Liver transplantation restores female reproductive endocrine function

Abstract

The effect of successful liver transplantation on menstrual function was assessed by questionnaire in 44 women transplanted for various types of end stage liver disease, acute liver failure or malignant disease. Significant amenorrhoea (>one year) was present in 48% of women with chronic liver disease before transplantation, and was reversed within 10 months of surgery in all but one of the pre-menopausal patients who had primary amenorrhoea and hypogonadotrophic hypogonadism. Two patients became pregnant five months and 1–5 years after transplantation, but in one instance the pregnancy was unsuccessful, possibly as a consequence of cyclosporin related intrauterine growth retardation. Seventeen female patients who underwent orthotopic liver transplantation between June 1973 and June 1987 became pregnant 5 months to 11 years after transplantation. Immunosuppression was maintained with combinations of prednisone, cyclosporine, and azathioprine prior to and during pregnancy. One patient discontinued immunosuppression after knowledge of pregnancy, taking only azathioprine sporadically. Mean age at time of delivery was 26 years. Twelve patients had no alteration in liver function studies; 7 patients demonstrated mild or moderate enzyme elevations prior to delivery, with one case of rejection confirmed by percutaneous liver biopsy. Major problems related to pregnancy were hypertension, anemia, and hyperbilirubinemia. Twenty live births occurred (2 patients had 2 separate pregnancies, one patient has a set of twins); 13 were by caesarian section, 7 by vaginal delivery. Eleven of the 13 caesarian births were premature by gestational age. All vaginal births were term. Toxemia of pregnancy and early rupture of membranes were the principal indications for caesarean section. There were no congenital abnormalities or birth defects and all the children are surviving well. Fifteen of 16 children older than one year have normal physical and mental development, with one child manifesting immature speech development. Four children are under one year, all with normal milestones thus far. Sixteen of the 17 mothers are alive from 2–18 years after transplantation; the only death was from a lymphoma, almost 4 years after transplantation and 2 1/2 years after delivery. This experience suggests that women undergoing liver transplantation can safely bear children despite an increased risk of premature caesarian births. The effect of chronic immunosuppression of female pediatric patients on their reproductive potential later in adulthood remains to be fully evaluated but the results so far are favorable.