A prospective cohort study of endometriosis and subsequent risk of infertility.

STUDY QUESTION: Is there a temporal relationship between endometriosis and infertility? SUMMARY ANSWER: Endometriosis is associated with a higher risk of subsequent infertility, but only among women age <35 years. WHAT IS KNOWN ALREADY: Endometriosis is the most commonly observed gynecologic pathology among infertile women undergoing laparoscopic examination. Whether endometriosis is a cause of infertility or an incidental discovery during the infertility examination is unknown. STUDY DESIGN, SIZE, DURATION: This study included data collected from 58 427 married premenopausal female nurses <40 years of age from 1989 to 2005, who are participants of the Nurses' Health Study II prospective cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our exposure was laparoscopically confirmed endometriosis. Multivariate Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for infertility risk (defined as attempting to conceive for >12 months) among women with and without endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 4612 incident cases of infertility due to any cause over 362 219 person-years of follow-up. Compared with women without a history of endometriosis, women with endometriosis had an age-adjusted 2-fold increased risk of incident infertility (HR = 2.12, 95% CI = 1.76-2.56) that attenuated slightly after accounting for parity. The relationship with endometriosis was only observed among women <35 years of age (multivariate HR <35 years = 1.77, 95% CI = 1.46-2.14; multivariate HR 35-39 years = 1.20, 95% CI = 0.94-1.53; P-interaction = 0.008). Risk of primary versus secondary infertility was similar subsequent to endometriosis diagnosis. Among women with primary infertility, 50% became parous after the endometriosis diagnosis, and among all women with endometriosis, 83% were parous by age 40 years. LIMITATIONS, REASONS FOR CAUTION: We did not have information on participants' intentions to conceive, but by restricting the analytic population to married women we increased the likelihood that pregnancies were planned (and therefore infertility would be recognized). Women in our cohort with undiagnosed asymptomatic endometriosis will be misclassified as unexposed. However, the small proportion of these women are diluted among the >50 000 women accurately classified as endometriosis-free, minimizing the impact of exposure misclassification on the effect estimates. WIDER IMPLICATIONS OF THE FINDINGS: This study supports a temporal association between endometriosis and infertility risk. Our prospective analysis indicates a possible detection bias in previous studies, with our findings suggesting that the infertility risk posed by endometriosis is about half the estimates observed in cross-sectional analyses. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Institutes of Health (grant numbers: UM1 CA176726, HD52473, HD57210, T32DK007703, T32HD060454, K01DK103720). We have no competing interests to declare.

Espinheira-santa (Maytenus ilicifolia Mart. ex Reiss.): saber de erveiros e feirantes em Pelotas (RS) / Espinheira-santa (Maytenus ilicifolia Mart. ex Reiss.): knowledge by herbalists and marketers in Pelotas (RS)

RESUMO O objetivo deste trabalho é descrever o conhecimento popular relacionado à espinheira-santa (Maytenus ilicifolia) entre erveiros e feirantes que comercializam a planta no centro de Pelotas, Rio Grande do Sul, Brasil. Foi realizada uma pesquisa de abordagem qualitativa, exploratória e descritiva, de agosto a outubro de 2013. Entrevistas semi-estruturadas, com questões sobre os saberes e práticas relacionados à espinheira-santa, foram aplicadas a cinco erveiros e três feirantes do mercado informal de plantas medicinais. Para a análise dos dados foi utilizada a proposta operativa de Minayo, sendo Capra o referencial teórico para este estudo. Foi verificado que o saber relacionado ao uso da espinheira-santa é transmitido de geração a geração, embora existam outras fontes de conhecimento. As indicações do uso popular da espinheira-santa com finalidade terapêutica estão relacionadas a distúrbios gástricos, cicatrização e depuração do sangue. As diferentes formas dos sujeitos deste estudo interagirem com o ambiente, com sua família e em outras relações interpessoais resultam em diferentes saberes relacionados à espinheira-santa.

ABSTRACT The aim of this study was to describe the popular knowledge related to the espinheira-santa (Maytenus ilicifolia) among herbalists and marketers that sell this plant in the center of Pelotas/Rio Grande do Sul State, Brazil. A qualitative, exploratory and descriptive research was performed between August and July of 2013. Semi-structured interviews, with questions regarding the knowledge and practices related to this plant, were applied to five herbalists and three marketers inserted in the informal market of medicinal plants. The operative proposal by Minayo was used in order to analyze the data, and the theoretical framework by Capra was used in the discussion. The popular knowledge related to the use of espinheira-santa is passed on from generation to generation, although nowadays there are other sources ofinformation. The popular clueswith therapeutic purposes are related to gastric disorders, healing and blood clearance. The study participants have different forms of interaction with the environment, the family and other interpersonal relationships, resulting in different popular knowledges related to this medicinal plant.

