Hypogonadotrophic Hypogonadism and Diminished Gonadal Reserve Accounts for Dysfunctional Gametogenesis in Thalassaemia Patients with Iron Overload Presenting with Infertility

Abstract

Improved care of β-thalassemia major (β-TM) patients has brought with it new challenges for the patient to have a family. We report our 15-year experience with 30 couples with 28 pregnancies following artificial reproductive techniques (ART). Sixty percent of females had hypogonadotrophic hypogonadism (HH) with diminished ovarian reserve and responded favorably to gonadotrophins with 80% success rate within three cycles. Pulsatile gonadotrophin-releasing hormone (GnRH) infusion was used in one and clomiphene in another patient which resulted in successful pregnancies. Males responded less favorably than females. Gonadotrophins were used in 14 pulsatile HH patients for 6-24 months with variable outcomes. Although successful paternity did not occur, successful spermatogenesis with oligoasthenospermia occurred in six men. Two had in vitro fertilization (IVF) and intracytoplasmic injections (ICSI), which resulted in healthy offspring. In conclusion, successful pregnancy and fertility are feasible in β-TM patients with diminished gonadal reserves. Better outcome is expected in females than males. We report the first two cases of paternity following IVF and ICSI in β-TM patients with HH.