Treatment of infertility in women with polycystic ovary syndrome: approach to clinical practice

Polycystic ovary syndrome represents 80% of anovulatory infertility cases. Treatment initially includes preconception guidelines, such as lifestyle changes (weight loss), folic acid therapy to prevent the risk of fetal neural tube defects and halting the consumption of tobacco and alcohol. The first-line pharmacological treatment for inducing ovulation consists of a clomiphene citrate treatment for timed intercourse. The second-line pharmacological treatment includes the administration of exogenous gonadotropins or laparoscopic ovarian surgery (ovarian drilling). Ovulation induction using clomiphene citrate or gonadotropins is effective with cumulative live birth rates of approximately 70%. Ovarian drilling should be performed when laparoscopy is indicated; this procedure is typically effective in approximately 50% of cases. Finally, a high-complexity reproduction treatment (in vitro fertilization or intracytoplasmic sperm injection) is the third-line treatment and is recommended when the previous interventions fail. This option is also the first choice in cases of bilateral tubal occlusion or semen alterations that impair the occurrence of natural pregnancy. Evidence for the routine use of metformin in infertility treatment of anovulatory women with polycystic ovary syndrome is not available. Aromatase inhibitors are promising and longer term studies are necessary to prove their safety

Endometrial injury in women undergoing assisted reproductive techniques

ACKNOWLEDGEMENTS We would like to express our appreciation to Dra Abha Maheshwari for her important authorial contribution to the previous version of this review. We also acknowledge the important help provided by the Cochrane Menstrual Disorders and Subfertility Group team, specially by Marian Showell, Trials Search Co-ordinator; by Helen Nagels, Managing Editor; and by Prof. Cindy Farquhar, Co-ordinating Editor. Finally, we would like to express our gratitude to the following investigators, who provided essential information for the preparation of this review: TK Aleyamma, Erin F Wolff, Lukasz Polanski, Nava Dekel, Neeta Singh, Suleyman Guven and Tracy YeungPeer reviewedPublisher PD

Imunologia da reprodução humana

O sistema imunológico, com sua função tradicional de defender o organismo humano contra agressões externas e endógenas, é visto, hoje, num âmbito mais amplo de caráter homeostático. Assim, participa de vários mecanismos fisiológicos, dentre os quais se inclui a reprodução humana, onde tem importante papel desde a deposição dos espermatozóides até o nascimento do feto. Entretanto, pouco conhecimento é disponível a respeito da importância precisa do sistema imunológico nas várias etapas do processo reprodutivo. Nesta revisão, foram considerados vários aspectos imunológicos da reprodução humana e de quadros clínicos correlatos, como o aborto recorrente e a endometriose, além de estratégias terapêuticas, como a fertilização in vitro e a imunoterapia celularThe immunological system, which defends the human organism against external and endogenous aggression, is viewed today within a broader homeostatic role. This system also participates in various physiological mechanisms including the reproduction where it plays an important role from the deposition of sperm to the birth of the fetus. However, little is known about the precise importance of the immunological system during the various stages of the reproductive process. In the present review, several immunologic aspects of human reproduction were considered along with correlated clinical conditions such as recurrent abortion and endometriosis and their therapeutic approaches, such as in vitro fertilization and cellular immunotherapy

Natural latex (Hevea brasiliensis) mold for neovaginoplasty

OBJETIVO: avaliar a utilização do molde de látex natural (Hevea brasiliensis) como modificação à neovaginoplastia de McIndoe e Bannister em pacientes portadoras da síndrome de Mayer-Rokitansky-Küster-Hauser (MRKH). MÉTODOS: análise retrospectiva de nove pacientes com o diagnóstico de síndrome de MRKH, submetidas à neovaginoplastia pela técnica de McIndoe e Bannister com molde de látex natural. Foram avaliadas epitelização, amplitude e profundidade das neovaginas, ocorrência de coitos bem como satisfação e complicações cirúrgicas. RESULTADOS: após cinco semanas do procedimento, oito pacientes apresentavam neovaginas epitelizadas, com profundidade de 7 a 12 cm. Houve um caso de estenose neovaginal completa em decorrência do uso incorreto do molde pela paciente no pós-operatório. Após seguimento mínimo de um ano, todas as pacientes mantinham neovaginas com profundidade de 4 a 8 cm e capacidade para o coito, com 66,7% de satisfação. Uma paciente apresentou fístula retovaginal precoce e episódios tardios de fistulização uretrovaginal. Duas pacientes apresentaram estenose distal das neovaginas a longo prazo. Uma delas e a paciente com fístulas foram submetidas a novo procedimento. CONCLUSÕES: o uso do molde de látex natural como modificação à técnica clássica de neovaginoplastia permitiu a criação de neovaginas morfológica e funcionalmente similares ao órgão normal em pacientes com estenose vaginal.PURPOSE: to evaluate the use of natural latex mold (Hevea brasiliensis) as a modification of McIndoe and Bannister neovaginoplasty in patients presenting Mayer-Rokitansky-Küster-Hauser (MKRH) syndrome. METHODS: we retrospectively included nine patients presenting MKRH syndrome, who had been submitted to McIndoe and Bannister neovaginoplasty modified by the use of natural latex mold. Neovaginal epithelization and depth, coitus occurrence and satisfaction, and surgical complications were evaluated. RESULTS: five weeks after the procedure, eight patients presented an epithelized 7 to 12 cm deep neovagina. There was one case of complete neovaginal stenosis, because of incorrect use of the mold. After at least one year, the others maintained 4 to 8 cm deep neovaginas and capacity for intercourse, with 66.7% satisfaction. One woman presented precocious rectovaginal fistula and late episodes of uretrovaginal fistulae. Two patients presented distal neovaginal stenosis in long-term follow-up. One of these and the patient with fistulae were submitted to a new procedure. CONCLUSIONS: the use of natural latex mold as a modification of classic neovaginoplasty technique allows the creation of neovaginas morphologically and functionally similar to the normal vagina in patients with vaginal agenesis

Cardiovascular risk markers in polycystic ovary syndrome in women with and without insulin resistance

