Female Infertility

Infertility is defined as an inability to conceive.
When couples try to conceive:

• 16% will still be unsuccessful at the end of 1 year
• 8% after 2 years
• 7% at the end of 3 years

Subfertility may be due to problems with one or both partners.

• Natural female fertility seems to decline quite rapidly after the age of 35, but this is just an average and the actual point of decline for any individual may vary significantly.¹
• Increasing maternal age occurs with increased obstetric risks and risk of miscarriage. This should be noted by women who choose to delay their family.

Some of the causes of failure of ovulation are relative rather than absolute which is why the term subfertility may be preferable, and these include problems of lifestyle. Infrequent ovulation carries a poor prognosis for conception, but is not a total bar.

Disorders of ovulation

They may occur at the level or pituitary of hypothalamus as well as at the level of the ovary. If there is amenorrhoea it should be investigated as such and oligomenorrhoea along similar lines.

• Pituitary tumours will displace or destroy normal tissue and the production of FSH and LH is often the first to be affected. Panhypopituitarism is also called Simmond's disease.
• Sheehan's disease is pituitary infarction following postpartum haemorrhagic shock.
• Hyperprolactinaemia may present with galactorrhoea or amenorrhoea. The control of prolactin is unlike the other releasing factors in that it is controlled by an inhibiting rather than a releasing factor from the hypothalamus into the hypothalamic-pituitary portal circulation. It is also released in response to thyrotrophin releasing factor, as is TSH, and so it is elevated if thyroxine is low.
• The pituitary gland may be responsible for other disorders such as Cushing's syndrome.
• A number of chromosome disorders result in inadequate ovaries and usually primary amenorrhoea.
  • These include Turner's syndrome in which the ovaries are just streaks.
  • The condition may be a mosaic.
  • In testicular feminisation there is primary amenorrhoea.
  • The karyotype is XY but there is androgen insensitivity.
  • XXY or Klinefelter's syndrome appears as a male.
  • The XXX karyotype is sometimes called super-female, but is anything but super.
• Premature ovarian failure or premature menopause causes secondary amenorrhoea. Premature ovarian failure occurs in about 1% of women and in the majority of cases no cause is found.²
• Polycystic ovarian syndrome is usually, but not always, associated with obesity. Sclerocystic ovaries fail to ovulate but they can be very sensitive to clomiphene

Problems of tubes, uterus or cervix

• The fallopian tubes are delicate structures whose cilia waft the ovum, or even early embryo, to its destination for implantation, more correctly called nidation.
  • Damage to the tubes may occur as a result of infection:
    • A history of pelvic inflammatory disease is highly suggestive of damage to tubes.
    • Everyone who may be investigated for infertility should be tested for chlamydia before any instrumentation of the genital tract.
    • Severe pelvic infection following illegal abortion is rarely seen in this country but still occurs in places where termination of pregnancy is illegal or difficult to secure.
    • Even a medical or spontaneous abortion can lead to infection of retained products of conception.
    • Postpartum infection can also affect fertility.
  • Previous caesarian section does not impair fertility.³
  • Infection with an IUCD in situ is also less common nowadays.
    • They are rarely used in the nulliparous and modern devices are changed after 5 years whereas the worst infections were often with plastic devices that had been in place for many years.
    • However, insertion of IUCD is a high risk time for introducing infection.
• Sexually transmitted diseases may cause infertility, largely through associated PID.
  • Chlamydia and gonorrhoea are the most important.
• Infection may be less direct and spread from appendicitis is possible, even without overt peritonitis. Risk factors include:
  • Late diagnosis
  • Having the disease before puberty - as the peritoneum in a little girl is less extensive and does not wall off the infection so readily
• Female sterilisation operations involved disruption of the tube and results of attempted reversal are poor.
  • Laparoscopic proof of patency of the tubes is not evidence that they function normally.
• Infection can also damage the uterus.
  • Adhesions in the uterus and cervix is called Asherman's syndrome.⁴
• Deformity of the uterus such as a septum or bicornuate uterus may be more likely to cause recurrent abortion than failure to conceive.
  • Significant distortion of the uterine cavity by fibroids can prevent implantation and hence fertility.
• The cervix may have been shorted and damaged by a cone biopsy.
• There may be problems of cervical mucus including hostility to sperm.
• Endometriosis may cause such inflammation, adhesion and distortion in the pelvis that causes tubal infertility.
  • Even when it is much less severe than that it is commonly associated with subfertility.⁵
  • Whether or not minor degrees of endometriosis contribute to subfertility is still debated.⁶

