化疗后生育力的变化

　　Resumption of menstrual cycles in breast cancer patients implies the recovery of ovarian function. However, in combination with FSH and estradiol levels, it does not necessarily imply fertility potential, as most infertile women still have menstrual periods. Amenorrhea is therefore not a good indicator for menopause or fertility.

　　乳腺癌患者月经周期的恢复意味着卵巢功能的恢复。但是，结合促卵泡激素和雌二醇水平来看，月经周期的恢复并不一定代表其仍有生育能力，因为大多数不育妇女仍然有月经期。 因此，闭经不能作为判断绝经或生育能力的参考标准。

　　Anti-Müllerian hormone (AMH) and primordial follicle counts can be helpful in evaluating the risk of undergoing amenorrhea (1). In a study of ovarian tissue cryopreservation for fertility preservation, lower primordial follicle counts in chemotherapy patients compared to the control group who had not received chemotherapy (5.4+/-1.3 versus 9.6+/-2.2)and lower counts in the alkylating agent groups than in the non-alkylating agent groups (2.9+/-1 versus 7.9+/-1.6) were seen (2). Another study, comparing 20 breast cancer survivors and 20 control women demonstrated that antral follicle count(AFC) and AMH levels were highly correlated(r=0.72) and were better indicators of ovarian reserve than FSH and inhibin B. (3) Interestingly, it also showed that survivors on tamoxifen had lower AFC, AMH and inhibin B and higher estradiol levels than non-tamoxifen-treated survivors. AMH, which is not cycle-day dependent, is indeed a better predictor of ovarian reserve and more accurately differentiates normal from abnormal ovarian reserve after chemotherapy than do FSH and estradiol levels. However, more prospective studies are needed to determine the predictive value of these tests for pregnancy after chemotherapy.

　　抗缪勒管激素(AMH)和原始卵泡数量有助于评估闭经的风险(数据参考见1)。在一项卵巢组织冷冻保存以保留生育力的研究中，与未接受化疗的对照组相比，化疗患者的原始卵泡数量较低(5.4 +/- 1.3对比9.6 +/- 2.2)，与非烷化剂组相比，烷化剂组的卵泡数量较低，(2.9 +/- 1对比7.9 +/- 1.6)(数据参考见2)。另一项研究比较了20名乳腺癌幸存者和20名对照女性，结果表明，与促卵泡激素(FSH)和抑制素B相比，基础卵泡数(AFC)和AMH指标高度相关(r = 0.72)，并且是卵巢储备功能的更佳判断指标(数据参考见3)。与非他莫昔芬治疗的幸存者相比，接受他莫昔芬治疗的幸存者的AFC，AMH和抑制素B含量较低，雌二醇水平更高。与FSH和雌二醇水平相比，AMH指标不随月经周期天数的改变而发生较大波动，是卵巢储备功能预测的更佳参考指标，并且在化疗后可以更准确地区分正常和异常卵巢储备，但是需要更多前瞻性研究来确定这些指标的预测价值。

　　Overall, the fertility potential among female cancer survivors is compromised after chemotherapy. But subsequent pregnancy after early stage breast cancer does not adversely affect the prognosis. (4) Patients are generally advised to wait at least two years to be free of disease before attempting to conceive after chemotherapy. The first two years after diagnosis are when recurrence rates are the highest. In addition, this delay allows the developing follicles with theoretical DNA damage from chemotherapy to be cleared from the ovary and new follicles to be recruited from surviving primordial follicles. (5)

　　总体而言，化疗后女性癌症幸存者的生育力受到损害。但是，早期乳腺癌患者的后续妊娠不会对预后产生不利影响(数据参考见4)。通常建议患者在接受化疗后等两年，确保没有复发后再尝试怀孕，确诊后的头两年是复发率最高的时候。 此外，等待的时间段能使卵巢中理论上DNA受到损伤的处于发育中的卵泡得以清除，并从存活的原始卵泡中募集了新的卵泡(数据参考见5)。

　　A recent mice study raised concern that some anticancer drugs might result in transgeneration algenomic instability manifesting in their offspring in mice model. (6) However, there had been several large scale studies looking into pregnancy outcomes in childhood cancer survivors who were able to conceive and who received chemotherapy and/or radiation therapy. There were no significant differences in pregnancy outcomes, including stillbirth, miscarriages, abortions, live birth, and birth weight. (7-9)

　　最近一项备受关注的小鼠研究发现，一些抗癌药物可能会导致小鼠模型中的后代表现出转基因的基因组不稳定性(数据参考见6)。不过，也有几项大规模研究，分析能够怀孕但接受了化学疗法和/或放射疗法的儿童癌症幸存者的妊娠结果，发现受试者的妊娠结果包括死产，流产，流产，堕胎，活产和出生体重都没有显着差异(数据参考见7-9)。

　　Reference 数据参考：

　　1. Anderson RA, Cameron DA. Pretreatment serum anti-mullerianhormone predicts long-term ovarian function and bone mass afterchemotherapy for early breast cancer. J Clin Endocrinol Metab.2011; 96 (5): 1336-43.

　　2. Oktem O, Oktay K. Quantitative assessment of the impact ofchemotherapy on ovarian follicle reserve and stromal function.Cancer. 2007; 110 (10): 2222-9.

　　3. Partridge AH, et al. Ovarian reserve in women who remainpremenopausal after chemotherapy for early stage breast cancer.Fertil Steril. 2010; 94 (2): 638-44.

　　4. Gelber S, et al.Effect of pregnancy on overall survival after thediagnosis of early-stage breast cancer. J Clin Oncol. 2001;19(6):1671-5.

　　5. Lawrenz B, et al. Pregnancy after breast cancer: case report andreview of the literature. Arch Gynecol Obstet. 2011;283(4):837-43.

　　6. Glen CD,Dubrova YE. Exposure to anticancer drugs can result intransgenerational genomic instability in mice. Proc Natl Acad Sci.USA. 2012; 109 (8): 2984-8.

　　7. Green DM,et al. Pregnancy outcome of female survivors of childhoodcancer:a report from the Childhood Cancer Survivor Study. Am JObstet Gynecol. 2002; 187 (4): 1070-80.

　　8. Chiarelli AM, Marrett LD, Darlington GA. Pregnancy outcomes infemales after treatment for childhood cancer. Epidemiology.2000;11 (2) : 161-6.

　　9. Reulen RC, et al. Pregnancy outcomes among adult survivors ofchildhood cancer in the British Childhood Cancer Survivor Study.Cancer Epidemiol Biomarkers Prev. 2009; 18(8): 2239-47.