Mats Brannstrom

University of Gothenburg | GU · Department of Obstetrics and Gynecology

Uterus transplantation (UTx) is currently the only available treatment for absolute uterine factor infertility. The International Society of Uterus Transplantation (ISUTx) was formally founded in 2017 and joined the Transplantation Society as a formal section in 2021. The Third International Congress of the ISUTx was held in Tübingen, Germany, in O...

High‐mobility group box 1 (HMGB1) is critical for inflammatory homeostasis and successful pregnancy, and there is a strong association between elevated levels of HMGB1, polycystic ovary syndrome (PCOS), chronic inflammation, and pregnancy loss. However, the mechanisms responsible for PCOS‐driven regulation of uterine HMGB1 and its candidate recepto...

During the last decade, uterus transplantation has evolved as the first treatment for absolute uterine factor infertility, caused by absence of a functional uterus. Current challenges in the area of uterus transplantation are organ shortage and side effects of immunosuppression. These hurdles may be solved with novel tissue engineering technologies...

Background: Uterus transplantation (UTx) is a novel type of transplantation to treat infertility in women with an absent or nonfunctioning uterus. The International Society of Uterus Transplantation (ISUTx) has developed a registry to monitor worldwide UTx activities while serving as a repository for specific research questions. Methods: The web...

Decellularized tissue is generally considered immune privileged after transplantation and is an attractive scaffold type for tissue regeneration, including applications for infertility treatment. However, the immune response following transplantation of decellularized tissue is insufficiently studied, in particular after they have been recellulariz...

Before the first live birth following uterus transplantation (UTx) in 2014, the 1-2% of women with an absent or nonfunctional uterus had no hope of childbearing. With 64 UTx cases and 32 births reported in the scientific literature, this emerging technology has potential for translation into mainstream clinical practice. However, limitations curren...

Introduction Vaginal progesterone supplementation is frequently given to patients receiving frozen embryo transfer (FET) in the natural cycle aiming to increase the chance of pregnancy and live birth. To date, only a few studies have investigated if progesterone supplementation is beneficial in these cycles and the level of evidence for progesteron...

Objective: To evaluate reproductive, obstetric, and long-term health of the first completed study of uterus transplantation (UTx). Design: Prospective. Setting: University hospital. Patient(s): Nine live donor UTx procedures were conducted and seven were successful. Donors, recipients, and children born were observed. Intervention(s): In v...

BACKGROUND To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones produced by the ovaries. Mature oocytes may be fertilized in the fallopian tubes, and the resulting zygote is transported toward the uterus, where it can implant and continue...

Absolute uterus factor infertility, whether congenital or acquired, renders the woman unable to carry a child. Although uterus transplantation (UTx) is being increasingly performed as a non-vital procedure to address this unfortunate condition, the immunosuppression required presents risks that are further compounded by pregnancy and during the pue...

Objective: Uterus transplantation (UTx) has evolved as the first true infertility treatment for absolute uterine factor infertility (AUFI), caused by a lack (congenital or surgical) of the uterus or presence of a non-functional uterus. Ever since the proof-of-concept of UTx as an infertility treatment, by the first live birth in 2014, the field has...

Objective: To review the current knowledge on uterus bioengineering and discuss potential future directives. Uterus bioengineering may solve two major hurdles in organ transplantation of a uterus, organ shortage and control of rejection by immunosuppression. Mechanism: Literature search using PubMed. Findings in brief: Sixty-seven references were s...

Background: Several studies have shown that younger women with polycystic ovary syndrome (PCOS) have decreased Health-Related Quality of Life (HRQoL) compared with women in general. Method: In this study peri-and postmenopausal women previously diagnosed with PCOS (n = 27) were compared with randomly selected, age-matched controls (n = 94). Mean ag...

Objective Despite the clear evidence of increased cardiovascular disease (CVD) risk factors, the long-term effect on CVD and mortality is still uncertain in women with PCOS, especially in the elderly. Studies in elderly women with PCOS are lacking. The objective was to study morbidity/mortality in PCOS women compared with a reference group up to a...

