Clinical trial NCT06144268: Live Birth Rate After Sperm Selection Using ZyMōt Multi (850µL) Device for Intra Uterine Insemination
Official title: Evaluation of Live Birth Rate After Sperm Selection Using Microfluidic Technology (ZyMōt Multi (850µL) Sperm Separation Device) for Intra Uterine Insemination.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Infertility
Fertility Disorders
Keywords: Intra Uterine Insemination
Live birth
Microfluidic sperm selection
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
First posted: 2023-11-22
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 36
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Cumulative live birth rate after 3 consecutive IUIs
timeFrame: 9 months following IUI
Secondary outcomes:
measure: Pregnancy rate
timeFrame: 14 days following IUI
measure: Miscarriages rate
timeFrame: 12 weeks following IUI
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: UZ Brussel CRG
Study officials:
affiliation: Universitair Ziekenhuis Brussel
name: Shari Mackens, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gode F, Bodur T, Gunturkun F, Gurbuz AS, Tamer B, Pala I, Isik AZ. Comparison of microfluid sperm sorting chip and density gradient methods for use in intrauterine insemination cycles. Fertil Steril. 2019 Nov;112(5):842-848.e1. doi: 10.1016/j.fertnstert.2019.06.037. Epub 2019 Sep 19.