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In an age where autoimmune rheumatic diseases are successfully managed with biologics, their discontinuation in pregnancy is inadvisable without careful forethought; maternal disease activity is associated with adverse pregnancy outcomes, which has long-term implications for both mother and offspring. We aim to provide clinicians with the necessary tools to facilitate decision-making – when a biologic should be used, when it can be discontinued in pregnancy if appropriate. The pathophysiology of these biologic molecules and their effect on fertility, pregnancy and parturition are discussed. A summary of the 2016 international guidelines (European League Against Rheumatism and British Society in Rheumatology) on biologics in pregnancy has been tabulated; more recent publications are discussed in depth. Data on transplacental-transfer ratios and breastmilk excretion rates are also included. Biologic effects on organogenesis, their implications for the exposed infant in terms of infection risks and vaccination requirements are included, and future directions for research proposed.

Neuronal networks controlling endocrine events present synchronous activity which is required for maintaining physiological functions, including reproduction. Although pulsatile hormone secretion is of paramount importance, the mechanism(s) by which secretory episodes are generated remain largely unknown. Nitric oxide (NO) has become the prototype of a new family of signaling molecules in the body. Nitric oxide diffuses from the source cell and controls activity of neighboring neurons as well as itself as a retrograde messenger. Cells of the luteinizing hormone-releasing hormone (LHRH) neuronal network, the key component in the control of reproduction, are scattered and loosely arranged in the anterior hypothalamus. A diffusible neurotransmitter could provide a means for establishing synchronous activation of the LHRH neuronal network leading to physiologically-relevant pulsatile LHRH secretion. In this study, we demonstrate that immortalized LHRH-producing neurons (GT1-7 cells) express NO synthase (NOS) mRNA and protein. Furthermore, GT1-7 cells are NADPH-diaphorase-positive (a marker of NOS activity) and the histochemical reaction can be abolished by treatment with a competitive NOS blocker. The presence of citrulline in these cells provides further evidence for the biological activity of NOS. These observations indicate that an active NO synthesizing machinery is present in immortalized LHRH neurons. In addition, we show that LHRH secretion is enhanced by NO in a cGMP-dependent manner. Since pulsatile LHRH secretion from immortalized LHRH neurons in vitro is abolished by NOS blockers and NO scavengers, it appears that NO is a unique neurotransmitter that is necessary to set LHRH neurons in phase to establish synchronized pulsatile LHRH secretion.

Objective. To describe pelvic sonographic findings in girls as old as 7 years, to compare prepubertal girls with girls who had isolated thelarche or central precocious puberty, and to verify the accuracy of sonographic variables for distinguishing prepubertal girls from girls with central precocious puberty. Methods. Ninety-six prepubertal girls and 2 reference groups (8 girls with isolated thelarche and 8 with idiopathic central precocious puberty) were included. Ovaries were classified morphologically as homogeneous, paucicystic, macrocystic, multicystic, and having isolated cysts. Receiver operating characteristic curves were used to choose the best cutoff points. Results. Chronologic and bone age were correlated with uterine length, area, and volume and ovarian volume in prepubertal girls (P

