Varicocele Repair for Men Undergoing IVF/ICSI (Varicocele)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Infertility, Male
• Intervention / Treatment: Procedure: varicocelectomy

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 Type: Interventional
• Enrollment (Anticipated): 2000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mohamed Fawzy, Ph.D; Phone Number: +201011122286; Email: drfawzy001@me.com
• Study Contact Backup: Name: Yasmin Magdi; Phone Number: +201282313979; Email: Yas.magdi@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: varicocelectomy arm; 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; microsurgical subinguinal varicocelectomy; Other Names: varicocele repair
No Intervention: Control (No varicocelectomy) arm; Couples with male-factor infertility and males were diagnosed clinically with varicocele will undergo ICSI

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Al-Yasmeen Fertility and Gynecology Center
• Collaborators: Banon IVF Center Assiut, Egypt; Elite Fertility and Gynecology Center, Cairo, Egypt; IbnSina IVF Center, Sohag, Egypt; Qena IVF Centre, Qena, Egypt; Amshaj IVF Center
• Investigators: Study Director: Mohamed Fawzy, Ph.D, IbnSina IVF Center, IbnSina Hospital, Sohag

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: October 11, 2020
• First Submitted That Met QC Criteria: October 28, 2020
• First Posted (Actual): October 29, 2020

Study Record Updates

• Last Update Posted (Actual): October 29, 2020
• Last Update Submitted That Met QC Criteria: October 28, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Infertility; Infertility, Male; Varicocele
• Other Study ID Numbers: 008-2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: 3-6 months
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No