Impact case study database

The F2B12H and F2B7A mAbs and assay protocols to measure AMH levels in blood serum have had a significant influence on the reproductive health field. Between 2005 and 2013, manual AMH assays using Groome’s AMH mAbs facilitated clinical studies that uncovered potential routine clinical applications of serum AMH levels for the improvements of women’s’ fertility and reproductive health. The impacts described here relate to these applications and the worldwide use of Groome’s mAbs in automated AMH assays (Beckman Coulter Access, [text removed for publication] platforms) since 2014 (S1).

In 2012, users of the Beckman Coulter Gen II AMH assay reported an issue with unreliable detection of AMH in fresh serum samples, resulting in an apparent increase in AMH levels over time while in storage. Groome, by then an Emeritus Professor at OBU, identified the problem and then worked with Beckman Coulter to rectify it (S2). This enabled Beckman Coulter to relaunch the Beckman Coulter AMH Gen II assay in a modified form in 2012 and launch a fully automated version on the Beckman Coulter Access platform in 2014. The impact of automating Groome’s AMH assay has been clearly stated by Professor Richard Fleming of Glasgow Centre for Reproductive Medicine Ltd: “The automated Access AMH will deliver increased sensitivity and precision, providing more reliable results for our patients, with absolute values with which we are familiar” (S3). Today, the automated assay is used routinely by IVF labs worldwide to aid prognosis and planning for couples with fertility problems (S4a, S4b). A survey completed by 796 globally distributed IVF clinics indicated that 60% of the respondent IVF clinics use the AMH assay as a first-line test; 54% reported it as the best test for evaluating ovarian reserve (S4b) and 89% reported that AMH results were extremely relevant or relevant to clinical practice (S4b).

The Beckman Coulter Access and [text removed for publication] automated AMH assays gained US Food and Drug Administration approval for diagnostic use in 2017 and 2018, respectively, allowing doctors to incorporate them into routine clinical practice in almost every country in the world. According to the 2018 survey of the College of American Pathologists (CAP), the main benefits of the automated platforms have been threefold: (i) shorter testing times (e.g. 18 minutes for [text removed for publication] AMH) compared with manual assays (3.5 hours) and traditional assays that measure follicle-stimulating hormone, luteinising hormone and oestrogen on the third day of a woman’s menstrual cycle; (ii) better performance than manual assays. Users state that “the [text removed for publication] and Beckman Coulter’s automated assay detect extremely low and high (0.03 to 23 ng/mL) and produce very little within-patient variability or lab-to-lab variability when using the same assay” (S5); (iii) accurate measurement of AMH. “AMH testing has been a huge advance in the field of reproductive medicine,” said Sara Barton, MD, reproductive endocrinologist at the Colorado Center for Reproductive Medicine in Denver. A major issue with the traditional testing approach for ovarian reserve was the duration of the assays (3 days). “But the problem with using only day-three hormone tests is by the time the FSH is abnormal, the prognosis for patients is compromised. They are often in perimenopausal transition. So while it offers an accurate identification of women with poor prognosis, it’s already too late to help some of them.” (S5). Karen Maruniak, Colorado Center for Reproductive Medicine stated: “The biggest advantage to us has been the time savings and the ability to run the test daily; before, we had to batch the manual test, which took three-and-a-half hours to run” (S5). Dr Robert Veve, US Speciality Labs, San Diego said: “The older test, with so many hands-on responsibilities, opened the door to errors… it is one of the main reasons why so much lab-to-lab variability was observed using the old assay” (S5). CAP surveys are highly significant because the CAP is a US programme that pools information on the productivity and proficiency of clinical laboratories.

The Beckman Coulter Access AMH Assay was winner of the 2015 Scientists’ Choice Award® for the Best New Clinical Laboratory Product of 2014, as an “innovative automated AMH test that is helping to improve fertility assessment and treatment” (S6).

