Use of clomiphene citrate protocol for controlled ovarian stimulation impairs endometrial maturity.

INTRODUCTION: Despite recent advances in assisted reproduction techniques and recent knowledge regarding embryo and endometrium quality, implantation and birth rates remain low. The objective of this study was to investigate whether clomiphene citrate alters endometrial maturation in infertile patients. METHODS: In a prospective self-matched cohort study, we assessed the ovulation of women in spontaneous and stimulated cycles (with clomiphene citrate). We determined the ovulation day by ultrasound scanning. In both cycles, we took four blood samples (BS1 - at early proliferative phase, BS2 - at mid proliferative phase, BS3 - after ovulation and BS4 - at mid luteal phase) to determine the serum concentrations of FSH, LH, estradiol and progesterone. We retrieved an endometrial biopsy five days after ovulation, followed by blinded analysis and classification according to Noyes criteria, in both cycles. RESULTS: Twenty-two participants completed the study. There were significant differences in FSH BS3 (p=0.001), in LH BS3 and BS4 (p<0.001 and p=0.049, respectively), in estradiol BS2, BS3 and BS4 (p<0.001, p=0.024 and p<0.001, respectively) and in progesterone BS3 and BS4 (p=0.028 and p<0.001, respectively). Considering Noyes criteria, there was a one-day delay when comparing the stimulated cycle with the spontaneous cycle (p=0.004), and a two-day delay when comparing the stimulated cycle with the biopsy day. CONCLUSION: This study indicates that ovarian stimulation with clomiphene citrate delays the endometrial maturity, and could possibly impair the implantation process due to asynchrony.

Efficacy, safety, and acceptability of thermocoagulation for treatment of cervical intraepithelial neoplasia in a hospital setting in Brazil.

OBJECTIVE: To analyze the acceptability, safety, and effectiveness of thermocoagulation for the treatment of histologically proven cervical intraepithelial neoplasia grade 2-3 (CIN2-3) lesions. METHODS: In a retrospective study, data were obtained for women treated for CIN2-3 lesions by thermocoagulation at the Hospital de Clínicas de Porto Alegre, Brazil, between March 6, 2012, and October 29, 2013, and followed up after 1 year. The proportions of women with no evidence of disease, adverse effects, or complications were determined. RESULTS: Among 52 women included, 44 (85%) had no evidence of disease 1year after thermocoagulation. The rate of no disease at follow-up was similar for women treated for CIN2 (17/20 [85%]) and CIN3 (27/32 [84%]). No serious adverse effects or complications requiring hospitalization were observed during the follow-up period. CONCLUSION: Thermocoagulation is useful in the management of ectocervical CIN and should be integrated into public health services for management of cervical cancer.

Short-term effects of a hypocaloric diet with low glycemic index and low glycemic load on body adiposity, metabolic variables, ghrelin, leptin, and pregnancy rate in overweight and obese infertile women: a randomized controlled trial.

BACKGROUND: Obesity is related to hormonal disorders that affect the reproductive system. Low-glycemic index (LGI) diets seem to exert a positive effect on weight loss and on metabolic changes that result from obesity. OBJECTIVE: We investigated the effects of a hypocaloric diet with an LGI and low glycemic load on anthropometric and metabolic variables, ghrelin and leptin concentrations, and the pregnancy rate in overweight and obese infertile women who were undergoing in vitro fertilization (IVF). DESIGN: The study was a randomized block-design controlled trial in which we analyzed 26 overweight or obese infertile women. Patients were assigned to a hypocaloric LGI-diet group or a control group and followed the protocol for 12 wk. Body weight, body mass index (BMI), percentage of body fat, glucose, insulin, homeostasis model assessment of insulin resistance, serum lipids, reproductive hormones, leptin, acylated ghrelin, number of oocytes retrieved in the IVF cycle, and pregnancy rate were determined. RESULTS: There were greater reductions in body mass, BMI, percentage of body fat, waist:hip ratio, and leptin in the LGI-diet group than in the control group (P < 0.05). Despite a change of 18% in mean values, there was no significant increase in acylated ghrelin concentrations in the LGI group compared with the control group (P = 0.215). The LGI-diet group had 85.4% more oocytes retrieved than did the control group (7.75 ± 1.44 and 4.18 ± 0.87, respectively; P = 0.039) in the IVF cycle. Three patients (21.4%) in the LGI group experienced a spontaneous pregnancy during the follow-up, which generated 3 live births. CONCLUSIONS: The hypocaloric LGI diet promoted a decrease in BMI, percentage of body fat, and leptin concentrations, which improved oocyte development and pregnancy rate. These results support the clinical recommendation to advise overweight and obese women to lose weight through a balanced diet before being submitted for treatment with assisted reproduction technologies. A hypocaloric diet combined with LGI foods seems to be beneficial for these patients, but additional studies are required before this treatment is recommended. This trial was registered at clinicaltrials.gov as NCT02416960.

