MicroRNA-210-3p Regulates Endometriotic Lesion Development by Targeting IGFBP3 in Baboons and Women with Endometriosis.

MicroRNAs (miRs) play an important role in the pathophysiology of endometriosis; however, the role of miR-210 in endometriosis remains unclear. This study explores the role of miR-210 and its targets, IGFBP3 and COL8A1, in ectopic lesion growth and development. Matched eutopic (EuE) and ectopic (EcE) endometrial samples were obtained for analysis from baboons and women with endometriosis. Immortalized human ectopic endometriotic epithelial cells (12Z cells) were utilized for functional assays. Endometriosis was experimentally induced in female baboons (n = 5). Human matched endometrial and endometriotic tissues were obtained from women (n = 9, 18-45 years old) with regular menstrual cycles. Quantitative reverse transcript polymerase chain reaction (RT-qPCR) analysis was performed for in vivo characterization of miR-210, IGFBP3, and COL8A1. In situ hybridization and immunohistochemical analysis were performed for cell-specific localization. Immortalized endometriotic epithelial cell lines (12Z) were utilized for in vitro functional assays. MiR-210 expression was decreased in EcE, while IGFBP3 and COL8A1 expression was increased in EcE. MiR-210 was expressed in the glandular epithelium of EuE but attenuated in those of EcE. IGFBP3 and COL8A1 were expressed in the glandular epithelium of EuE and were increased compared to EcE. MiR-210 overexpression in 12Z cells suppressed IGFBP3 expression and attenuated cell proliferation and migration. MiR-210 repression and subsequent unopposed IGFBP3 expression may contribute to endometriotic lesion development by increasing cell proliferation and migration.

Psycho-emotional acceptance in couple and single women who choose to undergo IVF treatment with donor eggs.

New family configurations are emerging concurrently with improved assisted reproduction techniques, including the use of donated gametes. Most indications for treatment when using donated eggs are caused by an age-related decrease in reproductive capacity. We evaluated the emotional state regarding accepting egg donation in participants who chose this option for in vitro fertilization cycles. This is a retrospective, Brazilian cohort study, based on data collected from sixty psychological counseling sessions with participants that opted to be enrolled in an egg donation program. A single professional conducted semi-structured psychological counselling sessions. The data were analyzed using a thematic analysis as the qualitative methodology. Two years after the psychological counseling sessions, participants were contacted to obtain information about their outcomes. Of 60 sessions, 19 (32%) were classified as involving participants with positive emotional state (group 1), 14 (23%) with unfavorable emotional state (group 2), and 27 (45%) without evident classification (group 3). Three couples did not undergo treatment until two years after the psychological counselling session and the other couples underwent treatment in a period ranging from 1-8 months after the session. This is the first study in the Brazilian population regarding the acceptance of egg donation. The process of acceptance of infertility and the impossibility to have a biological child is fundamental to gradually accepting a new way of becoming a parent. Psychological counseling can contribute to reflecting on the use of donated eggs, exploring its emotional implications and identifying the need for psychotherapeutic work to address conflict and suffering.

Human endometrial stromal cells inhibit the pro-angiogenic stimulus of hCG in vitro.

During embryo implantation, endometrial angiogenesis is regulated by signals originating from the endometrium itself and the developing embryo. It has been suggested that hCG may play a pro-angiogenic role; therefore, we sought to understand its regulatory role in blood vessel formation in human endometrium using in vivo and in vitro models. In the in vivo model, we screened 16 angiogenesis-related transcripts in the endometrium upon intrauterine administration of hCG. Oocyte donors were recruited and during their controlled ovarian stimulation cycle received a single dose of hCG or vehicle on the day of oocyte pick up during a cycle of ovarian stimulation. One hour before obtaining an endometrial sample, women received an intrauterine administration of vehicle or hCG (500, 1500 and 5000 IU). Transcript and protein analysis showed that MMP3 and VEGFA increased, whereas TIMP1 decreased. The in vitro analysis studied the angiogenic potential of conditioned medium (CM) from primary cultures of human endometrial stromal cells (ESC) stimulated with hCG. Using a 2D and 3D in vitro angiogenesis assays, our results indicate that CM from ESC almost completely inhibits the capillary-like structure formation in endothelial cells, overriding the pro-angiogenic effect of hCG; and this inhibition due to secreted factors present in CM specifically reduced the migration potential of endothelial cells. In conclusion, the endometrial stromal milieu seems to modulate the direct pro-angiogenic effects of hCG on endothelial cells during embryo implantation.

Postoperative imaging findings after laparoscopic surgery for deeply infiltrating endometriosis.

Deeply infiltrative endometriosis (DIE) is a common gynecologic disease affecting women of reproductive age and often causing chronic pelvic pain and infertility. Clinical treatment options and preventive actions are ineffective due to the lack of knowledge about the etiology of DIE. Surgical treatment is currently the only alternative to eradicate the disease. Diagnostic imaging plays a crucial role for surgical planning and postoperative evaluation. Transvaginal sonography (TVS) with a dedicated protocol and magnetic resonance imaging (MRI) can be used to evaluate recurrent disease. Extensive pelvic surgery may cause anatomical changes and a variable spectrum of postoperative findings. Residual disease and complications can be also evaluated and are of great importance to estimate pain relief and fertility prognosis. The most common imaging findings following radical surgery for DIE are fibrotic scars in the retrocervical space and bowel anastomosis, absence of the posterior vaginal fornix and loculated fluid in the pararectal spaces. Ovaries are the most frequent site of early recurrence. Complications include infection, hemorrhage, urinary/evacuatory voiding dysfunctions as well as bowel and ureteral stenosis. The purpose of this article is to review the surgical techniques currently used to treat endometriosis in the retrocervical space, vagina, bladder, bowel, ureters, and ovaries and to describe the most common imaging findings including normal aspects, residual disease, complications, and recurrence.

Prognostic factors for pregnancy after intrauterine insemination.

OBJECTIVE: To evaluate prognostic factors for pregnancy after intrauterine insemination (IUI). METHODS: A retrospective study was conducted among couples who underwent IUI at Universidade de São Paulo, Brazil, between January 31, 2008, and April 30, 2016. The main outcome was a positive ß human chorionic gonadotropin (ß-hCG) test result after IUI. Univariate analyses were used to determine predictors of pregnancy. Selected numerical variables were categorized to maximize the area under the receiver operating characteristic (ROC) curve. Logistic regression was performed using the backward method. The quality of the model was evaluated using the R2 (Nagelkerke) and Hosmer-Lemeshow tests. RESULTS: Of 355 insemination cycles, 56 (15.8%) resulted in a positive ß-hCG test result. The predictors and cutoff values that maximized the area under the ROC curve were as follows: follicle-stimulating hormone (<7.7 mIU/mL; P<0.001); duration of infertility (<62 menses; P<0.001); number of follicles greater than or equal to 14 mm (>1 follicle; P<0.001); baseline spermatozoa concentration (>52.0 million/mL; P=0.007); total ejaculate (>123.7 million; P=0.003); and grade B motility (>35%; P=0.013). These factors were able to predict 50.4% of the positive test results (R2 ). CONCLUSION: Prognostic factors for pregnancy identified approximately half of all successful outcomes after IUI.

Ovarian reserve in young juvenile idiopathic arthritis patients.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) occurs during reproductive age, however, there are no systematic data regarding ovarian function in this disease. METHODS: Twenty-eight post-pubertal JIA patients and age-matched 28 healthy controls were studied. Complete ovarian function was assessed during the early follicular phase of the menstrual cycle including anti-Müllerian hormone (AMH), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and antral follicle count (AFC) by ovarian ultrasound, and anti-corpus lutheum antibodies (anti-CoL). Demographic data, menstrual abnormalities, disease parameters and treatment were also evaluated. RESULTS: The mean current age (22.6 ± 6.59 vs. 22.5 ± 6.59 years, p = .952) was similar in JIA patients and healthy controls with a higher median menarche age [13(8-16) vs. 12(8-14) years, p = .029]. A lower median AMH levels [2.65(0.47-9.08) vs. 4.83(0.74-17.24) ng/mL, p = .029] with a higher LH [8.44 ± 4.14 vs. 6.03 ± 2.80 IU/L, p = .014] and estradiol levels [52.3(25.8-227.4) vs. 38.9(26.2-133.6) pg/mL, p = .008] were observed in JIA compared to control group. Anti-CoL and AFC were similar in both groups (p > .05). Further analysis of JIA patients revealed that current age, disease duration, number of active/limited joints, ESR, CRP, patient/physician VAS, JADAS 71, DAS 28, CHAQ, HAQ, patient/parents PedsQL, PF-SF 36, cumulative glucocorticoid and cumulative methotrexate doses were not correlated with AMH, FSH, estradiol levels or AFC (p > .05). CONCLUSION: The present study was the first to suggest diminished ovarian reserve, not associated to hypothalamic pituitary gonadal axis, in JIA patients during reproductive age. The impact of this dysfunction in future fertility of these patients needs to be evaluated in prospective studies.

Non-steroidal anti-inflammatory drug induces luteinized unruptured follicle syndrome in young female juvenile idiopathic arthritis patients.

To assess prospectively luteinized unruptured follicle (LUF) syndrome in juvenile idiopathic arthritis (JIA) patients with and without non-steroidal anti-inflammatory drugs (NSAIDs) and healthy controls. Twenty-three adolescent and young adult female JIA patients (ILAR criteria) and 11 female healthy subjects were studied by pelvic ultrasound monitoring for follicular development and ovulation in one menstrual cycle. LUF syndrome was prospectively investigated by pelvic ultrasound with a dominant ovarian follicle without signs of follicular rupture, with elevation of serum progesterone in the luteal phase of the menstrual cycle and luteinizing hormone (LH) detected in the urine. Comparison between JIA patients with (n = 8) vs. without NSAIDs (n = 15) and healthy controls (n = 11) revealed that LUF syndrome was significantly higher in the former group (2 (25%) vs. 0% vs. 0%, p = 0.049). These two patients with LUF syndrome had normal menstrual cycles without reduced ovarian reserve, and they were under naproxen 500 mg bid during the menstrual cycle. Disease duration was comparable in JIA with and without NSAIDs [19.8 (4.4-25) vs. 13 (3.1-33) years, p = 0.232]. Further comparison between JIA patients with and without NSAIDs and healthy controls showed similar mean anti-Müllerian hormone levels (p = 0.909), estradiol (p = 0.436), FSH (p = 0.662), LH (p = 0.686), and mean antral follicle count (p = 0.240) and ovarian volume (p = 0.363). No differences were evidenced in three groups regarding Caucasian race, body mass index, duration, and length of menstrual cycles (p > 0.05). This is the first study to identify that JIA patients have a high frequency of LUF without impaired ovarian reserve. Future prospective studies are necessary to determine if chronic/continuous use of NSAIDs in JIA will have an impact in these patients' fertility.

How general semen quality influences the blastocyst formation rate: Analysis of 4205 IVF cycles.

OBJECTIVE: To select embryos with higher implantation potential, the extended culture has been the most frequently applied strategy worldwide, and consequently leads to higher live birth rates per transfer. Sperm quality is a determining feature, and it may influence the outcomes of IVF from fertilization to embryo development. Therefore, we hypothesize that blastocyst formation may also be impaired by general semen quality. METHODS: We analyzed 4205 IVF cycles. Four study groups were designed according to semen quality: normal, mild alteration, severe alteration and epididymis. All cycles were intended to extend embryo culture until the blastocyst stage, and embryo development was evaluated. RESULTS: Regarding cleavage rate, the normal and mild alteration semen groups were equivalent, and the severe alteration and epididymis semen groups were equivalent to each other. The blastocyst formation rate decreased with semen quality. At least one blastocyst formed in 79.9% of cycles for the normal semen group, whereas the percentage of cycles with the formation of at least one blastocyst was slightly lower for the mild alteration (75.6%), severe alteration (76.4%) and epididymis (76.8%) semen groups. A multivariate logistic regression showed that for each additional cleaved embryo on day 3, the chance of having at least one blastocyst doubles. Additionally, the chance of having at least one blastocyst decreased when semen presented mild or severe alterations. CONCLUSION: The general quality of sperm is a good predictor of blastocyst formation, significantly affecting the likelihood of having at least one blastocyst at the end of the cycle. Based on our findings, it is necessary to consider general semen quality and the number of cleaved embryos when forecasting the possibility of blastocyst formation and transfer in an extended culture system.

Transfer of 2 Embryos Using a Double-Embryo Transfer Protocol Versus 2 Sequential Single-Embryo Transfers: The Impact on Multiple Pregnancy.

INTRODUCTION: Assisted reproductive technologies (ARTs) are associated with potential risks, mainly related to multiple pregnancies, which are around 20% to 25%. Iatrogenic multiple pregnancies due to ovarian stimulation with multiples embryos transferred can be avoided by the elective single-embryo transfer (eSET), a growing practice worldwide. Adequately applied eSET, which impact on the incidence of complications without compromising treatment success, is still a challenge. The aim of this study was to compare the cumulative success rates of elective transfer of 2 embryos when transferred one by one (eSET), versus the success rates of elective double-embryo transfer (DET) in a single procedure, in a good prognosis population. METHODS: This study evaluated 610 good prognosis infertile couples undergoing ART, split into 2 groups: eSET group which included those receiving first eSET (n = 237) and for those who did not become pregnant, they could receive a second frozen-thawed SET; and eDET group (n = 373) who received elective transfer of 2 good quality embryos in the first transfer. RESULTS: Clinical pregnancy outcomes after a transfer of 2 embryos were similar between the groups (DET: 46.6% vs accumulated SET: 45.9%; P = .898). Multiple pregnancy rate was significantly lower in the group receiving transfer of 2 embryos, one by one, compared to DET (DET: 32.2% vs accumulated SET: 6.7%; P < .001). CONCLUSIONS: The eSET policy should be stimulated for good prognosis couples, as it maintains the accumulated clinical pregnancy rates, avoids multiples pregnancies, and consequently the maternal and neonate complication and indirect costs of treatment when considering spending on the obstetrics are reduced.

Psychosocial benefits of fertility preservation for young cancer patients.

PURPOSE: The risk of ovarian failure after radiotherapy and/or chemotherapy is a concern among oncologic women. There is no doubt regarding the psycho-emotional benefits of fertility preservation (FP) after a cancer diagnosis because concerns about biological conception are a source of anxiety and can even affect the patient's cancer recovery. The aim of this study was to evaluate oncology patients' feelings, concerns, and life quality impacts related to FP. METHODS: This qualitative cross-sectional study was based on a questionnaire administered to a selected group of women diagnosed with cancer who underwent FP. Thirty-four eligible women (23-39 years old) completed this questionnaire. RESULTS: Two of the participants already had a child, and most of them (61.8%) stated a desire to have children at the time of FP. Their feelings primarily involved safety (44.1%) and hope (23.5%). Time and/or financial issues (82.4%) were the main challenge for FP. All of the women noted the importance of FP, with many stating that it is warranted to allow the possibility of a biological pregnancy due to the risk of infertility. Finally, questions about the impact on their lives if they had not undergone FP indicated emotional impairment, low quality of life, relationship problems, and uncertainty about maternity. CONCLUSIONS: FP for oncology patients is a positive strategy. The women in this study felt that FP was a worthwhile process and that the security of having undergone FP brought them peace during oncological treatment and contributed to their quality of life.

Translabial US and Dynamic MR Imaging of the Pelvic Floor: Normal Anatomy and Dysfunction.

