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Anovulation accounts for approximately 12 percent of all female infertility in the United States. Prior studies suggest women with high body mass index (BMI) have an increased risk of infertility, particularly obese women with abnormal cycle lengths. To date no studies have examined the relationship between measures of adiposity, including BMI and percent body fat measured by DXA scan (%BF), and anovulation among women with regular menstrual cycles assessed with biomarkers. We evaluated this association using data from the BioCycle study, a prospective cohort of 259 women with regular menstrual cycles. All measures of adiposity and covariates were collected at baseline. Anovulation was assessed via luteinizing hormone and progesterone levels in urine samples collected 16 times throughout two menstrual cycles. A total of 34 women had at least one anovulatory cycle during the study. Unadjusted models for BMI show a significant decrease in risk comparing highest BMI quartile to the lowest, (OR: 0.29; 95% CI .090-.968). Once multivariable logistic regression was used to adjust for age no significant associations were found in any BMI quartile, but point estimates did not change significantly. Similar trends were found using other measures of adiposity. Results show that there is a non-significant inverse trend between adiposity and anovulation in healthy women with regular menstrual cycles. This relationship can possibly be explained by age due to the influence of time since menarche (TSM). Further research is needed to examine this relationship.

Between 10-15% of women suffer from polycystic ovary syndrome (PCOS), making it the most common cause of female infertility. Clinical features of PCOS include high circulating levels of ovarian androgens (T and A4), anovulation and obesity. The aetiology of this reproductive endocrinopathy is likely to be multifactorial, through the interplay of genetics, epigenetics and environmental factors. Primate research into sexual behaviour development noted that fetally androgenised monkeys developed symptoms like those of PCOS. There are now multiple animal models of PCOS using primates, sheep, rats and transgenic mice. The investigations described in this thesis use rodent models to examine the role of androgens in the pathogenesis of female infertility. An attempt to generate a granulosa cell specific androgen receptor knockout mouse model will first be described, followed by several studies into the developmental programming of female Wistar rat infertility and metabolism by steroid hormones. Initial investigations showed that testosterone proprionate (TP) administered to female rats during different windows of fetal and neonatal life alters the reproductive and metabolic axes of the adult animals. Fetal plus neonatal TP exposure led to complete ovarian dysgenesis, while postnatal exposure produced a PCOS-like phenotype. Animals which received TP postnatally were heavier and had an increased proportion of primordial follicles in their ovaries by postnatal day (pnd) 90 of life. Evaluation of this PCOS model showed that neonatally androgenised rats had ovarian follicles with larger antra and a greater ovarian stromal compartment. In addition, these animals were heavier when compared to controls. However, unlike human studies, neonatally androgenised rats showed no differences in circulating gonadotrophin or ovarian androgen levels. Nor did they show any programming effect of neonatal TP upon the theca interna by pnd 90. Further investigations to narrow the windows and dose of TP required to produce a PCOS phenotype showed that TP administered in an early window of neonatal life, between postnatal days (pnd) 1-6 not only led to anovulation, but potentially reprogrammed the hypothalamic-pituitary axis, as there was minimal gonadotrophin response to reduced ovarian negative feedback (inhibin B and estradiol) in these rats. Neonatal TP also affected the rat metabolic axis with adult animals becoming heavier after weaning without any change in food intake. Animals developed mesenteric and retroperitoneal obesity along with insulin resistance (IR). Increased hepatic glucocorticoid turnover and altered adipokine expression were also noted in neonatally androgenised females, possibly contributing to the pathogenesis of obesity. No effect of TP dose upon the severity of infertility or metabolic abnormalities in adult animals was observed. To delineate which features of the rat PCOS model resulted from androgenic, estrogenic or corticosteroid action, a final study used administration of different steroids during the early window of postnatal life: TP, estradiol valerate (EV), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) and dexamethasone (DEX). The anovulatory PCO-like phenotype observed with TP was also seen in animals which received EV, but not those which received DHT, DHEA or DEX. TP and EV treatment also resulted in a reduction of ovarian follicle numbers and activated follicle proportions, with an increase in primordial follicle proportions. Although glucose tolerant, animals treated with TP and EV were highly IR. Unlike dexamethasone, DHT and DHEA also produced IR in adult animals, to a lesser extent than TP and EV. Taken collectively, the results described in this thesis demonstrate that the PCOS-like phenotype observed in the neonatally androgenised female rat is likely to be due to the estrogenic actions of testosterone, potentially through as yet unknown epigenetic mechanisms. The programming of the metabolic components described may additionally be due to the actions of androgens. Furthermore, these studies demonstrate a novel estrogenic effect of neonatal steroids upon primordial follicle populations and show that the neonatally androgenised rat may be a rational PCOS model in a poly-ovulatory species.

