Effects of Cytoreductive Therapy on Fertility and the Fetus

Gonadal suppression resulting in amenorrhea or azoospermia may occur in patients taking cytoreductive agents. High doses of HU, busulfan, and interferon-alpha have been shown to be harmful to spermatogenesis in experimental animals and busulfan has resulted in ovarian failure in older patients.125 However, fertility has been retained in patients treated with HU and inter-feron-alpha126,127 Anagrelide has no effect on fertility in male rats but in female rats, at high dosage, it disrupted implantation and retarded or blocked parturition. Five women have, however, become pregnant on anagrelide therapy. Treatment was stopped as soon as the pregnancy was detected and all five patients delivered normal babies.125

The use of cytoreductive therapy in pregnant patients with an MPD is associated with an increased risk of spontaneous abortion, congenital malformation, premature delivery, and intrauter-ine growth retardation128 (recently reviewed in Ref. 125). Fetal malformations and fetal loss have been reported with busulfan and HU taken in the first trimester and teratogenicity has been demonstrated in animals treated with HU.129 Interferon-alpha has been increasingly used in patients with MPD. There have been no reports of adverse effects on the fetus, and successful pregnancies have been reported.130,131 Interferon-alpha does not appear to cross the placenta to any significant extent;132 however, teratogenic or other adverse effects cannot be entirely ruled out and it should be used with caution. As many of the agents used to treat PV are excreted in human breast milk a decision should be made whether to discontinue breastfeeding or discontinue the drug, weighing the importance of the drug to the mother.

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