OBJETIVO: avaliar se a presença de resistência à insulina (RI) modifica fatores de risco cardiovascular em mulheres com síndrome dos ovários policísticos (SOP). MÉTODOS: estudo transversal no qual 60 mulheres com SOP, com idade entre 18 e 35 anos e sem uso de hormônios, foram avaliadas. A RI foi avaliada por meio do quantitative insulin sensitivity check index (QUICKI). RI foi definida como QUICKI <0,33. As seguintes variáveis foram comparadas entre o grupo com e sem RI: antropométricas (peso, altura, circunferência da cintura, pressão arterial e frequência cardíaca), laboratoriais (homocisteína, interleucina-6, fator de necrose tumoral-&#945;, testosterona, fração de androgênios livre, colesterol total e frações, triglicerídeos, proteína C reativa e insulina, glicose) e ultrassonográficas (distensibilidade e espessura íntima-média da carótida e dilatação mediada por fluxo da artéria braquial). RESULTADOS: Dezoito mulheres (30%) apresentaram RI. As mulheres com RI, comparadas às sem RI, apresentaram diferenças significativas nos seguintes marcadores antropométricos (SOP com RI e sem RI respectivamente): índice de massa corporal (35,5±5,6 versus 23,9±4,8 kg/m², p<0,01;), cintura (108,1±11,53 versus 79,5±11,1 cm, p<0,01) e pressão arterial sistólica (128,0±10,8 versus 114,0±8,9 mmHg, p<0,01) e pressão arterial diastólica (83,6±9,6 versus 77,0±7,5 mmHg, p=0,01). Também foram observadas diferenças significativas nos seguintes marcadores laboratoriais: triglicerídeos (120,0±56,5 versus 77,7±53,4 mg/dL, p=0,01), HDL (43,06±6,3 versus 40,4±10,8, p=0,01) e proteína C reativa (7,9±10,5 mg/L versus 2,6±3,2 mg/L, p<0,01), insulina (28,0±18,1 versus 5,3±2,4 µU/mL, p<0,01) e glicose (93,5±10,0 versus 87,5±8,7 mg/dL, p=0,02). Adicionalmente, dois dos três marcadores ultrassonográficos de risco cardiovascular também foram diferentes entre os grupos: distensibilidade carotídea (0,24±0,05 versus 0,30±0,08 mmHg-1, p<0,01) e espessura íntima-média da carótida (0,52±0,08 versus 0,43±0,09 mm, p<0,01). Além disso, a proporção de síndrome metabólica foi maior nas mulheres com RI (nove casos=50% versus três casos=7,1%, p<0,01). CONCLUSÕES: mulheres com SOP e RI apresentam diferenças significativas em vários marcadores ultrassonográficos, séricos e antropométricos que apontam para uma elevação no risco cardiovascular, quando comparadas a mulheres com SOP sem RI. Diante desses dados, a determinação sistemática da avaliação de RI em mulheres com SOP pode ajudar a identificar pacientes de risco cardiovascular.PURPOSE: to evaluate whether the presence of insulin resistance (IR) alters cardiovascular risk factors in women with polycystic ovary syndrome (POS). METHODS: transversal study where 60 POS women with ages from 18 to 35 years old, with no hormone intake, were evaluated. IR was assessed through the quantitative insulin sensitivity check index (QUICKI) and defined as QUICKI <0.33. The following variables have been compared between the groups with or without IR: anthropometric (weight, height, waist circumference, arterial blood pressure, cardiac frequency), laboratorial (homocysteine, interleucines-6, factor of tumoral-&#945; necrosis, testosterone, fraction of free androgen, total cholesterol and fractions, triglycerides, C reactive protein, insulin, glucose), and ultrasonographical (distensibility and carotid intima-media thickness, dilation mediated by the brachial artery flux). RESULTS: Eighteen women (30%) presented IR and showed significant differences in the following anthropometric markers, as compared to the women without IR (POS with and without IR respectively): body mass index (35.56±5.69 kg/m² versus 23.90±4.88 kg/m², p<0.01), waist (108.17±11.53 versus 79.54±11.12 cm, p<0.01), systolic blood pressure (128.00±10.80 mmHg versus 114.07±8.97 mmHg, p<0.01), diastolic blood pressure (83.67±9.63 mmHg versus 77.07±7.59 mmHg, p=0.01). It has also been observed significant differences in the following laboratorial markers: triglycerides (120.00±56.53 mg/dL versus 77.79±53.46 mg/dL, p=0.01), HDL (43.06±6.30 mg/dL versus 40.45±10.82 mg/dL, p=0.01), reactive C protein (7.98±10.54 mg/L versus 2.61±3.21 mg/L, p<0.01), insulin (28.01±18.18 µU/mL versus 5.38±2.48 µU/mL, p<0.01), glucose (93.56±10.00 mg/dL versus 87.52±8.75 mg/dL, p=0.02). Additionally, two out of the three ultrasonographical markers of cardiovascular risk were also different between the groups: carotid distensibility (0.24±0.05 mmHg-1 versus 0.30±0.08 mmHg-1, p<0.01) and carotid intima-media thickness (0.52±0.08 mm versus 0.43±0.09, p<0.01). Besides, the metabolic syndrome ratio was higher in women with IR (nine cases=50% versus three cases=7.1%, p<0.01). CONCLUSIONS: POS and IR women present significant differences in several ultrasonographical, seric and anthropometric markers, which point out to higher cardiovascular risk, as compared to women without POS and IR. In face of that, the systematic IR evaluation in POS women may help to identify patients with cardiovascular risk

Obesity and altered arterial structure in young women with micropolycystic ovary syndrome