The mechanisms through which the androgen-dependent activation of the androgen receptor (AR) regulates gravid uterine ferroptosis remain unknown. We show that while co-exposure of pregnant rats to the androgen 5α-dihydrotestosterone (DHT) and insulin (INS) triggered uterine ferroptotic signaling cascades, additional treatment with the anti-androgen...

Uterus transplantation is the first line of treatment for absolute uterine factor infertility, which is caused by the absence of a proper uterus or by a nonfunctional uterus. The group also includes women who have undergone hysterectomy for malignant disease, such as cervical cancer. Thus, this transplantation can be used for fertility preservation...

Introduction: The first live birth after uterus transplantation occurred in Sweden in 2014. Uterus transplantation has repeatedly, and at many centers worldwide, proven to be a feasible treatment for absolute uterine factor infertility. Hysterectomy in live donors and transplantation are well described in numerous reports. However, there are no re...

STUDY QUESTION How do women experience attempts to become pregnant, and the first years of motherhood, after uterus transplantation (UTx)? SUMMARY ANSWER Women who try to become pregnant after UTx experience the general strains typically associated with infertility and childlessness, such as failure of embryo transfer (ET), and specific worries ab...

One of modern healthcare's most controversial areas, reproductive medicine is an emerging discipline that fosters hugely divergent opinions on topics such as laboratory techniques, clinical management and ethical considerations. Highlighting over 50 contentious topics in reproductive medicine, this book presents expertly argued opinions are present...

The mechanisms that link hyperandrogenism and insulin resistance to the increased miscarriage rate in women with polycystic ovary syndrome (PCOS) remain elusive. Previous studies demonstrate that increased uterine and placental ferroptosis is associated with oxidative stress-induced fetal loss in a pre-clinical PCOS-like rat model. Here, we investi...

Objective To evaluate uterine arteries (UA) of potential living donors for uterus transplantation (UTx) by comparison of CT angiography (CTA), digital subtraction angiography (DSA), and MR angiography (MRA) with care taken to minimize radiation doses. Methods Prospective donors for a clinical UTx trial were included. CTA, DSA, and MRA measurements...

Purpose of review: Women with absolute uterine factor infertility, because of uterine absence, or the presence of a nonfunctional uterus, were regarded as being untreatable until 2014 when the first birth following uterus transplantation (UTx) took place in Sweden. This proof-of-concept occurred in a woman with Mayer-Rokitansky-Küster-Hauser syndr...

In this study, we show that during normal rat pregnancy, there is a gestational stage-dependent decrease in androgen receptor (AR) abundance in the gravid uterus and that this is correlated with the differential expression of endometrial receptivity and decidualization genes during early and mid-gestation. In contrast, exposure to 5α-dihydrotestost...

Purpose of review: Donor hysterectomy for live donor uterus transplantation was from the start performed by laparotomy, but minimal invasive surgery has entered the scene. In particular robotic-assisted laparoscopy is used since robotics is advantageous in the complex donor hysterectomy surgery in narrow space. This review covers the development a...

Objective To determine the temporal expression of ACE2, a receptor for SARS-COV-2, in dominant follicles across the periovulatory period in women and the regulatory mechanisms underlying ACE2 expression in human granulosa/lutein cells (hGLC). Design Experimental prospective clinical study and laboratory-based investigation. Setting University Med...

Data on how the immune system reacts to decellularized scaffolds after implantation is scarce and difficult to interpret due to many heterogeneous parameters such as tissue-type match, decellularization method and treatment application. The engraftment of these scaffolds must prove safe and that they remain inert to the recipient's immune system to...

Hyperandrogenism and insulin resistance perturb the implantation process and mitochondrial dysfunction through the defective androgen receptor signaling in the rat gravid uterus Supporting data include two Supplemental Tables, and 7 Supplemental Figures

Uterine factor infertility was considered incurable until recently when we reported the first successful live birth after uterus transplantation. However, risky donor surgery and immunosuppressive therapy are factors that may be avoided with bioengineering. For example, transplanted recellularized constructs derived from decellularized tissue resto...

