Sperm Selection by Microfluidic Separation Improves Embryo Quality
Condition: Sperm DNA Fragmentation; Embryo Quality; Fertility Disorders; Infertility; Infertility, Male; Infertility Unexplained
MeSH terms: Infertility; Infertility, Male
Study type: Interventional

Summary: 
      This is a randomized controlled trial of couples with a history of poor embryo quality
      undergoing a repeat in vitro fertilization (IVF) cycle for unexplained infertility. Couples
      will be randomized to sperm selection by the clinical standard of centrifugation and
      density-gradient processing compared to the microfluidic sperm sorting chip.
    

Detailed description: 
      More than 70 million couples worldwide are infertile and up to 40 million are actively
      seeking infertility care. In the year 2013, a total of 160,521 assisted reproductive
      technology (ART) procedures were performed in the United States. Isolation of motile and
      morphologically normal sperm is an integral part of assisted reproduction. Traditional sperm
      processing for assisted reproduction involves centrifugation and "swim up" techniques that
      employ a density gradient to isolate motile sperm. This technique involves several steps of
      centrifugation (200-1800g) with colloidal silica particles. In this process, sperm and other
      material form distinct bands. It is thought that this procedure allows for elimination of
      abnormal/immotile sperm as well as debris, thereby isolating motile human sperm.
      Nevertheless, the centrifugation process has been shown to induce DNA damage and produce
      reactive oxygen species, thereby potentially compromising sperm quality and subsequent
      laboratory outcomes such as fertilization rate and embryo quality. Increased sperm DNA damage
      has been associated with poor outcomes in assisted reproduction, including lower
      fertilization rates, impaired embryo progression, and decreased pregnancy rates. The details
      of the density gradient centrifugation process are not regulated by the FDA.

      In contrast, microfluidic-based sperm sorting has the capability of selectively isolating
      highly motile, morphologically normal sperm with high DNA integrity from an unprocessed semen
      sample. Microfluidic technology isolates healthy sperm by laminar flow, creating gradients
      through channels. The microfluidic chip we plan to study in our randomized clinical trial
      utilizes space-constrained microfluidic sorting to select highly motile and morphologically
      normal sperm in a flow and chemical-free design. Unlike the standard of density gradient
      centrifugation, no manipulation of sperm is required in this process. Raw semen is introduced
      into the inflow and only motile and morphologically normal sperm are able to swim through the
      chip to the outflow where it is collected for use.

      In semen samples from healthy male volunteers split into standard processing via
      centrifugation and swim-up procedure compared with microfluidic sperm sorting, a
      significantly higher percent motility and lower rate of sperm DNA fragmentation was detected
      with microfluidic sperm sampling. The microfluidic sperm sorting technique has thus proven to
      be an efficient and reliable means of sperm preparation compared with the centrifugation and
      swim-up procedure. While this microfluidic chip has been used clinically in Mexico, Turkey,
      South Africa, Italy, Greece, and Switzerland resulting in over 5,000 live births, its use in
      clinical practice has not been rigorously studied. We aim to compare traditional preparation
      and microfluidic sperm sorting on assisted reproductive technology outcomes including oocyte
      fertilization and embryo quality in subjects with a history of poor embryo quality electing
      to undergo a repeat in vitro fertilization cycle for infertility.
    

Intervention name(s): Microfluidic Sperm Sorting; in vitro fertilization
Intervention type(s): Device; Procedure
Intervention description(s): Microfluidic technology isolates healthy sperm by laminar flow, creating gradients through channels. The microfluidic chip we plan to study in our randomized clinical trial utilizes space-constrained microfluidic sorting to select highly motile and morphologically normal sperm in a flow and chemical-free design. Unlike the standard of density gradient centrifugation, no manipulation of sperm is required in this process. Raw semen is introduced into the inflow and only motile and morphologically normal sperm are able to swim through the chip to the outflow where it is collected for use.; ivf/icsi
Other intervention name(s): FERTILE device
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment