IVF Outcomes After Varicocele Repair

NCT ID: NCT03090438

Last Updated: 2017-03-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-31

Study Completion Date

2021-05-31

Brief Summary

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Infertility has been estimated to affect from 6-18% of couples trying to conceive. In 20-30% of cases, the problem is with the male. Varicocele is a common cause of male factor infertility (MFI) being responsible for 30-35 % of primary and 69-81 % of secondary MFI. Varicocele repair has been shown to improve sperm parameters and increase natural pregnancy rates and the results of assisted reproductive techniques (ART).

There are two possible treatment pathways for varicocele associated male factor infertility. 1) standard IVF/ICSI 2) varicocele repair followed by IVF/ICSI if there is no spontaneous pregnancy. There is however no consensus as to which pathway is preferable and no randomized comparative studies have been carried out.

IVF/ICSI is a standard treatment for infertility but frequently requires repeated treatments to achieve a live birth. The purpose of this study is to determine if the improved sperm parameters caused by prior treatment of the varicocele will result in improvements both in overall pregnancy/birth rates and in IVF/ICSI results.

Detailed Description

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A varicocele is an abnormal dilation of the pampiniform plexus caused by incompetence of the valves in the internal spermatic vein. Varicocele has a prevalence of 10-15 % in the general population and is a common cause of male infertility, being present in 30-35% of men with primary, and 69-81% of men with secondary infertility. There is more than one approach to the treatment of varicocele associated MFI One common approach is to treat by assisted reproductive techniques (ART). Patients with a total motile sperm count of \<10 million sperm are usually treated by IVF with or without ICSI. Fertilization of oocytes may be accomplished by isolating even a single adequate spermatozoa in the laboratory bypassing the majority of semen quality inadequacies in male factor infertility. The results of this treatment using fresh embryos with a maternal age of\<35 are 46% pregnancies and 40% live births per cycle.

Alternatively, varicocele associated MFI can be treated by repairing the varicocele to improve sperm quality. Occlusion of the spermatic veins by surgical and radiological methods is commonly performed in these circumstances to improve fertility. A large body of literature exists demonstrating post-treatment improvements in semen parameters and sperm DNA quality as well as improved spontaneous pregnancy rates compared to no treatment. There are also studies demonstrating improved results of ART after varicocele repair.

Both approaches have their advocates. ART often provide a relatively quick result and have a known excellent track record for both pregnancy and live birth rates. Unfortunately, these techniques are not without risks such as ovarian hyperstimulation syndrome and procedural complications. Multiple pregnancies are common with increased risk of premature labour and low birth weight. In addition the treatments are expensive and multiple treatments increase the financial burden on the health care system.

Varicocele occlusion is a minor procedure. If performed radiologically, there is often immediate return to normal activity. The complication rate is very low, mostly due to radiological contrast medium allergy. Modern equipment and careful technique enable the procedure to be completed with very low radiation doses that are well below the level proven to have any adverse biological effect.

If varicocele repair can be demonstrated to improve pregnancy outcomes in varicocele related MFI by spontaneous pregnancies or by improving pregnancy and live birth rates per ART implantation, then there are compelling health care and economic reasons for incorporating it as an initial treatment.

At present there have been no well constructed randomized trials to compare the outcomes of these two approaches.

Conditions

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Infertility, Male Varicocele In Vitro Fertilization

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Varicocele embolization before IVF

Participants will have catheterization and embolization of varicoceles six months before beginning IVF

Group Type ACTIVE_COMPARATOR

Varicocele embolization

Intervention Type PROCEDURE

Ultrasound guided right internal jugular vein access with placement of a vascular sheath. Fluoroscopically guided selective catheterization of the left and right (if bilateral) spermatic veins to the level of the inguinal ligament. Occlusion of the spermatic vein(s) by embolization coils and a sclerosing agent (sodium tetradecyl sulphate 3%).

IVF without varicocele embolization

Participants will proceed from enrollment directly to IVF

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Varicocele embolization

Ultrasound guided right internal jugular vein access with placement of a vascular sheath. Fluoroscopically guided selective catheterization of the left and right (if bilateral) spermatic veins to the level of the inguinal ligament. Occlusion of the spermatic vein(s) by embolization coils and a sclerosing agent (sodium tetradecyl sulphate 3%).

