Physiological intracytoplasmic sperm injection (PICSI) did not significantly increase the number of full-term live births compared with standard treatment using intracytoplasmic sperm injection (ICSI), according to results of the HABSelect randomised trial.
HABSelect - hyaluronic acid binding sperm selection - is the largest randomised trial of PICSI to date and the first to provide a robust measure of live births. It also reported clinical pregnancy miscarriage and premature birth rates.
David Miller, reader in andrology from Leeds University led the work and explained that, "the evidence to date suggests that hyaluronan-based sperm selection decreases miscarriage rates after ICSI, but not sufficiently to affect live birth rates".
The researchers also found that the hyaluronan-sperm binding score did not predict or influence treatment outcomes.
The study is published in the most recent edition of The Lancet.
PICSI versus ICSI
With the intracytoplasmic sperm injection (ICSI) fertilisation procedure, sperm selection criteria are visual, based on movement and appearance of sperm, with the sperm considered most suitable for fertilisation being chosen and injected into the egg. But with PICSI, a sperm’s ability to bind to hyaluronan (otherwise known as hyaluronic acid) is used to further enhance this sperm selection. Hyaluronan is found in the extracellular matrix surrounding ovulating eggs. The PICSI method mimics the natural binding of mature sperm to the hyaluronan by placing hyaluronan gel in a petri dish, and adding sperm to it. Those sperm that are mature, and best-adapted for fertilisation, attach to the gel and are selected this way. These sperm are preferred for fertilisation because they are thought to have reduced levels of DNA damage and aneuploidy.
ICSI (and PICSI) are normally used when a man’s sperm count is very low, or if sperm motility is restricted in some way, or sperm are otherwise abnormal. ICSI has led to the birth of 1·14 million babies per year globally, and is associated with live birth rates of around 24% per treatment cycle, but this success rate has been static for around a decade, prompting a need for improved selection procedures, and potentially improved live birth rates.
Earlier studies suggested that PICSI was associated with improved embryo quality and live birth rates as well as decreased miscarriage rates compared with ICSI. These studies were ultimately aimed at increasing live birth rates by focussing on male fertility rather than the more abundant research into female-based fertility.
In the HABSelect study, the researchers aimed to test the hypothesis that PICSI improves full-term (≥37 weeks' gestational age) live birth rates compared with ICSI. "We were interested in testing whether sperm binding to hyaluronan makes a difference to live birth outcomes, and incidentally to miscarriage outcomes," explained David Miller.
Couples were enrolled into the parallel, two-group, randomised trial at 16 assisted conception units across the UK. Participants were all recommended for ICSI by their respective clinics.
Men were aged 18–55 years, and women 18-43 years. Couples were randomised (1:1) to undergo PICSI, which is already offered in some fertility clinics, despite a lack of evidence that it increases full-term birth rates; or standard ICSI. Groups were balanced for maternal and paternal age, previous miscarriage, and hormonal indicators of ovarian reserve.
Women underwent ovarian stimulation, egg retrieval, and ICSI that was carried out to locally approved protocols with fresh embryo transfer. Half of the participants received the extra step of PICSI prior to the embryo transfer. Hyaluronan-sperm binding scores on the day of treatment were taken.
Live birth rate (full-term at ≥37 weeks' gestational age) comprised the primary outcome, while secondary outcomes included clinical pregnancy rates (defined as the presence of a foetal heartbeat or gestational sac at 6–9 weeks after fresh embryo transfer), miscarriage, and premature live birth rates before 37 weeks' gestational age.
Reduction in Miscarriage but No Difference in Full Term Live Birth Rate
A total of 2,772 couples were randomly assigned to receive PICSI (n=1387) or ICSI (n=1385), and of these, 2752 (1381 in the PICSI group and 1371 in the ICSI group) were included in the primary analysis.
The odds ratio for full-term live birth in the PICSI compared with the ICSI group was 1.12, which is not statistically significant. The rates of live birth at term were 25·2% [346/1371] in ICSI versus 27·4% [379/1381] in PICSI, which again did not reach statistical significance. There were no treatment-related adverse events.
"The 2.2% increase in live birth rate in the PICSI group did not reach statistical significance. But we did see a statistically significant reduction in miscarriage between the groups," explained David Miller.
The authors point out that the miscarriage results were found despite the study not being powered to investigate miscarriage, but the finding does reflect that of previous studies.
‘Although our results are largely consistent with those of previous reports, we have provided, for the first time, a robust measure of live birth following an hyaluronan-based sperm selection procedure,’ the authors note.
Miscarriage rates were 4.3% in the PICSI pregnancies versus 7.0% in the ICSI pregnancies; with an odds ratio of 0·61, representing a statistically significant reduction. The authors write that they ‘found no evidence of differential effects of treatment on miscarriage rates according to hyaluronan–sperm binding scores, maternal age, previous miscarriage, maternal follicle stimulating hormone (FSH) or anti-Müllerian hormone (AMH) concentrations, or paternal sperm concentrations'.
"I expected to see the miscarriage effect, but I had hoped to see a greater improvement in live births. But there were some other findings of interest in relation to characteristics of the sperm samples and the mechanism responsible that will be reported at a later date, and there will also be further research to investigate these findings some more, " remarked David Miller. "We are also keen to investigate whether there is any particular benefit of PICSI among older couples that could explain the PICSI effect."
Professor Yakoub Khalaf, medical director and consultant gynaecologist at Guy's and St Thomas' NHS Foundation Trust, co-authored the study. He explained that couples can be put under pressure to consider add-ons and other techniques that give them added hope and expectations of successful treatment. "But it is important that there is good evidence to support their use. We hope these new findings can help couples who are considering IVF to decide which treatments to choose."
COI: David Miller, PhD, declares he received a grant from Biocoat, outside of the submitted work, and personal fees from Origio to attend a meeting to report the submitted work.
Published in the 2 February 2019 edition of The Lancet
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Cite this: Becky McCall. PICSI Infertility Treatment 'Does Not Warrant Widespread Use' - Medscape - Feb 04, 2019.