BACKGROUND: Sperm selection strategies aimed at improving success rates of intracytoplasmic sperm injection (ICSI) include binding to hyaluronic acid (herein termed hyaluronan). Hyaluronan-selected sperm have reduced levels of DNA damage and aneuploidy. Use of hyaluronan-based sperm selection for ICSI (so-called physiological ICSI [PICSI]) is reported to reduce the proportion of pregnancies that end in miscarriage. However, the effect of PICSI on livebirth rates is uncertain. We aimed to investigate the efficacy of PICSI versus standard ICSI for improving livebirth rates among couples undergoing fertility treatment.
METHODS: This parallel, two-group, randomised trial included couples undergoing an ICSI procedure with fresh embryo transfer at 16 assisted conception units in the UK. Eligible women (aged 18-43 years) had a body-mass index of 19-35 kg/m2 and a follicle-stimulating hormone (FSH) concentration of 3·0-20·0 mIU/mL or, if no FSH measurement was available, an anti-müllerian hormone concentration of at least 1·5 pmol/L. Eligible men (aged 18-55 years) had not had a vasovasostomy or been treated for cancer in the 24 months before recruitment and were able, after at least 3 days of sexual abstinence, to produce freshly ejaculated sperm for the treatment cycle. Couples were randomly assigned (1:1) with an online system to receive either PICSI or a standard ICSI procedure. The primary outcome was full-term (≥37 weeks' gestational age) livebirth, which was assessed in all eligible couples who completed follow-up. This trial is registered, number ISRCTN99214271.
FINDINGS: Between Feb 1, 2014, and Aug 31, 2016, 2772 couples were randomly assigned to receive PICSI (n=1387) or ICSI (n=1385), of whom 2752 (1381 in the PICSI group and 1371 in the ICSI group) were included in the primary analysis. The term livebirth rate did not differ significantly between PICSI (27·4% [379/1381]) and ICSI (25·2% [346/1371]) groups (odds ratio 1·12, 95% CI 0·95-1·34; p=0·18). There were 56 serious adverse events in total, including 31 in the PICSI group and 25 in the ICSI group; most were congenital abnormalities and none were attributed to treatment.
INTERPRETATION: Compared with ICSI, PICSI does not significantly improve term livebirth rates. The wider use of PICSI, therefore, is not recommended at present.
FUNDING: National Institute for Health Research Efficacy and Mechanism Evaluation Programme.
Bibliographical noteFunding: National Institute for Health Research Efficacy and Mechanism Evaluation Programme.
Acknowledgments: This study was funded by the EME Programme (MREC 13/YH/0162; UKCRN ID 14845), a partnership of the Medical Research Council (MRC) and NIHR, and supported by the UK NIHR, the NIHR infrastructure in Leeds, and the UK Clinical Research Network. The views expressed in this publication are those of the authors and not necessarily those of the MRC, National Health Service, NIHR, or the UK Department of Health. The chief and principal investigators are thankful for the support of both the extended HABSelect Study Team and the NIHR Clinical Research Network, without whom the trial would not have been possible.
- Embryo Implantation
- Embryo Transfer
- Hyaluronic Acid/therapeutic use
- Middle Aged
- Pregnancy Outcome
- Pregnancy Rate
- Sperm Injections, Intracytoplasmic
- Treatment Outcome
- United Kingdom