Fertility in sickle cell disorders

THE term Sickle Cell Disorder(SCD) refers to a lifelong inherited single gene disorder. The most common types are individuals with the following haemoglobin genotypes: HbSS, HbSC and HbSThalt+.

The disorder, particularly in its severe form (HbSS), is characterized by premature breakdown of red blood cells, constant anaemia,vaso-occlusive crises, and stunted growth with chronic ill health.

With advances in sickle cell treatment, more and more individuals with SCD are reaching child bearing age. Many studies suggest sickle cell disorder causes infertility but currently there is no consensus on whether women with SCD are at increased risk of infertility.

Sickle cell disorder affects fertility in both males and females but more often in males. A delay in sexual maturation of 1.5-2 years on the average has been reported although most men with SCD go on to have normal sexual maturation. There is a delay in onset of puberty and sexual development due to low testosterone levels in such men.

Infertility in men with SCD appears to have multiple causes including hypogonadism, sperm abnormalities and erectile dysfunction due to priapism. The sperm density, motility and morphology all fall within the sub fertile range in men with SCD. Many of them have sexual problems such as impotence, frequent priapism and premature ejaculation, which could further reduce their fertility.

The possible underlying pathophysiologic mechanisms of the hypogonadism seen in men with SCD include disruptions in the hypothalamic pituitary gonadal axis leading to testicular failure. However, studies are inconsistent as to whether primary testicular failure or secondary hypothalamic pituitary dysfunction is the cause of the sperm abnormalities.

The onset of menstrual bleeding (menarche) is delayed in females with SCD but the menstrual bleeding pattern remains normal

Sickle cell disorder can cause a variety of complications to both mother and the baby during pregnancy and delivery. The mother may suffer complications such as severe anaemia, pre-eclampsia and eclampsia rupture of membranes and premature labour. Patients with SCD often suffer from miscarriages, stillbirths and neonatal deaths. A number of the babies are born small for their gestational age.

Sickle cells do a poor job of carrying oxygen and tend to die quickly leaving a shortage of the oxygen rich blood cells that the mother and baby could rely on. Lack of oxygen causes the expectant mother to experience tiredness, irritability, dizziness and light headedness and difficulty in breathing. The woman’s skin may be pale or there may be jaundice. Pregnant women with severe SCD often require blood transfusions especially when there is associated infection or sequestration. All of these complications increase the risks associated with pregnancy in women with SCD and makes SCD an important contributory factor to the high maternal mortality often encountered in our environment.

On account of the severe stress patients with SCD often experience when pregnant, limitation of family size to 2-3 children is often advised. Bilateral tubal ligation offers a safe permanent method of contraception. For child spacing, progesterone only contraceptive is recommended as it is associated with much lower incidence of thromboembolism than the combined oestrogen progesterone oral contraceptive. The use of copper T intra uterine device in birth spacing should be approached with caution in view of the attendant risk of infection and irregular vaginal bleeding.

Long term therapies for SCD such as chronic blood transfusion, hydroxyurea and haemopoetic stem cell transplantation(HSCT) have reduced SCD related morbidities. However, as utilization of these therapies increases, more attention is drawn to their associated adverse effects and intoxication.

There have been no known negative effects on fertility studied with hydroxyurea. Two reproductive issues that have been raised with the use of the agent in both paediatric and adult population are abnormal spermatogenesis and teratogenic effects.

A form of fertility preservation before HSCT, regardless of the conditioning regimen, might need to be considered.

Scd is very common in our environment and it is known to be associated with infertility and subfertility in men and poor pregnancy out comes in women.

Dr Akinde, Consultant Obstetrician and Gynaecologist,Living Spring Hospital,Ejigbo, Lagos &Consultant, Prenatal Diagnostic Clinic, Sickle Cell Foundation Nigeria, sent this material from Lagos, Nigeria.