Prevalence and risk factors related to anovular phenotypes in dairy cows.

The objective of the current study was to evaluate the relationship of body condition score (BCS) at 35 d in milk (DIM), milk production, diseases, and duration of the dry period with prevalence of anovulation at 49 DIM and then, specifically, with the prevalence of each anovular phenotype. We hypothesized that anovular follicular phenotypes, classified based on maximal size of the anovular follicle, have different etiologies. A total of 942 lactating Holstein cows (357 primiparous and 585 multiparous) from 1 herd had ovaries evaluated by ultrasonography at 35 ± 3 and 49 ± 3 DIM to detect the absence of a corpus luteum (CL), and to measure the diameter of the largest follicle. Cows were classified as cyclic at 49 DIM if a CL was observed in at least 1 of the 2 examinations, or anovular if no CL was observed at either examination. Cows considered anovular were divided into 3 groups based on the largest diameter of the largest follicle as follows: ranging from 8 to 13 mm, 14 to 17 mm, or ≥18 mm. Cows were evaluated for the following diseases: retained placenta, metritis, hyperketonemia, mastitis, lameness, respiratory problem, and digestive problem. At 35 DIM, BCS was determined, and milk yield for individual cows was recorded. A total of 28.5% (268/942) of cows were classified as anovular. Anovular cows had longer dry periods (90 vs. 71 d) and smaller BCS than cyclic cows (2.83 vs. 2.99). Cows with a single disease or multiple diseases had 2 and 3-fold increase in odds of being anovular, respectively. Anovular cows had follicles that ranged from 4 to 50 mm. The prevalence of anovular phenotype, among anovular cows, that had the diameter of the largest follicle ranging from 8 to 13 mm, 14 to 17 mm, and ≥18 mm was 29.9 (79/264), 37.5 (99/264), and 32.6% (86/264), respectively. Anovular cows with follicles of 8 to 13 mm had longer dry periods than those with follicles ≥18 mm (104 vs. 74 d), whereas anovular cows with medium size follicles had intermediate days dry (99 d). Cows with small and medium anovular follicles had smaller BCS and greater prevalence of multiple diseases than cyclic cows. For almost all risk factors, the cows with large anovular follicles (≥18 mm) were similar to cyclic cows and different from cows with smaller anovular follicles (8-13 mm). Thus, longer dry periods, less BCS at 35 DIM, and diseases were risk factors for anovulation. Moreover, the risk factors for the 3 distinct anovular follicle phenotypes differed.

Adiposity is associated with anovulation independent of serum free testosterone: A prospective cohort study.

BACKGROUND: Obesity, a body mass index (BMI) ≥30 kg/m2 , is linked to infertility, potentially through a greater risk of anovulation due to elevated androgens. Yet, previous studies have not directly assessed the impact of adiposity, or body fat, on anovulation in the absence of clinical infertility. OBJECTIVE: To characterise the associations between adiposity and anovulation among women menstruating on a regular basis. METHODS: Women from the EAGeR trial (n = 1200), a randomised controlled trial of low-dose aspirin and pregnancy loss among women trying to conceive, were used to estimate associations between adiposity and incident anovulation. Participants completed baseline questionnaires and anthropometry, and provided blood specimens. Women used fertility monitors for up to six consecutive menstrual cycles, with collection of daily first morning voids for hormone analysis in the first two menstrual cycles for prospective assessment of anovulation. Anovulation was assessed by urine pregnanediol glucuronide or luteinising hormone concentration or the fertility monitor. Weighted mixed-effects log-binomial regression was used to estimate associations between measures of adiposity and incident anovulation, adjusted for free (bioavailable) testosterone, anti-Mullerian hormone (AMH), serum lipids, and demographic and life style factors. RESULTS: 343 (28.3%) women experienced at least one anovulatory cycle. Anovulation risk was higher per kg/m2 greater BMI (relative risk [RR] 1.03, 95% confidence interval (CI) 1.01, 1.04), cm waist circumference (RR 1.01, 95% CI 1.00, 1.02), mm subscapular skinfold (RR 1.02, 95% CI 1.01, 1.03), and mm middle upper arm circumference (RR 1.04, 95% CI 1.01, 1.06) adjusted for serum free testosterone, AMH, lipids, and other factors. CONCLUSIONS: Adiposity may be associated with anovulation through pathways other than testosterone among regularly menstruating women. This may account in part for reported associations between greater adiposity and infertility among women having menstrual cycles regularly. Understanding the association between adiposity and anovulation might lead to targeted interventions for preventing infertility.

Sporadic anovulation is not an important determinant of becoming pregnant and time to pregnancy among eumenorrheic women: A simulation study.

BACKGROUND: Attaining pregnancy is conditional upon a series of complex processes, including adequately timed intercourse, ovulation, fertilisation, and implantation. Anovulation is a first-line treatment target for couples with difficulty conceiving and is frequently examined in studies of fecundability. OBJECTIVES: To identify whether sporadic anovulation is an important determinant of cumulative pregnancy rates and time to pregnancy among fertile women with regular menstrual cycles. METHODS: We simulated cumulative pregnancy rates and time to pregnancy for 12 consecutive menstrual cycles among 100 000 women based on data-driven probabilities of implantation, fertilisation, ovulation, and intercourse occurring in the fertile window. We assumed anovulation probabilities of 1%, 8%, or 14.5% and intercourse averaging once per week, every other day, or daily. The model incorporated reductions in implantation and fertilisation rates for successive cycles of non-pregnancy. RESULTS: After 12 cycles, a reduction in the per cycle incidence of anovulation from 14.5% to 1% resulted in a 4.0% higher cumulative pregnancy rate (86.7% vs 90.7%) and similar time to pregnancy (1-cycle median difference). In contrast, increasing mean unscheduled sexual intercourse frequency from weekly to every other day was associated with a 5-cycle median reduction in time to pregnancy (weekly: 7 cycles; every other day or daily: 2 cycles) and a 28.9% increase in the cumulative pregnancy rate (weekly: 59.9%, every other day: 88.8%; daily: 91.6%). CONCLUSIONS: In presumed fertile women with regular menstrual cycles, routine investigation of anovulation may not be an informative outcome in studies of fecundability, and routine testing to ensure ovulation and treatment of anovulation are unlikely to be medically necessary. While biomarkers or cervical fluid may help time intercourse to the fertile window, time to pregnancy can also be improved through increasing the frequency of unscheduled intercourse. These findings need corroboration in large preconception time to pregnancy studies.

Prevalence of metabolic syndrome in women with polycystic ovary syndrome and the factors associated: A cross sectional study at a tertiary care center in Hyderabad, south-eastern India.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) and polycystic ovary syndrome (PCOS) are two interrelated but distinct endocrine problems with several health consequences secondary to insulin resistance. This study aimed to determine the prevalence of MetS in women with PCOS. METHODS: This was a cross sectional study carried out from May 2017 to October 2017 at the gynecology outpatient clinic of a tertiary care private hospital in Hyderabad, India. Eligible women diagnosed with PCOS according to Rotterdam criteria were enrolled. The primary outcome was the prevalence of MetS diagnosed by the modified NCEP ATP III criteria. RESULTS: The study comprised 382 patients with a mean age of 26.8 ± 5.3 years. MetS was present in 147 (38.5%) women with PCOS. The most frequently observed individual components of MetS were increased waist circumference and decreased HDL cholesterol. When predictors for MetS were analyzed by multivariate regression, BMI (aOR 1.14; 1.06-1.23; p ≪0.001) and age (aOR 1.12; 1.06-1.17; p ≪0.001) were significantly associated with MetS; however, the effect size was modest. CONCLUSION: A high prevalence of MetS was observed in women with PCOS at this tertiary center in Hyderabad, with abdominal obesity and low HDL cholesterol as predominant components. We believe that universal screening of all PCOS women is a reasonable option.

Preconception folate status and reproductive outcomes among a prospective cohort of folate-replete women.

BACKGROUND: Most studies of folate metabolism and reproduction have been conducted after pregnancy and in folate-deficient populations. However, measurement of maternal folate status preconceptionally may be most relevant to certain folate-linked early processes preceding a successful pregnancy, and there has been a major increase in folate concentrations in women of childbearing age in high resource settings. OBJECTIVE: To examine associations between preconceptional biomarkers of maternal folate status (folate and homocysteine) and reproductive outcomes in folate-replete women. STUDY DESIGN: Cohort nested within the Effects of Aspirin in Gestation and Reproduction trial, a block-randomized, double-blind, placebo-controlled trial whereby women were randomized to daily low-dose aspirin (81 mg/day) or placebo and all women received folic acid (400 µg/day). In total, 1228 women with 1-2 previous pregnancy losses and no documented infertility were recruited from 4 clinical sites in the United States (2006-2012) and were attempting pregnancy for up to 6 menstrual cycles. Log-binomial regression models were used to estimate relative risks and 95% confidence intervals between preconception serum folate and plasma homocysteine for anovulation, pregnancy, and pregnancy loss. RESULTS: Greater plasma homocysteine was nonlinearly associated with greater risks of pregnancy loss only among women with 2 previous losses: a relative risk of 1.43 (95% confidence interval, 1.08-1.89) was found for plasma homocysteine concentrations at the study median of 8.0 µmol/L compared with a US population median of 6.0 µmol/L. No meaningful relationships were found between serum folate and any reproductive outcome or between plasma homocysteine and anovulation or becoming pregnant. CONCLUSION: These data justify further study of the role of folate and homocysteine metabolism in normal and abnormal early pregnancy.