AMH assays based on Groome’s mAbs have enabled millions of women across the world to make informed life decisions, such as freezing their eggs to give themselves a better chance of getting pregnant after chemotherapy for cancer (S7a) or later in life: “In addition to having less follicles, my level of AMH—which gives a snapshot of your ovarian reserve—was low… This didn't mean I wasn't a candidate for egg freezing, it just meant I'd have to pump myself up with more drugs to get these eggs to mature…” (S7b).

Fertility issues affect 1 in 10 couples globally. This number has increased steadily over recent decades, mainly because women are choosing to have their first child in their mid-30s or later, when their fertility is declining. AMH assays underpin personalised IVF treatments. Ovarian response to stimulation varies considerably from woman to woman and unexpected extreme responses may produce failure from hypostimulation or serious health problems due to hyperstimulation (hyperstimulation syndrome). These problems are avoided by using a recombinant follicle-stimulating hormone (Rekovelle®) dosing algorithm, which is based on a woman’s AMH level and body weight (S8). Rekovelle® is more effective than GONAL-f (follitropin alpha), another fertility medicine, at stimulating the ovaries of women undergoing controlled ovarian stimulation for IVF. A trial showed that around 31% of women (204 out of 665) treated with Rekovelle® became pregnant compared with around 32% of women (209 out of 661) treated with GONAL-f. Implantation rates were also similar: around 35% with Rekovelle® versus around 36% with GONAL-f (S8).

AMH assays are also used in paediatrics to investigate abnormal sexual development in boys (S9a). Pubertal delay and congenital hypogonadotropic hypogonadism (HH) share the same clinical manifestation of delayed sexual maturation in prepubertal boys. Levels of gonadotropin and testosterone are very low in prepubertal boys and therefore have little clinical significance. Hence, AMH measurements are useful in the differential diagnosis of pubertal delay and congenital HH. In boys with congenital HH, AMH concentrations are abnormally low; while in pubertal delay AMH concentrations are within the prepubertal reference interval. Low or undetectable levels of AMH are also typical of disorders such as cryptorchidism, anorchia or functional failure or Klinefelter syndrome (S9a).

In combination with Inhibin B or Inhibin A, AMH assays are also used to monitor ovarian tumour recurrence or progression. Elevated levels of any of these markers can indicate the presence of ovarian cancer (S9a). Other uses include the assessment of menopausal status and the ovarian function of women with polycystic ovarian syndrome (S9b).

Beckman Coulter reported worldwide sales of the manual and automated AMH assays of [text removed for publication] from August 2013 to July 2020, giving OBU royalty income of [text removed for publication]. Three sub-licences covering human health, including the multinational healthcare company [text removed for publication], together with two sub-licences for animal health applications, have led to worldwide sales of [text removed for publication] between August 2013 and July 2020, the latter giving OBU royalty income of [text removed for publication] (S10).

Nekaris’ work on slow lorises has improved the welfare and conservation of this critically endangered primate by: driving changes in legislation; the development of more effective rehabilitation, reintroduction and translocation protocols; and by increasing international awareness of the plight of slow lorises through social media and education programmes. Much of this has been accomplished through the Little Fireplace Project (LFP) and its field site in Java, Indonesia, as a platform to engage local communities, and zoos and rescue centres around the world.

Nekaris’ work has played a critical role in increasing awareness of the extent of the illegal loris trade in Japan [S1], which (according to the Convention on International Trade in Endangered Species, CITES) imports the greatest number of slow lorises in the world. Her work informed the Japanese campaign against the wildlife trade that led to improved legislation on the pet trade of animal species listed in CITES Appendix I, including slow lorises. As stated by the Secretary General of the Japan Wildlife Conservation Society: “ Prof. Anna Nekaris has directly contributed to reduction of illegal pet trade of slow lorises and animal welfare for over 10 years in Japan… Prof. Nekaris was instrumental in helping to change this legislation through collating data on international trade in slow lorises, including presenting a report from Japan Wildlife Conservation Society (JWCS) on seizures in Japan”. The Secretary General has also highlighted the impact of Nekaris on Japanese society’s awareness of slow lorises: “Prof. Nekaris cooperated with Japanese national broadcasting corporation (NHK) on filming for the TV documentary ‘Darwin Coming’ and this programme was broadcasted on February 2016 in Japan, which was seen by millions of viewers and was the most popular show of that day on Japanese television” [S2]. Following the approval of the new legislation in 2017, all permits issued in Japan must now have an expiry date and registered animals require a microchip [S3].