Scaffolds derived from decellularized tissue possess many advantages for bioengineering applications, including for novel infertility treatments. However, the decellularization process results in allogenic‐independent damage associated molecular patterns (DAMPs). This field is poorly studied, in particular for uterus bioengineering applications. An...

Study question: Do therapeutic levels of cyclosporine-A and tacrolimus affect ovulation in a rat gonadotrophin-induced ovulation model? Summary answer: Cyclosporine-A, but not tacrolimus, decreases ovulation rate when administered for 5 days before induced ovulation. What is known already: The mainstays of immunosuppression in solid organ tran...

This new edition provides a much-needed reference book to accommodate emerging and expanding knowledge in fertility preservation, the rapidly growing field of reproductive medicine associated with advances in oncology. Written by a team of world-leading experts in the field and comprehensive in its scope, the book covers the full range of technique...

Neurotensin (NTS) is a tridecapeptide that was first characterized as a neurotransmitter in neuronal cells. The present study examined ovarian NTS expression across the periovulatory period in the human and the rat. Women were recruited into this study and monitored by transvaginal ultrasound. The dominant follicle was surgically excised prior to t...

Cervical and endometrial cancer may impact women interested in future fertility in approximately 5–25% of cases. The recommended treatment for patients with early stage disease is hysterectomy and/or radiation leading to infertility. This is referred to as absolute uterine factor infertility. Such infertility was considered untreatable until 2014,...

Immune cell differentiation is critical for adequate tissue-specific immune responses to occur. Here, we studied differentiation of human uterine natural killer cells (uNK cells). These cells reside in a tissue undergoing constant regeneration and represent the major leukocyte population at the maternal-fetal interface. However, their physiological...

Background Low-grade chronic inflammation is commonly seen in polycystic ovary syndrome (PCOS) patients with elevated levels of inflammatory cytokines in the endometrium. However, our understanding of the mechanisms underlying cytokine synthesis and increased endometrial inflammation in PCOS patients remains limited. Methods Endometrial biopsy sam...

Uterus transplantation (UTx) is the first treatment for absolute uterine factor infertility. The first birth after human UTx in Sweden occurred in 2014 and very favourable results of the Swedish trial performed with laparotomy raised great hope. Several teams are leading their own trial among the world, but UTx is still in its experimental phase. S...

Background: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also referred to as Müllerian aplasia, is a congenital disorder characterized by aplasia of the uterus and upper part of the vagina in females with normal secondary sex characteristics and a normal female karyotype (46,XX). Main body: The diagnosis is often made during adolescence follo...

STUDY QUESTION What are the costs of live donor uterus transplantation in a European setting? SUMMARY ANSWER The total costs for preoperative investigations, including IVF, and live donor uterus transplantation including postoperative costs for 2 months, were calculated to be €74 564 (mean), with the costs of recipient being somewhat higher than f...

Context There is a lack of knowledge about hormonal and anthropometric changes in women with polycystic ovary syndrome (PCOS) after the menopause. Objective To study reproductive hormones and anthropometry in women with PCOS up to an age above 80 years. Design Prospective cohort study. Setting University Hospital. Patients A well-defined cohort...

Background The first live birth after uterus transplantation took place in Sweden in 2014. It was the first ever cure for absolute uterine factor infertility. We report the surgery, assisted reproduction, and pregnancy behind the first live birth after uterus transplantation in the Middle East, North Africa, and Turkey (MENAT) region. A 24-year old...

Purpose of review: Uterus transplantation (UTx) is the first existing infertility treatment for women with no uterus and for women with a present nonfunctional uterus, which is unable to carry a pregnancy. This type of transplantation is a novel addition within the field of vascularized composite allografts and is the first ephemeral kind of trans...

Absolute uterine factor infertility (AUFI) was considered untreatable until recently, when uterus transplantation (UTx) proved its potential as an effective treatment (Brännström et al., Lancet 385:607–616, 2015). In 2014, live births were reported after transplantation, using an altruistic living donor (Brännström et al., Lancet 385:607–616, 2015)...

