Dr Ernest Hung Yu NG
Department of Obstetrics & Gynaecology
The University of Hong Kong
Infertility
Inability to conceive after one or two years of regular unprotected intercourse
10-15 % of couples affected
Sypnosis
Normal fertility
Causes of infertility
Basic investigations
Treatment
Normal Fertility
Pregnancy rates
peak monthly pregnancy rate ~ 30%
cumulative preg. rate in 1 year ~ 85%
cumulative preg. rate in 2 years ~ 95%
important in the interpretation of pregnancy rate by assisted methods
Cumulative PR
Causes of Infertility
Causes of infertility
Multiple factors are common
Female factors (2/3)
ovulatory (15%)
tubal (20%)
endometriosis (25%)
others: cervical, immunological, coital
Causes of infertility
Male factors (1/3)
subnormal semen due to production defects e.g. idiopathic, endocrine, trauma, genetic
no sperm due to obstructive defects e.g. absent vas, vasectomy
coital
Unexplained
ovulation, patent tubes and normal semen
Three important causes
Ovulatory dysfunction
Tubal problems
Male factors
History
Age
Menstrual cycle
regularity
History of PID or pelvic surgery
Previous investigations and treatment
Age / occupation
Past health
Coital history
Smoking/alcoholic
Physical examination
Body weight
Vaginal examination
uterine size
mobility
adnexal mass
? Necessary
Testicular size
Vas & epididymis
Varicocele
Early referral
>35 years old
Irregular cycles
Previous pelvic surgery
Previous STD
Abnormal pelvic examination
Basic Investigations
Investigations--
Basic semen analysis:
2 to 3 samples after 2-7 days of sexual abstinence
WHO criteria:
volume: >=2.0 ml
concentration: >=20 million / ml
motility: >=50% forward progression or >=25% rapid progression
normal forms: ??? 20% at QMH
Predictive values
Sperm Functions
Investigations--
Ovulation
Mid-luteal progesterone
Irregular cycles
FSH/LH, prolactin, thyroxine
Ultrasound--ovarian morphology (PCO)
Regular cycles
prolactin or thyroxine not indicated
Transvaginal scanning
Investigations--
Tubal patency
Hysterosalpingogram
Laparoscopy-diagnostic / therapeutic
Ultrasound examination
Investigations
Not indicated in routine practice:
Serum antisperm antibody
Postcoital test
Sperm function test
Endometrial biopsy
Hysteroscopy
USS of endometrium
Treatment
General advice (Female)
0.4 mg folic acid whilst trying to conceive and during the first 12 wks of pregnancy to prevent neural tube defects
Reduce body weight in obese women
Stop smoking
Avoid excessive alcohol
General advice (Male)
Stop smoking
Avoid excessive alcohol
Men with poor quality sperm advised to
wear loose fitting underwear and trousers and
avoid occupational or social situations that might cause testicular hyperthermia
Causes of infertility
Ovulatory
Tubal factors
Male factors
Unexplained/min. endometriosis
Aim
Development of a single follicle
Ovulation induction
Weight reduction
Drugs
Clomiphene citrate
Gonadotrophin releasing hormone agonist--pulsatile manner via a pump
Gonadotrophin
Insulin sensitising agents (metformin)
Surgery
ovarian drilling
Clomiphene citrate
Started from day 5 for 5 days
Dose: 50-250 mg daily for 6-9 months
Ovulation: 60-80%; pregnancy rate: 30-40%
Higher failure in obese women and those with greater ovarian volume on scanning
SE: multiple pregnancy (10%); hot flushes, hair loss, visual change, ?ovarian cancer
Clomiphene citrate
Not indicated in patients with regular ovulations
Not useful in improving pregnancy rates!
Side-effects
Anti-oestrogenic effects on cervical mucus / endometrium
Long term risks e.g. risk of ovarian CA
Problems in ovulation induction by gonadotrophin
Unpredictable responses
Exaggerated responses
High risk of multiple pregnancy and ovarian hyperstimulation syndrome
High risk of abortion
Expensive: drugs, monitoring, preterm baby
Causes of infertility
Ovulatory
Tubal factors
Male factors
Unexplained/min. endometriosis
Tubal Factors
Tubal surgery
microsurgical technique
laparotomy or laparoscopy
adhesiolysis, re-anastomosis, salpingostomy
results
IVF/ET
Tubal Surgery Vs IVF/ET
The lesions
The infertile couple
The medical service
Causes of infertility
Ovulatory
Tubal factors
Male factors
Unexplained / endometriosis
Male Infertility
Effective Treatments
Vasectomy reversal/overcome correctable obstruction
Gonadotrophins or GnRH for hypogonadotrophic hypogonadism
Bromocriptine for sexual dysfunction associated with hyperprolactinaemia
Male Infertility
Varicocele treatment may improve semen quality and pregnancy rate in oligozoospermic men , but not in infertile men with normozoospermia
Ovarian stimulation+insemination
IVF/ET
Male Infertility
Ineffective Rx or Rx of Doubtful Value
Anti-oestrogens, androgens, bromocriptine & kinin-enhancing drugs for abnormalities of semen quality
Antioxidants, mast cell blockers & alpha blockers need further evaluation
Systemic corticosteroids for antisperm antibodies
Minimal/ mild endometriosis
Medical treatment does not enhance fertility
Surgical ablation (diathermy or laser) improves fertility in infertile women
Ovarian stimulation+insemination
IVF/ET
Assisted Reproduction Procedure
Density gradient centrifugation
Superovulation & IUI--efficacy
932 women with ovulation and patent tubes
up to 4 treatment cycles
TreatmentPR/patient (%)
ICI 23/233 (10)
IUI42/234 (18)
COH/ICI44/234 (19)
COH/IUI77/231 (33)
(Guzick et al., 1999)
Factors affecting the outcome
Ovarian stimulation regimens
Clomiphene citrate (CC)
hMG/FSH (gonadotrophins)
CC + hMG/FSH
GnRH agonist (long protocol) + hMG/FSH
GnRH agonist (short protocol) + hMG/FSH
GnRH agonist (ultrashort) + hMG/FSH
Transvaginal ultrasound-guided oocyte retrieval (TUGOR)
Intracytoplasmic sperm injection
Sources of sperm for ICSI
Preimplantation biopsy
Unfertilized egg
Polar body biopsy
Cleavage stage embryo
Blastomere biopsy
Blastocyst (IVF or flushed)
Trophectoderm biopsy
Psychosocial care
Explanation
Counselling
Support
Psychosocial clinic at QMH