Made available in DSpace on 2014-06-11T19:32:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2006Bitstream added on 2014-06-13T19:02:57Z : No. of bitstreams: 1 lamaita_rm_dr_botfm.pdf: 547479 bytes, checksum: e9a0318c757e33e40fe31e2eccda034f (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação para o Desenvolvimento Médico e Hospitalar (Famesp) / A anovulação crônica é o distúrbio ovariano mais freqüente associado com quadros de infertilidade. Mecanismos inflamatórios apresentam um importante envolvimento na determinação da anovulação crônica. Esse estudo foi realizado para avaliar a resposta inflamatória no líquido folicular e soro de pacientes com infertilidade causada pôr anovulação crônica comparadas a pacientes ovulatórias e com ciclos Jegulares, submetidas à injeção intracitoplasmática de espermatozóides (ICSI). Métodos: Treze pacientes com anovulação crônica (casos) e 23 mulheres ovulatórias e com ciclos regulares (grupo controle) foram estudadas prospectivamente. As dosagens de N-acetilglucosaminidase (NAG), Mieloperoxidase (MPO), proteína quimioatrativa de monócitos-1 (MCP-1) e proteína C reativa (PCR) foram avaliadas no soro e líquido folicular obtidos no período da coleta dos oócitos. Resultados: A media de idade das pacientes variou de 20 a 37 anos (28,9±0,6 anos). O valor médio do índice de massa corporal (IMC) foi 21,7±0,4 kg/cm2 (17,6 to 28,0 kg/cm2). Não houve diferenças entre os grupos com relação à média de idade, IMC e dosagens de hormônio folículo estimulante (FSH). As pacientes com anovulação crônica apresentaram níveis maiores de hormônio luteinizante (LH), contagem de folículos antrais e volume ovariano. Nas pacientes com anovulação crônica foram observadas atividades elevadas de NAG (p=0,025) e MPO (p=0,030) no líquido folicular quando comparadas a mulheres ovulatórias, submetidas a ICSI. Os níveis de MCP-1 no líquido folicular foram maiores que no soro em todas as pacientes. O PCR no fluido folicular (p=0,025) e soro (p=0,024) estavam mais elevados nas pacientes com anovulação crônica que no grupo controle. A ocorrência de síndrome do hiperestímulo ovariano (SHO) foi associada... / Chronic anovulation is the most frequently occurring ovarian disorder associated with infertility. Inflammatory mechanisms may play an important role in determining chronic anovulation. This study was performed to evaluate the inflammatory response in follicular fluid and serum in patients with infertility caused by chronic anovulation and.•..no~_mally ovulating women undergoing intracytoplasmic sperm injection (ICSI). Methods: Thirteen patients with chronic anovulation (cases) and 23 normally ovulating women (control group) were prospectively studied. Nacetylglucosaminidase (NAG), Myeloperoxidase (MPO), Monocyte chemoattractant protein-1 (MCP-1) and Reactive C protein (PCR) concentrations were evaluated in serum and in follicular fluids obtained at the time of oocyte retrieval. Results: The age of the patients ranged from 20 to 37 years (28.9±0.6 years). The average body mass index (BMI) was 21.7±0.4 kg/cm2 (17.6 to 28.0 kg/cm2). There were no differences between groups regarding mean age, BMI, follicle-stimulating hormone (FSH). The patients with chronic anovulation were associated with higher levels of luteinizing hormone (LH), antral follicles count and ovarian size. The patients with chronic anovulation presented higher NAG (p=0.025) and MPO (p=0.030) activity in follicular fluid compared to normally ovulating women undergoing ICSI. The MCP-1 levels in follicular fluid were higher than the serum levels in ali patients. The PCR in follicular fluid (p=0.025) and serum (p=0.024) were higher in patients with PCR chronic anovulation to the control group. The occurrence of ovarian hyperstimulation syndrome (OHSS) was associated with higher follicular fluid levels of MCP-1 (p=0.038) and serum PCR (p=0.016). Conclusions: Patients with chronic anovulation are associated with higher follicle... (Complete abstract click electronic access below)

Thesis (M.S.)--University of Florida, 2004. / Typescript. Title from title page of source document. Document formatted into pages; contains 176 pages. Includes Vita. Includes bibliographical references.

Submitted by Diogo Misoguti (diogo.misoguti@gmail.com) on 2016-07-07T18:49:46Z No. of bitstreams: 1 cp078451.pdf: 1963747 bytes, checksum: 8df763273b9205acc5055fd0cbc3d714 (MD5) / Approved for entry into archive by Diogo Misoguti (diogo.misoguti@gmail.com) on 2016-07-07T18:50:39Z (GMT) No. of bitstreams: 1 cp078451.pdf: 1963747 bytes, checksum: 8df763273b9205acc5055fd0cbc3d714 (MD5) / Made available in DSpace on 2016-07-07T18:50:39Z (GMT). No. of bitstreams: 1 cp078451.pdf: 1963747 bytes, checksum: 8df763273b9205acc5055fd0cbc3d714 (MD5) Previous issue date: 2008 / Objetivo: Avaliar, do ponto de vista histológico, o efeito do transplante de tecido adiposo sobre o útero e os ovários de camundongas obesas e anovuladoras. Métodos: Foram utilizadas camundongas B6.V-Lepob/J com 2 e 3 meses de idade, subdivididas em grupos experimentais: 1.Controle (B6.V-Lepob/J fêmeas, com peso normal); 2.Obesidade (B6.V-Lepob/J fêmeas, obesas); 3.Obesidade + Transplante de tecido adiposo de camundongas doadoras com peso normal após 7 dias (B6.V-Lepob/J fêmeas e obesas, que receberam aproximadamente 1g de tecido adiposo de camundongas com peso normal isogênicas); 4.Obesidade + Transplante de tecido adiposo de camundongas doadoras com peso normal após 15 dias (B6.V-Lepob/J fêmeas e obesas, que receberam aproximadamente 1g de tecido adiposo de camundongas com peso normal isogênicas); 5.Obesidade + Transplante de tecido adiposo de camundongas doadoras com peso normal após 45 dias (B6.V-Lepob/J fêmeas e obesas, que receberam aproximadamente 1g de tecido adiposo de camundongas com peso normal isogênicas). Após 7, 15 e 45 dias do transplante, os animais foram sacrificados. Foram verificados o peso corporal e a glicemia, além da análise histológica dos úteros e dos ovários (H/E). Resultados e Conclusões: O grupo das obesas (n=6) apresentou elevação no peso corporal (52,0± 1,3*) e na glicemia (418,4±33,0*) em relação ao controle (24,0±0,7 e 100,2±2,2, respectivamente, n=5). Os transplantes após 7 dias (n=5) e 15 dias (n=9) foram eficazes na redução da glicemia (390,2±34,0 e 270,0±38,0*, pré e pós-Tx 7 dias; e 460,0±31,4 e 125,0±8,4*, pré e pós-Tx 15 dias, respectivamente), mas não modificaram o peso corporal. Porém, após 45 dias de transplante (n=7) houve redução da glicemia (467,0±28,0 e 209,0±18,0*, pré e pós-Tx, respectivamente), assim como tendência à diminuição no peso corpóreo observado pré e pós-Tx (50,4±2,4 e 44,0±3,3). Valores adotados para *p< 0,0001. A histologia revelou que, após 7 e 15 dias de Tx, os animais apresentavam ovários semelhantes aos das obesas, incluindo presença de inúmeros folículos, interstício abundante e ausência de corpos lúteos. Nos úteros notou-se intensa estimulação hormonal e glandular, mitoses, raros eosinófilos e epitélio superficial íntegro e sem renovação, sugerindo que tempos precoces de Tx são incapazes de reverter tais alterações. Entretanto, no grupo Tx 45 dias foram visualizados úteros praticamente iguais aos do controle, com grande número de leucócitos e remodelação do epitélio superficial, além de ovários com reduzida quantidade de folículos e presença de corpos lúteos, indicando ovulação. As camundongas B6.V-Lepob/J obesas apresentam formações polimicrocísticas e estroma abundante, mimetizando os achados ovarianos das pacientes anovuladoras. O Tx de tecido adiposo, a longo prazo, parece ter papel na diminuição da obesidade, mostrando-se eficiente na reversão da hiperglicemia e das alterações ovarianas e uterinas, presentes nas camundongas obesas, restabelecendo a ovulação. / Objective: To assess from the histological point of view the effect of adipose tissue transplantation onto the uterus and ovaries of obese, anovulating mice.en Method: B6.V-Lepob/J mice were used and the following experimental groups evaluated: 1.Control group (B6.V-Lepob/J female, average weight); 2.Obesity (B6.V-Lepob/J female, obese); 3.Obesity plus adipose tissue transplant from mice donors which were average