| 1. |
- Akhi, Shamima N, et al.
(författare)
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Uterine rejection after allogeneic uterus transplantation in the rat is effectively suppressed by tacrolimus.
- 2013
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Ingår i: Fertility and sterility. - : Elsevier BV. - 1556-5653 .- 0015-0282. ; 99:3, s. 862-870
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the effects of the immunosuppressant tacrolimus on rejection of a transplanted uterus and on uterine expression of markers of inflammation and implantation. DESIGN: Experimental study. SETTING: University laboratory. ANIMAL(S): Female rats. INTERVENTION(S): Uteri from brown Norway rats were transplanted to Lewis rats, receiving either tacrolimus or no treatment. Sham groups underwent either hemihysterectomy or tacrolimus treatment. MAIN OUTCOME MEASURE(S): Gross morphology, histology, density of T-lymphocytes by immunohistochemistry, and mRNA levels of interleukin (IL)-1α, leukemia inhibitory factor (LIF), galectin-1, CD200, IL-15, interferon-inducible protein-10 (IP-10), and nuclear factor-κB (NF-κB) at 14 days' post-transplantation. RESULT(S): Nontreated uterine grafts showed rejection with necrosis. Sham groups and the tacrolimus-treated transplanted group exhibited normal uterine morphology with low numbers of T-lymphocytes in all uteri except in two out of seven uteri of the tacrolimus-treated transplant group. Uteri of the nontreated transplanted group showed elevated mRNA expression of IL-1α and IP-10 and reduced galectin-1, compared with the tacrolimus-treated transplanted group. There was no difference between any groups concerning uterine expression of LIF, NF-κB, IL-15, and CD200. CONCLUSION(S): Tacrolimus monotherapy suppresses rejection of an allotransplanted uterus and normalizes the expression of IL-1α and IP-10 and prevents T-lymphocyte infiltration.
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| 2. |
- Akouri, Randa R., et al.
(författare)
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First live birth after uterus transplantation in the Middle East
- 2020
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Ingår i: Middle East Fertility Society Journal. - : Springer Science and Business Media LLC. - 1110-5690 .- 2090-3251. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- 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 woman with congenital absence of the uterus underwent transplantation of the uterus donated by her 50-year-old multiparous mother. In vitro fertilization was performed to cryopreserve embryos. Both graft retrieval and transplantation were performed by laparotomy. Donor surgery included isolation of the uterus, together with major uterine arteries and veins on segments of the internal iliac vessels bilaterally, the round ligaments, and the sacrouterine ligaments, as well as with bladder peritoneum. Recipient surgery included preparation of the vaginal vault, end-to-side anastomosis to the external iliac arteries and veins on each side, and then fixation of the uterus. Results One in vitro fertilization cycle prior to transplantation resulted in 11 cryopreserved embryos. Surgical time of the donor was 608 min, and blood loss was 900 mL. Cold ischemia time was 85 min. Recipient surgical time was 363 min, and blood loss was 700 mL. Anastomosis time was 105 min. Hospital stay was 7 days for both patients. Ten months after the transplantation, one previously cryopreserved blastocyst was transferred which resulted in viable pregnancy, which proceeded normally (except for one episode of minor vaginal bleeding in the 1st trimester) until cesarean section at 35 + 1 weeks due to premature contractions and shortened cervix. A healthy girl (Apgar 9-10-10) weighing 2620 g was born in January 2020, and her development has been normal during the first 6 months. Conclusions This is the first report of a healthy live birth after uterus transplantation in the MENAT region. We hope that this will motivate further progress and additional clinical trials in this area in the Middle East Region, where the first uterus transplantation attempt ever, however unsuccessful, was performed already three decades ago.
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| 3. |
- Al-Alem, Linah, et al.
(författare)
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Chemokine Ligand 20: A Signal for Leukocyte Recruitment During Human Ovulation?
