Download Can We Prevent or Reverse Male Infertility?

www.uconnfertility.com
An academic affiliate of UCONN School of Medicine
John Nulsen, MD
Claudio Benadiva, MD, HCLD
David Schmidt, MD
Lawrence Engmann, MD, MRCOG
Andrea DiLuigi, MD
Can We Prevent or Reverse Male Infertility?
By Stanton Honig, MD
Male factor infertility accounts for approximately 50%
of all infertility. For this reason, evaluation and treatment of the male is critical to a comprehensive program for the infertile couple. Because there are many
treatable, reversible and preventable causes of male
factor infertility, early evaluation and treatment is
very important.
In 1994, Drs. Honig, Jarow and Lipshultz reported the
incidence of significant medical pathology associated
with the evaluation and treatment of male factor infertility. In 1% of patients, a significant medical condition, sometimes life-threatening (such as a cancer of
the testis, brain or spinal cord tumor) caused male
infertility. Subsequent studies have shown a significantly higher incidence of testis cancer in infertile
men despite variable semen quality. Early intervention
was crucial to treat the life-threatening condition and
improve the couple’s overall chance of conceiving.
We believe that early evaluation of the male should include a semen analysis and, if abnormal, an early consultation with a urologist well-trained in male infertility
disorders. This should occur before or in conjunction
with assisted reproductive technologies.
Interestingly, new data suggest that testis cancer can
CAUSE infertility, CAN BE FOUND on a male infertility evaluation and patients with male factor infertility
have an OVERALL HIGHER CANCER RISK than the
general population!
What can be done as “preventive medicine”
for male factor infertility?
Prevention starts with avoiding lifestyle issues that
may be detrimental to sperm quality. Acquired causes
of male infertility include exposure to toxins such as illicit drugs (marijuana, cocaine, anabolic steroids, etc.),
heavy alcohol use, cigarette smoking, medications
and excessive heat to the scrotal area.
It is becoming increasingly clear that recreational
drugs can have an adverse effect on the testes and
sperm quality. Chronic marijuana use may lower
testosterone levels and affect sperm quality. This has
become more of a problem since laws requiring marijuana use have loosened. Cocaine has been shown to
have direct effects on germ cell apoptosis, and may
affect sperm concentration, motility and DNA integrity. Anabolic steroids used for bodybuilding clearly
have direct effects on the testis through lowering the
body’s ability to make its own testosterone. It also
decreases spermatogenesis and azoospermia, which
06/2016
is sometimes irreversible. Education of high school
and college students regarding the negative impact of
anabolic steroids and other recreational drugs is critical to prevent male fertility problems down the road.
Cigarette smoking and heavy alcohol use have been
shown in clinical and research studies to affect hormone levels, as well as direct toxic effects on the testicle. Basic science data has shown increased testicular
apoptosis when exposed to environmental toxins.
Many medications used for treatment of unrelated
medical conditions may have negative effects on
sperm quality, as well. It is the job of the reproductive specialist to educate physicians and the public
on these effects. Some medications that may affect sperm quality are testosterone, calcium channel blockers for high blood pressure, sulfasalazine
(Crohn’s disease-bowel disease), cyclosporine (organ
transplants) and chemotherapy for cancers or rheumatologic disease.
Many of these medications can be interchanged with
similar drugs that have less toxic side effects. For
example, we have seen a MAJOR increase in the use
of testosterone in men of reproductive age. This has
been driven by the sense that testosterone will bring
“the fountain of youth”. Unfortunately, this “overuse”
in men has resulted in lowering of sperm counts, in
some cases to zero. Luckily, most of the time, this is
reversible. In addition, there are other medications
that can increase testosterone via the hypothalamic
pituitary axis that can be utilized instead to improve
libido, sexual function, energy level, etc. With high
blood pressure, it appears that calcium channel
blocker medication may directly affect the sperm’s
ability to bind to egg receptors. Switching to a different medication may remove this risk. In irritable bowel
disease, mesalazone may be substituted for sulfasalazine having less reproductive side effects with similarly good disease control results.
Chemotherapy for cancer and other chronic diseases
(like rheumatoid arthritis, renal disease, autoimmune
illnesses) can also affect sperm quality. Important
considerations include freezing sperm prior to starting
any toxic drug regimens and using the least toxic chemotherapy regime with equal survival results. Younger
males with prostate cancer should be asked about future fertility interests prior to definitive therapy. Radical prostatectomy, radiation therapy and hormone
deprivation therapy have specific deleterious effects
on spermatogenesis and/or sperm transport.
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Occupational exposure to toxins may also affect
sperm quality. Agents like pesticides, cadmium, lead
and manganese may interfere with reproductivity, so
checking and removing work exposures is important.