The LFP, an award-winning conservation project [S4a] directed by Nekaris, under the auspices of Oxford Brookes University, is dedicated to the study of the ecology of slow and slender lorises and contributes to the conservation and ecology of loris species throughout their ranges [S4b]. As stated by The Zoo Review: “ One organisation which is very active in the field, helping to protect slow lorises, is the Little Fireface Project. Many zoos that work with slow lorises have stepped up to support this organisation in its goals to save slow lorises” [S4c]. The zoos do this not only through funding the project, but by creating posters and outreach materials; co-writing the handbook for care of lorises in European Association of Zoos and Aquaria facilities; providing veterinary advice to the LFP field team; providing gum for rescued lorises; providing microchips for rescued and wild lorises; and organising keeper exchanges whereby zoo staff get to see lorises in the wild. In return, Nekaris and colleagues have worked with zoos to validate scientific equipment such as accelerometers; developed a pen pal programme between UK and Indonesian children for which they received a BIAZA Bronze Award; and attended keeper workshops and provided advice on housing of captive lorises. These achievements are largely due to the collaborative approach of the LFP, which has led to the development of a worldwide network of zoos and rescue centres that work together to create effective protocols to ensure the welfare of captive and wild slow lorises. Due to her internationally-recognised expertise, Nekaris is writing six out of 18 chapters of the protocols [S4b].

The LFP’s work to improve understanding of the behavioural ecology, feeding and captive breeding of slow lorises has improved their welfare and aided their reproduction in captivity in several zoos. According to feedback from the Curator of Conservation of the Cleveland Metroparks Zoo (USA), a collaborator and donor to the LFP: “ information such as including wild diets and behaviour were almost completely unknown before Nekaris’ work” [S5a]. The Director of NaturZoo Rheine Germany has stated: “ We also value the results of Prof. Nekaris and her department’s studies on feeding ecology, habitat use and social organization having led to considerably improved management and propagation of slow lorises in zoological gardens” [S5b]. Other institutions that partner with the LFP, including the European Association of Zoos and Aquaria Prosimian (EAZA) Taxon Advisory Group [S5c], Shaldon Wildlife Trust (UK) [S5d], and Gauhati University (India) [S5e] have also attested that the work of Nekaris and the LFP, have guided the development of their protocols for maintaining slow lorises in captivity and shaped their campaigns to make the general public aware of the plight of these animals.

The work of Nekaris and the LFP, on the rehabilitation and translocation of endangered lorises, has directly influenced the efforts of rescue centres throughout South and Southeast Asia, improving survival rates in captivity and developing effective protocols for lorises to be released to the wild. The Director of the Indonesian foundation Yayasan Peduli Kelestarian Satwa Liar (Wildlife Preservation Foundation), a project partner of LFP, affirmed that “Prof. Nekaris’ research on the feeding ecology, social organisation, habitat use, and behaviour of slow and slender lorises has directly influenced our management of these animals in our rescue and rehabilitation centre. Her work has significantly helped improve the welfare of the slow lorises and also speed up their rehabilitation process [S6]. With the limited capacities of rescue centres and the unsuitability of most confiscated lorises for reintroduction, rescue centres face difficult decisions about euthanasia. However, Nekaris has advocated for compassionate conservation, which balance the need for conservation with the demands of animal welfare. The Yayasan Peduli Kelestarian Satwa Liar Foundation has stated that “Compassionate conservation, rehabilitation and translocation of Indonesian slow lorises (Moore, Wihermanto & Nekaris, 2014) has been one of the essential study materials and guidelines for us when establishing the rescue program” [S7]. It is important to note that, previously, slow lorises were often so little known in rescue centres that they would typically die within weeks. Through training sessions in nine Asian countries (including Indonesia 2013, Japan 2017, Vietnam 2018 and with Love Wildlife Foundation in Thailand in 2019,) and more than 700 attendees in total, Nekaris has enabled many rescue centres to identify, for the first time, the animals entering their care, resulting in improved outcomes.

