Hodgkin’s lymphoma is frequently diagnosed in women of reproductive age but has a high healing rate under adequate cytotoxic therapy. According to a calculation of the cancer register of the Saar region (www.krebsregister.saarland.de), more than 150 women aged between 15 and 34 develop Hodgkin’s lymphoma (HL), but the 5-year survival rate for all age groups is as high as 89% (von Wolff et al. Gynäkologische Endokrinologie 2006, 4:189-196). Therefore, all women with HL who have not completed their family planning should present to an experienced centre to receive advice on fertility protection immediately after the lymphoma is diagnosed (contacts).
Risk of therapy-induced ovarian damage
Due to limited data, it is difficult to estimate therapy-induced ovarian damage. Some published articles are based on small case numbers or date back to the 1980s and cannot therefore be interpreted because of the change in chemotherapeutic regimens.
In a study published in 1981, 11 out of 24 patients (46%) developed secondary amenorrhea after therapy for HL based on the MOPP regimen (Mechlorethamine, Vincristine, Procarbacine, Prednisone) (Schilsky et al. Am J Med 1981, 70:552-556).
According to a study published in 1983, 17 out of 44 patients (39%) with HL developed a secondary amenorrhea after being treated with the MVPP regimen (Mechlorethamine, Vincristine, Procarbacin und Prednisone) (Whitehead et al. Cancer 1983, 52:988-993).
In 2003, a study was published in which 34 out of 84 patients (40%) developed amenorrhea after receiving treatment for HL or NHL (Franchi-Rezgui et al. Hematol J 2003, 4:116-120).
In 2005, a major study was carried out with 405 patients in an attempt to determine the amenorrhea rate as a function of age and the type of chemotherapy applied (Behringer et al. J Clin Oncol 2005, 23:7555-7564). In women < 30 years, the rate of amenorrhea was between 5-40 % and in women ≥ 30 years, it was between 5-70%. Low amenorrhea rates were found after chemotherapies using the ABVD regimen. The rate was much higher after treatment with the COPP, BEACOOP and especially after the intensified-dose BEACOOP regimen.
This study supports other data (Andre et al. Hematol Cell Ther 1997, 39:59-65; Busamolino et al. Haematologica 2000, 85:1032-1039), showing that after treatment with the ABVD regimen applied in the early stages of the lymphoma, the rate of amenorrhea is low. Therefore, it may be possible to avoid fertility protection measures when the ABVD regimen is followed.
Possibilities of fertility protection
As a rule, the full range of fertility protection measures can be offered since the cytotoxic therapy is often only initiated two weeks after the diagnosis or can be postponed so that there is a sufficient time window available.
The following fertility protection measures are possible:
As an alternative especially for patient below 35, ovarian tissue may be laparoscopically retrieved and cryopreserved. The risk of metastasis when the tissue is retransplanted must however be discussed although no such metastasis has been reported in humans after the transplantations performed so far.
In addition to the measures mentioned, GnRH analogues may be administered during chemotherapy. However, there is no clear evidence of the effectiveness of GnRH agonists yet. The general conclusion from the nine controlled studies published so far points to a protective effect, however (Blumenfeld & von Wolff Hum Reprod Update 2008 in press).
Cryopreservation of sperm is an established procedure. Before the cytotoxic therapy, one or several sperm samples are obtained by ejaculation. Cryopreservation is also useful when the sperm quality is poor. If the cryopreserved sperm is to be used at a later stage, there is a choice between the relatively simple intrauterine insemination or ICSI treatment. In principle, the prophylactic preservation of sperm can be recommended before the cytotoxic therapy is started.