embryonic selection, laboratory handling and clinical decision-making, ultimately informing practice to balance efficacy with ethical considerations and long-term offspring health.
Research from Nature Portfolio
Recent studies have demonstrated that blastocyst quality and development kinetics strongly influence the sex ratio at birth. High-quality trophectoderm grades and advanced expansion degree in frozen-thawed single blastocyst transfers correlate with a higher proportion of male offspring, irrespective of fertilisation method. Transfers performed on day 6 show an even greater male bias than those on day 5, and these trends persist in both IVF and ICSI subgroups. Foundational cohort analyses have similarly shown that blastocyst transfer elevates the secondary sex ratio in singleton births compared with cleavage-stage embryos, while ICSI tends to reduce male prevalence in twin deliveries. These insights underscore the interplay of embryo morphology, culture duration and fertilisation technique in shaping sex-specific survival and implantation dynamics.
Sex Ratio Outcomes in Assisted Reproductive Technologies publication trend
The graph below shows the total number of articles in sex ratio outcomes in assisted reproductive technologies across all publications each year (not limited to Nature Index journals).
Technical terms
Secondary sex ratio (SSR): The ratio of male to female live births.
In vitro fertilisation (IVF): Fertilisation of an oocyte by sperm in a laboratory dish.
Intracytoplasmic sperm injection (ICSI): Injection of a single sperm into the cytoplasm of an oocyte.
Blastocyst: Embryo at day 5–6 post-fertilisation, comprising the trophectoderm and inner cell mass.
Cleavage-stage embryo: Embryo at day 2–3 post-fertilisation with dividing blastomeres.
Trophectoderm (TE): Outer cell layer of a blastocyst that forms the placenta.
Inner cell mass (ICM): Cluster of cells within a blastocyst that develops into the foetus.
References
- Factors affecting male-to-female ratio at birth in frozen-thawed embryo transfer cycles: a large retrospective cohort study. Frontiers in Endocrinology (2023).
- Sex ratio shift after frozen single blastocyst transfer in relation to blastocyst morphology parameters. Scientific Reports (2024).
- Changes in sex ratio from fertilization to birth in assisted-reproductive-treatment cycles. Reproductive Biology and Endocrinology (2014).
- The sex ratio of singleton and twin delivery offspring in assisted reproductive technology in China. Scientific Reports (2017).
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