weight after 7 days (B6.V-Lepob/J obese females which received adipose tissue from thin, isogenic mice); 4.Obesity plus adipose tissue transplant from mice donors which were average weight after 15 (B6.V-Lepob/J obese females which received adipose tissue from thin, isogenic mice); 5.Obesity plus adipose tissue transplant from mice donors which were average weight after 45 days (B6.V-Lepob/J obese females which received adipose tissue from thin, isogenic mice);. Within 7, 15 and 45 days of the transplant the animals were sacrificed. The age range was between 2 and 3 months old. In addition to the histological analyses of uteri and ovaries (H/E), these animals’ corporal weight and glycemia were verified. Results and Conclusion: The obese group (n=6) presented with elevation in corporal weight (52,0 ± 1,3*)and glycemia (418,4± 33,0*) in relation to the control group (24,0 ± 0,7 and 100,2± 2,2 respectively, n=5). The transplants after 7 days (n=5) and 15 days (n=9) were effective in reducing glycemia (390,2 ± 34,0 and 270,0 ± 38,0*, 7 days pre and post transplant; and 460,0 ± 31,4 and 125,0 ± 8,4*, 15 days pre and post transplant respectively), but not in changing corporal weight. However, within 45 days of the transplant (n=7) there was a reduction in glycemia (467,0 ± 28,0 and 209,0 ± 18,0*, pre and post- transplant respectively), as well as a tendency to reduce corporal weight observed pre and post transplant (50,4 ±2,4 and 44,0 ± 3,3). Values used for *p< 0,0001. Histology revealed that within 7 and 15 days of the transplant, the animals presented with ovaries similar to those in the obese group, containing countless follicles, abundant interstice and absence of corpora lutea. The uteri revealed intense hormonal and glandular stimulation, mitosis, scarse eosinophils and the superficial epithelium whole, without renovation, indicative of the inability of short term transplantations to reverse such alterations. In the 45-day-group, however, the uteri looked very much the same as those of the control group, with a great number of leucocytes and remodellation of the superficial epithelium, as well as ovaries with a reduced amount of follicles and presence of corpora lutea, suggesting ovulation. The obese B6.V-Lepob/J mice present with polymicrocystic formation and abundant oestrone, mimicking the ovarian findings of the anovulating patients. The long term adipose tissue transplantation, on the other hand, seems to play a part in reducing obesity, proving to be efficient in reversing hypoglycemia and the ovarian and uterine alterations present in obese mice, re-establishing ovulation

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2016-04-06T14:30:58Z No. of bitstreams: 2 Tese - Eliane Gouveia de Morais Sanchez - 2015.pdf: 1194460 bytes, checksum: 67eee577cf08aa1bdca9f0cbdddad7f1 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-04-06T14:33:14Z (GMT) No. of bitstreams: 2 Tese - Eliane Gouveia de Morais Sanchez - 2015.pdf: 1194460 bytes, checksum: 67eee577cf08aa1bdca9f0cbdddad7f1 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2016-04-06T14:33:14Z (GMT). No. of bitstreams: 2 Tese - Eliane Gouveia de Morais Sanchez - 2015.pdf: 1194460 bytes, checksum: 67eee577cf08aa1bdca9f0cbdddad7f1 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2015-10-29 / Infertility reflects the inability of a couple to achieve pregnancy after one year of sexual intercourse without contraception. Most common causes are related to ovulatory disorders such as hyperprolactinaemia, polycystic ovary syndrome, thyroid dysfunction, corpus luteum deficiency, among others, and can be identified mainly by ultrasound and hormonal dosage. The overall objective of this study was to evaluate the influence of prolactin ovulation in infertile women suffering from regular cycles. It is case-control study, whose sample consisted of 343 women with age range 20-40 years old, attended from 2000 to 2014 in LabRep-HC / UFG and an