Mucosa-associated invariant T (MAIT) cells are non-classical T cells important in the mucosal defense against microbes. Despite an increasing interest in the immunobiology of the endometrial mucosa, little is known regarding human MAIT cells in this compartment. The potential role of MAIT cells as a tissue-resident local defense against microbes in...

Uterus transplantation (UTx) can provide a route to motherhood for women with Mayer–Rokitansky–Küster–Hauser syndrome (MRKHS), a congenital disorder characterized by uterovaginal aplasia, but with functional ovaries. Based on our four successful living-donor transplantations and two resulting births, this analysis presents parameters relevant to st...

Objective To perform a stepwise development of the surgical method for robotics-assisted laparoscopy in donor hysterectomy for uterus transplantation (UTx), a unique treatment for absolute uterine-factor infertility. Design Prospective observational study. Setting University hospital. Patient(s) Eight donors, aged 38–62 years, underwent surgery...

Background: Fertility preservation is particularly challenging in young women diagnosed with hematopoietic cancers, as transplantation of cryopreserved ovarian cortex in these women carries the risk for re-introducing cancer cells. Therefore, the construction of a bioengineered ovary that can accommodate isolated small follicles was proposed as an...

Uterus transplantation has proved to be a feasible treatment for uterine factor infertility. Herein, we report on recipient outcome in the robotic uterus transplantation trial of 2017–2019. The eight recipients had congenital uterine aplasia. The donors were six mothers, one sister, and one family friend. Donor surgery was by robotic-assisted lapar...

Uterus transplantation has enabled women with absolute uterine factor infertility to carry a pregnancy. The first human uterus transplantation trial was initiated in 2013 in Gothenburg, Sweden. It was completed with seven transplantations with long‐term allograft survival and nine children born from six women. In the present study we describe the h...

Study question: How is a women's self-image affected by uterus transplantation (UTx)? Summary answer: Women experienced receiving a uterus in both positive and negative ways, but in general, their self-image was positively affected; regardless of whether they have given birth to a child or not, recipients describe themselves as being 'back to no...

Objective To assess the psychosocial outcomes of recipients and their partners 2 and 3 years after entering this first clinical uterus transplantation study. Design Prospective observational study. Setting University hospital. Patient(s) Nine women with absolute uterine factor infertility and their male partners participated. Intervention(s) Ps...

Previous studies in rats showed that maternal exposure to 5α-dihydrotestosterone (DHT) and insulin (INS) from gestational day 7.5 to 13.5 induces hyperandrogenism and insulin resistance (HAIR) and subsequently leads to placental insufficiency and fetal loss. We therefore hypothesized that maternal HAIR triggers ferroptosis in the uterus and placent...

Ferroptosis, a form of regulated necrotic cell death, plays roles in diverse physiological processes and diseases. Women with polycystic ovary syndrome (PCOS) have hyperandrogenism and insulin resistance (HAIR) and an increased risk of miscarriage and placental dysfunction during pregnancy. However, whether maternal HAIR alters mechanisms leading t...

Growing evidence suggests that epithelial-mesenchymal transition (EMT) and its regulator mitogen-activated protein kinase (MAPK) contribute to endometria-related reproductive disorders. However, the regulation of EMT and MAPK signaling components in the endometrium from polycystic ovary syndrome (PCOS) patients has not been systematically investiga...

Introduction: The proof-of-concept of uterus transplantation, as a treatment for absolute uterine factor infertility, came with the first live birth after uterus transplantation, which took place in Sweden in 2014. This was after a live donor procedure, with laparotomy in both donor and recipient. In our second, ongoing trial we introduced a robot...

Uterus transplantation is a novel treatment to treat uterine factor infertility. This type of infertility is due to absence of an anatomical or functional uterus. This review covers important research findings in the field, and this research formed the base for introduction of uterus transplantation as an experimental clinical procedure. The basic...

Uterus tissue engineering may dismantle limitations in current uterus transplantation protocols. A uterine biomaterial populated with patient-derived cells could potentially serve as a graft to circumvent complicated surgery of live donors, immunosuppressive medication, and rejection episodes. Repeated uterine bioengineering studies on rodents have...

