Many of these drugs target tyrosine kinase, an important enzyme that regulates signaling pathways involved with cell division, diferentiation, and apoptosis. With irst-trimester use, embryo toxicity or teratogenicity has been attributed to these. Thus, this speciic group of targeted agents is considered for use in pregnancy only if the potential beneit to the pregnant woman justifies the potential risk to the fetus (Lodish, 2013).
Of other agents, the monoclonal antibody trastuzumab (Herceptin) inhibits the human epidermal growth factor receptor type 2 (HER2), which some breast cancers express. Although not teratogenic, its use in the second and third trimesters is associated with oligohydramnios, which appears to be reversible upon stopping the drug (Sarno, 2013; Zagouri, 2013b). Because of sparse available data, other HER2 inhibitors are best avoided in pregnancy (Lambertini, 2015).
Fertility may be diminished after chemotherapy or radiotherapy. Counseling ideally takes place before cancer treatment, and guidelines for this have been developed (American Society for Reproductive Medicine, 2013a; Lambertini, 2016; Loren, 2013; Peccatori, 2013). Prior to therapy, cryopreservation of embryos or of oocytes is a recognized fertility-preserving option (American Society for Reproductive Medicine, 2013b,c). Surgical transposition of the ovaries can be considered if pelvic radiation is planned. For this, ovaries and their intact primary blood supply are carried out of the pelvis and ixed to the lateral abdominal wall at a site 3 to 4 cm above the level of the umbilicus. In one review, functional preservation was reported in 65 to 94 percent, depending on radiotherapy type (Gubbala, 2014). Also, such transposition requires transabdominal egg retrieval if later in vitro fertilization is planned (American Society for Reproductive Medicine, 20 13a).
Ovarian suppression with gonadotropin-releasing hormone agonists is not beneficial, according to a recent review (Elgindy, 2015). At this time, cryopreservation of ovarian tissue is considered investigational. These methods currently are limited to referral centers.
In counseling cancer survivors, evidence suggests that exposure to most radiotherapy or chemotherapy agents in childhood or adulthood does not signiicantly increase the risk of congenital anomalies or genetic disease in their ofspring (Haggar, 2014; Signorello, 2012; Stensheim, 2013; Winther, 2012). In those treated as children with chemotherapy, studies also do not show a consistent link to adverse obstetrical outcomes (Melin, 2015; Reulen, 2009). Data are limited regarding those with cancer treated as an adult, and some studies have shown slightly higher rates of preterm birth and cesarean delivery (Haggar, 2014; Stensheim, 2013).
Notably, prior abdominopelvic radiation more convincingly afects neonatal outcomes. Adverse efects include elevated rates of abortion, low birthweight, stillbirth, and preterm birth (Signorello, 2006, 2010; Winther, 2008). Radiation may lower reproductive potential by creating reduced uterine volume, a thinned endometrium, and impaired uterine blood flow (Critchley, 1992; Larsen, 2004). Greater efects are seen with direct uterine radiation and with radiotherapy at younger ages (Teh,r2014).
Importantly, many cancer survivors conceive by assisted reproductive technology, which by itself has associated obstetrical risks. his is discussed in Chapter 8 (p. 151).