Polycystic ovary syndrome in adult women. / Síndrome de ovario poliquístico en la mujer adulta.

Polycystic ovary syndrome is the most prevalent endocrine-metabolic pathology in pre-menopausal women. Its etiopathogenesis is complex, multifactorial and heterogeneous, including the interaction of genetic, epigenetic and environmental factors. Androgenic excess constitutes the disease's main physiopathological mechanism and results in reproductive, metabolic and cosmetic alterations which negatively impact these patients' quality of life. The criteria established in the Rotterdam consensus and their correct application form the necessary basis for this syndrome's proper diagnosis. In the absence of an aetiological treatment, the aim is to improve the clinical signs and symptoms derived from hyperandrogenism, ovarian dysfunction and existing metabolic complications, and, therefore, they must be chronic and individualised.

Oligo-anovulation is not a rarer feature in women with documented endometriosis.

OBJECTIVE: To study the prevalence of oligo-anovulation in women suffering from endometriosis compared to that of women without endometriosis. DESIGN: A single-center, cross-sectional study. SETTING: University hospital-based research center. PATIENT (S): We included 354 women with histologically proven endometriosis and 474 women in whom endometriosis was surgically ruled out between 2004 and 2016. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Frequency of oligo-anovulation in women with endometriosis as compared to that prevailing in the disease-free reference group. RESULTS: There was no difference in the rate of oligo-anovulation between women with endometriosis (15.0%) and the reference group (11.2%). Regarding the endometriosis phenotype, oligo-anovulation was reported in 12 (18.2%) superficial peritoneal endometriosis, 12 (10.6%) ovarian endometrioma, and 29 (16.6%) deep infiltrating endometriosis. CONCLUSION(S): Endometriosis should not be discounted in women presenting with oligo-anovulation.

Understanding variation in prevalence estimates of polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) prevalence estimates vary when different diagnostic criteria are applied. Lack of standardization of individual elements within these criteria may contribute to prevalence differences. OBJECTIVE AND RATIONALE: A systematic review of studies reporting prevalence of PCOS, using at least one of the National Institutes of Health (NIH), Rotterdam or Androgen Excess Society (AE-PCOS) criteria, was conducted. The aim was to investigate the impact on prevalence reporting of different definitions of the clinical elements for PCOS diagnosis. SEARCH METHODS: A systematic search of Ovid MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Emcare and BIOSIS was conducted. The search was limited to English language and studies published between January 1990 and January 2018. Included articles needed to define PCOS by at least one of the NIH, Rotterdam or AE-PCOS criteria, be of an unselected population and be published as a full text article. Risk-of-bias was assessed. OUTCOMES: A total of 21 studies met the inclusion criteria. The random-effects pooled prevalence of PCOS in studies that used the NIH criteria (7% [95% CI: 6-7%]), was significantly different from that identified in studies that used the Rotterdam criteria (12% [95% CI: 10-15%], P < 0.0001) but not studies that used the AE-PCOS criteria (10% [95% CI: 6-13%], P = 0.075). The pooled estimates for Rotterdam and AE-PCOS were not significantly different from each other (P = 0.201). Pooled prevalence estimates were compared between studies separated on the basis of: oligo-amenorrhoea vs oligo-amenorrhoea plus short cycles, clinical androgen excess requiring hirsutism vs any clinical androgen excess, use of different versions and cut-offs for the Ferriman-Gallwey (F-G) score, and inclusion vs non-inclusion of oral contraceptive users. There were no statistically significant differences for any of these comparisons. There was insufficient information to allow subgroup analyses of definitions of polycystic ovaries. WIDER IMPLICATIONS: Inclusion of ovarian morphology results in statistically significantly higher pooled prevalence estimates for PCOS. Heterogeneity in prevalence estimates for PCOS reflect the broad clinical spectrum of the condition, lack of standardization of the elements within each set of diagnostic criteria and the use of a range of diagnostic cut-offs, as well as potential differences between study populations. The use of different definitions for anovulation and clinical androgen excess did not appear to contribute to differences in the estimated prevalence of PCOS in this study. However, as the number of studies in most of the comparison groups was small, real differences may have been missed. Uncertainty surrounding the diagnosis of PCOS urgently needs to be addressed in order to provide clinicians and their patients with greater diagnostic certainty, and hence reduce inappropriate labelling and the potential psychological harm that may accompany misdiagnosis.