OBJETIVO: Identificar alterações na coagulação sangüínea em mulheres submetidas à fertilização in vitro (FIV). MÉTODOS: Trata-se de um estudo prospectivo onde foram incluídas 15 pacientes submetidas à FIV. No período pré-ovulatório imediato, do ciclo menstrual precedente à FIV, foi coletada amostra sangüínea para coagulograma, com dosagem de Estradiol, Hemograma, Fibrinogênio, Tempo de Protrombina, Tempo de Tromboplastina Parcial Ativada, Tempo de Coagulação e Plaquetas. Durante a hiperestimulação ovariana para FIV, nova amostra para coagulograma foi coletada no dia da aplicação da Gonadotrofina Coriônica Humana. Os dados referentes à análise das duas amostras foram avaliados usando teste estatístico Paired T-Test. RESULTADOS: O estudo comparativo das médias das amostras identificou aumento significativo nos níveis de fibrinogênio, 304,9 pg/ml na primeira amostra e 383,1 pg/ml na segunda (p=0,01), já os níveis de hematócrito tiveram um decréscimo significativo, com valores de 40,5% e 38,4%, respectivamente (p=0,0001). As demais provas de coagulação não apresentaram diferença significativa. As médias do estradiol foram significativamente diferentes, sendo 167pg/ml na primeira amostra e 1435pg/ml na segunda (p=0,0001). CONCLUSÕES: Os Dados refletem uma tendência a um estado de hipercoagüabilidade sangüínea, o que é esperado nas situações de hiperestrogenismo. Apesar da significância estatística nos níveis de fibrinogênio e hematócrito, esses resultados têm pouca expressão clínica, visto que os valores máximos das duas amostras permaneceram dentro dos limites da normalidade. A pesquisa sugere que, apesar do grande aumento nos níveis de estradiol e mudanças nas provas de coagulação, os programas de FIV mostram-se seguros quanto aos riscos tromboembólicos.BACKGROUND: Hyperestrogenic conditions have been related to alterations in the coagulation parameters. The objective of this study was to identify changes in coagulation parameters in women undergoing in vitro fertilization and embryo transfer (IVF-ET). METHODS: A group of 15 patients was studied prospectively, immediately before and during the course of an IVF-ET cycle. Blood was drawn in the preovulatory period of the cycle preceeding IVF-ET for complete blood count, fibrinogen, prothrombin time (TP), thromboplastin partial actived time (ATTP), coagulation time and estradiol. A another blood sample for the same tests was collected during controlled ovarian hyperstimulation, on the hCG day. Both samples were compared by a paired t-test RESULTS: There was an increase in fibrinogen (340.9 pg/mL to 383.1 pg/mL, p = 0.01). On the other hand, hematocrit levels decreased (40.5% to 38.4 %, p = 0.0001). The other coagulation tests showed no difference. Estradiol levels increased (167 pg/mL to 1435 pg/ml, p=0.0001), as expected during such treatment. CONCLUSIONS: The data suggest a tendency towards an increase in coagulability, as expected in hyperestrogenic situations. However, even considering the statistical significance of the results, they might have limited clinical impact, since they were within the normal range. This study suggests that, despite the marked increase in estradiol and changes in coagulation parameters, IVF-ET is a safe procedure in terms of thromboembolic risks.

