INTRODUCTION — Uterus transplantation is an experimental procedure for the treatment of absolute uterine factor infertility (AUFI). AUFI refers to infertility that is completely attributable to uterine absence (congenital or surgical) or an abnormality (anatomic or functional) that prevents embryo implantation or completion of pregnancy to term. This topic will review the surgeries for the donor and recipient, immunosuppression, and obstetric issues involved in uterus transplantation. The intent of this topic is to provide an overview of the critical issues for clinicians and patients; the topic is based on the experience of the authors and should not be used for treatment decisions.

Related discussions on the ethical issues, patient selection, and consent involved in uterus transplantation, as well as topics on solid organ transplantation, are presented separately.

●(See "Uterus transplantation for absolute uterine factor infertility: Ethics, patient selection, and consent".)

●(See "Kidney transplantation in adults: Overview of care of the adult kidney transplant recipient".)

●(See "Transplantation immunobiology".)

INDICATIONS, ETHICS, AND PATIENT SELECTION — The indications, ethics, and patient selection for uterus transplantation are reviewed separately. (See "Uterus transplantation for absolute uterine factor infertility: Ethics, patient selection, and consent".)

SURGERY — Uterus transplantation is a complex, multi-step process that involves a uterus donor, uterus recipient, and genetic father (figure 1). The uterus recipient is also the genetic mother, as embryos are created using her eggs and the genetic father's sperm prior to the transplantation procedure. Surgical removal of the donor uterus requires a radical-type hysterectomy (figure 2). Uterus transplantation involves extensive vascular surgery. The discussion below highlights key points specific to uterus removal and transplantation.

Uterus removal — The uterus can be removed from a living or deceased donor. The challenges and benefits of each approach are presented separately. (See "Uterus transplantation for absolute uterine factor infertility: Ethics, patient selection, and consent", section on 'Use of living or deceased donor'.)

Living donor

Procedure — The surgical technique for removing a uterus from a living donor has been described in detail [1]. We perform a vertical midline incision, starting above the umbilicus and extending to the pubic symphysis, to ensure adequate exposure of pelvic structures up to the level of the bifurcation of the internal and external iliac arteries. Of note, at least one group has reported use of robot-assisted laparoscopy for procurement of the donor uterus, although it is not known if the shorter operating time and less-invasive approach outweigh the potential risks (both known and unknown) of using a less established surgical approach for an experimental procedure [2]. The procedure for uterus removal is similar to a radical-type hysterectomy in that the vessels are ligated as far laterally as possible to ensure long vascular pedicles for transplantation (figure 2). However, additional dissection is required to preserve critical structures for the donor while obtaining the best possible graft for transplantation. To date, uterus procurement surgery has required 10 to 13 hours [3]. (See "Radical hysterectomy", section on 'Types of radical hysterectomy' and "Radical hysterectomy", section on 'Operative technique'.)

Key steps in removing a uterus from a living donor include:

●Removal of a large flap of bladder peritoneum (almost to the level of the bladder dome) with the uterus – This peritoneal flap will later be used to secure the grafted uterus in the recipient and cover the open vesicouterine fossa, with the goal of minimizing the risk of intestinal herniation in this pelvic area.

●Identification of the ureters just distal to their passage over the iliac vessels – During further dissection of the ureter, care is taken to avoid any damage to the overriding uterine artery and the uterine veins that are both crossing over and under the ureter in the ureteric tunnel. All small branches from the uterine vessels at this location should be ligated or sutured to avoid leakage after reperfusion of the organ in the recipient.

●Dissection of the fallopian tubes from their vascular supply – The authors tie the freed tubes together in a knot to create a functional handle that allows them to manipulate the uterus without directly touching it.

●Dissection of the upper uterine or ovarian vein – In our approach, the branch from the uterine cornua that merges with the ovarian vein and forms a true utero-ovarian vein is dissected free and flushed with heparinized saline. This branch may be used for end-to-side anastomosis (during back-table preparation) to the uterine vein or to one end on the internal iliac vein segment in order to increase blood flow from the uterus after anastomosis. Alternately, some authors have suggested using only the ovarian veins to provide venous outflow [4,5].

