Investigation of infertility

Infertility exists when a couple trying for pregnancy have not achieved this after 12 months. Eight in 10 healthy couples will become pregnant in the first 12 months of trying, so it is reasonable to commence investigations if pregnancy has not been achieved in this time

Physiology The sperm meets the egg in the tubal ampulla

and an understanding of the complexity of the process leading to that moment and the subsequent fertilization (Fig. 1) and implantation is important to the understanding of infertility. The human female starts life with many eggs and 'wastes' most: Fetus 2 000 000 ova at about 20 weeks Birth 750 000 ova Puberty 250 000 Reproductive life 200 - 300 ovulations Menopause a few residual ova but

unresponsive to follicle stimulating hormone

Eggs are held in prophase of first meiosis. Meiotic division resumes as the follicle matures and is complete by the time of ovulation. A regular 28-day menstrual cycle results in 13 ovulations per year. Couples should be encouraged to have regular intercourse throughout the menstrual cycle.

The early conceptus produces human chorionic gonadotrophin (hCG) which is necessary for the continuation of the pregnancy and is the basis of urine and blood tests to confirm pregnancy. The production of progesterone by the corpus luteum is also essential for at least the first 9 weeks of pregnancy, until placental production takes over this role

Infertility affects 1 in 10 couples with varying causes predominating in different countries. The common causes of infertility in the UK (usually a combination of causes) are: unexplained 28% sperm problem 21% ovulatory failure 18% tubal damage 14% endometriosis 6% coital problems 5% cervical mucus hostility 3% other male problems 2%

In the USA the male factors can account for 40% of cases of infertility

Female factors (e.g. tubal blockage secondary to pelvic inflammatory disease) are high in the Caribbean and West Indies. The tendency for women in 'advanced' countries to delay childbearing whilst establishing a career may result in more cases of infertility as fecundity decreases with increasing maternal age. There are increasing numbers of anovulatory cycles and the oocytes are ageing whilst there is a lower frequency of sexual activity with increasing age

Investigations

Investigation of an infertile couple (Fig. 2) needs to rapidly assess ovulation, patency of tubes and presence of sperm. A diagnosis allows formulation of a management plan to help allay anxiety and ensure that older couples do not miss the chance of assisted conception

Check the rubella status and offer vaccination if negative - remember to advise avoiding pregnancy within 1 month of vaccination. Advice to take folic acid whilst trying to conceive is appropriate, along with advice to stop smoking and reduce alcohol intake to a minimum. A body mass index (BMI) over 30 necessitates a supervised weight loss programme. The male partner should also be advised to stop smoking and limit alcohol to optimize his reproductive performance. Intercourse two to three times per week throughout the cycle should optimize the chance of conception

Fig. 1 The physiology of fertilization.

Fig. 2 Investigation of the infertile couple.

Semen analysis

The World Health Organization normal values are: volume 2-5 ml sperm count > 20 million sperm per ml motility > 50% progressive motility Morphology > 30% normal forms white blood cells < 1 million/ml liquefaction time within 30 mins

Counts below 20 million sperm per ml are associated with lower pregnancy rates. Over recent years decreased sperm counts have been noted - possibly due to environmental pollutants such as agricultural chemicals, stress,intercurrent illness and jet lag. With azoospermia, luteinizing hormone (LH) and follicle stimulating hormone (FSH) should be checked - high FSH suggests failure of sperm production and needs further investigation with chromosome study. Normal FSH may imply a blockage to the outflow of sperm. A sperm migration test will assess the number of viable sperm with good forward motility (normal value > 5 million/ml). Antibodies can be detected in semen (IgA and IgG) using immunofluorescent techniques. Antibodies may be found on the head [affecting ability to fertilize the egg ortail (affecting sperm motility).

Tests of ovulation

Measurement of serum progesterone in the mid-luteal phase confirms ovulation if > 30 nmol/1. Ultrasound 'tracking' of the ovaries can follow developing follicles during ovulation induction cycles (Fig. 3)

Tubal function

Hysterosalpingography (HSG) and diagnostic laparoscopy are complementary methods for assessment of tubal patency. Before instrumentation of the uterus, screen for Chlamydia trachomatis or give appropriate antibiotic prophylaxis. At HSG, radioopaque dye is introduced through the cervix and outlines the uterine shape and fallopian tubes, determining their patency (Table 1)

Laparoscopy allows assessment of the pelvis for endometriosis (see p. 128) and peritubal adhesions due to infection (see p. 100). There may be an obvious corpus luteum (evidence of ovulation) and free fluid from the pouch of Douglas can be assessed bacteriologically to rule out pelvic infection. Dye injected through the cervix can be observed flowing from the fimbriae of the tubes in healthy cases

Fig. 3 Ultrasound scan showing a follicle being measured

Table 1 Assessing the results of hysterosalpingography

Findings at HSG

Uterine synechiae

Irregular uterine cavity

Septum in cavity

Cornual blockage

Tubal distension

Peritoneal spread of dye

Presumptive diagnosis

Asherman's syndrome

Uterine fibroids

Congenital abnormality of uterus

Spasm of tubes

Blocked tubes

Normal tubal patency

Investigation of infertility

Infertility investigations can commence after 12 months of intercourse not resulting in pregnancy

An investigation plan should enable couples to learn rapidly the cause of their infertility

Investigation should always be in parallel for male and female partners