Physiological, hyaluronan-selected intracytoplasmic sperm injection for infertility treatment (HABSelect): a parallel, two-group, randomised trial

Abstract

Summary 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/m 2 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.

IVF, from the past to the future: the inheritance of the Capri Workshop Group

“…Overcoming this challenge is fundamental in guiding the development of assisted reproduction, and much has already been done. Over the last few years, there have been growing outstanding contributions in the high-quality scientific literature aimed at disentangling the effective from the non-effective interventions that have entered into clinical practice ( Chen et al , 2016 ; El-Toukhy et al , 2016 ; Smit et al , 2016 ; Wang et al , 2017 ; Farquhar et al , 2018 ; Shi et al , 2018 ; Smith et al , 2018 ; Vuong et al , 2018 ; Lensen et al , 2019 ; Miller et al , 2019 ; Wei et al , 2019 ).…”

Effect of paternal age on outcomes in assisted reproductive technology cycles: systematic review and meta-analysis

“…A number of studies have observed that the use of ICSI mitigated the effect of increased sperm DNA fragmentation (51, 52). The recent large hyaluronan-selected intracytoplasmic sperm injection for infertility treatment randomized controlled trial found no improvement in live birth but noted a significant reduction in miscarriage when using physiological ICSI rather than conventional ICSI (57).…”

An update on the management of male infertility

“…PICSI is therefore not recommended for routine clinical care. 78 The hypo-osmotic swelling (HOS) test evaluates the functional integrity of the sperm plasma membrane and can be useful to assess sperm viability if motility is very poor. Live spermatozoa placed in hypo-osmotic media swell, particularly the tail, because water and small compounds influx into the cytoplasm.…”