●Dissection of the arterial supply to the uterus – The arterial vasculature of the uterus is dissected proximally to the bifurcation between the major anterior branch of the iliac artery and the posterior portion (gluteal artery). Then all branches from the anterior portion, including the umbilical artery, are divided to gain one major trunk of the arterial supply through the interior iliacs. The arterial segment between the bifurcation of the posterior branch of the iliac artery and cervix is kept in the graft, while all the other branches (iliolumbar artery, lateral sacral artery, gluteal [superior and inferior] arteries, pudendal artery, middle rectal artery, vaginal artery, obturator artery, and umbilical artery) are ligated and remain in the donor.

●Dissection of the ureter – The uterine artery, which is over-riding the ureter, is then dissected free from its attachment to the ureter. Several small arterial branches going from the uterine artery to the ureter (posterior surface) and upper bladder are ligated.

●Dissection of the uterine veins – Dissection of the veins begins on the pelvic sidewall, in order to identify the internal iliac vein, and progresses toward the uterus. The goal of venous dissection is to create an outflow conduit on each side of the uterus. The sizes and the positions of the veins determine whether one large and dominating uterine vein is chosen or whether several smaller uterine veins will be used for venous drainage. The venous vascular pedicle should, at its end, contain a segment or a patch of the internal iliac vein, in order to get a vein with well-defined walls that will make anastomosis surgery in the recipient easier. If the outflow through the uterine vein(s) on one side is anticipated to be low because of the small size of the vessels, the uterine branch of the utero-ovarian vein is dissected and later anastomosed to the internal iliac venous segment to increase venous drainage. All veins must be dissected off the ureter.

●Dissection of the rectovaginal space – The rectovaginal space is then opened and the uterosacral ligaments are divided, preferably 10 to 15 mm from the uterine cervix, to facilitate subsequent uterine fixation in the recipient. The extensive dissection of the vagina increases its mobility which allows it to be moved backward towards the proximal edge of the uterosacral ligaments (that remain in the donor) to perform a McCall culdoplasty. Thus, the posterior vaginal apex is drawn up to the supporting uterosacral structures and thereby elevated to a normal position.

●Dissection of the vaginal vascular supply – The vaginal arteries and veins that are firmly attached to the lateral portions of the upper vagina are divided. The vagina is then transected and a 15 to 20 mm vaginal rim is left on the uterine side.

●Uterus removal – After the dissections are completed, the uterus is only attached by the bilateral arterial and venous vascular pedicles. Vascular clamps are then placed, first on the internal iliac arteries just distal to the branching of the gluteal arteries, and on the internal iliac veins to obtain segments or patches of this on each side. The vessels are divided just distal to the clamps, and the uterus is quickly taken to the back-table, where it is cooled down by flushing cold preservation solution through the arteries. Any vascular leakage is repaired on the back-table, and vascular reconstructions, such as anastomosis of the upper uterine vein, are performed. The donor surgery is completed by closure of the open vascular pedicles and the vaginal vault.

Complications — Surgical complications can be intra- or postoperative. The most serious intraoperative complications, in order of descending importance, are lacerations of a vein, artery, ureter, or bladder wall.

More common postoperative complications include wound infection, venous thromboembolism, bleeding, vaginal cuff infection or dehiscence, or ureteric/bladder injury with fistula formation. In the clinical trial of nine uterus transplantations, one donor was diagnosed with a ureterovaginal fistula on postoperative day (POD) 16, which was treated with a pyelostomy catheter and subsequent ureteral reimplantation on POD 134 [1]. Detailed discussions of the prevention or treatment of these complications are presented separately.

●(See "Antimicrobial prophylaxis for prevention of surgical site infection in adults".)

●(See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients".)

●(See "Management of hemorrhage in gynecologic surgery".)

●(See "Posthysterectomy pelvic abscess".)

●(See "Vaginal cuff dehiscence after total hysterectomy".)