Ocorrência de cochonilhas em espinheira-santa (Maytenus ilicifolia Mart. ex Reissek) / Occurrence of mealybugs in "espinheira-santa" (Maytenus ilicifolia Mart. ex Reissek)

Maytenus ilicifolia é uma espécie medicinal nativa do Brasil que vem sendo cultivada para atender a crescente demanda do mercado. Os fatores que interferem na produção, tal como a incidência de pragas e doenças, devem ser estudados para garantir o incremento na produtividade. O objetivo deste trabalho foi registrar a ocorrência e a identificação de cochonilhas associadas a 15 acessos de espinheira-santa (Maytenus ilicifolia) do Banco Ativo de Germoplasma da Embrapa Clima Temperado e do Instituto Federal Sul-rio-grandense. Foi registrada a quantidade de plantas infestadas em cada acesso e identificado, em laboratório, as espécies de cochonilhas infestantes. O número de plantas infestadas variou entre os acessos. Foram identificadas as cochonilhas Ceroplastes sp. e Saissetia oleae, família Coccidae. Dos 10 acessos infestados, 23 (11,3%) plantas apresentaram infestação com Ceroplastes sp. e, apenas uma (0,5%), com Saissetia oleae. O acesso 133 mostrou a maior incidência de Ceroplastes sp. (33,3%), seguido do acesso 130 (25,0%). O acesso 123 foi o que apresentou menor quantidade de plantas infestadas (4,8%). Saissetia oleae ocorreu em apenas uma planta, pertencente ao acesso 136 (5,6%).

Maytenus ilicifolia is a medicinal species native to Brazil which has been cultivated to meet the growing market demand. Factors that interfere with the production, such as the incidence of pests and diseases, should be studied to ensure increased productivity. The aim of this study was to record the occurrence and the identification of mealybugs associated with 15 "espinheira-santa" (Maytenus ilicifolia) accessions from the Active Germplasm Bank of "Embrapa Clima Temperado" and "Instituto Federal Sul-rio-grandense". The quantity of infested plants in each accession was recorded and the species of infested mealybugs were identified in the laboratory. The number of infested plants varied among accessions. The identified mealybugs were Ceroplastes sp. and Saissetia oleae, family Coccidae. Of 10 infested accessions, 23 plants (11.3%) showed infestation with Ceroplastes sp., and only one (0.5%) with Saissetia oleae. Accession 133 showed the highest incidence of Ceroplastes sp. (33.3%), followed by accession 130 (25.0%). Accession 123 had the least amount of infested plants (4.8%). Saissetia oleae occurred in only one plant, belonging to accession 136 (5.6%).

Plantas medicinais utilizadas por idosos com diagnóstico de Diabetes mellitus no tratamento dos sintomas da doença / Medicinal plants used by elderly people with Diabetes mellitus in the treatment of the disease symptoms

Este trabalho teve como objetivo investigar as plantas medicinais utilizadas por idosos assistidos em uma Unidade Básica de Saúde de Pelotas-RS, com diagnóstico de Diabetes mellitus, como terapia complementar no tratamento dos sintomas da doença. Caracterizou-se por pesquisa qualitativa, realizada em julho de 2009, no município de Pelotas-RS. Foram entrevistados 18 idosos com idade entre 60 e 77 anos, sendo 14 do sexo feminino. Os participantes citaram 20 plantas medicinais utilizadas como terapia complementar no tratamento do Diabetes mellitus. Entre estas, as mais citadas utilizadas para diminuir os níveis de glicose no sangue foram Sphagneticola trilobata, Bauhinia spp. e Syzygium cumini, sendo que para as duas últimas há comprovação científica do efeito hipoglicemiante. A infusão foi a forma de preparo predominante. Considera-se importante a realização de estudos farmacológicos que investiguem os efeitos das plantas utilizadas pela população, a fim de que o uso proporcione os benefícios desejados e não cause danos à saúde.

