Uterine Transplantation

A uterine transplant, or womb provides a potential treatment for women who cannot become pregnant carry pregnancy because they do not have womb, that is unable to maintain pregnancy. This estimated affect one in 500 women. Options those wish start family include adoption and surrogacy, but these are associated with legal, cultural, ethical religious implications may be appropriate some their families. transplant undertaken when the woman ready family, removed following completion of family. Womb transplants been performed all over world, more than 70 procedures carried out so far. At least 23 babies born as result, demonstrating can work. While procedure offers different option it significant risks, including multiple major surgeries need take medications help dampen immune system prevent rejection womb. To date there has 30% risk being unsuccessful. Although number still relatively small, globally growing, providing an opportunity learn from experience gained paper looks at issues encountered, which arise each step process, proposes framework future. However, long term follow-up cases will essential draw reliable conclusions about any overall benefits this procedure. Uterine transplantation (UTx) therapeutic intervention absolute factor infertility (AUFI). AUFI widely considered 1 childbearing age, impact 200 000 Europe, 85 USA up 1.5 million worldwide.1, 2 refers secondary absence uterus presence anatomically physiologically dysfunctional. The established routes motherhood many suitable options. only options complex financial, factors, allow UTx overcome while giving conceive using assisted reproductive technologies themselves. time publication paper, live births published, reported media.3-5 Following development International Society Transplantation establishment teams performing globally, anticipated transition research concept clinical care purpose Scientific Impact Paper summarise pertinent published literature on propose establishing sustainable programme UK. data presented herein refer 45 cases,5 17 peer reviewed journals date. includes Saudi Arabia, Turkey, Sweden, Xian (China), Czech Republic, Cleveland (USA), Dallas Brazil, Germany India. Reproductive planning involves numerous factors derive individual's/partner's values, influenced by social cultural norms, resources available them. Women traditionally remained childless surrogacy. There pros cons surrogacy is, therefore, important ensure well-informed For adoption, UK, gain information through government websites, HFEA (Human Fertility Embryology Authority) signposted sources obtain (Surrogacy Brilliant Beginnings, Childlessness [COTS]). Moreover, specialist fertility counsellors considering NHS, privately accredited therapists accessed organisations such British Infertility Counselling Association (BICA). provide mothers, restore anatomical issue underlying cause infertility. therefore never menstruation, part female shown small study involving 12 participants contribute gender identity.6 Furthermore, give pregnancy, demonstrated primary motivator 63% request UTx.7 greater physical risk, necessity immunosuppression donor situ, does recipients overcomes legal no direct alternative UTx, consideration given counselling process UTx. ensures consent fully informed, additional risks appropriately context perceived individualised benefits. Potential undergo age AUFI, causes congenital acquired, summarised Appendix I. Out cases, 40 (89%) were Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome. Four (9%) hysterectomy (one postpartum haemorrhage,8 after cervical cancer,9 two failed myomectomy5). One (2%) case was Asherman syndrome underwent preparatory UTx.10 MRKH incidence 5000 women.11 It arises due incomplete Müllerian ducts. manifests uterus, although rudimentary bulbs fallopian tubes remain, along variable degrees vaginal shortening. Therapeutic often required optimise diameter depth enable sexual function. Various methods exist dilator therapy, Vecchietti formation surgically-created vagina, referred neovagina, skin, peritoneum, amnion intestine.12, 13 novel use autologous vitro cultured tissue also promising results.14 Generally, normally functioning ovaries, making them candidates assessing perceptions among showed almost two-thirds willing procedure, full understanding involved.15 specific preoperative requirements. normal length vagina (measuring 7 cm more) requisite teams, excludes neovagina. surface composed stratified squamous epithelium, protective mechanism desquamates into lumen, concomitantly removing adherent micro-organisms.16 Vaginal epithelium contributes innate response facilitating recognition pathogens stimulating production antimicrobial peptides proinflammatory cytokines.17 These immunomodulatory mechanisms maintenance commensal microbiome, outcomes UTx.18 example, second global intestinal neovagina,19 where despite fertilisation attempts