Fertility of children exposed in utero to chemotherapy

Concerns regarding gonadal function and reproductive capacity after in utero exposure to chemotherapy and radiation are emerging, and their exact full effects are not well defined. There is a lack of large, prospective studies to fully answer this question, and conclusions were made based on a few cohorts, heterogeneous patient populations and chemotherapy regimens, and substantial case report bias [1–5]. It is well known that most drugs reach the fetus in significant concentration after maternal administration as the placenta is not an effective barrier. Although, some authors agree the use of certain chemotherapy regimens (especially in the second or third trimester) is safe as the risk of acute or late complication are low, the risk in the first trimester is yet to be evaluated [1]. Fetal malformations have been reported in children born to mothers who received chemotherapy during the first trimester [1]. Safety guidelines of chemotherapy agents during pregnancy are based on relatively few cohorts and case reports. The effects of chemotherapy on the offsprings' gonadal function stem mainly from different reports of germ cell depletion after administration of alkylating agents in childhood cancer survivors. However, as most of these studies have focused on adults, it was unclear whether exposure to chemotherapy during early childhood and especially in utero is associated later with gonadal dysfunction. Gonadal Function It has been estimated that the dose of radiation required to destroy 50% of immature oocytes is less than 2 Gy [6]. Destruction of primordial follicles results in impaired ovarian hormone production due to inadequate estrogen exposure [6]. Bath et al. studied ovarian function in cancer survivors treated with total-body irradiation. Women with ovarian failure had small uterine volume and undetectable blood flow. Young girls who were exposed to irradiation prepuberty also did not respond well to a sex steroid replacement regimen [7]. In men, administration of alkylating agents with or without radiation to sites below the diaphragm was associated with a fertility deficit of approximately 60% [8].