Clinical trial NCT04477356: SU Versus GD for Sperm Preparation in IUI
Official title: The Effectiveness of Swim-up Versus Gradient Density for Sperm Preparation in Patients Undergoing Intrauterine Insemination: A Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility
Keywords: Swim-up (SU)
Gradient density (GD)
IUI
Lead sponsor: Mỹ Đức Hospital
Sponsor class: OTHER
Collaborators: name: Mỹ Đức Phú Nhuận Hospital
First posted: 2020-07-20
Enrollment: 912
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Intrauterine insemination (IUI) is the first-line treatment for couples with unexplained and mild male factor infertility. The result of IUI depends on many factors including the sperm preparation techniques. Swim-up (SU) and Density Gradient (DG) are the two most commonly used techniques in sperm preparation for IUI. There is discussion about the effectiveness of these two techniques for IUI outcomes. The effectiveness of SU and DG methods on IUI success rate is not clearly understood and is controversial. This multicenter, randomized controlled trial will be conducted to determine which method (DG or SU) is better for IUI treatment.

Detailed description: Potentially eligible patients will be given information about the study on day 2 or day 3 of the menstrual cycle, when the ovarian stimulation starts. Screening for eligibility will be performed by treating physicians on the day of IUI, after having obtained the semen qualified for inclusion criteria from the husband. Eligible participants will be invited to a full discussion with investigators about the study and will be given the informed consent form. Couples will have enough time to decide if they agree to participate in the study or not. Written informed consent will be obtained by the investigators from all couples prior to enrolment. When a participant signs an informed consent, she is considered to be enrolled in the study.

Eligible patients who have provided informed consent will be randomized in a 1:1 ratio to either SU or GD. Assignment to treatment allocation will be done via a web portal hosted by HOPE Research Center, Vietnam. The randomization schedule will be computer-generated at HOPE Research Center, with a permuted random block size of 2, 4, and 6. Blinding will not be possible due to the nature of interventions.

Ovarian stimulation will be performed by using human menopausal gonadotrophins (hMG) (IVF-M, LG Life science, Korea) and follicular development will be monitored by transvaginal ultrasound every 3 - 5 days begin on day 2 or day 3 of the menstrual cycle. An injection of human chorionic gonadotropin (hCG) (IVF-C 5000 IU, LG Life Science, Korea) will be given to trigger ovulation when the mean diameter of the dominant follicle reached ≥ 18 mm. Those who have more than 7 follicles ≥ 14 mm will be subjected to cancel or convert to IVM. IUI will be scheduled 36 - 38 hours after hCG injection.

A sperm sample will be obtained in the clinic by masturbation after 2-5 day of abstinence. Spoken and written instructions about the collection of the semen sample will be given in advance. The time between semen production and processing will be up to 1 hour. Sperm preparation will be performed after the patient agrees to participate in the study.

In couples allocated to the sperm swim-up technique (SU): the normal and highly motile sperm will move against the gravity and separate from the dead or abnormal sperms to swim up to the upper media culture layer In couples allocated to the sperm density gradient centrifugation technique (GD): the density in which mature and normal sperms are capable of passing through filtration layer to be isolated from dead or abnormal sperms in semen Prepared sperms will be transferred into uterus by soft catheter (Gynétics, Belgium). Luteal-phase support will be done with vaginal progesterone 400 mg per day (Cyclogest 200 mg, Actavis, UK) until 7th week of gestation. In both groups, clinicians who perform insemination will be blinded to the intervention.

