Sperm Selection by Microfluidic Separation Improves Embryo Quality

NCT ID: NCT03085433

Last Updated: 2025-12-31

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

393 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-20

Study Completion Date

2022-04-30

Brief Summary

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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

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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.

Conditions

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Sperm DNA Fragmentation Embryo Quality Fertility Disorders Infertility Infertility, Male Infertility Unexplained

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Microfluidic Sperm Sorting

Intervention Type DEVICE

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 vitro fertilization

Intervention Type PROCEDURE

ivf/icsi

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.

Group Type ACTIVE_COMPARATOR

in vitro fertilization

Intervention Type PROCEDURE

ivf/icsi

Interventions

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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.

Intervention Type DEVICE

in vitro fertilization

ivf/icsi

Intervention Type PROCEDURE

Other Intervention Names

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FERTILE device

Eligibility Criteria

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Inclusion Criteria

* The target population includes couples planning in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI).
* Subjects with and without a history of prior IVF cycles will be included.
* 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:

o 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mitchell Rosen, M.D

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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University of California San Francisco

San Francisco, California, United States

Site Status

Countries

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United States

References

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Quinn MM, Ribeiro S, Juarez-Hernandez F, Simbulan RK, Jalalian L, Cedars MI, Rosen MP. Microfluidic preparation of spermatozoa for ICSI produces similar embryo quality to density-gradient centrifugation: a pragmatic, randomized controlled trial. Hum Reprod. 2022 Jun 30;37(7):1406-1413. doi: 10.1093/humrep/deac099.

Reference Type DERIVED
PMID: 35522187 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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16-21273

Identifier Type: -

Identifier Source: org_study_id