FEMALE INFERTILITY Chapter28 pg 343

Infertility is a complaint relating to a couple; both Most common aetiological factors in women:
partners should be involved in investigation & ovulatory failure & tubal damage
treatment.

DEFINITION

Infertility
 inability to achieve pregnancy after 1 yr of adequate
sexual exposure.
LIFESTYLE & ENVIRONMENTAL FACTORS
Reproductive failure
 the repeated failure to carry a pregnancy to viability • Weight
After 35, reduction of female fertility usually - Overweight = BMI > 25
Primary female infertility experienced: - Hypothalamic GnRH & pituitary
 implies the woman has never conceived gonadotropin secretion abnormalities
- Reason unclear
relatively common in overweight, obese &
Secondary infertility - Suggests primary cause of age-dependant  in
underweight (BMI <17)
 at least 1 previous conception fecund ability &  in incidence of spontaneous
• Smoking
miscarriage is an  prevalence of aneuploidy
Sterility - Fertility lower in both men and women
in ageing oocytes resulting from disordered
 used when an individual has a condition, so-called • Other substances
regulatory mechanisms governing meiotic
absolute factor, which prevents conception; condition is - Marijuana: inhibits GnRH secretion + can
spindle formation & function
irreversible. suppress reproduction in both sexes,
- Occurrence of luteal insufficiency with
interferes with ovulatory function
advancing age can cause infertility and 
- Cocaine: markedly  risk of tubal disease
incidence of miscarriage
INCIDENCE - Alcohol: lower pregnancy rates achieved
Teratozoospermia is most NB cause of infertility with ART
Approximately 15-20% of couples
among males - Perchlorethylene in dry cleaning, toluene in
Causes and frequencies of infertility printing, ethylene oxide & mixed solvents:
Duration of sexual exposure indicates when infertility
 fecundity
investigations should be initiated
- Herbicides & fungicides:  fertility in
- Each ovulatory cycle, normal couple only has woman
10-25% chance of achieving pregnancy
- When obvious cause for infertility found, treat
immediately
 EVALUATION MANAGEMENT

History Help couple see infertility from a wide perspective

Show empathy, important to understand that some Culturing menstrual fluid for M. tuberculosis mandatory
conditions can be solved w/out advanced tech
Classify patients into ovulatory or anovulatory
Infertility-related hx:
✓ Age of partner
✓ 1o or 2o infertility
✓ Prev. marital & reproductive hx – live births,
miscarriages, ectopic pregnancies + puerperal
infections
✓ Menstrual hx – age of menarche, regularity & length
of cycle, dysmenorrhoea; woman w/ normal, regular
menstrual cycle most probably ovulatory
✓ Prev. contraception & complications if any
✓ Prev. pelvic infections
✓ Breasts – thelarche, development, galactorrhoea &
premenstrual tenderness
✓ Skin abnormalities – acne, abnormal hair growth
✓ Mass – sudden  or 

General hx

Social hx:
Ovulatory patient
✓ Socioeconomic factors, for practical importance
Properties of mid-cycle cervical mucus should be evaluated
Family hx
Periovulatory period – pt should be examined daily for
cervical mucus secretion
Physical examination
Adequate mucus should have following characteristics:
❖ Stature, body length & mass
➢ Sufficient amount
❖ Secondary sexual characteristics & hair distribution
➢ Ability of mucus to stretch (spinn-barkeit): 8-10cm
❖ Breast development & exclusion of galactorrhoea
or more
❖ Abdominal exam – scars, tenderness, masses
➢ Watery, thin, clear & transparent
❖ Gynae exam
➢ Dried on slide: distinct micro pattern  ferning
❖ Rectovaginal exam – exclude endometriosis
Poor mucus at mid-cycle
- physical barrier which  sperm penetration, may
require procedure to achieve fertilisation e.g.
artificial insemination

‘LH kits’
- detect mid-cycle LH surge in urine
- ovulation predictor kits turn positive when urinary
LH concentration exceeds threshold level normally
seen only during LH surge
- surge lasts up to 48hrs

