Late Effects of the Reproductive System
Fertility was evaluated among the 6,224 male CCSS participants aged 15 to 44 years who were not surgically sterile. They were less likely to sire a pregnancy than siblings (hazard ratio [HR] 0.56; 95% CI, 0.49-0.63). Among survivors, the HR of siring a pregnancy was decreased by radiation therapy greater than 750 cGy to the testes (HR = 0.12; 95% CI, 0.02-0.64), higher summed AAD score or treatment with cyclophosphamide (third tertile - HR = 0.42; 95% CI, 0.31-0.57) or procarbazine (second tertile - HR = 0.48; 95% CI, 0.26-0.87; third tertile - HR = 0.17; 95% CI, 0.07-0.41). The HR of siring a pregnancy was inversely related to the summed AAD score (P -value for linear trend = <.001). Those who had a summed AAD score of 2 (HR = 0.67; 95% CI, 0.51-0.88; P = .004), 3 (HR = 0.48; 95% CI, 0.36-0.65; P <.001), 4 (HR = 0.34; 95% CI, 0.22-0.52; P <.001), 5 (HR = 0.38; 95% CI, 0.22-0.66; P <.001), or 6 to 11 (HR = 0.16; 95% CI, 0.08-0.32; P <.001) were also less likely to ever sire a pregnancy compared with those who did not receive any alkylating agents. Compared with siblings, the HR for ever siring a pregnancy for survivors who had an AAD score = 0 and a hypothalamic/pituitary radiation dose of 0 cGy and a testes radiation dose of 0 cGy was 0.91 (95% CI, 0.73-1.14; P = .41).
Fertility was evaluated among the 5,149 female CCSS participants and 1,441 female siblings of CCSS participants, aged 15 to 44 years. The RR for ever being pregnant was 0.81 (95% CI, 0.73-0.90; P < .001) compared with female siblings. In multivariate models among survivors only, those who received a hypothalamic/pituitary radiation dose of greater than 3,000 cGy (RR = 0.61; 95% CI, 0.44-0.83) or an ovarian/uterine radiation dose greater than 500 cGy were less likely to have ever been pregnant (RR = 0.56 for 500-1000 cGy; 95% CI, 0.37-0.85; RR = 0.18 for >1000 cGy; 95% CI, 0.13-0.26). A summed AAD score of 3 (RR = 0.72; 95% CI, 0.58-0.90; P = .003) or 4 (RR = 0.65; 95% CI, 0.45-0.96; P = .03) was associated with lower observed risk of pregnancy compared with those with no alkylating agent exposure. Those with a summed AAD score of 3 or 4 or who were treated with lomustine or cyclophosphamide were less likely to have ever been pregnant.
Fertility may be impaired by factors other than the absence of sperm and ova. Conception requires delivery of sperm to the uterine cervix, patency of the fallopian tubes for fertilization to occur, and appropriate conditions in the uterus for implantation. Retrograde ejaculation occurs with a significant frequency in men who undergo bilateral retroperitoneal lymph node dissection. Uterine structure may be affected by abdominal irradiation. A recent study demonstrated that uterine length was significantly shorter in ten women with ovarian failure who had been treated with whole abdomen irradiation. Endometrial thickness did not increase in response to hormone replacement therapy in three women who underwent weekly ultrasound examination. No flow was detectable with Doppler ultrasound through either uterine artery of five women, and through one uterine artery in three additional women.