miscarriages, birth yet occur.20 atypical MRKH, specifically renal abnormalities, Caution should taken unilateral agenesis, affects around quarter cases,21 owing two-fold increased hypertensive disorders pre-eclampsia.22 In Swedish cohort three had kidney developed disorder during necessitated early birth.23 Those pelvic kidneys require assessment utilising magnetic resonance imaging computerised tomography scanning, localise determine if would impediment subsequent Reasons benign gynaecological disease, cancer (such cancer) severe haemorrhage. having previous diagnoses, recurrence consequence postoperatively. transplantation, history death recipient.24 across solid organ transplants, meta-analysis found all-cause mortality, cancer-specific mortality developing new malignancy pre-transplant diagnosis compared malignancy.25 As such, women, prudent period 5 years remission before meaningful conclusion single case, cancer, cervix, gave babies,23 hysterectomy, reports diagnoses cancer. syndrome, present dysfunctional endometrium, 1.5% age.26 Characterised adhesions inside and/or condition amenorrhea, recurrent miscarriage restoration achieved hysteroscopic adhesiolysis, high rates infertility, miscarriage, poor implantation abnormal placentation remain.27 Performing other exhausted. Under Equality Act (2010), individuals proposing undergo, currently undergoing, undergone reassignment subjected discrimination based characteristic alone. Subsequently, becomes (encompassing both cis-women trans women) EU UK legislation will, provision compelling justification, unlawful perform (or transgender) Despite anatomical, psychosocial, physiological, obstetric considerations further transgender overwhelming argument against procedure.28 Other less common anomalies, radiotherapy damage complete androgen insensitivity Owing nature conditions, role unclear. Living donors used 80% far (n = 36),5, 9, 10, 29-34 remaining deceased 9; 20%).5, 19, 34-36 parity known 43), majority multiparous 40; 93%) nulliparous (7%).19, 34 Logistically, diverse array multidisciplinary expertise required, elective surgery living straightforward on-call arrangement needed donation. routine investigations apply equally donors, microbiological screening transmitted infection HIV, hepatitis B C, cytomegalovirus, Epstein-Barr virus, syphilis, toxoplasma, human T-cell lymphotropic virus. allows minimum smear/human papillomavirus testing, tests exclude sexually infections (chlamydia, gonorrhoea trichomoniasis) culture Candida species bacterial vaginosis. transvaginal ultrasound scan structural angiography computed vessel morphology, calibre patency. Just half 36 related 19; 53%), maternal relation 16), sister aunts donated. remainder 17) unrelated. first-degree relatives immunological benefit,37 older factors. Significantly, increasing correlates atherosclerotic change arteries, result insufficient quality implantation.29 even macroscopic histological evidence atherosclerosis evident, arterial inflammation,38 increase likelihood post-transplant graft vasculopathy.39 addition, irrespective recipient increases rate acute allograft transplants.40 feasibility type difficult refute 20 donors. disadvantage donor. Regarding surgical morbidity far, four (11.4%) suffered complications requiring intervention. Two whom sustained intraoperative ureteric lacerations repaired immediately;30, re-presented uretovaginal fistula initial pyelostomy months – attributed diathermy partial injury retrieval.9 1%, 10% cases.41 higher oncological pathology-related complexity, whereas retrievals virtue selection criteria. preserve veins view unpredictable tortuous course particularly close proximity ureter, presents retrievals. Evolution technique,42 ovarian utero-ovarian instead veins,31, 32 reduce future cases. complication under general anaesthesia cuff dehiscence.31 Ten experienced deviation postoperative pharmacological treatment. included urinary tract infections,5, 38 faecal impaction,31 wound infection,9 bladder hypotonia,34 leg/buttock pain,31 anaemia,5 respiratory failure anaesthesia5 depression.31 Extensive essential, thorough explanation informed consent, undue pressure coercion. ultimately negates radical dissection, enables larger vessels taken, theoretically reducing thrombosis. reached animal research, smaller anastomoses, vessels, resulted gradual thrombosis.43 Subsequent studies patch techniques substantiated concept, successful pregnancies large models.44-46 successfully retrieved multiorgan retrieval adverse upon organs retrieved. lifesaving cases,47, 48 others.49-51 Appropriate investigation undertaken, scan, screen cytology/human testing expedited results within pre-retrieval period. optimised preliminary investigations. Donor optimisation sees shift management strategy directed towards resuscitation cerebral injury, focuses physiological metabolic homeostasis deterioration. Donation dependent consented, required. Initial