office of Obstetrics and Gynecology, private network in Goiânia, Goiás, Brazil. Data collection was performed by analyzing the physical records stored in Medical Records and Health Information Service (SAMIS) and electronics made available by the database (Sisfert) (© Approbato, 2013). The patients were classified according to the ovulation state measured by progestogen dosage (≥ 5.65 ng / ml and 5.65 - 9.9 ng / ml) and ovulation by monitoring the ultrasound being divided into four groups: (I ) probable ovulation, (II) likely anovulation. In Groups I and II were compared with the percentages of patients who do not ovulate with normal prolactin (3 to 20 ng / ml) versus moderately elevated prolactin (21 to 29 ng / ml). In group III were evaluated Normal progesterone levels (≥ 10 ng / mL) versus low progesterone (Group IV) (5.65 - 9.9 ng / ml) was considered as LUF (non-luteinized ruptured follicle). The groups were comparable for comparable as to age, body mass index (BMI), duration of infertility, FSH (ng / ml) TSH (mIU / l), LH (IU / l) and oestradiol (ng / dL) . SPSS Statistics 20.0 software and Bioestat (version 5.3) were used to for data analysis and chi-square test (X2) to assess differences between proportions. Where it is not for statistical analysis were calculated mean and standard deviation of the variables under study. The results demonstrated that moderate elevation of prolactin (21-29 ng / ml) caused a significant reduction (p = 0.03) in the ovulation rate of infertile patients with regular cycles considering as a criterion for ovulation progesterone levels ≥5, 65 ng / ml. When evaluated the influence of low progesterone on ovulation monitored by ultrasound was observed that these levels can significantly reduce the percentage of ovulation. It is concluded that a moderate hyperprolactinaemia and low progesterone can negatively influence the regulation of ovulation in infertile women with regular menstrual cycles. / A infertilidade reflete a incapacidade de um casal conseguir gravidez após um ano de relações sexuais sem contracepção. Causas mais comuns estão relacionadas a disfunções ovulatórias como a hiperprolactinemia, síndrome de ovário policístico, disfunções da tireóide, deficiência de corpo lúteo, entre outras, e que podem ser identificadas, principalmente, por dosagem hormonal e ultrassonografia. O objetivo geral desse estudo foi avaliar a influência dos níveis de prolactina na ovulação de mulheres inférteis portadoras de ciclos regulares. Trata-se de estudo caso-controle, cuja amostra foi composta por 343 mulheres com faixa etária compreendida de 20 a 40 anos, atendidas no período de 2000 a 2014 no LabRep-HC/UFG e em um consultório de Ginecologia e Obstetrícia da rede particular em Goiânia, Goiás, Brasil. A coleta de dados foi feita pela análise dos prontuários físicos armazenados no Serviço de Arquivo Médico e Informações em Saúde (SAMIS) e eletrônicos disponibilizados pelo banco de dados (Sisfert) (©Approbato, 2013). As pacientes foram classificadas de acordo com o estado ovulatório avaliado pela dosagem de progesterona (≥ 5,65 ng/ml e de 5,65 – 9,9 ng/ml) e monitorização da ovulação pelo ultrassom sendo divididas em quatro grupos: (I) provável ovulação, (II) provável anovulação. Nos grupos I e II foram comparadas as porcentagens de pacientes que não ovulavam com prolactina normal (3 a 20 ng/ml) versus prolactina moderadamente elevada (21 a 29 ng/ml). No grupo III foram avaliados os níveis de progesterona normal (≥ 10 ng/ml) versus progesterona baixa (Grupo IV) (5,65 – 9,9 ng/ml) considerada como LUF (Folículo Luteinizado não-roto). Os grupos foram pareados para a comparabilidade quanto a idade, índice de massa corporal (IMC), duração da infertilidade, FSH (ng/ml), TSH (mUI/l), LH (UI/l) e estradiol (ng/dl). Os programas SPSS Statistics 20.0 e Bioestat (versão 5.3) foram utilizados para para a análise dos dados e o teste Qui quadrado (X2) para avaliar as diferenças entre proporções. Onde não coube análise estatística foram calculadas média e desvio padrão das variáveis em estudo. Os resultados demonstraram que a elevação moderada da prolactina (21-29 ng/ml) provocou a redução significativa (p=0,03) na porcentagem de ovulação das pacientes inférteis portadoras de ciclos regulares considerando como critério de ovulação níveis de progesterona ≥5,65 ng/ml. Quando avaliada a influência da progesterona baixa sobre a ovulação monitorada pelo ultrassom foi observado que esses níveis podem reduzir de forma significativa a porcentagem de ovulação. Conclui-se que a hiperprolactinemia moderada e a progesterona baixa podem influenciar negativamente na regulação da ovulação de mulheres inférteis com ciclos regulares.

Polycystisktovarialsyndrom (PCOS) förekommer hos 5-10% av alla kvinnor och är den vanligaste orsaken till anovulatorisk infertilitet. Andra delar av syndromet är hyperandrogena och metabola symtom. Infertilitet behandlas med klomifencitrat. Akne och hirsutism behandlas i första hand med kombinerade p-piller med östrogenprofil. Förhöjda blodsockernivåer, hypertoni, dyslipidemi och övriga komplikationer till syndromet behandlas farmakologiskt vid behov. Hyperandrogenism och insulinresistens tycks spela en huvudroll i uppkomsten av sjukdomen. Då metformin förbättrar insulinkänsligheten, och tros kunna påverka patofysiologin, har det föreslagits som en alternativ förstahandsbehandling. Denna litteraturstudie syftade till att undersöka vilket vetenskapligt underlag som finns för att ändra behandlingsrekommendationerna vid PCOS. De studier som jämfört resultatet av metformin och klomifencitrat vid anovulatorisk infertilitet visar att klomifencitrat mer effektivt framkallar ovulation och graviditet hos kvinnor med PCOS och övervikt, men att metformin är lika effektivt hos normalviktiga kvinnor. Medan metforminbehandling är en välbeprövad och säker behandling med få biverkningar har klomifencitrat allvarliga biverkningar i form av risk för flerbörd och ovarialthyperstimuleringssyndrom. De få studier som undersökt metformins påverkan på fostret finner inga belägg för teratogena effekter. Metformin har positiva effekter på hyperandrogena symtom vid PCOS, och man har inte kunnat se någon signifikant skillnad i effekt mellan metformin och p-piller då det gäller att minska akne och hirsutism. Dessutom finns det belägg för att metformin kan ha en positiv påverkan på BMI och blodtryck, förbättra lipidprofilen genom att sänka nivåerna av LDL kolesterol, samt minskar risken hos denna patientgrupp att utveckla typ 2 diabetes. Sammantaget kan dock sägas att det vetenskapliga underlaget ännu är för svagt för att man ska ändra den rådande behandlingsrekommendationen. Det finns behov av större, blindade studier där man jämför metforminbehandling med klomifencitrat och tittar på en kombination av faktorer och utfall kopplade till symtombilden vid PCOS.

15 à 20 % des couples français sont amenés à consulter pour un problème de fertilité. Les étiologies principales de la stérilité féminine sont les troubles de l'ovulation, les salpingites infectieuses, l'endométriose, le syndrome Distilbène, les troubles de la glaire cervicale et les malformations cervico-vaginales. Un bilan d'exploration de la femme complet, précis et méthodique doit être établi pour situer l'origine du trouble afin d'appliquer le traitement le plus adapté. Le traitement de la stérilité se fait essentiellement par chirurgie et par induction de l'ovulation. En cas d'échecs répétés, une procréation médicalement assistée peut être proposée aux couples. L'insémination intra-utérine et la fécondation in vitro classique sont les deux techniques principales indiquées dans la stérilité féminine. Malgré les progrès de la science, un tiers des couples stériles ne peuvent réaliser leur projet parental par la médicalisation. Pour aboutir à ce désir d'enfant, ils peuvent avoir recours soit aux dons de gamètes ou d'embryons, soit à l'adoption.

