For the first time, a woman has given birth to two children after her fertility was restored using transplants of ovarian tissue that had been removed and frozen during her cancer treatment and then restored once she was cured.
Following her ovarian transplant, Mrs Stinne Holm Bergholdt gave birth to a girl in February 2007 after receiving fertility treatment to help her become pregnant. But then, in 2008, she discovered she had conceived a second child naturally and gave birth to another girl in September 2008.
Her doctor, Professor Claus Yding Andersen, reports her case today (Thursday) in Europe's leading reproductive medicine journal Human Reproduction . "This is the first time in the world that a woman has had two children from separate pregnancies as a result of transplanting frozen/thawed ovarian tissue," he said. "These results support cryopreservation of ovarian tissue as a valid method of fertility preservation and should encourage the development of this technique as a clinical procedure for girls and young women facing treatment that could damage their ovaries."
So far, nine children have been born worldwide as a result of transplanting frozen/thawed ovarian tissue (including Mrs Bergholdt's two). Three have been born in Denmark after treatment carried out by Prof Andersen, who is Professor of Human Reproductive Physiology at the University Hospital of Copenhagen (Denmark). "Mrs Bergholdt gave birth to the first and the third babies and another woman delivered the second baby. This is the highest number of children born from one ovarian cryopreservation programme worldwide. It is interesting to note that nearly all of the nine pregnancies have occurred in Europe and so Europe is in the absolute forefront with this technology," he said.
Mrs Bergholdt, from Odense, Denmark, who is also one of the authors of the paper, was diagnosed with Ewing's sarcoma when she was 27 in 2004. Before she began chemotherapy, part of her right ovary was removed and frozen (her left ovary had been removed some years before because of a dermoid cyst, a type of benign ovarian tumour). Her cancer treatment was successful but, as expected, the drugs caused a menopause. In December 2005 six thin strips of ovarian tissue were transplanted back on to what remained of her right ovary. Her ovary began to function normally again and, after mild ovarian stimulation, she became pregnant and gave birth to her first daughter, Aviaja, in February 2007.
She breast-fed Aviaja until October 2007 and in January 2008 she returned to Prof Andersen's fertility clinic for additional IVF treatment so that she could conceive again. However, a pregnancy test revealed she was already pregnant naturally, and in September she gave birth to a healthy girl, Lucca.
Prof Andersen said: "This showed that the original transplanted ovarian strips had continued to work for more than four years and that Mrs Bergholdt still has the capacity to conceive and give birth to healthy children. It is an amazing fact that these ovarian strips have been working for so long and it provides information on how powerful this technique can be. She continues to have natural menstrual cycles and, at present, is using pregnancy-preventing measures to avoid becoming pregnant again.
"She has seven more ovarian strips in the liquid nitrogen tank and may return, if she wishes so, to have more tissue transplanted in order to maintain her ovarian function once the current strips stop working. So, in total, by having around one third of an ovary removed she has the possibility of maintaining her ovarian function for many years. As long as the tissue remains properly stored in liquid nitrogen, it could remain functional for as long as 40 years. However, we do not know this for certain at present."
Mrs Bergholdt, who is now 32, said: "When I found out I was pregnant for the first time I was of course very happy and excited - but also very afraid and sceptical since I found it very hard to believe that my body was really working again. My cancer had been diagnosed very late because the doctors didn't take my complaints seriously at that time and kept on telling me that nothing was wrong, so I also wondered if it was really true that I was completely recovered from it. But eventually I started to believe that the pregnancy was really happening and began to enjoy every aspect of it.
"The second time it was quite a surprise to find out I was pregnant since we hadn't been working on it - we thought we needed assistance like the first time. We had an appointment at the fertility outpatient clinic to talk about the possibility of a second baby, but it turned out that I was already pregnant - naturally. It was a very nice surprise to find out that my body was now functioning normally and that we were having a baby without having to go through the fertility treatment. It was indeed a miracle!"
Mrs Bergholdt said she and her husband had not decided yet whether they wanted more children. "The girls are still so small and need a lot of attention, but maybe in a couple of years we might think about it again."
 The first woman to give birth to two children following transplantation of frozen/thawed ovarian tissue: case report. Human Reproduction journal. doi:10/1093/humrep/deq033