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Thank you very much for the critical comments. Any critical comment on the use of GnRH analogs (GnRHa) to protect fertility during chemotherapy is of great value in further discussions of the controversial data and the controversial attitudes of endocrinologists and ocologists. We fully agree with the authors of the letter that several studies support the efficacy of GnRHa to protect the ovaries, which we have also demonstrated in a review summarizing nine studies on the use of GnRHa [1]. We also agree with the authors that the efficacy of other fertility preserving techniques such as cryopreservation and transplantation of ovarian tissue need further evaluation and that their safety has still not absolutely been proven, as stated in our recent review about cryopreservation of ovarian tissue [2]. Finally, we are fully aware that GnRHa provide several additional advantages during chemotherapy such as reducing the risk of thrombocytopenia-associated menorrhagia. However, we do not agree that GnRHa, in combination with cryopreservation of ovarian tissue and follicular aspiration, should be offered to all patients. We rather think that the current status of scientific data needs critical reflection and consequently, the patients need to be counseled carefully about the pros and cons of all available technical options, resulting in highly individualized fertility preservation approaches. We would like to comment on the letter in detail: First, as stated in recent reviews, previous studies did support the efficacy of GnRHa to protect the ovaries [1, 3]. However, the scientific quality of these studies was limited as none of the studies was randomized. Four recently published randomized studies have provided the following data: The study by Badaway et al. [4] involving 78 breast cancer patients, co-treated with GnRHa or untreated, revealed regular menstruations in 90 and 33%, respectively. The study by Ismail-Khan et al. [5], involving 49 breast cancer patients, revealed regular menstruations in 88 and 84%, respectively and the study by Gerber et al. [6] involving 60 breast cancer patients revealed regular menstruations in 93 and 97%, respectively. Behringer et al. [7] analyzed Hodgkin’s lymphoma patients. Eleven patients were treated with escalated BEACOPP, receiving GnRHa, and 12 controls with oral contraceptives. They found a difference neither in the rate of amenorrhea nor in the concentration of anti-Mullerian hormone. As only one of these four studies did demonstrate a GnRHa induced protective effect on the ovaries, it is not justified to argue that all patients should receive GnRHa. The only scientifically acceptable conclusions are, first, that the available data are still controversial, second, that further studies are needed, and third, that patients can be offered GnRHa but need to be informed about the controversial data. Second, we agree with the authors that the safety and efficacy of cryopreservation of ovarian tissue need further evaluation. We also support their attitude that M. von Wolff (&) P. Stute M. Nitzschke Department of Gynecological Endocrinology and Reproductive Medicine, Woman’s University Hospital of Bern, Effingerstrasse 102, 3010 Bern, Switzerland e-mail: Michael.vonWolff@insel.ch

Comments on the letter “Fertility preservation and GnRHa for chemotherapy: debate”