Intervention Type PROCEDURE

Other Intervention Names

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Varicocele repair Varicocele occlusion

Eligibility Criteria

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Inclusion Criteria

Patient complies to varicocele treatment indications as per ASRM 2014 guidelines

1. Palpable varicocele on physical exam
2. The female partner has normal fertility or a potentially treatable cause of infertility
3. Male has abnormal semen parameters

Age of female partner \< 35 years

Exclusion Criteria

Sub-clinical varicocele

Isolated teratospermia
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Shaare Zedek Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Anthony G Verstandig, MD

Role: PRINCIPAL_INVESTIGATOR

C

Ruth Ronn, MD

Role: PRINCIPAL_INVESTIGATOR

V

Central Contacts

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Anthony G Verstandig, MD

Role: CONTACT

972 508685879

Ruth Ronn, MD

Role: CONTACT

972 549964878

References

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Gorelick JI, Goldstein M. Loss of fertility in men with varicocele. Fertil Steril. 1993 Mar;59(3):613-6.

Reference Type BACKGROUND
PMID: 8458466 (View on PubMed)

Agarwal A, Deepinder F, Cocuzza M, Agarwal R, Short RA, Sabanegh E, Marmar JL. Efficacy of varicocelectomy in improving semen parameters: new meta-analytical approach. Urology. 2007 Sep;70(3):532-8. doi: 10.1016/j.urology.2007.04.011.

Reference Type BACKGROUND
PMID: 17905111 (View on PubMed)

Diegidio P, Jhaveri JK, Ghannam S, Pinkhasov R, Shabsigh R, Fisch H. Review of current varicocelectomy techniques and their outcomes. BJU Int. 2011 Oct;108(7):1157-72. doi: 10.1111/j.1464-410X.2010.09959.x. Epub 2011 Mar 24.

Reference Type BACKGROUND
PMID: 21435155 (View on PubMed)

Verstandig AG, Shamieh B, Shraibman V, Raveh D. Radiation dose reduction in fluoroscopic procedures: left varicocele embolization as a model. Eur Radiol. 2015 Jun;25(6):1639-45. doi: 10.1007/s00330-014-3556-4. Epub 2014 Dec 19.

Reference Type BACKGROUND
PMID: 25523457 (View on PubMed)

Esteves SC, Roque M, Agarwal A. Outcome of assisted reproductive technology in men with treated and untreated varicocele: systematic review and meta-analysis. Asian J Androl. 2016 Mar-Apr;18(2):254-8. doi: 10.4103/1008-682X.163269.

Reference Type BACKGROUND
PMID: 26510504 (View on PubMed)

Kim KH, Lee JY, Kang DH, Lee H, Seo JT, Cho KS. Impact of surgical varicocele repair on pregnancy rate in subfertile men with clinical varicocele and impaired semen quality: a meta-analysis of randomized clinical trials. Korean J Urol. 2013 Oct;54(10):703-9. doi: 10.4111/kju.2013.54.10.703. Epub 2013 Oct 15.

Reference Type BACKGROUND
PMID: 24175046 (View on PubMed)

Schauer I, Madersbacher S, Jost R, Hubner WA, Imhof M. The impact of varicocelectomy on sperm parameters: a meta-analysis. J Urol. 2012 May;187(5):1540-7. doi: 10.1016/j.juro.2011.12.084. Epub 2012 Mar 14.

Reference Type BACKGROUND
PMID: 22425089 (View on PubMed)

Li F, Yamaguchi K, Okada K, Matsushita K, Ando M, Chiba K, Yue H, Fujisawa M. Significant improvement of sperm DNA quality after microsurgical repair of varicocele. Syst Biol Reprod Med. 2012 Oct;58(5):274-7. doi: 10.3109/19396368.2012.692431. Epub 2012 Jul 2.

Reference Type BACKGROUND
PMID: 22979920 (View on PubMed)

The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. World Health Organization. Fertil Steril. 1992 Jun;57(6):1289-93.

Reference Type BACKGROUND
PMID: 1601152 (View on PubMed)

Other Identifiers

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SZMCvarivf

Identifier Type: -

Identifier Source: org_study_id

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