●(See "Urinary tract injury in gynecologic surgery: Epidemiology and prevention".)

●(See "Urinary tract injury in gynecologic surgery: Identification and management".)

●(See "Urogenital tract fistulas in females".)

●(See "Rectovaginal and anovaginal fistulas".)

Deceased donor — In removing the uterus from a deceased donor, the goal is to remove the organ with the longest vascular pedicles possible. To that end, the uterus is typically removed with the uterine vessels intact and attached to portions of the internal iliac vessels, and potentially to the common iliac vessels (figure 3). Having long vascular pedicles facilitates transplantation of the organ into the recipient. One advantage of organ procurement from a deceased donor compared with a living donor is that the ureters can be transected because they are no longer needed for function. The ureters are transected both caudally and cranially from the point where they cross the uterine vessels and thus the need to dissect the vessels off of the ureters is eliminated. The branches from the vascular pedicles on the graft side can be ligated at the time of transection or after the entire organ has been removed (ie, back-table preparation).

One challenge of deceased-donor surgery is that, in the setting of a multi-organ donor, the uterus is typically not the first organ removed (life-saving organs are usually removed first). The uterus is flushed with heparinized preservation solution while the vital organs are removed. In the first reported donor uterus surgery that resulted a live birth, the total uterus ischemic time was nearly eight hours [6]. In contrast to the traditional flushing technique in solid organ transplantation, which is done from the lower aorta in a cranial direction, one research group has reported flushing of the uterus through cannulation of the femoral arteries [7]. Total time for graft procurement (flushing, removal, and back-table preparation) has been reported to range between 30 and 120 minutes [6-8]. Different groups have reported performing the hysterectomy first, prior to procurement of other organs and before the cross-clamping of the aorta [5,8-10]. When the hysterectomy is performed first, the surgery becomes a clean-contaminated case, which should be discussed with all surgical teams involved in organ procurement.

Uterus transplantation

Procedure — The surgery on the organ recipient is not begun until approximately 30 minutes before the predicted time for organ removal from the donor and once the surgeons have confirmed that the graft is well perfused by the remaining isolated vascular pedicles. In the authors' trial, when the graft donor was a postmenopausal woman, the authors delayed the recipient surgery until the graft organ had been removed from the donor and was clearly well perfused with preservative solution because of the smaller size of the uterine arteries after menopause. Of note, the recipient receives her first dose of immunosuppressive medication at the onset of surgery.

Surgery is begun by making an infraumbilical midline incision. The next steps are determined by the recipient woman's pelvic anatomy:

●For women without a uterus (the majority of recipient women), the initial surgery involves separation of the bladder and the rectum from the vaginal vault. The dissection is aided by use of a vaginal sacropexy probe to displace the vagina upward.

●For women who have a uterus in place (eg, women with Asherman syndrome), a traditional total hysterectomy is performed with removal of the fallopian tubes.

●For women with rudimentary uterus or similar structure above the vaginal vault (eg, women with Mayer-Rokitansky-Küster-Hauser [MRKH] syndrome), the rudimentary uterus is cleaved.

The external iliac arteries and veins are then dissected and cleared over a distance of approximately 3 to 4 cm to give space for later anastomosis. The authors place non-resorbable fixation sutures (1-0) bilaterally in the uterosacral ligaments, the round ligaments, and in the tissue that will be lateral to the cervix (cardinal ligaments or, in the case of MRKH, the cleaved uterine rudiment above the vaginal vault).

The cooled and flushed uterus is then placed in the pelvis and traditional end-to-side anastomosis surgery is performed (figure 2). On each side, the vein is attached first and then the artery. Each anastomosis requires approximately 15 to 30 minutes. Once all anastomoses have been completed, the vascular clamps are removed and the organ is perfused. Any anastomotic leaks are repaired. The vagina of the recipient is then opened with a vertical incision to avoid injury to the ureters. The vertical incision length is extended to correspond to the diameter of the vaginal ring of the graft. The vaginal rim of the grafted uterus is then anastomosed end-to-side to the opened vaginal vault with a continuous absorbable suture. The uterus is then fixed bilaterally to the sutures of the sacrouterine ligaments, round ligaments and paracervical tissues. As a last point of fixation, the bladder peritoneum is sutured on the top of the bladder fundus. The abdomen is then closed. To date, uterus transplantation has required approximately four to five hours [3].

