Long-term outcomes of fertility preservation counseling in women of reproductive age prior to gonadotoxic therapy

As survival rates for reproductive-aged women with cancer improve, the importance of fertility preservation (FP) prior to gonadotoxic chemotherapy has increased. This study evaluated long-term FP outcomes by comparing return rates and clinical pregnancy rates across FP strategies —oocyte and embryo cryopreservation and GnRH agonist use—and analyzed longitudinal ovarian reserve changes via serum anti-Müllerian hormone (AMH).

Among 399 women analyzed, breast cancer was the most common diagnosis (72.4%). Serum AMH declined profoundly at 6 months post-chemotherapy (3.07 to 0.08 ng/mL, p < 0.01), with partial recovery at 12 months (0.30 ng/mL), remaining significantly below baseline throughout 60-month follow-up. Longitudinal AMH data were available only for GnRH agonist-treated patients, precluding direct comparison with untreated patients. The return rate for pregnancy counseling was highest in the embryo cryopreservation group (63.4%). Total CPR among returning patients were significantly higher in the oocyte cryopreservation (70.5%) and embryo cryopreservation (69.2%) groups versus the counseling-only group (28.5%) (p = 0.020 and p = 0.014, respectively). Notably, all cryopreservation patients also received GnRH agonists; comparisons therefore reflect GnRH agonist plus cryopreservation versus GnRH agonist alone versus no active FP. GnRH agonist use alone did not show a significant advantage over counseling only.

Chemotherapy is associated with a substantial and lasting reduction in ovarian reserve despite GnRH agonist co-treatment. Oocyte and embryo cryopreservation were associated with significantly higher CPR compared with counseling or GnRH agonist use alone, though causal inference is precluded by the retrospective design. The independent effect of GnRH agonists on ovarian reserve could not be fully assessed due to the absence of a GnRH agonist-naive control group with longitudinal follow-up. Cancer patients represent a distinct FP population with higher return rates than social FP cohorts, underscoring the importance of cancer-specific evidence for counseling. These findings support early FP counseling and suggest cryopreservation offers reproductive benefits beyond GnRH agonist use alone.