Abstract

Abstract Study question Does iron overload affect ovarian reserve markers in women with transfusion-dependent beta thalassaemia major? Summary answer Ovarian reserve markers were lower in women with transfusion dependent beta thalassaemia major as compared to controls suggesting an impact of iron overload on ovary What is known already Although spontaneous fertility and successful pregnancies have been reported in well-chelated and transfused women with beta thalassaemia major (BTM), majority of women are subfertile due to hypogonadotropic hypogonadism (HH). Little is known about the effect of iron overload on ovarian follicles and whether ovarian reserve is affected by the disease or treatment status. Study design, size, duration This study compares the markers of ovarian reserve in women with transfusion-dependent beta thalassaemia major over a period of ten years with healthy women from a control population. It is a 10-year mixed (retrospective and prospective) longitudinal study in 17 women with transfusion-dependent beta thalassaemia major from thalassaemia clinic in a tertiary teaching hospital between July 2007 to June 2017. The results were compared with 52 age-matched healthy women without any medical conditions (control population). Participants/materials, setting, methods Study compared 17 women with transfusion-dependent beta thalassaemia major with 52 age-matched healthy women without any medical conditions attending fertility clinic. Patient demographics, medical history, menstrual history, hormonal parameters (serum levels of FSH, estradiol, TSH and AMH) and antral follicle count (AFC) were recorded in all women from both groups. Serum levels of ferritin, cardiac T2*, liver iron concentration, thyroid function (TSH) and liver function test results were also recorded at three different time points. Main results and the role of chance Serum AMH levels, estradiol levels and antral follicle count were significantly lower in women with beta thalassaemia major compared with the control group (p < 0.05 for all). Low AMH levels were noted in both groups of women (with and without hypogonadotropic hypogonadism) with a background of beta thalassaemia major. Due to part retrospective nature of study, bias arising from patient selection and completeness of information available from medical records cannot be entirely ruled out. Limitations, reasons for caution The sample size was small, and bias cannot be entirely ruled out due to part retrospective nature of the study. We could not verify how many of the BTM women with amenorrhoea needed induction of puberty with certainty. Wider implications of the findings The belief that the gonad might be spared from effects of transfusional iron overload in women with BTM is questionable. Ovarian reserve markers were significantly lower in women with transfusion dependent BTM compared to controls. Further studies are required to elucidate mechanisms by which iron overload can adversely affect ovaries. Trial registration number Not applicable

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