OBJETIVO: comparar os fatores ecográficos de risco cardiovascular em pacientes obesas e não obesas, com síndrome dos ovários micropolicísticos (SOMP). MÉTODOS: foram incluídas 30 pacientes obesas com SOMP (Índice de massa corporal, IMC>30 kg/m²) e 60 não obesas (IMC<30 kg/m²), com idade entre 18 e 35 anos neste estudo transversal. Foram avaliados: a dilatação mediada por fluxo (DMF) da artéria braquial, espessura íntima-média da artéria carótida (IMT), o índice de rigidez da artéria carótida (&#946;), as medidas antropométricas, pressão sanguínea sistólica (PAS) e diastólica (PAD). As mulheres estavam sem nenhum tratamento prévio e nenhuma delas apresentava qualquer comorbidade (além da SOMP e/ou da obesidade).Na análise estatística, foram utilizados os testes t não-pareado ou de Mann-Whitney. RESULTADOS: as pacientes obesas com SOMP apresentaram maior peso em relação às não obesas (92,1±11,7 kg versus 61,4±10,7 kg, p<0,0001), bem como a medida da cintura que também, foi mais elevada nas pacientes obesas (105,0±10,4 cm versus 78,5±9,8 cm, p<0,0001). A PAS das pacientes obesas foi superior quando comparadas às não obesas (126,1±10,9 mmHg versus 115,8±9,0 mmHg, p<0,0001) e a IMT também foi maior nas obesas (0,51±0,07 mm versus 0,44±0,09 mm, p<0,0001). Não houve diferença entre os grupos quanto à dilatação mediada por fluxo (DMF) da artéria braquial ou ao índice de rigidez da artéria carótida (&#946;). CONCLUSÕES: a obesidade em portadoras jovens de SOMP está associada a níveis pressóricos mais elevados e à alteração da estrutura arterial, representada pela maior espessura íntima-média da artéria carótida.PURPOSE: to compare echographical cardiovascular risk factors between obese and non-obese patients with micropolycystic ovarian syndrome (MPOS). METHODS: in this transversal study, 30 obese (Body Mass Index, BMI>30 kg/m²) and 60 non-obese (BMI<30 kg/m²) MPOS patients, aging between 18 and 35 years old, were included. The following variables were measured: flow-mediated dilatation (FMD) of the brachial artery, thickness of the intima-media of the carotid artery (IMT), anthropometric data, systolic arterial pressure (SAP) and diastolic arterial pressure (DAP). The women had no previous medical treatment and no comorbidity besides MPOS and obesity. For statistical analysis, the non-paired tand Mann-Whitney's tests were used. RESULTS: obese weighted more than non-obese patients (92.1±11.7 kg versus 61.4±10.7 kg, p<0.0001) and had a larger waist circumference (105.0±10.4 cm versus 78.5±9.8 cm, p<0.0001). The SBP of obese patients was higher than that of the non-obese ones (126.1±10.9 mmHg versus 115.8±9.0 mmHg, p<0.0001) and the IMT was also bigger (0.51±0.07 mm versus 0.44±0.09 mm, p<0.0001). There was no significant difference between the groups as to FMD and carotid rigidity index (&#946;). CONCLUSIONS: obesity in young women with MPOS is associated with higher blood pressure and alteration of arterial structure, represented by a thicker intima-media of the carotid artery

Assessment of symptoms of urinary incontinence in women with polycystic ovary syndrome

OBJECTIVES: The pelvic floor muscles are sensitive to androgens, and due to hyperandrogenism, women with polycystic ovary syndrome can have increased mass in these muscles compared to controls. The aim of this study is to compare reports of urine leakage and quality of life between women with and without polycystic ovary syndrome. METHODS: One hundred thirteen 18-to 40-year-old nulliparous women with polycystic ovary syndrome or without the disease (controls) were recruited at the University Hospital of School Medicine of São Paulo University at Ribeirão Preto City, Brazil. The subjects were not taking any hormonal medication, had not undergone previous pelvic surgery and did not exercise their pelvic floor muscles. The women were divided into the following four groups: I-polycystic ovary syndrome with normal body mass index (n = 18), II-polycystic ovary syndrome with body mass index >25 (n = 32), III-controls with normal body mass index (n = 29), and IV-controls with Body Mass Index >25 (n = 34). Quality of life was evaluated using the SF-36 questionnaire, and the subjects with urinary complaints also completed the International Consultation on Incontinence Questionnaire Short Form to evaluate the severity of their urinary incontinence. RESULTS: The replies to the International Consultation on Incontinence Questionnaire Short Form revealed a significant difference in urinary function between groups, with 24% of the subjects in group IV reporting urinary incontinence. The mean scores for the SF-36 questionnaire revealed that group II had the lowest quality of life. CONCLUSIONS: The control obese group (IV) reported a higher prevalence of urinary incontinence. There was no difference in the reported frequency of urine loss between the polycystic ovary syndrome and control groups with normal body mass index or between the polycystic ovary syndrome and control groups with body mass index >25