Complications — The major intraoperative risk for the uterus recipient is anastomotic leakage. Leakage is typically immediately visible and is repaired with polypropylene suture. Prior to closing, the authors place a passive drain in the pelvis, posterior to the uterus, to help identify intra-abdominal bleeding during the immediate postoperative period. In the trial of nine uterus transplantations, one woman developed a retroperitoneal hematoma and required a blood transfusion [1].

The routine surgical complications for the recipient are similar to those of the donor and include wound infection and bleeding. A complication that is unique to the graft recipient is the thrombosis of any uterine vessel anastomoses. The authors routinely measure the blood flow with an intraoperative probe during surgery. The graft uterine arteries are monitored with external Doppler measurements using an abdominal probe. The authors assessed the uterine artery flow every day during the first week post-transplant and then once a week until the end of the first month. After the first month, no further Doppler measurements were routinely performed. If there is concern for vessel thrombosis, the authors may repeat the laparotomy to assess the patency of the blood vessels and to clear any thrombosis with possible reconstruction of the graft vessels or anastomosis sites.

GRAFT COMPLICATIONS — The most serious complications that affect the grafted uterus are rejection, thrombosis, and infection.

Rejection — When detected early, organ rejection can often be reversed with a temporary increase in maintenance immunosuppression or a short course of corticosteroids. The authors monitor transplant recipients with cervical biopsies to detect rejection [11]. In their research protocol, the predetermined time points for cervical biopsy were one, two, and four weeks post-transplantation and monthly thereafter [3]. Additional biopsies were performed for clinical symptoms that could represent organ rejection such as vaginal discharge, fever, or abdominal pain. Physical examination findings suggestive of graft rejection can include cervical discoloration, focal epithelial erosions, ulcerations, or areas of necrosis. The authors have developed a preliminary grading system for assessing allograft rejection of the human uterus based on studies of cervical biopsies [11]. This grading system is in its initial phase; the means to detect and grade rejection will likely develop further in the future.

If rejection is detected in the biopsy specimen, the authors perform follow-up biopsies on a weekly basis until the histology normalizes. In their research trial of seven women, rejection was seen in five patients. Less than 10 percent of all protocol biopsies met the criteria for organ rejection. All rejection events were subclinical; no pathological findings were identified on ultrasound or gynecologic examination. The histologic findings of the mild rejection episodes consisted of a mixed inflammatory cell infiltrate (continuous or patchy), dominated by lymphocytes, at the interface of the superficial stroma and basal epidermal layer. In the few cases of severe rejection, histologic evaluation revealed a major diffuse, mixed inflammatory cell infiltrate [11].

Thrombosis — Arterial and venous thrombosis have been described after other types of abdominal organ transplantation and are also a factor for uterus transplant [12-15]. While the data are limited, thrombosis of the uterine arteries and veins occurred in one of nine cases in the authors' trial. In the initial United States living-donor transplant trial, three of the initial five transplant procedures required graft removal as a result of vascular complication [16]. Ultrasound and cross-sectional imaging techniques are effective at detecting clots in the graft's vessels [13,14]. Possible explanations include thrombus formation secondary to low initial arterial blood flow, venous outflow problems, or constrictions of the anastomosis lines.

Infection — A transplanted uterus may be more susceptible to intrauterine infection because of the immunosuppressed state of the recipient. In order to prevent infection, patients are given 4 g piperacillin/tazobactam preoperatively and three times daily for three days. In the trial of nine women undergoing transplantation, one transplanted uterus required removal on postoperative day 105 because of persistent infection with Enterococcus faecalis that did not respond to intravenous antibiotic therapy or surgical drainage [17]. Histopathologic analysis reported extensive areas of necrosis and neutrophil-dominated inflammation but no signs of rejection. A different clinical team that attempted a deceased-donor uterus transplant reported removal of the graft on postoperative day 12 because of Candida infection that disrupted one of the vascular anastomoses of the graft and led to bleeding [18]. A different group reported need for removal of a deceased-donor graft because of uterus injury (lack of endometrial development, fibrotic obliteration of the uterine cavity and cervical canal) resulting from herpes simplex virus-2 infection [5]. Based on these events, future protocols for uterus transplantation could include preoperative testing for herpes simplex virus and vaginal fungal cultures or fungal prophylaxis.