Introdução: A reserva ovariana (RO) refere-se à quantidade e, para alguns autores, à qualidade de folículos presentes nos ovários em um dado momento. É a medida pela qual se avalia a produção de oócitos e consequente potencial reprodutivo. Ela pode ser inferida mediante dosagem dos níveis séricos do hormônio folículo estimulante (FSH), estradiol, inibina B e hormônio antimülleriano (HAM), e ainda, ultrassonograficamente, através da contagem de folículos antrais (CFA). Na década de 50 observou-se que mulheres submetidas à quimioterapia (QT) apresentavam falência ovariana mais precocemente, efeito atribuído à gonadotoxicidade quimioterápica. Objetivos: Estudar o HAM como marcador da RO em mulheres com câncer de mama expostas à QT gonadotóxica comparando-o com outros marcadores da RO e determinar preditores de risco da ocorrência de anovulação (amenorreia ou ciclos irregulares) nessas mulheres. Métodos: Foi realizado estudo de coorte com 52 mulheres com diagnóstico de câncer de mama e necessidade de QT com ciclofosfamida, com idade até 40 anos, ciclos menstruais regulares e sem histórico de tratamento quimioterápico prévio. As pacientes realizaram coleta de sangue e ultrassonografia pélvica transvaginal (USTV) antes da QT (T1) e 2 (T2) e 6 (T3) meses após seu término. Resultados: A idade média das pacientes estudadas foi 35,3 ± 3,8 anos e o tempo médio de seguimento foi de 14 ± 3 meses. A prevalência de anovulação foi de 40% durante a QT, 85% 2 meses após o término da QT (4 a 6 ciclos de ciclofosfamida) e de 60% 6 meses após a QT. A média de idade das pacientes que se tornaram anovulatórias foi de 36,5 ± 3,8 anos, enquanto que nas que permaneceram ovulatórias foi de 32,9 ± 3,5 anos com p = 0,02. O FSH acompanhou o status menstrual, apresentando aumento e queda significativos em T2 e T3. O HAM diminuiu significativamente de T1 (2,53 (1 - 5,31) ng/mL) para T2 (valores abaixo do detectável) com p < 0,0001 e não se modificou de T2 para T3, mesmo com uma parcela de pacientes retomando a ciclicidade menstrual. CFA em T1 foi 11 (8 - 13,5) folículos, sendo estatisticamente maior que nos tempos T2 e T3 (p < 0,0001). Entre T2 e T3 não houve diferença. As pacientes que mantiveram ciclos ovulatórios após o término da QT apresentaram no final do estudo níveis significativamente mais baixos de HAM do que previamente à QT (1,46 (< 0,08 - 4,31) ng/ml versus 6,17 (3,19 - 10,07) ng/mL) e CFA (7 (5,5 - 10) folículos versus 13 (11 - 15,5) folículos). HAM e CFA apresentaram correlação negativa e significativa com a idade. Trinta e dois anos foi a idade que apresentou sensibilidade de 96% e especificidade de 39% para predição de anovulação, mesmo que sem amenorreia, com área sob a curva (ASC) ROC de 0,77. Os marcadores de RO e os respectivos pontos de corte com poder de predizer ocorrência de anovulação em pacientes expostas à QT foram HAM < 3,32 ng/ml (sensibilidade de 85%, especificidade de 75% e ASC de 0,86) e CFA < 13 folículos antrais (sensibilidade de 81%, especificidade de 62% e ASC de 0,81). Para a predição de amenorreia exclusivamente, o HAM teve como ponto de corte o valor de 1,87 ng/ml (sensibilidade de 82%, especificidade de 83% e ASC de 0,84) e a CFA valor de 9 folículos (sensibilidade de 71%, especificidade de 78% e ASC de 0,73 ). As avaliações dos marcadores de RO não foram influenciadas pelo número de ciclos de QT (4 ou 6 ciclos), nem pela dose de quimioterápico utilizado por área corporal. Conclusão: O HAM e a CFA são igualmente capazes de determinar a queda da RO em pacientes submetidas à QT gonadotóxica. Pacientes com diagnóstico de câncer de mama que necessitam de QT com ciclofosfamida devem ser alertadas para o risco de