Impact of repeated ovarian hyperstimulation on the reproductive function.

One of six couples (17.5 % of the adult population) worldwide is affected by infertility during their lifetime. This number represents a substantial increase in the prevalence of this gynecological condition over the last decade. Ovulatory dysfunction and anovulation are the main causes of female infertility. Timed intercourse, intrauterine insemination, and assisted reproductive technology (ART), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), are the most common interventions for infertile couples. Ovulation induction protocols for IVF/ICSI routinely use supraphysiological doses of gonadotropins to stimulate many preovulatory follicles. Animal and human studies suggested that ovarian hyperstimulation, alone or repeatedly, for ART cycles can induce changes in the immune response and increase the oxidative stress (OS) in the ovarian microenvironment. The consequences of repeated ovarian hyperstimulation on the human ovary remain poorly understood, particularly in relation to the effects of ovarian stimulation on the immune system and the potential for ovarian stimulation to cause OS. Animal studies have observed that repeated cycles of ovarian hyperstimulation can accelerate ovarian aging. Changes in ovarian hormone levels, accelerated loss of ovarian reserve, disorders in ovarian ultrastructure, ovarian senescence, and decreased reproductive performance represent possible long-term effects of repeated ovarian hyperstimulation. The short and long-term impact of the combination of antioxidant agents in ovarian hyperstimulation protocols in women undergoing ART must urgently be better understood. The recent increase in the number of ART and fertility preservation cycles may accelerate ovarian aging in these women, promoting consequences beyond the reproductive function and including health deterioration.

Repeated ovarian hyperstimulation promotes depression-like behavior in female mice.

Controlled ovarian hyperstimulation (COH) is a common step for treating infertile couples undergoing assisted reproductive technologies and in female fertility preservation cycles. In some cases, undergoing multiple COHs is required for couples to conceive. Behavioral changes such as anxiety and depression can be caused by ovulation-inducing drugs. Sex steroids play a role in locomotor activity, behavioral changes, and nociception, specifically during fluctuations and sudden drops in estrogen levels. This study evaluated the effect of repeated ovarian hyperstimulation (ROH) on weight, locomotor activity, anxiety-like and depression-like behavior, and nociception in female mice. The animals were divided into two groups: control (placebo; Control) and treated (ROH; Treatment). Ovulation was induced once weekly for 10 consecutive weeks. Locomotor activity (open field test), anxiety-like behavior (elevated plus maze, hole board, and marble burying tests), depression-like behavior (splash and forced swim tests), and nociception (hot plate and Von Frey tests) were evaluated before and after ROH. Statistical analysis was conducted using two-way analysis of variance to evaluate the effects of ROH, age of mice, and their interaction. The results suggested that ROH contributed to weight gain, increased locomotor activity, and induced depression-like behavior in female mice. Furthermore, the age of the mouse contributed to weight gain, increased locomotor activity, and induced anxiety-like and depression-like behavior in female mice. ROH could change the behavior of female mice, particularly inducing depression-like behavior. Further studies are required to evaluate various COH protocols, specifically with drugs that prevent fluctuations and drastic drops in estrogen levels, such as aromatase inhibitors.

Calcineurin inhibitors in the management of recurrent miscarriage and recurrent implantation failure: Systematic review and meta-analysis.

Recurrent miscarriage (RM) affects up to 2.5% of couples of reproductive age. Up to 10% of couples using assisted reproductive technology experience recurrent implantation failure (RIF). Immunosuppressive drugs, such as calcineurin inhibitors (CNIs), has been proposed for RM and RIF management. This systematic review and meta-analysis (SRMA) aimed to evaluate the efficacy and safety of CNIs in RM and RIF treatment. We searched in the three databases. Review Manager 5.4.1 was used for statistical analysis. This review included 8 studies involving 1042 women (485 women in the CNIs group and 557 women in the control group). CNI treatment (cyclosporine [CsA] and tacrolimus [TAC]) increases live birth rate (LBR, odds ratio [OR]: 2.52; 95% confidence interval [CI]: 1.93-3.28, p < 0.00001) and clinical pregnancy rate (OR: 2.25; 95% CI: 1.54-4.40, p < 0.0001) and decreases miscarriage rate (OR: 0.45 95% CI: 0.32-0.63, p < 0.00001) when compared to the control. Side effects and obstetric and neonatal complications was similar in both groups. In conclusion, CNIs increased LBR in women with RM and RIF but there is a moderate risk of bias. Subgroup analysis revealed that CNIs improved LBR in women with RM with a low risk of bias. However, in women with RIF, with moderate to high risk of bias. The use of CsA and TAC, in low doses and for a short period, for managing reproductive failures in women seems to be safe, not causing serious side effects nor increasing the risk of obstetric and neonatal complications.

Obesity and recurrent miscarriage: The interconnections between adipose tissue and the immune system.

Currently, obesity is considered a global public health problem. It is the main risk factor for noncommunicable diseases and reproductive complications, such as recurrent miscarriage (RM). RM affects approximately 1% of couples of reproductive age, and recent studies suggest that its prevalence is increasing. Immunological abnormalities may be responsible for a significant number of cases of unexplained RM. Obesity is recognized as a chronic low-grade inflammatory condition. The accumulation of fat in obese adipose tissue promotes changes in the local and systemic immune response. Adipokines, exosomes, micro-RNAs, lipids, and other factors released or secreted by adipose tissue are responsible for the interconnection between obesity and the immune system. Obesity-induced dysregulation of the innate and acquired immune response is also involved in the immunopathology of pregnancy loss in patients with unexplained RM. Therefore, understanding the communication pathways between maternal adipose tissue and the immune response in women living with obesity and RM is an important objective. Thus, diagnostic tools and new immunomodulatory therapies may be proposed for the management of patients with concurrent obesity and RM.

Screening for coronavirus disease 2019 in pregnant women admitted for delivery: an observational study.

OBJECTIVE: The aim of this study was to examine the impact of symptom-based screening on the prevalence and outcomes of neonatal coronavirus disease 2019 in pregnant women admitted for delivery. METHODS: A retrospective observational study was conducted from June to August 2020 at Gonzaga Mota of Messejana Hospital, Fortaleza, CE, Brazil. All pregnant women were screened for coronavirus disease 2019 based on symptoms. Reverse transcription-polymerase chain reaction or immunology assays for severe acute respiratory syndrome coronavirus 2 were performed when a patient reported a symptom. All newborns of symptomatic patients were submitted for Reverse transcription-polymerase chain reaction. Newborns were divided into groups according to the Reverse transcription-polymerase chain reaction results to identify the relationship between maternal symptoms and neonatal coronavirus disease 2019. RESULTS: A total of 55 (55/1,026, 5.4%) and 50 (50/1,026, 4.8%) pregnant women reported symptoms and had a positive confirmatory test, respectively. The most common symptom of coronavirus disease 2019 among the pregnant women with positive confirmatory test was cough (n=23, 46%). Seven newborns (7/50, 14%) of symptomatic mothers had positive Reverse transcription-polymerase chain reaction. Upon birth, no newborn had serious complications. CONCLUSION: Universal screening of pregnant women admitted for delivery can reduce the perinatal transmission of coronavirus disease 2019. Symptom-based screening can be an alternative for regions with a low prevalence of the disease where a better allocation of financial resources is necessary.

Self-made transvaginal ultrasound simulator: new training equipment in ultrasound evaluation of controlled ovarian stimulation and oocyte retrieval.

Aim: We sought to create and describe a self-made simulator designed and created for teaching purposes: a high-fidelity ultrasound phantom for demonstrating antral follicle count, ultrasound supervision of controlled of ovarian stimulation, and ultrasound-guided oocyte retrieval. Materials and methods: The uterus and ovaries of the ultrasound phantom were made from beef tongue, a male condom, latex gloves, cotton suture threads, bi-distilled water, and ultrasound gel. The components were placed in a pelvis created using three-dimensional (3D) printing. The phantom was presented to and evaluated by a group of 14 physicians pursuing a postgraduate course in reproductive medicine. Two training stations were structured: one to simulate antral follicle count and controlled ovarian stimulation and the other to simulate ultrasound-guided oocyte retrieval. Future specialists were requested to complete a feedback questionnaire evaluating the self-made simulator and the two practice stations. Results: The transvaginal ultrasound phantom was successfully created, making it possible to simulate antral follicle count, ultrasound control of ovarian hyperstimulation, and oocyte retrieval, and to capture ultrasound images. A review of the answers provided in the feedback questionnaire showed that the phantom had a good appearance and design, was realistic, helped to improve motor coordination, and could be a useful tool in the training of specialists in assisted reproduction. Conclusion: This phantom was designed to enable instruction and practice in the evaluation of ovarian follicles and ultrasound-guided oocyte retrieval in a supervised training environment. This self-made simulator is proposed as a training tool that could be included in the curricular structure of residency and postgraduate programs in reproductive medicine.

The use of immunotherapies for recurrent miscarriage: An overview of systematic reviews and meta-analysis.

Immunotherapies have been a treatment proposed for recurrent miscarriages (RMs). The use of immunotherapies remains not recommended in the management of couples with RM. This overview of systematic reviews and meta-analysis (SRs-MAs) aims to identify and evaluate the quality of SRs-MAs that studied the effectiveness of immunotherapies in the treatment of RM patients. SRs-MAs were searched in PubMed/Medline, Embase, and Web of Science. SRs-MAs were analyzed using AMSTAR-2, PRISMA 2020, Risk of Bias in Systematic (ROBIS), and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools to evaluate the methodological quality, reporting quality, risk of bias, and evidence quality of included SRs-MAs, respectively. This review included 20 SRs-MAs that evaluated the following immunotherapies: intravenous immunoglobulin (13 publications), lymphocyte immunotherapy (6 publications), corticosteroids (3 publications), and lipid emulsion (1 publication). SRs-MAs were rated as high methodological, moderate, and critically low quality in 14 (70 %), 1 (5 %), and 5 (25 %) SRs-MAs and high reporting, moderate, and low quality in 13 (65 %), 4 (20 %), and 3 (5 %) SRs-MAs, respectively. The overall risk of bias revealed a low risk of bias for three-quarters of the SRs-MAs. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) analysis resulted in 23 outcomes, of which 4, 3, 5, and 11 results were of high, moderate, low, and very low quality, respectively. An improvement has been observed over the past few years in the quality of systematic reviews (SR)-MAs that have investigated the efficacy of intravenous immunoglobulin, lymphocyte immunotherapy, lipid emulsion therapy, and corticosteroids as a therapy for RM.

Peripheral blood natural killer cell cytotoxicity in recurrent miscarriage: a systematic review and meta-analysis.

Dysregulated natural killer (NK) cells have been associated with recurrent miscarriages (RM). Studies have suggested that high peripheral blood NK cell cytotoxicities (pNKCs) are associated with an increased risk of RM. The aim of this systematic review (SR) and meta-analysis (MAs) is to investigate the difference in pNKC between nonpregnant and pregnant women with RM and controls and determine whether pNKC is reduced by immunotherapy. We searched the PubMed/Medline, Embase, and Web of Science databases. The MAs were conducted to compare pNKCs between women with and without RM before and during pregnancy as well as pre- and post-immunotherapy. Risk of bias in nonrandomized studies was assessed by the Newcastle-Ottawa Scale. Statistical analysis was performed using the Review Manager software. A total of 19 studies were included in the SR and 14 studies in the MAs. The MAs revealed higher pNKCs among nonpregnant women with RM compared to controls (MD, 7.99 95 %CI 6.40-9.58; p < 0.00001). pNKCs were also higher in pregnant women with RM than in pregnant controls (MD, 8.21 95 %CI 6.08-10.34; p < 0.00001). Women with RM showed significantly decreased pNKCs after the immunotherapy compared to before (MD, -8.20 95 %CI -10.20 - -6.19; p < 0, 00001). Additionally, there is an association between high pNKCs and the risk of pregnancy loss in women with RM. However, included studies showed substantial heterogeneities regarding the inclusion criteria of patients, techniques measuring pNKC, and types of immunotherapies. More studies are needed to evaluate the clinical efficiency of pNKCs in managing RM.

Influence of design implant and apical depth in post-extraction sockets: an in vitro simulated study.

BACKGROUND: Implant design and apical stability are principal parameters involved in achieving successful primary stability. Using polyurethane models to simulate post-extraction sockets, we investigated the effects of using differing blade designs on the primary stability of tapered implants and the impact of apical depth. METHOD: Six polyurethane blocks were used to simulate post-extraction pockets. One of the implants presented self-tapping blades (Group A), while the other (Group B) did not. Seventy-two implants were placed at 3 different depths (5 mm, 7 mm, and 9 mm), and a torque wrench was used to measure the stability of the implants. RESULTS: When evaluating the implants (placed at 5 mm, 7 mm, and 9 mm apical to the socket), we observed that the torque of the Group B implants was higher than that of Group A implants (P < 0.01). At the 9-mm depth, there was no difference between the groups (Drive GM 34.92 Ncm and Helix GM 32.33 Ncm) (P > 0.001), and considering the same implant groups, those placed at 7-mm and 9-mm depths presented higher torques (p < 0.01) than those placed at 5-mm (p > 0.01). CONCLUSION: Considering both groups, we concluded that an insertion depth of greater than 7 mm is needed for initial stability, and in situations involving reduced supportive bone tissue or low bone density, a non-self-tapping thread design improves implant stability.

Kisspeptin as a predictor of miscarriage: a systematic review.

OBJECTIVE: A highly accurate serum marker for predicting viable pregnancy needs to be developed. Recent studies have demonstrated that kisspeptin is a potential biomarker for this purpose. METHODS: This systematic review evaluated the available data in the literature on the role of kisspeptin as a miscarriage biomarker. A literature search was conducted in the PubMed/Medline, Embase, Web of Science, and Scopus databases using the following keywords: (kisspeptin) AND (miscarriage OR pregnancy loss OR spontaneous abortion OR reproductive failure). RESULTS: Seven case-control studies were selected for the systematic review. The included papers described the potential role of kisspeptin as a putative biomarker of pregnancy loss. Furthermore, two studies reported that changes in kisspeptin levels may be associated with unexplained infertility and low rates of embryo implantation in women undergoing assisted reproductive technology. CONCLUSION: Kisspeptin might be used as a potential biomarker of pregnancy viability in the near future. However, studies with better evidence are needed to establish the applicability of kisspeptin as a diagnostic and prognostic tool.

Ovarian aging in humans: potential strategies for extending reproductive lifespan.

Ovarian reserve is a term used to estimate the total number of immature follicles present in the ovaries. Between birth and menopause, there is a progressive decrease in the number of ovarian follicles. Ovarian aging is a continuous physiological phenomenon, with menopause being the clinical mark of the end of ovarian function. Genetics, measured as family history for age at the onset of menopause, is the main determinant. However, physical activity, diet, and lifestyle are important factors that can influence the age of menopause. The low estrogen levels after natural or premature menopause increased the risk for several diseases, resulting in increased mortality risk. Besides that, the decreasing ovarian reserve is associated to reduced fertility. In women with infertility undergoing in vitro fertilization, reduced markers of ovarian reserve, including antral follicular count and anti-Mullerian hormone, are the main indicators of reduced chances of becoming pregnant. Therefore, it becomes clear that the ovarian reserve has a central role in women's life, affecting fertility early in life and overall health later in life. Based on this, the ideal strategy for delaying ovarian aging should have the following characteristics: (1) be initiated in the presence of good ovarian reserve; (2) maintained for a long period; (3) have an action on the dynamics of primordial follicles, controlling the rate of activation and atresia; and (4) safe use in pre-conception, pregnancy, and lactation. In this review, we therefore discuss some of these strategies and its feasibility for preventing a decline in the ovarian reserve.

Screening for coronavirus disease 2019 in pregnant women admitted for delivery: an observational study

SUMMARY OBJECTIVE: The aim of this study was to examine the impact of symptom-based screening on the prevalence and outcomes of neonatal coronavirus disease 2019 in pregnant women admitted for delivery. METHODS: A retrospective observational study was conducted from June to August 2020 at Gonzaga Mota of Messejana Hospital, Fortaleza, CE, Brazil. All pregnant women were screened for coronavirus disease 2019 based on symptoms. Reverse transcription-polymerase chain reaction or immunology assays for severe acute respiratory syndrome coronavirus 2 were performed when a patient reported a symptom. All newborns of symptomatic patients were submitted for Reverse transcription-polymerase chain reaction. Newborns were divided into groups according to the Reverse transcription-polymerase chain reaction results to identify the relationship between maternal symptoms and neonatal coronavirus disease 2019. RESULTS: A total of 55 (55/1,026, 5.4%) and 50 (50/1,026, 4.8%) pregnant women reported symptoms and had a positive confirmatory test, respectively. The most common symptom of coronavirus disease 2019 among the pregnant women with positive confirmatory test was cough (n=23, 46%). Seven newborns (7/50, 14%) of symptomatic mothers had positive Reverse transcription-polymerase chain reaction. Upon birth, no newborn had serious complications. CONCLUSION: Universal screening of pregnant women admitted for delivery can reduce the perinatal transmission of coronavirus disease 2019. Symptom-based screening can be an alternative for regions with a low prevalence of the disease where a better allocation of financial resources is necessary.

Quality analysis of prior systematic reviews of carpal tunnel syndrome: an overview of the literature

ABSTRACT BACKGROUND: Carpal tunnel syndrome (CTS) is a common condition greatly affects patients' quality of life and ability to work. Systematic reviews provide useful information for treatment and health decisions. OBJECTIVE: This study aimed to assess the methodological quality of previously published systematic reviews on the treatment of CTS. DESIGN AND SETTING: Overview of systematic reviews conducted at the Brazilian public higher education institution, São Paulo, Brazil METHODS: We searched the MEDLINE and Cochrane Library database for systematic reviews investigating the treatment of CTS in adults. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and measurement tool to assess systematic reviews (AMSTAR) were applied by two independent examiners. RESULTS: Fifty-five studies were included. Considering the stratification within the AMSTAR measurement tool, we found that more than 76% of the analyzed studies were "low" or "very low". PRISMA scores were higher when meta-analysis was present (15.61 versus 10.40; P = 0.008), while AMSTAR scores were higher when studies performed meta-analysis (8.43 versus 5.59; P = 0.009) or when they included randomized controlled trials (7.95 versus 6.06; P = 0.043). The intra-observer correlation demonstrated perfect agreement (> 0.8), a Spearman's correlation coefficient of 0.829, and an ICC of0.857. The inter-observer correlation indicated that AMSTAR was more reliable than PRISMA. CONCLUSION: Overall, systematic reviews of the treatment of CTS are of poor quality. Reviews with better-quality conducted meta-analysis and included randomized controlled trials. AMSTAR is a better tool than PRISMA because it has a better performance and should be recommended in future studies. REGISTRATION NUMBER IN PROSPERO: CRD42020172328 (https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42020172328)

Quality analysis of prior systematic reviews of carpal tunnel syndrome: an overview of the literature.

BACKGROUND: Carpal tunnel syndrome (CTS) is a common condition greatly affects patients' quality of life and ability to work. Systematic reviews provide useful information for treatment and health decisions. OBJECTIVE: This study aimed to assess the methodological quality of previously published systematic reviews on the treatment of CTS. DESIGN AND SETTING: Overview of systematic reviews conducted at the Brazilian public higher education institution, São Paulo, Brazil. METHODS: We searched the MEDLINE and Cochrane Library database for systematic reviews investigating the treatment of CTS in adults. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and measurement tool to assess systematic reviews (AMSTAR) were applied by two independent examiners. RESULTS: Fifty-five studies were included. Considering the stratification within the AMSTAR measurement tool, we found that more than 76% of the analyzed studies were "low" or "very low". PRISMA scores were higher when meta-analysis was present (15.61 versus 10.40; P = 0.008), while AMSTAR scores were higher when studies performed meta-analysis (8.43 versus 5.59; P = 0.009) or when they included randomized controlled trials (7.95 versus 6.06; P = 0.043). The intra-observer correlation demonstrated perfect agreement (> 0.8), a Spearman's correlation coefficient of 0.829, and an ICC of0.857. The inter-observer correlation indicated that AMSTAR was more reliable than PRISMA. CONCLUSION: Overall, systematic reviews of the treatment of CTS are of poor quality. Reviews with better-quality conducted meta-analysis and included randomized controlled trials. AMSTAR is a better tool than PRISMA because it has a better performance and should be recommended in future studies. REGISTRATION NUMBER IN PROSPERO: CRD42020172328 (https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42020172328).