If pt is ovulatory
- problem usually more complex in nature, requiring
more sophisticated lab facilities
- Tubal factors & male factors most common causes
- Colleague w/ necessary expertise should evaluate
reproductive organs, esp. Fallopian tubes
- Decision whether pt should have reconstructive
surgery or in vitro fertilisation (IVF) is made
laparoscopically, usually in conjunction w/
hysterectomy or hysterosalpingogram +
chromopertubation - hysteroscopy
Chronic anovulation
Diagnosis made by history & special investigations
Obesity
- should lose weight
- may cause anovulation
- cause resistance to clomiphene
Hyperprolactinaemia
- must be excluded by determining serum
prolactin values
- elevated levels should be investigated &
treated
- Hypothyroidism must be excluded by
determining serum TSH levels
Male factor
- Excluded w/ semen analysis
- Pt w/ semen abnormalities should be
referred for specialist treatment
Polycystic ovary syndrome (PCOS)
- Should be treated w/ great care
- Very sensitive to clomiphene & may react w/
hyperstimulation
Clomiphene therapy GnrH stimulant
- Dosage: 25mg/day for 5 days (day 5-9 of
cycle)
- Pt usually ovulates between day 5 and 8
after last tablet
- During periovulatory period (day 13-16), pt
needs to be followed up on a daily basis to
determine amount & quality of her cervical
mucus
- If mucus adequate
 rx can be repeated for 3 menstrual cycles
 couple must be advised about the most
probable time of ovulation for timing of
intercourse.
- If mucus inadequate/pt not pregnant after 3
cycles
 refer to specialist
 uncontrolled administration of
clomiphene C/I; may lead to multiple
pregnancy & can have contraceptive effect
Transvaginal ultrsonography (TVUS) & saline
due to anti-oestrogenic action causing
sonohysterography
thickening of cervical mucus w/ subsequent
reduction of sperm penetration - TVUS another method for evaluation of
- Anatomic & functional uterine abnormalities uterine factors
that can impair fertility can also adversely - 2 layers of endometrium comprise
affect outcome of pregnancy – special endometrial lining, changes in appearance +
investigations can be done thickness during menstrual cycle
- In proliferative phase, endometrium is relative
Hysterosalpingogram (HSG)
hypoechoic & gets thicker until it forms
- Limitations for assessing tubal patency; 75% prominent trilaminar pattern
correlation between HSG + laparoscopy - Saline sonohysterography more accurate in
- Most effective way to evaluate Fallopian diagnosing double uterine cavity & shape of
tubes & uterus  combo of laparoscopy & fundal contour
HSG or hysterectomy & chromopertubation - TVUS more sensitive than HSG in detecting
- Alone can be of value, but cannot evaluate submucous myomas & endometrial polyps;
motility of Fallopian tubes + fimbrial ends also highly accurate for diagnosing intramural
- Disadvantages: pain during procedure, + subserosal myomas
provides no information concerning
Hysteroscopy
presence of other peritoneal diseases e.g.
endometriosis & adnexal adhesions - Gold standard for diagnosis & treatment of
- Before HSG is done: cervicitis should be intra-uterine pathology e.g. resection of
