A woman, whose ovaries had failed due to damage caused by chemotherapy and radiotherapy, has received a successful ovarian transplant from her genetically non-identical sister. The transplant restored her ovarian function, she started to menstruate and, after a year, doctors were able to recover two mature oocytes from her ovaries and fertilise them to produce two embryos.

This first case of a successful transplantation of ovarian tissue between two non-identical sisters is reported today by Professor Jacques Donnez, head of the department of gynecology and professor and chairman at the Catholic University of Louvain in Brussels, Belgium, who led the team that carried out the work.

In 1990, when she was 20, doctors treated Teresa Alvaro for beta-thalassemia – an inherited blood disorder characterised by reduced or absent haemoglobin, which is the oxygen-carrying protein in red blood cells. She received chemotherapy and radiotherapy before having a bone marrow transplant from her 17-year-old sister, Sandra Alvaro, who had an identically matched tissue type (human leukocyte antigen (HLA) type), which meant that Teresa’s immune system would not recognise her sister’s bone marrow as “foreign” and reject it.

The treatment was successful and Teresa was cured. However, in 1990 there were no procedures available for preserving her fertility before commencement of the treatment by, for instance, removing and freezing her eggs or ovarian tissue. The treatment caused complete ovarian failure, and her ovaries never recovered.

In July 2005, now aged 35, Teresa consulted Prof Donnez and his colleagues about the possibility of ovarian tissue transplantation from her sister to give her a chance of becoming pregnant.

Prof Donnez said: “Having already provided bone marrow in 1990, her sister, who was now aged 32 and had never become pregnant, badly wanted to help her sister by donating some of her own ovarian tissue.

“Although the option of oocyte donation from the sister to the patient was discussed, the patient refused this option. She preferred a transplant because she wanted to be ‘responsible’ for the follicular maturation and considered that it was more natural than egg donation, for which her sister would have to undergo ovarian stimulation with follicle stimulating hormones and then oocyte retrieval. In addition, her sister had asked expressly to be the tissue donor and had refused to undergo ovarian stimulation for oocyte donation.”

Analysis of the sisters’ HLA type showed that their genetically different cells coexisted successfully together (chimaerism) and that, therefore, no immuno-suppressive treatment would be required to prevent the ovarian graft being rejected. The earlier bone marrow transplant and resulting mixing of the sisters’ cells meant that Teresa’s immune system would recognise Sandra’s ovarian tissue as “self” rather than “foreign”.

In February 2006, Teresa and Sandra were anaesthetised together and three small sections of ovarian tissue were removed from Sandra via laparoscopy and within less than a minute were being sewn on to one of Teresa’s atrophied ovaries, also via laparoscopy. The sisters were discharged from hospital the day after surgery.

After six months Teresa started menstrual bleeding and this, together with differences in hormone levels, confirmed that ovarian function had been restored. Her menstrual cycles have continued ever since. A year after the transplant, the doctors retrieved two mature oocytes from her ovary and fertilised them with her husband’s sperm via ICSI (intracytoplasmic sperm injection) – they decided to use ICSI rather than attempting natural conception because the husband had a low sperm count. One of the resulting embryos developed to the two-cell stage and the other to the three-cell stage, but then both ceased to develop further, and so the embryos were not transferred to her uterus.

Prof Donnez said: “We do not know why the embryos ceased to develop, but this also happens during normal cycles of IVF. The patient is planning more IVF attempts in the future.”

He said that it was too early to say whether this procedure would ever be successful enough to enable a woman to become pregnant successfully and give birth to a live baby. However, the work did give hope to women who had not had an opportunity to freeze either their eggs or their ovarian tissue, and it emphasised the importance of leaving at least one ovary in place during any treatment because the ovary offered an excellent site for a subsequent transplant of ovarian tissue.

“This method is an option for women who have not had their ovarian tissue cryopreserved, either because chemotherapy was given before 1996, or because cryopreservation was not proposed or not available in the hospital where the patient was treated,” he said.

“In theory, the procedure could also be used between two, unrelated women, as long as the two women were HLA compatible and if the donor had previously given bone marrow to the recipient, as in the case we are reporting here,” he concluded.

Teresa Alvaro said: “Early in 2005 my gynaecologist told me that the chemotherapy that I had to go through in 1990 in preparation for my bone marrow transplant had severely affected my fertility. A few months later I happened to read an article on an American woman who got pregnant after she had ovarian tissue transplanted from her twin sister. I didn’t hesitate for a second and went to see Prof Donnez together with my sister. Our antigens appeared to be identical, and therefore the chances of rejection were minimal. The operation was a success. I can get pregnant the natural way. That’s something I could never have hoped for a couple of years ago.”

Source: Human Reproduction. doi:10.1093/humrep/dem211