Pelvic floor dysfunction (PFD) is a common condition that typically affects women older than 50 years and decreases the quality of life. Weakening of support structures can involve all three pelvic compartments and cause a combination of symptoms, including constipation, urinary and fecal incontinence, obstructed defecation, pelvic pain, perineal bulging, and sexual dysfunction. The causes of PFD are complex and multifactorial; however, vaginal delivery is considered a major predisposing factor. Physical examination alone is limited in the evaluation of PFD; it frequently leads to an underestimation of the involved compartments. Imaging has an important role in the clinical evaluation, yielding invaluable information for patient counseling and surgical planning. Three- and four-dimensional translabial ultrasonography (US) is a relatively new imaging modality with high accuracy in the evaluation of PFD such as urinary incontinence, pelvic organ prolapse, and puborectalis avulsion. Evaluation of mesh implants is another important indication for this modality. Dynamic magnetic resonance (MR) imaging of the pelvic floor is a well-established modality for pelvic floor evaluation, with high-resolution images yielding detailed anatomic information and dynamic sequences yielding functional data. Specific protocols and dedicated image interpretation are required with both of these imaging methods. In this article, the authors review the normal anatomy of the female pelvic floor by using a practical approach, discuss the roles of translabial US and MR imaging in the investigation of PFD, describe the most appropriate imaging protocols, and illustrate the most common imaging findings of PFD in the anterior, middle, and posterior compartments of the pelvis. Online supplemental material is available for this article. ©RSNA, 2018.

Atypical Sites of Deeply Infiltrative Endometriosis: Clinical Characteristics and Imaging Findings.

Endometriosis is defined as the presence of endometrial tissue that is located outside the uterine cavity and associated with fibrosis and inflammatory reaction. It is a polymorphic and multifocal disease with no known cure or preventive mechanisms. Patients may be asymptomatic or may experience chronic pelvic pain, dysmenorrhea, dyspareunia, or infertility. The pelvic cavity is the most common location for endometriotic implants, which usually affect the retrocervical space, ovaries, vagina, rectosigmoid colon, bladder dome, and round ligaments. Atypical endometriosis is rare and difficult to diagnose. The most common atypical locations are the gastrointestinal tract, urinary tract, lung, umbilicus, inguinal area, breast, and pelvic nerves, as well as abdominal surgical scars. Gastrointestinal lesions are the most common extragenital manifestation, and the diaphragm is the most frequent extrapelvic site. The catamenial nature of the symptoms (occurring between 24 hours before and 72 hours after the onset of menstruation) may help suggest the diagnosis, but imaging by specialists is fundamental to evaluation. Depending on the area affected, radiography, ultrasonography, thin-section computed tomography, or magnetic resonance imaging can be used to assess suspected lesions. Because isolated extragenital endometriosis is rare, concomitant evaluation of the pelvic cavity is mandatory. Surgical excision is the only therapeutic option for definitive treatment, and comprehensive disease mapping is necessary to avoid residual disease. The authors review atypical locations for endometriosis and emphasize the most appropriate imaging protocols for investigation of various clinical manifestations. Online supplemental material is available for this article. ©RSNA, 2018.

Successful Pregnancies After Adequate Hormonal Replacement in Patients With Combined Pituitary Hormone Deficiencies.

CONTEXT: Women with hypopituitarism have lower pregnancy rates after ovulation induction. Associated pituitary hormone deficiencies might play a role in this poorer outcome. OBJECTIVE: We evaluated fertility treatment and pregnancy outcomes in five women with childhood-onset combined pituitary hormone deficiencies (CPHD). PATIENTS AND METHODS: Five women with CPHD were referred for fertility treatment after adequacy of hormone replacement was determined. Patients were subjected to controlled ovarian stimulation (COS) for timed intercourse, intrauterine insemination, or in vitro fertilization, according to the presence or absence of other infertility factors (male or tubal). RESULTS: All women became pregnant. The number of COS attempts until pregnancy was achieved varied between 1 and 5. The duration of COS resulting in at least one dominant follicle varied between 9 and 28 days, and total gonadotropin consumed varied between 1200 and 3450 IU. Two patients with severely suppressed basal gonadotropin levels since an early age had a cancelled COS cycle. All pregnancies were singleton except one (monochorionic twin gestation). The gestational ages at birth ranged from 35 weeks to 39 weeks and 4 days; three patients underwent cesarean section, and two had vaginal deliveries. Only one newborn was small for gestational age (delivered at 35 weeks). CONCLUSION: Adequate hormonal replacement prior to ovarian stimulation resulted in successful pregnancies in patients with childhood-onset CPHD, indicating that hormone replacement, including growth hormone, is an important step prior to fertility treatments in these patients.

Positive rheotaxis extended drop: a one-step procedure to select and recover sperm with mature chromatin for intracytoplasmic sperm injection.

PURPOSE: The purpose of this study was to develop a novel one-step ICSI approach to select sperm with better chromatin maturity than the conventional method. METHODS: This was a pilot diagnostic study, which prospectively recruited men during a 6-month period in a University-affiliated infertility centre. Forty consecutive semen samples were provided for analysis. The positive rheotaxis extended drop (PRED) was set up creating a pressure and viscosity gradient. Each semen sample was divided into four aliquots: one aliquot for density gradient centrifugation (DGC), two aliquots for PRED (fresh semen (PRED-FS) and processed semen (PRED-DGC)), and one aliquot as the control (FS). In PRED, a mean of 200 spermatozoa were collected consecutively without selection from the outlet reservoir. The aniline blue assay was used to assess chromatin immaturity. RESULTS: The mean channel length, measured from inlet to outlet, was 32.55 ± 0.86 mm, with a mean width of 1.04 ± 0.21 mm. In 82.5% of cases (33/40), at least 50 spermatozoa were captured between 15 and 30 min. Improved chromatin maturity after the DGC preparation and the PRED approach was observed in all samples. This was reflected by a mean reduction from 28.65 ± 8.97% uncondensed chromatin in the native ejaculates to 17.29 ± 7.72% in DGC and 0.89 ± 1.31% in the PRED approach (P < 0.01). CONCLUSIONS: The PRED method may improve the current ICSI technique by providing it with its own sperm selection process. ICSI would probably become an even more complete technique comprising selection, capture and injection of the male gamete.

Egg donation of vitrified oocytes bank produces similar pregnancy rates by blastocyst transfer when compared to fresh cycle.

PURPOSE: Advances in reproductive techniques, mainly the introduction of oocyte vitrification, have provided the opportunity to conceive from oocyte banks. The aim of this study was to compare the clinical outcomes of fresh and vitrified oocytes in an egg donation program following blastocyst transfer. METHODS: This retrospective observational study included 504 oocyte donation cycles. All donor women were younger than 30 years of age. The recipient cycles were divided into two groups: fresh oocytes (n = 78) or vitrified oocytes (n = 426). All oocytes were fertilized by ICSI using ejaculated sperm, followed by blastocyst transfer. Endometrium preparation was performed with estradiol valerate plus micronized progesterone according to standard protocols. RESULTS: Recipients were of similar age (fresh 42.0 ± 4.5 years vs vitrified 41.8 ± 4.8 years; p = 0.790). The fresh group received more mature oocytes for injection compared to the vitrified group (10.1 ± 2.8 vs 9.2 ± 2.2; p = 0.005). The two pronuclei (2PN) rate (74.5 vs 77.4%; p = 0.195) and blastocyst rate (48.8 vs 51.6%; 0.329) were similar between the fresh and vitrified groups, respectively. The rates of clinical pregnancy were 60.9% in the fresh and 59.0% in the vitrified groups (p = 0.771). CONCLUSIONS: Our findings suggest that vitrified oocytes result in similar pregnancy rates when compared to fresh oocytes with blastocyst transfer in an egg donation program. Moreover, vitrified oocytes may allow for a better cycle schedule, starting with a lower number of oocytes to be fertilized. Therefore, we hypothesize that egg banks with vitrified oocytes could be safely utilized in an egg donation program.

Small leucine-rich proteoglycans (SLRPs) in the endometrium of polycystic ovary syndrome women: a pilot study.

