Tricky ten minutes – ‘we’ve been trying to get pregnant for 18 months, what can we do now?’

A woman is born with one to two million oocytes which decline in number and quality with age – fastest from the late 30s.  All fertility treatments are less successful in women over 35 years, compared with younger women, and success rates decline sharply in women over 40 years (with the exception of egg donation).  On average, a woman is half as fertile aged 35-39 years as she is aged 25 years. 

Infertility affects around one couple in seven and is defined as the inability to conceive after 12 months of regular unprotected sex.  Basic investigations should be offered to couples after this time, ideally sooner where the woman is aged over 35 years or if she is at risk of reduced ovarian reserve for other reasons.

History

Ask the woman about:

• Menstrual cycle length Short menstrual cycles – less than 26 days – can indicate reduced ovarian reserve and cycles shorter than 24 days are likely to be anovulatory.  Cycles over 35 days long are also likely to be anovulatory, but are commonly because of polycystic ovary syndrome and are associated with more successful fertility treatment.
• Heavy or light periods Heavy periods can indicate fibroids or polyps and may cause iron-deficient anaemia, which should be corrected before pregnancy. Short or light periods – especially if irregular – can be due to anovulatory bleeding.  If there has been a change following Evacuation of Retained Products of Conception or a surgical termination, consider Asherman’s syndrome.
• Pelvic pain Dysmenorrhoea and dyspareunia are associated with endometriosis.
• Previous pregnancies The method of conception and the outcome of previous pregnancies, including any obstetric problems, should be noted.
• Medical history This might highlight a cause for the problems, for example a ruptured appendix may have caused pelvic adhesions, or a condition that should be optimised prior to conception, such as sub-optimally controlled diabetes. Ovarian surgery such as cystectomy or treatment for ovarian endometriosis can reduce the ovarian reserve and is associated with adhesions and tubal problems. 

Ask the man about:

• Testicular injuries Swellings or surgeries, such as orchidopexy, can be associated with a low sperm count.

Ask both partners about:

• Frequency of intercourse Discuss this along with any difficulties either partner has, such as dyspareunia or erectile dysfunction.
• Medication Some drugs are contraindicated when trying to conceive, for example statins for women. Others can interfere with conception, such as anabolic steroids for men.  Women should be encouraged to take folic acid (400µg daily). 
• Lifestyle Give advice on smoking cessation and reducing alcohol consumption.

Examination

There are few benefits in routinely examining either partner – unless indicated by the history – apart from calculating the woman’s BMI.  A pre-pregnancy BMI of less than 19kg/m² is associated with low birth weight and so these women should be advised to increase their weight. A BMI greater than 30kg/m² is associated with low success rate for fertility treatment, and a BMI greater than 35kg/m² with low conception rate per ovulation and obstetric risks to mother and baby. Half of maternal deaths between 2006 and 2008 in the UK were related to the woman being overweight or obese¹. 

Give lifestyle advice and refer for surgery those women with a BMI above 35kg/m² if they are unable to reduce their weight, and if local restrictions allow (infertility is a recognised co-morbidity). Obese women should be prescribed folic acid 5mg daily instead of the standard 400µg and should also take vitamin D 400iu daily from preconception until delivery.

Investigations 

Basic fertility tests for women:

• FSH, LH and oestradiol should be measured in the early follicular phase (day two to five of the cycle) to assess ovarian reserve.  If cycles are longer than 42 days, measurements can be taken on any day.  FSH levels can fluctuate between cycles, but levels greater than 10iu/l are associated with declining reserve. 
• Ovulation should be confirmed in women with cycle lengths less than 42 days by measuring serum progesterone in the mid-luteal phase (seven days before the next period is due).Progesterone measurements over 20nmol/l indicate ovulation has occurred.
• A pelvic ultrasound scan should look for fibroids, polyps, abnormal uterine structure, ovarian cysts and polycystic ovaries.
• Measurement of basal body temperature is generally not helpful.
• Anti-Mullerian hormone is relatively stable across cycles and is useful, especially with an ultrasound of the ovarian antral follicle counts.  Anti-Mullerian hormone tests are not readily available on the NHS and antral follicle counts are best assessed by specialist ultrasonographers.

Basic fertility tests for men:

• Take a sample for semen analysis, even if the patient has fathered a pregnancy before. Repeat the test at least six weeks later  if samples fall below the WHO criteria².

Any significant history – including if the woman is over 35 years old – or abnormality in the basic investigations should prompt referral.  Local policy may dictate when a couple with normal investigations and a negative history should be referred. Couples who have been trying to conceive for a year, but have normal tests, can be reassured that they have a 50% chance of conceiving in the next year.  It is difficult to quantify the effect of stress on conception, but having normal investigations reassures many couples.

General information

Urine ovulation predictor kits are of limited usefulness – false positive or negative results can cause unnecessary anxiety.  They also tend to encourage intercourse only around the time of expected ovulation – this can be detrimental to the relationship and reduce the chance of conception, as abstinence for longer than seven days is associated with a decrease in sperm quality. Frequency of intercourse is an issue for many couples, sometimes for psychosexual reasons but often because working arrangements keep them apart.  Advise couples to have intercourse at least two to three times a week (there is no maximum) throughout the cycle to optimise chances of success.