Male Fertility and Male Reproductive Health South/Sun_Room5_0830... · • Advised to do weekly...
Transcript of Male Fertility and Male Reproductive Health South/Sun_Room5_0830... · • Advised to do weekly...
Male Fertility and Male
Reproductive Health
Dr Sarah Wakeman
Medical Director Fertility Associates
Christchurch
FRANZCOG, CREI
Disclaimer
• Attendance paid for by Fertility Associates
Christchurch
- Medical Director of Fertility Associates
Christchurch
• Fertility Associates holds the public contract
for provision of tertiary fertility services for
Canterbury, Nelson Marlborough and West
Coast regions
Outline
• Impact of age on male fertility
• Impact of modern lifestyle on male fertility
• Are sperm counts really declining?
• Assessment of male fertility
• Newer tests and treatment options for men
with fertility problems
• Case studies
Male Age Does Not Matter
Male age and fertility
• Average age of having children is
increasing/has increased
– IN NZ in 2008 average age of father at birth of
child was 33 yrs, 4 yrs older than their own fathers
when they were born.
– 1/100 babies born in 2008 had a father over 50 yrs
– Backed by other data from overseas showing
older fathers – Germany, UK, US
Male age and fertility
• Effect of age on semen quality
– Auger et al 1995
• 2.6% dec in sperm concentration for each successive
year’s increase in age
• 0.6% dec in motility for each yr of age
• 0.9% dec in percentage of normal forms for each yr of
age
– Inconclusive as to whether a dec in sperm conc
with age, but is a dec in total sperm count
• Evidence of decrease semen volume with age
Male age and fertility
• Effect of age on semen quality
– Evidence of increased sperm DNA damage
• Evidence of increasing FSH levels and
decreasing testosterone levels with inc age
– Poor libido, fatigue, memory impairment
– More sexual dysfunction
– Less frequent sexual activity
Assessment of sperm DNA damage
• Higher levels of sperm DNA damage (cut off
of 30% often used)
– Longer time to pregnancy
– Lower chance of pregnancy
– Lower preg rates with IUI and IVF (but poss not
ICSI)
– Increased rate of pregnancy loss
– ? Increased rate birth defects
• We use SCSA = sperm chromatin structure
assay
Male age and fertility
• Effect of male age on reproductive success
– Some studies showing an effect
• Longer time to pregnancy esp with males older than 45
or 50 years
• Donor egg study (1023 men) showed poor outcomes for
men over 50 yrs
– Some studies showing no effect
• Donor egg study (558) cycles – no effect of male age
– Several studies showing an effect only when
female partner 35 or older
Male age and fertliity
• Effect of age on health of children
– Evidence of an increase in a number of genetic
syndromes (most rare)
– Thought that as men age and have repeated
cycles of spermatogenesis, results in more
spontaneous de novo mutations
– Many of these mutations are of single base pairs
and less likely to be detected and repaired by
DNA repair mechanisms in the germ cells
• Eg achondroplasia – single base pair mutation in FGFR3
gene
Male age and fertility
• Effect of male age on health of children
– Some evidence for increased pregnancy
complications
• Pre-term labour
• PET
• Abruption, placenta praevia
• Stillbirth
Impact of modern lifestyle on male
fertility
• More sedentary
• More obesity
• Exposure to phalates and other
environmental chemicals
• Parenting at older ages
Impact of modern lifestyle
• Smoking – bad for sperm
– Difficult in studies to separate out effect of female
smoking
– Decreases in sperm count, motility and
morphology – these don’t always translate into
lower pregnancy rates
– Reduced anti-oxidant capacity of semen
Impact of modern lifestyle
• Alcohol
– Very high intake – decreased libido and semen
volume, testicular atrophy
• Heat
– Saunas, laptops, prolonged cycling
• Weight
– Increased BMI and waist circumference assoc
with reduced semen volume and total sperm
concentration and inc sperm DNA damage
Are sperm counts decreasing?
• Ie is male fertility decreasing,
regardless of age?
Are sperm counts decreasing?
• Number of studies to show a decrease in
sperm counts over time
– US, Europe, Australia
• Also a number of studies to show no
decrease in sperm counts over time
– In total more than 100000 men included in studies
showing no decrease cp to 70-80000 in studies
showing a decrease
Are sperm counts decreasing?
• Increased incidence of testicular cancer,
cryptorchidism, hypospadias in some
countries (eg Denmark)
– Testicular dysgenesis syndrome (TDS) – above
and poor semen quality
• Theories/concern about increased
environmental estrogen exposure and other
environmental pollutants causing this
– Endocrine disruptors
– E may suppress FSH in fetus/young children and
result in less Sertoli cell development in the testis
Are sperm counts decreasing?
• 2 most recent reviews = NO
– Pastuszak et al Asian Journal Andrology 2013
– Coccuzza et al Scientific World Journal 2014
Causes of Infertility – Male
• Genetic
• Developmental
• Physical injury
• Chemicals / hormones
• Medical
• Infection
• Lifestyle factors
• Raised body temperature
Assessment of male fertility
• History
– Previous paternity
– Testicular surgery or injury
– STIs
– Hernia repair
– Sexual function
– General health – BMI, exercise, lifestyle
Assessment of male fertility
• Examination
– BMI
– Chance to check BP etc…
– Testis volume and consistency, presence of vas,
epididymis
Assessment of male fertility
• Semenalysis
– IF ABNORMAL REPEAT
• Swabs/urine for STIs if appropriate
Semen analysis
• WHO 2010 criteria
– Values taken from SAs of 4500 men across 14
countries
• At least 1800 were fertile meaning time to pregnancy of
female partner of less than 12 months
– Reduction in percentage normal sperm required
for “normal” sample, and in sperm count
– Up to 15% men previously classified as abnormal,
now normal
WHO Standard(World Health Organisation)
15 million / ml
FA Semen analysis - (Original signed copy with Lab)
Number of days since last ejaculation: 0.5
All ejaculate collected: Yes
Sample collected by: Masturbation
Semen collected at: Clinic
Have you had any significant health issues in the last 3 months: No
Consent for partner to receive results: Yes
Semen sample
Date 18/06/14
Analyst CTIN
Time to analysis 15 min
Reference Range
Viscosity 2 (1-4)
2
Volume 0.6 ml
> 1.5 ml
Sperm conc 92 M/ml
> 15 m/ml
Total motility 60 %
> 40%
Progressive motility 55 %
> 32%
Rapid 49 %
Slow 6 %
Non-progressive 5 %
Conc. Of Motile 55 M/ml
# motile 33 M
Con non-sperm M/ml
<1M/ml
Sperm MAR binding0 % NEGATIVE >50% positive
Morphology of motile sperm 4+ % Normal (wetslide)
Comments:
Assessment of male fertility
• Specialist level tests
– Test of sperm DNA fragmentation SCSA
– For severe oligospermia
• FSH, testosterone
• Karyotype
• Y chromosome microdeletion testing
– For azoospermia – depending on obstructive/non-
obstructive
• Above
• CF gene mutations (CBAVD)
Assessment of male fertility
• Azoospermia
– Diagnostic testicular biopsy
– If sperm found frozen for IVF with ICSI
– Histology
Treatment options for male infertility
• Optimise lifestyle
• Frequent ejaculation
• Menevit/antioxidants
• ? Varicocele repair
• Vasectomy reversal
• IVF with ICSI
• IMSI
• PICSI
• Donor sperm
Treatment options - lifestyle
• Address smoking, weight, inactivity
• Decrease heat stress to testes
• Frequent ejaculation can improve sperm
quality
Treatment options – antioxidants
• Oxidative stress
– Proposed mechanism for deterioration of cells and
tissues with aging
• Antioxidants protect cells against free-radical
induced damage
– Vit C, E etc are anti-oxidants
• Oxidative stress causes sperm DNA damage
– Sperm very susceptible as lots of polyunsaturated
fatty acids on plasma membrane
– Seminal plasma should be rich source of
antioxidants to protect sperm
Treatment options - antioxidants
• More than 25% of infertile men have high
levels of semen ROS
• Reducing smoking, heat stress, varicocele,
infection will dec oxidative stress
• Oral antioxidants should help free radical
scavenging capacity of semen
• Some study evidence to show antioxidants
improve semen parameters and dec
percentage sperm DNA damage in infertile
men - studies not perfect
Treatment options for male infertility
• Varicocele repair
• 2011 meta analysis (Bazeem et al)– 4 RCTS,
non-signif inc in preg rate after repair, signif
increase in sperm conc and motility.
• Cochrane review 2012 – similar findings.
Repair MAY improve chance of pregnancy,
and does improve semen parameters
Treatment options for male infertility
• Vasectomy reversal
– Success time dependent
• If less than 3 yrs 90% sperm in ejaculate
• If 5 yrs 70% sperm in ejaculate
• If 10 yrs 50% sperm in ejaculate
• About 2/3 of those with sperm in ejaculate will achieve
pregnancy
– After 10 years perhaps IVF better option
– Microsurgical
– Female partner should be assessed too
Treatment options for male infertility
• IVF with ICSI
– Female partner has ovaries stimulated and eggs
collected
– A single sperm is selected for injection in to each
egg
Intra-Cytoplasmic Sperm Injection (ICSI)
• A single sperm is
injected directly into
each mature oocyte
• Male factor infertility
or previous
poor/failed fertilisation
with conventional IVF
insemination
IMSI
• What is it?
• Much higher magnification to select sperm for
ICSI
– ICSI sperm magnified 200-400x
– IMSI sperm magnified >6300x
• With IMSI can see sperm morphology in more
detail especially sperm head vacuoles.
• Evidence of improved outcomes for couples
with previous poor icsi outcome
PICSI
• What is it?
– A test of sperm function, hyaluronan binding.
- Hyaluronan is a high molecular weight
glycosaminoglycan and is a major component of the
cumulus oophorus matrix surrounding the human
oocyte.
– Developmentally mature sperm bind to hyaluron
– Evidence of a lower rate of miscarriage after
sperm chosen using PICSI (for ICSI)
Case
• TR and SC
– TR 38 yrs, SC 32 yrs
– S GOPO TTC >5 yrs, irregular cycles, past
chlamydia, ex-smoker, AMH 37.5, Hep C pos
– T – ex-smoker, 2 SAs <0.1mill per ml
• Testes 7-10ml bilat and soft
– Raised FSH (27), normal testo
– Rpt SA reported same but phone call to lab =
azoospermia
– Testicular biopsy – Sertoli cell only pattern
Case
• KE (35yrs) and CS (37 yrs)
– GOPO, no contraception 7 yrs
– K well, reg pds
– C, daily marajuana use, discomfort L testis at
times, testes 15-20ml bilat, ? Vas absent
bilaterally, L varicocele
– 2x SA = azoo
• C – FSH and testo normal, CF gene mutation
consis with CBAVD
– Testic biopsy – sperm found and frozen
Case continued
• K – CF gene mutation testing – carrier.
• Plan – IVF with ICSI using sperm retrieved
from testes and PGD
– Also referred to urologist for consideration of
repair of varicocele.
Case
• JL (38)and KL(53)
– Son born 2010, 5/12 TTC, term SVD
– 2011 14/40 TOP for multiple abnormalities, 6/12
TTC
– Total 27/12 TTC
– J reg periods and well
– K well. One episode painful ejaculation
• 2 x SA azoospermia
• Testes 20-25 ml bilat
– USS testes – small epididymal cyst
Case continued
• Urology referral – nil to do
• Testicular biopsy – sperm found and
histology = normal spermatogenesis
• Very early miscarriage occurred soon after
• Further SA = azoo
• IVF cycle
– Good response, 2 embryos transferred day 5, not
pregnant (testicular biopsy sperm used as nil in
ejaculate)
Case continued
• Advised to do weekly semen samples until
ready to do next IVF cycle
– 1st sample sperm in ejaculate, frozen, ICSI quality
• 2nd IVF cycle
– Good response, SET day 5 and 3 embryos frozen
– Currently 10/40 pregnant
Questions and comments