Impact case study database

The work of Professor Groome has had both significant commercial and clinical impact. The Inhibin B assay has benefitted millions of women and men around the world affected by fertility problems or granulosa cell malignant ovarian tumours.

OBU licensed the 46A/F antibodies and test exclusively to Beckman Coulter, which launched an improved Inhibin B manual assay, the Gen II Inhibin B ELISA, in 2012 [S1]. Worldwide sales reported by Beckman Coulter, in more than 60 countries, totalled [text removed for publication] between August 2013 and July 2020, giving OBU an income of [text removed for publication] [S2].

The increased detection range of the Gen II Inhibin B ELISA has led to the establishment of reliable and updated reference ranges for Inhibin B in plasma. The first-generation Inhibin B assay was of limited use in the assessment of testicular function due to a lack of reliable reference ranges. Although the majority of medical decisions are based on information provided by clinical tests, these by themselves are of little value unless they are supported by relevant information for their interpretation. With the Gen II Inhibin B ELISA, reliable reference ranges have been established for Inhibin B in male body fluids. These reference ranges have been key in improving the diagnosis of a number of male genital conditions, including disorders of spermatogenesis and testicular development [S3].

Infertility is estimated to affect 10-15% of couples. Approximately 40% of all infertility cases can be attributed entirely to male factors. Serum Inhibin B levels were rapidly established as an important, sensitive marker of male fertility. Analysis of serum Inhibin B reflects the relationship between Inhibin B, Sertoli cell function and spermatogenesis. Serum Inhibin B is a better marker of male fertility status than FSH because Inhibin B is produced by the Sertoli cells in the testes. Thus, serum Inhibin B has a positive correlation with sperm count and is used for the evaluation of male infertility as a non-invasive predictor of spermatogenesis. The Gen II Inhibin B ELISA is widely used by the National Health Service (NHS) in the UK, and health providers around the world, to assess male fertility, impacting positively on the well-being and fertility outcomes of millions of men and their families [S4]. The increased sensitivity and accuracy of the assay has led to its use as an indicator of the presence of sperm in testes in men with azoospermia. Azoospermia is defined as the complete absence of sperm in ejaculate and is responsible for 10-15% of all infertility in men. Men with azoospermia who test positive for testicular sperm can recover the sperm through testicular extraction procedures and use it for fertility purposes [S5].

The amount of Inhibin B measured in serum during the start of a new menstrual cycle is directly related to the number and health of small growing follicles. The Beckman Coulter Gen II Inhibin B ELISA is used by fertility clinics to assess ovarian reserve [S6, S7], which assesses the potential number of eggs a woman has in her ovaries. This information is critically important to establish adequate fertility treatments. The Beckman Coulter Gen II Inhibin ELISA is used as an adjunct to FSH and anti-Müllerian (AMH) hormone testing because the combined measurement of these hormones and Inhibin B can better predict ovarian response and pregnancy outcome than FSH or AMH alone [S6, S7]. Before the introduction and validation of these assays as a measure of ovarian reserve, the only evidential source of guidance for mature women interested in their reproductive futures, for whatever reason, was their age. The use of Inhibin B plus the other assays has significantly improved the clinical advice women receive about their fertility status and is key in enabling them to make life decisions pertaining to their fertility on solid scientific grounds.

Ovarian cancer remains the seventh most common cancer, and eighth most common cause of death from cancer, in women in the world. Although there has been significant improvement in the visualisation of ovarian tumours (e.g. transvaginal sonography), ovarian cancer remains a substantial challenge because of late diagnosis and high mortality rates. However, the discovery that Inhibin B expression is restricted to ovarian granulosa cells in women has led to Inhibin B levels being established as a useful serum marker of granulosa cell turnover. Today, testing for Inhibin B is key in the diagnosis of granulosa cell tumours and mucinous epithelial ovarian tumours [S8]. Ovarian cancer is classified into 3 types: epithelial (80%); germ cell tumours (10-15%); and stromal sex-cord tumours (5-10%), with granulosa cell tumours representing the majority of stromal sex-cord tumours. Inhibin B levels are increased by approximately 60-fold over the range of reference values in 89–100% of patients with granulosa cell tumours [S8]. Inhibin B is also a serum marker for mucinous epithelial tumours, with 55–60% having increased Inhibin B levels, and has a better performance in muscinous and granulosa ovarian cancer than the tumour marker CA125 [S8]. The major impact of Inhibin B testing on women’s treatment and outcomes is illustrated by the following comments from a patient with ovarian cancer: “ In Aug 2010 I received a letter from my consultant advising me that my Inhibin levels had risen from their usual bottom of the scale levels and I went to see him. 2 CT scans Sept and Dec 10 showed nothing but my Inhibin B had climbed to 344. I went into hospital for an exploratory laparoscopy in Jan 11, for the docs to discover a 7cm tumour in my abdomen and several small tumours in the pelvic gutter” [S9].

Professor Groome’s active pursuit of new international collaborations with scientists and clinicians has led to the discovery that the 46A/F antibody can be used as a biomarker for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [S10]. ME/CFS affects around 0.4% of people worldwide and causes unexplained, persistent, and sometimes disabling, fatigue, with no definitive diagnostic tests or treatments available. However, recent clinical studies that have used the 46A/F antibody to monitor levels of Activin B in patients with ME/CFS have shown that levels of this protein are approximately 2-fold higher in patients with ME/CFS compared with controls. 46A/F is able to detect Activin B because this protein is made of two βB peptides, which are recognised by the 46A/F antibody. These studies offer, for the first time, hope of a reliable and accurate test to diagnose ME/CFS and monitor the effectiveness of treatment [S10].