Following Hodgkin's lymphoma treatment, conception more likely with fertility methods


Pre-treatment cryopreservation of semen may double men's odds of conception after treatment for Hodgkin's lymphoma, according to Dutch investigators.

Overall, 79% of men had successful conception with cryopreserved semen compared with 74% of men without frozen semen, a nonsignificant difference. But after adjustment for patient age, treatment with alkylating agents, and receipt of second-line therapy, the odds of post-treatment conception increased to 2.03 for men who froze semen before starting therapy versus those who did not.

Examination of factors that influenced a man's decision to preserve semen prior to treatment distinguished the study from prior investigations, Marleen A.E. van der Kaaij, MD, of VU Medical Center in Amsterdam, and co-authors reported online in Human Reproduction.

"The vital role of semen cryopreservation in securing chances of post-treatment fatherhood is underlined by the fact that among those wishing to become fathers after Hodgkin's lymphoma treatment, men who had cryopreserved semen had twice greater odds of succeeding compared with those who did not cryopreserve their semen," the authors concluded.

"Twenty-three percent of men unable to conceive spontaneously did not have cryopreserved semen available and did not become fathers. Information about fertility preservation and access to cryopreservation facilities among cancer patients should be optimized."

The improvement in conception rate with cryopreserved semen comes as no great surprise, a U.S. fertility specialist told MedPage Today by email.

"It's not new. Indeed the American Cancer Society has stated that all individuals facing gonadotoxic therapies should be offered counseling about the potential of preserving fertility by cryopreserving gametes," said David Cohen, MD, of the University of Chicago. "To me this study simply validates what is already known; it is not surprising."

Any patient of reproductive age, male or female, should be offered cryopreservation prior to potential fertility-threatening treatment, he added. Of note, some malignancies might harbor a germ-line mutation that can be transmitted to a next generation, making investigation of potential genetic associations with a patient's tumor an essential part of counseling and informed consent.

In Europe, cryopreservation of semen prior to cancer therapy has been available since the early 1970s. However, little is known about factors that influence men to have semen samples frozen for future use, either for themselves or other infertile individuals. To explore the reasons, van der Kaaij and colleagues analyzed data on men who had undergone treatment for lymphoma since 1974, focusing on Hodgkin's lymphoma because of its frequency in reproductive-age men.

The study included 3,399 men from 13 European countries who participated in randomized trials of Hodgkin's lymphoma therapy from 1974 to 2004. The most commonly used treatment regimens consisted of chemotherapy with or without radiotherapy. Addresses at last follow-up for 1,849 survivors were updated in 2008.

Investigators distributed the Life Situation Questionnaire (LSQ) to study survivors in France, Belgium, the Netherlands, Italy, and Switzerland. The LSQ includes questions related to cryopreservation, fertility, and fatherhood. Subsequently, 927 men returned questionnaires and signed consent forms.

After excluding men because of treatment protocol violations or incomplete data, van der Kaaij and colleagues analyzed 902 completed questionnaires, consisting of 363 men who had frozen semen samples and 539 who did not.

The study participants had a median age of 31 at the time of treatment for Hodgkin's lymphoma and a median follow-up of 13 years. Men 30 to 39 and those 40 and older had progressively lower rates of cryopreservation as compared with younger men (OR 0.22, OR 0.01, P<0.001 for both comparisons).

Higher disease stage had a negative effect on cryopreservation (OR 0.54, P=0.02). Factors that increased the odds of cryopreservation were treatment with chemotherapy (OR 4.26, P<0.001), second-line treatment for progression or relapse (OR 2.03, P=0.01), and higher levels of education (OR 1.60, P=0.01).

The authors found that 78 (21%) of the men with cryopreserved semen used their samples. Factors that increased the likelihood that samples would be used were year of treatment (60% for 1994 to 2004, 29% for 1984 to 1993, and 10% for 1974 to 1983), treatment with alkylating agents (OR 9.86, P<0.001), and second-line treatment (OR 7.50, P<0.001).

Among 285 men who did not use their cryopreserved semen, 134 (47%) had not tried to conceive since treatment for Hodgkin's lymphoma, and 129 (45%) conceived without use of cryopreserved semen.

The data showed that 334 men tried to conceive after treatment, including 83 of 112 (74%) without cryopreserved semen and 175 of 222 (79%) with frozen semen. In the adjusted analysis, the chances of achieving fatherhood increased significantly with the use of cryopreserved semen (P=0.02).


Source: MedPage Today:

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