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Sperm Selection by Microfluidic Separation Improves Embryo Quality in Patients With a History of Poor Embryo Quality (SPERM)

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ClinicalTrials.gov Identifier: NCT03085433
Recruitment Status : Recruiting
First Posted : March 21, 2017
Last Update Posted : November 13, 2019
Sponsor:
Information provided by (Responsible Party):
Mitchell Rosen, M.D., University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE March 19, 2017
First Posted Date  ICMJE March 21, 2017
Last Update Posted Date November 13, 2019
Actual Study Start Date  ICMJE March 17, 2017
Estimated Primary Completion Date January 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 19, 2017)
Day 3 high quality embryo proportion [ Time Frame: 3 days following fertilization ]
The primary outcome, day 3 high quality embryo proportion will be defined as proportion of all viable embryos on day 3 with at least 6 cells and fragmentation/symmetry scores of 1-2.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03085433 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 19, 2017)
  • Fertilization rate [ Time Frame: 1 day following fertilization ]
    The primary outcome, day 3 high quality embryo proportion will be defined as proportion of all viable embryos on day 3 with at least 6 cells and fragmentation/symmetry scores of 1-2.
  • Pregnancy rate [ Time Frame: 14 days following embryo transfer ]
    Pregnancy rate will be defined as clinical pregnancy (ultrasound demonstrating gestational sac with yolk sac) per transfer
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sperm Selection by Microfluidic Separation Improves Embryo Quality in Patients With a History of Poor Embryo Quality
Official Title  ICMJE Sperm Selection by Microfluidic Separation Improves Embryo Quality in Patients With a History of Poor Embryo Quality
Brief 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Sperm DNA Fragmentation
  • Embryo Quality
  • Fertility Disorders
  • Infertility
  • Infertility, Male
  • Infertility Unexplained
Intervention  ICMJE
  • Device: Microfluidic Sperm Sorting
    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.
    Other Name: FERTILE device
  • Procedure: in vitro fertilization
    ivf/icsi
Study Arms  ICMJE
  • Experimental: Microfluidic sperm sorting
    Couples undergoing in vitro fertilization randomized to microfluidic sperm sorting will have raw semen sorted by the microfluidics chip prior to fertilization with IVF/ICSI.
    Interventions:
    • Device: Microfluidic Sperm Sorting
    • Procedure: in vitro fertilization
  • Active Comparator: Conventional sperm preparation
    Couples undergoing in vitro fertilization randomized to conventional methods for sperm processing will undergo separation of semen by density gradient centrifugation prior to IVF/ICSI.
    Intervention: Procedure: in vitro fertilization
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 19, 2017)
62
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 1, 2020
Estimated Primary Completion Date January 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:The target population includes couples planning in vitro fertilization (IVF) with or without intracytoplasmic sperm injection for unexplained infertility at the UCSF Center for Reproductive Health with a history of poor embryo quality as defined by < =40% high quality D3 embryos in a prior IVF cycle. All eligible couples where both partners are >=18 years of age will be asked to join the study.

Exclusion Criteria:

Male partner with severe oligoasthenospermia (concentration < 5 x 10^6 spermatozoa/mL; motility< 10%) Female partner with anovulation (PCOS, FHA) Female partner age >41 Female partner AFC< 7 Female partner with obstructed fallopian tubes (assessed in all patients prior to IVF) Use of oocyte donor

Either Partner:

Cancer diagnosis in either partner Any significant disease or psychiatric disorder that would interfere with consenting process

Treatment History:

History of >1 prior cycle cancellation due to poor response

Treatment Plan:

Embryo co-culture Use of adjunctive non-gonadotropin medications to improve embryo quality: growth hormone, sildenafil

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Mitchell Rosen, M.D 4153537475 Mitchell.Rosen@ucsf.edu
Contact: Flor Juarez-Hernandez 4155146387 Flor.Juarez-Hernandez@ucsf.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03085433
Other Study ID Numbers  ICMJE 16-21273
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Mitchell Rosen, M.D., University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mitchell Rosen, M.D University of California, San Francisco
PRS Account University of California, San Francisco
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP