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STUDY QUESTION Is summer associated with a higher live birth rate after fresh IVF/ICSI? SUMMARY ANSWER There was no support for a higher live birth rate after fresh IVF/ICSI when treatment was performed during the summer season. WHAT IS KNOWN ALREADY Seasonal variations in human natural conception and birth rates are well described. It has been hypothesized that serum vitamin D, levels of which are associated with sun exposure, may have a role in human natural conception rates. However, the association between seasons and IVF outcomes has not yet been clarified and conflicting reports have been published. Furthermore, it has been suggested that women with normal vitamin D levels have a better pregnancy outcome after ART compared to those with vitamin D insufficiency. STUDY DESIGN, SIZE, DURATION A nationwide, register-based cohort study including all first-time fresh IVF/ICSI treatments (n = 52 788) leading to oocyte retrieval in Sweden between 2009 and 2018 was carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS All first-time fresh IVF/ICSI cycles leading to oocyte retrieval were identified in the National Quality Registry of Assisted Reproduction. Data collected included patient characteristics as well as information about the treatment cycle and pregnancy outcome. The patients were divided into season subgroups, (summer, autumn, winter and spring) based on the date of oocyte retrieval. The primary outcome was live birth rate, which was defined as the number of live births per oocyte retrieval and embryo transfer (ET). Other outcomes included clinical pregnancy per ET and miscarriage per clinical pregnancy. Logistic regression with multiple imputation was performed to evaluate whether there was an association between season and IVF/ICSI outcomes, with summer as reference. Adjustments were made for woman's age, year of treatment, BMI, total FSH/hMG dose, type of treatment, fertilization type, embryonic stage at ET and number of embryos transferred. MAIN RESULTS AND THE ROLE OF CHANCE Live birth rate per oocyte retrieval ranged between 24% and 26% among seasons. A significantly higher live birth rate was seen for spring compared with summer, 26% versus 24%, respectively (adjusted odds ratio (OR) 1.08, 95% CI 1.02–1.16, P  =   0.02). No significant association was seen when winter and autumn were compared with summer. Live birth rate per ET ranged between 29% and 31% among seasons. A significantly higher live birth rate was seen for spring and autumn compared with summer, at 31% and 31%, respectively versus 29% (adjusted OR 1.08, 95% CI 1.01–1.16, P  =   0.04 and adjusted OR 1.09, 95% CI 1.01–1.16, P  =   0.02), respectively. No significant association was seen when winter was compared with summer. Clinical pregnancy rate varied between 36% and 38% and miscarriage rate between 16% and 18%, with no significant seasonal associations. LIMITATIONS, REASONS FOR CAUTION Possible limitations are the retrospective design of the study and unmeasured confounders. Another limitation is that a generalized estimating equation (GEE) model was not used. The use of a GEE model would have made it possible to include all started fresh IVF/ICSI cycles since it allows for correction for any dependence between cycles within women. WIDER IMPLICATIONS OF THE FINDINGS The results of this large registry study give no support for the hypothesis that IVF/ICSI treatments performed during summer season, with the highest degree of sunlight and vitamin D synthesis, is associated with higher pregnancy and live birth rates. In fact, our results showed significantly lower live birth rates during summer compared with spring and autumn. However, the magnitude of this difference was small and unlikely of clinical value. We suggest that season should not be taken into consideration when planning and performing fresh IVF/ICSI treatments. STUDY FUNDING/COMPETING INTEREST(S) Financial support was received through the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-70 940) and grants from the Hjalmar Svensson's Research Foundation (HJSV2021019 and HJSV2021037). None of the authors declare any conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Background: Uterus transplantation (UTx) is an emerging therapy for women with uterine infertility. However, critical questions remain with this procedure including the mechanisms involved in graft rejection., Methods: In this study, we analyzed the immune profile of ectocervical biopsies from 5 patients after UTx before and during their first episode of rejection using RNA sequencing, quantitative polymerase chain reaction, and imaging mass cytometry., Results: We identified 530 upregulated and 207 downregulated genes associated with graft rejection. Enrichment databases revealed abnormalities of skin-associated genes and the immune system, in particular activation of T and B lymphocytes, and macrophages. Imaging mass cytometry confirmed these observations; in cervical biopsies of 3 women, rejection was associated with the presence of B-cell structures linked to tertiary lymphoid structures, and 2 biopsies from 1 woman with severe rejection episodes and poor prognosis of graft function (repeated miscarriage and implantation failures) were associated with an accumulation of HLA-DR- macrophages, producing granzyme B at the surface of the epithelium., Conclusions: We showed that rejection of a UTx graft was associated with major alterations of immune markers including the involvement of tertiary lymphoid structures, the most organized of which may be a sign of chronic rejection, and with an increase in HLA-DR- macrophages expressing granzyme B in the case of grade 3 rejection episodes according Mölne's classification. We identified potential emerging biomarkers to predict or diagnose graft rejection (Keratin 1 granzyme B, IL1β). These findings could lead to development of improved strategies for the identification, prevention, and/or treatment of uterus graft rejection., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Sophisticated culturing conditions are required to grow cells in a three-dimensional (3D) environment. Cells then require a type of scaffold rich in proteins, growth factors, and signaling molecules that simulates their natural environment. Tissues from all species of animals have an organ-specific extracellular matrix (ECM) structure that plays a key role in cell proliferation and migration. Hence, the scaffold composition plays a significant role for any successful 3D cell culturing system. We developed a whole rat uterus ECM scaffold by the perfusion of detergents and ionic solutions through the vascular system of an isolated normal rat uterus in a process termed "decellularization." The generated rat uterus scaffolds consist of a cell-free ECM structure similar to that of the normal rat uterus, and are thus excellent platforms on to which new cells can be added. Rat uterus 3D cell culturing systems based on these scaffolds could become valuable to decidual differentiation- and embryo implantation studies, or for investigating invasion mechanisms of endometrial cancer cells. They could also be used for the creation of tissue engineered uterine tissue, for partial or whole organogenesis developed for transplantation applications to treat absolute uterine infertility. This is a condition affecting about 1 in 500 women, and is only treatable by a uterus transplantation. This article provides valuable troubleshooting notes and describes in detail how to generate rat uterus scaffolds, including the delicate surgery required to isolate the uterus with an intact vascular tree which facilitates vascular perfusion and re-transplantation.

Background: Uterine transplantation could serve as a tool in studies of the physiology of implantation/pregnancy, and is also a possible future treatment for patients with absolute uterine infertility. Here, the first live-born offspring in any uterine transplantation model is reported., Methods: A syngeneic mouse model with a uterus transplanted, by end-to-side aorta/vena cava vascular anastomoses, alongside the native uterus was used. The cervix was attached to a cutaneous stoma. Pregnancy rate and offspring (birth weight, growth and fertility) was evaluated after blastocyst transfer to the native and the grafted uterus of transplanted mice and to controls., Results: Pregnancy rates were comparable in the grafted uterus (8/12 animals became pregnant) and the native uterus (9/12 pregnant) of transplanted animals and controls (8/13 pregnant). In a separate set of animals, the native uterus was removed at transplantation to exclude influences from the native uterus on the pregnancy potential of the graft; two of four animals became pregnant after blastocyst transfer. The weights/lengths of fetuses (gestational day 18) and gestational lengths were similar in all groups. Offspring were delivered and the growth trajectories (up to 8 weeks) of offspring delivered from grafted or native uteri of transplanted mice were similar as compared with controls, and all were fertile. The second-generation offspring from transplanted animals were all fertile with normal birth weights., Conclusions: These observations document the capacity of a transplanted uterus to harbour pregnancies to term, and reveal that offspring from a transplanted uterus develop to normal fertile adults.

Uterine factor infertility is either due to congenital malformation or acquired. Most women with uterine factor infertility have no chance to become genetic mothers, except by the use of gestational surrogacy. The logical but radical approach for treatment would be replacement of the unfunctional or absent uterus. Uterine transplantation could allow these women to become both genetic and gestational mothers. The present work reviews the existing literature on the history and recent development around this topic. We also briefly describe a newly developed model for heterotopic uterine transplantation in the mouse, in which pregnancies have been accomplished. Some specific issues that are required to be solved prior any further attempts to transplant the uterus in humans are also addressed.