Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial.
BACKGROUND
In the HD14 trial, 2×BEACOPPescalated+2×ABVD (2+2) has improved the primary outcome. Compared with 4×ABVD, this benefit might be compromised by more infertility in women. Therefore, we analyzed gonadal function and fertility.


METHODS
Women≤45 years in ongoing remission at least 1 year after therapy were included. Hormone parameters, menopausal symptoms, measures to preserve fertility, menstrual cycle, pregnancies, and offspring were evaluated.


RESULTS
Three hundred and thirty one of 579 women addressed participated (57.2%) and 263 per-protocol treated patients qualified (A=ABVD: 137, B=2+2: 126, mean time after therapy 42 and 43 months, respectively). Regular menstrual cycle after treatment (A: 87%, B: 83%) and time to recovery (≤12 months) were not different. Follicle-stimulating hormone and anti-Muellerian hormone were significantly better in arm A. However, pregnancies after therapy favored arm B (A: 15%, B: 26%, P=0.043) and motherhood rates were equivalent to the German normal population. Multivariate analysis revealed prophylactic use of gonadotropin-releasing hormone (GnRH) analogues as highly significant prognostic factor for preservation of fertility (odds ratio=12.87, P=0.001). Severe menopausal symptoms were frequent in women≥30 years (A: 21%, B: 25%).


CONCLUSIONS
Hormonal levels after 2+2 indicate a reduced ovarian reserve. However, 2+2 in combination with GnRH analogues does not compromise fertility within the evaluated observation time.
First Department of Internal Medicine, University Hospital of Cologne, and Institute for Clinical Chemistry, University of Cologne, Cologne, Germany.
K
K
Behringer
I
I
Thielen
H
H
Mueller
H
H
Goergen
A D
AD
Eibl
J
J
Rosenbrock
T
T
Halbsguth
D A
DA
Eichenauer
M
M
Fuchs
K S
KS
Reiners
J H
JH
Renno
K
K
van der Ven
M
M
Kuehr
M
M
von Wolff
V
V
Diehl
A
A
Engert
P
P
Borchmann
D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000009:adverse effects / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D003606:Dacarbazine / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000627:therapeutic use; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D016015:Logistic Models; D008593:Menopause / Q000187:drug effects; D008597:Menstrual Cycle / Q000187:drug effects; D008875:Middle Aged; D015999:Multivariate Analysis; D010053:Ovary / Q000187:drug effects / Q000503:physiopathology*; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011247:Pregnancy; D011344:Procarbazine / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D017741:Survivors; D014747:Vinblastine / Q000009:adverse effects / Q000627:therapeutic use; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
D001761:Bleomycin; D007987:Gonadotropin-Releasing Hormone; D011344:Procarbazine; D014750:Vincristine; D014747:Vinblastine; D005047:Etoposide; D003606:Dacarbazine; D004317:Doxorubicin; D054304:Anti-Mullerian Hormone; D003520:Cyclophosphamide; D005640:Follicle Stimulating Hormone; D011241:Prednisone