Download Infertility

Dr. Mohammed Bassil
Definition of infertility
 Failure of conception after at least 12 months of
unprotected intercourse. The chance of a normal
couple conceiving is estimated at 20%-25% per month,
75% by 6 months, and 90% at 1 year.
 Epidemiology
 Up to 50% of infertility is due to male factors. Up to
25% of couples may be affected at some point in their
reproductive years.
Pathophysiology
 Failure of fertilization of the normal ovum due to
defective sperm development, function, or inadequate
numbers. There may be abnormalities of morphology
(teratospermia), motility (asthenospermia), low sperm
numbers
(oligospermia),
or
absent
sperm
(azoospermia). Abnormal epididymal function may
result in defective spermatozoa maturation or
transport, or induce cell death
Etiology
•Idiopathic (25%)
•Varicocele (present in 40%)
•Cryptorchidism (undescended testes)
•Functional sperm disorders: immunological infertility
(sperm antibodies); head or tail defects; Kartagener's
syndrome (immotile cilia); dyskinetic cilia syndrome
•Erectile or ejaculatory problems
•Testicular injury: orchitis (post-pubertal, bilateral mumps
orchitis); testicular torsion; trauma; radiotherapy
Etiology
 Endocrine disorders: Kallmann's syndrome (isolated
gonadotrophin deficiency causing hypogonadism);
Prader–Willi syndrome (hypogonadism, short
stature, hyperphagia, obesity); pituitary gland
adenoma, radiation, or infection.
 Hormone excess: excess prolactin (pituitary tumour);
excess androgen (adrenal tumour, congenital adrenal
hyperplasia, anabolic steroids); excess oestrogens
Etiology
•Genetic disorders: Kleinfelter's syndrome (47XXY) involves
azoospermia, ↑ FSH/LH and ↓ testosterone; XX male;
XYY syndrome
•Male genital tract obstruction: congenital absence of vas
deferens; epididymal obstruction or infection; M‫أ‬ullerian
prostatic cysts; groin or scrotal surgery
•Systemic disease: renal failure; liver cirrhosis; cystic
fibrosis
•Drugs: chemotherapy; alcohol; marijuana; sulphasalazine;
smoking
•Environmental factors: pesticides; heavy metals; hot baths
History
•Sexual: duration of problem; frequency and timing of
intercourse; previous successful conceptions; previous
birth control; erectile or ejaculatory dysfunction.
•Developmental: age at puberty; history of
cryptorchidism; gynaecomastia.
•Medical and surgical: detailed assessment for risk
factors—recent febrile illness; post-pubertal mumps
orchitis; varicocele; testicular torsion, trauma, or
tumour; sexually transmitted diseases; genitourinary
surgery; radiotherapy; respiratory diseases associated
with ciliary dysfunction; diabetes.
History
•Drugs and environmental: previous chemotherapy;
exposure to substances which impair spermatogenesis or
erectile function; alcohol consumption; smoking habits;
hot baths.
•Family: hypogonadism; cryptorchidism.
Examination
Perform a full assessment of all systems, with attention to general
appearance (evidence of secondary sexual development; signs of
hypogonadism; gynaecomastia). Urogenital examination should
include assessment of the penis (Peyronie's plaque, phimosis,
hypospadias); measurement of testicular consistency, tenderness,
and volume with a Prader orchidometer (normal >20ml; varies with
race); palpate epididymis (tenderness, swelling) and spermatic
cord (vas deferens present or absent, varicocele); digital rectal
examination of prostate.
Investigation of male infertility
Basic investigations
Semen analysis 2 or 3 specimens over several weeks, collected after
3-7 days of sexual abstinence. Deliver specimens to the laboratory
within 1h. Ejaculate volume, liquefaction time, and pH are noted .
Microscopy techniques measure sperm concentration, total
numbers, morphology, and motility. The mixed agglutination
reaction (MAR test) is used to detect antisperm antibodies. The
presence of leucocytes (>1 /106 —‫أ‬ml of semen) suggests infection,
and cultures should be requested.
Hormone measurement Serum FSH, LH, and testosterone. In cases
of isolated low testosterone level, it is recommended to test
morning and free testosterone levels. Raised prolactin is associated
with sexual dysfunction, and may indicate pituitary disease.
Investigation of male infertility
Special investigations
Chromosome analysis
Indicated for clinical suspicion of an abnormality
(azoospermia or oligospermia, small atrophic testes with
↑ FSH).
Testicular biopsy
Performed for azoospermic patients, to differentiate
between idiopathic and obstructive causes. May also be
used for sperm retrieval.
Investigation of male infertility
Sperm function tests
•Post coital test: cervical mucus is taken just before ovulation,
and within 8 hours of intercourse, and microscopy performed.