Nekaris’ understanding of the cultural drivers underpinning the loris trade in South and Southeast Asia has allowed her to develop diverse education programmes that are implemented through the LFP. The programmes educate and inform school children, teachers and the general public about the plight of lorises. In addition, conservation activities, such as the installation of water-pipe bridges in the Cipangati region in Java, benefit not only the lorises, through increasing in their home ranges and landscape accessibility, but also provide benefits to local communities (water irrigation), helping to improve local farmers’ attitudes towards wildlife. In 2019, Nekaris and colleagues helped farmers to certify their coffee as Wildlife Friendly by setting a requirement for a total hunting ban in the region. After the ban in 2019, Nekaris’ team, which had found traps almost weekly, has not detected a single trap [S8]. Since 2013, the LFP has run several local education programmes, including the Nature Club (Klub Alam) and the Slow Loris Forest Protector [S4b]. Each week, approximately 60 local students aged 3-17 come to Klub Alam to learn about their local ecology. Through the Slow Loris Forest Protector programme, an interactive approach that combines creativity and science to educate children on the conservation of habitats, wild flora and fauna, the LFP has reached more than 1,800 children aged 11-13 across Western Indonesia [S4b]. At the heart of this programme is a children’s book written by Nekaris, Slow Loris Forest Protector, that has now been translated into eight languages, including Indonesian, Vietnamese, Urdu, Spanish, French, Japanese, Greek and German, with at least 8500 copies distributed [S4b]. The educational campaigns of the LFP are supported by diverse teachers’ packs developed by Nekaris and her team, including Building Bridges for Slow Loris Conservation taught to 100 children in Java and shared online [S4b]. The LFP also implements other outreach activities such as the Slow Loris Outreach Week (S.L.O.W.), which has run every year since 2013. This consists of a worldwide week of activities to increase awareness of loris conservation and the impact of the trade on the species [S9]. Activities include the launching of short films and animations; partner zoos doing various activities and each year an education pack has been developed that is shared with the project partners (more than 50 zoos, rescue centres, other conservation groups). The National Geographic Society has endorsed the Outreach Week and stated: “Professor Anna Nekaris and team once again lead us overactive humans to S.L.O.W. down for Slow Loris Outreach Week. The third annual S.L.O.W. has been drawing attention to the struggles of this small and distant relative of ours via the Facebook page of the Little Fireface Project, encouraging people to update their background image with a poster about slow lorises to help spread the word” [S10]. Nekaris’ YouTube study (R2) was used as the basis for International Animal Rescue’s ‘Tickling is Torture’ campaign ( https://www.ticklingistorture.org) as well as the Kukang Rescue Programme’s ‘I am not a toy’ campaign ( https://www.kukang.org/en/i-am-not-your-toy).The LFP also engages with the local and international community through various social media platforms to increase awareness of slow lorises. Its Twitter account (>4,600 tweets and 1,443 followers), Facebook page (>12,000 followers) where publications have reached a milestone of 8,000 likes and YouTube channel (531 subscriptions and 205,000 views) with a post that had more than 90,000 views, are key tools for increasing awareness about the plight of slow lorises [S4b].

