Ovarian tissue transplant - read about the procedure, who is eligible, preparation and life after transplant from Singapore General Hospital.
WHEN DOES A PATIENT REQUIRE AN OVARIAN TISSUE TRANSPLANT?
The ovaries are vital to normal female reproductive function and fertility because they contain the female egg cells (oocytes) and secrete the female reproductive hormones.
Cancer treatment – in particular chemotherapy and radiotherapy – often destroys oocytes and ovarian function, and the woman’s chances of bearing children permanently.
Ovarian tissue freezing (cryopreservation) and transplantation offers an opportunity for reproductive-aged women to preserve their fertility while undergoing cancer treatment.
OVARIAN TISSUE TRANSPLANT ELIGIBILITY AND PREPARATION
There are several options for fertility preservation e.g. ovarian tissue freezing and transplant, oocyte (egg) storage for invitro fertilisation (IVF) later, as well as embryo storage. Therefore, thorough counselling by our fertility specialists is crucial.
The patient is assessed by our transplant team at the Centre for Assisted Reproduction (CARE),
Singapore General Hospital (SGH) to determine her suitability for ovarian tissue retrieval and freezing. She should be:
- Pre-menopausal at most 40 years old with early-stage cancer that does not involve her ovaries, and
- Should not have an increased risk of developing ovarian cancer (e.g carriers of the BRCA gene).
The patient’s ovarian tissue is harvested via an operation which can usually be performed through a ‘key-hole’ incision. The operation lasts for one hour and requires general anaesthesia.
For optimal results, it should be performed before the patient starts her cancer treatment. Should she require surgical treatment for her cancer, the two operations may be scheduled at the same time if feasible.
OVARIAN TISSUE TRANSPLANT PROCEDURE
After the ovarian tissue is harvested, it is prepared for storage by our laboratory staff using specialised freezing techniques (cryopreservation).
The stored ovarian tissue is thawed and transplanted back into the body via a second operation. Given the limited lifespan of ovarian tissue grafts, transplantation should be postponed until the patient is ready to conceive or experiences symptoms of ovarian hormone deficiency.
The patient should also have:
- Completed her cancer treatment,
- Be in remission from her disease, and
- Undergone full assessment by her cancer specialist and our transplant team.
If needed, she may also be referred to an obstetric specialist to discuss about potential pregnancy complications unique to cancer survivor.
TYPES OF OVARIAN TISSUE TRANSPLANT
There are two methods of ovarian tissue transplantation:
- Orthotopic ovarian tissue transplantation involves grafting of ovarian tissue back to its natural location in the body with the aim of allowing natural pregnancy to occur. It is currently the most effective technique for transplantation and has resulted in a series of live births.
- Heterotopic ovarian tissue transplantation involves grafting of ovarian tissue to another site in the body which allows easy access to the egg cells, most commonly underneath the skin of the forearm or the abdomen.
As heterotopic transplantation avoids major abdominal surgery, this approach is beneficial for patients in whom repeat abdominal surgery may be complicated.
However, the main disadvantage of this technique is that it would not allow natural pregnancy and in-vitro fertilisation would be needed for conception (‘test-tube baby’).
In addition, while live births from experimental heterotopic transplants performed in primates have been reported, one human birth has been reported to-date.
In our Centre, orthotopic ovarian tissue transplantation is performed whenever feasible because of the uncertain effectiveness of heterotopic ovarian tissue transplantation in restoring fertility in humans.
LIFE AFTER AN OVARIAN TISSUE TRANSPLANTATION
Unlike in conventional organ transplants, patients do not need to take any long-term immunosuppressive medications after ovarian tissue transplant surgery. This is because the ovarian tissue that is harvested and re-implanted back to the body is the patient’s own, so there is no risk of organ rejection.
The lifespan of the graft is very variable and depends on the amount of tissue transplanted and the age of the female when the ovarian tissue was first removed. Graft survival ranging from a few months to up to ten years has been reported.
It is currently not possible to predict how long the graft will function after transplant.
In general, the patient can expect to resume normal menstrual cycles within 4-9 months after transplantation. Among women who were trying to conceive after ovarian tissue transplant, a spontaneous pregnancy rate of about 30% has been reported.
FREQUENTLY ASKED QUESTIONS
What are the benefits of ovarian tissue freezing and transplantation compared to the other methods of fertility preservation (e.g. egg storage, embryo storage)?
Ovarian tissue freezing represents a more efficient way of preserving thousands of oocytes at one time, without the need for hormonal stimulation and a source of sperm.
Therefore it is an ideal option for patients who lack a male partner and require cancer treatment urgently.
In contrast, egg and embryo freezing require a period of hormonal stimulation and only allow small numbers of eggs and embryos respectively to be preserved with each treatment cycle.
I have completed my family but am worried about premature menopause after completing chemotherapy. Would ovarian tissue freezing and transplant be suitable for me?
Because of the limited duration of graft function, ovarian tissue transplant is unlikely to be effective for preserving the long-term hormonal function of the ovary. Currently it should only be performed with the aim of preserving fertility.
It is not recommended as a strategy for long-term hormone replacement and should not be performed to prevent premature menopause in women who do not wish to conceive after cancer treatment.
Are there any risks involved with ovarian tissue transplantation?
There are surgical risks involved as two operations are needed to retrieve the ovarian tissue and graft the cryopreserved tissue back into the body.
It is not possible to test the retrieved ovarian tissue for tumour cells because the testing process will invariably destroy the ovarian tissue. There are theoretical concerns that there may be hidden tumour cells in the ovarian tissue which can be reseeded back into the body with the transplant.
Therefore, careful patient selection is needed and we restrict the procedure to cancer patients with a low risk of ovarian involvement.
To-date, we have not encountered any reports of cancer recurrence resulting from reseeding of cancer cells from an ovarian tissue transplant.
As ovarian tissue transplant is a relatively new procedure, there has yet to be a published report of the short- and long-term outcomes of the children conceived by this method.
HISTORY AND SUMMARY OF THE OVARIAN TISSUE TRANSPLANT PROGRAMME
|1999||First ovarian transplant of cryopreserved ovarian tissue performed in the United States|
|2004||First successful live birth after ovarian tissue transplant reported in Belgium|
|2010||First ovarian tissue cryopreservation operation done at SGH|
|2012||First ovarian tissue transplant operation done at SGH|
Centre for Assisted Reproduction
Block 5, Level 1
Singapore General Hospital
Tel: 6321 4292
GPs can call for appointments at the Centre for Assisted Reproduction at 6321 4292, or scan the QR code for more information.
Assoc Prof Yu Su Ling is a Senior Consultant with the Department of Obstetrics & Gynaecology; Singapore General Hospital
Assoc Prof Yu is an accredited IVF specialist, Director of Centre for Assisted Reproduction. She sees patients with general gynaecology and obstetrics problems, and her special interests are in subfertility, menopause, and endoscopic surgery.