Date Published: February 22, 2019
Publisher: Public Library of Science
Author(s): Julia Kopeika, Adeola Oyewo, Sinthiya Punnialingam, Nivedita Reddy, Yacoub Khalaf, Jo Howard, Sofia Mononen, Eugene Oteng-Ntim, Monika R. Asnani.
It has been proposed that ovarian sickling and/or iron overload in women with sickle cell disease (SCD) could contribute to gonadal dysfunction, but there are very few published studies. We hypothesised that the above phenomena might impair ovarian reserve.
A total of 50 SCD patients were case-matched by age, ethnicity, and presence of regular cycles (28±5 days) with 73 patients without a known haemoglobinopathy who required anti-Müllerian hormone (AMH) assessment in a gynaecology clinic. SCD patients had AMH levels taken as part of routine care. The patients were case-controlled and matched with patients who had no haemoglobinopathy in a tertiary centre over a period of one year.
The mean AMH in the SCD case group was 7.6 pmol/l compared with 13.4 pmol/l in the control group (p<0.001). The AMH distributions were subsequently categorised. This showed that SCD patients had a significantly higher chance of having lower AMH in comparison with the control group (OR 2.6 (CI 1.1–6.5, P = 0.02). The proportion of women with AMH > 20 pmol/l was significantly lower in the SCD group (6%) in comparison with the control group (19%) (P = 0.04).
This is the first study showing that women of reproductive age with SCD are more likely to have a low ovarian reserve at a younger age in comparison with patients with no haemoglobinopathy.
Sickle cell disease (SCD) is an autosomal recessive haemoglobin disorder that includes the homozygous (HbSS) genotype and various compound heterozygous genotypes (eg, sickle cell HbSC disease and sickle cell β-thalassemia disease (HbSβ thal). SCD is characterised by a lifelong chronic haemolytic anaemia and intermittent vaso-occlusive pain crises, as well as chronic multi-organ dysfunction including an increased risk of stroke, cardiorespiratory disease, renal failure and infection (due to hyposplenism). It is also associated with a reduced lifespan. In the UK, individuals are identified by the newborn screening programme and medically followed up, allowing for early initiation of infection prophylaxis.
A total of 50 SCD patients were compared to 73 controls of the same age (range 25 to 45) and ethnicity. The mean and median ages in case and control groups were 35.1 and 35 vs 35.8 and 36 years respectively. There was no statistical difference in age between these two groups (P = 0.43, Mann-Whitney test).
This report is the first to show that women with SCD have a significantly greater incidence of negligible or low levels of AMH, when compared to age-matched controls without haemoglobinopathy. This is due to decreased ovarian reserve in patients with SCD. Serum AMH level has been shown to decline throughout a woman’s reproductive lifespan ; our study showed that it declines faster in women with SCD than in a control population from the age of 30 (Fig 2).
In conclusion, to the best of our knowledge our study is the first to show that women of reproductive age with SCD have significantly lower AMH levels, which may be indicative of reduced ovarian reserve when compared to healthy controls. Further studies in women with SCD to assess ovarian function and its impact on reproduction are needed in order to ensure that these patients are adequately supported and informed of reproductive choices that best suit them.