Infertility management and referring patients

A diagnosis should be reached in order to know how to manage and where to refer infertile patients.

Hysterosalpingogram showing tubal occlusion (Photograph: SPL)

Infertility affects one in seven couples during their lifetime and has an annual incidence of one couple per 1,000 total population, which has remained stable over the past 20 years.1

It is defined as a failure to conceive following two years of unprotected intercourse, based on population estimates that 92 per cent of 'normal' couples will have achieved a pregnancy in that time.2

NICE recommends further clinical investigation for couples who have not conceived after one year of regular unprotected intercourse.2

A recent innovation in fertility management in primary care has been the introduction and evaluation of open access hysterosalpingography (HSG) to assess the tubal status of women having difficulty conceiving. HSG is recommended as a first-line investigation by NICE.

Women who are not known to have comorbidities (PID, endometriosis or previous ectopic pregnancy) should be offered HSG to screen for tubal occlusion, because HSG is reliable for ruling this out, is less invasive and makes more efficient use of resources than laparoscopy.2

In simple terms, the causes of infertility may be expressed as sperm problems, disorders of ovulation, tubal problems and unexplained infertility. Initial investigation in primary care should evaluate the three main causes of infertility.

An initial assessment of the infertile couple in primary care includes semen analysis, serum midluteal progesterone, day two to five serum FSH and HSG.

During these investigations, a couple may be found to have an abnormal semen analysis, which denies access to HSG. It is likely that such a couple will require assisted reproduction in the form of intracytoplasmic sperm injection (ICSI) and the women will undergo superovulation and harvesting of eggs, making the knowledge of tubal status redundant.

Similarly, if an ovulatory disorder is discovered, this will require further detailed investigation, including TFTs, prolactin, estradiol, testosterone, dehydroepiandrosterone sulphate, 17a-hydroxyprogesterone, SHBG and karyotype. Following evaluation of anovulation, knowledge of tubal status may be of value before ovulation induction with clomifene.

A normal semen analysis, midluteal progesterone and FSH will lead to a request for open access HSG. An abnormal HSG will require referral for IVF and a normal HSG will give a working diagnosis of unexplained infertility in a couple under 35 years of age.

Weight loss and lifestyle
General advice includes folic acid supplementation, smoking cessation, reducing caffeine intake, reviewing prescription drugs, avoiding recreational drug use and avoiding or limiting alcohol intake to one to two units per week.

Obese women have reduced fertility and reduced success with assisted reproduction compared with non-obese women.3 However, a 5 per cent reduction in weight or a loss of about 6.5kg is associated with resumption of ovulation in a proportion of women.4

The most effective form of treatment for anovulatory infertility associated with simple obesity or obese women with polycystic ovary syndrome (PCOS) is weight loss.5 Patients should be encouraged to reduce consumption by 500kcal per day. Most women with anovulatory infertility have PCOS.

Ovulation induction
One in 10 patients who present with an ovulatory disorder have clomifene therapy initiated by their GP.1 Clomifene induces ovulation in 70 per cent of women with PCOS, with a conception rate of 50 per cent and an incidence of twin pregnancies of 10 per cent.6

NICE recommends ultrasound monitoring of clomifene treatment,2 but this remains controversial; some authors suggest monitoring by ultrasound is not essential for a good outcome. Primary care physicians continue to monitor clomifene cycles with midluteal progesterone.

Unexplained infertility
A working diagnosis of unexplained infertility may be reached in primary care for a woman aged less than 35 years with normal midluteal progesterone and HSG, and semen analysis for her partner.

Although it is an unsatisfactory diagnosis with no agreed diagnostic threshold, the couple's chance of achieving a pregnancy in the next two years is about 46 per cent.7 Referral for IVF after three years of infertility is then appropriate.2

Options for referral
Fertility services include non-Human Fertilisation and Embryology Authority (HFEA) licensed treatments (commonly ovulation induction with clomifene in secondary care) and HFEA-licensed treatments (commonly IVF/ICSI in tertiary care).

To know where to refer the couple, a diagnosis based on a full initial assessment as described above must be reached. Couples with sperm problems or tubal occlusion are likely to require IVF/ICSI with a referral to an HFEA-licensed unit.

Approximately 38 per cent of couples referred to non-HFEA licensed secondary care units have either a semen or a tubal problem.1 These misdirected referrals may be prevented by implementing a simplified management algorithm.

Seventy per cent of IVF cycles in the UK are delivered privately,8 commonly as a result of couples failing to meet PCT social and/or clinical criteria for NHS funding. Only 5 per cent of all couples presenting in general practice are referred privately,1 the rest being referred to NHS secondary or tertiary care, which in turn refers couples for private treatment. Inappropriate referrals may be prevented by implementing a pathway or referral blueprint.

There is a need for primary care commissioners to reappraise fertility pathways. They need to address the problem of inappropriate or misdirected infertility referrals.

Book now to attend MIMS Women's Health in Primary Care conference, Manchester, 16 November 2010

Dr Wilkes is a GP in Amble, Northumberland, and honorary clinical senior lecturer in primary care at Newcastle University.

Competing interests: None declared

This article was originally published in MIMS Women's Health

1. Wilkes S, Chinn DJ, Murdoch A et al. Epidemiology and management of infertility. Fam Pract 2009; 26: 269-74.

2. NICE. Fertility: assessment and treatment for people with fertility problems. CG11. London, NICE, 2004.

3. Lintsen AM, Pasker-de Jong PC, de Boer EJ et al. Effects of subfertility cause, smoking and body weight on the success rate of IVF. Hum Reprod 2005; 20: 1867-75.

4. Clark AM, Thornley B, Tomlinson L et al. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod 1998; 13: 1502-5.

5. Wilkes S, Murdoch A. Obesity and female fertility: a primary care perspective. J Fam Plann Reprod Health Care 2009; 35: 181-5.

6. Hamilton-Fairley D, Taylor A. Anovulation. BMJ 2003; 327: 546-9.

7. Snick HK, Snick TS, Evers JL et al. The spontaneous pregnancy prognosis in untreated subfertile couples. Hum Reprod 1997; 12: 1582-8.

8. Bridsen PR. Implementing the 2004 NICE guidelines on providing infertility treatment in the UK: the potential role of the private sector. New Generalist 2004; 2(2): 18-9.

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