excluded to prevent organisms from being polyps, submucous myomas, septum resection
introduced to upper tract causing salpingitis; for septate uterus + recurrent pregnancy loss
salpingitis should also be excluded - Method of choice for intra-uterine adhesion rx
 SURGERY
Treatment of infertility due to tubal disease most
successful if disease localised in distal portion of
tube
Fimbrioplasty
 lysis of fimbrial adhesions or dilatation of
fimbrial structures
Neosalpingostomy
 creation of new tubal opening in Fallopian tube
w/ distal occlusion
Poor prognostic factors:
▪ Tubal diameter of >20mm
▪ Absence of visible fimbriae
▪ Dense pelvic adhesions
▪ Ovarian adhesions
▪ Advanced age of female partner
▪ ultrasonographically by means of serum
Long duration of infertility
One of the most successful surgical procedures –
microsurgical reanastomosis of Fallopian tubes
after surgical sterilisation
Clinical characteristics ass. w/ high success rate:
• Female partner younger than 40
• Tubal length > 4cm
• Fallope ring, Filshie clip or Pomeroy tubal
ligation
• Absence of ass. pelvic disease
Cumulative pregnancy rates of 50-80% 1 year after
reanastomosis can be achieved
SPECIALIST TREATMENTS
Artificial insemination
• w/ partner’s washed spermatozoa
• mainly indicated in pts w/ a cervical factor
i.e. thick mucus
In vitro fertilisation (IVF)
• spectrum of conditions can be successfully
treated
• Pts are hyperstimulated w/ various
ovulation-inducing agents, which include:
- Clomiphene w/ or w/out human
menopausal gonadotropins (HMG)
and/or hCG
- Pure FSH
- GnRH and GnRH analogues
• Follicular maturation monitored
oestradiol.
• Serum LH – value in intercepting a
premature LH surge
• Oocyte retrieval done by ultrasonically
guided transvaginal follicular aspiration
• Embryo transfer performed by trans-cervical
passage of Teflon catheter loaded w/
embryos at the 2- to 8-cell stage
• Indications for IVF:
- Absent/irreparably damaged Fallopian
tube
- Idiopathic infertility
- Endometriosis
- Male factor
- Female antisperm antibodies
Gamete intra-Fallopian transfer (GIFT)
• Performed only if at least 1 Fallopian tube is
patent
• Core concept: Fallopian tube may be better
site for nurturing interaction of oocytes +
sperm than synthetic culture medium in
plastic dish kept in incubator
• 2-3 oocytes w/ washed spermatozoa
transferred into Fallopian tube immediately
after oocyte retrieval
• Indications:
- Idiopathic infertility
- Infertility ass. w/ endometriosis
- Male factor infertility
- Adhesions to Fallopian tube
Pronuclear stage transfer (PROST) & zygotes intra-
Fallopian transfer (ZIFT)
• Both combine features of IVF + GIFT
• PROST – pronuclear stage embryo is
transferred
• ZIFT – embryos of ≥2 transferred
- Theoretical advantage of providing direct
observation of the success of fertilisation
process in vitro (not possible in GIFT)
followed by the incubation of conceptus
in Fallopian tube
Cryopreserved embryos
• Excess oocytes can be inseminated
• If fertilisation + cleavage up to 8 cell stage
take place, embryos can be frozen & stored
• Thawed embryos - placed directly into uterine
cavity or laparoscopically into Fallopian tube
Micromanipulation of gametes

