Livebirth after cryopreserved ovarian tissue transplantation – Authors' reply

www.thelancet.com Vol 380 July 14, 2012 107 Authors’ reply Since 2003, Corinne Hubinont and colleagues have had open access to all documents and protocols archived in the clinical database (Medical Explorer) at our university. Here we respond to their specifi c concerns. The patient was undoubtedly in primary ovarian failure: she was amenorrhoeic; concentrations of antiMullerian hormone and inhibin were at 0; concentrations of luteinising hormone and follicle-stimulating hormone were greater than 80 IU/L; and biopsy of the native ovary revealed no primordial follicles. Occasional ovulations are known to occur in patients in primary ovarian failure after chemotherapy, and we expressly stated that the patient had three ovulatory cycles over 3 years. We also clearly mentioned that a small corpus luteum was visible on the left ovary, and this of course implies the presence of progesterone. We would like to reiterate the numerous lines of evidence that lend support to our assertion that the origin of the pregnancy was the auto transplanted cryopreserved tissue. First, the patient had only a few ovulatory cycles over more than 3 years, all of which originated from the left native ovary, as proved by laparoscopy, echography, or both. The native right ovary showed no signs of ovarian activity. Second, laparoscopy done 4 months after the fi rst reimplantation showed, by direct visualisation, development of a follicle from the grafted tissue (see original fi gure 3A), clearly at some distance from the native atrophic right ovary. Biopsy of this follicle was done and histology of the follicular wall showed the presence of cells expressing inhibin A (fi gure 3B). Third, 5 months after reimplantation, the patient had regular menstrual bleeding with progesterone concentrations of greater than 10 μg/L. Vaginal echography revealed the presence of a preovulatory follicle at the reimplantation site during the cycle leading to the pregnancy. No follicles were seen on either of the native ovaries. Bilateral oophorectomy was never done for obvious ethical reasons, so the presence of isolated follicles in the atrophic native ovary cannot be absolutely excluded, as clearly stated in the Discussion section of our original paper. However, a woman who under went bilateral oophorectomy for bilateral abscesses in endometrial cysts recently gave birth to a healthy baby after orthotopic (broad ligament) reimplantation of ovarian tissue that was frozen at the time of bilateral oophorectomy, and we believe this corroborates our arguments beyond doubt. This is the 20th livebirth after cryopreserved ovarian tissue transplantation worldwide since 2004 (the fourth in our department), clearly showing that ovarian tissue cryopreservation should be regarded as an eff ective procedure that should be off ered to all young women diagnosed with cancer, in conjunction with other existing options for fertility preservation such as immature oocyte retrieval, in-vitro maturation of oocytes, oocyte vitrifi cation, and embryo cryopreservation.