Fertility preservation: knowledge, awareness, and attitude of university students and professors.

BACKGROUND: Delayed pregnancy is a worldwide trend, especially in Western countries. University students and professors are at high risk of presenting age-related reproductive difficulties due to this new reproductive profile. Thus, through this study, we aimed at exploring the knowledge, awareness, and attitude of university students and professors related to fertility and fertility preservation (FP). METHODS: We adopted a prospective cross-sectional study design and included students and professors from private university located in the Northeast of Brazil. Eligible participants (male and female) were invited through an online message. The participants accessed the online questionnaire through a link. RESULTS: We performed 256 surveys (100 students and 156 professors). The overall mean age of participants was 35.8 ± 13.1 years (from 18 to 67 years). Fertility was considered relevant by all participants, being very important among a greater number of students compared to professors, 61% versus 30.1%, p < 0.001, respectively. The main reasons why participants could have postponed parenthood were reach financial stability (62.1%), career building (51.2%), health issues (37.9%), and not having a partner (33.9%). Students demonstrated a better understanding of FP and highlighted the importance of the age of females at the time of the oocyte cryopreservation. Very few students and professors already discussed reproductive planning with a health professional. CONCLUSIONS: We observed a deficiency in the knowledge of Brazilian university students and professors about female fertility and FP options. Thus, exposing the population to information related to FP should be hyped in the university environment.

Evidence of Nest Reactivation and Perennial Colonies in the Neotropical Bumble Bee Bombus brevivillus (Hymenoptera: Apidae: Bombini).

Bombus brevivillus Franklin is a Neotropical Bombus species whose colonies are disappearing from most of its native range, and little is known about its biology and reproductive habits to help conservation or breeding efforts. Unlike Bombus species from temperate climates whose colonies perish every winter, there are suggestions of perennial colonies that Neotropical Bombus species can present. In this work, we investigated the development of two B. brevivillus colonies (i.e., number of workers, gynes, males, new cocoons, and brood area) between August 2012 and March 2013. We realized that while one colony collapsed and died after the males' and gynes' production, and the reduction of numbers of adult workers, in the other, a new queen assumed the posture at this phase and reactivated the old nest. Despite the reduced number of colonies investigated, this study shows the possibility of nest reactivation in the studied species in queen supersedure events in resemblance to perennial colonies of eusocial bees like Apis species and stingless bees. Such behavior has never been directly described to B. brevivillus in previous studies and opens the possibility for further research in the existence and the extension of perennial colonies in Neotropical Bombus species due to its importance to the species conservation in the tropical environment.

The Dietary Inflammatory Index as a predictor of pregnancy outcomes: Systematic review and meta-analysis.

Unhealthy diets have been linked to low-grade chronic inflammation, a condition known to play a role in the pathophysiology of non-communicable diseases as well as pregnancy complications. The Dietary Inflammatory Index (DII) is a tool for evaluating the inflammatory potential of various diets. The goal of this systematic review and meta-analysis is to assess the current state of evidence on the use of DII as a predictor of pregnancy outcomes in pregnant women. This study was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PROSPERO, number CRD42021288966). DII was evaluated as a predictor of obstetric complications in observational studies. The search was conducted in PubMed/Medline, Embase, and Web of Science. Data from eligible studies were extracted independently by two reviewers. The Newcastle-Ottawa Scale was used to assess the methodological quality of the studies. A total of eight studies were eligible for the review. In a meta-analysis of continuous and categorical variables, DII was a predictor of any obstetric complications [mean difference: 0.39, 95 %CI 0.02-0.75, (p = 0.04); and odds ratio: 1.24, 95 %CI 1.11-1.40, (p = 0.0002)]. High DII was associated with pregnancy complications, particularly preeclampsia/hypertensive disorder of pregnancy and preterm birth. The DII is a tool that can assist in the food and therapeutic planning of pregnant women with obstetric risks. Well-designed clinical trials are necessary, especially studies that focus on recurrent pregnancy losses and implantation failures.