Introduction: Human ovulation is a biologically complex process that involves several biochemical factors, promoting follicular rupture and release of a fertilizable oocyte. Proteins which are present in follicular fluid at high concentrations during ovulation are likely to be active participants in the biochemical pathways of ovulation. The aim o...

Study question: What are the predictive factors for later development of type 2 diabetes (T2DM) in women with polycystic ovary syndrome (PCOS)? Summary answer: Obesity and abdominal fat distribution in women with PCOS in the mid-fertile years were the major risk factors for T2DM development 24 years later when lifestyle factors were similar to c...

Background: Uterus transplantation is an emerging surgical innovation offering the option of genetic and gestational motherhood to women with absolute uterine factor infertility. More than 15 centres worldwide have now commenced clinical trials, but the procedure has not been performed in Australia. Aim: To explore the awareness, attitudes and p...

At uterus transplantation into the recipient, surgical fixation of the uterus is important and performed after anastomoses of the vasculature and the vagina which has been done in order to minimize warm ischemia and secure optimal location of the uterus with its vessels. At the stage of fixation, the uterine graft is reperfused. The fixation of the...

A uterine allograft should at some stage be removed, even after proved functionality, in terms of harbouring a pregnancy with live birth. Thus, uterus transplantation is the first type of allogeneic organ transplantation that is ephemeral, with the graft not intended for life-long use. There are several situations when removal of an allogenic trans...

The ultimate goal of uterus transplantation is a successful pregnancy, with birth of a healthy baby. This has been accomplished repeatedly after live donor uterus transplantation and up until mid-2019, two times after deceased donor uterus transplantation. Pregnancy is established by embryo transfer in either natural cycle or hormone replacement cy...

A critical part of the uterus transplantation procedure, both in live donor and in deceased donor uterus transplantation, is the technique used and the decisions taken during flushing and evaluation during back-table preparation. This chapter provides details on preparation of the back-table as well as on the procedures to provide cold ischemia and...

The domestic species that have been used in modern research in UTx are the pig and the sheep. An advantage of these animals, as compared to most other experimental animals, is their similarity in size of body, uterus, and vasculature to humans. Initial experiments were performed with the pig to evaluate anastomosis sites, surgical technique, and sh...

Customized grafts that include a scaffold populated with the patient’s own cells could become a major advantage in the field of uterus transplantation since it may overcome problematic donor issues and negative side effects from immunosuppression. So far, bioengineering was only utilized to personalize bone structure grafts and less complex organs...

The accumulated experience in live donor uterus transplantation is that the qualities of the uterus and the vasculature of the graft are critical factor for successful outcome of the transplantation procedure. Thus, the medical screening procedure to exclude possible cases with suboptimal donor organs is important for high success rate, in terms of...

A successful result following uterus transplantation is naturally evidenced by a resulting live birth. Whilst the critical factors when screening the donor have been shown to be uterine graft quality and adequate vasculature, there are several essential factors associated with the recipient that are associated with the chances of success. This chap...

One major part of surgery in uterus transplantation is surgery of the live donor. Early attempts have shown that this is the most challenging part of live donor uterus transplantation and the duration of donor surgery is around two times that of recipient surgery. Traditionally, live donor surgery was by laparotomy, but during the last few years mi...

This chapter provides details on surgical preparations of the recipient before uterus transplantation. In both deceased and live donor uterus transplantation, the recipient should be surgically prepared so that the uterus can be brought into the pelvis of the recipient, as soon as the graft is prepared at the back-table. A synchronized preparation...

This book discusses all aspects of the uterus transplantation procedure in women who are childless because of a dysfunctional or missing uterus, from initial pre-operative investigations to follow-up after the uterine graft has been removed. All the international experts who are engaged in clinical activities and/or research in this field have cont...

Uterus transplantation has reached its current status of being an experimental clinical procedure in the human, after comprehensive research in a number of animal models but also following a small number of preclinical studies on human tissue/settings. These latter studies have explored the effects of cold ischemia, techniques for organ procurement...