In 2007, with support from OBU’s Research & Business Development Office and investment of approximately GBP375,000, OET was founded to exploit the new baculovirus technology developed by King and Possee through marketing a range of kits, and by providing specialist services to commercial and academic users worldwide (S1). The patents granted to OBU and NERC’s CEH were licenced to the new company in return for shares and a royalty income stream. Since 2007, OET’s ethos has been to invest in research & development (R&D) to ensure its platform technologies remain competitive and at the forefront of new expression vector development, through in-house and collaborative R&D with a range of UK and international commercial, and academic, partners (S1). Since 2013, OET has launched four improved versions of its core flashBAC^TM expression platform, including one that increases transduction of mammalian cells to enhance gene therapy applications, and has sub-licensed the core technology for use in both veterinary and clinical applications in biotech, diagnostic and vaccine companies including [text removed for publication]. Since 2015, OET has also been successful in gaining GBP2,421,953 Innovate UK contracts and grants and co-invested c.GBP750,000 own funds to enable it to capitalise on its own innovative platform technologies to develop diagnostics and vaccines for emerging viral diseases in a strategic partnership with PHE Porton Down and others. Between 2014 and 2020, OET has more than doubled its scientific staff from 7 to 16 with 50% at PhD level (S2), and increased annual turnover 4.5-fold to [text removed for publication] and profit by six-fold (S3), much of which has been reinvested in R&D and growing the company. Today OET is acknowledged as a world-renowned centre of excellence for baculovirus expression technologies, benefitting global academic and commercial end users for research, diagnostic and vaccine purposes (S1, S4).

The innovative technology ( flashBAC^TM) developed by King and Possee has resulted in a range of easy-to-use kits that enable users to make recombinant proteins in a rapid and convenient one-step process (S5). The benefits of the technology for end users relate partly to the simplification of the process, which enables a wide variety of academic and commercial laboratories to access the technology to make recombinant proteins without the need for a high level of virology-related skills. The simplified process is also quicker, thus saving several days’ time and resources in producing proteins at research scale through to bioreactors for commercial production. flashBAC^TM technology also has unique properties, which comprise: (1) its capacity for high-throughput production of multiple recombinant viruses, (2) improvements to the genetic backbone of the virus to generate higher yields of good-quality ‘difficult-to-express’ proteins and (3) avoidance of sequences that can lead to long-term genetic instability of the viral vector backbone.

While competitor baculovirus expression products exist (for example, Thermo Fisher’s BAC2BAC and BD Biosciences’ BACULOGOLD), the genetic backbones of these vectors have not been further developed since launching in the mid-1990s, and BAC2BAC retains bacterial sequences that can cause long-term genetic instability, often decreasing expression yields to almost zero over six or more passages of the virus and thus making it difficult to amplify virus for use at scale in bioreactors;. flashBAC^TM is the only baculovirus expression platform that has been genetically modified to improve the yield and quality of ‘difficult-to-express’ proteins (by deleting non-essential virus genes including chitinase, cathepsin and P10) and, at the same time, enabling high-throughput, simultaneous production of virus vectors in a simple one-step process. During the process of homologous recombination to insert foreign genes into the flashBAC^TM genome, bacterial artificial chromosome sequences (used to produce stocks of flashBAC^TM DNA) are deleted from the final vector sequences and hence recombinant flashBAC^TM vectors are genetically stable over the long-term, which ensures yields do not diminish during scale-up, for example, when providing a vaccine.

OET’s technology is now being used by multinational pharmaceutical (e.g. [text removed for publication]), biotech (e.g. [text removed for publication]), animal health companies (e.g. [text removed for publication]) and leading research institutions (e.g. PHE, the Francis Crick Institute and Universities of Oxford, Cambridge, Bristol, Manchester, Leicester, Reading, Gdansk, Aarhus, Wageningen, Harvard, Yale, Berlin, Tokyo, German Diabetes Centre, Animal & Plant Health Agency, APHA) worldwide to advance their drug discovery, biotherapeutic, diagnostic or vaccine development programmes. In addition, >100 companies and universities (many listed above) have also outsourced expression vector and protein production in insect cells to OET for ‘proteins to sell’ (e.g. [text removed for publication]) or incorporation into diagnostic assays or vaccines for veterinary (e.g. [text removed for publication]) and clinical purposes (e.g. [text removed for publication]); a number (>20) of larger academic research groups outsource construction of complex or challenging gene expression projects to OET’s experts, e.g. membrane proteins, virus-like particles and multiprotein complexes (e.g. Universities of [text removed for publication]).

