Impact of ABVD chemotherapy on ovarian reserve after fertility preservation in reproductive-aged women with Hodgkin lymphoma.

RESEARCH QUESTION: How is ovarian reserve affected by chemotherapy in patients with Hodgkin lymphoma (HL) who undergo fertility preservation (FP)? METHODS: A retrospective study was conducted by reviewing medical records of 105 HL patients referred to the FP unit before starting adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. Ovarian reserve was evaluated before chemotherapy and at the last follow-up using anti-Müllerian hormone (AMH) and antral follicle count (AFC) measurements. The decrease in AMH was compared with that expected from normograms. AMH was compared between patients who underwent cryopreservation of ovarian tissue and those who underwent cryopreservation of mature oocytes. RESULTS: After ABVD, 15% of patients required hematopoietic stem cell transplantation. At a median follow-up of 33 months, the median decrease in AMH was 0.88 ng/mL, which was significantly greater than that of the general population of this age group (p < 0.001). Of the 82 women who only had ABVD, 38 underwent FP by cryopreservation of mature oocytes and 44 underwent cryopreservation of the ovarian cortex. There was no significant difference in AMH or AFC at the last follow-up between FP techniques. CONCLUSION: Although ABVD is considered to be of low gonadotoxic risk, the decrease in AMH was greater than expected for patients' age, and 15% of patients needed more aggressive therapy during follow-up. Type of FP was not associated with decline in ovarian reserve. Reproductive-aged women with HL should have the opportunity for FP counseling before starting treatment.

Optimizing ovarian tissue quality before cryopreservation: comparing outcomes of three decortication methods on stromal and follicular viability.

OBJECTIVE: To evaluate whether specific ovarian decortication techniques vary in promoting ovarian cortex cryopreservation and transplant outcomes. DESIGN: Experimental design. SETTING: University hospital. ANIMAL(S): Nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) female mice. INTERVENTION(S): Human ovarian biopsy samples allocated to one of the following decortication procedures: scratching with scalpel blade (B), cutting with microsurgical scissors (M), separation with slicer (S), or no-separation (control, C). Parallel, in vivo experiment: decortication techniques combined with slow freezing (SF) and vitrification (VT) before xenograft into immunodeficient mice. MAIN OUTCOME MEASURE(S): Follicular counts, apoptosis, shear stress, Hippo pathway and inflammation. In vivo: recovered grafts analyzed for follicular counts, angiogenesis, proliferation, and fibrosis. RESULT(S): There were no differences in follicular density or number of damaged follicles between the decortication techniques in the in vitro study. Nevertheless, the M samples showed statistically significantly increased stromal damage compared with the controls and S samples, and up-regulation of Hsp60 shear stress gene expression. Decortication by both M and S inhibited the Hippo pathway, promoting gene expression changes. In the 21-day xenograft, total follicular density statistically significantly decreased compared with the nongrafted controls in all groups. Nevertheless, no differences were observed between the decortication techniques. Ovarian stroma vascularization was increased in the vitrified samples, but among the slow-freezing samples, the B samples had the lowest microvessel density. The M decorticated xenografts had increased fibrosis. CONCLUSION(S): Decortication with a slicer causes less damage to ovarian tissue than other commonly used methods although microsurgical scissors seem to preserve slightly increased follicular numbers. Nevertheless, blade decortication seems to be a reliable technique for maintaining acceptable follicular conditions without inducing serious stromal impairment.