COVID-19: A Challenge to the Safety of Assisted Reproduction.

There is an increased risk of becoming pregnant through fertility treatments using assisted reproductive technology (ART) during the COVID-19 pandemic. The aim of this review is to gather comprehensive data from the existing literature on the potential risks of fertility management during the pandemic period, and outline strategies to mitigate them, with a focus on the hormonal and surgical procedures of ART. A comprehensive search of the scientific literature on COVID-19 in relation to fertility was conducted in the PubMed database using the keywords "coronavirus," "COVID-19," "SARS-CoV-2" and "pregnancy," "fertility," "urogenital system," "vertical transmission," "assisted human reproduction," "controlled ovarian stimulation," "oocyte retrieval," "in vitro fertilization," "hormones," "surgical procedures," "embryos," "oocytes," "sperm," "semen," "ovary," "testis," "ACE-2 receptor," "immunology," "cytokine storm," and "coagulation," from January 2020-July 2022. Published data on pregnancy and COVID-19, and the interaction of the urogenital system and SARS-CoV-2 is reported. The immunologic and prothrombotic profiles of patients with COVID-19, and their increased risks from controlled ovarian stimulation (COS) and ART surgeries, and how these procedures could facilitate COVID-19 and/or contribute to the severity of the disease by enhancing the cytokine storm are summarized. Strategies to prevent complications during COS that could increase the risks of the disease in pre-symptomatic patients are considered. The impact of SARS-CoV-2 on pre-symptomatic infertile patients presents a challenge to find ways to avoid the increased hormonal, immunologic, and prothrombotic risks presented by the use of COS in ART protocols during the COVID-19 outbreak. Safe ART procedures and recommendations are highlighted.

Reproduction, skin aging, and sleep in middle-aged women.

There is a growing trend for women to delay having children, with a significant number of women postponing motherhood until the third or fourth decade of life. At the same time, these middle-aged women may be more concerned about skin aging and use dermatologic procedures to delay or repair the effects of aging, environmental factors, and oxidative stress on the skin. It has been suggested that the use of skin cosmetics and procedures may play a role in the reproductive system, although their possible effects have not yet been clearly elucidated. Another crucial factor that needs to be raised in this context is poor sleep, which seems to have an important relationship with both reduced fertility and accelerated skin aging, especially when it is associated with greater oxidative stress and hormonal imbalance. This review discusses the important triad of sleep, dermatology, and reproduction, a subject that has received relatively little attention; and, given its potentially wide-ranging implications, one that deserves more frequent and detailed consideration in future studies. Understanding this complex web of interactions could help to provide outcomes that include healthier skin, safety, improved self-esteem, and successful fertility treatments, all of which can directly affect quality of life.

COVID-19: Uncertainties from Conception to Birth.

Scientific information on the impact of the new coronavirus (SARS-CoV-2) on the health of pregnant women, fetuses and newborns is considered of limited confidence, lacking good-quality evidence, and drawing biased conclusions. As a matter of fact, the initial impressions that the evolution of COVID-19 was no different between pregnant and non-pregnant women, and that SARS-CoV-2 was not vertically transmitted, are confronted by the documentation of worsening of the disease during pregnancy, poor obstetric outcomes, and the possibility of vertical transmission. The present article aims to compile the data available on the association of COVID-19 and reproductive events, from conception to birth.

As informações científicas sobre o impacto do novo coronavírus, SARS-CoV-2, na saúde de gestantes, fetos e recém-nascidos são consideradas de confiabilidade limitada, sem evidências de boa qualidade, e levam a conclusões enviesadas. De fato, as impressões iniciais de que a evolução da Covid-19 não era diferente entre mulheres grávidas e não grávidas, e de que o SARS-CoV-2 não era transmitido verticalmente, são confrontadas pela documentação de agravamentos da doença durante a gravidez, resultados obstétricos negativos, e a possibilidade de transmissão vertical. Este artigo tem como objetivo compilar os dados disponíveis sobre a associação entre a Covid-19 e os eventos reprodutivos, desde a concepção até o nascimento.

Covid-19: Uncertainties from conception to birth / Covid-19: incertezas desde a concepção até o nascimento

Abstract Scientific information on the impact of the new coronavirus (SARS-CoV-2) on the health of pregnant women, fetuses and newborns is considered of limited confidence, lacking good-quality evidence, and drawing biased conclusions. As a matter of fact, the initial impressions that the evolution of COVID-19 was no different between pregnant and non-pregnant women, and that SARS-CoV-2 was not vertically transmitted, are confronted by the documentation of worsening of the disease during pregnancy, poor obstetric outcomes, and the possibility of vertical transmission. The present article aims to compile the data available on the association of COVID-19 and reproductive events, from conception to birth.

Resumo As informações científicas sobre o impacto do novo coronavírus, SARS-CoV-2, na saúde de gestantes, fetos e recém-nascidos são consideradas de confiabilidade limitada, sem evidências de boa qualidade, e levam a conclusões enviesadas. De fato, as impressões iniciais de que a evolução da Covid-19 não era diferente entre mulheres grávidas e não grávidas, e de que o SARS-CoV-2 não era transmitido verticalmente, são confrontadas pela documentação de agravamentos da doença durante a gravidez, resultados obstétricos negativos, e a possibilidade de transmissão vertical. Este artigo tem como objetivo compilar os dados disponíveis sobre a associação entre a Covid-19 e os eventos reprodutivos, desde a concepção até o nascimento.

Increased prevalence of endocervical Mycoplasma and Ureaplasma colonization in infertile women with tubal factor.

OBJECTIVE: Most women suffering from tubal factor infertility do not have a history of pelvic inflammatory disease, but rather have asymptomatic upper genital tract infection. Investigating the impacts of such infections, even in the absence of clinically confirmed pelvic inflammatory disease, is critical to understanding the tubal factor of infertility. The aim of this study was to investigate whether the presence of endocervical bacteria is associated with tubal factors in women screened for infertility. METHODS: This retrospective cross-sectional study involved 245 women undergoing hysterosalpingography (HSG), screened for endocervical colonization by Chlamydia trachomatis, Neisseria gonorrhea, Ureaplasma urealyticum and Mycoplasma hominis, as part of a routine female infertility investigation between 2016 and 2017. RESULTS: endocervical bacterial colonization by Chlamydia trachomatis, Ureaplasma urealiticum, Mycoplasma hominis and other bacteria corresponded to 3.7%, 9.0%; 5.7% and 9.8%, respectively. There was no colonization by Neisseria gonorrhea. The prevalence of tubal factor was significantly higher in patients with positive endocervical bacteria colonization, regardless of bacterial species. When evaluating bacteria species individually, the women who were positive for endocervical Mycoplasma hominis had significantly higher rates of tubal factor. Associations between endocervical bacterial colonization and tubal factor infertility were confirmed by multiple regression analysis adjusted for age and duration of infertility. CONCLUSION: Besides the higher prevalence of Mycoplasma and Ureaplasma infectious agents, the findings of this study suggest the possible association of endocervical bacterial colonization - not only Chlamydia trachomatis and Neisseria gonorrhea, but also Mycoplasma species with tubal performance.

Estimulação ovariana em usuárias do sistema intrauterino liberador de levonorgestrel para preservação de fertilidade / Ovarian stimulation in users of the levonorgestrel releasing intrauterine system for fertility preservation

O objetivo deste estudo foi buscar evidências sobre a interferência do uso do SIU-LNG em mulheres submetidas a ciclos de hiperestimulação ovariana para preservação de fertilidade. Através de uma revisão integrativa, com busca nas bases de dados Lilacs, Pubmed e Cochrane, utilizamos algumas palavras-chaves, relacionando inicialmente 43 artigos, totalizando após aplicação dos critérios de inclusão e exclusão em 30 estudos. Os artigos abordados foram selecionados baseados nos itens: autor principal, ano de publicação, desenho do estudo, nível de evidência científica e assunto principal. Os estudos foram separados conforme os seguintes temas de abrangência: preservação de fertilidade, preservação de fertilidade e métodos contraceptivos, SIU-LNG e preservação de fertilidade, SIU-LNG e farmacocinética e SIU-LNG e gestação. Existem poucos estudos na literatura avaliando mulheres usuárias do SIU-LNG submetidas à estimulação ovariana em ciclos de reprodução assistida. Em dois estudos disponíveis, ambos com doadoras de oócitos, não foram observadas diferenças estatisticamente significantes entre as doadoras usuárias do SIU-LNG em relação aos controles, quando comparados os parâmetros descritos: número de ampolas de gonadotrofinas utilizadas na estimulação, número de folículos recrutados, número de oócitos, taxas de fertilização, taxas de clivagem e número de embriões por receptora. O impacto do uso do SIU-LNG em mulheres submetidas à estimulação ovariana em ciclos de preservação oocitária ainda não está claro, assim como o protocolo ideal. As evidências atuais são insuficientes para definir o real efeito do uso do SIU-LNG durante os ciclos de estimulação ovariana. Entretanto, o SIU-LNG não parece ter efeito negativo sobre o crescimento folicular, sobre a qualidade oocitária e a qualidade embrionária, podendo ser utilizado durante este processo. Há a necessidade de estudos randomizados controlados avaliando uma nova opção terapêutica nos ciclos de reprodução assistida.(AU)

The objective of this study was to search for evidence on the interference of the use of LNG-SIU in women submitted to cycles of ovarian hyperstimulation for preservation of fertility, through an integrative review, with search in the databases Lilacs, Pubmed and Cochrane. Using related keywords 43 articles were examined, totaling, after inclusion and exclusion criteria, in 30 studies. The articles were classified according to a synoptic table organized in topics: main author, year of publication, study design, level of scientific evidence and main subject. The studies were separated according to the topics covered: preservation of fertility, preservation of fertility, and contraceptive methods, SIU-LNG and preservation of fertility, SIU-LNG and pharmacokinetics and SIU-LNG and gestation. It was observed that there are few studies in the literature evaluating women users of LNG-IUS who undergo ovarian stimulation in cycles of assisted reproduction. In two of them, both induding oocyte donors, no statistically significant differences were observed among donors using the LNG-IUS as compared to controls regarding the described parameters: number of gonadotrophin ampules used in stimulation, number of recruited follicles, number of oocytes, fertilization rates, cleavage rates and number of embryos per recipient. The impact of the use of IUS-LNG in women submitted to ovarian stimulation in oocyte preservation cycles is still unclear, as it is the ideal protocol. Current evidence is insufficient to define the real effect of the use of LNG-SIU during cycles of ovarian hyperstimulation in assisted reproduction. However, although there is little research available, the LNGSIU does not seem to have a negative effect on follicular growth, on oocyte quality and on embryo quality, and it can be used during this process. There is a need for randomized controlled trials and other research in this context to evaluate a new therapeutic option in the cycles of assisted reproduction.(AU)

Tratamento da endometriose associada à infertilidade - revisão da literatura / Treatment of endometriosis associated with infertility - a literature review

A endometriose é uma desordem estrogênio-dependente definida pela presença de tecido endometrial fora da cavidade uterina, e é uma das principais causas de infertilidade feminina. A melhor escolha para seu tratamento, associado à infertilidade, ainda permanece obscura. As evidências científicas disponíveis indicam que a supressão da função ovariana, apenas com o tratamento hormonal, não melhora as taxas de gravidez. O tratamento cirúrgico é, entretanto, provavelmente eficaz em todos os estágios da doença. Nos casos de endometriose mínima e leve, corrigida cirurgicamente e com anatomia pélvica normal, a inseminação intrauterina (IIU), acompanhada de hiperestímulo ovariano controlado, é recomendada. Em casos de endometriose avançada, especialmente se estiver associada a alterações tubárias, fatores masculinos ou falha de tratamento prévio, após laparoscopia, a melhor opção é a Fertilização in vitro (FIV). O sucesso pode ser maior com o tratamento de análogos de gonadotropina (GnRH) de três a seis meses antes da FIV. Finalmente, é importante ressaltar que as recomendações acima deverão ser revistas à medida que estudos clínicos randomizados e controlados mostrarem evidências mais concretas e confiáveis dessa enigmática doença.

Endometriosis is an estrogen-dependent disorder defined as the presence of endometrial tissue outside of the uterine cavity, and is a leading cause of female infertility. The optimal choice for its treatment associated with infertility remains obscure. The available scientific evidence indicates that suppression of ovarian function with hormonal treatment is not effective and should not be offered for this indication alone, and it does not get better pregnancy rates. Surgery treatment is probably efficacious for all stages of the disease. Intrauterine insemination (IUI) with controlled ovarian stimulation is effective in endometriosis minimal-mild and surgically corrected when the pelvic anatomy is normal. In advanced endometriosis cases, especially if tubal function is compromised, if there is also male factor infertility, and other treatments have failed, in vitro fertilization (IVF) is the appropriate treatment. The success may increase with gonadotropin-releasing hormone analog treatment (GnRH) for three to six months before IVF. Finally, it is important to emphasize that the recommendation above should be revised as randomized controlled clinical trials with more concrete and reliable evidence of this enigmatic disease.

Células natural Killer deciduais na regulação da produção e interleucina 10 pelo trofoblasto no período de implantação embrionária e gravidez precoce / The emerging role of decidual NK cells for regulation of trophoblast IL-10 synthesis in implantation and early pregnancy

Objetivo: Estudar a comunicação entre as células Natural Killer deciduais (NKu) e o trofoblasto, a qual regula a produção de citoquinas do tipo Th2 pelo trofoblasto, em especial a de Interleucina 10 (IL-10). Tal comunicação pode teoricamente ocorrer por contato celular direto, ou, mais provavelmente, por meio de fatores imunomoduladores solúveis. Métodos: Úteros de fêmeas de camundongo, aloimunizadas, grávidas de 8 dias, foram micro dissecados, separando-se a decídua do trofoblasto. Separaram-se as células trofoblásticas e linfocitárias (NKu) da decídua. Metade destas células foi incubada em placas de cultura transwe1® por 24 horas. No compartimento superior colocaram-se células deciduais e no inferior trofoblastos. A outra metade das células deciduais foi incubada com anticorpo anti-NK (anti-Asialo GM 1) e colocada no compartimento superior do transwell®, no inferior, colocaram-se trofoblastos. Após 24 horas, o sobrenadante de cada compartimento foi submetido a teste de ELISA para dosagem da concentração de IL-10. Como a produção de IL-10 foi menor no compartimento sob a ação do anticorpo, foi suposto que a regulação da produção de IL-10 ocorre por meio de um fator imunomodulador. Na tentativa de identificá-lo, repetiu-se todo o processo utilizando-se anticorpo Anti-GM-CSF. Realizou-se novamente a dosagem da concentração de IL-10. Repetiu-se todo o processo com Anticorpo anti-M-CSF. Como o fator não é o GM-CSF ou o M-CSF, então, submeteu-se o sobrenadante de cultura de células linfocitárias deciduais à Cromatografia Líquida de Alta Performance (HPLC) com coluna de peso molecular. As frações obtidas, de diferentes pesos moleculares, foram incubadas com trofoblastos. Dosou-se novamente a IL-10. Identificou-se a fração ativa como sendo a de maior produção de IL-10 no intuito de determinar o peso molecular do fator imunomodulador solúvel. Resultados: A mediana da concentração de IL-10 na cultura decidual depletada para células NKu foi 42,0 (3,0-263,0) pg/ml, na cultura decidual controle foi 94,0 (16,0- 258,0)pg/ml (p<0,001), na cultura trofoblástica depletada foi 49,5(2,0-166,0) pg/ml e na cultura trofoblástica controle foi 83,5 (8,0-217,0)pg/ml (p<0, 001)...

Clinical and laboratory evaluation of hospitalized patients with severe ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is an important complication of ovarian stimulation and IVF that enhances patients' morbidity. To evaluate any increased incidence of hospitalization from severe OHSS during 2000, this study analysed certain clinical, ultrasound and laboratory characteristics of hospitalized patients with severe OHSS. These studies were carried out on women undergoing IVF who were hospitalized because of severe OHSS between 1996 and 2000 at the Hôpital Antoine Béclère. Patients' ages and serum hormone concentrations were collected on day 3 of ovarian stimulation for various assays, and laboratory and ultrasound measurements taken during ovarian stimulation for IVF were compared. An increase was noted during last year in the frequency of the severe form of OHSS requiring hospitalization (0.9 versus 1.8%, P < 0.05). Patients' ages and hormonal characteristics on day 3 of menstrual cycle, and laboratory and ultrasound variables were similar between the two groups. In addition, the increased incidence of OHSS during 2000 was not associated with any special laboratory or ultrasound parameter, and the policy of ovarian induction had not changed. It is essential to introduce a simple ovarian stimulation protocol providing acceptable IVF results with a minimum of risk.

Assessment of leukemia inhibitory factor levels by uterine flushing at the time of egg retrieval does not adversely affect pregnancy rates with in vitro fertilization.

OBJECTIVE: To assess intrauterine levels of leukemia inhibitory factor (LIF) by uterine flushing at the time of egg retrieval and to confirm that the procedure has no detrimental effect on pregnancy rates. DESIGN: Prospective study. SETTING: Assisted reproductive unit of a university hospital. PATIENT(S): Uterine flushing was performed in 148 IVF patients. The first 100 patients were compared with a matched control group. INTERVENTION(S): Uterine flushing at the time of egg retrieval. MAIN OUTCOME MEASURE(S): IVP-ET results, pregnancy rates, and intrauterine LIF levels. RESULT(S): Pregnancy rates were not different in the group of patients with (27%) or without uterine flushing (28%). Leukemia inhibitory factor was detected in 60 patients (46%). Pregnancy rates did not differ between patients' detectable LIF and those in whom LIF was undetectable. Mean levels of LIF were 30.1 +/- 49.3 pg/mL and 28.6 +/- 51.2 pg/mL in pregnant and nonpregnant patients respectively. CONCLUSION(S): The flushing procedure at the time of egg retrieval did not adversely affect pregnancy rates. Leukemia inhibitory factor was detected in 46% of patients at the time of egg retrieval, but no correlation were observed with better pregnancy rates in patients with detectable LIF. Mean LIF levels did not differ in pregnant and nonpregnant women. Access to endoluminal secretions of the endometrium during IVF-ET may represent a new research in human implantation.