Definition and classifications
Infertility is defined as the inability to conceive. As this inability is often not absolute, the term 'subfertility' is preferred.
Primary infertility is where the couple have not conceived before, while Secondary infertility describes the situation where there has been a previous conception, though not necessarily resulting in a live child. To some extent, some degree of failing to conceive is normal. Female fertility naturally declines rapidly after the age of 35, though there is considerable variation in some women. Of those actively trying to conceive, most will do so within the first year. Of those who do not conceive (around 16%), half of those will conceive by the end of the second year.
Epidemiology of Subfertility
Causes of Subfertility
In general the causes of subfertility can be divided into:
- Disorders of ovulation
- Tube problems
- Uterine or cervix problems
- Male factors e.g. sperm dysfunction
The problem can stem from both female and male problems. Generally, the source of infertility is:
- Exclusively with the female in approx. 30 - 40% of cases
- Exclusively with the male in approx. 10 - 30% of cases
- A combination of both partner abnormalities in 15 - 30% of cases.
In 25-30% of cases no cause is identified.
Regarding female causes, ovulation disorders and tubule dysfunction are the most common causes. The incidences of female causes of infertility are shown in the figure below.
Female causes of subfertility
- Duration of subfertility: How long have they been trying to conceive?
- Any ongoing medical problems/symptoms?
Intercourse: How frequent? Satisfactory penetration? 3+ times per week is optimum for conception. Problems such as retrograde ejaculation, erectile dysfunction and dyspareunia will reduce the chances of conception.
Anatomy: Previous gynae problems? Dyspareunia or post-coital bleeding may indicate ongoing infection.
Psychosocial: emotional / relationship problems, depression etc.
Gynae & Obstetric history:
- NSAIDs can impair the rupture of ovaian follicles
- Phenothiazines and metoclopramide can increase prolactin.
Past Medical History
Ask specifically about:
Systemic Disease: Chronic disease can impair fertility. Think about rheumatological disease and antiphospholipid syndrome, diabetes mellitus, thyroid disease, coeliac disease and renal disease.
Lifestyle: excessive alcohol consumption and smoking can reduce fertility as well as have effects on the potential foetus.
Exercise: excessive exercise can cause amenorrhoea.
BMI: Below 19 is associated with amenorrhoea. High BMIs may be associated with PCOS.
Illicit drugs: Cannabis may impair ovulation, cocaine may cause tubular infertility.
General: BMI, signs of endocrine disorder e.g. PCOS (look for acne, hirsuitism, acanthosis nigricans), signs of thyroid disease, check visual fields (prolactinoma reduces fertility).
Pelvic examination: inspect for pathology such as adnexal masses, fibroids, endometriosis. Carry out a cervical smear and screen for STIs e.g. chlamydia.
First line investigations:
- Semen analysis to detect azoospermia, oligospermia (<20million per mL), or motility problems (asthenospermia).
- Cervical smear
- Swabs for Chlamydia and Gonorrhoea
- Bloods: FBC, syphillis, rubella and HIV. If a woman has attended during the luteal phase of her menstual cycle, blood may be tested for progesterone, to see if she is ovulating (>30nmol/L confirms). Baseline hormone profile including FSH, LH, prolactin, testosterone and TSH.
Assessment of Tubal Patency
- Hysterosalpingography using radio-opaque dye can detect intrauterine or fallopian tube abnormalities and can be done as a day case, though involves x-rays.
- Hysterosalpingocontrast sonography is a more recent investigation and uses transvaginal ultrasound and galactose solution for more accurate visualisation of the fallopian tubes.
- Laproscopy with dye can detect patency of the fallopian tubes, any peritubal adhesions and endometrial deposits
- For suspected cervical hostility (sperm failing to penetrate the cervical mucus), a post coital test may be carried out, which involves mucus sampling within 12 hours of intercourse to detect number of moving sperm present. This test is still carried out, though the value of it is uncertain.
- Azoospermia is an absolute barrier to conception. Donor insemination (DI) is an option. If sperm can be recovered from the epididymus, a spermatozoon can be microinjected into the ovum, with around 30% success rate.
- In severe oligospermia, one option is to concentrate a seminal sample and fertilise ova using IVF technology.
- Anovulation (with amennorhoea) can be treated with clomifene, an antioestrogen, interfering with negative feedback, resulting in increased FSH and LH. It is successful in around 80%.
- Tubal damage may be corrected with surgery, to increase patency of the tubes (40% conceive within 2 years of surgery)
- Assisted Insemination with partner's sperm - sperm are transferred by catheter into uterus or fallopian tubes. Used for impotence, retrograde ejaculation, or localised cervical or uterine problems.
- In Vitro Fertilisation (IVF) - fertilised eggs are transferred into the uterus or fallopian tube. Used for oligospermia, presence of sperm antibodies, endometriosis, damaged fallopian tubes or unexplained fertility. 10-25% success rate.
- Gamete Intra-Fallopian Transfer (GIFT) - unfertilised eggs and sperm are transferred into one or both fallopian tubes using laproscopy or transvaginal ultrasound. Used for moderate oligospermia or endometriosis. 30-40% success rate per cycle.
- Intra-Cytoplasmic Sperm Injection (ICSI) - involves injection of sperm directly into the egg, and is the treatment of choice for severe oligospermia. 50% success rate per cycle.
Access to fertility treatment (UK)
The NICE guideline states that up to three cycles of in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection (ICSI) should be available to:
- Women aged 23 - 39
- Those who have an identifiable cause of infertility such as an absence of sperm, or blocked fallopian tubes
- Those who have had more than three years of fertility problems.
The number of fertility treatment cycles available on the NHS varies from region to region. Decision making on the amount of funding is made at a local level by Primary Care Trusts. Some PCTs in England fund one cycle, some two, and others the full three cycles.
The woman is given ovulatory drugs (FSH, gonadotrophin-releasing hormone agonists and human chorionic gonadotrophin) > superovulation
The eggs are retrieved from the ovaries by the transvaginal route, under ultrasound guidance
Healthy ova are selected for the next stage
Sperm are added to the selected eggs in vitro
1 -3 fertilised eggs are transferred into the uterus or Fallopian tubes
Oats, J. and Abraham, S. Fundamentals of Obstetrics and Gynaecology, 9th Edition, 2010. Mosby Elsevier.
Drife, J. and Magowan, B. Clinical Obstetrics and Gynaecology, 2004. Elsevier Saunders. Chapter 13.
Collins, S. Arulkumaran, S. Hayes, K. Jackson, S. and Impey, L. Oxford Handbook of Obstetrics and Gynaecology, 2nd Edition, 2008. Oxford University Press.
Human Fertilisation Authority Website