• Coitus must be satisfactory and occurring on a frequent basis, preferably at least 3 times a week.
  • Perhaps her partner is away much of the time of there may be physical or emotional problems.
  • Is penetration adequate?
• Anatomical considerations:
  • Congenital abnormalities of the vagina will cause problems, as may dyspareunia from whatever cause.
  • In certain parts of the world, mainly the Horn of Africa, female genital mutilation is still performed and this can impair coitus and fertility.
• There may be psycho-sexual dysfunction presenting as infertility.
• Systemic disease may well impair fertility, probably by interference with the hypothalamic-pituitary axis:
  • This may include autoimmune disease such as rheumatoid disease or SLE although the latter, like antiphospholipid syndrome may be associated with recurrent abortion. Anti-phospholipid antibodies should not be part of routine testing for infertility.⁷
  • Chronic renal failure will impair fertility.
  • Poorly controlled diabetes mellitus needs correction not just to improve fertility but the demands of diabetes in pregnancy dictate that control should be immaculate from the outset.
  • Undiagnosed coeliac disease is a poorly recognised problem.⁸

Medication history

A thorough review of all medication is required with a view to both fertility and possible adverse effects on pregnancy including teratogenicity.

• Legal drugs taken for legitimate purposes may also cause problems.
  • Phenothiazines and the older typical antipsychotics as well as metoclopramide increase levels of prolactin.⁹
  • NSAIDs can impair the rupture of ovarian follicles to release an ovum.¹⁰
• The patient may be taking drugs like immunosuppressants for autoimmune disease or after transplantation.

Past medical history

This may reveal a cause for infertility such as previous treatment for malignancy.¹¹ Chemotherapeutic agents, such as those used in childhood leukaemia, may result in subsequent sterility. Surgery and radiotherapy may be relevant if they involved the pelvic region.

General health

Even in the absence of systemic illness, poor general health will impair fertility.

• Being over zealous about fitness with an obsession to run many miles a week may also be counter-productive but this is probably quite rare.
  • Athletic amenorrhoea, related to excessive training and not being underweight is uncommon.
  • The commonest reason for failing to start the London marathon, is pregnancy.
• Aim for an ideal BMI.
  • A BMI below 19 is often associated with amenorrhoea as occurs with anorexia nervosa.
  • At the other end of the scale a BMI below 25 should be the aim, but NICE give a BMI above 29 as cause for concern.¹²
  • It may be associated with polycystic ovary disease.
• Smoking cigarettes impairs fertility¹³ and smoking in pregnancy increases the risk of miscarriage, obstetric complications, intrauterine growth retardation and even delayed reading ability at least to the age of 7.
• Excessive alcohol consumption also impairs fertility¹⁴ as well as risking fetal alcohol syndrome and fetal alcohol effects that occur at lower levels of consumption.
• Any association between excessive caffeine consumption and subfertility is controversial.¹⁵
• Illicit drugs should be avoided. Some have adverse effects on fertility or the fetus or both and for most the question of teratogenicity has not been adequately addressed.¹⁶ Cannabis can impair ovulation and cocaine can cause tubal infertility. There is also reason to be concerned about the effect these drugs may have in pregnancy.

The search for the cause of infertility or subfertility should be systematic and led by clinical features, not a blind screening process for everything.
They are covered in more detail in 'Infertility: investigations and management'.