Introduction

A diagnosis of subfertility is made if a couple fails to conceive in one year of regular, unprotected sexual intercourses. It is estimated that one in seven couples in the UK has difficulty conceiving.

Epidemiology

  • With regular sexual intercourse, 84% of couples will conceive within one year of trying (within normal reproductive age range)
  • 92% within two years

Causes of subfertility

  • 30-40% of cases due to female problem
  • 10-30% due to male problem (sperm production problem)
  • 10-30% due to combination of factors
  • 25-30% of cases no cause identified

Female Causes

  • 30% aovulation
  • 25% tubal blockage
  • 5% Cervical problem (scarring after surgery, mucus dysfunction)
  • 5% Sexual problem
  • 30% Defective implantation due to endometrial problem (fibroids, adhesions or polyps)

Sometimes causes of subfertility remain unexplained. Couples should be advised that modifiable factors such as increased BMI, use of recreational drugs and heavy smoking can reduce fertility.

For women, Polycystic ovary syndrome (PCOS) is by far the commonest cause. Other causes of aovulation include hypothalamic hypogonadism, hyperprolactinaemia, premature ovarian failure and thyroid disease (both hyper- or hypothyroidism can cause subfertility)

History and Examination

  • Age, occupation – female fertility significantly declines after the age of 40; occupational exposure to pesticides, nitrous oxide, formaldehyde, and solvents can reduce fertility
  • Any previous pregnancies  – to identify whether it is primary or secondary subfertility
  • (Male partner) Fathered any previous pregnancies?
  • Length of time spent trying for pregnancy
  • Length of time since stopping contraception and type of contraception – make sure that there are no problems that may explain the inability to conceive, such as a ‘lost’ intrauterine contraceptive device.
  • Coital frequency– to identify any difficulty with intercourse
  • Menstrual history
  • Previous history of pelvic inflammatory disease – Pelvic inflammatory disease (PID), most likely caused by past chlamydia infection, is a common cause of tubal blockage
  • (Male partner) History of mumps or measles – oligospermia due to previous testicular infection, testicular trauma, surgery to testis
  • Previous medical and surgical history
  • Previous fertility treatment
  • Previous sterilisation
  • Cervical smear history
  • General health – screen for history of thyroid disorders, diabetes, excessive exercise, weight loss, or psychological distress.

 

  • General BP. pulse, height and weight  – Increased BMI is associated with reduced fertility
  • Pelvic examination – Any uterine pathology such as fibroids?
  • (Male partner) Testicular examination – testicular volume, consistency, masses, absence of vas deferens (associated with Cystic Fibrosis), variocele, evidence of surgical scars

 

Investigations

Female

  • Day 2-5 (baseline) profile – FSH, LH, TSH, prolactin, testosterone – to check for hypothalamic-pituitary-ovarian axis dysfunction
  • Mid-luteal progesterone (should be raised if woman have ovulated)
  • Rubella and chlamydia screening
  • Anti-Mullerian Hormone (AMH) produced by ovarian granulosa cells is a useful marker for ovarian reserve. Women with premature ovarian failure will have very low AMH count and post-menopausal women will have an undetectable AMH count
  • Check tubal patency by hysterosalpinogram (HSG): dye injected into the uterus and view under X-ray or hysterocontrast synography (HyCoSy0: using ultrasound [both screening tests] or operative laparoscopy and dye test [the diagnostic test]

Male

  • Semen analysis (after patient have abstained from sexual intercourse for 3-4 days)
  • Normal parameters for semen analysis (WHO criteria)
Volume >2mL
pH >7.2
Sperm concentration >20 million per mL
Total sperm number >40 million per ejaculate
Motility >50% grade a or b  (that move forward)
Morphology >30% normal forms

 

Management

There are three types of infertility treatment.

Medical

Ovulation induction with anti-oestrogen drugs

  • Clomifene is an effective treatment for anovulation and may be used in women in PCOS, then hCG (function similar to LH here) is injected to induce final oocyte maturation and its release  – Clomifene SE: hot flushes and reversible ovarian enlargement; hCG injection can cause ovarian hyperstimulation syndrome (OHSS), with the development of vascular hyperpermeability and the resulting shift of fluids into the third space – causing pleural effusion and ascites
  • Metformin may be added in women with PCOS and a BMI greater than 25 who are unresponsive to clomifene.
  • Gonadotrophins
  • These may be offered to women with clomifene-resistant anovulatory infertility, but they carry a significant risk of multiple pregnancy.
  • Dopamine agonists can be considered for women with ovulatory disorders secondary to hyperprolactinaemia.

Surgical

Tubal surgery may be effective in women with mild tubal disease. Tubal catheterization or cannulation improves the chance of pregnancy in women with proximal tubal obstruction.
Laparoscopic surgery appears to improve the chance of pregnancy in women with all grades of endometriosis
Surgical correction of epididymal blockage in men with obstructive azoospermia is likely to restore patency of the duct and improve fertility.

Assisted Conception

Intrauterine insemination (IUI)

  • In this process, which is timed to coincide with ovulation, sperm is placed in the woman’s uterus using a fine plastic tube.
  • Recommended for for couples with mild male factor fertility problems, unexplained fertility problems, or minimal to mild endometriosis
  • Women must have patent Fallopian tubes

In-vitro fertilization (IVF)

  • This involves retrieval of one or more eggs, which are mixed with sperm and incubated for 2–3 days; the resultant embryo is then injected into the uterus via the cervix.
  • Recommended for all couples in which the woman is aged 23–39 years at the time of treatment and who have an identified cause for their fertility problems (e.g. azoospermia or bilateral tubal occlusion) or who have infertility of at least 3 years’ duration be offered up to three stimulated cycles of IVF
  • Women must have functional ovaries

Intracytoplasmic sperm injection (ICSI)
This involves injecting an individual sperm directly into the egg, to bypass natural barriers that prevent fertilization.

Other methods include donor insemination (for male with little to no sperm, absent vas deferen), oocyte donation (for female with premature ovarian failure), embryo donation and Gamete intrafallopian transfer (GIFT) – less recommended than IVF

Related entries