Association of testosterone and antimüllerian hormone with time to pregnancy and pregnancy loss in fecund women attempting pregnancy.

OBJECTIVE: To examine whether higher T and/or antimüllerian hormone (AMH) was associated with anovulation, time to pregnancy (TTP), or pregnancy loss risk among healthy, fecund women without diagnosed polycystic ovary syndrome. DESIGN: Prospective cohort study conducted as a secondary analysis from the Effects of Aspirin in Gestation and Reproduction randomized trial. SETTING: University medical centers. PATIENT(S): A total of 1,198 healthy, eumenorrheic women aged 18-40 years attempting spontaneous pregnancy with one to two prior pregnancy losses were included. Women were categorized by baseline antimüllerian hormone (AMH), as a surrogate marker of antral follicle count, and T concentrations; the highest quartile for each was "high," and below the top quartile (i.e., lower 75% of values) was "norm," forming four groups: norm T/norm AMH (n = 742), norm T/high AMH (n = 156), high T/norm AMH (n = 157), and high T/high AMH (n = 143). INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Anovulation, pregnancy incidence, TTP, and pregnancy loss incidence. RESULT(S): Women with high T/high AMH had a greater anovulation risk (risk ratio 1.58, 95% confidence interval 1.13-2.22) compared with women with norm T/norm AMH, but with imprecise differences in incidence of pregnancy, TTP, or pregnancy loss. CONCLUSION(S): Women with higher T and AMH had more frequent anovulatory cycles but with marginal impacts on TTP or pregnancy loss. A continuum of mild inefficiency in reproductive function may be related to higher T and AMH, including in fecund women with normal menstrual cycles and no clinical diagnosis of polycystic ovary syndrome, but with unclear effects on fecundability and pregnancy loss. CLINICAL TRIAL REGISTRATION NUMBER: NCT00467363.

Rates of Anovulation in Adolescents and Young Adults with Moderate to Severe Primary Dysmenorrhea and Those without Primary Dysmenorrhea.

STUDY OBJECTIVE: To evaluate rates of presumptive anovulation in eumenorrheic adolescents and young adults with moderate to severe primary dysmenorrhea and those without primary dysmenorrhea. DESIGN: Participants completed luteinizing hormone surge ovulation predictor test kits. Anovulatory cycles were defined by never receiving a positive result before the next menstrual period; participants were grouped as anovulatory if they experienced at least 1 anovulatory cycle during study participation. Participants rated daily level of menstrual pain on a 0-10 numeric rating scale. SETTING: A university-based clinical research laboratory. PARTICIPANTS: Thirty-nine adolescents and young adults (ages 16-24) with primary dysmenorrhea and 52 age-matched control girls. INTERVENTIONS AND MAIN OUTCOME MEASURES: Rates of presumptive anovulation. RESULTS: One hundred sixty-eight cycles were monitored, 29.8% (N = 50) of which were anovulatory (37.1% [39/105] vs 17.5% [11/63] of cycles in control and dysmenorrhea groups, respectively). During study participation, control girls were significantly more likely to have had at least 1 anovulatory cycle than were girls with primary dysmenorrhea (44.2% [23/52] vs 17.9% [7/39] of participants, respectively; P < .01). Cycle length and number of bleeding days between ovulatory and anovulatory cycles were similar. The primary dysmenorrhea group's maximum menstrual pain ratings did not differ between ovulatory and anovulatory cycles (4.77 and 4.36, respectively; P > .05). CONCLUSION: Our data support previous findings of increased rates of ovulation in primary dysmenorrhea. However, menstruation after anovulatory cycles can be as painful as menstruation after ovulatory cycles. These data support the idea that regular menses do not necessarily indicate that a normal ovulatory cycle has occurred. Previous implications that ovulation is necessary for the development of substantial menstrual pain are incomplete.

