Factors of importance for implantation and problems after treatment for childhood cancer

The uterus is of fundamental importance to reproduction; it nourishes the e arly embryo and accommodates growth and differentiation of the developing f etus. It is thus possible that the modalities employed to treat childhood c ancer, that is; chemotherapeutic agents, and particularly irradiation, may result in damage to the uterine structure (musculature and local vasculatur e), with potential impairment of normal uterine function and thus increased risk of subsequent defective implantation. This may result in an impaired reproductive outcome (increased risk of spontaneous abortion, preterm labou r, and low-birth-weight infants). Thus the reproductive problems foreseen f ollowing treatment of childhood cancer will be ii ovarian failure or impair ed ovarian activity and 2) uterine/endometrial structural and functional da mage. The mode of treatment and age at its administration will be the major determinants of residual ovarian and uterine function. To understand the m echanisms that may be responsible for potential problems in reproductive fu nction after treatment, it is essential to consider the mechanisms governin g normal early pregnancy. Ovarian estradiol (E) and progesterone (P) secret ed in a cyclical manner orchestrate the spatial and temporal morphological and functional changes in the endometrium required for implantation. In the absence of sex steroids, the endometrium is inactive. implantation takes p lace in the midsecretory phase, that is, 5-9 days postovulation. E and P ac t sequentially to regulate cellular concentrations of their respective rece ptors and in turn gene transcription events are initiated to prepare the en dometrium for implantation. A complex inter action exists between the netwo rk of uterine cells (epithelial, stroma, vascular, haemopoietic) and the en docrine system. Several key factors implicated in the implantation process will be addressed. There is published evidence that reports the risk of pub ertal failure and early menopause after treatment for childhood cancer and, in those women who continue with ovarian activity and achieve pregnancy, a risk of poor reproductive outcome. It is likely that radiation damage to t he uterus will adversely effect pregnancy potential. Our own group has repo rted impaired uterine characteristics in women after abdominal irradiation. More recently, we have shown that lower doses of radiotherapy las with tot al-body irradiation) may be associated with a potential for improved uterin e characteristics in response to physiological sex steroid replacement. The outlook after chemotherapy alone may be more optimistic; our early data su pport a normal uterine morphological response. Reproductive out come in the se patients remains unpredictable, so simple noninvasive assessment of uter ine characteristics may provide data of predictive value with respect to fu ture fertility potential. Med. Pediatr. Oncol. 33:9-14, 1999. (C) 1999 Wile y-Liss, Inc.