indicated uptake families, few 6% families agreeing procurement uterus.49 recent French donation readily accepted, refusals 14) negative organs.51 drawback systemic brain-death inflammation influence quality.52 logistical challenges retrieving hospital implantation, cold ischaemic hours 42 minutes, 50 minutes cases.5 ischaemia–reperfusion chronic rejection, well dysfunction.53, 54 models grafts tolerated times 24 hours,51, 55, 56 prolonged seen uncertain significance. fungal greater, contamination sterile organisms non-sterile cuff, exemplified unsuccessful first brain death, haemorrhage candida-associated vasculitis vessels.36 occurred Brazil 2017, type.35 long-term accurate comparison efficacy between types undertaken. entails surrounding ligamentous connective tissues, blood supplying draining uterus. predominantly midline laparotomy approach 39), minimally invasive proposed,57 recently implemented six laparoscopic-assisted, utilised robotic approach.10, 33, 39 unpublished, several illustrate already progress. With regards survival, just 13) subsequently emergency hysterectomy. most indication thrombosis, 7).9, 30, 31, Three prompted infective causes: infection/abscess respond conservative measures;9 another anastomosis;36 herpes simplex graft.34 ischaemia unspecific aetiology.31 final complicated led resultant failure.5 Postoperatively, three-quarters 7) hysterectomies 15 days. regard type, survival 75% (27/36), 56% (5/9). Seven pregnancies. continue grafts. All menstruation without supplementary hormone therapy; indicator functionality ongoing wellbeing. addition failures, five necessitating vesicovaginal 1) stenosis uterine-vaginal anastomosis dilation stenting 4).34 Five expected treatment, pleural effusions 2)9 3).34, 58 Rejection defined destruction host's response, activated graft's alloantigens difference donor-recipient genes. implanted deleterious host transplanted organs. burden immunosuppressive offset improvement life. agents smallest dose possible, avoiding steroids possible. tacrolimus preferred agent, initially combination mycophenolate mofetil (MMF), prednisolone. MMF later withdrawn anticipation embryo transfer, its teratogenic nature,59 usually replaced azathioprine. An regimen, azathioprine immediately recently, episodes.60 symptoms abdominal pain, fever discharge/bleeding, apparent once firmly established. grading proposed baboons, concluded biopsies consistent, achievable means detecting graft.61 26 episodes recipients. proven histology 24), biopsies,9, 62 diagnosed presentation suggestive terms raised serum lymphocyte subpopulations.34, histologically 21; 88%) mild moderate, (12%) severe.57 managed 3-day intravenous methylprednisolone, antithymocyte globulin. unique advantage temporary, woman's complete, removed, allowing cessation immunosuppression. Given immunosuppression-associated morbidity, diabetes nephrotoxicity, duration dependant,63 lifelong order facilitate manipulation, post ectopic prior creation cryopreservation embryos Not guarantee availability postoperatively reduces egg collections anatomy distorted introduction vitrification techniques, success vitrified now similar fresh embryos,64 minimises quality. Multiple gestation problematic added complications, preterm labour, pre-eclampsia gestational diabetes, greatly potentiates antenatal risk. Consequently, transfer always Embryo delayed until postoperatively,65 per standard guidance.66 cases,38 6 adopted, sufficient healing stabilisation regime. review unsafe Tacrolimus consistently safe administer abnormality.67 potentially immunosuppression, MMF, stopped weeks used, reduced 3 months, cumulative exposure.60 Twenty-three UTx; operations.4 Outcomes cases.68 Antenatal 3), cholestasis 2) prelabour rupture membranes 1). 31 35 gestation, weight age.23 fertilisation,69 postmenopausal uteri, inherently elastic vasculature could pregnancy,70 noted kidney.23 risk–benefit ratio clearly exclusion certain studies,71 inclusion others.34 subchorionic haematoma resolved spontaneously,72 episode pyelonephritis inpatient antibiotics.35 offspring delivered lower section caesarean section. primarily uncertainty regarding support vascular supply labour. concomitant peripartum hysterectomy.68 infants good abnormality. fetus, theoretical reversible neonatal hyperkalaemia impairment, requires postnatally. excreted breast milk, infant ingestion 1% dosage,73 breastfeeding concentrations birth, safe.74 inability conceive, psychological sequelae. More third infertile develop depression suicide.75 bear children personal femininity negatively life.76 interrelationship wellbeing, evaluation, and, applicable, aspects recipients77, 78 donors79 examined, relationships, managing childlessness, relationship donor, knowledge risks. Participants, partners, did report baseline, nor events, confirmed quantitively SF-36 Quality Life (FertiQoL), Hospital Anxiety Depression Scale (HADS) Dyadic Ad