The incidence of metabolic syndrome in adolescents with different phenotypes of PCOS.

OBJECTIVES: To evaluate the incidence of metabolic syndrome in Turkish adolescents with different phenotypes of polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: This cross-sectional study was performed on the Youth Center clinic of a tertiary referral hospital in Turkey. Adolescents with PCOS (n = 144) were classified into four phenotype groups according to the presence of oligo/anovulation (O), hyperandrogenism (H), and polycystic ovarian morphology (P) as follows: Phenotype A (O + H + P), Phenotype B (H + O), Phenotype C (H + P), Phenotype D (O + P). The adolescents gave early follicular phase blood samples for endocrine and metabolic tests. The incidence and the presence of parameters of metabolic syndrome were assessed among the four groups. RESULTS: In total, 54.9% of the adolescents with PCOS were overweight and 25.7% had metabolic syndrome. The incidence of metabolic syndrome in Phenotypes A-D were as follows: 39.5%, 20.5%, 26.5%, and 15.2%, respectively. Although body mass index was higher in the Phenotype A group, insulin resistance was similar in all of the phenotype groups. The most common dyslipidemia was low HDL-C levels and this was present in more than half of the adolescents with PCOS. Both body mass index and total testosterone levels were significantly higher in adolescents with metabolic syndrome in comparison to those without metabolic syndrome. CONCLUSIONS: Although low HDL-C levels and insulin resistance are common PCOS findings in adolescents, the metabolic profile seems to be worse in Phenotype A than the other phenotypes. Therefore, screening programs should evaluate patients based on the known risk factors and phenotypes for adolescents with PCOS.

Metabolic syndrome and metabolic risk profile according to polycystic ovary syndrome phenotype.

AIM: It is unknown which phenotype of polycystic ovary syndrome (PCOS) has a greater metabolic risk and how to detect this risk. The aim of this study was therefore to compare the incidence of metabolic syndrome (MetS) and metabolic risk profile (MRP) for different phenotypes. METHODS: A total of 100 consecutive newly diagnosed PCOS women in a tertiary referral hospital were recruited. Patients were classified into four phenotypes according to the Rotterdam criteria, on the presence of at least two of the three criteria hyperandrogenism (H), oligo/anovulation (O) and PCO appearance (P): phenotype A, H + O + P; phenotype B, H + O; phenotype C, H + P; phenotype D, O + P. Prevalence of MetS and MRP were compared among the four groups. RESULTS: Based on Natural Cholesterol Education Program Adult Treatment Panel III diagnostic criteria, MetS prevalence was higher in phenotypes A and B (29.6% and 34.5%) compared with the other phenotypes (10.0% and 8.3%; P < 0.001). Although the prevalence of obesity was similar, the number of patients with homeostatic model assessment insulin resistance index (HOMA-IR) >3.8 was significantly higher in androgenic PCOS phenotypes. After logistic regression analysis, visceral adiposity index (VAI) was the only independent predictor of MetS in PCOS (P = 0.002). VAI was also significantly higher in phenotype B, when compared with the others (P < 0.01). CONCLUSION: Phenotypes A and B had the highest risk of MetS among the four phenotypes, and VAI may be a predictor of metabolic risk in PCOS women.

Revisión: Actualización en el tratamiento del sangrado menstrual abundante / Review: An update on the treatment of heavy menstrual bleeding

El sangrado menstrual abundante (SMA) es un trastorno con un gran impacto en la mujer que conlleva un empeoramiento de su calidad de vida. Los objetivos que persigue su tratamiento incluyen la corrección de la anemia, la disminución de la cantidad de sangrado, la prevención de recurrencias y de las consecuencias a largo plazo de la anovulación, y la mejora de la calidad de vida de la mujer. La elección del tratamiento debe basarse en la decisión de la mujer tras conocer las ventajas y efectos adversos de las diferentes opciones, teniendo en cuenta sus deseos reproductivos y preferencias personales. El tratamiento farmacológico debe considerarse cuando no se hayan identificado anomalías estructurales como causa del SMA. El tratamiento farmacológico no hormonal, es de primera elección en pacientes con SMA con ciclos ovulatorios, con deseos genésicos o con limitaciones al tratamiento hormonal; incluye los aintiinflamatorios no esteroideos y los antibibrinolíticos (especialmente ácido tranexámico). El tratamiento farmacológico hormonal es la opción más adecuada ante alteraciones de la ovulación que causan SMA. En España tienen indicación específica el DIU-LNG, de primera elección en mujeres que no planean un embarazo, y un combinado cuatrifásico con valerato de estradiol y dienogest (VE2-DNG) oral. Los SMA de causa orgánica requieren el abordaje quirúrgico de los procesos patológicos que los provocan. Las opciones terapéuticas que han demostrado eficacia son la ablación endometrial y la resección endometrial (mínimamente invasivas pero no siempre completamente exitosas) y la histerectomía (cirugía mayor). En la presente revisión se analizan todas ellas

