Ovarian sickling as a proposed mechanism for premature ovarian failure necessitating ovum donation

Introduction

Gonadal dysfunction has been reported in female patients with sickle cell disease (SCD) as a result of iron overload. ¹ To date there has been no report in the literature of ovarian sickling being a reason for gonadodysgenesis (premature ovarian failure [POF]) in women. This case report describes POF in a woman with SCD and suggests ovarian sickling as its cause.

Case

A 40-year-old Nigerian woman became pregnant from ovum donation and in vitro fertilization after a 15-year history of primary infertility. She was diagnosed as having SCD (Hb SS disease) at the age of two years. She had only mild manifestations of SCD in her childhood years, and as a result had only one blood transfusion at the age of eight. She had otherwise remained well and in steady state throughout her life. She had her menarche at the age of 15 years; however by the age of 25 years, she was amenorrhoeic. Detailed endocrine assessment was consistent with POF. During this time she did not have significant alteration in her weight, which was stable at 55 kg with a height of 1.64 m; thus this could not explain the POF. She was not on any medication apart from her prophylactic folic acid and penicillin V. She was not on any chemotherapeutic agent or hydroxyurea, and her other endocrine function tests, which included thyroid function tests and the oral glucose tolerance test, were normal. She was advised to consider adoption or egg donation should she contemplate having children. She entered an egg donation programme; the donor and her partner had normal haemoglobin (AA). She conceived following her first ovum donation cycle. Her antenatal progress was uneventful and at 39 weeks of gestation delivered a live male infant weighing 2.6 kg.

Discussion

Gonadal insufficiency and other endocrine disorders have been reported secondary to systemic iron overload in patients with SCD. ¹ This was not the case in our patient, who did not have a history of repeated blood transfusions and showed no evidence of iron overload. There was no other cause of her ovarian failure found, and thus we propose that frequent episodes of intravascular sickling, vessel occlusion and infarction as well as tissue hypoxia associated with chronic anaemia could account for the ovarian dysgenesis and hence POF. This mechanism has been well described in the literature for testicular failure in men ² with SCD but has not been postulated in women.

Primary infertility is not increased in women with SCD, although age of menarche and age at first pregnancy are delayed. ^3,4 As the life expectancy of women with SCD increases, ^5,6 we may see an increased incidence of infertility. This case report therefore highlights the need to consider screening for ovarian dysfunction in patients with SCD. It also raises the need for detailed research on endocrine disorders in association with SCD as these patients are now living longer.

Competing interests

None declared.