• Male factor infertility due to many types of

semen abnormalities (next chapter)
• Gamete micromanipulation in the form of
intracytoplasmic sperm injection (ICSI) offers NB
advantages for couples w/ severe male factor
infertility
• Testicular biopsy- spermatozoa retrieved from
tubuli + used for ICSI
• Major predictors of success:
- Age of female partner
- Early follicular FSH levels & FSH response to
clomiphene challenge
• May completely transform diagnostic +
treatment approach to male factor infertility
• NB operative question is whether live
spermatozoa can be obtained from infertile male,
if so, couple is eligible

Gamete donation

• Artificial insemination w/ donor sperm may be

considered in cases w/ azoospermia or gross
abnormal semen parameters
• In ovarian failure, oocyte donation is another
option, combined w/ IVF or GIFT procedure
• Selection of donors & recipients is subject to a nr
of stringent regulations
 Chapter29 pg 353
MALE INFERTILITY

40-50% of infertile couples the male is infertile = 5-10% of all male partners Causes of male infertility
1. Pretesticular or pregerminal causes
DEFINITIONS ▪ Central gonadotropin deficiency:
Normospermia - Hypothalamic: congenital GnRH deficiency;
tumour, infection, head trauma
 normal semen parameters, ejaculate likely to be fertile (>5% normal morphology) - Pituitary: congenital FSH/LH deficiency; tumour,
infarction, infection, trauma
Oligozoospermia (amount) - Other: sarcoidosis, haemochromatosis
 sperm count <15 million/ml ▪ Endocrine excess syndromes:
- Oestrogen: functional tumour of adrenal gland;
Asthenozoospermia (motility) cirrhosis
 < 30% motile spermatozoa w/ forward progression of less than 2 (scale of 0-4) - Androgen: congenital adrenal hyperplasia;
congenital-producing tumour
Teratozoospermia (morphology) - Glucocorticoid: Cushing’s syndromes; steroid
 < 5% spermatozoa w/ normal morphology treatment (ulcerative colitis, asthma)
▪ Other:
Oligoastheno-teratozoospermia - Hypothyroidsim
- Diabetes mellitus
 signifies disturbance of all 3 variables (amount, motility, morphology). Combos of
2. Testicular causes
only 2 parameters may also be possible. ▪ Chromosomal abnormalities:
- Klinefelter’s syndrome (47, XXY)
Azoospermia ▪ Cryptorchidism, uni- or bilateral
 no spermatozoa in ejaculate ▪ Radiation, chemotherapy
▪ Mumps, viral orchitis
Globozoospermia ▪ Trauma
 sperm w/ round head & no visible acrosome ▪ Sertoli-cell-only syndrome
▪ Idiopathic maturation arrest
Aspermia ▪ Androgen receptor abnormality:
 no ejaculate - Androgen insensitivity syndrome
3. Post-testicular causes
▪ Congenital ductal obstruction:
- Vas deferens, epididymis
▪ Acquired ductal block:
- Infection: gonorrhoea, tuberculosis
- Vas ligation
▪ Impaired motility:
- Kartagener’s syndrome
- Immotile cilia syndrome
- Enzyme deficiencies
- Protein carboxymethylase
4. Genitourinary infections
5. Immunological causes
 EVALUATION
Thorough history
Obtain knowledge of couple’s perception of ‘fertile
period’ & ensure adequate intercourse is taking place
during that time
Always use ovulation & anovulation in female partner
as guideline:
Anovulatory
• Do serum prolactin & TSH
• Do semen analysis (SA) on partner
- If SA and other 2 tests normal, proceed w/
ovulation induction
Ovulatory AND infertility for >2yrs w/ hx of regular
intercourse around time of ovulation → more serious
problem
• Male factor will be responsible, causing
infertility in +/- 40% infertile couples
At this stage, GP can request an SA from recognised SPECIAL INVESTIGATIONS
andrology lab
Basic semen analysis (SA)
If subfertile SA obtained, pt can be referred to
▪ Cornerstone of tests
specialist in human reproduction
▪ Specimen usually obtained by masturbation;
Guidelines: must be collected after 2-3 days of
abstinence
✓ Interpret SA w/ care
▪ Make use of lab w/ necessary expertise
✓ Don’t rely on 1 abnormal SA
▪ Spermatozoal abnormality often ass. w/
✓ Choose wording carefully & inform pt that
disorders of the testes e.g. varicocoele; male
presence of abnormal semen requires
infertility likely to present if >95% of
further investigation; not necessarily male
abnormal forms are encountered
factor but expert’s opinion is necessary
▪ Quality of semen judged by nr of
✓ Second SA thus necessary; quality and
spermatozoa in millions/ml, % of normal
characteristics of ejaculate may be improved
forms, % and type of abnormal forms &
by:
motility and forward progression
- Restricting smoking + excessive alcohol
