P-701 Type, quality, and utility of research into Anti-Mullerian Hormone in relation to fertility from 1990-2021: retrospective and non-randomised cohort studies prevail

Abstract

Study question What trends can be observed in the type, quality and utility of research conducted from 1990-2021 assessing Anti-Mullerian hormone (AMH) in relation to fertility? Summary answer The large majority of AMH-research in relation to fertility is conducted through non-randomised retrospective cohort studies and has limited clinical utility. What is known already The last decades have seen strong increases in in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), partly due to a delay in childbearing age. In the last 30 years the integral role of AMH in female reproductive function has gained increasing attention. AMH, expressed by follicles in the ovary at levels proportional to the number of growing follicles, is predictive of the ovarian response to stimulation, live birth rate, and time to menopause. In this capacity, AMH is used to predict and maximise the success of ART and estimate the end of a woman’s reproductive lifespan. Study design, size, duration We investigated trends in design/execution of AMH research. We searched Web of Science and PubMed. Inclusion criteria were a primary research article conducted in humans, investigating AMH in relation to fertility. Basic research, e.g. investigations of the mechanism of action of AMH, were also included. Animal studies, AMH unrelated to fertility (e.g., as an anti-cancer drug), and studies using AMH as a surrogate measurement of ovarian reserve in the context of other research were excluded. Participants/materials, setting, methods After inclusion, we extracted the question being addressed, the country, region (based on the World Health Organisation (WHO) world region classifications), funding, study design and direction of data collection, sample size and its calculation, and statement of data availability. Finally, using a checklist of features thought to reflect the clinical utility of a study, a sub-group of research was assessed. These features include problem base, context placement, information gain, pragmatism, patient-centredness, feasibility and transparency. Main results and the role of chance We detected 701 studies on AMH in relation to fertility published between 1990 and 2021. The majority of research is conducted in the European (48%) and Western Pacific (21%) regions, closely followed by the American region (18%). We identified 18/701 (2.5%) studies as randomized controlled trials. A non-randomised cohort design was used in 541/701 (77%) of studies, and of these 541, 68% were retrospective. Furthermore, excluding in vitro and case-report studies, 284/529 (55%) studies are prognostic in nature, with arguably insufficient associative evidence (42%) in support of the widespread use of AMH as a prognostic tool. When we assessed the clinical utility of AMH research, studies performed poorly on information gain and transparency. In terms of information gain, only 62/701 (9%) studies contained any mention of a sample size calculation. Many studies reported on outcomes such as clinical/biochemical pregnancy and oocytes retrieved, with live birth being the primary outcome in only 35/701 (5%) studies assessed. For transparency, 47% of the studies assessed failed to mention a funding source, and 93% made no mention of data availability. Limitations, reasons for caution A limitation is that only two databases were searched, and inclusion of more studies may have altered the overall snapshot of the current state of research. Furthermore, information was extracted from the abstract where possible before the full article was addressed, which may have impacted the extraction/classification of studies. Wider implications of the findings These findings suggest that research and publication systems require changes to promote better research. Encouraging large-scale, multi-national, clinical trials and more data-sharing will produce more informative studies and greater improvements to clinical care. Reduced emphasis on importance of being the lead, corresponding or senior author may also encourage more collaboration. Trial registration number Not-applicable