Heavy menstrual bleeding (HMB) is a disorder with a major impact on the woman which is associated with a worsening of their quality of life. The objectives pursued with its treatment are correction of anemia, decrease of the amount of bleeding, prevention of recurrence and long-term consequences of anovulation, and improving the quality of life of women. The choice of treatment should be based on the decision of the woman after knowing the benefits and adverse effects of different options, taking into account their reproductive desires and personal preferences. Drug therapy should be considered when structural abnormalities have not been identified as the cause of HMB. Non-hormonal drug treatment is the first choice in patients with HMB with ovulatory cycles, with reproductive desires or limitations to hormone treatment; It includes non-steroidal anti-inflammatories and antifibrinolytics (especially tranexamic acid). The hormonal drug treatment is the best option in HMB caused by ovulation disorders. In Spain, the LNG-IUD has this specific indication, of first choice in women who may become pregnant, and an oral quadriphasic combined with estradiol valerate and dienogest (VE2-DNG). The HMB with organic cause require the surgical approach of the pathological processes that cause them. The treatment options that have proven efficacy are endometrial ablation and endometrial resection (minimally invasive but not always completely successful) and hysterectomy (major surgery). In this paper, we analyze all of them

Ovulation Prevalence in Women with Spontaneous Normal-Length Menstrual Cycles - A Population-Based Cohort from HUNT3, Norway.

BACKGROUND: Ovulatory menstrual cycles are essential for women's fertility and needed to prevent bone loss. There is a medical/cultural expectation that clinically normal menstrual cycles are inevitably ovulatory. Currently within the general population it is unknown the proportion of regular, normal-length menstrual cycles that are ovulatory. Thus, the objective of this study was to determine the population point prevalence of ovulation in premenopausal, normally menstruating women. The null hypothesis was that such cycles are ovulatory. METHODS: This is a single-cycle, cross-sectional, population-based study-a sub-study of the HUNT3 health study in the semi-rural county (Nord Trøndelag) in mid-Norway. Participants included >3,700 spontaneously (no hormonal contraception) menstruating women, primarily Caucasian, ages 20-49.9 from that county. Participation rate was 51.9%. All reported the date previous flow started. A single, random serum progesterone level was considered ovulatory if ≥9.54 nmol/L on cycle days 14 to -3 days before usual cycle length (CL). RESULTS: Ovulation was assessed in 3,168 women mean age 41.7 (interquartile range, [IQR] 36.8 to 45.5), cycle length 28 days (d) (IQR 28 to 28) and body mass index (BMI) 26.3 kg/m2 (95% CI 26.1 to 26.4). Parity was 95.6%, 30% smoked, 61.3% exercised regularly and 18% were obese. 1,545 women with a serum progesterone level on cycle days 14 to -3 were presumed to be in the luteal phase. Of these, 63.3% of women had an ovulatory cycle (n = 978) and 37% (n = 567) were anovulatory. Women with/ without ovulation did not differ in age, BMI, cycle day, menarche age, cigarette use, physical activity, % obesity or self-reported health. There were minimal differences in parity (96.7% vs. 94.5%, P = 0.04) and major differences in progesterone level (24.5 vs. 3.8 nmol/L, P = 0.001). CONCLUSION: Anovulation in a random population occurs in over a third of clinically normal menstrual cycles.

Assisted reproductive technology treatment in women with severe eating disorders: a national cohort study.