Unplanned graft removal — The surgical technique for unplanned graft removal (hysterectomy) is relatively straightforward when the surgery occurs within the initial two weeks following transplantation because firm adhesions have not yet formed and access can be easily regained through the midline incision. Cessation of blood flow through the uterine arteries is confirmed with intraoperative Doppler ultrasound and manual palpation of the uterine arteries before hysterectomy is started. The fixation points of the uterus and the vaginal-vaginal anastomosis line are easily identified. These suture lines are opened first to make it easier to dissect the uterine vessels up to the anastomosis points on the external iliac vessels. It is important to remove the entirety of the grafted vessels in order to avoid weakening, and possibly rupture, at these spots when immunosuppression is stopped and rejection of any retained foreign tissue will occur.

IMMUNOSUPPRESSION

Our approach — In their clinical trial, the authors used a combined immunosuppressive protocol similar to that used for other type of composite tissues such as the face or the arm [1,19]. Immunosuppression induction was achieved with 1 g mycophenolate mofetil preoperatively and 500 mg methylprednisolone together with antithymocyte antibodies to deplete T lymphocytes during transplantation. A second dose of antibodies was given 12 hours later (monoclonal or polyclonal antibodies were used indistinctly) [1].

Maintenance immunosuppressive therapy was continued with tacrolimus, mycophenolate mofetil, and prednisolone. Target tacrolimus levels were 10 to 15 ng/mL for the first five weeks and then 5 to 10 ng/mL thereafter. Mycophenolate doses were calculated to achieve an area under the curve of 40 to 60 mg h/L. Oral prednisolone was given at 5 mg/day for the first four days after transplantation and then discontinued. In the event of acute rejection episodes, methylprednisolone intravenous was administered at a dose of 500 mg/day for three days, and then followed by five to seven days of oral prednisolone. In women with more than one rejection episode during the initial eight months, mycophenolate was changed to azathioprine to avoid the teratogenic effects of the former at embryo transfer, which was anticipated to start approximately 12 months post-transplantation [3]. In women with no or only one early mild rejection episode, tacrolimus was the only immunosuppressive agent in use after eight months. The immunosuppressive regimen has since been modified to include azathioprine rather than mycophenolate at the onset of transplant and the IL-2 agonist basiliximab instead of antithymocyte antibodies [20].

Uterine rejection chronology has been well characterized in rodent models [21]: It begins with neutrophil and CD8+ lymphocyte infiltration of the myometrium on day 2 after transplantation, and it spreads to the endometrium on day 5. CD4+ lymphocytes only increase transiently on day 5 after transplant, and CD19+ cell density remains low during all the rejection process. The histological characteristics of mild, moderate, and severe rejection of human uterine grafts are described in the literature [11]. Human transplant immunobiology is discussed in detail separately. (See "Transplantation immunobiology".)

Treatment risks — The use of immunosuppressants has been related to the development of comorbidities such as kidney disease [22], diabetes [23], infections [24], and malignancies [25]. Such comorbidities are often a direct consequence of the use of immunosuppressants and can compromise directly or indirectly the survival rates of the patients.

●(See "Kidney function and non-kidney solid organ transplantation".)

●(See "Kidney transplantation in adults: Posttransplantation diabetes mellitus".)

●(See "Infection in the solid organ transplant recipient".)

●(See "Malignancy after solid organ transplantation".)

●(See "Overview of dermatologic problems following liver transplantation".)