OBJETIVO: Identificar alterações na coagulação sangüínea em mulheres submetidas à fertilização in vitro (FIV). MÉTODOS: Trata-se de um estudo prospectivo onde foram incluídas 15 pacientes submetidas à FIV. No período pré-ovulatório imediato, do ciclo menstrual precedente à FIV, foi coletada amostra sangüínea para coagulograma, com dosagem de Estradiol, Hemograma, Fibrinogênio, Tempo de Protrombina, Tempo de Tromboplastina Parcial Ativada, Tempo de Coagulação e Plaquetas. Durante a hiperestimulação ovariana para FIV, nova amostra para coagulograma foi coletada no dia da aplicação da Gonadotrofina Coriônica Humana. Os dados referentes à análise das duas amostras foram avaliados usando teste estatístico Paired T-Test. RESULTADOS: O estudo comparativo das médias das amostras identificou aumento significativo nos níveis de fibrinogênio, 304,9 pg/ml na primeira amostra e 383,1 pg/ml na segunda (p=0,01), já os níveis de hematócrito tiveram um decréscimo significativo, com valores de 40,5% e 38,4%, respectivamente (p=0,0001). As demais provas de coagulação não apresentaram diferença significativa. As médias do estradiol foram significativamente diferentes, sendo 167pg/ml na primeira amostra e 1435pg/ml na segunda (p=0,0001). CONCLUSÕES: Os Dados refletem uma tendência a um estado de hipercoagüabilidade sangüínea, o que é esperado nas situações de hiperestrogenismo. Apesar da significância estatística nos níveis de fibrinogênio e hematócrito, esses resultados têm pouca expressão clínica, visto que os valores máximos das duas amostras permaneceram dentro dos limites da normalidade. A pesquisa sugere que, apesar do grande aumento nos níveis de estradiol e mudanças nas provas de coagulação, os programas de FIV mostram-se seguros quanto aos riscos tromboembólicos. BACKGROUND: Hyperestrogenic conditions have been related to alterations in the coagulation parameters. The objective of this study was to identify changes in coagulation parameters in women undergoing in vitro fertilization and embryo transfer (IVF-ET). METHODS: A group of 15 patients was studied prospectively, immediately before and during the course of an IVF-ET cycle. Blood was drawn in the preovulatory period of the cycle preceeding IVF-ET for complete blood count, fibrinogen, prothrombin time (TP), thromboplastin partial actived time (ATTP), coagulation time and estradiol. A another blood sample for the same tests was collected during controlled ovarian hyperstimulation, on the hCG day. Both samples were compared by a paired t-test RESULTS: There was an increase in fibrinogen (340.9 pg/mL to 383.1 pg/mL, p = 0.01). On the other hand, hematocrit levels decreased (40.5% to 38.4 %, p = 0.0001). The other coagulation tests showed no difference. Estradiol levels increased (167 pg/mL to 1435 pg/ml, p=0.0001), as expected during such treatment. CONCLUSIONS: The data suggest a tendency towards an increase in coagulability, as expected in hyperestrogenic situations. However, even considering the statistical significance of the results, they might have limited clinical impact, since they were within the normal range. This study suggests that, despite the marked increase in estradiol and changes in coagulation parameters, IVF-ET is a safe procedure in terms of thromboembolic risks.

Objective To report a case of ureterovaginal fistula secondary to transvaginal oocyte retrieval (TVOR). Design Case report. Setting IVF Center IN a private hospital. Patient(s) A 31-year-old woman presented immediately after TVOR with right lower abdominal pain with irradiation to the suprapubic area and vaginal discharge. Intervention(s) Vaginal examination, creatinine dosage in plasma and vaginal discharge, excretory urography. A double-J catheter was inserted under general anesthesia. Main Outcome Measure(s) Clinical follow-up. Result(s) Vaginal leakage ceased a few hours after catheter insertion. Transfer of two embryos was performed 3 days after TVOR, but no pregnancy occurred. The double-J catheter was removed 21 days after its placement. Imaging studies done 6 weeks later demonstrated a normal urinary tract morphology. Conclusion(s) Given the elective nature of TVOR and IVF, patients should be informed about all potential complications, including ureterovaginal fistula.

A falência ovariana prematura (FOP) acomete aproximadamente 1:1000 mulheres antes dos 30 anos, 1:250 em torno dos 35 anos e de 1:100 aos 40 anos. Manifesta-se como amenorréia primária ou amenorréia secundária, não podendo ser considerada definitiva em todas as pacientes, uma vez que a concepção espontânea pode ocorrer em até 5–10% das FOP. Na maioria dos casos apresenta-se na forma esporádica, pois apenas 5% apresentam história familial. Entre as causas conhecidas estão as alterações cromossômicas, dos genes ligados ao cromossomo X e cromossomos autossômicos, doenças autoimunes, alterações tóxicas e iatrogênicas. Com relativa freqüência, a causa etiológica não é obtida, sendo então denominada de idiopática. O diagnóstico da FOP é feito baseado na história clínica e níveis elevados do hormônio folículo estimulante (FSH), sendo posteriormente investigadas as causas mais específicas. O manejo clínico visa o suporte emocional, o tratamento hormonal com estrogênios e progestogênios, a abordagem da infertilidade e a prevenção de co-morbidades como a osteoporose e potencial maior risco cardiovascular. Premature ovarian failure occurs in approximately 1:1000 women before 30 years, 1:250 by 35 years and 1:100 by the age of 40. It is characterized by primary or secondary amenorrhea and cannot be considered as definitive because spontaneous conception may occur in 5 to 10% of cases. In 95% of cases, premature ovarian failure is sporadic. The known causes of premature ovarian failure include chromosomal defects, autoimmune diseases, exposure to radiation or chemotherapy, surgical procedures, and certain drugs. Frequently, however, the etiology is not clear and these cases are considered to be idiopathic. Premature ovarian failure is defined by gonadal failure and high serum follicle-stimulating hormone (FSH) levels. Clinical approach includes emotional support, hormonal therapy with estrogens and progesterone or progestogens, infertility treatment, and prevention of osteoporosis and potential cardiovascular risk.

