Varicocele Repair for Men Undergoing IVF/ICSI

Not Applicable

• Conditions: Infertility, Male
• Interventions: Procedure: varicocelectomy

• Registration Number: NCT04608864
• Lead Sponsor: Al-Yasmeen Fertility and Gynecology Center

Brief Summary

For infertile men undergoing intracytoplasmic sperm injection (ICSI), data from retrospective studies suggested that varicocele repair may be beneficial and associated with improved livebirth and pregnancy rates, however, its role remains uncertain and disputed. To date, the investigators are not aware of published randomized controlled trail (RCT) that have evaluated whether varicocele repair would improve ICSI outcomes on patients with male-factor infertility.

Detailed Description

Varicocele repair in the era of assisted reproductive technology (ART) has been a point of dispute. The American Society for Reproductive Medicine (ASRM) Practice Committee recommended has considered ART as a primary treatment for female factor, regardless of the presence of varicocele and abnormal semen parameters.

A systematic review of 7 studies involving 1,241 men with a clinical varicocele and abnormal semen parameters showed improved livebirth and pregnancy rates after varicocelectomy in infertile men undergoing IVF/ICSI. Studies included in this systematic review were retrospective nature with a considerable heterogeneity. Evidence to support varicocelectomy for men with abnormal semen analysis undergoing IVF/ICSI has therefore remained inconclusive.

Study Timeline

• Status Verified: 2020-10
• Study First Submitted: 2020-10-11
• Study First Submitted QC: 2020-10-28
• Last Update Submitted: 2020-10-28
• Study First Posted: 2020-10-29
• Last Update Posted: 2020-10-29
• Study Start: 2020-12-01
• Primary Completion: 2022-12-01
• Study Completion: 2023-08-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 2000

Inclusion Criteria

1. Couples able to provide informed consent.
2. Couples with at least 12 months of infertility
3. Couples with male-factor infertility
4. Couples counseled for ICSI procedure by reproductive specialist.
5. Couples undergoing their first ICSI cycle or their second ICSI cycle after a previously successful treatment.
6. Female: age between 18-43; body mass index (BMI) between 19.0-35.0 kg/m2; FSH level 3.0-20.0 miU/mL and/or AMH ≥1.5 pmol/L; with regular menstrual cycles (defined as 25 to 35 days in duration), evidence of ovulation (by biphasic basal body temperature, ovulation predictor kits, or luteal serum progesterone level ≥3 ng/mL), have no uterine abnormality by ultrasound; anticipated normal responder (≥5 antral follicle count or ≥5.4 pmol/L Anti- mullerian hormone (AMH).
7. Male: age: 18-55; able to produce freshly ejaculated sperm for the treatment cycle; diagnosed with clearly palpable varicocele; have at least one abnormal semen parameter on a semen analysis in the preceding 3 months: sperm concentration ≤15 million/mL (oligospermia), total motility≤40% (asthenospermia), or normal morphology ≤4% (teratospermia); normal hormonal profile

Exclusion Criteria

1. Patients who willing to undergo ICSI with preimplantation genetic diagnosis.
2. Female: have previous two cycles of implantation failure at fresh transfer; with unilateral oophorectomy; PCOs; have any uterine pathology (myomas, adenomyosis, endocrinopathies, thrombophilia, chronic pathologies, acquired or congenital uterine abnormalities); have severe endometriosis; have uni- or bilateral hydrosalpinx; have history of recurrent pregnancy loss, takes any medical condition that affect fertility.
3. Male: have varicocele associated with hydrocele or inguinal hernia; secondary and recurrent varicocele, varicocele complicated by thrombophlebitis; varicocele with infertility due to other causes (demonstrated by andrologists), if they have a sperm concentration <1 million/mL on the screening semen analysis or if they were taking fertility medication or testosterone. Men are required to refrain from taking any medications for 4 weeks before randomization.
4. Abnormal karyotyping for female or male partners.
5. Uncontrolled diabetes, liver or renal disease, history of malignancy or borderline pathology of male or female partners.
6. Previous participation in the trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
varicocelectomy arm	varicocelectomy	The varicocelectomy procedure will be performed three months before ICSI for men with with male-factor infertility and were diagnosed clinically with varicocele

Primary Outcome Measures

Name	Time	Method
Livebirth rate	up to 37 weeks	the percentage of women who underwent randomization and will have a livebirth after at least 37 completed weeks of gestation

Secondary Outcome Measures

Name	Time	Method
Biochemical pregnancy	up to 2 weeks	positive βhCG ≥10 IU/L at 14 days after egg retrieval
Clinical pregnancy	up to 7 weeks	registered sacs with a heartbeat on ultrasound \>7th week of gestation
Ongoing pregnancy	up to 20 weeks
Miscarriage	up to 20th weeks
stillbirth	up to 20 weeks	intrauterine death at \>20 weeks
Fertilization rate	up to 16-18 hours after ICSI	number of oocytes fertilized per oocytes retrieved
Top quality embryos	up to 3 days after ICSI	number of top quality embryos at Day 3 per number of fertilized oocytes
cryopreservation rate	up to 3-6 days after ICSI	number of embryos cryopreserved per randomized woman
Blastocyst formation rate	up to 5 or 6 days after ICSI	number of blastocyst at Day 5 or 6 per number of fertilized oocytes
implantation rate	up to 7 weeks	number of intrauterine gestational sacs detected by ultrasound over the total number of embryos transferred