Endometrioma, the follicular fluid inflammatory network and its association with oocyte and embryo characteristics.

RESEARCH QUESTION: What is the association between endometrioma-affected ovaries, their follicular fluid inflammatory microenvironment, and ovary-specific oocyte and embryo yield and quality? DESIGN: Exposure-matched prospective cohort study conducted at a university-affiliated infertility clinic. Thirty-four women presenting for oocyte retrieval were enrolled between 2012 and 2013: women with unilateral endometrioma and no other observed peritoneal or deep lesions (n = 10) and women with no signs or symptoms of endometriosis (n = 24). Follicular fluid was aspirated at the time of oocyte retrieval. Samples from each ovary were analysed using a 27-plex immunoassay panel. The associations were evaluated by ovary-specific endometrioma exposure status (affected, unaffected, unexposed) with cytokine levels, oocyte yield and embryo quality. RESULTS: Levels of interleukin (IL)-8 and monocyte chemoattractant protein-1 were higher in fluid obtained from endometrioma-affected ovaries compared with the unexposed ovaries from women without endometriosis, with intermediate levels observed in the contralateral unaffected ovaries. More modest differences were observed for IL-1ß and IL-6. The affected ovaries of women with endometriosis yielded fewer oocytes (mean ± SD = 4.6 ± 2.3) compared with both the unaffected (6.0 ± 3.8) and unexposed (7.9 ± 5.6) ovaries. After adjusting for potential confounders and variables generated in a cytokine principal components analysis, oocyte yield remained slightly lower for the endometrioma-affected ovaries compared with unexposed ovaries. No informative differences among ovary groups for embryo quality parameters were observed. CONCLUSIONS: The results suggest that the inflammatory milieu of ovarian endometriosis is strongly localized and has a more modestly systemic effect. The effect of endometriomas on infertility, however, cannot be entirely explained by increased inflammation.

Oxidative stress biomarkers in patients with endometriosis: systematic review.

PURPOSE: Since the first description about oxygen toxicity made by Joseph Priestley, the oxidative stress has been enrolled as a key factor in the pathogenesis of endometriosis. Our aim was to review oxidative stress biomarkers measured in patients with endometriosis. METHODS: Relevant studies were identified by searches of the MEDLINE database from 1990 to March 2011 using endometriosis, free radical and oxidative stress as mesh terms. We only included manuscripts in English, and review articles were excluded. In addition, free radical chemistry and oxidative stress history were discussed. RESULTS: After inclusion and exclusion criteria, 19 articles were selected to be included in this systematic review. A total of 36 oxidative stress biomarkers (20 different markers) were measured in patients with endometriosis. Some of the markers were measured in more than one manuscript. They were arranged in five subgroups: Enzymatic activity (n = 3), Anions/free radicals (n = 5), Lipoperoxidation markers (n = 7), DNA Damage markers (n = 1), and Protein oxidation (n = 4). Of those 36 markers, 23 were found to be significantly higher in patients with endometriosis comparing with control patients. CONCLUSION: Oxidative stress plays an important role in the pathogenesis and progression of endometriosis.

Hysterosalpingography using Magnetic Resonance Imaging for infertility patients.

OBJECTIVE: Some studies have shown that it is possible to evaluate tubal permeability through MRI. Our aim is to perform a prospective study and to perform a comprehensive review in the literature regarding HSG-MRI. METHODS: We carried out a PUBMED search using the following keywords: hysterosalpingogram, hysterosalpingography, magnetic resonance imaging and MRI. As inclusion criteria, we included only papers published in English, and exams ran on humans. We also conducted a prospective inclusion of patients who had visited a human reproduction clinic between May/2017 and April/2019 for laboratory image diagnoses using HSG-MRI. RESULTS: Following the inclusion and exclusion criteria, we included seven original papers. Review papers and those written in a language other than English, were excluded. Between the period of May/2017 and April/2019, we selected ten patients for our study. The average exam duration was 30 minutes. Cervical catheterization was possible in all cases. There were no major complications. We highlight that in 8/9 of patients, we could directly visualize uterine tubes with contrast (excluding one patient with bilateral tubal ligation). CONCLUSIONS: Our initial experience with HSG-MRI shows promise. We demonstrated an optimized protocol for conducting an HSG-MRI (with excellent image quality). HSG-MRI had some advantages, such as not using ionized radiation, less pain and being able to analyze pelvic anatomy. Patients referred for a pelvic MRI as part of a more detailed investigation into infertility can also benefit from undergoing a simultaneous HSG using MRI.

A meta-analysis on uterine transplantation: Redefining the limits of reproductive surgery.

In September 2014, the first baby grown in a transplanted uterus was born, which represented an astonishing scientific progress that will mark the history of human reproduction. The recipient was a 32-year-old woman with Rokytanski syndrome who became pregnant after a successful embryo transfer and had an uneventful pregnancy, giving birth to a healthy newborn and marking the beginning of a new era. Patients who do not have a uterus or have a dysfunctional uterus now have the chance of dreaming with pregnancy and motherhood. Combining principles of solid organ transplantation and techniques of human reproduction, uterus transplantation is the first ephemeral transplant performed in order to promote reproductive potential of women and may be removed after successful pregnancy. Worldwide, 11 uterine transplantations were performed in patients. Of these, seven maintained their reproductive potential, with viable transplanted uteri and regular menstrual cycles.

Oxidative cell injury as a predictor of endometriosis progression.

BACKGROUND: There is increasing evidence that oxidative stress is one of the key factors for progression of endometriosis. In this prospective controlled trial, we measured 6 different biomarkers of oxidative stress targeting protein, lipid, and DNA to quantify the severity and progression of endometriosis and establish a diagnostic marker for the disease. METHODS: A total of 62 consecutive patients were identified and enrolled in this study. After exclusion criteria, 44 patients were allocated to 3 groups: stage I/II (n = 14), stage III/IV (n = 16), and a control group (n = 14). The levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-oxoguanine DNA glycosylase (OGG1), protein carbonyl (PC), lipid peroxidation (LPO), reactive oxygen species (ROS), and total antioxidant capacity (TAC) were accessed in peritoneal fluid and tissue. RESULTS: Significantly higher levels of 8-OHdG and PC were seen in patients with endometriosis, in addition OGG1 expression was found to be significantly lower in patients with endometriosis (P < .001, P = .001, P = .033, respectively); ROS, TAC, and LPO were similar in stages I/II, stages III/IV, and control group. A predictive model was built using multivariable analyses and receiver-operating characteristics curves. The ability to predict and distinguish between patients without endometriosis, stage I/II endometriosis, and stage III/IV was very high. This model was highly discriminatory and had a concordance index of 0.87. CONCLUSION: In this cohort, higher DNA damage and lower DNA repair activity was related to endometriosis progression. Our results indicate that oxidative stress as a biomarker of cell injury can be used as a reliable quantitative test of endometriosis severity.

Mapping histological levels of 8-hydroxy-2'-deoxyguanosine in female reproductive organs.

Oxidative stress is associated with many disease states including gynecologic disease. This process can damage lipids, proteins and DNA. The present study highlights the role of oxidative stress induced DNA damage as measured by 8-hydroxy-2-deoxyguanosine in development of benign gynecological conditions (BGC). Our aim was to map the oxidative DNA damage on female reproductive organs and highlight the high amount found in a variety of benign gynecologic disorders. Seventeen biopsy specimens from female pelvic organs were divided in two groups: healthy organs tissue and BGC tissue. Healthy organs biopsy tissue included the cervix, tubes, uterus, peritoneum, and topic endometrium in secretory phase. Benign gynecological biopsy tissue included hydrosalpinges, leiomyoma, adenomyosis and tubal cysts. Immunohistochemical staining showed significantly higher levels of DNA damage between BGC and healthy organs [19.36 % (6.20; 32.51) vs. 4.61 % (0.63; 8.53); P < 0.0344]. Our results highlight the involvement of oxidative stress DNA damage in female benign pelvic disease. Hydrosalpinges, leiomyoma, and adenomyosis exhibit the highest amounts of oxidative DNA damage in the pelvic cavity.

Minimal and mild endometriosis negatively impact on pregnancy outcome.

Endometriosis, a highly prevalent gynecological disease, can lead to infertility in moderate to severe cases. Whether minimal stages are associated with infertility is still unclear. The purpose of this systematic review is to present studies regarding the association between pregnancy rates and the presence of early stages of endometriosis. Studies regarding infertility, minimal (stage I, American Society of Reproductive Medicine [ASRM]) and mild (stage II, ASRM) endometriosis were identified by searching on the MEDLINE database from 1985 to September 2011 using the following MESH terms: endometriosis; infertility; minimal; mild endometriosis; pregnancy rate. 1188 articles published between January of 1985 and November of 2011 were retrieved; based on their titles, 1038 citations were excluded. Finally, after inclusion and exclusion criteria, 16 articles were selected to be part of this systematic review. Several reasons have been discussed in the literature to explain the impact of minimal endometriosis on fertility outcome, such as: ovulatory dysfunction, impaired folliculogenesis, defective implantation, decrease embryo quality, abnormal immunological peritoneal environment, and luteal phase problems. Despite the controversy involving the topic, the largest randomized control trial, published by Marcoux et al. in 1997 found a statistically different pregnancy rate after resection of superficial endometrial lesions. Earlier stages of endometriosis play a critical role in infertility, and most likely negatively impact pregnancy outcomes. Further studies into stage I endometriosis, especially randomized controlled trials, still need to be conducted.

