1. Reproductive Organ
Transplantation. A scientific
overview.
Dr/ Mahmoud Abdel-aleem
Professor of obstetrics and gynecology, Assiut university

2. • Reproductive organ transplantation are old ideas acquiring fresh
courtesy.
• During the last 2–3 decades the clinical fields of transplantation surgery
and reproductive medicine have been the birthplaces of several clinical
innovations.
• In the last decade, the discipline of transplantation surgery is including:
• Transplantation essential for life to continue.
• Transplantation essential to have better quality of life.

3. • The inability to experience a pregnancy, give birth, and bring up a child
because of infertility issues may be one of the most traumatic and
devastating situations to affect a woman or couple, with the capacity to
have a severely detrimental effect on the quality of life of both parties
• In this presentation, I will discuss an overview on ovarian and uterine
transplantation.

4. Uterine Transplantation (Utx) (Utn)

5. Scope of the problem
• Absolute uterine factor infertility patients is present in 3% of all infertile couples.
• 12000-15000 potential uterus transplantation patients in UK
• 2000-3000 potential uterus transplantation patients in the Nordic countries
• Uterine infertile patients can today has one of 4 options:
• Attain genetic parenthood by use of gestational surrogacy, which is permitted in
some countries although most societies disapprove of its use because of ethical,
religious or legal reasons.
• Adoption.
• Lifetime infertility
• Uterine transplantation.

6. Possible
indications
for uterine
transplantati

7. A snapshot at the
past

8. 2000, Wafa Fageeh: 99
days. 2 menses then
amenorrhea.
Thrombosed uterus
9/8/2011, dr/ Omar
Ozkan. Turkey. Dead-
to-living uterus
donation. Mrs sert got
pregnant by ICSI but
missed miscarriage
14/05/2013
2012,
Brannstrom.
Sweden.
Mother-to-
daughter
donation.
10/2014.
Brannstrom. Sweden
first baby born to
uterine transplant. 31
weeks. PET. CS. Male.
2010, Diaz-Garcia,
Sweden, first
successful allogenic u
terus transplantation,
in a rat, with healthy
offspring

9. Why Utx is coming too late?
• Uterus is a dynamic, complex organ. It is hugely blood-flow dependent
• It warrants many additional but essential steps:
• IVF.
• Hysterectomy of the transplanted uterus. after 1-2 child bearings. It is
ephemeral.
• It is expensive and there are some alternate ways of management.
• It isn’t a life saving but rather life-improving surgery.

10. • Maintaining a healthy pregnancy that is defined as:
• Without evidence of malformations in the newborn
• Without worsening of graft function in the mother.
• The initial story of Dr wafa case !!!!

11. Learning much from a painful lesson !!!
• UTn was first performed in a human in 2000 on a 26year-old female who had previously
lost her uterus as a result of PPH.
• The lesson was:
1- Uterine transplantation should follow a slow methodological approach.
2- Animal based studies are a must.
3- Simultaneous working by different institutions.
4- Simultaneous working on several important issues:
Surgery.
Immunity.
Reproduction.

12. Why Utx is assumed to progress rapidly?
1- Considerable improvements in 2 fields; surgical methodology and immunology. since
1956, the date of first successful renal transplant, the field progressed rapidly because of
2- The concept of "syngenic" or "syngeneic" graft: means genetically identical, or
sufficiently identical and immunologically compatible as to allow for transplantation.
3- Good knowledge about nonspecific suppression of the host immune system and other
drawbacks : bacterial and viral infections, nephrotoxicity and neurotoxicity with chronic
renal failure, newly diagnosed DM, hyperlipidaemia, leucopoenia, and even cancer

13. 4- Abolishing the old thinking that IAs are perfect
teratogens !!. Since their first record of the use of in
pregnancy was in 1967, it is now realized that the
risks posed by including the potential teratogenicity
of certain agents are overestimated. > 14,000 births
among transplant women have been reported
worldwide.
Successful pregnancies are now considered the
norm in transplant recipient. However, there is
increased risk of prematurity, SGA, preeclampsia.

14. Principles in Uterine Transplantation
1. Counselling.
2. Donor uterus.
3. Investigations for the recipient.
4. IVF for the recipient.
5. The process of Uterine transplantation.
6. Ensuring stability of the graft for 1.5 years by immunosuppressives.
7. Embryo transfer.
8. Careful close observation of pregnancy till the end.
9. Hysterectomy of the transplanted uterus.
10. Adhering to ethical issues as regards transplantation discipline.

15. Why IVF before Utx ?
• To ascertain that fertility, in terms of fertilization and initial embryo
development, existed within the couple. The candidate patient may have
lower than normal response and fertilization rates.
• IVF procedure after transplantation might be more difficult than before
transplantation:
• Abnormal uterine vascular pedicles and anastomosis sites that might
increase the risk of bleeding at oocyte pick-up.
• The immunosuppressed patient may have an increased risk of pelvic
infection after the pick-up procedure.

16. Technical steps of uterine transplantation
1. Surgery and vascular anastomosis
2. Fixation of transplanted uterus
3. Avoiding Ischemia – reperfusion injury
4. Immunosuppression
5. Management of rejection.