Use in pregnancy — The main issues regarding immunosuppression in pregnancy are teratogenicity and pharmacokinetics. Most of the data come from studies of women with other types of solid organ transplants (ie, kidney or liver).

One of the major criticisms of uterus transplantation is fetal exposure to multiple drugs. Mycophenolate mofetil appears to be a teratogen and is therefore not advised for use in women attempting pregnancy [26,27]. While azathioprine has not been identified as a human teratogen, in utero exposure in rodents resulted in congenital anomalies, although this outcome has not been seen in human women undergoing other solid organ transplants [26,28]. (See "Kidney transplantation in adults: Overview of care of the adult kidney transplant recipient", section on 'Immunosuppressive medication during pregnancy'.)

Physiological changes during pregnancy include increased volume of distribution and induction of different enzyme complexes that result in altered metabolism of immunosuppressant agents [29]. Thus, levels of immunosuppressive drugs must be closely monitored during pregnancy.

OBSTETRIC ISSUES

Impact of immunosuppressive agents — The American Society of Transplantation criteria advise that pregnancy be delayed for at least one year following solid organ transplantation and that no episodes of rejection have occurred during the prior six months [30]. This approach is based, in part, on the use of mycophenolate during the first year following solid organ transplantation. Mycophenolate is a known teratogen that is tapered and stopped prior to attempts at conception [27]. In years 2 and 3 following transplantation, azathioprine, tacrolimus, and glucocorticoids are typically used for immunosuppression in solid organ transplant protocols. Although azathioprine is likely mildly teratogenic, it is believed that, at low doses, the benefits outweigh risks. As of 2006, more than 14,000 births had been reported from women with transplanted organs who were receiving immunosuppressive therapy without a noticeable increase in structural malformations [31].

Obstetric complications — Among potential obstetric complications, the authors particularly monitor women with uterus transplants for evidence of preeclampsia and gestational diabetes (for women receiving glucocorticoids or tacrolimus). A review of 52 transplant recipients reported 6 of 16 (37.5 percent) experienced major obstetric complications [32]. For women with renal transplants, volunteer patient registries have reported increased rates of adverse perinatal outcomes, particularly hypertension and preeclampsia [31,33]. In a population-based study comparing pregnancy outcome before and after organ transplantation (multiple types), women with organ transplants experienced increased risk of preeclampsia, preterm birth, low birth weight, and small for gestational age infants [34]. However, when births just before and after transplantation were compared, the perinatal outcomes were found to be similar. This study suggests that the major cause for these pregnancy complications in transplanted patients was the organ disease that led to the transplantation procedure and not the immunosuppressant medication or the transplantation procedure itself. Until more data are available, the obstetric and fetal risks for uterus transplantation patients are extrapolated from the solid organ transplantation data. Women with other types of solid organ transplants undergo surveillance for preeclampsia, serial ultrasounds for fetal growth assessment beginning by 24 weeks of gestation, antenatal testing beginning by 32 weeks of gestation, and early and standard screening for diabetes [35].

In the first pregnancy after uterus transplantation, the patient was followed every third week, including fetal and maternal assessment [3]. The pregnancy was uneventful until week gestational week 31 day 5, when the patients was admitted to the hospital and underwent an emergency cesarean section because of preeclampsia, contractions, and signs of fetal distress [3]. A healthy boy weighing 1775 g was delivered.

PLANNED GRAFT REMOVAL — Uterus transplantation is the first type of organ or tissue transplantation that is only temporary and not intended to stay with the host for life. The uterus is removed when childbearing is deemed complete to limit the amount and duration of immunosuppressive medication and thereby reduce the risk for immunosuppressive side effects such as nephrotoxicity and increased risk of certain malignancies.

Major challenges anticipated at the time of the graft removal surgery are adhesions that have formed around the graft's vessels and the non-anatomic location of the vessels. In addition, the ureters may be positioned close to the graft vessels on the pelvic sidewalls and difficult to separate. Preoperative insertion of ureteric double J stents can be helpful to aid in palpating the ureters. Identification of the native and graft vaginal edges can also be challenging.

