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Investigation and management of subfertility
  1. Layla Thurston,
  2. Ali Abbara,
  3. Waljit S Dhillo
  1. Section of Investigative Medicine, Division of Diabetes and Endocrinology, Imperial College London, London, UK
  1. Correspondence to Professor Waljit S Dhillo, Imperial College London, London SW7 2AZ, UK; w.dhillo{at}


Subfertility affects one in seven couples and is defined as the inability to conceive after 1 year of regular unprotected intercourse. This article describes the initial clinical evaluation and investigation to guide diagnosis and management. The primary assessment of subfertility is to establish the presence of ovulation, normal uterine cavity and patent fallopian tubes in women, and normal semen parameters in men. Ovulation is supported by a history of regular menstrual cycles (21–35 days) and confirmed by a serum progesterone >30 nmol/L during the luteal phase of the menstrual cycle. Common causes of anovulation include polycystic ovary syndrome (PCOS), hypothalamic amenorrhoea (HA) and premature ovarian insufficiency (POI). Tubal patency is assessed by hysterosalpingography, hystero-contrast sonography, or more invasively by laparoscopy and dye test. The presence of clinical or biochemical hyperandrogenism, serum gonadotrophins (luteinising hormone/follicle stimulating hormone) / oestradiol, pelvic ultrasound to assess ovarian morphology / antral follicle count, can help establish the cause of anovulation. Ovulation can be restored in women with PCOS using letrozole (an aromatase inhibitor), clomifene citrate (an oestrogen antagonist) or exogenous gonadotrophin administration. If available, pulsatile gonadotrophin releasing hormone therapy is the preferred option for restoring ovulation in HA. Spermatogenesis can be induced in men with hypogonadotrophic hypogonadism with exogenous gonadotrophins. Unexplained subfertility can be treated with in vitro fertilisation after 2 years of trying to conceive. Involuntary childlessness is associated with significant psychological morbidity; hence, expert assessment and prompt treatment are necessary to support such couples.

  • biochemistry
  • endocrinology
  • fertility
  • laboratory tests
  • diagnostics

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  • Handling editor Tahir S Pillay.

  • Contributors LT, AA and Professor WD contributed to the writing of the manuscript.

  • Funding LT is funded by an NIHR Academic Clinical Fellowship. AA is funded by an NIHR Clinician Scientist Award. WSD is funded by an NIHR Research Professorship. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Section of Endocrinology and Investigative Medicine is funded by grants from the MRC, BBSRC, NIHR, an Integrative Mammalian Biology (IMB) Capacity Building Award, an FP7- HEALTH- 2009- 241592 EuroCHIP grant and is supported by the NIHR Biomedical Research Centre Funding Scheme.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.