Abstract
Study question
Does the cause of subfertility affect any age-related changes observed in anti-Mullerian hormone (AMH) and follicle-stimulating hormone (FSH)?
Summary answer
There was no significant effect of the cause of subfertility on AMH and FSH, however women with unexplained subfertility were significantly older than controls.
What is known already
Ovarian reserve and consequently female fecundity irreversibly diminish with age. Subfertility is an increasingly prevalent clinical presentation with a multitude of underlying pathologies. Ovarian reserve testing, including biomarkers, plays a crucial role in the management of subfertility, particularly in predicting ovarian response during in-vitro fertilisation (IVF) treatment. For some couples, no cause can be identified and their subfertility remains unexplained thus making prognosis and treatment challenging. It has been proposed that these couples may have an ovarian reserve at the extreme lower end of normal. Study design, size, duration: This clinical audit retrospectively investigated 864 subfertile healthy women who had undergone investigation at the Royal Derby Hospital fertility clinic. Data were collected in Excel including age, serum AMH, serum FSH if available, and subfertility diagnosis. The data were collected from a pre-existing database produced by a group of researchers pre–2016 at the Royal Derby Hospital. The researchers had access to pathology lab reports and computerised hospital records containing clinical details. Participants/materials, setting, methods: Subfertility diagnoses were categorised by cause: male factor and tubal factor were combined and served as a control group, oligo-anovulatory factor, endometriosis factor, and unexplained subfertility. If multiple factors were present, oligo-anovulation was taken as the presiding factor. One-way ANOVA using Minitab was used for statistical analysis to assess the effect of cause of subfertility on age, on AMH, and on FSH. For AMH and FSH, age was incorporated as a covariate.
Main results and the role of chance
AMH significantly decreased with age (p < 0.001) and FSH significantly increased with age (p < 0.05). The age-related change in AMH was more pronounced than in FSH. The cause of subfertility had a statistically significant effect on age. The nature of this was that the unexplained group was significantly older than the control group and the oligo-anovulatory group (p < 0.001). Compared to the control group, AMH was lower in the unexplained and endometriosis groups and higher in the oligo-anovulatory group. However, after adjusting for age, the effect of cause of subfertility on AMH was not significant (R2(adj)=24.91%, p > 0.05). Compared to the control group, FSH was lower in the unexplained, oligo-anovulatory, and endometriosis groups. However, after adjusting for age, the effect of cause of subfertility on FSH was not significant (R2(adj)=2.05%), p > 0.05).
Limitations, reasons for caution
The previous group of researchers may have exhibited selection bias and clinical interpretation during data collection. The study population was unevenly distributed across the different causes of subfertility. Only the effect of age was accounted for despite many factors being known to affect female fertility.
Wider implications of the findings: Respective nomograms for AMH and FSH according to cause of subfertility provide a reference point for clinicians, especially to predict ovarian response during IVF treatment. Although AMH was not significantly lower in the unexplained group compared to the control group, the women were significantly older implying a lower ovarian reserve.
Trial registration number
Not applicable
To compare the effectiveness of recombinant gonadotropin versus the combination of recombinant follicle stimulating hormone and highly purified human menopausal gonadotropin versus urinary human menopausal gonadotropin alone for ovarian stimulation in women undergoing in vitro fertilisation or intracytoplasmic sperm injection treatment cycles
