HYPERSPERM, A NOVEL APPROACH TO IMPROVE EMBRYO DEVELOPMENT IN ART

Introduction

One of the main issues of in vitro fertilization (IVF) treatments is their inefficiency, just ~30% success rate overall, often requiring costly and painful repetitions to achieve a live birth. This drives prohibitive costs and crushing access barriers for most patients worldwide. Fecundis was founded with the mission to improve IVF by developing novel treatments based on a deeper understanding of the molecular and cellular mechanisms of reproduction. Fecundis first product, HyperSperm, is a sperm activator which increases sperm capacitation. Scientists at Fecundis have shown that the way sperm are handled before insemination has long range effects on embryo development and can be manipulated to provide more high-quality embryos from each patient.

Materials & Methods

HyperSperm is composed by 3 proprietary media that are used sequentially to process the semen sample for IVF. Preclinical studies of HyperSperm in mice were carried out in hybrid (BABL/c x C57BL/6) F1. Female mice were superovulated according to standard protocols. Egg–cumulus complexes were collected 13–14h after hCG and pooled. Mouse sperm were recovered by incising and incubating the cauda epididymis in TYH-HEPES for 15 min at 37˚C. Sperm were either capacitated in TYH-HEPES or treated with HyperSperm, as appropriate. Cumulus-intact eggs were inseminated with 0.5 × 10^6 cell/ml spermatozoa for 4 h at 37˚C. Embryos were cultured in KSOM and development was evaluated 3 days later and the number of embryos at the blastocyst stage was recorded. Embryos were either transferred to pseudo-pregnant females to test implantation potential and reproductive outcomes in offspring.
For initial clinical validation, 10 couples undergoing IVF with donated oocytes were included in a human trial. Sperm samples were divided into two halves and either processed by swim-up (Control) or treated with HyperSperm. Fourteen cumulus-oocyte complexes were assigned to each patient, 7 in each arm, and inseminated with the corresponding sperm preparation. Embryos were cultured in an Esco Miri time-lapse incubator to blastocyst stage. The primary outcome was blastocyst rate. Secondary outcomes were fertilization rate and developmental morphokinetics.

Results

In mice, HyperSperm increased both fertilization rate (71.9±6.4% vs 51.9±5.5%; p=0.032; n=10 experiments) and blastocyst rate (85.1±5.8% vs 65.1±6.2%; p=0.029; n=10 experiments) compared to the control, respectively (Figure 1). Further, implantation tests showed that HyperSperm blastocysts implant at a higher frequency than controls (76.0±11.2% vs 48.7±10.3%; p=0.163). Pups born from HyperSperm were all healthy at birth, of normal weight. Mating tests showed that both males and females were fertile.
In human, while fertilization rate was similar, the blastocyst rate was significantly higher in the HyperSperm group (36/53, 67.9% vs. 21/47, 44.7%; p=0.0159, Figure 2). HyperSperm increased blastocyst numbers in 8/10 cases, with an average 1.5 more blastocysts available for each patient. Morphokinetic development of HyperSperm blastocysts was not different from Control (p>0.05).

Discussion

Fecundis’s first development, HyperSperm, may have the potential to increase IVF efficiency by increasing the proportion of high-quality, competent blastocysts derived from a treatment, potentially lowering costs and repetitions in IVF. Full sperm capacitation may provide long range effect on embryo development.