Clinical trial NCT00100269: Menevit Study: Menevit Anti-Oxidant Therapy for the Treatment of Male Infertility
Official title: A Randomized Control Trial of the Menevit Anti-Oxidant Therapy for the Treatment of Male Infertility
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infertility, Male
Oxidative Stress
Keywords: Male infertility
sperm
pregnancy
IVF (in vitro fertilisation)
oxidative stress
free radicals
DNA damage
Lead sponsor: Repromed
Sponsor class: OTHER
First posted: 2004-12-28
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Oxidative stress related damage to sperm is believed to be a major cause of male infertility. The object of the Menevit study is to investigate the role of a novel anti-oxidant preparation (Menevit) on sperm function, embryo quality and pregnancy rates in an in vitro fertilization (IVF) setting.

Detailed description: Men will be screened for oxidative stress (free radical) related damage to their sperm. This will include screening for lipid peroxidation of sperm using the LPO-586 assay, HOST test and for sperm DNA fragmentation using the Tunel technique. Those men found to have free radical related damage will be enrolled in a randomized control trial in which they will receive either the Menevit anti-oxidant or placebo (in a 2:1 randomization ratio respectively). The Menevit anti-oxidant is a capsule containing several different anti-oxidants, taken orally once per day. The placebo is identical in appearance and taste. After 3 months of Menevit/placebo the female partners of these men will undergo an IVF oocyte retrieval operation and embryo transfer. Pregnancy rates and embryo quality will be compared between groups. Changes in semen characteristics (count, motility, morphology, membrane integrity) and lipid peroxidation (LPO-586) plus sperm DNA fragmentation (Tunel assay) will be assessed at trial entry, 6 weeks and 3 months. Comparisons between the patients embryo quality in the IVF cycle immediately before and during the Menevit trial will also be compared when possible

Eligibility criteria: Inclusion Criteria:

* Evidence of oxidative stress to sperm on LPO-586 assay or poor HOST result or clinical evidence for oxidative stress (heavy smoker, varicocele, poor motility in the abscence of anti-sperm antibodies etc)
* Evidence of significant sperm DNA damage (25% or more DNA fragmentation as assessed by Tunel assay).
* Female partner willing to undergo IVF treatment within 3 months of starting Menevit trial

Exclusion Criteria:

* Female partner 40 years of age or older at trial entry.
* Significantly reduced ovarian reserve in female partner (day 3-5 FSH \> 10 iu/L if no prior IVF cycle or less than 5 oocytes on a prior IVF cycle.
* Sperm count below 0.5 million per ml (impossible to conduct all sperm function assays

Primary outcomes:
measure: Embryo quality (morphology score, progression to blastocyst rates, number of embryos available for freezing/transfer per cycle)
measure: Embryo quality is a good measure of pregnancy potential and is also an indicator of sperm DNA integrity, making it the ideal primary endpoint.
Secondary outcomes:
measure: sperm DNA fragmentation
measure: sperm count
measure: sperm motility (total motile sperm per ejaculate)
measure: sperm morphology
measure: sperm membrane integrity (as assessed by hypo-osmolar swelling test)
measure: levels of sperm lipid peroxidation (LPO-586 assay)
measure: retrospective comparison of embryo quality between the Menevit IVF cycle and the preceding non-Menevit IVF cycle.
measure: miscarriage rate (clinical and biochemical)
measure: clinical pregnancy rates (number of fetal hearts seen on first trimester scan)
measure: adverse side effects
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Repromed
state: South Australia
Study officials:
affiliation: Repromed, University of Adelaide
name: Kelton P Tremellen, MB BS (Hons) PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aitken RJ, Baker MA. Oxidative stress and male reproductive biology. Reprod Fertil Dev. 2004;16(5):581-8. doi: 10.10371/RD03089.
citation: Aitken RJ, Gordon E, Harkiss D, Twigg JP, Milne P, Jennings Z, Irvine DS. Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa. Biol Reprod. 1998 Nov;59(5):1037-46. doi: 10.1095/biolreprod59.5.1037.
citation: Benchaib M, Braun V, Lornage J, Hadj S, Salle B, Lejeune H, Guerin JF. Sperm DNA fragmentation decreases the pregnancy rate in an assisted reproductive technique. Hum Reprod. 2003 May;18(5):1023-8. doi: 10.1093/humrep/deg228.
citation: Henkel R, Hajimohammad M, Stalf T, Hoogendijk C, Mehnert C, Menkveld R, Gips H, Schill WB, Kruger TF. Influence of deoxyribonucleic acid damage on fertilization and pregnancy. Fertil Steril. 2004 Apr;81(4):965-72. doi: 10.1016/j.fertnstert.2003.09.044.
citation: Carrell DT, Liu L, Peterson CM, Jones KP, Hatasaka HH, Erickson L, Campbell B. Sperm DNA fragmentation is increased in couples with unexplained recurrent pregnancy loss. Arch Androl. 2003 Jan-Feb;49(1):49-55. doi: 10.1080/01485010290099390.
citation: Agarwal A, Nallella KP, Allamaneni SS, Said TM. Role of antioxidants in treatment of male infertility: an overview of the literature. Reprod Biomed Online. 2004 Jun;8(6):616-27. doi: 10.1016/s1472-6483(10)61641-0.
citation: Gomez E, Irvine DS, Aitken RJ. Evaluation of a spectrophotometric assay for the measurement of malondialdehyde and 4-hydroxyalkenals in human spermatozoa: relationships with semen quality and sperm function. Int J Androl. 1998 Apr;21(2):81-94. doi: 10.1046/j.1365-2605.1998.00106.x.