This study aimed to investigate medicinal plants used as complementary therapy by the elderly with diabetes mellitus, assisted by a Health Basic Unit in Pelotas (RS, Brazil). This qualitative research was conducted in July 2009. Eighteen 60 to 77 years old elderly (14 of them female) were interviewed. The participants identified 20 medicinal plants used as complementary therapies in the treatment of diabetes mellitus. Among these, the most used ones to reduce the levels of glucose in the blood were Sphagneticola trilobata, Bauhinia spp. and Syzygium cumini. For the last two plants, there are scientific proofs of hypoglycemic effects. The infusion was the predominant form of preparation. Studies to investigate the pharmacological effects of plants used by the population have become very important, for providing scientific information on their possible health benefits and side effects.

Diversidade genética entre acessos de espinheira-santa (Maytenus ilicifolia Mart. ex Reis.) coletados no estado do Rio Grande do Sul, Brasil / Genetic diversity of "espinheira-santa" (Maytenus ilicifolia Mart. ex Reis.) accessions collected in Rio Grande do Sul State, Brazil

Maytenus ilicifolia Mart. ex Reis., popularmente conhecida como espinheira-santa, é espécie autóctone pertencente à família Celastraceae, usada para tratamento de úlceras gástricas e gastrites. Devido à importância medicinal, houve aumento no extrativismo das populações naturais, tornando-a uma espécie prioritária para a conservação, a fim de evitar a erosão genética. Buscou-se com este trabalho analisar a diversidade genética de 20 acessos de M. ilicifolia coletados em diferentes localidades no Rio Grande do Sul. Utilizando marcadores moleculares do tipo AFLP, foram testadas oito combinações de primers, que geraram 455 bandas eletroforéticas, 100 por cento polimórficas. As combinações de primers E-ACC/M-CAA, E-ACG/M-CTA, E-ACG/M-CTC apresentaram o maior número de bandas eletroforéticas, 71 cada, totalizando 46,80 por cento do polimorfismo total. Os valores de similaridade genética calculada pelo coeficiente simple matching foram utilizados para gerar o dendrograma de similaridade pelo método UPGMA. Foi obtido alto coeficiente de correlação cofenética (r=0,94), demonstrando elevada representatividade dos dados de similaridade genética no dendrograma. Pela AMOVA verificou-se que 89,33 por cento da diversidade total ocorreram entre indivíduos dentro das populações. A caracterização molecular de acessos de Maytenus ilicifolia por meio de AFLP foi eficiente para identificar diversidade genética. Através da análise de similaridade genética o banco de germoplasma poderia ser composto com os acessos que apresentaram menor similaridade e maior número de alelos, permitindo com que estes fornecessem ampla cobertura do genoma que compõem Maytenus ilicifolia. Os acessos que ficaram agrupados em mesmo cluster e com número reduzido de alelos podem ser descartados deste banco. A diversidade genética intrapopulacional identificada por esse marcador foi muito maior do que aquela entre populações.

Maytenus ilicifolia Mart. ex Reis., popularly known as "espinheira-santa", is an autochthonous species belonging to the Celastraceae family. This species is used to treat ulcers and gastritis. Due to its medicinal importance, the exploitation of natural populations has increased, making the conservation of this species essential to prevent genetic erosion. The aim of this work was to analyze the genetic diversity of 20 M. ilicifolia accessions collected in different localities of Rio Grande do Sul State. Using AFLP-type molecular markers, eight primer combinations were tested, producing 455 electrophoretic profiles, with 100 percent polymorphism. The primer combinations E-ACC/M-CAA, E-ACG/M-CTA and E-ACG/M-CTC presented the largest number of electrophoretic profiles, 71 each, totaling 46.80 percent of the total polymorphism. The values of genetic similarity estimated by Simple Matching Coefficient were used to produce the dendrogram of similarity by the UPGMA method. A high cophenetic correlation coefficient (r = 0.94) was obtained, demonstrating high representativeness of the data of genetic similarity in the dendrogram. Using AMOVA, 89.33 percent of the total diversity were observed among individuals from the same population. The molecular characterization of Maytenus ilicifolia accessions by AFLP allowed the identification of genetic diversity. The genetic similarity analysis indicated that the germplasm bank could be composed of the accessions presenting the lowest similarity and the largest numbers of alleles, providing a comprehensive coverage of Maytenus ilicifolia genome. The accessions that were grouped into one same cluster and with a reduced number of alleles could be disposed of this bank. The genetic diversity identified by this marker within populations was much greater than that between populations.