- 2015
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 156:9, s. 3358-69
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Tidskriftsartikel (refereegranskat)abstract
- Ovulation is one of the cornerstones of female fertility. Disruption of the ovulatory process results in infertility, which affects approximately 10% of couples. Using a unique model in which the dominant follicle is collected across the periovulatory period in women, we have identified a leukocyte chemoattractant, chemokine ligand 20 (CCL20), in the human ovary. CCL20 mRNA is massively induced after an in vivo human chorionic gonadotropin (hCG) stimulus in granulosa (>10 000-fold) and theca (>4000-fold) cells collected during the early ovulatory (12-18 h) and late ovulatory (18-34 h) periods after hCG administration. Because the LH surge sets in motion an inflammatory reaction characterized by an influx of leukocytes and CCL20 is known to recruit leukocytes in other systems, the composition of ovarian leukocytes (CD45+) containing the CCL20 receptor CCR6 was determined immediately prior to ovulation. CD45+/CCR6+ cells were primarily natural killer cells (41%) along with B cells (12%), T cells (11%), neutrophils (10%), and monocytes (9%). Importantly, exogenous CCL20 stimulated ovarian leukocyte migration 59% within 90 minutes. Due to the difficulties in obtaining human follicles, an in vitro model was developed using granulosa-lutein cells to explore CCL20 regulation. CCL20 expression increased 40-fold within 6 hours after hCG, was regulated partially by the epithelial growth factor pathway, and was positively correlated with progesterone production. These results demonstrate that hCG dramatically increases CCL20 expression in the human ovary, that ovarian leukocytes contain the CCL20 receptor, and that CCL20 stimulates leukocyte migration. Our findings raise the prospect that CCL20 may aid in the final ovulatory events and contribute to fertility in women.
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| 4. |
- Al-Alem, L., et al.
(författare)
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Neurotensin: A neuropeptide induced by hCG in the human and rat ovary during the periovulatory period
- 2021
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Ingår i: Biology of Reproduction. - : Oxford University Press (OUP). - 0006-3363 .- 1529-7268. ; 104:6, s. 1337-1346
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Tidskriftsartikel (refereegranskat)abstract
- 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 the luteinizing hormone (LH) surge (preovulatory phase) or women were given 250 μg human chorionic gonadotropin (hCG) and dominant follicles collected 12-18 h after hCG (early ovulatory), 18-34 h (late ovulatory), and 44-70 h (postovulatory). NTS mRNA was massively induced during the early and late ovulatory stage in granulosa cells (GCs) (15 000 fold) and theca cells (700 fold). In the rat, hCG also induced Nts mRNA expression in intact ovaries and isolated GCs. In cultured granulosa-luteal cells (GLCs) from IVF patients, NTS expression was induced 6 h after hCG treatment, whereas in cultured rat GCs, NTS increased 4 h after hCG treatment. Cells treated with hCG signaling pathway inhibitors revealed that NTS expression is partially regulated in the human and rat GC by the epidermal-like growth factor pathway. Human GLC, and rat GCs also showed that Nts was regulated by the protein kinase A (PKA) pathway along with input from the phosphotidylinositol 3- kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. The predominat NTS receptor present in human and rat GCs was SORT1, whereas NTSR1 and NTSR2 expression was very low. Based on NTS actions in other systems, we speculate that NTS may regulate crucial aspects of ovulation such as vascular permeability, inflammation, and cell migration. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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| 5. |
- Alshaikh, Ahmed Baker, et al.
(författare)
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Decellularization and recellularization of the ovary for bioengineering applications; studies in the mouse.
- 2020
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Ingår i: Reproductive biology and endocrinology : RB&E. - : Springer Science and Business Media LLC. - 1477-7827. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- 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 alternative to minimize the risk of malignancy transmission. Various options for viable bioengineered scaffolds have been reported in the literature. Previously, we reported three protocols for producing mouse ovarian scaffolds with the decellularization technique. The present study examined these scaffolds further, specifically with regards to their extracellular composition, biocompatibility and ability to support recellularization with mesenchymal stem cells.Three decellularization protocols based on 0.5% sodium dodecyl sulfate (Protocol 1; P1), or 2% sodium deoxycholate (P2), or a combination of the two detergents (P3) were applied to produce three types of scaffolds. The levels of collagen, elastin and sulfated glycosaminoglycans (sGAGs) were quantified in the remaining extracellular matrix. Detailed immunofluorescence and scanning electron microscopy imaging were conducted to assess the morphology and recellularization efficiency of the constructs after 14days in vitro utilizing red fluorescent protein-labelled mesenchymal stem cells.All protocols efficiently removed the DNA while the elastin content was not significantly reduced during the procedures. The SDS-protocol (P1) reduced the sGAG and the collagen content more than the SDC-protocol (P2). All scaffolds were biocompatible and recellularization was successful, particularly in several P2-derived scaffolds. The cells were extensively distributed throughout the constructs, with a denser distribution observed towards the ovarian cortex. The cell density was not significantly different (400 to 550 cells/mm2) between scaffold types. However, there was a tendency towards a higher cell density in the SDC-derived constructs. Scanning electron microscope images showed fibrous scaffolds with a dense repopulated surface structure.While there were differences in the key structural macromolecules between protocols, all scaffolds were biocompatible and showed effective recellularization. The results indicate that our SDC-protocol might be better than our SDS-protocol. However, additional studies are necessary to determine their suitability for attachment of small follicles and folliculogenesis.
