Key messages
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Advanced sperm selection techniques can be used in patients trying to get pregnant using assisted reproduction procedures (vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI)). The aim of using the advanced techniques is to increase the chances of selecting the best sperm, leading to successful fertilisation, but the current evidence is unclear.
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Selecting sperm that attach to a natural substance in the body called hyaluronic acid (HA-ICSI (hyaluronic acid selected sperm-intracytoplasmic sperm injection)) probably reduces the risk of miscarriage slightly compared to the standard method of sperm selection. HA-ICSI may make no difference to or may slightly increase the likelihood of delivering a living baby.
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Evidence for other techniques is very limited. More studies are needed to find out whether advanced sperm selection techniques make IVF more effective than the standard method currently used.
What is assisted reproductive technology?
Assisted reproductive technology is used to bring about pregnancy by artificial means. In vitro fertilisation (IVF), collection of a woman's egg or eggs from the ovaries then fertilisation with sperm in a laboratory, is a commonly used treatment for people diagnosed with infertility who want to get pregnant. Intracytoplasmic sperm injection (ICSI) is sometimes used as well. In ICSI, a single sperm is directly injected into the egg. Currently, IVF laboratories use standard methods to select healthy-looking sperm for fertilisation. It is thought that selecting sperm of high quality may improve the chances of pregnancy and the birth of a healthy baby.
What are advanced sperm selection techniques?
Advanced sperm selection techniques are complex methods used to select sperm for fertilisation that are healthy, mature, and structurally sound (the right shape and size). These techniques can be used to improve sperm selection in infertility that results from male factors (such as low sperm count or sluggish sperm). Despite the use of these techniques in many assisted reproduction centres worldwide, their effectiveness is unclear.
What did we want to find out?
We wanted to find out which, if any, of the advanced sperm selection techniques that are used for assisted reproduction increase the chances of:
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live birth (giving birth to a living baby);
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miscarriage (losing the baby before 20 weeks of development in the womb);
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clinical pregnancy (having a positive pregnancy test confirmed by ultrasound);
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foetal abnormalities (something wrong with the baby).
This review is the second update of a review originally published in 2014 and first updated in 2019.
What did we do?
We searched medical databases online for randomised studies that compared advanced sperm selection techniques in IVF to standard methods or to other advanced sperm selection techniques. In randomised studies, participants are randomly allocated to two or more groups to ensure that their treatment is similar other than the aspect that is being compared (sperm selection in this case). We then combined results from all relevant studies and rated our confidence in the evidence based on the quality of the studies (e.g. the way they were designed and the number of people they involved).
What did we find?
We found five studies that involved a total of 3752 women. Two studies evaluated sperm selection by the sperm's ability to bind a substance called hyaluronic acid during the process of ICSI (HA-ICSI) versus ICSI on its own. One study compared HA-ICSI to a technique called SpermSlow (a special solution that helps to select healthier sperm). One study evaluated selecting sperm that have a slight electrical charge on their surface ('zeta potential') versus ICSI. One study evaluated sperm selected by a sorting system called Microfluidic Sperm Sorting versus ICSI.
Four of the studies reported live birth; four reported miscarriage; five reported clinical pregnancy; and none reported whether there were foetal abnormalities.
Main results
The studies in our review showed that, in comparison to ICSI, HA-ICSI:
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may result in no difference or a slight increase in live births (1 study, 2772 people);
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probably slightly decreases miscarriage (2 studies, 3327 people); and
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may make no difference to the chance of getting pregnant (2 studies, 3327 women).
We are uncertain whether the other sperm selection techniques affect live birth, miscarriage, or pregnancy rates.
No studies reported on foetal abnormalities.
Further studies of suitable quality are required before any of these advanced sperm selection techniques can be recommended for use in clinical practice.
What are the limitations of the evidence?
The main limitations were due to the small numbers of people taking part in the studies. It is possible that people in the studies were aware of the treatment being given, which may have had an effect on how the results were reported. Not all studies covered important things to consider when people undergo assisted reproduction. For example, there was no information about foetal abnormalities. More high-quality studies with a large number of participants are needed to know whether advanced sperm selection techniques are worthwhile for patients undergoing IVF.
How up to date is this evidence?
This review updates our previous review. The evidence is current to February 2025.
Читать полную аннотацию (абстракт)
Assisted reproductive technologies (ART) including in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), combine gametes to enhance the probability of fertilisation and pregnancy. Advanced sperm selection techniques are increasingly employed in ART, most commonly in cycles utilising ICSI. Advanced sperm selection techniques are proposed to improve the chance that structurally intact and mature sperm with high DNA integrity are selected for fertilisation. Strategies include selection according to surface charge; sperm apoptosis; sperm birefringence; ability to bind to hyaluronic acid; and sperm morphology under ultra-high magnification. These techniques are intended to improve ART outcomes.
Задачи
To evaluate the benefits and harms of advanced sperm selection techniques on assisted reproductive technologies (ART) outcomes.
Методы поиска
We conducted a systematic search of electronic databases (CENTRAL via the Cochrane Register of Studies Online, MEDLINE, and Embase) for relevant randomised controlled trials (RCTs). We handsearched the reference lists of included studies and similar reviews. The search was conducted on 24 February 2025.