BACKGROUND: Small leucine-rich proteoglycans (SLRPs) play an important role in tissue homeostasis and cell proliferation since these proteoglycans sequester multiple growth factors. However, the content of SLRPs in the endometrium of polycystic ovary syndrome (PCOS) women is unknown. Our purpose was to test the hypothesis that excessive endometrial proliferation in PCOS may be partly related to abnormalities in SLRPs. METHODS: In a cross section study a total of 20 endometrial samples were collected from 10 patients with PCOS and 10 ovulatory women during their proliferative (pre-ovulatory) phase. The study subjects were matched for age, body mass index and race. The age range was 20 to 35 years. All volunteers were evaluated in reproductive endocrinology clinic, Gynecology Division, Clinics Hospital, University of São Paulo Medical School Profile and concentration of small leucine-rich proteoglycans (decorin, lumican, fibromodulin and biglycan) were determined by immunohistochemical testing and Western blotting. RESULTS: Decorin and lumican demonstrated higher immunoreactivity and relative expression in the endometrium of women with PCOS compared to that of women with regular menstrual cycles. CONCLUSION: Our data suggests that the endometrium of PCOS women demonstrate a greater content of SLRP than controls; decorin and lumican, in particular, were found in higher concentrations in the endometrium of PCOS women during the proliferative phase. These differences may, in part, explain the excess of endometrial proliferation frequently observed in PCOS. Further studies are warranted.

Knowledge regarding fertility preservation in cancer patients: a population-based survey among Brazilian people during the Pink October awareness event.

OBJECTIVE: The aim of this study was to assess the knowledge about the risk of infertility in cancer patients after treatment, and the options for fertility preservation based on a survey carried out during the 2013 Pink October campaign. METHODS: This survey was carried out during the 2013 Pink October event in the most important public park of São Paulo, Brazil. Approximately 900 people expressed interest in learning about breast cancer prevention and fertility preservation by participating in workshops, and 242 people filled out a questionnaire. RESULTS: Most of the respondents (78.5%) were women, and one-fourth (25%) had at least one relative with gynecological cancer. Among women over 40 years of age, 86.3% had been screened for breast cancer at some point. However, few participants (34.0%) were aware that cancer treatment can lead to infertility or had heard about fertility preservation options (22.0%). Having a relative with cancer did not influence their knowledge about fertility preservation (22.4% versus 21.3%; p=0.864). However, a higher educational level was significantly associated with more knowledge about the effects of cancer on fertility and options for fertility preservation. CONCLUSIONS: The majority of participants did not have knowledge about the impact of oncologic treatment on fertility and did not know that there are options to preserve fertility in cancer patients. Awareness of infertility risk factors is an essential first step to safeguard future fertility, and therefore, more educational initiatives are needed to spread knowledge about oncofertility.

Progesterone Resistance in Endometriosis Is Modulated by the Altered Expression of MicroRNA-29c and FKBP4.

Context: Endometriosis results in aberrant gene expression in the eutopic endometrium (EuE) and subsequent progesterone resistance. MicroRNA (miR) microarray data in a baboon model of endometriosis showed an increased expression of miR-29c. Objectives: To explore the role of miR-29c in progesterone resistance in a subset of women with endometriosis. Design: MiR-29c expression was analyzed in the endometrium of baboons and women with or without endometriosis. The role in progesterone resistance and decidualization was analyzed by transfecting human uterine fibroblast cells with miR-29c. Patients: Subjects diagnosed with deep infiltrative endometriosis (DIE) by transvaginal ultrasound with bowel preparation underwent surgical excision of endometriosis. Eutopic secretory endometrium was collected pre- and postoperatively. Women with normal EuE and without DIE served as controls. Results: Quantitative reverse transcription polymerase chain reaction demonstrated that miR-29c expression increased, while the transcript levels of its target, FK506-binding protein 4 (FKBP4), decreased in the EuE of baboons following the induction of endometriosis. FKBP4 messenger RNA and decidual markers were statistically significantly decreased in decidualized human uterine fibroblast cells transfected with a miR-29c mimic compared with controls. Human data corroborated our baboon data and demonstrated higher expression of miR-29c in endometriosis EuE compared with normal EuE. MiR-29c was significantly decreased in endometriosis EuE postoperatively compared with preoperative tissues, and FKBP4 showed an inverse trend following radical laparoscopic resection surgery. Conclusions: We demonstrate that miR-29c expression is increased in EuE of baboons and women with endometriosis, which might contribute to a compromised progesterone response by diminishing the levels of FKBP4. Resection of DIE is likely to reverse the progesterone resistance associated with endometriosis in women.