SUMMARY AND RECOMMENDATIONS

●Uterus transplantation is a complex, multi-step process that involves a uterus donor, uterus recipient, and genetic father (figure 1). (See 'Surgery' above.)

●The uterus can be removed from either a living or deceased donor. The procedure for uterus removal from a living donor is similar to a radical-type hysterectomy in that the ligaments and vessels are ligated as far laterally as possible to ensure long vascular pedicles for transplantation (figure 2). In removing the uterus from a deceased donor, the organ can be removed with longer vascular pedicles than in living uterus donation. Transection of the ureters simplifies the surgery in a deceased donor. The uterus is typically removed with the uterine vessels intact and attached to the internal iliac vessels, and potentially to the common iliac vessels (figure 3). (See 'Uterus removal' above.)

●The surgery on the organ recipient is not begun until approximately 30 minutes before the predicted time for organ removal from the donor and once the surgeons have confirmed that the graft is well perfused by the remaining isolated vascular pedicles. For women without a uterus (the majority of recipient women), the initial surgery involves separation of the bladder and the rectum from the vaginal vault. For women who have a uterus in place (eg, women with Asherman syndrome), a traditional total hysterectomy is performed with removal of the fallopian tubes. For women with rudimentary uterus or similar structure above the vaginal vault (eg, women with Mayer-Rokitansky-Küster-Hauser syndrome), the rudimentary uterus is cleaved. (See 'Procedure' above.)

●The major intraoperative risk for the uterus recipient is anastomotic leakage. Leakage is typically immediately visible and is repaired with polypropylene suture. The routine surgical risks for the recipient are similar to those of the donor and include wound infection and bleeding. A complication that is unique to the graft recipient is the thrombosis of any uterine vessel anastomoses. (See 'Complications' above.)

●The most serious postoperative complications of the grafted uterus are rejection, thrombosis, and infection. When detected early, organ rejection can often be reversed with a temporary increase in maintenance immunosuppression or a short course of corticosteroids. While the data are limited, thrombosis of the uterine arteries and veins appears to occur occasionally in this early phase after uterus transplantation. Ultrasound and cross-sectional imaging techniques are effective at detecting clots in the graft's vessels. A transplanted uterus may be more susceptible to intrauterine infection because of the immunosuppressed state of the recipient. Antibiotic prophylaxis is given prior to the start of the surgery, which may be expanded to include antifungal agents in the future. (See 'Graft complications' above.)

●In the author's clinical trial, they used a combined immunosuppressive protocol similar to that used for other type of composite tissues such as the face or the arm. The main issues regarding immunosuppression in pregnancy are teratogenicity and pharmacokinetics. Most of the data come from studies of women with other types of solid organ transplants (ie, kidney or liver). Mycophenolate mofetil appears to be a teratogen and is therefore not used in women attempting pregnancy. (See 'Our approach' above.)

●Physiological changes during pregnancy include increased volume of distribution and induction of different enzyme complexes that result in altered metabolism of immunosuppressant agents. Thus, levels of immunosuppressive drugs must be closely monitored during pregnancy. (See 'Use in pregnancy' above.)

●The American Society of Transplantation criteria advise that pregnancy be delayed for at least one year following solid organ transplantation and that no episodes of rejection have occurred during the prior six months of that year. Among potential obstetric complications, the authors particularly monitor women with uterus transplants for evidence of preeclampsia and gestational diabetes (for women receiving glucocorticoids or tacrolimus). Volunteer patient registries of women with renal transplants have reported increased rates of adverse perinatal outcomes, particularly hypertension and preeclampsia. (See 'Obstetric complications' above.)

●Uterus transplantation is the first type of organ or tissue transplantation that is only temporary and not intended to stay with the host for life. The uterus is removed when childbearing is deemed complete to limit the amount and duration of immunosuppressive medication, and thereby reduce the risk for immunosuppressive side effects such as nephrotoxicity and increased risk of certain malignancies. Major challenges anticipated at the time of the graft removal surgery are adhesions that have formed around the graft's vessels and the non-anatomic location of the vessels. (See 'Planned graft removal' above.)