Divergência genética entre acessos de espinheira-santa (Maytenus ilicifolia Mart. ex Reissek e M. aquifolium Mart.) com base em caracteres morfológicos e fisiológicos / Genetic divergence among espinheira-santa (Maytenus ilicifolia Mart. ex Reiss. and M. aquifolium Mart.) accessions based on morphological and physiological traits

Maytenus ilicifolia e M. aquifolium (espinheira-santa) são espécies medicinais nativas do Brasil ameaçadas de extinção devido à forte ação antrópica nas populações naturais. O objetivo deste trabalho foi avaliar a divergência genética em germoplasma de espinheira-santa, e agrupar os acessos através de análises multivariadas, com base em caracteres morfo-fisiológicos das progênies. Foram avaliados 89 acessos do banco ativo de germoplasma de espinheira-santa da Embrapa Clima Temperado/Universidade Federal de Pelotas. Os caracteres avaliados foram dias da semeadura à emergência; altura e diâmetro à base do caule, aos 90, 180, 270 e 360 dias; crescimento em altura e diâmetro à base do caule; comprimento e largura de folha e número de espinhos por folha. O delineamento experimental foi em blocos casualizados, com quatro repetições e cinco plantas por parcela. Os dados foram submetidos à análise de variância e análise de variância multivariada, sendo estimadas as variáveis canônicas. Os caracteres avaliados foram eficientes para separar os acessos em três grupos. As variáveis altura, diâmetro à base do caule aos 360 dias e número de folhas aos 180 dias são as mais importantes para caracterização do germoplasma de espinheira-santa.

Maytenus ilicifolia and M. aquifolium (espinheira-santa) are medicinal species native to Brazil. They are endangered due to the strong anthropic action in natural populations. The aim of this work was to evaluate the genetic divergence in "espinheira-santa" germplasm and to cluster accessions by multivariate analyses based on morphophysiological traits of progenies. Eighty-nine accessions of the "espinheira-santa" active germplasm bank from the Brazilian Agricultural Research Corporation (EMBRAPA) Temperate Agriculture, Pelotas Federal University, Pelotas Municipality, Rio Grande do Sul State, Brazil, were evaluated regarding days from sowing to emergence; height and stem-base diameter at 90, 180, 270 and 360 days; height and stem-base diameter growth; leaf length and width; and number of thorns per leaf. Experimental design was in randomized blocks, with four replicates and five plants per plot. The results were subjected to analysis of variance and multivariate analysis of variance, and canonical variables were estimated. The evaluated traits were efficient for separating the accessions into three clusters. Height and stem-basal diameter at 360 days and leaf number at 180 days were the most important for "espinheira-santa" germplasm characterization.

Metformin for the treatment of the polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS) is characterized by increased secretion of LH, insulin and androgens. The main clinical complaints of women with PCOS include: oligo- or amenorrhea, dysfunctional uterine bleeding, hirsutism, obesity and/or anovulatory infertility. The first line treatment for these problems include: 1) estrogen-progestin therapy for oligomenorrhea and dysfunctional uterine bleeding; 2) estrogen-progestin therapy and/or antiandrogens for hirsutism; 3) lifestyle changes such as diet and exercise for obesity and 4) weight loss or clomiphene for anovulatory infertility. However, clinical trials have indicated that metformin is effective second line therapy when first line therapy has not been effective, is not acceptable to the patient or is medically contraindicated. The addition of metformin to the armamentarium of the gynecological endocrinologist represents an important advance.

Serum prolactin and TSH in an in vitro fertilization population: is there a link between fertilization and thyroid function?

PURPOSE: Measurements of TSH and prolactin are generally included in the evaluation of female infertility, but their value in women coming to in vitro fertilization (IVF) has been questioned. METHODS: In this study, we sought to investigate whether prolactin or TSH, measured in 509 specimens collected prior to therapy, predicted outcome in a prospective study of couples undergoing IVF between 1994 and 2001. RESULTS: TSH was higher in women whose fertility problem was attributed to a male factor, and prolactin was lower if the measurement was taken during menses. TSH and prolactin were positively correlated (p < 0.0001). Neither TSH nor prolactin levels correlated with overall IVF outcome; however, TSH levels were significantly higher among women who produced oocytes that failed to be fertilized and this finding persisted after adjustment for several covariates, including sperm motility. Among women who had a least one oocyte inseminated, the likelihood that they would have fewer than 50% of their eggs fertilized was significantly related to higher TSH levels in a multivariate model. CONCLUSION: We conclude that TSH may predict poor fertilization in IVF and reflect the importance of thyroid hormones in oocyte physiology.

Determinants of early follicular phase gonadotrophin and estradiol concentrations in women of late reproductive age.

BACKGROUND: FSH and estradiol measured during the menstrual (basal) phase of cycles predict the success of infertility treatment; but the role of these hormones as markers for ovarian reserve in normal populations needs further study. METHODS AND RESULTS: From a cohort study of depressed and non-depressed women, a subset of 406 non-depressed women between the ages of 36 and 45 years with spontaneous periods were selected and their concentrations and determinants of basal hormones measured at study entry, 6 and 12 months later were described. FSH and LH increased significantly over the 12 months of observation (P

The initial fertility consultation: recommendations concerning cigarette smoking, body mass index, and alcohol and caffeine consumption.

Obstetrician-gynecologists are frequently consulted by couples who are concerned about their fertility potential. During the initial fertility consultation, questions may arise concerning the potential impact of lifestyle choices on fertility. For the female partner, common exposures associated with a decrease in fertility are cigarette smoking, alcohol consumption of >4 drinks per week, and caffeine intake of >250 mg daily. For the female partner, a body mass index of >27 kg/m2 or <17 kg/m2 is associated with decreased fertility. On the basis of the evidence from epidemiologic studies, couples who are concerned about their fertility potential should stop the use of tobacco products. In addition, the female partner should limit alcohol consumption to no more than 4 drinks per week, decrease caffeine intake to no more than 250 mg daily, and adjust calorie intake and exercise levels to achieve a body mass index between 20 and 27 kg/m2.

Early follicular phase hormone levels in relation to patterns of alcohol, tobacco, and coffee use.

OBJECTIVE: To examine the effects of alcohol, caffeine, and tobacco use on early follicular phase FSH, LH, E2, and sex hormone-binding globulin (SHBG). DESIGN: Cross-sectional study. SETTING: Academic medical center. PATIENT(S): Four hundred ninety-eight women selected from the general population, ages 36-45, who were not currently pregnant, breast feeding, or using exogenous hormones. INTERVENTION(S): A general questionnaire assessing demography, anthropometry, and smoking habits and a standardized dietary questionnaire assessing food and beverage frequencies, including sources of alcohol and caffeine. MAIN OUTCOME MEASURE(S): FSH, LH, E2, and SHBG levels measured during the early follicular phase of the menstrual cycle. RESULT(S): Significant associations observed in a univariate analysis included age > or =40 and current smoking associated with higher FSH; higher body mass index (BMI) associated with lower SHBG levels; and daily alcohol use, cholesterol consumption greater than the median, and coffee use >1 cup/d associated with higher E2 levels. In a multivariate model, total caffeine use was significantly associated with E2 levels after adjustment for age, BMI, total calories, current smoking, alcohol, cholesterol consumption, and day of sampling. Early follicular phase E2 increased from 28.2 pg/mL for women consuming < or =100 mg of caffeine to 45.2 pg/mL for women consuming > or =500 mg of caffeine per day, about a 70% increase. CONCLUSION(S): Coffee consumption and total caffeine use may increase early follicular phase E2 levels independent of related habits of alcohol or tobacco use.

Serum and follicular fluid hormone levels during in vitro fertilization after short- or long-course treatment with a gonadotropin-releasing hormone agonist.

OBJECTIVE: To examine the impact of flare (short) vs. down-regulation (long) GnRH agonist (GnRH-a) on serum and follicular fluid (FF) LH and androgen concentrations in women undergoing IVF treatment cycles. DESIGN: Prospective observational study. SETTING: IVF clinic. PATIENT(S): One hundred sixteen ovulatory subjects undergoing IVF. INTERVENTION(S): Fifty-eight ovulatory patients undergoing a down-regulation regimen matched with 58 undergoing the flare regimen as part of an IVF cycle. MAIN OUTCOME MEASURE(S): Serum concentrations of LH, FSH, Progesterone (P4), Androstenedione (A), T, and E(2) on the day of hCG administration were compared between the two groups. In addition, the FF P4, 17OHP4, A, T, and E(2) levels were compared in the two groups. RESULT(S): Serum LH was significantly higher with the flare regimen (15.2 +/- 1.14 IU/L, P<.05) when compared with results with the down-regulation protocol (9.5 +/- 0.77 IU/L). In addition, FF A was significantly higher in the flare protocol (57.3 +/- 13.3 ng/mL, P<.05) compared with in the down-regulation protocol (27 +/- 2.44 ng/mL). Serum and FF P4, 17OH P4, T, and E(2) were not statistically significantly different between the two groups. CONCLUSION(S): Serum LH and FF A are significantly higher in the flare regimen in comparison with the down-regulation regimen. Circulating LH appears to play a role in determining FF A concentration.

