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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