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| 6. |
- Alshaikh, Ahmed Baker, et al.
(författare)
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Decellularization of the mouse ovary: comparison of different scaffold generation protocols for future ovarian bioengineering.
- 2019
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Ingår i: Journal of ovarian research. - : Springer Science and Business Media LLC. - 1757-2215. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- In order to preserve fertility in young women with disseminated cancer, e.g. leukemia, an approach that has been suggested is to retransplant isolated small follicles within an ovarian matrix free from malignant cells and with no risk for contamination. The present study evaluates the first step to create a bioengineered ovarian construct that can act as growth-supporting tissue for isolated small follicles that are dependent on a stroma for normal follicular maturation. The present study used the intact mouse ovary to develop a mouse ovarian scaffold through various protocols of decellularization.Potential Immunogenic DNA and intracellular components were removed from whole mouse ovaries by agitation in a 0.5% sodium dodecyl sulfate solution (Protocol 1; P1), or in a 2% sodium deoxycholate solution (P2) or by a combination of the two (P3). The remaining decelluralized ovarian extracellular matrix structure was then assessed based on the DNA- and protein content, and was further evaluated histologically by haematoxylin and eosin-, Verhoeff's van gieson- (for elastin), Masson's trichrome- (for collagens) and Alcian blue (for glycosaminoglycans) staining. We also evaluated the decellularization efficiency using the mild detergent Triton-X100 (1%).Sodium dodecyl sulfate efficiently removed DNA and intracellular components from the ovarian tissue but also significantly reduced the integrity of the remaining ovarian extracellular matrix. Sodium deoxycholate, a considerably milder detergent compared to sodium dodecyl sulfate, preserved the ovarian extracellular matrix better, evident by a more distinct staining for glycosaminoglycan, collagen and elastic fibres. Triton-X100 was found ineffective as a decellularization reagent for mouse ovaries in our settings.The sodium dodecyl sulfate generated ovarian scaffolds contained minute amounts of DNA that may be an advantage to evade a detrimental immune response following engraftment. The sodium deoxycholate generated ovarian scaffolds had higher donor DNA content, yet, retained the extracellular composition better and may therefore have improved recellularization and other downstream bioengineering applications. These two novel types of mouse ovarian scaffolds serve as promising scaffold-candidates for future ovarian bioengineering experiments.
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| 7. |
- Ayoubi, Jean Marc, et al.
(författare)
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Case Report: Post-Partum SARS-CoV-2 Infection After the First French Uterus Transplantation
- 2022
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Ingår i: Frontiers in Surgery. - : Frontiers Media SA. - 2296-875X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- 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 puerperium period. These vulnerabilities require avoidance of SARS-CoV-2 infection in pregnant UTx recipients especially during the third trimester, as accumulating evidence reveals increased risks of morbidity and mortality. Here we describe a successful UTx case with delivery of a healthy child, but in which both mother and neonate developed asymptomatic SARS-CoV-2 infection seven days after RNA vaccination, on day 35 post-partum. Although the patient was successfully treated with a combination therapy comprised of two monoclonal antibodies, this case highlights the challenges associated with performing UTx in the era of Covid-19. More broadly, the risks of performing non-vital organ transplantation during a pandemic should be discussed among team members and prospective patients, weighing the risks against the benefits in improving the quality of life, which were considerable for our patient who achieved motherhood with the birth of a healthy child.
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| 8. |
- Ayoubi, J. M., et al.
(författare)
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Laparotomy or minimal invasive surgery in uterus transplantation: a comparison
- 2019
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282. ; 112:1, s. 11-18
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Tidskriftsartikel (refereegranskat)abstract
- Uterus transplantation (UTx) is the first available treatment for absolute uterine factor infertility, a condition due to absence of the uterus or presence of a non-functional uterus. The proof-of-concept of UTx as an infertility treatment for this group of patients occurred in 2014 in Sweden by the first birth after human UTx. That and subsequent cases of the Swedish trial were live-donor UTx procedures with laparotomy of both donor and recipient. Although results of the initial Swedish clinical UTx trial were very favorable in terms of take-home-baby rate, the drawback was the long duration (>10 h) of donor surgeries and associated long recovery periods. There exist three later publications, with uterus procurements from live donors by laparotomy with a range of surgical durations of 5.3 hours to 13 hours. Our collaborative Swedish-French team has initiated efforts to introduce minimal invasive surgery in one trial in Sweden and one in France. The principle of these UTx trials is to use modern concepts of robotic-assisted laparoscopy primarily in the live donor. There also exists a small number of published UTx procedures with donor surgery by partial conventional laparoscopy and one published case with total robotic-assisted laparoscopy procedure. This review discusses open versus minimal invasive surgery in relation to the accumulated knowledge in the field. Moreover, we propose some future directions for the development of this surgery in UTx. © 2019
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| 9. |
- Aziz, Adel, 1951, et al.