The prepared sperms will be proceeded to medical doctor who will carry the IUI and have no information about the semen preparation step. After insemination, the patient will be asked to immobilize for 15 minutes. The patient will receive luteal phase support using vaginal micronized progesterone for 14 days. In both groups, blood hCG will be measured at day 14 after insemination, and positive results indicate biochemical pregnancy. If the gestational sac is observed with ultrasonography at week 7 after transferring, clinical pregnancy will be confirmed. At the 11th and 12nd weeks of gestation, participants will be referred to the Outpatient clinic, OB/GYN Department at My Duc hospital or at My Duc Phu Nhuan hospital for prenatal care until delivery. When the participant attends for delivery, data on labor and delivery, any complications experienced by participant, and the neonates will be collected. For those who cannot participate the prenatal care program at either the two hospitals, for any reasons, we will contact the participants via telephone/email monthly until delivery to collect data. We also ask these participants to scan their profile in every contact.

All analyses will be conducted on an intention-to-treat basis using the R statistical program The rate of live birth and the associated 95% confidence interval (CI) will be estimated and compared between groups using the exact method for binomial proportion.

Differences between groups in secondary outcome variables will be analyzed using Student t-test or Wilcoxon signed-rank test for normally distributed or skewed variables, and Fisher's exact test for categorical variables, and reported as relative risk (RR) with 95% CI. Besides that, we will conduct the subgroup analysis to compare the effectiveness of DG and that of SU for each of criteria within the following categories including causes of infertility, quality of pre-washing semen, and total number of post-washing motile sperms. For the number of motile sperms after washing, we divide it into 5 subgroups including \< 1 million sperms, 1-5 million sperms, 5-10 million sperms, 10-20 million sperms, and \> 20 million sperms.

For missing population characteristics, first, we will analyze by removing the missing data; then we perform multiple imputations of lost values and perform another analysis to estimate the certainty of these obtained results. In case of losing track of patients or making protocol mistakes, we will try performing sensitivity analysis to evaluate the effects of these factors in the study. A statistical analysis plan will be made and signed before data-lock.

Eligibility criteria: Inclusion Criteria:

* Patient undergoing IUI
* Undergone ≤ 2 previous IUI cycles
* Progressive motility (PR) before sperm preparation: ≥ 32%
* Sperm concentration before sperm preparation: ≥ 5 million/ml
* Total progressive motility sperm count before sperm preparation: \> 5million
* Agree to participate in the study

Exclusion Criteria:

* Using frozen semen
* High viscosity semen

Primary outcomes:
measure: Live birth rate
timeFrame: At 24 weeks of gestation
Secondary outcomes:
measure: Total motile sperm count after sperm preparation
timeFrame: At 5 minutes after sperm preparation for IUI
measure: Biochemical pregnancy rate
timeFrame: At 14 days after insemination
measure: Clinical pregnancy rate
timeFrame: At 7 weeks of gestation
measure: Ongoing pregnancy rate (OPR)
timeFrame: At the 12 weeks of gestation
measure: Ectopic pregnancy rate
timeFrame: At 5-7 weeks of gestation
measure: Multiple pregnancy rate
timeFrame: At 7 weeks of gestation
measure: Vanishing twin rate
timeFrame: In the first trimester pregnancy
measure: Miscarriage rate
timeFrame: Before 22 weeks of gestational age
measure: Gestational age at delivery
timeFrame: At birth
measure: Stillbirth rate
timeFrame: After 28 completed weeks of gestational age
measure: Preterm labor rate
timeFrame: At birth
measure: Spontaneous preterm birth rate
timeFrame: At birth
measure: Iatrogenic preterm birth rate
timeFrame: At birth
measure: Birth weight
timeFrame: At birth
measure: Low birth weight rate
timeFrame: At birth
measure: Very low birth weight rate
timeFrame: At birth
measure: High birth weight rate
timeFrame: At birth
measure: Very high birth weight rate
timeFrame: At birth
measure: 1-minute Apgar score
timeFrame: 1 minute after delivery
measure: 5-minutes Apgar score
timeFrame: 5 minutes after delivery
measure: Admission to NICU rate
timeFrame: 7 days after delivery
measure: Congenital abnormalities rate
timeFrame: At birth
Other outcomes:
Locations:
city: Hochiminh city
country: Vietnam
facility: Dang Q Vinh
Study officials:
References: