Infertility Flashcards
Action of FSH
Normal level
semniferous tubules secrete inhibin from sertoli cells and produce sperm
2-12 IU/L
Action of LH
Normal level
leydig cells produce testosterone
2-9 IU/L
maturation of sperm
time taken
1) primary spermatocytes 46 chromosome
2) second meiotic division to form spermatids 23 chromosome
3) spermatozoa
process takes 72 days
structure of sperm
head
body
tail
head contains nucleus and acromosome capn with vesicles containing lytic enzyme
body contains mitochondria and contractile filaments extending into tail
tail
testosterone
normal level
bound to SHBG %
normal range in males is about 270-1070 ng/dL with an average level of 679 ng/dL
60% bound to SHBG
38% bound to albumin
2% is free
Definition infertility
Failure of conception after 12 months of regular unprotected sex
Infertility is defined by the inability of a sexually active, non-contraceptive couple to achieve spontaneous pregnancy within 1 year
chance of conception per month healthy couple and per year
20-25% per month
75% 6 months
90% one year
% couples affected infertility
14-25% couples affected at some point
frequency of intercourse during ovulation recommended
once a day
Normal sperm parameters
Volume = > 1.4 ml
Total sperm number (10^6 ejaculate) 39 million
Concentration (10^6/ml) 16 million/ml
Total mobility (progressive and non progressive) 42%
Progressive mobility = 30%
Morphology % normal forms = 4
PH = >7.2
Peroxidase positive leucocytes <1 million
Seminal fructose (micromole/ejaculate) = >13
scrotal temp vs body temp
2-4 degrees lower
drugs affecting fertility
irreversible affect
Testosterone Anabolic steroids ADT Chemotherapy Opiates 5ARI Alpha blockers
some antibiotics, spironolactone, cimetidine, nifedipine, sulfasalazine, and colchicine
Marijuana
Alcohol
Smoking
Sulfasalazine Azathioprine, Mycophenolate mofetil and Methotrexate
Testosterone, Sulfasalazine, Anabolic steroids, Cyproterone acetate, Opioids, Tramadol, GhRH analogues and Sartan - AgII receptor antagonists
increased risk of testicular cancer with infertility HR compared with fertile control subjects
3.3 to 11.9 HR
incidence testicular cancer
3-10 new cases per 100,000 males per year
sperm maturation time testes and epididymis transit time
64 days completes
5-10 days of epididymal transit time
incidence varicocele normal population and infertile
% with improved parameters after varicocele treatment
15% in general population, and 40% in infertility clinics
Improved semen parameters in approx. 70% of patients after repair
EAU recommendations varicocele
Treat in adolescents with ipsilateral reduction in volume
Clinical varicocele with abnormal semen and good female reserve
Failed assisted reproductive techniques/miscarriage
Do no treat varicocele in infertile men who have normal semen analysis and in men with subclinical varicocele
microdeletions
One of three non overlapping regions of Y chromosome
AZF a, b, c
AZFa – Sertoli only, rare 5%
AZFb – maturation arrest
Azoospermic factor c – severe oligozoospermia, can find sperm in 10-15%
Transmitted to male offspring, need genetic counselling before ART
CBAVD
found in % infertility and OA
semen volume and PH indicators
CBAVD is found in 2% men with infertility and is present in 6% with obstructive azoospermia
>95% of men with CF have CBAVD
particularly those with a semen volume < 1.0 mL and acidic pH < 7.0.