Comparative analysis of two cryopreservation systems of ovarian tissues in female Wistar rats.

OBJECTIVE: The aim of this study was to determine the most efficient protocol for cryopreservation of ovarian tissue using the automatic Freeze Control® system and to test two different cooling curves combined with two different cryoprotectants: dimethyl sulfoxide (DMSO) and ethylene glycol (EG). METHODS: In this study, 20 female Wistar rats underwent bilateral oophorectomy. The ovaries were divided into two groups: one cryopreserved in 1.5M DMSO and the other in 1.5M EG. Two cooling curves, slow (1h 50min) and rapid (35min) were analyzed. Tissue samples were frozen, thawed, fixed, and stained with hematoxylin and eosin to analyze oocyte integrity. Follicular analysis was performed under optical microscopy (400x magnification) and preantral follicles were classified as primordial or primary according to developmental stage. ANOVA was performed, and Tukey's test was used for comparison between means, with P<0.05 defined as significant. RESULTS: In cryopreserved tissue, the follicles with preserved integrity in each ovary were 79% primordial and 29% primary. In non-frozen (control) tissue, all follicular types were observed (primordial, primary, secondary, preantral, and antral). Reversible changes included cytoplasmic vacuolization and irregular cell outline. Irreversible changes included pyknosis. EG was more efficient than DMSO, preserving a greater number of viable primordial and primary follicles. Comparison of both cooling curves revealed no statistically significant differences between them. CONCLUSION: The EG is more effective as a cryoprotectant than DMSO for obtaining higher viable numbers of primordial and primary follicles from rat ovarian tissue. Further studies are needed to demonstrate ovarian functionality, such as detection of hormone levels.

Ovarian stimulation with GnRH analogues.

OBJECTIVE: Analysis and compare data between two induction protocols (long agonist and flexible antagonist) in patients submitted an assisted reproduction technique in Porto Alegre. METHODS: Cross-sectional study comparing the intermediate results with the use of two different ovarian stimulation protocols with gonadotropin-releasing hormone agonist versus antagonist to assisted reproductive techniques. The statistical analysis of the retrieved data (age, body mass index, number of oocytes recovered, number of fertilized oocytes, number of oocytes cleaved, total dose of FSH used and ovarian hyperstimulation syndrome) was performed by Student's t-test for parametric data and analysis of covariance for the dependent variables. RESULTS: A total of 50 patients, 25 in each group, met the criteria for inclusion in the study between January and March in the year 2010. There was statistically significant difference only in the middle ages between the groups (P = 0.031). There was no statistical difference for the remaining data analyzed (body mass index, number of oocytes recovered, number of fertilized oocytes, number of oocytes cleaved and dose of FSH utilized). There were no cases of ovarian hyperstimulation syndrome. CONCLUSION: Both protocols are equal in terms of results. The agonist has advantages about scheduling of the procedure, but it takes too long to start the stimulation and have possibility to start medication in a pregnant patient. Added to this, we have the possibility of getting the ovarian hyperstimulation syndrome as complication. In the antagonist group, is clear the ease-of-use of the medication and the fastest start of stimulation.

Assisted reproduction: what factors interfere in the professional's decisions? Are single women an issue?