INTRODUCTION: This national retrospective cohort study investigates the prevalence of women with severe eating disorders in assisted reproductive technology (ART) treatment compared with an age-matched background population without ART treatment. It assesses the frequency distribution of the first and last eating disorder diagnosis before, during, and after ART treatment, and evaluates differences in obstetric outcomes between women with and without a severe eating disorder. MATERIAL AND METHODS: Hospital-diagnosed eating disorders among 42,915 women in the Danish National ART cohort (DANAC), registered during 1994-2009 in the mandatory Psychiatric Central Research Register, were compared with a non-eating disorder ART cohort of 42,644 women and an age-matched background population of 215,290 women without a history of ART treatment for the main outcome measures prevalence of eating disorders, frequency distribution of diagnoses before/during/after ART treatment, as well as ART treatment and obstetric outcomes. RESULTS: In the ART cohort, 271 women (0.63%) had an eating disorder diagnosis compared with 0.73% in the background population (p = 0.025). The prevalence of ovulatory disorder was significantly higher in women with a severe eating disorder compared with the ART cohort without eating disorders. Obstetric outcomes were similar in ART-treated women with and without an eating disorder. CONCLUSION: Women with severe eating disorders were identified in the ART cohort, although significantly less often than in the age-matched background population. Women with severe eating disorders suffered more often from anovulatory infertility than the ART comparison cohort without this disease. Obstetric outcomes appeared reassuring in the ART cohort with eating disorders.

Ovulation rate and cycle characteristics in a subsequent clomiphene citrate cycle after stair-step protocol.

OBJECTIVE: To determine the ovulation rate after ovulation induction with clomiphene citrate (CC) in women who had previously been ovulatory after a stair-step (CC-SS) ovulation induction. DESIGN: Retrospective cohort. SETTING: University-based tertiary fertility center. PATIENT(S): 61 anovulatory patients <40 years of age with polycystic ovary syndrome who underwent ovulation induction with a CC-SS protocol and a subsequent CC cycle. INTERVENTION(S): Ovulation induction with CC. MAIN OUTCOME MEASURE(S): Ovulation rates and cycle characteristics. RESULT(S): Of 61 patients who underwent a subsequent CC cycle, 15 (25%) failed to ovulate at the previously ovulatory dose. Of those 15 patients, 13 (86.7%) ovulated after an increase in dose. The total number of follicles ≥15 mm (2.8 ± 1.2 vs. 1.6 ± 0.7) and peak estradiol (E2) levels (604 ± 272 pg/mL vs. 447 ± 218 pg/mL) were statistically significantly higher in the CC-SS cycle compared with the subsequent CC cycle, respectively. The endometrial lining was statistically significantly thinner in the CC-SS than the CC cycle (7.8 ± 1.8 vs. 9.2 ± 2.7, respectively). CONCLUSION(S): The majority of patients who ovulate after a CC-SS protocol will ovulate after taking the previously ovulatory CC dose in a subsequent cycle. Those who do not ovulate will likely ovulate with a further increase in CC dose.

[Polycystic ovary syndrome: is there a rise in the prevalence?]. / Síndrome de ovario poliquístico: Ha aumentado su prevalencia?

OBJECTIVE: To determine the prevalence of polycystic ovary syndrome (PCOS) according to the three major diagnostic criteria previously described in an unselected group of women from Spain and to identify the most common phenotypes of the disease. MATERIAL AND METHOD: An observational, transversal prevalence study was carried out between July 1 2014 and October 31 2014. All participants received a questionnaire and underwent a physical and trans-vaginal ultrasound examination. Blood samples were also collected for analysis of metabolic markers and hormones. PCOS was diagnosed according to three major criteria: NIH, Rotterdam and AE-PCOS criteria. Following diagnosis women with PCOS were assigned to one of four phenotypes. RESULTS: A total of 242 women were involved in the study. The prevalence for each major criteria was as follows: National Institute of Health (NIH) criteria had a prevalence of 1 4.88%, Rotterdam criteria had a prevalence of 29.34% and Androgen Excess and PCOS Society criteria presented a prevalence of 17.36%. The prevalence for each phenotype was: A, 40.85%; B, 25.35%; C, 8.45%; and D, 25.35%. PCOS women had more prevalence of hirsutism (36.61 %), infertility (25.35%), obesity (21.1 2%) and metabolic syndrome (11 .26%) than controls (7.01%, 6.43%, 5.84% and 2.33% respectively). CONCLUSION: There is a rise in the prevalence of PCOS in Caucasian population with the classic phenotype (oligo-anovulation, hyperandrogenism, polycystic ovaries) being the most common presentation of the syndrome.

Assessment of anovulation in eumenorrheic women: comparison of ovulation detection algorithms.

