Live Birth Rate After Sperm Selection Using ZyMōt Multi (850µL) Device for Intra Uterine Insemination (FERTINSEM)

Universitair Ziekenhuis Brussel

Status: Enrolling

Conditions: Fertility Disorders; Infertility

Treatments: Device: ZyMōt Multi (850µL); Other: Density Gradient Centrifugation

Study type: Interventional

Funder types: Other

Identifiers

NCT06144268

EC-2023-257

Details and patient eligibility

About

This single centre interventional pilot randomized control study intends to compare two methods of sperm preparation for couples referred for Intra Uterine Insemination (IUI) procedure. Couples will be randomly allocated to one of the two sperm selection methods: Density Gradient Centrifugation (DGC, standard) or ZyMōt Multi (850µL) device (treatment) groups. The study will compare the live birth rate (number of live births per number of IUI procedures) between the treatment and standard groups.

Full description

Intrauterine insemination is a commonly used method for Medically Assisted Reproduction for patients with mild male factor infertility, anovulation, endometriosis, and unexplained infertility. It is also the procedure of choice in cases of lesbian couples or single women, using donor sperm.

During the IUI procedure, the sperm suspension is introduced into the uterus through the cervix canal using an insemination catheter containing 0.4 ml sperm. Before sperm can be used in IUI, it must first be processed. The aim of semen preparation is to select the best sperm cell population (highly motile, morphologically normal spermatozoa with minimal DNA damage) with the highest fertilization potential.

One of the most used sperm preparation technique is DGC. This technique allows the separation of sperm cells based on their density. Morphologically normal and abnormal spermatozoa have different densities. A mature morphologically normal spermatozoon has a slightly higher density, whereas an immature and morphologically abnormal spermatozoon has a lower density. During this procedure, raw semen sample is placed on 2 gradients: a lower phase (80%) and an upper phase (40%) followed by centrifugation. The composition of the gradients include a colloidal suspension of silica particles. At the end of centrifugation, each spermatozoa is situated at the gradient level that matches its density. The highly motile, morphologically normal, viable spermatozoa form a pellet at the bottom of the tube. This procedure is relatively easy to perform but both the centrifugation steps and the silica particle are considered to have a negative impact on DNA integrity.

Recently, microfluidic technology was introduced as an alternative to the conventional sperm sorting techniques. As this procedure does not require semen processing, it reduces the sperm preparation time and eliminates sperm DNA damaging procedures (e.g. by centrifugation). This technology is a chemical-free method of sorting healthy normal sperm using a sterile disposable ZyMōt Multi (850µL) sperm separation device. Sperm selected by this device proved to have better motility and less DNA damage compared to DGC procedure. More recently, the efficacy of this device has been reported to significantly increase ongoing pregnancy rate when compared with DGC in IUI cycles. However, large, correct studies that investigate live birth rate are missing.

The present study aims to determine whether the use of ZyMōt Multi (850µL) device for sperm selection improves the live birth rate in IUI patients as compared to the standard DGC procedure. Couples undergoing IUI procedure will be included in the study if they are planned for IUI with fresh autologous ejaculate.

Patients that fulfill the inclusion criteria will be randomly allocated to one of the two sperm selection methods: DGC (standard) or ZyMōt Multi (850µL) device (treatment) groups. The randomization will be performed based on an electronically generated list. A patient participation to the study will be limited to 3 consecutive IUI attempts (within a period of 6 months). Same semen preparation protocol used in the 1st IUI attempt [ZyMōt Multi (850µL) or DGC] will be used in the next 2 consecutive IUIs. Following the IUI procedure (with sperm selected with either one of the two methods), the patients will be monitored for pregnancy, clinical pregnancy and neonatal outcome.

Enrollment: 240 estimated patients

Sex: All

Ages: 18 to 36 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Fresh autologous ejaculate
• Female age: <37 at start of the first insemination
• 1st IUI ever here, maximum 3 consecutive IUIs during max 6 months
• BMI <35
• All natural cycles, ovulation induction allowed
• Presence of 1 or 2 follicles at the last ultrasound
• Regular menses (26-35 days)
• >1 million Total Progressive Motile Sperm Count (TPMC) after previous routine capacitation with DGC
• Presence of at least 1 potent tube after Hyfosy

Exclusion criteria

• Presence of intracavitary pathology at ultrasound
• Evidence of advance endometriosis (Grade 3 and 4)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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240 participants in 2 patient groups

Density Gradient Centrifugation (DGC)

Active Comparator group

Description:

During this procedure, raw semen sample is placed on 2 gradients: a lower phase (80%) and an upper phase (40%) followed by centrifugation. The composition of the gradients include a colloidal suspension of silica particles. At the end of centrifugation, each spermatozoa is situated at the gradient level that matches its density. The highly motile, morphologically normal, viable spermatozoa form a pellet at the bottom of the tube.

Treatment:

Other: Density Gradient Centrifugation

ZyMōt Multi (850µL)

Experimental group

Description:

ZyMōt Multi (850µL) is a flow-free dual chambered single-use device. The first chamber contains a sample inlet and a fluid channel separated from the second collection chamber by an 8-μm microporous membrane. Channel dimension and membrane porosity are designed to optimize the sorting and collection of the most motile sperm. Sorting is accomplished by the passage of sperm through the micropores of the membrane. This procedure does not require any preliminary semen processing, all centrifugation steps being eliminated.

Treatment:

Device: ZyMōt Multi (850µL)