BACKGROUND: With the development of medical technology, many countries around the world have been implementing ethical guidelines and laws regarding Medically Assisted Reproduction (MAR). A physician's reproductive decisions are not solely based on technical criteria but are also influenced by society values. Therefore, the aim of this study was to analyze the factors prioritized by MAR professionals when deciding on whether to accept to perform assisted reproduction and to show any existing cultural differences. METHODS: Cross-sectional study involving 224 healthcare professionals working with assisted reproduction in Brazil, Italy, Germany and Greece. Instrument used for data collection: a questionnaire, followed by the description of four special MAR cases (a single woman, a lesbian couple, an HIV discordant couple and gender selection) which included case-specific questions regarding the professionals' decision on whether to perform the requested procedure as well as the following factors: socio-demographic variables, moral and legal values as well as the technical aspects which influence decision-making. RESULTS: Only the case involving a single woman who wishes to have a child (without the intention of having a partner in the future) demonstrated significant differences. Therefore, the study was driven towards the results of this case specifically. The analyses we performed demonstrated that professionals holding a Master's Degree, those younger in age, female professionals, those having worked for less time in reproduction, those in private clinics and Brazilian health professionals all had a greater tendency to perform the procedure in that case. A multivariate analysis demonstrated that the reasons for the professional's decision to perform the procedure were the woman's right to gestate and the duty of MAR professionals to help her. The professionals who decided not to perform the procedure identified the woman's marital status and the child's right to a father as the reason to withhold treatment. CONCLUSION: The study indicates differences among countries in the evaluation of the single woman case. It also discloses the undervaluation of bioethics committees and the need for a greater participation of healthcare professionals in debates on assisted reproduction laws.

Psychological distress as predictor of quality of life in men experiencing infertility: a cross-sectional survey.

BACKGROUND: Infertility is associated with impairment in human life. The quality of life (QOL) construct allows measuring the impact of health conditions in a broader way. The study aimed to explore the impact of the psychological distress on QOL's dimensions in men experiencing infertility. METHODS: 162 men were completed a socio-demographic form, SF-36, WHOQOL-BREF, Beck Anxiety Inventory and Beck Depression Inventory. Hierarchical regressions included demographic and clinic variables, and subsequently depression and anxiety were added. RESULTS AND DISCUSSION: Model 1 was not accurate in predicting QOL. R2 values ranged from 0.029 (Social Functioning) to 0.149 (Mental Health). Eight domains were not associated with any of the predictors. In the second model, a R2increase was observed in all domains. R2 of QOL scores ranged from .209 (Role Physical) to .406 (Social Functioning). The intensity of the depression was a significant predictor for all outcomes. The load of depression was higher than the ones of the socio-demographic and clinical variables. Anxiety levels have also presented the same effect, but with less intensity. CONCLUSION: Subthreshold depression and anxiety were major predictors of QOL in men experiencing infertility. Health professionals need to include assessment of psychological symptomatology to plan more efficient interventions to infertile patients.

Investigating quality of life and health-related quality of life in infertility: a systematic review.

OBJECTIVE: To review the findings on quality of life (QOL) and health-related quality of life (HRQOL) among infertile women, men and couples. DESIGN: Systematic review. METHODS: Publications between January 1980 and July 2009 in Medline, PsycInfo, Embase and Health and Psychosocial Instruments were compiled using the following inclusion criteria: papers published in peer-reviewed journals; written in English, French, Spanish or Portuguese; presented original findings; assessed quality of life or health-related quality of life as an outcome; included infertile subjects without other clinical conditions; used validated measures. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Quality of life and health-related quality of life. RESULTS: Fourteen studies were included in the review. Educational level, will to have children, poor marital relationship, previous in-vitro fertilisation attempt and duration of the infertility were predictors of lower mental health scores in infertile men. Women had significant lower scores on mental health, social functioning and emotional behaviour. Among infertile subjects, women had lower scores in several QOL or HRQOL domains in comparison to men. CONCLUSIONS: Evidences indicate important QOL or HRQOL impairments in infertile women. Among men, it does not appear to be intense. There is scarce knowledge regarding the impact of infertility on couples.

Germinative testicular cells and bone marrow mononuclear cells transplanted to a rat model of testicular degeneration.

The aim of this study was to evaluate the ability of rat mononuclear bone marrow cells to recover testis cell associations and multiplication in busulfan-treated rats, and to compare these data to germinative testicular cell transplant. The germinative testicular cells were obtained by the trypsin digestion method, and bone marrow cells were harvested from femurs and tibias, and purified using by Ficoll gradient. Cell transplantation was performed by the injection of cells through the efferent ducts into the rete testis in busulfan-treated animals. Fifteen days after transplantation, the recipient rats were sacrificed and the testes were collected and analyzed by histology (hematoxilin-eosin and DAPI staining). Results demonstrated that germ cells transplantation promoted cellular reorganization of seminiferous epithelium 15 days later. On the other hand, no improvement in spermatogenesis regeneration was found after heterologous mononuclear bone marrow cell transplantation.

Value of the International Federation for Cervical Pathology and Colposcopy (IFCPC) Terminology in predicting cervical disease.