Normal results shows >10 sperm per high-powered field, the
majority demonstrating progressive motility. Abnormal results
indicate inappropriate timing of the test; cervical mucus antisperm
antibodies; abnormal semen; inappropriately performed coitus.
•Sperm penetration test: a sample of semen is placed directly
onto pre-ovulatory cervical mucus on a slide and the penetrative
ability of spermatozoa observed.
•Sperm-cervical mucus test: a specimen of semen (control), and
one mixed with cervical mucus are placed separately on a slide, and
observed for 30 minutes. More than 25% exhibiting jerking
movements in the mixed sample (but not the control) is a positive
test for antisperm antibodies.
Treatment options for male factor
infertility
General
Modification of life style factors (reduce alcohol
consumption; avoid hot baths).
Medical treatment
Correct any reversible causative factors.
Treatment options for male factor
infertility
Hormonal
•Secondary hypogonadism (pituitary intact) may
respond to human chorionic gonadotrophin (hCG)
2000IU subcutaneously 3 times a week, which stimulates
an increase in testosterone and testicular size. If the
patient remains azoospermic after 6 months of
treatment, FSH is added (human recombinant FSH or
human menopausal gonadotrophin). Alternatively,
pulsatile LHRH can be administered subcutaneously via
a minipump.
Treatment options for male factor
infertility



Testosterone deficiency
replacement therapy.
Hyperprolactinaemia
agonists.
is
requires
treated
with
testosterone
dopamine
Anti-oestrogens (clomiphene citrate 25mg OD) are
often used empirically to increase LHRH, which
stimulates endogenous gonadotrophin secretion.
Treatment options for male factor
infertility
Erectile and ejaculatory dysfunction
Erectile dysfunction may be treated conventionally (oral,
intraurethral, intracavernosal drugs; vacuum devices or
prostheses). Ejaculatory failure may respond to
sympathomimetic drugs (desipramine) or electroejaculation
(used in spinal cord injury), where an electrical stimulus is
delivered via a rectal probe to the postganglionic sympathetic
nerves that innervate the prostate and seminal vesicles.
Antisperm antibodies
Corticosteroids have been used, but assisted conception
methods are usually required.
Treatment options for male factor
infertility
Surgical treatment
Genital tract obstruction
•Epididymal obstruction can be overcome by microsurgical
anastomosis between the epididymal tubule and vas
(epididymovasovasostomy).
•Vas deferen obstruction is treated by microsurgical
reanastomosis of ends of the vas, and is used for vasectomy
reversal.
•Ejaculatory duct obstruction requires transurethral resection
of the ducts.
Varicocele
Repaired by embolization or open/laparoscopic surgical
ligation.
Treatment options for male factor
infertility
Assisted reproductive techniques (ART)
Sperm extraction
Used for obstructive azoospermia. Sperm are removed
directly from the epididymis by microsurgical epididymal
sperm aspiration (MESA) or by percutaneous retrieval
(PESA). If these methods fail, testicular sperm extraction
(TESE) or aspiration (TESA) may be tried. Sperm undergo
cryopreservation until required. Later, they are separated
from seminal fluid by dilution and centrifuge methods, with
further selection of motile sperm and normal forms using
Percoll gradiant techniques.
Treatment options for male factor
infertility
Assisted conception
•Intrauterine insemination (IUI) Following ovarian stimulation, sperm
are placed directly into the uterus.
•In vitro fertilization (IVF) Controlled ovarian stimulation produces
oocytes which are then retrieved under transvaginal USS-guidance.
Oocytes and sperm are placed in a Petri dish for fertilization to occur.
Embryos are transferred to the uterine cavity. Pregnancy rates are
20–30% per cycle.
•Gamete intrafallopian transfer (GIFT) Oocytes and sperm are mixed
and deposited into the fallopian tubes via laparoscopy. Variations include
zygote intrafallopian transfer (ZIFT) and tubal embryo transfer (TET).
•Intracytoplasmic Sperm injection (ICSI) A single spermatozoon is
injected directly into the oocyte cytoplasm (through the intact zona
pellucida). Pregnancy rates are 15–22% per cycle.
Disorders of erectile function
(impotence)
Impotence: evaluation
Definition
Impotence (also called erectile dysfunction or ED)
describes the persistent inability to achieve or maintain
a penile erection sufficent for sexual intercourse.
Epidemiology
Moderate to severe ED is found in ~10% of men aged 4070 years. Prevalence increases with age.
Aetiology
ED is generally divided into psychogenic and organic
causes , although it is often multifactorial.
Impotence: evaluation
History
Sexual: onset of ED (sudden or gradual); duration of problem;
presence of erections (nocturnal, early morning, spontaneous);
ability to maintain erections (early collapse, not fully rigid); loss of
libido; relationship issues (frequency of intercourse and sexual
desire, relationship problems).