(författare)
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Differences in aspects of personality and sexuality between perimenopausal women making different choices regarding prophylactic oophorectomy at elective hysterectomy
- 2005
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Ingår i: Acta Obstet Gynecol Scand. ; 84:9, s. 854-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Retrospective studies have indicated differences in sexuality and general psychological well-being between women who have undergone hysterectomy only and those undergoing hysterectomy and oophorectomy. These differences may be the result of dissimilarities in the groups of women who choose the respective operation. OBJECTIVE: To compare the preoperative characteristics of women who choose to undergo prophylactic oophorectomy with the corresponding characteristics of those who choose to retain their ovaries when undergoing hysterectomy on benign indication. POPULATION: Perimenopausal women (aged 45-55), scheduled for hysterectomy on benign indication, were evaluated within 2 months before surgery. A total of 217 women chose hysterectomy only and 106 women chose hysterectomy with concomitant prophylactic oophorectomy. METHODS: Socioeconomic and health data, personality (Karolinska Scale of Personality), sexuality (McCoy's Female Sexuality Questionnaire), well-being (Psychological General Well-Being index), the prevalence of climacteric symptoms (modified Kupperman's index) and the women's attitude to hormone replacement therapy were investigated. RESULTS: Women who later underwent prophylactic oophorectomy in addition to hysterectomy had higher anxiety-related scores, lower sexual variable scores and poorer emotional partner relationships. This group was also characterized by more episodes of irregular bleeding, a greater prevalence of climacteric symptoms and a more extensive use of hormonal replacement therapy, in comparison with women who later underwent hysterectomy only. CONCLUSION: Personality, sexuality and the nature and severity of preoperative symptoms in women who chose prophylactic oophorectomy differ markedly from the same variables in those who chose to keep their ovaries at elective hysterectomy. These differences must be taken into consideration when evaluating studies comparing these aspects of quality of life after hysterectomy or hysterectomy with concomitant oophorectomy. Furthermore, psychosexual aspects such as sexuality and well-being can not be reliably studied with a retrospective design in these patient groups.
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| 10. |
- Aziz, Adel, 1951, et al.
(författare)
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Perimenopausal androgen decline after oophorectomy does not influence sexuality or psychological well-being
- 2005
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Ingår i: Fertil Steril. ; 83:4, s. 1021-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether oophorectomy during the perimenopause, with the associated decline in ovarian androgens, affects sexual function and psychological well-being negatively. DESIGN: Prospective, observational study comparing sexuality and psychological well-being in women after hysterectomy only (HYST) vs. hysterectomy and concomitant oophorectomy (HYST+BSO). SETTING: University hospital and district general hospital. PATIENT(S): Three hundred sixty-two perimenopausal women scheduled for elective hysterectomy on benign indication were recruited and 323 (89%) completed the 1-year follow-up (217 in the HYST group and 106 in the HYST+BSO group). INTERVENTION(S): The patients were evaluated preoperatively and 1 year after surgery. Postoperatively, estrogen replacement therapy was recommended to all women in the HYST+BSO group and to HYST group subjects with climacteric symptoms. MAIN OUTCOME MEASURE(S): Sex steroids (T, androstenedione, DHEA-S, and E(2)) and sex hormone-binding globulin (SHBG) were measured. Free androgen index and free E(2) index were calculated. Sexuality (McCoy's Female Sex Questionnaire) and psychological well-being (Psychological General Well-Being Index) were evaluated. RESULTS(S): Preoperatively, no hormonal differences were found between the two groups. At 1-year follow-up, all sex steroid levels and indices were decreased and SHBG was increased in the HYST+BSO group. Ovarian sex steroids were decreased in the HYST group, whereas DHEA-S and SHBG were unaltered. Sexuality was unaltered in the HYST+BSO group, whereas decreased scores were found in 3 of 14 sexual variables in the HYST group. Psychological well-being was improved in both groups. There were no correlations between the observed changes (data 1 year after surgery, compared with preoperative data) in androgen levels and index and the observed changes in any aspect of sexuality or psychological well-being. CONCLUSION(S): Hormonal changes after oophorectomy in conjunction with perimenopausal hysterectomy do not significantly change postoperative (1-year) sexual or psychological well-being.
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