Friday, 30 October 2015

The approach to Infertility

Key points:

  • Infertility is a complex topic. GPs can start initial investigation and refer appropriately.
  • Definition of infertility: absence of conception after a period of 12 months of normal unprotected sexual intercourse.
  • In determining the cause of the sub fertility, three basic fertility parameters should be investigated:
    • the right number of sperm have to be placed in the right place at the right time
    • the woman must be ovulating 
    • the tubes must be patent and the pelvis sufficiently healthy to enable fertilisation and implantation 

  • Significant causes of infertility 
    • Female factors
      • Ovulation factors 
        • Hypothalamic/pituitary disorders
        • hyperprolactinaemia 
        • other endocrine disorders
        • ovarian failure (e.g. oocyte ageing)
        • stress
        • PCOS
        • weight-related ovulation disorders
        • idiopathic eugonadotropic anovulation 
      • Tubal disease:
        • PID
        • endometriosis 
        • previous ectopic pregnancy
        • previous tubal ligation 
        • previous peritonitis
      • Uterine and cervical abnormalities
        • congenital 
        • acquired
      • Endometriosis 
    • Male factors
      • Reduced sperm production 
        • congenital cryptorchidism 
        • inflammation (e.g. mumps orchitis)
        • antispermatogenic agents
          • chemotherapy 
          • drugs
          • irradiation 
          • heat
        • Idiopathic
        • Klinefelter syndrome (46XXY)
        • Sperm autoimmunity
      • Hypothalamic pituitary disease
        • hypogonadotropic disorder
      • Disorders of coitus
        • Erectile dysfunction 
        • psychosexual ejaculatory failure
        • retrograde ejaculation 
          • genitourinary surgery 
          • autonomic disorders (e.g. diabetes)
          • congenital abnormalities
        • Ductal obstruction 
    • Couple factors
      • joint sub fertility
      • psychosexual dysfunction 

History to cover:

Female factors

Ovulatory function 
- Are her period regular? Cycles from 28-35 days are considered regular. Irregular cycles may indicate involution, with possible underlying causes including polycystic ovarian syndrome, hyperprolactinaemia, thyroid dysfunction and premature ovarian failure. 

- Is there inter menstrual bleeding?

Tubal function 
- Previous STD?
- Pelvic surgery for treatment of conditions such as ovarian cysts, fibroids or endometriosis
- Ruptured appendix
- IUD use
- Infection after previous termination pregnancy
- Severe dysmenorrhoea, dyspareunia or pelvic pain ? Clinical findings of suggestive of endometriosis include a fixed retrieved uterus, thickening of the uteros aural ligaments, cup-de-sac modularity or pelvic tenderness during examination

Male Factors

- Previous infertility, for example, in a previous relationship 
- Testicular injury, torsion, surgery or infection 
- Undescended testes 
- Varicocele
- Hernia or urinary tract surgery including vasectomy reversal 
- Sexually transmitted disease
- Impotence 
- Ejaculatory problems, for example, no ejaculation or retrograde ejaculation
- History of disease or illness that my affect fertility such as diabetes, cystic fibrosis or testicular involvement in mumps
- Drug therapy that may affect fertility such as chemotherapy and hormonal therapy including ETOH
  • Medications that could affect fertility
    • ETOH
    • Chemotherapy
    • Anabolic steroids
    • Aminoglycoside abx
    • Sulphasalazine
    • Cimetidine/ranitidine
    • Colchicine
    • Spironolactone 
    • Antihypertensive agents
    • Narcotics
    • Phenytoin
    • Nitrofurantoin
    • Nicotine
    • Marijuana
Physical examination 

- Female: breast, abdominal and pelvic examination, pay particular attention of fibroids or ovarian cysts
- Male: if the sperm count is abnormal or there is a history of sexual problems

Investigations:
- Female: Pelvic ultrasound +/- hysterosalpingogram (HSG), ovulation may be confirmed by measurement of the serum progesterone level in the mid-luteal phase. If periods are irregular, 2-3 blood samples should be taken over two-week period. A high level of progesterone indicates the woman is ovulating.
- If not ovulating, measure LF, FSH and prolactin. Rubella immunity may be checked with the same blood sample. 
- High LH: FHS ratio may indicate polycystic ovarian syndrome. Elevated FSH may be a sign of approaching or premature menopause. A high prolactin level may be associated with pituitary micro adenoma. Marginally elevated prolactin may warrant a repeat test.
- Investigation of free androgen index may be of benefit if polycystic ovary syndrome is suspected
- TSH measurement may help. 
- urine specimen should be taken to exclude chlamydia 

Sperm assessment:
- A sperm count sample should be collected in a clean, non sterile jar, kept warm and taken to the pathologist within 1-2 hours 
- Semen analysis is normal if the count is more than 20 million/ml, motility is greater than 50 % and there are adequate normal forms. If the sperm count is abnormal, it should be repeated before conclusions are made. 

Advice to patients:
- Have sex at least every second day around the time of ovulation 
- Stop smmoking 
- Limit ETOH intake
- Avoid unnecessary medications; for example : NSAIDs may interfere with ovulation by blocking oocyte release 
- Eat a healthy diet
- Weight loss may increase chances of conception in obese people 
- Commence preconception folate therapy in the female  partner 

Referral:
- Women under 35 years in whom there is a lack of obvious pathology may be advised to keep trying of up to 12 months. Refer if conception has not occurred after 12 months. 
- Couples where the woman is over 35 years may be advised to persevere for no more than six months if investigations reveal correctable factors that can be managed in general practice, such as lifestyle changes. 
- Early referral is appropriate in women over 35 years with no apparent abnormalities because the influence of age of fertility; and in couples with abnormal results of investigations or whose history reveals risk factors for infertility

References: 
- John Murtagh General Practice 5th edition The subfertile couple 
- http://www.australiandoctor.com.au/clinical/therapy-update/investigating-infertility
- http://www.australiandoctor.com.au/cmspages/getfile.aspx?guid=0fd498f2-572c-4484-ac6f-16da37f733a9









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