Varicocele Repair for Men Undergoing IVF/ICSI

Study Overview
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Brief Summary
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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
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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.

Official Title
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Varicocele Repair for Infertile Men Undergoing IVF/ICSI: a Parallel, Two-group, Randomized Trial

Conditions
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Infertility, Male

Intervention / Treatment
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* Procedure: varicocelectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Couples able to provide informed consent. Couples with at least 12 months of infertility Couples with male-factor infertility Couples counseled for ICSI procedure by reproductive specialist. Couples undergoing their first ICSI cycle or their second ICSI cycle after a previously successful treatment. 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). 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: Patients who willing to undergo ICSI with preimplantation genetic diagnosis. 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. 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. Abnormal karyotyping for female or male partners. Uncontrolled diabetes, liver or renal disease, history of malignancy or borderline pathology of male or female partners. Previous participation in the trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: varicocelectomy arm<br>The varicocelectomy procedure will be performed three months before ICSI for men with with male-factor infertility and were diagnosed clinically with varicocele | Procedure: varicocelectomy<br>* microsurgical subinguinal varicocelectomy<br>* Other names: varicocele repair;|
| No Intervention: Control (No varicocelectomy) arm<br>Couples with male-factor infertility and males were diagnosed clinically with varicocele will undergo ICSI | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Livebirth rate | the percentage of women who underwent randomization and will have a livebirth after at least 37 completed weeks of gestation | up to 37 weeks | 

Secondary Outcome Measures

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