Sperm Selection by Microfluidic Separation Improves Embryo Quality (SPERM)

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.

Study Overview

• Status: Completed
• Conditions: Infertility; Fertility Disorders; Infertility, Male; Infertility Unexplained; Sperm DNA Fragmentation; Embryo Quality
• Intervention / Treatment: Device: Microfluidic Sperm Sorting; Procedure: in vitro fertilization

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: Interventional
• Enrollment (Actual): 393
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • University of California San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: FERTILE device; Procedure: in vitro fertilization; ivf/icsi
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; ivf/icsi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Day 3 High Quality Embryo Percentage	The primary outcome for intent to treat analysis. Day 3 high quality embryo percentage rate will be defined as the percentage of all viable 2PN embryos on day 3 with at least 6 cells and fragmentation/symmetry scores of 1-2. Scale: 1-6 for either fragmentation or symmetry. Lower scores are better. Calculated as ( the number of high-qualify-grade embryos yielded by a participant / the number of all viable 2PN embryos yielded by the participant x 100)	3 days following fertilization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Egg Fertilization Rate	Number of eggs successfully fertilized (2PN embryo count) per number of mature eggs (MII egg count) retrieved per participant. 2PN grade indicates a successfully fertilized embryo. MII grade indicates a metaphase II stage egg which is mature enough to undergo fertilization. (The percentage is calculated for each participant as the number of 2PN embryos obtained / the number of MII eggs obtained x100). The resulting percentages were then averaged to determine the average fertilization rate for participants in each study arm.	1 day following fertilization
Pregnancy Rate	Pregnancy rate will be defined as achieving a clinical pregnancy ( an ultrasound demonstrating gestational sac with yolk sac) per embryo transfer procedure attempt.	14 days following embryo transfer

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Mitchell Rosen, M.D, University of California, San Francisco

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2017
• Primary Completion (Actual): October 30, 2021
• Study Completion (Actual): April 30, 2022

Study Registration Dates

• First Submitted: March 19, 2017
• First Submitted That Met QC Criteria: March 19, 2017
• First Posted (Actual): March 21, 2017

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Male Urogenital Diseases; Infertility; Infertility, Male; Investigative Techniques; Therapeutics; Reproductive Techniques, Assisted; Reproductive Techniques; Fertilization in Vitro
• Other Study ID Numbers: 16-21273

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes