48 J Fam Plann Reprod Health Care 2012;38:48–52. doi:10.1136/jfprhc-2011-0103 Review Abstract Infertility affects one in seven couples during their lifetime. Approximately one-quarter of these will have an ovulatory disorder contributing to their inability to conceive. Ovulatory disorders represent the simplest form of infertility to treat, and where this is not a result of ovarian failure or poor ovarian reserve most women require ovulation induction with clomifene citrate (CC). This review aims to examine the role of CC in a general practice setting. CC is a simple, relatively safe, easily administered and well- tolerated efficacious drug. There is, however, a 10% risk of multiple births associated with its use. CC has been used in general practice for many years and continues to be used. Currently, guidelines do not describe its use in the general practice setting and the evidence for monitoring its use with mid-luteal progesterone estimation or ultrasound scanning is conflicting. Introduction Clomifene citrate (CC) has been used widely for ovulation induction since the 1960s on account of its effectiveness, ease of administration and minimal side effects. Ovulation disorders represent one-quarter of all couples who present to their general practitioner (GP) seek- ing assistance with reproduction. 1–3 Approximately one-third of women seek- ing assistance for their fertility receive CC as a first-line treatment strategy. 4 This article reviews the effectiveness, risks, clinical guidelines, monitoring strategies and the use of CC in general practice. It is beyond the scope of this review to consider other drugs including aromatase inhibitors and metformin. Literature search The Cochrane database, MEDLINE, ISI Web of Science and PubMed were searched for the period December 2000 to December 2010 with the following term ‘clomifene’ linked to ‘infertility’, ‘ovulation induction’, ‘polycystic ovary syndrome’, ‘primary care’ or ‘family prac- tice’. A total of 2854 citations were found. Following removal of duplicate papers and scrutiny of the abstracts, 31 papers were relevant to the current review. In addi- tion, the reference lists of the papers were reviewed and relevant articles, papers, guidelines and consensus statements were considered. Efficacy and effectiveness The efficacy of CC is well established through its capacity to produce increased levels of follicle-stimulating hormone (FSH). The mechanism of action of CC is thought to be via the blockage of estrogen receptors in the pituitary, interfering with negative feedback with resultant increase in FSH, subsequent follicle maturation and ovulation. Its effectiveness in pro- ducing clinical pregnancies in differing cohorts of subfertile women has been the subject of study for many years. Ovulation disorders are probably the easiest form of infertility to treat success- fully 5 6 with pregnancy rates approach- ing those of normally fertile couples. 7 Ovulation induction with CC for women with oligomenorrhoea shows an increase in ovulation rate [odds ratio (OR) 7.47, 95% confidence interval (CI) 3.24–17.23] and an increase in pregnancy rate per treatment cycle compared to placebo (OR 5.8, 95% CI 1.6–21.5). 8 CC is simple to 1 General Practitioner and Honorary Clinical Senior Lecturer, Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UK 2 Consultant in Reproductive Medicine and Head of Department, Newcastle Fertility Centre at LIFE, BioScience Centre, International Centre for Life, Newcastle upon Tyne, UK Correspondence to Dr Scott Wilkes, Institute of Health & Society, Newcastle University, Baddiley-Clark Building, Richardson Road, Newcastle upon Tyne NE2 4AX, UK; scott.wilkes@newcastle.ac.uk Received 14 March 2011 Accepted 30 June 2011 Published Online First 7 August 2011 Ovulation induction with clomifene: a primary care perspective Scott Wilkes, 1 Alison Murdoch 2 Key message points ▶ Clomifene citrate (CC) is a simple, safe, effective and inexpensive drug used to induce ovulation. The risk of multiple pregnancy (mainly twin) is of the order of 10%. ▶ Clinical guidelines support the use of CC in women with proven ovulatory dysfunction only. There is no role for CC in couples with a diagnosis of unexplained infertility. ▶ One in ten couples who receive clomifene have their treatment initiated in general practice. CC use in general practice should be limited to six cycles only. ▶ CC cycles can be monitored using either mid-luteal progesterone or ultrasound scanning. group.bmj.com on April 11, 2016 - Published by http://jfprhc.bmj.com/ Downloaded from