| 11. |
- Brännström, Mats, 1958, et al.
(författare)
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Global results of human uterus transplantation and strategies for pre-transplantation screening of donors
- 2019
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282. ; 112:1, s. 3-10
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Tidskriftsartikel (refereegranskat)abstract
- Absolute uterine factor infertility, due to absence or non-function of the uterus, is one of the few major subgroups of infertility that has remained without any treatment. Uterus transplantation has now been proposed as treatment for this type of infertility. The first attempt of human uterus transplantation was in 2000. This was a live donor case, but due to suboptimal surgical solutions it resulted in a necrotic uterus being removed after 99 days. This first human case, although a failure, inspired several research groups around the globe to initiate animal-based studies to investigate uterus transplantation in relation to surgery, immunosuppression, rejection and pregnancy outcome. The research was carried out in several animal species and advanced the field substantially. In 2011, the second uterus transplantation attempt was performed, and this involved a deceased donor procedure. Although the case was surgically successful, with resumed menstruations, clinical pregnancy with live birth could not be achieved. The first clinical trial of uterus transplantation was initiated in Sweden in 2013 and involved nine live donor procedures. The world's first live birth was reported from that trial in September 2014 and this was followed by two more births within that trial in November 2014. Births after uterus transplantation has since been reported from Sweden and other centers in Europe, North America, Latin America, and Asia. Thirty human uterus transplantation procedures have been reported in the scientific literature so far but by our personal knowledge the double number of procedures have been performed. The published cases will be reviewed in detail, and we will also describe the pregnancies of the live births that have been published. A small number of graft failures have occurred. These may in part be linked to suboptimal selection of donors, specifically concerning the quality of the uterine arteries. Consequently, we will also address the issue of strategies for pre-surgical screening of donors. © 2019
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| 12. |
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| 13. |
- Brännström, Mats, 1958, et al.
(författare)
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Uterus transplantation: A Rapidly Expanding Field
- 2018
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 102:4, s. 569-577
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Forskningsöversikt (refereegranskat)abstract
- Uterus transplantation (UTx) has been successfully introduced as a treatment option for women with absolute uterine factor infertility (AUFI). AUFI representing approximately 3% to 5% of the female general population is linked to either congenital uterine agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome), major congenital uterine malformation (hypoplastic uterus, fraction of bicornuate/unicornuate uterus), a surgically absent uterus, or an acquired condition (intrauterine adhesions, leiomyoma) linked to uterine malfunction that causes implantation failure or defect placentation. The world's first clinical uterus transplant was performed in 2000. However, a hysterectomy became necessary shortly after the surgery due to uterine necrosis. In 2011, a group in Turkey reported on a surgically successful deceased donor transplant; however, this procedure has, to date, not resulted in a healthy live birth, the ultimate goal of UTx. Building on an extensive experimental background in various animal models, including primates, the Gothenburg group led by Brannstrom reported on the first delivery of a healthy baby in a recipient of a live donor UTx in 2014. This event did not only show the feasibility of UTx, it also helped defining relevant areas of clinical and basic research. Use of a gestational surrogate carrier, is, at least in theory, an alternative for a woman with AUFI seeking genetic motherhood. However, in the clear majority of countries worldwide, gestational surrogacy is not practiced based on legal, ethical, or religious concerns. Of note, the overwhelming majority of surveyed women in the United Kingdom, a country which permits surrogacy, preferred UTx over gestational surrogacy and adoption. Moreover, randomly selected women of fertile age in Sweden preferred UTx over gestational surrogacy. A recent large survey in Japan with more than 3000 participants revealed that UTx had a twofold higher acceptance rate compared with gestational surrogacy. In a recent US survey exploring the potential of donating vascularized composite allografts, uterus donation achieved the highest priority. Thus, the acceptance of UTx as infertility treatment for women with AUFI is high, although the procedure remains in its infancy. Here, we provide an update of clinical activities, summarize achievements and challenges, and submit areas of research interests.
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| 14. |
- Brännström, Mats, 1958, et al.
(författare)
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Uterus transplantation and fertility preservation
- 2019
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Ingår i: Best Practice & Research Clinical Obstetrics & Gynaecology. - : Elsevier BV. - 1521-6934. ; 55, s. 109-116
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Tidskriftsartikel (refereegranskat)abstract
- Absolute uterine factor infertility (AUFI), with uterine absence or presence of a non-functional uterus, was considered untreatable until 2014, when the first child was born after transplantation of a uterus from a postmenopausal woman to a woman of fertile age who was born with no uterus, as a part of the Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. Concerning gynaecological cancer, AUFI may occur after hysterectomy for malignancy or after surgery/radiation that will preserve the uterus but causing non functionality in terms of future implantation and pregnancy. This review summarises the research preparations that paved the way for the clinical introduction of uterus transplantation (UTx) as a treatment for AUFI. We also summarise the human UTx attempts that have been published as well as the live births reported thus far. The clinical use and procedures for UTx are also proposed for a number of gynaecological malignancies.
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| 15. |
- Brännström, Mats, 1958, et al.