Premature ovarian failure occurs in approximately 1:1000 women before 30 years, 1:250 by 35 years and 1:100 by the age of 40. It is characterized by primary or secondary amenorrhea and cannot be considered as definitive because spontaneous conception may occur in 5 to 10% of cases. In 95% of cases, premature ovarian failure is sporadic. The known causes of premature ovarian failure include chromosomal defects, autoimmune diseases, exposure to radiation or chemotherapy, surgical procedures, and certain drugs. Frequently, however, the etiology is not clear and these cases are considered to be idiopathic. Premature ovarian failure is defined by gonadal failure and high serum follicle-stimulating hormone (FSH) levels. Clinical approach includes emotional support, hormonal therapy with estrogens and progesterone or progestogens, infertility treatment, and prevention of osteoporosis and potential cardiovascular risk.

Hyperestrogenic conditions have been related to alterations in the coagulation parameters. The objective of this study was to identify changes in coagulation parameters in women undergoing in vitro fertilization and embryo transfer (IVF-ET).A group of 15 patients was studied prospectively, immediately before and during the course of an IVF-ET cycle. Blood was drawn in the preovulatory period of the cycle preceeding IVF-ET for complete blood count, fibrinogen, prothrombin time (TP), thromboplastin partial actived time (ATTP), coagulation time and estradiol. A another blood sample for the same tests was collected during controlled ovarian hyperstimulation, on the hCG day. Both samples were compared by a paired t-test.There was an increase in fibrinogen (340.9 pg/mL to 383.1 pg/mL, p = 0.01). On the other hand, hematocrit levels decreased (40.5% to 38.4 %, p = 0.0001). The other coagulation tests showed no difference. Estradiol levels increased (167 pg/mL to 1435 pg/ml, p=0.0001), as expected during such treatment.The data suggest a tendency towards an increase in coagulability, as expected in hyperestrogenic situations. However, even considering the statistical significance of the results, they might have limited clinical impact, since they were within the normal range. This study suggests that, despite the marked increase in estradiol and changes in coagulation parameters, IVF-ET is a safe procedure in terms of thromboembolic risks.

Objective To assess the results obtained in our clinic with intracytoplasmic sperm injection (ICSI) in severe male factor infertility and failed fertilization and to determine if the age of the female has any impact on those results. Design Retrospective study. Setting Private high-complexity Human Reproduction Center. Patients One hundred five couples with a total of 114 procedures. Eighty-six were classified as severe male factor and 19 were classified as previous failed fertilization. Interventions Treatment was performed by ICSI. Main Outcome Measure Normal fertilization, cleavage, and implantation, total, term, and ongoing pregnancy rates in the total population and in different age brackets. Results Excellent fertilization, cleavage, and implantation rates were obtained with this procedure (78%, 85%, and 13.5%, respectively). The total pregnancy rates were 43% and 46% per cycle and per transfer and 31.5% and 33.6% in terms of term and ongoing pregnancy rates. A significant reduction in implantation and total, and term and ongoing pregnancy rates was seen after the age of 35 years. Conclusions The results obtained with ICSI are quite satisfactory with proper equipment and careful training. The age of the female is an important parameter in determining prognosis and treatment outcome.