▪ Morphology assessed after using a staining
intake
procedure, and morphologic rating should
- Proper diet, adequate rest, relief of
include counting of apparently normal
emotional tension & rx of any chronic
spermatozoa; most NB as it gives best
illness or metabolic disease
information regarding fertility; expressed as
- Avoid underwear that keeps testicles in
% of normal forms or normal morphology
contact w/ body & heat exposure during
▪ Total volume, pH & viscosity also NB
excessively prolonged hot tubs or steam
- large volume may produce low sperm
baths
concentration
- Taking specific hormone therapy
- increased presence of leukocytes (>2-5
per HPF) suggests prostatitis or other
infection
- WCC then done, abnormal if > 1
million/ml
- Don’t confuse white cells w/ immature
spermatozoa, appearance is similar
- Aerobic & anaerobic cultures of
ejaculate should always be requested
 ▪ Motility assessed under constant temp
conditions immediately after liquefaction +
4 hrs later
▪ Several specialised tests available
- Specialists use these
- Essential to know what these
investigations measure and for what
reason
▪ NB: most information regarding fertility
can be obtained by basic SA
Mixed agglutination reaction test (MAR test)
▪ Simple screening method for sperm
antibodies
▪ Detects IgG antibodies in semen sample
▪ Considered abnormal if values >50%
Immunobead test
▪ If MAR test postivie, immunobead is done
next
▪ Employs immunoglobulin-coated latex
particles as indicator source
▪ Also uses antiglobulin to produce mixed
agglutination between antibody-bound
sperm and indicator
▪ Not only demonstrates presence of
antibodies but also indicates the region of
binding of sperm surface, determines the
class and/or subclass of immunoglobulin
involved
▪ Types of antibodies detected: IgG, IgA &
IgM
Hemizona assay (HZA)
▪ Looks at tight binding of spermatozoa to
human zona pellucida
▪ Oocytes from ovaries obtained from pts
undergoing hysterectomy + oophorectomy
are cut into halves
▪ 1 half (hemizona) used to assess pts
spermatozoa binding ability
▪ Other half serves for comparison w/ proven
fertile male
▪ Test w/ promising ability to predict chance
of fertilisation in vitro
TREATMENTS FOR VARIOUS MALE FACTOR
CONDITIONS
Azoospermia
▪ Retrograde ejaculation should always be
excluded – ask pt to pass urine after semen
sample is obtained
▪ Always be referred to specialist to decide
whether surgical or medical rx can be
offered
▪ ICSI after testicular biopsy treatment of
choice
▪ Intrauterine insemination (IUI) can be
offered in cases w/ retrograde ejaculation
Asthenozoospermia
▪ NB to repeat SA
▪ Abnormality found in at least 3 specimen
samples, referral for further rx indicated
▪ Pt can benefit from sperm manipulation
procedures
▪ Problem w/ infertility can be treated w/ IUI,
GIFT, IVF or ICSI in severe cases
Teratozoospermia
▪ These couples take longer to achieve pregnancy
▪ If infertility present for > 2yrs  IVF or ICSI
▪ If sperm motility between 0 and 4% normal
forms, but has normal count and motility 
40% chance of pregnancy every cycle w/ ICSI
▪ If morphology between 5 and 14% normal forms
 40-60% chance per cycle w/ IVF
▪ Consider ICSI for poor prognosis group (0-4%)
normal forms if no pregnancy has occurred after
3-4 IUI attempts
Antisperm antibodies
▪ Assisted reproductive methods can be
employed i.e. artificial insemination (IUI)
▪ Sperm separation procedures are used to
improve sample and motility
▪ If >500 000 sperm can be obtained after
preparation, prognosis is good and IUI should be
offered (3-4 cycles allowed)
▪ Systemic corticosteroids not indicated
▪ ICSI treatment of choice if low sperm
morphology (0-4% normal forms) w/ anti-sperm
antibodies
ICSI
▪ Injects selected sperm into oocyte
▪ Indications:
- Oligozoospermia
- Severe asthenozoospermia
- Severe teratozoospermia
- Azoospermia
▪ In case of azoospermia, spermatozoa can be
obtained & injected after testicular biopsy
 ▪ Biopsy specimen can also be frozen in small
quantities & used when required, w/ excellent
results
▪ In these cases, ICSI can be applied w/ IVF to
achieve pregnancy
▪ Current rate: 40% per cycle in most severe cases if
embryo quality was good
▪ Cumulative rate: +/- 60-70% in 3 rx cycles in pts
for whom no pregnancy chance or rx could be
offered a few years ago

CONCLUSION

Assisted reproduction has opened new doors

NB to refer the infertile couple w/ a possible male factor

asap for specialised treatment