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Fertility Preservation
spermatogenesis.
35,36
Since stem cells are capable of self-regeneration Ethics
and replication, transplantation can offer long-term restoration of There are a number of ethical concerns with reproductive organ
natural fertility. Spermatogonial stem-cell transplantation has had a transplantation. First and foremost, the preservation of fertility should
number of successes in various animals: mice, rats, pigs, goats, not come at the expense of delay of cancer treatment, as this may
monkeys and even humans.
37–39
have a more negative impact on the individual. This potential dilemma
exists when a patient is awaiting approval for clinical trials in
Female reproductive organ research and thus delays life-saving treatment.
Ovarian Transplant Another potential complication and ethical dilemma is the potential
In 2004, Donnez et al. presented the first successful pregnancy and spread of disease, or the failure to completely remove the disease in
live birth from a patient who had received frozen–thawed ovarian attempting to preserve the tissue. Care must be taken to examine the
tissue autotransplantation.
3
The patient was a 25-year-old female who graft prior to transplant to ensure that it is free of disease and cancer.
suffered from stage IV Hodgkin’s lymphoma requiring extensive Also, it is imperative that the allograft is free of cancer prior to
treatment. Before initiation of her chemotherapy and radiotherapy, 69 cryopreservation and re-implantation. Despite ongoing research in
fragments of ovarian tissue were obtained and cryopreserved until immune suppression for organ transplantation, every mother will still
after cancer treatment had finished. The tissues were then thawed have to take immunosuppressive therapy to prevent rejection and
and implanted near the ovarian vessels and fimbria. The patient graft versus host disease (GvHD). A number of suppressive agents
attempted to conceive the following year. Her follicle-stimulating have negative side effects on the mother and potential teratogenicity
hormone (FSH) levels had returned to baseline by 9.5 months, and a and embryotoxicity. Bedaiway et al. have outlined the most common
2.6cm ovarian follicle developed. Ultimately, the patient went on to side effects and teratogenicity with current immunosuppressive
conceive naturally and delivered a healthy female infant.
3,40
medications.
6
Each mother must be aware of all of these side effects
and the potential for a foetus with abnormal development secondary
Uterine Transplant to the terotogenic and embryotoxic effect of these medications. The
In April 2000 in Saudi Arabia, Fageeh et al. preformed the first human individual must then make an informed decision of whether to use
uterus transplant.
41
The uterus of a 46-year-old woman was reproductive organ transplant as a treatment modality.
transplanted into a 26-year-old who had previously had a
hysterectomy for post-partum haemorrhage but who wanted more Advances in Immune Suppression
children. The graft was functional (it was responding to oestrogen and Embryonic stem (ES) cells represent a new opportunity for
progesterone with endometrial proliferation and withdrawal establishing and developing novel methods of treatment, including
bleeding). However, at 99 days post-operatively the patient developed transplantation tolerance induction. ES cells have unique
an acute vascular thrombotic event and the graft had to be removed characteristics that support their use in transplantation: lack of major
secondary to uterine necrosis. Fageeh et al. attributed the outcome to histocompatibility complex (MHC) antigens and T cells that can
inadequate structural support rather than graft rejection or failed trigger GvHD reaction and poor expression of co-stimulatory
anastomosis of blood supplies. molecules. Medawar et al. demonstrated that transplantation
tolerance can be acquired and is strongly associated with donor
Since then, various investigators have been looking at different leukocyte chimerism.
46,47
Bone marrow cells are able to induce stable
aspects of transplantation in the hope that the graft may be tolerated mixed chimerism under the specific conditioning regimen of the
by the host. One area of development is different methods of storing host, conveying the induction of transplant tolerance. Nevertheless,
the harvested organ and the cryopreservation method used in order in order to achieve chimerism with allogeneic hematopoietic cells,
for proper maintenance of uterine contractility. Various freezing the recipient needs extreme pre-conditioning regimens that could
protocols have been used to cryopreserve the organ. The uteri were aggressively immunocompromise the patient.
48,49
then thawed out and evaluated for survival of myocytes by observing
contraction within the uterus.
42
Ramirez et al. recently presented a In a case report, Trivedi et al. reported tolerance induction in a renal
modified uterine transplant procedure using the sheep model: a total allograft recipient using nuclear transfer–human ES cell (NT-hESC)-
of 10 sheep underwent complete uterine transplant with a modified induced haematopoietic chimerism with synergistic use of adult bone
surgical method. After six months inside the host, hysterectomies marrow.
50
Later, Bonde et al.
51
demonstrated for the first time the
were preformed on all recipients and the uterine tissues were efficacy of ES-derived CD45
+
haematopoietic progenitor cells (HPCs) to
evaluated histologically. By observing the number of vascular engraft in allogenic recipients without the use of immunosuppressive
patencies and the amount of viable uterine tissue, they determined agents. In a large-animal model,
52
fractionated total lymphoid irradiation
that six of the 10 allografts had achieved successful transplantation.
43
and intrathymic or perithymic donor-specific bone marrow showed
induced tolerance to renal and skin allografts, interestingly without
Brannstrom et al. recently published a commentary on uterus inducing haematopoietic chimerism. A low-intensity conditioning
transplantation.
44
They predict that more experimental human uterus regimen of total lymphoid irradiation and antithymocyte globulin was
transplants will occur within the next two years. Brannstrom stated attempted to achieve tolerance of kidney transplant in some patients
the importance of proper preparation for both pre- and post- without the administration of donor haematopoietic cells.
53,54
One of the
procedure, for example using a team approach including a novel theories is that the mechanism of tolerance may originate from
gynaecological oncologist, maternal–foetal medicine physician, central deletion to a peripheral mechanism that may include regulatory
obstetrician, anaesthesiologist and transplant surgeon. Our group T cells and high levels of FOXP3
+
, which confers the kidney allograft the
recently published our 10 years of experience in uterus transplant in ability to maintain the tolerant state.
55
The sequence of steps
primates; it is our hope that we will stimulate more interest in uterus responsible for stable and consistent graft function without
transplant research.
45
immunosuppression remains a topic of analysis and research.
44 EUROPEAN OBSTETRICS & GYNAECOLOGY
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