17. A- Surgery and vascular anastomosis
1. Procurement (technique similar to radical hysterectomy)
1. Dissection of ureters
2. Isolation of arterial supply: isolation of the uterus with bilateral, long venous, and arterial vascular
pedicles.
2. Back table preparation
3. Vascular anastomosis: end-to-side bilateral vascular anastomoses
1. Connect the uterine veins to the external iliac veins (with 8-0 polypropylene sutures).
2. Connect the anterior divisions of the internal iliac arteries to the external iliac arteries (with 7-0
polypropylene sutures).
Ensure that good pulses existed distal to the arterial anastomosis sites and that the uterine
tissue changed from pale to reddish, which is a sign of peripheral tissue perfusion.
Blood flow : 40 mL per min.

19. B- Fixation of transplanted uterus
• Vaginal rim anastomosis.
• Round ligaments.
• the extensive bladder peritoneum on the uterine graft on top of
the recipient’s bladder to provide extra structural support.
Avoid spontaneous labor

20. C- Prevention of Ischemia (cold/warm) –
Reperfusion injury
• Cold ischemia (+4°C) at preservation of graft ex vivo
• Energy depletion
• Membrane polarity change
• Warm ischemia and reperfusion
• Major damage
• Organelle destruction (ROS)
• Inflammation
24 h preservation at 4º C in UW [University of Wisconsin preservation] / PER [Perfadex].
Metabolic stabilization at reperfusion within 1 h after 3h ischemia (1 h cold, 2h warm)

21. D- Pregnancy Rate
• Pregnancy rate
• Animal studies: normal rate.
• Human studies: successful pregnancy outcome is reported.

22. E- Rejection
Types:
Hyperacute rejection (min to h)
Acute rejection (days to months)
Chronic rejection (from day 1, slow process)
Indicators:
CD+4/CD+8 ratio in blood.
Doppler of uterine blood flow.
Cervical/endometrial biopsy.

23. Induction immunosuppressive.
IV anti-thymocyte globulin 2・5 mg/kg just before surgery and 12 h later.
IV methylprednisolone: 500 mg just before uterine reperfusion.
Maintenance immunosuppressive.
Oral tacrolimus aiming at trough levels of 5–10 ng/mL
Myco phenolate mofetil aiming at trough levels of 40–60 mg for the first 10 months
Azathioprine 2 mg/kg per day replaced MM after 10 months, to avoid the potentially
teratogenic effects of mycophenolate mofetil in the run-up to the embryo transfer attempts.
Prednisolone 5 mg daily is added from month 6 post-transplantation.

24. Ethics (Montreal Criteria)
Recipie
nt
Prospectiv
e father
Surgical
innovation
Laboratory
background
Future
child
Institutiona
l stability
Risk-
benefit
analysis

26. Ovarian Transplantation

27. • Major advances in oncological treatments and diagnosis have resulted in
a marked improvement in the survival of children and young adults with
cancer over the last decade.
• Preservation of reproductive tissue is achieved through cryopreservation.
• Transplantation of ovarian tissue is, at present, the only clinical option
available to restore fertility using cryopreserved ovarian tissue

28. • Aim: preserving reproductive potential prior to gonadotoxic medical treatments. On
completion of gonadotoxic treatment and confirmed fitness for pregnancy, the harvested
autologous tissue may be transplanted back to the patient.
• Cryopreservation refers to the cooling of cells and tissues to sub-zero temperatures in
order to achieve complete cessation of biological activity. The temperature that is
generally used for the storage of mammalian cells is – 196°C, the temperature of liquid
nitrogen.
• Slow freezing.
• Vitrification: ultra-rapid cooling.

29. Options

30. Factors potentially affecting the performance of
ovarian transplants
1. Age of donor
2. Number of primordial follicles
3. Tissue mass/cortical thickness
4. Duration of ischemia/proximity to host vasculature
5. Immunological compatibility
6. Site of transplantation
7. Cryopreservation/ vitrification
8. Reactive oxygen species

31. Homogenic vs Allogenic
• Homogenic: extract her own tissues, cryo- them then return them
back. Orthotopic homo-transplantation of frozen-thawed ovarian
tissue is today perfectly feasible, with >40 babies having been born.
• Allogenic: obtain the specimen from a donor then transfer them to
recipient. Can be done between monozygotic twins, as well as
between genetically different sisters

32. Heterotopic Vs Orthotopic sites

33. Ovarian cortex vs Whole ovary
• Ovarian cortex: slicing the ovarian cortex into 1-2 mm thickness
slices.
• Whole ovary: transplanting the ovary with its intact vascular
pedicle.

36. Heterotopic
transplantation results
in a consistent
restoration of
endocrine function,
but it may not provide
an optimal
environment for
follicular development.

37. Pregnancy: assisted then natural
• 2004: The lady, Stinne Holm Bergholdt, was diagnosed with Ewing's sarcoma, at age 27.
• Before undergoing toxic cancer treatments, doctors retrieved part of her right ovary and
preserved it by freezing. Her left ovary had been removed previously because of a cyst.
• 12/ 2005: doctors transplanted six thin strips of ovarian tissue from what remained of her right
ovary. The ovary began working again. She underwent mild ovarian stimulation in Andersen's
fertility clinic and became pregnant.
• 02/ 2007: giving birth to her first daughter Aviaja
• 01/ 2008: Bergholdt, went back to do another IVF treatment to achieve a second pregnancy.
But she found out she was already pregnant -- having conceived naturally –
• 09/ 2008: giving birth to her daughter Lucca.