What is sperm preparation, and how do gradient, swim-up and washing differ? An overview of selection techniques such as IMSI, PICSI and MACS.
Sperm preparation is the laboratory step in which, before insemination or IVF, motile and normal-looking sperm are separated from the seminal fluid in the semen sample and made ready for use. Additional sperm selection techniques, on the other hand, aim to select sperm from the prepared sample by different criteria; in a current assessment prepared for Europe, the routine use of none of them is recommended, and only for the microfluidic method does the expression "may be considered" appear. In insemination studies too, no superiority has been shown between the standard preparation methods. Your doctor and the laboratory decide together what is suitable in your own situation.
Why is the sperm prepared before insemination?
In insemination (IUI), the aim is for the sample to be placed in the uterus to contain sperm that are free of seminal fluid, motile and normal-looking. Preparation is the step that processes the sample for this purpose.
In IVF, are preparation and selection the same stage?
In IVF, the sperm to be brought together with the eggs, or to be selected one by one in ICSI, are also taken from the prepared sample. That is, preparation is a stage that comes before selection and is separate from the selection itself.
Is sperm taken surgically also prepared?
Sperm obtained from the testis or epididymis is also processed in the laboratory; surgical retrieval methods are a separate subject.
What are the standard sperm preparation methods?
All three methods share the same aim: to separate motile and normal-looking sperm from the seminal fluid. Density gradient centrifugation, swim-up and washing are the standard approaches used for this purpose. Which one is used depends on the characteristics of the sample and the laboratory's practice.
Is one of the preparation methods more effective?
The answer to this question today is "uncertain". A review that compared the three methods in terms of clinical pregnancy in couples having insemination could not determine which was more effective. The reliability of this evidence is very low, and none of the studies reported live birth. The authors state that studies measuring live birth are needed.
How is sperm selected in ICSI?
In ICSI a single sperm is selected for each egg. Additional techniques aim to change the criterion by which this selection is made; the selection itself is within ICSI.
How are additional sperm selection techniques distinguished?
- IMSI: Examining the sperm under very high magnification and selecting it according to its shape. The current assessment on this subject does not recommend its routine use; the regulator in the United Kingdom classifies this practice in the uncertain (grey) category.
- PICSI: Selection according to the property of binding to hyaluronic acid. The same assessment does not recommend it; the regulator classifies it in the lowest category in terms of live birth.
- MACS: A method aimed at separating sperm thought to be damaged. The current assessment on this subject does not recommend it for routine use.
- Microfluidic selection: Sperm are separated on a chip with very fine channels. The same assessment uses the expression "may be considered" for this method; this expression does not mean "recommended" and rests on weak evidence.
The details and the evidence table of each technique require separate assessment. Category systems cannot be translated into one another; for example, the regulator's categories and the "not recommended" expression of the other assessment are not parts of the same scale.
Why is the benefit of additional selection techniques uncertain?
The update of a review reports, for selection with hyaluronic acid, no difference in live birth or a possible very small increase, and with low reliability a possible decrease in miscarriage. For MACS, selection based on zeta potential and other comparisons, the effect is not known, and the reliability of this evidence remains very low. The authors say that there is no evidence that would give a routine recommendation for any technique. In addition, a technique improving laboratory measurements in the sample such as motility, shape or DNA integrity does not mean that it provides a benefit in live birth. A meta-analysis done on the microfluidic method also could not find a significant difference in clinical pregnancy.
Does a DNA damage result make a particular selection technique mandatory?
Additional selection techniques are often raised because of concern about sperm DNA damage. The current assessment on this subject does not recommend routine use of the sperm DNA damage test, and the value of the test in predicting the treatment outcome is uncertain. In the regulator's assessment concerning sperm DNA damage in the United Kingdom too, selecting sperm by gradient or MACS and then applying ICSI or PICSI is classified in the uncertain (grey) category in infertility due to a male factor. That is, a DNA damage finding does not show that a particular selection technique is necessary.
Does the preparation result determine the treatment outcome?
No, not on its own. The quality of the sample obtained after preparation is important information; however, the outcome of treatment also depends on many other factors. For this reason you should not interpret the preparation result as a binding verdict about the future. The stress you feel while giving the sample is understandable too; you can share your concerns on this with your doctor.
What can you ask your doctor and the laboratory?
- Which preparation method is planned for my sample?
- If an additional selection technique is recommended, what is the reasoning?
- What changes in my plan if this additional technique is not done?
- Is there a separate charge for the additional technique?
- How does the sample-giving arrangement work, and whom should I tell if I have a special need?
Frequently Asked Questions
Does the sperm preparation procedure carry a risk for the man?
According to the current assessment on this subject, sperm separation methods carry no risk to the man because they are applied to the sperm in the ejaculate. The safety of additional selection techniques for the embryo and the baby is a separate question: the same assessment states that there are no safety data for MACS and microfluidic selection, and says that no safety problem has been shown for selection with hyaluronic acid.
Is it worth paying a separate fee for an additional selection technique?
Couples who bear the cost of treatment themselves can also consider several standard cycles instead of a single cycle with an unproven add-on. Whether the additional technique is charged for varies with the centre, and you can ask before the procedure.
Is there an international guideline on sperm preparation?
An international laboratory manual has been published for the examination and processing of semen; its current edition is dated 2021. This is of the nature of a guideline and should not be described as a binding standard. Which preparation method will be used for which sample is decided by the laboratory and your doctor together.
Are sperm preparation and sperm selection the same procedure?
No. Preparation is the separation of the sample from the seminal fluid and making it ready for use. Selection concerns determining which sperm will be used from the prepared sample.
Is the sperm prepared before insemination?
Yes. The aim is for the sample to be placed in the uterus to contain sperm that are free of seminal fluid, motile and normal-looking.
Is sperm taken from the testis or epididymis also processed in the laboratory?
Yes. Sperm obtained surgically is also processed. The surgical retrieval method is a stage separate from laboratory preparation.
Has one of gradient, swim-up and washing been shown to be more effective?
Which is more effective could not be determined in couples having insemination. The reliability of the evidence is very low; no live birth was reported in the studies.
Does an additional sperm selection technique need to be added to every ICSI cycle?
No. There is no evidence that would support the routine use of any of the additional techniques. The expression "may be considered" used for the microfluidic method does not mean recommended either.
Do IMSI and PICSI select sperm by the same criterion?
No. IMSI looks at shape under high magnification; PICSI uses binding to hyaluronic acid. Their evidence is assessed separately.
Does improvement in motility or DNA integrity mean a benefit in live birth?
No. An improvement in laboratory measurements does not mean that a benefit has been provided in live birth. The evidence on clinical outcomes must be assessed separately.
Does a DNA damage result make a particular selection technique necessary?
No. The value of the DNA damage test in predicting the treatment outcome is uncertain. The finding does not show that a particular selection technique is necessary.
Does the preparation result determine the outcome of treatment on its own?
No. Although the quality of the prepared sample is important, treatment depends on many other factors. You should not interpret the result as a binding verdict about the future.
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