(författare)
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Uterus transplantation: current state and future perspectives
- 2017
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Ingår i: Journal of Endometriosis and Pelvic Pain Disorders. - : SAGE Publications. - 2284-0265 .- 2284-0273. ; 9:1, s. 2-8
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Tidskriftsartikel (refereegranskat)abstract
- Absolute uterine factor infertility (AUFI) has traditionally been regarded as untreatable. Gestational surrogacy (GS) is not permitted in most countries and societies in the world due to ethical, religious or legal reasons. The interest in uterus transplantation (UTx) as a treatment for AUFI started in the 1960s and, after some disappointing results, raised again in the new century, when our and other groups obtained live off-spring after UTx in the mouse, and here we review extensively the results of animal research. In September 2014, the first baby was born after human UTx and this proof-of-concept of UTx as an infertility treatment has been followed by several more births. All cases described in the literature are also reviewed. The overall evidence suggests that the clinical introduction of UTx as the first available treatment for AUFI has been successful. However, UTx will stay at experimental stage for several years whilst optimizing the procedure and ensuring its safety from a medical and psychological perspective.
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| 16. |
- Dahm-Kähler, Pernilla, 1964, et al.
(författare)
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Centralized primary care of advanced ovarian cancer improves complete cytoreduction and survival - A population-based cohort study
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258. ; 142:2, s. 211-216
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate centralized primary care of advanced ovarian and fallopian tube cancers in a complete population cohort in relation to complete cytoreduction, time interval from surgery to chemotherapy and relative survival. Methods. A regional population-based cohort study of women diagnosed with primary ovarian and fallopian tube cancers and included in the Swedish Quality Registry (SQR) during 2008-2013 in a region where primary care of advanced stages was centralized in 2011. Surgical, oncological characteristics, outcomes, follow-ups and relative survivals were analyzed. Results. There were 817 women diagnosed with ovarian and fallopian tube cancers during 2008-2013 and 523 were classified as FIGO stage III-IV and further analyzed. Primary debulking surgery (PDS) was performed in 81% and neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in 11%. Complete cytoreduction at PDS was performed in 37% before compared to 49% after centralization (p < 0.03). The chemotherapy protocols were identical in the cohorts and they received and completed the planned chemotherapy equally. The time interval between PDS and chemotherapy was 36 days (median) before compared to 24 days after centralization (p < 0.01). The relative 3-year survival rate in women treated by PDS was 44% compared to 65% after centralization and the estimated excess mortality rate ratio (EMRR) was reduced (RR 0.58; 95% CI 0.42-0.79). Comparing the complete cohorts before and after centralization, regardless primary treatment, the relative 3-year survival rate increased from 40% to 61% with reduced EMRR (RR 0.59; 95% CI 0.45-0.76). Conclusion. Centralized primary care of advanced ovarian and fallopian tube cancers increases complete cytoreduction, decreases time interval from PDS to chemotherapy and improves relative survival significantly. (C) 2016 Elsevier Inc. All rights reserved.
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| 17. |
- Dahm-Kähler, Pernilla, 1964, et al.
(författare)
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Human uterus transplantation in focus.
- 2016
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Ingår i: British medical bulletin. - : Oxford University Press (OUP). - 1471-8391 .- 0007-1420. ; 117:1, s. 69-78
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Tidskriftsartikel (refereegranskat)abstract
- Uterus transplantation (UTx) is introduced as the first treatment for absolute uterine factor infertility (AUFI), affecting 1:500 fertile aged women. This review presents potential patients, research and human UTx cases.
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| 18. |
- Dahm-Kähler, Pernilla, 1964, et al.
(författare)
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Population-based study of survival for women with serous cancer of the ovary, fallopian tube, peritoneum or undesignated origin - on behalf of the Swedish gynecological cancer group (SweGCG)
- 2017
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 144:1, s. 167-173
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin. Methods. Nation-wide population-based study of women 18 years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models. Results. Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulldng surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P<0.001), moderate (RR 1.90, P<0.047) and poor differentiation (RR 2.20, P<0.009), neoadjuvant chemotherapy (RR1.33, P<0.022), residual tumor (RR 2.65, P<0.001) and platinum single (2.34, P<0.001) compared to platinum combination chemotherapy. Conclusion. Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer. (C) 2016 Elsevier Inc. All rights reserved.
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| 19. |
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| 20. |
- Falconer, Henrik, et al.
(författare)
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Robot-assisted approach to cervical cancer (RACC) : an international multi-center, open-label randomized controlled trial
- 2019
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Ingår i: International Journal of Gynecological Cancer. - : BMJ Publishing Group Ltd. - 1048-891X .- 1525-1438. ; 29:6, s. 1072-1076
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Tidskriftsartikel (refereegranskat)abstract
- Background: Radical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival.Primary Objective: To investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy.Study Hypothesis: Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes.Trial Design: Prospective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden.Major Inclusion/Exclusion Criteria: Women over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years.Primary Endpoint: Recurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer.Sample Size: The clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (alpha) of 5% and a power (1-beta) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients.Estimated Dates for Completing Accrual and Presenting Results: Trial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter.
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