Induction of ovulation in infertile women with hyperandrogenism and insulin resistance.

The polycystic ovary syndrome is a common cause of anovulatory infertility. Women with severe insulin resistance are a unique subset of polycystic ovary syndrome. The syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN syndrome) is one presentation of the insulin-resistant subset of polycystic ovary syndrome. Insulin resistance and hyperandrogenism are caused by genetic and environmental factors. In women with anovulatory infertility caused by hyperandrogenism and insulin resistance, clomiphene citrate treatment often fails to result in pregnancy. For these women, weight loss and insulin sensitizers can be effective methods of inducing ovulation and pregnancy and may reduce the number of clomiphene-resistant women with polycystic ovary syndrome who are treated with gonadotropins, ovarian surgery, or in vitro fertilization-embryo transfer.

Dietary fat intake and endogenous sex steroid hormone levels in postmenopausal women.

PURPOSE: To examine the relationship between plasma levels of reproductive sex steroid hormones in postmenopausal women and their reported fat intake. METHODS: We measured plasma sex steroid hormones levels in plasma collected in 1989 and 1990 from 381 healthy postmenopausal women. For each woman, we measured fat intake in 1986 and 1990 by a food-frequency questionnaire. The cross-sectional associations between the percentage of energy from total and specific types of dietary fat intake and plasma hormone levels were assessed by linear regression, controlling for energy intake, obesity, and protein intake. RESULTS: The plasma estradiol level was 4.3% lower (95% confidence limits, -8.3%, -0.2%) for a substitution of 5% of energy from fat intake for an equivalent amount of energy from carbohydrate when adjusted for obesity and other covariates. Estradiol was also inversely associated with all other fat types except trans fat; the inverse associations with vegetable fat and marine omega-3 fats were statistically significant. CONCLUSION: We observed an inverse association between total fat intake averaged over 4 to 5 years and estradiol levels. This result is inconsistent with the hypothesis that fat intake predisposes to breast cancer risk by raising endogenous estrogen levels.

The prognostic value of age and follicle-stimulating hormone levels in women over forty years of age undergoing in vitro fertilization.

PURPOSE: Basal follicle-stimulating hormone (FSH) and age are predictors of successful outcome in in vitro fertilization (IVF). More recently, the clomiphene citrate challenge test (CCCT) has been proposed as a better way to predict IVF outcome than FSH alone. The purpose of this study was to determine which indicator of ovarian reserve--basal (day 3) FSH or the CCCT--is the better predictor of IVF success in the critical age group of women over the age of 40. METHODS: In this retrospective study, basal FSH and clomiphene-stimulated FSH levels from 104 women who underwent 175 cycles of IVF were analyzed. RESULTS: Neither basal FSH level nor stimulated FSH level alone were statistically significant predictors of IVF success; however, no patient with a day 3 FSH level > 11.1 mIU/ml or a stimulated day 10 FSH level > 13.5 mIU/ml conceived and carried a pregnancy. All ongoing pregnancies occurred in the first two cycles of IVF. CONCLUSIONS: Clear prognostic cutoff values were found to predict IVF success in women over age 40. IVF programs should consider limiting the number of cycles of IVF in women above age 40.

Reproductive hormones, cancers, and conditions in relation to a common genetic variant of luteinizing hormone.