Medical and surgical: hypertension; cardiac disease; peripheral
vascular disease; diabetes mellitus; endocrine or neurological
disorders; pelvic surgery, radiotherapy, or trauma (damaging
innervation and blood supply to the pelvis and penis).
Drugs: enquire about current medications and ED treatments
already tried (and outcome).
Social: smoking, alcohol consumption.
Impotence: evaluation
Examination
Full
physical
examination
(CVS,
abdomen,
neurological); digital rectal examination to assess
prostate; external genitalia assessment to document
foreskin phimosis and penile lesions (Peyronie's
plaques); confirm presence, size, and location of
testicles. The bulbocavernosus reflex can be performed
to test integrity of spinal segments S2–4 (squeezing
the glans causes anal sphincter and bulbocavernosal
muscle contraction).
Investigation
•Blood tests:fasting glucose; PSA; serum testosterone;
sex hormone binding globulin; LH/FSH; prolactin;
thyroid function test; fasting lipid profile.
•Nocturnal penile tumescence testing: Rigiscan
device contains 2 rings which are placed around base
and distal penile shaft to measure tumescence and
number, duration, and rigidity of nocturnal erections.
•Colour Doppler USS: measures arterial peak systolic
and end diastolic velocities,1 pre and post
intracavernosal injection of PGE1.
Causes of erectile dysfunction
IMPOTENCE
Inflammatory
Prostatitis
Mechanical
Peyronie's disease
Psychological
Depression; anxiety; relationship difficulties; lack of attraction; stress
Occlusive
factors
vascularArteriogenic: hypertension; smoking;
mellitus; peripheral vascular disease
hyperlipidaemia;
diabetes
Venogenic: impairment of veno-occlusive mechanism (due to
anatomical or degenerative changes)
Causes of erectile dysfunction
IMPOTENCE
Trauma
Pelvic fracture; spinal cord injury; penile trauma
Extra
factors
Iatrogenic:
pelvic
surgery;
Other: increasing age; chronic renal failure; cirrhosis
prostatectomy
Neurogenic CNS: multiple sclerosis (MS); Parkinson's disease; multi-system atrophy; tumour
Spinal cord: spina bifida; MS; syringomyelia; tumour
PNS: pelvic surgery or radiotherapy; peripheral neuropathy (diabetes, alcoholrelated)
Causes of erectile dysfunction
IMPOTENCE
Chemical Antihypertensives (beta-blockers, thiazides, ACE inhibitors)
Anti-arrhythmics (amiodarone)
Antidepressants (tricyclics, MAOIs, SSRIs)
Anxiolytics (benzodiazepine)
Anti-androgens (finasteride, cyproterone acetate)
LHRH analogues
Anticonvulsants (phenytoin, carbamazepine)
Anti-Parkinson drugs (levodopa)
Statins (atorvastatin)
Alcohol
EndocrineHypogonadism; hyperprolactinaemia; hypo and hyperthyroidism; diabetes mellitu
Impotence: treatment
Psychosexual therapy
Aims to understand and address underlying psychological issues,
and provides information and treatment in the form of sex
education, instruction on improving partner communication skills,
cognitive therapy, and behavioural therapy (programmed relearning of couple's sexual relationship).
Oral medication
Phosphodiesterase type-5 (PDE5) inhibitors: sildenafil (Viagra);
tadalafil (Cialis); vardenafil (Levitra). PDE5 inhibitors enhance
cavernosal smooth muscle relaxation and erection by blocking the
breakdown of cGMP. Sexual stimulus is still required to initiate
events. Side-effects: headache; flushing; visual disturbance.
Contraindications: patients taking nitrates; recent myocardial
infarction; recent stroke; hypotension; unstable angina.
Impotence: treatment
Androgen replacement therapy
testosterone replacement is indicated for hypogonadism. It is
available in oral, intramuscular, pellet, patch, and gel forms.
In older men, it is recommended that PSA is checked before
and during treatment.
Intraurethral therapy
alprostadil (MUSE). Synthetic prostaglandin E1 (PGE1) pellet
administered into the urethra via a specialized applicator.
Once inserted, the penis is gently rolled to encourage the
pellet to dissolve into the urethral mucosa, from where it
enters the corpora. Side-effects: penile pain; priapism; local
reactions.
Impotence: treatment
Intracavernosal therapy
alprostadil/Caverjet (synthetic PGE1); papaverine
(smooth muscle relaxant)
±phentolamine (aadrenoceptor agonist).
Vacuum erection device
Penile prosthesis
semi-rigid, malleable, and inflatable penile prostheses
are available for surgical implantation into the corpora to
provide penile rigidity and sufficient erectile size for
sexual intercourse. Side-effects: mechanical failure;
erosions; infections.