Критерии отбора
We included RCTs comparing advanced sperm selection techniques versus standard IVF, ICSI, or another technique. We excluded studies of intracytoplasmic morphologically selected sperm injection (IMSI), as they are subject to a separate Cochrane Review. Primary outcomes measured were live birth and miscarriage per woman randomly assigned. Secondary outcome measures included clinical pregnancy per woman randomly assigned. Secondary adverse events measured included miscarriage per clinical pregnancy and foetal abnormality.
Сбор и анализ данных
Two review authors independently assessed study eligibility and risk of bias and extracted data. Any disagreements were resolved by consultation with a third review author. We consulted study investigators to resolve queries. Risk ratios (RRs) were calculated with 95% confidence intervals (CIs). We combined studies using a fixed-effect model. We evaluated the quality of the evidence using GRADE methods.
Основные результаты
We included eight RCTs (4147 women). The quality of evidence ranged from very low to low. The main limitations were imprecision, performance bias, and attrition bias.
Hyaluronic acid selected sperm-intracytoplasmic sperm injection (HA-ICSI) compared to ICSI
Two RCTs compared the effects of HA-ICSI versus ICSI on live birth. The quality of the evidence was low. There may be little or no difference between groups: 25% chance of live birth with ICSI versus 24.5% to 31% with HA-ICSI (RR 1.09, 95% CI 0.97 to 1.23, 2903 women, I2 = 0%, low-quality evidence). Three RCTs reported on miscarriage. HA-ICSI may decrease miscarriage per woman randomly assigned: 7% chance of miscarriage with ICSI versus 3% to 6% chance with HA-ICSI (RR 0.61, 95% CI 0.45 to 0.83, 3005 women, I2 = 0%, low-quality evidence) and per clinical pregnancy: 20% chance of miscarriage with ICSI compared to 9% to 16% chance with HA-ICSI (RR 0.62, 95% CI 0.46 to 0.82, 1065 women, I2 = 0%, low-quality evidence). Four RCTs reported on clinical pregnancy. There may be little or no difference between groups: 37% chance of pregnancy with ICSI versus 34% to 40% chance with HA-ICSI (RR 1.00, 95% CI 0.92 to 1.09, 3492 women, I2 = 0%, low-quality evidence).
HA-ICSI compared to SpermSlow
One RCT compared HA-ICSI to SpermSlow. The quality of the evidence was very low. We are uncertain whether HA-ICSI improves live birth compared to SpermSlow (RR 1.13, 95% CI 0.64 to 2.01, 100 women) or clinical pregnancy (RR 1.05, 95% CI 0.66 to 1.68, 100 women). We are uncertain whether HA-ICSI reduces miscarriage per woman (RR 0.80, 95% CI 0.23 to 2.81, 100 women) or per clinical pregnancy (RR 0.76, 95% CI 0.24 to 2.44, 41 women).
Magnetic-activated cell sorting (MACS) compared to ICSI
One RCT compared MACS to ICSI for live birth; three reported clinical pregnancy; and two reported miscarriage. The quality of the evidence was very low. We are uncertain whether MACS improves live birth (RR 1.95, 95% CI 0.89 to 4.29, 62 women) or clinical pregnancy (RR 1.05, 95% CI 0.84 to 1.31, 413 women, I2 = 81%). We are also uncertain if MACS reduces miscarriage per woman (RR 0.95, 95% CI 0.16 to 5.63, 150 women, I2 = 0%) or per clinical pregnancy (RR 0.51, 95%CI 0.09 to 2.82, 53 women, I2=0)
Zeta sperm selection compared to ICSI
One RCT evaluated Zeta sperm selection. The quality of the evidence was very low. We are uncertain of the effect of Zeta sperm selection on live birth (RR 2.48, 95% CI 1.34 to 4.56, 203 women) or clinical pregnancy (RR 1.82, 95% CI 1.20 to 2.75, 203 women). We are also uncertain if Zeta sperm selection reduces miscarriage per woman (RR 0.73, 95% CI 0.16 to 3.37, 203 women) or per clinical pregnancy (RR 0.41, 95% CI 0.10 to 1.68, 1 RCT, 62 women).
MACS compared to HA-ICSI
One RCT compared MACS to HA-ICSI. This study did not report on live birth. The quality of the evidence was very low. We are uncertain of the effect on miscarriage per woman (RR 1.52, 95% CI 0.10 to 23.35, 78 women) or per clinical pregnancy (RR 1.06, 95% CI 0.07 to 15.64, 37 women). We are also uncertain of the effect on clinical pregnancy (RR 1.44, 95% CI 0.91 to 2.27, 78 women).
Выводы авторов
The evidence suggests that use of HA-ICSI may make no difference to or may slightly increase live-birth rate and probably slightly reduces miscarriage rate. We do not know the effect of the other advanced sperm selection techniques on live birth or miscarriage, or clinical pregnancy, principally because of the very low certainty of the evidence.
Further high-quality studies, including awaited data from 19 ongoing studies, are required to evaluate whether any of these advanced sperm selection techniques can be recommended for use in routine practice.
Финансирование
This Cochrane review had no dedicated funding.
Регистрация
Original review (2014) DOI: 10.1002/14651858.CD010461.pub2
