Live Birth After Orthotopic Autotransplantation of Cryopreserved Ovarian Tissue: A Newsmaker Interview With Jacques Donnez, MD, PhD

Laurie Barclay, MD

September 27, 2004

Sept. 27, 2004 -- Editor's Note: On Sept. 23, a 32-year-old Belgian woman gave birth to a healthy baby seven years after cryopreservation of her ovarian tissue, according to a research article published online by The Lancet on Sept. 24. Both mother and infant are doing well.

Before starting chemotherapy for Hodgkin's lymphoma in 1997, this patient had ovarian biopsy for tissue cryopreservation, and she subsequently became menopausal. Orthotopic autotransplantation of her ovarian tissue in 2003 led to ovulation five months later, and pregnancy by natural fertilization 11 months after retransplantation. This is the first case of a human live birth after successful orthotopic autotransplantation of cryopreserved ovarian tissue,

To learn more about the indications for and expected outcomes from this procedure, Medscape's Laurie Barclay, MD, interviewed lead investigator Jacques Donnez, MD, PhD, a gynecologist at the Cliniques Universitaires Saint-Luc and Catholic University of Louvain in Brussels, Belgium.

Medscape: What is the rationale behind orthotopic autotransplantation of cryopreserved ovarian tissue?

Dr. Donnez: For some women with cancer, chemotherapy is necessary. Chemotherapy is sometimes toxic for the ovaries, depending on age, drug, and quantity of drug used. In some women, chemotherapy causes menopause. So the rationale is to propose that women suffering from cancer undergo ovarian biopsy before chemotherapy. It is really important that it is done before even one regimen of chemotherapy, in other words before any chemotherapy is started. It must be considered as an emergency, because there is no question of delaying chemotherapy in young women with cancer. After we have removed part of the ovary, cryopreservation is carried out before chemotherapy commences. Then we have to wait until the patient is cured and disease-free. If she then wants to get pregnant, we propose reimplanting the ovarian tissue.

This woman had Hodgkin's disease in 1997. Before chemotherapy, we removed part of the ovary for cryopreservation and, after she was cured, pieces of the ovary were grafted in 2003 in the hope that this could restore some ovarian function.

Medscape: Please describe how this procedure worked for this woman, and how she and her baby are doing.

Dr. Donnez: We reimplanted the ovarian tissue in February 2003, and in fact waited for four months before we saw anything. At that time, we were a little disappointed. In June 2003, we did a laparoscopy to check the graft and there were viable follicles in a biopsy of the graft. We then grafted the remaining cubes. A few months later, she started to menstruate again and had ovulatory cycles. Eleven months after the reimplantation, the patient suddenly had no menstrual bleeding; she was pregnant!

The pregnancy went very well, no problems at all, but unfortunately we couldn't do an amniocentesis because the placenta was on the anterior wall of the uterus. But according to echography, the baby was developing normally.

The patient was here [last week] at 38 weeks of gestation, and the baby seemed to be quite big. The weight was estimated at 3 kg, 900 g, so we decided to induce labor. After a few hours of contractions, the patient delivered a female baby weighing 3 kg, 720 g at 7:05 pm [on Sept. 23]. Both the baby and the mother are doing very well.

Medscape: How effective, safe, and cost-effective is this procedure?

Dr. Donnez: It's important to mention that I received a scientific grant from Belgium allowing me to do research in my department for more than 10 years now. So far, my department of gynecology has taken the financial responsibility for this type of therapy on itself. So we didn't ask for any money from the patient. It's not that we consider it to be experimental, but we had no guarantee of the results when we started this technique. So far, all patients included in the program of cryopreservation have been treated free of charge, with costs paid for by the department itself and the research grant.

If we were to start asking patients for money, it would be the price of two laparoscopies, one hospitalization and the cryopreservation technique, which is quite similar to the cryopreservation we use for fertilization in medically assisted procreation. So it's not that expensive.

Medscape: How does this technique compare with other options for fertility preservation?

Dr. Donnez: One other option for fertility preservation is embryo cryopreservation but, firstly, that implies a delay before starting chemotherapy, and oncologists and hematologists don't like to delay treatment for cancer. Secondly, it requires a partner, and, in very young women of 14 to 15 years of age, there's no partner available, making embryo cryopreservation impossible, even though it's highly effective.

The other option is cryopreservation of oocytes, but again this will delay chemotherapy. Also, mature oocytes are not very resistant to cryopreservation. But ovarian tissue cryopreservation can be done immediately, as soon as the diagnosis has been made, before any type of chemotherapy is initiated. From the moment the tissue is cryopreserved, we have two options: orthotopic transplantation as proposed in The Lancet, or transplantation under the skin of the abdomen.

Medscape: Do you think a lot of centers will use this technique and that a lot of women will be able to have this procedure?

Dr. Donnez: I really hope so. I think that you, the media, have a big role to play as the first to convince oncologists, hematologists, and pediatricians that they should propose cryopreservation of ovarian tissue to all women suffering from cancer. You are a woman -- how can you explain that for the last 20 or 30 years now, if a man has cancer and must receive chemotherapy, we will systematically have the man provide sperm two or three times to preserve millions of spermatozoa, but we don't go through comparable procedures with women? I'm really convinced, as a gynecologist, that as a first step at least, every woman suffering from cancer should be offered the option of having her ovarian tissue cryopreserved.

Two or three weeks ago I did a second transplantation. I have no idea of the result; it's too early, but I'm sure that we have to wait for a few cases before we can say that this is the right technique. I'm sure that other options are possible in the future, such as transplanting primordial follicles, and we are working very hard in our labs to improve the technique.

Medscape: Are there potential long-term risks to the mother or infant?

Dr. Donnez: It depends on the disease. In the case of this woman, it was Hodgkin's disease, so the probability of having malignant cells in the cryopreserved ovarian tissue is nil. But in the case of leukemia, there is a potential risk of reimplanting malignant cells. So, in some diseases, we have to find another option, such as reimplanting primordial follicles. We are working very hard and I hope we will find a solution very soon.

Medscape: Do you think that women who are not having chemotherapy for cancer might have this procedure to bank their ovarian tissue in the same way that men bank frozen sperm? Are there any ethical concerns about that?

Dr. Donnez: I work at the Catholic University of Louvain in Brussels, where we perform in vitro fertilization and many other procedures, but we have very strict political limitations that I fully agree with. So far, the only indication for this technique in my department is to try to preserve fertility in young women suffering from cancer.

Medscape: Is there anything you would like to add?

Dr. Donnez: I would like to quote what our patient said in the press conference [the] morning after she gave birth. She said: "I was suffering from cancer. The doctors told me that I would be in the menopause after chemotherapy. What happened today is a message of hope for all women." I think that finishing the interview with a message of hope for women with cancer is great.

Disclosure: Dr. Donnez reports no financial conflicts of interest.

Lancet. Published online Sept. 24, 2004.

Reviewed by Gary D. Vogin, MD


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