amenorreia especialmente quando a idade for de 32 anos ou mais, dosagens séricas de HAM abaixo de 3,32 ng/ml, CFA < 13, devendo receber informações a respeito da preservação da fertilidade. Dentre esses marcadores, o HAM foi o de maior poder em predizer a ocorrência de amenorreia. / Introduction: Ovarian reserve (OR) refers to quantity and, to some authors, quality of follicles present in ovaries at a given time. It is the measure used to assess the capacity of the ovary to produce oocytes. Its evaluation is trough serum analysis of FSH, estradiol, inhibin and anti-Müllerian hormone (AMH) and trough ultrassonography to count de antrals follicles (AFC). In the 50s, it was observed that women exposed to chemotherapy experienced premature ovarian failure, effect attributed to chemotherapy. Objectives: To ascertain OR by means of AMH in young women with breast cancer exposed to chemotherapy comparing them with another ovarian reserve tests. To define risk predictors of anovulation (oligomenorrhea or amenorrhea) in those women. Methods: A cohort study with 52 eumenorrheic patients (age < 40years) with breast cancer who received chemotherapy with cyclophosphamide. Assessment was carried out with serum samples and pelvic ultrasonography before chemotherapy (T1), and 2 (T2) and 6 (T3) months after chemotherapy. Results: Mean age was 35.3 ± 3.8 years. Mean duration of follow-up was 14 ± 3 months. Anovulation was present in 40% of women during the chemotherapy, 85% 2 months after and 60% 6 months after chemotherapy. Mean age of anovulatory women in T3 was 36.5 ± 3.8 years. Women with regular cycles was 32.9 ± 3.5 years (p = 0.02). FSH levels rises and decreased significantly in T2 and T3. AMH levels declined significantly, down to undetectable levels at T2 from a median of 2.53 (1 –5.31 ng/mL) at T1 (p < 0.0001) and remained unchanged from T@ and T3, even though some patients resumed normal menses. Median AFC was 11 ( 8.0 – 13.5) follicles at T1 and significantly lower at T2 and T3 (p < 0.0001). No difference was found between T2 and T3 in patients who resumed ovulation cycles after completion of chemotherapy, AMH and AFC levels were significantly lower as compared with baseline: 1.46 (< 0.08 – 4.31) ng/mL vs. 6.17 (3.19 – 10.07) ng/mL and 7 (5.5 - 10) follicles vs. 13 (11 – 15.5) follicles. In patients who remained ovulatory during chemotherapy or resumed normal menses, FSH and estradiol levels remained unchanged relative to baseline. AMH and AFC presented significantly negative correlation with age. The age of thirty-two years presented 96% of sensitivity and 39% of specificity to predict anovulation with ROC area under the curve (AUC) of 0.77. The ovarian reserve (OVR) tests with power to predict anovulation in women exposed to CT were AMH < 3.32 ng/mL (sensitivity of 85%, specificity of 75% and AUC of 0.87) and AFC < 13 follicles (sensitivity of 81%, specificity of 62% and AUC of 0.81). The AMH cut off to predict amenorrhea was 1,87 ng/mL (sensitivity of 82%, specificity of 83% and AUC of 0,84) and the AFC cut off was 9 follicles (sensitivity of 71%, specificity of 78% and AUC of 0.73 ). The analysis was not influenced by the number of cycles or dose of CT. Conclusions: AMH and AFC are equally able to determine the OVR decline in chemotherapy exposed women. FSH is not adequate for this purpose, except in women who become amenorrheic. Thirty-two year old or older women, AMH levels < 3.32 ng/mL and AFC < 13 follicles determined significantly higher risk of anovulation after CT with cyclophosphamide. These women should be encouraged to preserve their fertility. Among the OVR tests, AMH was the powerful to predict the anovulation.