Serum markers of oxidative stress in infertile women with endometriosis

OBJETIVO: comparar marcadores séricos de estresse oxidativo entre pacientes inférteis com e sem endometriose e avaliar a associação destes marcadores com o estadiamento da doença. MÉTODOS: estudo prospectivo envolvendo a inclusão consecutiva de 112 pacientes inférteis, não-obesas, com idade inferior a 39 anos, divididas em dois grupos: Endometriose (n=48, sendo 26 com endometriose mínima e leve - Estádio I/II e 22 com endometriose moderada e grave - Estádio III/IV) e Controle (n=64, com fator tubário e/ou masculino de infertilidade). Durante a fase folicular precoce do ciclo menstrual, foram coletadas amostras sanguíneas para análise dos níveis séricos de malondialdeído, glutationa e níveis totais de hidroperóxidos, por espectrofotometria e vitamina E, por cromatografia líquida de alto desempenho. Os resultados obtidos foram comparados da seguinte forma: os grupos endometriose versus controle; endometriose estádio I/II e controle, endometriose estádio III/IV e controle e entre os dois subgrupos de endometriose. Em todas as análises, foi considerado o nível de significância de 5% (p<0,05). RESULTADOS: os níveis de vitamina E e glutationa foram mais baixos no soro de mulheres inférteis com endometriose moderada/grave (21,7±6,0 µMol/L e 159,6±77,2 nMol/g proteína, respectivamente) quando comparadas a mulheres com endometriose mínima e leve (28,3±14,4 µMol/L e 199,6±56,1 nMol/g proteína, respectivamente). Os níveis totais de hidroperóxidos foram significativamente mais elevados no grupo endometriose (8,9±1,8 µMol/g proteína) em relação ao Grupo Controle (8,0±2 µMol/g proteína) e nas portadoras de doença III/IV (9,7±2,3 µMol/g proteína) em relação à I/II (8,2±1,0 µMol/g proteína). Não se observou diferença significativa nos níveis séricos de malondialdeído entre os diversos grupos. CONCLUSÕES: foi evidenciada uma associação positiva entre infertilidade relacionada à endometriose, avanço do estadiamento da doença e aumento dos níveis séricos de hidroperóxidos, sugerindo aumento da produção de espécies reativas em portadoras de endometriose. Esses dados, associados à redução dos níveis séricos de vitamina E e glutationa, sugerem a ocorrência de estresse oxidativo sistêmico em portadoras de infertilidade associada à endometriose.PURPOSE: to compare serum markers of oxidative stress between infertile patients with and without endometriosis and to assess the association of these markers with disease staging. METHODS: this was a prospective study conducted on 112 consecutive infertile, non-obese patients younger than 39 years, divided into two groups: Endometriosis (n=48, 26 with minimal and mild endometriosis - Stage I/II, and 22 with moderate and severe endometriosis - Stage III/IV) and Control (n=64, with tubal and/or male factor infertility). Blood samples were collected during the early follicular phase of the menstrual cycle for the analysis of serum malondialdehyde, glutathione and total hydroxyperoxide levels by spectrophotometry and of vitamin E by high performance liquid chromatography. The results were compared between the endometriosis and control groups, stage I/II endometriosis and control, stage III/IV endometriosis and control, and between the two endometriosis subgroups. The level of significance was set at 5% (p<0.05) in all analyses. RESULTS: vitamin E and glutathione levels were lower in the serum of infertile women with moderate/severe endometriosis (21.7±6.0 mMol/L and 159.6±77.2 nMol/g protein, respectively) compared to women with minimal and mild endometriosis (28.3±14.4 mMol/L and 199.6±56.1 nMol/g protein, respectively). Total hydroxyperoxide levels were significantly higher in the endometriosis group (8.9±1.8 µMol/g protein) than in the Control Group (8.0±2 µMol/g protein) and among patients with stage III/IV disease (9.7±2.3 µMol/g protein) compared to patients with stage I/II disease (8.2±1.0 µMol/g protein). No significant differences in serum malondialdehyde levels were observed between groups. CONCLUSIONS: we demonstrated a positive association between infertility related to endometriosis, advanced disease stage and increased serum hydroxyperoxide levels, suggesting an increased production of reactive species in women with endometriosis. These data, taken together with the reduction of serum vitamin E and glutathione levels, suggest the occurrence of systemic oxidative stress in women with infertility associated with endometriosis. The reproductive and metabolic implications of oxidative stress should be assessed in future studies