A meta-analysis on uterine transplantation: Redefining the limits of reproductive surgery / Uma metanálise sobre o transplante de útero: redefinindo os limites da cirurgia reprodutiva

SUMMARY In September 2014, the first baby grown in a transplanted uterus was born, which represented an astonishing scientific progress that will mark the history of human reproduction. The recipient was a 32-year-old woman with Rokytanski syndrome who became pregnant after a successful embryo transfer and had an uneventful pregnancy, giving birth to a healthy newborn and marking the beginning of a new era. Patients who do not have a uterus or have a dysfunctional uterus now have the chance of dreaming with pregnancy and motherhood. Combining principles of solid organ transplantation and techniques of human reproduction, uterus transplantation is the first ephemeral transplant performed in order to promote reproductive potential of women and may be removed after successful pregnancy. Worldwide, 11 uterine transplantations were performed in patients. Of these, seven maintained their reproductive potential, with viable transplanted uteri and regular menstrual cycles.

RESUMO Em 2014, nasce o primeiro bebê oriundo de um útero transplantado, um avanço científico que ficará marcado na história da reprodução humana. A paciente, portadora da síndrome de Rokytanski, engravidou após transplante de útero e transferência de embrião. Teve uma gestação sem complicações e deu à luz um recém-nascido saudável, marcando o início de uma nova realidade. Pacientes que não possuem útero ou possuem útero disfuncional agora podem sonhar em ser mães e gestar um filho. Combinando princípios de transplante de órgão sólido e técnicas de reprodução humana, o transplante de útero consiste no primeiro transplante efêmero realizado com o intuito de promover potencial reprodutivo à mulher, podendo ser removido após gestação bem-sucedida. Mundialmente, 11 transplantes de útero foram realizados em humanos. Dentre os casos, sete mantêm potencial reprodutivo, com úteros viáveis e ciclos menstruais regulares.

Minimal and mild endometriosis negatively impact on pregnancy outcome / Endometriose mínima e leve e seu impacto negativo sobre a gravidez

Endometriosis, a highly prevalent gynecological disease, can lead to infertility in moderate to severe cases. Whether minimal stages are associated with infertility is still unclear. The purpose of this systematic review is to present studies regarding the association between pregnancy rates and the presence of early stages of endometriosis. Studies regarding infertility, minimal (stage I, American Society of Reproductive Medicine [ASRM]) and mild (stage II, ASRM) endometriosis were identified by searching on the MEDLINE database from 1985 to September 2011 using the following MESH terms: endometriosis; infertility; minimal; mild endometriosis; pregnancy rate. 1188 articles published between January of 1985 and November of 2011 were retrieved; based on their titles, 1038 citations were excluded. Finally, after inclusion and exclusion criteria, 16 articles were selected to be part of this systematic review. Several reasons have been discussed in the literature to explain the impact of minimal endometriosis on fertility outcome, such as: ovulatory dysfunction, impaired folliculogenesis, defective implantation, decrease embryo quality, abnormal immunological peritoneal environment, and luteal phase problems. Despite the controversy involving the topic, the largest randomized control trial, published by Marcoux et al. in 1997 found a statistically different pregnancy rate after resection of superficial endometrial lesions. Earlier stages of endometriosis play a critical role in infertility, and most likely negatively impact pregnancy outcomes. Further studies into stage I endometriosis, especially randomized controlled trials, still need to be conducted.

RESUMO O objetivo desta revisão sistemática é apresentar estudos sobre a associação entre as taxas de gravidez e a presença de fases iniciais de endometriose. Estudos relacionados com a infertilidade e estágios mínimos e leves (estágios I,II, American Society of Reproductive Medicine [ASRM]) foram identificados por busca na base de dados MEDLINE, de 1985 a setembro de 2011. Os seguintes termos foram usados como palavras-chave: endometriose, infertilidade, taxa de gravidez; estágio mínimo; estágio leve de endometriose. Entre janeiro de 1985 e novembro de 2011, 1188 artigos foram recuperados; com base no título, 1038 citações foram excluídas e, finalmente, depois de critérios de inclusão e exclusão, 18 artigos foram selecionados para fazer parte desta revisão sistemática. Várias razões têm sido discutidas na literatura na tentativa de explicar o impacto da endometriose mínima no resultado da fertilidade, tais como: disfunção ovulatória, foliculogênese alterada prejudicada, defeito na implantação, baixa qualidade embrionária, ambiente peritoneal inflamatório e hostil e problemas da fase lútea. Apesar de toda polêmica envolvendo o tópico, o maior ensaio clínico randomizado foi publicado por Marcoux et al. Os autores encontraram uma taxa de gravidez estatisticamente significante após a ressecção de lesões superficiais de endometriose. Estágios iniciais de endometriose desempenham um papel crítico relacionado à infertilidade e, provavelmente proporcionam um impacto negativo nas taxas de gravidez em pacientes com endometriose. Outros estudos envolvendo estágios iniciais de endometriose, especialmente ensaios clínicos randomizados, ainda precisam ser realizados.