OBJECTIVE: To evaluate the colposcopic accuracy according to the International Federation for Cervical Pathology and Colposcopy (IFCPC) 2002 terminology. MATERIALS AND METHODS: A series of 3,040 women derived from a general population were screened by means of Pap smear, unaided visual inspection, and high-risk human papillomavirus testing. All colposcopic examination results with abnormal findings and with biopsy confirmation (n = 468) were recorded, reviewed by 2 blinded colposcopists according to the IFCPC nomenclature, and included in this analysis. RESULTS: The IFCPC terminology was easily reproduced by the 2 observers with excellent interobserver agreement (kappa =.843). Colposcopy had a sensitivity of 86% and a specificity of 30.3% in distinguishing healthy cervix from that with cervical intraepithelial neoplasia (CIN)/carcinoma. In distinguishing healthy cervix/low-grade lesions (CIN 1) from that with high-grade lesions (CIN 2/3)/carcinoma, colposcopy had a sensitivity of 61.1% and a specificity of 94.4%. Colposcopic findings graded as major changes had the highest positive predictive value for detecting high-grade lesion/carcinoma. The colposcopic abnormalities within the transformation zone and large lesions were more closely related to high-grade lesion/carcinoma, whereas a sharp outer border, multiple colposcopic abnormalities, and iodine negativity were not statistically related to severe lesions. CONCLUSIONS: Colposcopy using the new IFCPC classification is a potentially effective screening method; when used for diagnosis, a histological sampling is necessary. The categorization of major changes and minor changes is appropriate. It is important to describe the lesion localization in relation to the transformation zone and the lesion size because these characteristics are related to high-grade lesions.

Effect of the copper-intrauterine device (TCu 380A) on subendometrial microvascularization and uterine artery blood flow.

During this cohort study, the copper-intrauterine device (IUD) did not modify subendometrial microvascularization. However, subendometrial blood flow increased in patients who experienced IUD-induced side effects.

Hysteroscopy and three-dimensional ultrasonography in uterine diverticulum diagnosis: a case report.

The authors describe a case report of a uterine diverticulum in a postmenopausal woman with abnormal uterine bleeding, confirmed by 3-dimensional ultrasonography and hysteroscopy. They comment on the clinical significance of this rare lesion.

Hepatite C em casais inférteis do setor de Reprodução Humana do Hospital de Clínicas de Porto Alegre / Hepatitis C virus in a population of infertile couples

A possibilidade transmissão do vírus da hepatite C através dos gametas pode acarretar riscos para o pessoal técnico, bem como para os envolvidos no processo e para o próprio feto. Este estudo teve como objetivo determinar a prevalência e os fatores de risco da infecção pelo vírus da hepatite C em um grupo de casais inférteis. Em 409 pacientes atendidas no ambulatório de infertilidade do Hospital de Clínicas de Porto Alegre (HCPA), entre 1997 e 1998, realizou-se triagem sorológica para anti-HCV (ELISA) e HBsAg (ELFA). A infecção pelo vírus da hepatite C (HCV) e a viremia seminal também foram investigadas com detecção de HCV-RNA. A prevalência geral de anti-HCV foi de 3,2 por cento (8/248) entre as mulheres e 3,7 por cento (6/161) entre os homens. Todos os indivíduos eram negativos para o vírus da hepatite B (HBV) e HIV. Das 14 pacientes HCV-positivas, duas foram perdidas, e foi coletado soro das 12 pacientes remanescentes para detecção de HCV-RNS, resultando em cinco casos HCV- positivos (uma mulher e quatro homens). Apenas um dos casos positivos tinha nível de viremia > 500.000 cópias de RNA/ml. Houve uma associação de risco significativa da positividade para HCV nas mulheres com parceiros HCV-positivos (P<0,001). Em pacientes masculinos, a correlação entre uso de drogas endovenosas e positividade para HCV também foi significativa (P<0,001). Pacientes inférteis deveriam ser triados para HCV antes dos procedimentos de tecnologia de reprodução assistida (TRA), uma vez que o risco de infecção vertical e laboratorial pelo HCV não está bem determinado e a prevalência do HCV não é desprezível neste grupo.

