Description of the condition
In vitro fertilisation (IVF) is a form of assisted reproductive technology (ART) used for treating infertility, a condition affecting an estimated 15% of the population. IVF usually involves controlled ovarian hyperstimulation, surgical oocyte retrieval, in vitro fertilisation and embryo transfer. Intra-cytoplasmic sperm injection (ICSI) is a form of ART where instead of relying on spontaneous entry of the sperm into the oocyte, a single sperm is injected into the cytoplasm of each oocyte to achieve fertilisation. ICSI is commonly used as a treatment for male factor infertility where semen parameters are poor, when sperm has been surgically retrieved or following repeated failed fertilisation with standard IVF (Palermo 1992).
Successful embryo development and subsequent pregnancy outcome are likely to be impacted by the quality of the sperm which fertilises an oocyte (Sakkas 2000). Ideally only sperm with a high chance of successful fertilisation and subsequent embryo growth would be used for ART. These sperm would be viable, mature, have high DNA integrity and be structurally sound.
Sperm preparation and selection in IVF is limited to semen washing, density gradient centrifugation and the use of the swim-up techniques (Boomsma 2007). In ICSI, routine sperm selection is based on motility and gross morphology (sperm are examined under a microscope at 200 to 400x magnification) after one or more of the above methods of semen preparation. Advanced sperm selection techniques based on alternative characteristics might enable further selection of the most appropriate sperm for use in ART.
Description of the intervention
Advanced sperm selection techniques have developed as a means of improving ART outcomes in certain clinical scenarios. Techniques can be categorised as follows:
1. Surface charge selection
Electrophorectic sperm selection and sperm zeta potential are surface charge selection protocols utilised in both IVF and ICSI. The zeta potential of the sperm is the electric potential between the sperm membrane and its surroundings. The zeta potential decreases with capacitation and normally differentiated sperm are charged electronegatively. Semen is placed into an electrophoretic device and a current applied. Normally differentiated negatively charged sperm are rapidly separated and collected from an adjacent chamber (Ainsworth 2005).
2. Sperm apoptosis
Selection of non-apoptotic sperm for use in ART is based on the presence of phosphatidylserine on the external surface of the sperm membrane in the early stages of apoptosis. Magnetic activated cell sorting (MACS) and glass wool separation columns utilise the magnetic properties of phosphatidylserine to separate apoptotic sperm from non-apoptotic sperm (Grunewald 2001).
3. Hyaluronic acid binding
Hyaluronic acid binding sites on the sperm plasma membrane indicate sperm maturity. Sperm are placed in a PICSITM dish, which is an IVF petri dish that carries a hyaluronic acid spot. Mature sperm preferentially bind to the hyaluronan impregnated sites (Huszar 2007).
4. Sperm birefringence
The mature sperm nucleus has high intrinsic birefringence due to longitudinally orientated subacrosomal protein filaments. Using polarised light microscopy sperm birefringence can be evaluated and a mature sperm selected (Gianaroli 2008).
5. Sperm morphology
Subtle defects in sperm morphology (acrosome, nucleus, mitochondria, tail, postacrosomal lamina and neck) can be observed using ultra-high magnification (6000x) microscopy (motile sperm organelle morphology examination, 'MSOME') (Bartoov 2002). Intracytoplasmic morphologically selected sperm injection (IMSI) is a modification of ICSI utilising this technique (Bartoov 2003).
How the intervention might work
Through the use of advanced sperm selection techniques a structurally intact and mature sperm with high DNA integrity may be selected for fertilisation. Each modality utilises differing characteristics of sperm structure, physiology or function to allow selection of the most normal sperm. Advanced sperm selection protocols aim to improve ART outcomes and may limit the possible deleterious effects on offspring of using sperm with defective DNA (Aitken 2007).
Why it is important to do this review
Advanced sperm selection techniques are hypothesised to improve ART outcome through the selection of sperm with a variety of 'beneficial characteristics'. Despite individual small studies suggesting that these techniques have clinical benefit, there remains no comprehensive review of randomised controlled trials (RCTs) in this area. A systematic review on advanced selection methods was published in 2011, however this incorporated non-randomised data (Said 2011). The current review aims to include only RCTs so that the results can better guide clinical practice and further research efforts.