A variant of the beta-subunit of luteinizing hormone (v-LH) is more common among populations also at higher risk for breast and ovarian cancer. To explore the possible relationship between these cancers and v-LH, we examined its frequency in premenopausal women, including 100 with a family history of ovarian cancer, 94 with carcinoma- in-situ of the breast, and 153 age and residence-matched controls. Reproductive histories were assessed and v-LH status measured by immunological assays from plasma drawn during the early follicular phase of cycles. For the entire study population, 283 (81.5%) were wild type; 61 (17.6%) were heterozygous; and three (0.9%) were homozygous for v-LH. Carrier frequency was not elevated among women with a family history of ovarian cancer or personal history of carcinoma-in-situ of the breast compared with controls. Women with the v-LH variant were less likely to report menstrual weight gain or ovarian cysts, more likely to report infertility, and have higher early follicular phase LH concentrations compared with women who were wild type. While there is no evidence from this study that v-LH increases risk for ovarian or breast cancer, we conclude that possession of v-LH may impact on some aspects of reproductive history and LH concentrations.

Predictive value of serum and follicular fluid leptin concentrations during assisted reproductive cycles in normal women and in women with the polycystic ovarian syndrome.

Leptin is an adipocyte-derived hormone which plays a central role in the regulation of body weight and energy homeostasis and in signalling to the brain that adequate energy stores are available for reproduction. Although leptin may affect reproduction by regulating the hypothalamic-pituitary-gonadal axis, recent in-vitro observations indicate that leptin may also have direct intra-ovarian actions. Leptin concentrations were measured in women who succeeded in becoming pregnant within three cycles of in-vitro fertilization (IVF) or gamete intra-fallopian transfer (n = 53), in women who failed to become pregnant within three cycles (n = 50), and in women with polycystic ovarian syndrome (PCOS) (n = 22). It was found that lower follicular fluid leptin concentrations were a marker of assisted reproduction treatment success in normal women. Women with PCOS had higher leptin concentrations than women without such a diagnosis, but this was due to their higher body mass index (BMI). After adjustment for age and BMI, women with PCOS who became pregnant tended to have lower mean follicular fluid leptin concentrations than women with PCOS who did not succeed at becoming pregnant. Further studies exploiting the strengths of the IVF model are needed to assess whether the prognostic role for follicular fluid leptin in human reproduction is independent of other factors, and to elucidate the underlying mechanisms.

Recent trends in assisted reproductive techniques and associated outcomes.

OBJECTIVE: We examined recent trends in success rates for assisted reproduction and determined the influence of changes in patient selection and treatment characteristics on these trends. METHODS: We collected baseline information and abstracted treatment-related details and outcomes on 1244 couples accepted for in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) at three clinics in greater Boston from 1994-1998. RESULTS: Delivery rates per initiated cycle improved significantly from 14.9% for IVF and 20.6% for GIFT in 1994-1995 to 22.5% for IVF and 28.0% for GIFT in 1997-1998 (P < or = .001). After adjusting for female age, the two treatment-related variables that appeared most likely to explain this trend were decreased use of GnRH agonists in short course (flare) regimens and increased use of highly purified forms of urinary gonadotropins. CONCLUSION: There were significant improvements in the success rates for IVF and GIFT from 1994-1998 that correlated with changes in ovulation induction regimens.

Reproducibility of plasma and urinary sex hormone levels in premenopausal women over a one-year period.

Although endogenous sex steroid hormones in premenopausal women may be associated with the risk of breast cancer and other illnesses, direct evidence to support this hypothesis is limited in large part by methodological issues in the conduct of relevant studies. One major unresolved issue is whether a single blood sample (such as is available in most epidemiological studies), collected in a specific phase of the menstrual cycle, reflects long-term levels in that phase. To address this issue, two sets of blood and urine samples were obtained from 87 premenopausal women over a 1-year period in both the follicular and luteal phases. Plasma estradiol, estrone, and estrone sulfate were measured in the blood samples obtained in both phases, whereas progesterone and urinary 2- and 16a-hydroxyestrone were measured in luteal-phase samples only. For all of the women combined, intraclass correlation coefficients (ICCs) ranged, with one exception, from 0.52 to 0.71 for the plasma estrogens and the urinary estrogen metabolites. The sole exception was for estradiol in the luteal phase (ICC = 0.19); inclusion of only women who were ovulatory in both cycles and who collected each sample 4-10 days before their next period resulted in a substantially higher ICC for estradiol in the luteal phase (ICC = 0.62; 95% confidence interval, 0.43-0.78). These data indicate that, for several plasma and urinary sex hormones, a single follicular- or luteal-phase measurement in premenopausal women is reasonably representative of hormone levels in that phase for at least a 1-year period.