Trial Outcomes & Findings for A Sibling Oocyte Study- Comparison of ZyMotTM Microfluidics Device to Density Gradient for Sperm Selection During ICSI (NCT NCT04818593)

Results Overview

Good quality embryos will be defined as blastocyst stage embryos on day 5 or 6 of culture with an overall quality grade of good or fair. Embryo morphology assessment includes two parts: an Overall Grade and the Stage. Grading is a subjective assessment of the overall quality of the embryo as good, fair, or poor, and is based on assessment of certain characteristics of the embryo, such as fragmentation, symmetry, inner cell mass (ICM) quality and trophectoderm quality. The percentage will be reported for both arms (ZyMot compared to density gradient).

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

108 participants

Primary outcome timeframe

Culture Day 5 or 6

Results posted on

2023-06-05

Participant Flow

The trial enrolled 108 unique individuals grouped into 54 patient/sperm-source dyads. Each enrolled dyad produced oocyte units. Oocytes from the same dyad were assigned to the density gradient (control) arm, ZyMot (treatment) arm, or both depending on the criteria met by the oocyte units, meaning the same 54 dyads were assigned to both study arms. Dyads who produced insufficient samples for ZyMot processing were withdrawn.

Unit of analysis: Oocytes

Participant milestones

Participant milestones
Measure	ZyMot Separation Device (Treatment) 850 uL of untreated semen will be directly deposited into the inlet port of the ZyMotTM Multi device, followed by placement of 750 uL culture medium in the outlet port and throughout the upper collection chamber. The device will then be incubated in a humidified 37C CO2 incubator for 30 minutes. During incubation, the healthiest and most motile sperm will swim through the microporous filter and into the upper collection chamber, where they will be recovered via the outlet port. 500 uL of the sperm sample will be removed and placed in a separate tube for analysis and insemination. Control: Density Gradient Centrifugation: Density gradient centrifugation will be performed using a one-layer preparation of 90% Isolate in 15 mL conical tubes. Semen will be layered over 1 mL of gradient and then centrifuged for 15 min at 300xg. The supernatant will be removed and discarded. The sperm pellet will be washed by mixing with Multipurpose Handling Medium Complete and centrifuging the sample for 5 min at 400xg. After the wash, the supernatant is removed and discarded and the pellet is re-suspended in culture medium, assessed for sperm parameters, and held at room temperature until insemination.	Density Gradient Centrifugation (Control) Density gradient centrifugation will be performed using a one-layer preparation of 90% Isolate in 15 mL conical tubes. Semen will be layered over 1 mL of gradient and then centrifuged for 15 min at 300xg. The supernatant will be removed and discarded. The sperm pellet will be washed by mixing with Multipurpose Handling Medium Complete and centrifuging the sample for 5 min at 400xg. After the wash, the supernatant is removed and discarded and the pellet is re-suspended in culture medium, assessed for sperm parameters, and held at room temperature until insemination.
Overall Study STARTED	54 231	54 225
Overall Study COMPLETED	34 231	34 225
Overall Study NOT COMPLETED	20 0	20 0

Reasons for withdrawal

Reasons for withdrawal
Measure	ZyMot Separation Device (Treatment) 850 uL of untreated semen will be directly deposited into the inlet port of the ZyMotTM Multi device, followed by placement of 750 uL culture medium in the outlet port and throughout the upper collection chamber. The device will then be incubated in a humidified 37C CO2 incubator for 30 minutes. During incubation, the healthiest and most motile sperm will swim through the microporous filter and into the upper collection chamber, where they will be recovered via the outlet port. 500 uL of the sperm sample will be removed and placed in a separate tube for analysis and insemination. Control: Density Gradient Centrifugation: Density gradient centrifugation will be performed using a one-layer preparation of 90% Isolate in 15 mL conical tubes. Semen will be layered over 1 mL of gradient and then centrifuged for 15 min at 300xg. The supernatant will be removed and discarded. The sperm pellet will be washed by mixing with Multipurpose Handling Medium Complete and centrifuging the sample for 5 min at 400xg. After the wash, the supernatant is removed and discarded and the pellet is re-suspended in culture medium, assessed for sperm parameters, and held at room temperature until insemination.	Density Gradient Centrifugation (Control) Density gradient centrifugation will be performed using a one-layer preparation of 90% Isolate in 15 mL conical tubes. Semen will be layered over 1 mL of gradient and then centrifuged for 15 min at 300xg. The supernatant will be removed and discarded. The sperm pellet will be washed by mixing with Multipurpose Handling Medium Complete and centrifuging the sample for 5 min at 400xg. After the wash, the supernatant is removed and discarded and the pellet is re-suspended in culture medium, assessed for sperm parameters, and held at room temperature until insemination.
Overall Study Low Oocyte Yield	8	8
Overall Study Not ICSI Insemination	7	7
Overall Study Poor Sperm Quality	2	2
Overall Study Withdrawal by Subject	2	2
Overall Study Conversion to IUI due to low response	1	1

Baseline Characteristics

A Sibling Oocyte Study- Comparison of ZyMotTM Microfluidics Device to Density Gradient for Sperm Selection During ICSI

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study Population n=66 Participants Individuals in patient/sperm-source dyads with oocyte units that were analyzed.
Age, Continuous	36.9 years STANDARD_DEVIATION 0.6 • n=93 Participants
Sex: Female, Male Female	33 Participants n=93 Participants
Sex: Female, Male Male	33 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	65 Participants n=93 Participants

PRIMARY outcome

Timeframe: Culture Day 5 or 6

Population: Participants refer to dyads. Information form one of the completed dyads was not collected.

Good quality embryos will be defined as blastocyst stage embryos on day 5 or 6 of culture with an overall quality grade of good or fair. Embryo morphology assessment includes two parts: an Overall Grade and the Stage. Grading is a subjective assessment of the overall quality of the embryo as good, fair, or poor, and is based on assessment of certain characteristics of the embryo, such as fragmentation, symmetry, inner cell mass (ICM) quality and trophectoderm quality. The percentage will be reported for both arms (ZyMot compared to density gradient).

Outcome measures

Outcome measures
Measure	ZyMot Separation n=231 Oocytes Treatment ZyMot Multi Sperm Separation Device (850 ul): 850 uL of untreated semen will be directly deposited into the inlet port of the ZyMotTM Multi device, followed by placement of 750 uL culture medium in the outlet port and throughout the upper collection chamber. The device will then be incubated in a humidified 37C CO2 incubator for 30 minutes. During incubation, the healthiest and most motile sperm will swim through the microporous filter and into the upper collection chamber, where they will be recovered via the outlet port. 500 uL of the sperm sample will be removed and placed in a separate tube for analysis and insemination.	Density Gradient Centrifugation n=225 Oocytes Control Density Gradient Centrifugation: Density gradient centrifugation will be performed using a one-layer preparation of 90% Isolate in 15 mL conical tubes. Semen will be layered over 1 mL of gradient and then centrifuged for 15 min at 300xg. The supernatant will be removed and discarded. The sperm pellet will be washed by mixing with Multipurpose Handling Medium Complete and centrifuging the sample for 5 min at 400xg. After the wash, the supernatant is removed and discarded and the pellet is re-suspended in culture medium, assessed for sperm parameters, and held at room temperature until insemination.
Percentage of Good Quality Blastocyst Formation	51.4 percentage of embryos Standard Deviation 5.1	51.7 percentage of embryos Standard Deviation 5.4

Adverse Events

ZyMot Separation

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Density Gradient Centrifugation

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Rani Fritz, DO, PhD, FACOG

NYU Langone Health

Phone: 718-935-9766

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place