CUAVD
Congenital unilateral absence of the vas deferens (CUAVD) is usually associated with ipsilateral absence of the kidney (26% with UAVD there is absent kidney on ipsilateral side) and probably has a different genetic causation
indications karyotype
karyotype analysis is currently indicated in men with azoospermia or oligozoospermia (spermatozoa < 10 million/mL)
treatment retrograde ejaculation
pseudoephrine, Sudafed over the counter, try 60mg one tablet for a week, and an hour before do another semen analysis (120mg orally 90 minutes before ejaculation)
success rate 58%
Imiprimine 25mg
Centrifugation and resuspension (using sodium bicarbonate orally 1hr before), pregnancy rate 15%
Collegen injection into bladder neck
Acupuncture 68%
incidence azoospermia
1-3% male population
10-15% of male infertile population
Causes azoospermia OA
Epididymal obstruction is most common cause of OA affecting 30-67% of azoospermic men
Other sties of obstruction are intra testicular 15%, ED obstruction 1-5% and vas deferens
Congenital causes epididymal obstruction as CBAVD, detached epididymis in UDT
causes NOA
UDT Infective – STI, UTI, mumps Torsion Hormonal - hypogonadism Testicular tumours Varicocele
UDT and GCT
In 5-10% of testicular cancers there is history of UDT
Risk of GCT 3.6 to 7.4 x higher than general population
2-6% of all men with history of UDT will develop testicular cancer
Even with early orchidopexy still harbour higher risk of GCT
indications ART
Surgically unable to reoncstruct eg congenital absence of vas
Men with few viable sperm in ejaculate
Azoospermic men with varicoceles - as half will achieve enough sperm to have IVF with ICSI after varicocele repaired
Men with non obstructive azoospermia
success rate ICSI
Indicated in cases of severe male factor infertility
In couples with prior failed IVF
Or in cases of sperm with significant fertilising ability defects
In 2006 ICSI represented 47% of all IVF treatments in UK
Success rates pregnancy rate 20-37% per cycle
36% in women <35 years
10% in women > 40 years
Klinefelters features chromosone incidence hormone profile
1 in 650 live male births 47XXY tall stature, long extremities, absent frontal balness, fewer chest hairs, wide hips, narrow shoulders breast development small testicles and penis high FSH low testosterone Azoospermia
Kallman syndrome
facial asymmetry UDT anosmia pituitary dysfunction colour blindness
azf c
chance of finding sperm on tese
Seen in 60% of cases of microdeletions
Can find sperm on TESE in 50%
OA vs NOA ratio
Azoospermia in general pop vs infertile men
60% NOA, 40% OA
general population 1%, infertility 10-15% azoospermia
NOA vs OA FSH, testicular size and volume
OA
normal testis
normal FSH
low semen volume
treatment: reconstruction or SSR/ICSI
NOA small testis raised FSH normal volume treatment: SSR (microtese, icsi), hormonal
Causes of OA: volume, ph, fructose, urine Vasal/epididymal EDO Retograde ejaculation Antegrade loss ejaculation
Vasal/epididymal: normal volume and fructose and PH
EDO: low volume <1.5cc, acidic low PH and low fructose
Retograde ejaculation: low/none volume, more than 10 sperm phf in urine
Antegrade loss ejaculation: none volume, no sperm in urine and normal PH and fructose
treatment of retograde ejaculation pseudofed dosing
60-120mg 1-2 hours before ejaculation 7-10 days before ovulation
can also add / exchange in imipramine 25mg
AD treatment (risk of electroejaculation and injury above T6)
BP >20 above baseline or above 150 sit up loosen tight clothing, remove stimulus nifedipine IR 10mg sublingual or chew 1-2 sprays GTN, repeat after 30 mins monitor BP a few hours for rebound hypertension
pros of embolisation varicocele
can treat both sides
no risk arterial injury hydrocele
low learning curve
cons chronic pain migration coils unable to access R>L radiation
papers for varicocele treatment
Evers MA Lancet No benefit however flawed analysis when choose clinically significant varicoceles with semen impaired pregnancy rate is 36% vs 20%
Abel Meguid SR
OR 3.04, NNT 5
spont pregnancy rate 32% vs 13%
varicocele incidence gen pop vs primary infertility vs secondary infertility
15% gen pop
35% primary infertility
75% secondary infertility
vasectomy reversal paper
Belker 1991
< 3 years patentcy 97%, pregnancy 76%
>5 years, patency 71%, pregnancy 30%
9-14 years, 80% patency 44% pregnancy
semen quality orchidectomy papers
Rives 2012
semen quality
Peterson JCO 1999
50% drop in semen parameters post orchidectomy
10% will become azoospermic post orchidectomy
10% will be azoospermic before orchidectomy
LH and FSH level
lab
LH 1.3-8.0mlU/ml
FSH 1.6-11.0mIU/ml
causes of SV obstruction
Congenital atresia
Stone
Stenosis due to infection
Inflammation
doing TURED
Joint procedure with radiology under GA
Appropriately consented pt – aware of risk of failure (early/ late- due to recurrent obstruction), small risk incontinence and retrograde ejaculation, recurrent chemical epididymitis
Transrectal probe to guide needle into dilated SV
Aspirate fluid for SA. If sperm – excludes proximal obstruction Fill SV with methylene blue
Place resection scope, and resect veru/ ejaculatory ducts, until see flush of blue into urethra. Preserve BN and sphincter
Use transrectal probe to ensure decompression of cyst and both SV’s
If no sperm on aspirate of SV, needs vasogram to exclude proximal obstruction.
May require Epididmovasostomy/ vasovasostomy/ or SSR with TESE dependent on level of obstruction
