Clinical trial NCT04608864: Varicocele Repair for Men Undergoing IVF/ICSI
Official title: Varicocele Repair for Infertile Men Undergoing IVF/ICSI: a Parallel, Two-group, Randomized Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Infertility, Male
Lead sponsor: Al-Yasmeen Fertility and Gynecology Center
Sponsor class: OTHER
Collaborators: name: Elite Fertility and Gynecology Center, Cairo, Egypt
name: Banon IVF Center Assiut, Egypt
name: IbnSina IVF Center, Sohag, Egypt
name: Qena IVF Centre, Qena, Egypt
name: Amshaj IVF Center
First posted: 2020-10-29
Enrollment: 2000
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Livebirth rate
timeFrame: up to 37 weeks
Secondary outcomes:
measure: Biochemical pregnancy
timeFrame: up to 2 weeks
measure: Clinical pregnancy
timeFrame: up to 7 weeks
measure: Ongoing pregnancy
timeFrame: up to 20 weeks
measure: Miscarriage
timeFrame: up to 20th weeks
measure: stillbirth
timeFrame: up to 20 weeks
measure: Fertilization rate
timeFrame: up to 16-18 hours after ICSI
measure: Top quality embryos
timeFrame: up to 3 days after ICSI
measure: cryopreservation rate
timeFrame: up to 3-6 days after ICSI
measure: Blastocyst formation rate
timeFrame: up to 5 or 6 days after ICSI
measure: implantation rate
timeFrame: up to 7 weeks
Other outcomes:
Locations:
Study officials:
affiliation: IbnSina IVF Center, IbnSina Hospital, Sohag
name: Mohamed Fawzy, Ph.D
role: STUDY_DIRECTOR
References:
citation: Kohn TP, Kohn JR, Pastuszak AW. Varicocelectomy before assisted reproductive technology: are outcomes improved? Fertil Steril. 2017 Sep;108(3):385-391. doi: 10.1016/j.fertnstert.2017.06.033.
citation: Kirby EW, Wiener LE, Rajanahally S, Crowell K, Coward RM. Undergoing varicocele repair before assisted reproduction improves pregnancy rate and live birth rate in azoospermic and oligospermic men with a varicocele: a systematic review and meta-analysis. Fertil Steril. 2016 Nov;106(6):1338-1343. doi: 10.1016/j.fertnstert.2016.07.1093. Epub 2016 Aug 12.
citation: Practice Committee of the American Society for Reproductive Medicine; Society for Male Reproduction and Urology. Report on varicocele and infertility: a committee opinion. Fertil Steril. 2014 Dec;102(6):1556-60. doi: 10.1016/j.fertnstert.2014.10.007. Epub 2014 Nov 25.