Metabolic abnormalities in polycystic ovary syndrome women: obese and non obese

OBJETIVO: Comparar as características metabólicas de mulheres jovens do sudeste brasileiro, obesas e não obesas com síndrome dos ovários policísticos (SOP). MÉTODOS: Estudo transversal que incluiu 218 mulheres de idade reprodutiva com diagnóstico de SOP - 90 mulheres não obesas (IMC entre 18,5 e 29,9 kg/m²) e 128 pacientes obesas (IMC &gt;30 kg/m²), selecionadas no momento do diagnóstico. Foram comparadas as frequências de resistência insulínica (RI), intolerância à glicose (IG), síndrome metabólica (MetS) e diabetes mellitus tipo 2 (DM2) e os valores médios de colesterol total (CT), triglicérides (TG), lipoproteínas de alta (LDL) e baixa densidade (HDL), entre as pacientes obesas e não obesas com SOP. Foram comparadas também as características clínicas e hormonais (hormônio folículo estimulante, luteinizante, prolactina, hormônio tireoestimulante, testosterona total, sulfato de dehidroepiandrostenediona e 17-hidroxiprogesterona) nos dois grupos. A análise estatística foi realizada com o auxílio do software SAS 9.0. Para análise das variáveis com distribuição normal, utilizou-se o teste t de Student não pareado; na ausência desta característica, o teste utilizado foi Mann-Whitney bicaudal. Para as variáveis qualitativas utilizou-se o teste Exato de Fisher. Em todas as análises, foi considerado o nível de significância de 5% (p<0,05). RESULTADOS: As frequências de RI, IG e MetS foram significativamente mais elevadas em pacientes com SOP obesas do que não obesas (66,7, 29,9 e 63% versus 24,7, 12,2 e 16.4%, respectivamente). As pacientes obesas apresentaram maiores níveis de CT e TG (189,8±35.8 mg/dL e 145.4±71.1 mg/dL, respectivamente) do que as não obesas (172,1±38.4 mg/dL e 99,3±54 mg/dL, respectivamente). Ambos os grupos apresentaram níveis médios de HDL abaixo de 50 mg/dL. CONCLUSÕES: Mulheres obesas jovens com SOP apresentam maior frequência de RI, IG e SM do que as não obesas. Todavia, a ocorrência dos distúrbios metabólicos é elevada também na pacientes não obesas, sugerindo que a presença da síndrome favoreça o desenvolvimento de comorbidades metabólicas, com potenciais repercussões a médio e longo prazos.PURPOSE: To compare the metabolic characteristics of obese and non-obese young women with polycystic ovary syndrome (POS) from the Brazilian Southeast. METHODS: This was a cross-sectional study conducted on 218 women of reproductive age with a diagnosis of POS - 90 non-obese women (BMI between 18.5 and 29.9 kg/m²), and 128 obese patients (BMI &gt;30 kg/m²) selected at the time of diagnosis. The frequency of insulin resistance (IR), glucose intolerance (GI), metabolic syndrome (MetS) and type 2 diabetes mellitus (DM2) and mean values of total cholesterol (TC), triglycerides (TG), high-density (HDL) and low-density lipoproteins (LDL), were compared between obese and non-obese patients with POS. The two groups were also compared in terms of clinical and hormonal characteristics (follicle stimulating hormone, prolactin, thyroid stimulating hormone, total testosterone, dihydroepiandrostenedione sulfate, and 17-hydroxyprogesterone). Statistical analysis was performed using the SAS 9.0 software. Quantitative variables were compared by the Student´s t-test (data with normal distribution) or by the Mann-Whitney test (non-parametric distribution). Qualitative variables were compared by the Fisher test. The level of significance was set at 5% (p<0.05) in all analyses. RESULTS: The frequency of IR, GI and MetS was significantly higher in obese than non-obese patients with POS (66.7, 29.9, and 63% versus 24.7, 12.2, and 16.4%, respectively). Obese patients had higher TC and TG levels (189.8±35.8 mg/dL and 145.4±71.1 mg/dL, respectively) than non-obese patients (172.1±38.4 mg/dL and 99.3±54 mg/dL, respectively). Both groups had mean HDL levels below 50 mg/dL. CONCLUSIONS: Young obese women with POS have a higher frequency of IR, GI and MS than non-obese. However, the occurrence of metabolic disorders is elevated also in the non-obese patients, suggesting that the presence of the syndrome may favor the development of metabolic comorbidities with potential medium- and long-term repercussions