Over the last few years, OET has completed increasing numbers of licence deals (>15) to enable companies to progress target vaccines or biotherapeutics through to clinical trials, or to commercialise products, (e.g. diagnostic assays) prepared using OET’s technology. For example, under a sub-licence agreement, OET produces many different proteins for [text removed for publication] for incorporation into its veterinary diagnostic assays for major avian (e.g. [text removed for publication]) and porcine (e.g. [[text removed for publication]) infectious diseases. In 2018, OET sub-licenced flashBAC^TM to [text removed for publication] for [text removed for publication] vaccine targets, two of which have successfully completed Phase 1 and 2 clinical trials for [text removed for publication]. In November 2020, [text removed for publication] vaccine for SARS-CoV-2 (the virus responsible for the Covid-19 global pandemic) (S6). The [text removed for publication] (S7). In August 2020, the UK Government [text removed for publication] (S8), and more recently [text removed for publication] (S9). In May 2020, OET agreed terms to licence its technology to Vaxine Pty, Australia for a vaccine for Covid-19, and in August 2020 Innovate UK provided GBP681,000 funding to OET to help Vaxine progress to a Phase 1 clinical trial.

The first commercial sales of flashBAC kits began in 2008 and the new technology has been widely adopted by the biotechnology sector (S4). Clients are both commercial and academic from across the globe, including all continents, either directly from OET’s Oxford base or through a number of international distributors (e.g. BioNovus for Australia, Cell Concepts for Germany, MirusBio for the US, Cosmo for Japan and Dakewe for Hong Kong and China) (S10), with non-UK kit sales comprising 80%. Approximately 43% of OET’s sales income ([text removed for publication]; 27% turnover, S3) over the assessment period derives from kit & product sales and, of this, approximately 40% through distributors and 60% direct sales. To access the American markets, the technology was licenced under Original Equipment Manufacturer agreements to [text removed for publication] and continues to be sold under the brand name [text removed for publication].

The flashBAC^TM technology is also used in-house by OET to produce recombinant proteins for customers unable to make them in their own laboratories and this accounts for approximately 43% [text removed for publication] of sales income (27% turnover). OET has thus established itself in the rapidly expanding market for ‘off-the-shelf’ research services that enable companies to avoid setting up their own dedicated facilities, enable them to outsource when in-house facilities are at capacity, or use OET’s expertise for complex or challenging projects. Since August 2014, OET has worked with >100 companies including [text removed for publication] plus government laboratories such as [text removed for publication] and many UK and global universities. We have enabled these companies and institutions to advance their drug discovery, diagnostic kit and/or vaccine development programmes by producing proteins more quickly and efficiently, and to increased yields and quality more than was possible previously. Companies utilizing OET technology are based in Europe, North and South America, South East Asia, Australia, the Middle East and China, as well as in the UK.

An increasing proportion of OET’s income comes from license deals to enable companies or organisations to use OET’s technology for commercial use including clinical trials for vaccine development (e.g. [text removed for publication]), Adeno-associated virus gene therapy vector production (e.g. [text removed for publication]) and multiple licences for commercial protein production (e.g. [text removed for publication]). A specific example of the licensed use of the technology has been in the development of vaccines for [text removed for publication], which have progressed to Phase 1, 2 and 3 clinical trials, respectively. Commercial protein production varies from simple preparation of proteins for sale to use of proteins in in vitro diagnostic assays (e.g. [text removed for publication]). Licence sales income accounted for 14% of OET’s sales income (8% of turnover; S4) in the designated period with individual licences ranging from [text removed for publication].

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].