Effect of epilepsy on female fertility and reproductive abnormalities.

Sir,

Epilepsy is a common neurological disorder in males and females.[12] Reproductive abnormalities and infertility are two to three times more common in epileptic females than in the general population.[12] It may be a direct effect of epileptiform discharges on pituitary and hypothalamus. Seizure can lead to an increase in the serum prolactin level and an acute increase in the luteinizing hormone (LH) and follicle stimulating hormone (FSH). Epileptic women have a higher rate of reproductive and endocrine disorders. They have more variation in the LH pulse frequency and lower LH concentrations than non-epileptic women.[2] Around 50% of the epileptic women have menstrual abnormalities and higher frequency of anovulatory cycles.[2] The incidence of anovulatory cycles are more commonly reported in left temporal lobe epilepsies.[2] The incidence of reproductive abnormalities, for example, hypogonatropichypogonadism is reported to be higher in epileptic patients, especially in those women having epileptiform foci on the right side; and the incidence of polycystic ovary disease (PCOD) is higher in epileptic women, and they were found in 41% of women with idiopathic generalized epilepsy, and 26% of women with focal epilepsy, especially those having left-sided epileptiform foci.[23]

Reduction in libido is reported in one-third of epileptic women or epileptic men.[24] In epileptic females hyposexuality and orgasmic dysfunction was reported to be around 8-68%, which is more common in focal seizures as compared to generalized seizure activity.[2] Shukla et al, have reported hyposexuality or sexual dysfunction in 64% of women having partial epilepsies, compared to 8% having generalized epilepsies.[4] Lower birth rates in women with epilepsy may also be due to social inhibitions, poor self-esteem, fear of seizure during relationships or intercourse, fear of the effects of epilepsy and its treatment on pregnancy, late marriage, fear of development of seizure in subsequent children, and sexual dysfunction due to social and cognitive factors.[5]

Antiepileptic drugs used during the management of women with epilepsy may also produce reproductive and endocrinal disturbances.[2] They may interfere with the hypothalamic pituitary axis and produce amenorrhea, oligomenorrhea, and prolonged and irregular cycles.[2] Higher incidence of PCOD is also reported in women taking valproate sodium, and a retrospective series reported PCOD in 43% of women taking valproate for epilepsy.[26] A recent study done in India, concluded that infertility was least common (7.1%) in those epileptic women who were not on antiepileptic drug (AED) exposure compared to those who were with AED exposure (31.8% with one AED exposure, 40.7% with two AED exposures, and 60.3% with three or more AED exposures).[1] Epileptic women who were taking phenobarbital had a significantly higher risk of infertility, but no such trend was observed with other AED drugs.[1] Infertility was also common in epileptic women who were older in age, with lower education.[1]

After reviewing the articles, we concluded that the problem of infertility in epileptic women was complex and multifactorial. There were many factors involved, for example, age, education, type of epilepsy, frequency of seizures, site of ictal onset, as well as, how many and which AED was used for management.[12] If an epileptic patient presented with infertility to the reproductive medicine clinic, careful evaluation should be done for both partners.[2] For women with epilepsy, a detailed history of the type of seizure, frequency of seizures, whether controlled with AED or not, andwhat AED the patient was taking to control the seizures, should be taken.[2] Apart from this, serum LH and FSH level should also be measured. Pelvic ultrasonography to rule out PCOD should be done.[2] Proper evaluation of AED should be carried out, if possible monotherapy of AED should be promoted for seizure control, and phenobarbital should be avoided in epileptic women who have not attained fertility.[1] Valproate sodium should also be avoided in these women. If the patient was already on valproate sodium for seizure control and presented with infertility, valproate sodium should not be stopped, unless she was diagnosed with PCOD.[2] Proper counseling should be given with regard to the disease process and it should be made clear that the disease would have no effect on pregnancy if it was controlled, especially in the case of illiterate women.[15]