Direct heat to the testis can be a major cause of diminished sperm quality and male infertility. Varicoceles
are one of the most common, treatable and reversible
causes of male factor infertility. Although the exact
mechanism of how varicoceles affects sperm quality
is not known, it is believed that this is usually through
an increased heat effect. Multiple studies have shown
that scrotal temperature is increased in patients with
varicoceles. Varicocele repair has been shown to improve sperm concentration, motility, morphology and
DNA integrity. Minimally invasive ligation of varicoceles
can significantly improve the chances of pregnancy
as compared to natural intercourse. In varicoceleassociated infertility, multiple studies have shown that
it is more cost effective to perform varicocele repair
as compared to going directly to IVF/ICSI in moderate male factor infertility cases. In addition, varicocele
repair may upgrade semen quality to allow couples to
proceed with less invasive/less costly hyperstimulation/IUI as opposed to going directly to IVF/ICSI.
External heat effects on the testis may affect semen
quality as well. We recommend abstinence of hot tub
use or lowering the temperature to 97 degrees (same
as scrotal temperature). Conventional lay information
regarding types of underwear is vastly overplayed. Scientific studies have shown that there is no difference in
sperm quality between boxer shorts and briefs.
Coital factors are extremely important in achieving
pregnancy. Although timing intercourse with ovulation
may be tedious, it is critical with male factor patients.
Timing with basal body temperature or ovulation
predictor kits is extremely useful to determine approximate timing of intercourse. Intercourse every 24-48
hours around the time of ovulation is critical to achieving pregnancy naturally. Some patients maintain good
semen parameters despite frequent ejaculation, and in
these patients, intercourse every 24 hours or so may
be beneficial. In addition, avoidance of spermatoxic
lubricants such as K-Y jelly, surgilube and lubrifax, is
important. A natural lubricant, such as “Replens” or
“Pre-seed”, may be substituted and is not sperm toxic.
Are vitamins and supplements helpful?
Scientific data is quite mixed. Some supplements used
for other reasons (depression, memory loss, “prostate
health”) may affect semen quality, while others have
been studied to determine if they’ll improve semen
quality in patients with male infertility. Below are vitamins and supplements that are recommended:
Vitamin C 500-1000 mg/daily
Carnitine and/or L-acetyl carnitine
Vitamin E 3gms/daily
400 -800 iu/daily
There is a large amount of literature evaluating the
effects of antioxidant vitamins (C and E) on sperm.
These studies have been performed on patients taking
these vitamins by mouth as well as mixing them with
semen. It appears clear that some male factor patients have an increase in “reactive oxygen species” or
oxidants in their semen. Reactive oxygen species may
have affects both directly on the sperm and indirectly
on the sperm environment. Vitamins C and E are antioxidants and may serve to lower the level of reactive
oxygen species and, therefore, negate its deleterious
effects. Many of these studies suffer from being non
randomized, non placebo controlled studies, so definitive conclusions are difficult to ascertain.
Carnitine appears to play an important role in both the
function of the epididymis and possibly in sperm energy/motility. Some studies from Italy have suggested
some benefit in using this supplement (mostly with improvement in sperm motility), with no significant side
effects. We recommend 3gms of carnitine and L-acetyl
carnitine. Be careful with supplements that claim they
are “Male Fertility Supplements”, as they may contain
only tiny amounts of the recommended supplements.
Most other supplements (such as zinc, selenium, folate,
coenzyme Q-10) are not necessary if a balanced diet is
maintained, since most are present in healthy foods.
Not all nutritional supplements are good for sperm.
Saw palmetto may have a negative effect on sperm
production and ejaculate volume. It is thought that
saw palmetto lowers levels of dihydrotestosterone
(DHT), which is thought to be important for sperm
production and ejaculation. Studies on the effects of 1
mg of finasteride (Propecia-for male pattern baldness)
showed no negative effects on sperm quality. Saw palmetto may work similar to a higher dose of this drug
used for benign prostate enlargement. It would be my
recommendation that any patient trying to achieve a
pregnancy stop using saw palmetto until further studies show that there are no deleterious effects.
Summary
Preventive medicine has an important role in male
factor infertility. A thorough evaluation and physical
examination by a physician familiar with male infertility
is important to identify treatable, reversible and potentially life-threatening medical conditions. In addition, modification of lifestyle behaviors, and avoiding
toxic recreational drugs such as anabolic steroids may
improve chances of pregnancy. Avoiding supplements
that may negatively affect male infertility and using
other vitamins and supplements that may positively
impact male fertility related disorders are important to
consider, as well.
Patients should ask their physicians and seek out
organizations like RESOLVE, the American Society for
Reproductive Medicine (www.asrm.org), The Society
for the Study of Male Reproduction (www.ssmr.org),
American Urological Association (www.urologyhealth.
org/urologic-conditions/male-infertility), and path2parenthood (www.path2parenthood.org/library/category/male-reproductive-health-1.
Dr. Honig works closely with The Center for Advanced Reproductive Services and is a Clinical Professor of Surgery in the Department of Urology
at UConn Health. He is also the Director of Men’s Health and a full time faculty member at Yale University Department of Urology. Dr. Honig sees
patients in New Haven, the Shoreline and in Farmington. He can be reached at 203-789-2222 or 860-679-4100. Find the series–Urology Nerds
Drinking Beer, a webseries about Men’s Health issues at http://www.path2parenthood.org/library/category/male-reproductive-health-1.