Histerossalpingografia e imunofluorescência indireta pra clamídia no dignóstico do fator tubo-peritoneal em pacientes inférteis / Hysterosalpingography and chlamydia trachomatis antibody titers in diagnosis tubal disease in infertility patients

Foi realizado um estudo retrospectivo que avaliou a imunofluorescência indireta para clamídia e a histerossalpingografia (HSG), em relaçao à laparoscopia, no diagnóstico de infertilidade de causa tubo-peritoneal em pacientes inférteis. Foram selecionados 93 casos que realizaram HSG, imunofluorescência indireta para clamídia ou laparoscopia em nosso Serviço. Dezessete pacientes possuíam dados de HSG e laparoscopia, e 13 de imunofluorescência indireta para clamídia e laparoscopia. Na comparaçao, a HSG apresentou: sensibilidade de 100 por cento, especificidade de 18 por cento, valor preditivo positivo de 40 por cento e valor preditivo negativo de 100 por cento. A imunofluorescência indireta para clamídia apressentou resultados inferiores à HSG com uma sensibilidade de 60 por cento, especificidade de 38 por cento, valor preditivo positivo de 38 por cento e valor preditivo negativo de 60 por cento. As diferenças nao foram estatisticamente significativas, para o teste exato de Fisher com a<0,05. A HSG parece ser superior à imunofluorescência indireta para clamídia na avaliaçao de fator tubo-peritoneal. No entanto, nenhum dos exames contém as características ideais de exame de triagem. Ambos possuem seu papel na investigaçao inicial e, em associaçao, sao capazes de realizar melhor rastreamento de pacientes inférteis que devem ser submetidos a laparoscopia para a pesquisa de fator anatômico, do que isoladamente.

Incidência de Chlamydia trachomatis e Neisseria gonorrhoeae em mulheres assintomáticas näo promíscuas e com doença inflamatória pélvica aguda / Incidence of Chlamydia trachomatis and Neisseria gonorrhoeae in asynptomatic non-promiscuous women and with acute inflammatory pelvic disease

Levando-se em conta a importância epidemiológica da Chlamydia trachomatis e Neisseria gonorrhoeae e das possíveis complicaçoes provenientes destes patógenos, os autores investigaram l86 mulheres que visitaram o Serviço de Orientaçao e Planejamento Familiar e a Emergência do Hospital de Clínicas de Porto Alegre, no período de fevereiro de 1987 a fevereiro de 1988. As pacientes foram divididas em dois grupos: o primeiro era composto por mulheres assintomáticas nao promíscuas e o segundo por pacientes com doença inflamatória pélvica aguda. Foi coletado material do canal endocervical para cultura de gonococo e para pesquisa de clamidia. O grupo de mulheres assintomáticas mostrou a incidência de 4 por cento para Chlamydia trachomatis e 2 por cento para Neisseria gonorrhoeae, já o grupo de pacientes com doença inflamatória pélvica aguda apresentou clamídia em 27,94 por cento das amostras e gonococo em 21,32 por cento. Os autores concluíram que Chlamydia trachomatis e Neisseria gonorrhoeae podem ser isoladas de mulheres assintomáticas nao promíscuas e estao associadas significativamente com doença inflamatória pélvica aguda.

Avaliaçäo do comportamento anticoncepcional de puérperas internadas no Hospital de Clínicas de Porto Alegre / Evaluation of contraceptive behavior of puerperae inpatients in the Hospital de Clínicas de Porto Alegre

Os autores entrevistaram 792 puérperas internadas no Hospital de Clínicas de Porto Alegre. As pacientes foram questionadas sobre dados de identificaçao, história gineco-obstétrica e métodos anticoncepcionais na tentativa de identificar fatores de risco para a nao-adesao à anticoncepçao. Observou-se que a grande maioria das mulheres já tinha, em algum momento, utilizado algum método anticonceptivo, bem como fazia consultas periódicas ao ginecologista. Apesar disso, a maioria continua tendo gestaçoes nao-planejadas, o que demonstra uma dificuldade na adesao ao método de escolha. O presente estudo apresenta fatores de risco na adesao aos métodos contraceptivos.

Tratamento de gestaçäo ectópica através de laparoscopia / Treatment of ectopic pregnancy through laparoscopy

A gestaçäo ectópica tem sido tratada classicamente através da salpingectomia por laparotomia. Os autores apresentam um caso de gestaçäo ectópica tratado através de laparoscopia. É descrita a técnica, sendo enfatizado o tratamento conservador em detrimento de técnicas mais agressivas. É realizada uma revisäo de literatura abordando este tipo de tratamento. Os autores consideram este tipo de procedimento seguro, tecnicamente fácil, com menor morbilidade e tempo de hospitalizaçäo quando comparado com a laparotomia. A morbimortalidade näo está aumentada com o uso laparoscopia