Sperm Motility Enhancement in Assisted Reproductive Technologies

Sperm motility is a critical determinant of successful fertilisation in vitro, underpinning both conventional in vitro fertilisation and intracytoplasmic sperm injection procedures. Assisted reproductive technologies increasingly address male factor infertility through interventions that restore or augment motile function in normozoospermic and asthenozoospermic samples alike. Approaches range from pharmacological stimulation using phosphodiesterase inhibitors and bioactive lipids to physical selection techniques such as density gradient centrifugation and microfluidic sorting. Advances in high-throughput screening have uncovered novel small molecules that target cyclic nucleotide pathways, ion-channel regulation and metabolic enzymes. Concurrently, structure-guided design of motility enhancers has yielded second-generation analogues with improved efficacy and safety profiles. Together, these strategies not only optimise the selection of viable spermatozoa for injection but also improve post-thaw performance in cryopreserved specimens, with the ultimate aim of elevating fertilisation rates and embryo quality across diverse patient cohorts.

Research from Nature Portfolio

Structure-guided redesign of a widely used phosphodiesterase inhibitor has produced novel analogues that bind more tightly to sperm PDE isoforms, slowing premature acrosome reaction while enhancing progressive motility and DNA integrity. Ex vivo assays demonstrate that a lead analogue, active at substantially lower concentrations than the parent compound, prolongs sperm longevity and yields embryos of superior morphological quality. This work illustrates how in silico modelling and empirical binding studies can inform the rational optimisation of pharmacological agents for assisted conception.

Sperm Motility Enhancement in Assisted Reproductive Technologies publication trend

The graph below shows the total number of articles in sperm motility enhancement in assisted reproductive technologies across all publications each year (not limited to Nature Index journals).

Technical terms

Asthenozoospermia: A condition characterised by reduced sperm motility in the ejaculate, often impairing fertility outcomes.

Intracytoplasmic Sperm Injection (ICSI): A micromanipulation technique whereby a single spermatozoon is injected directly into an oocyte to achieve fertilisation.

Phosphodiesterase (PDE) Inhibitors: Pharmacological agents that prevent the breakdown of cyclic nucleotides, thereby enhancing flagellar activity and progressive motility.

Hyperactivation: A specialised motile state marked by high-amplitude and asymmetrical flagellar beating essential for zona pellucida penetration.

Capacitation: The series of physiological and biochemical modifications that enable spermatozoa to fertilise an oocyte, including membrane fluidity changes and ion fluxes.

References

1. Pregnancy and neonatal outcomes of ICSI using pentoxifylline to identify viable spermatozoa in patients with frozen-thawed testicular spermatozoa. Frontiers in Endocrinology (2024).
2. Structure-based redesigning of pentoxifylline analogs against selective phosphodiesterases to modulate sperm functional competence for assisted reproductive technologies. Scientific Reports (2021).
3. Lysophosphatidic Acid Improves Human Sperm Motility by Enhancing Glycolysis and Activating L-Type Calcium Channels. Frontiers in Endocrinology (2022).
4. Compounds enhancing human sperm motility identified using a high-throughput phenotypic screening platform. Human Reproduction (2022).