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 : October 29, 2018
|Condition or disease||Intervention/treatment||Phase|
|Sperm DNA Fragmentation Embryo Quality Fertility Disorders Infertility Infertility, Male Infertility Unexplained||Device: Microfluidic Sperm Sorting Procedure: in vitro fertilization||Phase 3|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||62 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Sperm Selection by Microfluidic Separation Improves Embryo Quality in Patients With a History of Poor Embryo Quality|
|Actual Study Start Date :||March 17, 2017|
|Estimated Primary Completion Date :||July 1, 2019|
|Estimated Study Completion Date :||July 1, 2019|
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.
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
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.
Procedure: in vitro fertilization
- 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.
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03085433
|Contact: Mitchell Rosen, M.D||4153537475||Mitchell.Rosen@ucsf.edu|
|Contact: Flor Juarez-Hernandez||4155146387||Flor.Juarez-Hernandez@ucsf.edu|
|United States, California|
|University of California San Francisco||Recruiting|
|San Francisco, California, United States, 94158|
|Contact: Mitchell Rosen, M.D 415-353-7475 Mitchell.Rosen@ucsf.edu|
|Contact: Flor Juarez-Hernandez (415) 514-6387 Flor.Juarez-Hernandez@ucsf.edu|
|Principal Investigator:||Mitchell Rosen, M.D||University of California, San Francisco|