OBJECTIVE: To compare previously used algorithms to identify anovulatory menstrual cycles in women self-reporting regular menses. DESIGN: Prospective cohort study. SETTING: Western New York. PATIENT(S): Two hundred fifty-nine healthy, regularly menstruating women followed for one (n=9) or two (n=250) menstrual cycles (2005-2007). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Prevalence of sporadic anovulatory cycles identified using 11 previously defined algorithms that use E2, P, and LH concentrations. RESULT(S): Algorithms based on serum LH, E2, and P levels detected a prevalence of anovulation across the study period of 5.5%-12.8% (concordant classification for 91.7%-97.4% of cycles). The prevalence of anovulatory cycles varied from 3.4% to 18.6% using algorithms based on urinary LH alone or with the primary E2 metabolite, estrone-3-glucuronide, levels. CONCLUSION(S): The prevalence of anovulatory cycles among healthy women varied by algorithm. Mid-cycle LH surge urine-based algorithms used in over-the-counter fertility monitors tended to classify a higher proportion of anovulatory cycles compared with luteal-phase P serum-based algorithms. Our study demonstrates that algorithms based on the LH surge, or in conjunction with estrone-3-glucuronide, potentially estimate a higher percentage of anovulatory episodes. Addition of measurements of postovulatory serum P or urine pregnanediol may aid in detecting ovulation.

Birth weight and ovulatory dysfunction.

OBJECTIVE: To explore the association between birthweight and ovulatory dysfunction in adulthood. DESIGN: Case-control study. SETTING: Northeast of Scotland University Hospital, hosting the regional fertility centre and maternity unit. POPULATION: A total of 18,846 mother-daughter record pairs from the Aberdeen Fertility Centre Data Set and the Aberdeen Maternity and Neonatal Databank (AMND). Cases were the daughters with ovulatory dysfunction attending the Aberdeen Fertility Centre between 1992 and 2007, Control group 1 included the daughters attending the fertility centre with confirmed ovulation, and Control group 2 included all women naturally fertile who gave birth in Aberdeen during the same period. METHODS: The electronic maternity records of the mothers of women in the three groups were retrieved from AMND and compared. MAIN OUTCOME MEASURES: Daughters' birthweight and standardised birthweight, characteristics of mothers and daughters at delivery and current daughters' characteristics. RESULTS: Cases, Control group 1 and Control group 2 included 466, 548 and 17,832 daughters, respectively. The mean birthweight (standard deviation) in grams was comparable between Cases 3203 (522), Control group 1, 3235 (482) P = 0.30, and Control group 2, 3226 (495) P = 0.31. The proportions of daughters born small for gestational age, large for gestational age, or preterm were comparable between the Cases group and each Control group, as was the mode of delivery and Apgar scores at 1 and 5 minutes. The age at delivery, body mass index, social class or pregnancy complications were comparable in the mothers of the Cases and each Control group. CONCLUSIONS: Ovulatory dysfunction does not appear to be related to birthweight or perinatal events.

Negative spinal bone mineral density changes and subclinical ovulatory disturbances--prospective data in healthy premenopausal women with regular menstrual cycles.

Subclinical ovulatory disturbances (anovulation or short luteal phases within normal-length menstrual cycles) indicate lower progesterone-to-estrogen levels. Given that progesterone plays a bone formation role, subclinical ovulatory disturbances may be associated with bone loss or less than expected bone gain. Our purpose was to perform a meta-analysis of prospective studies in healthy premenopausal women to determine the overall relationship of subclinical ovulatory disturbances to change in bone mineral density. Two reviewers independently identified from serial literature searches 6 studies meeting inclusion criteria: a 2-year study in 114 young adult women, 2006-2009, Vancouver, Canada; a 2-year study in 189 premenopausal women, 2000-2005, Toronto, Canada; a single-cycle study in 14 young women, 1996-1997, Melbourne, Australia; an 18-month study in 53 women, 1990-1995, Santa Clara, California; a 4-year study in 27 women, 1988-1995, Vancouver, Canada; and a 1-year study in 66 women, 1985-1988, Vancouver, Canada. This meta-analysis included a combined sample size of 473 observations in 436 premenopausal women studied over 1-4 years and aged 14-47 years. The percentage of women with ovulatory disturbances varied significantly from 13% to 82%. Women with more frequent ovulatory disturbances had more negative percentage changes in spine bone mineral density (weighted mean difference = -0.86; P = 0.040) for random-effects analysis. There was significant heterogeneity among these 6 studies (I(2) = 80%). In summary, these data show that regularly menstruating women with more frequent ovulatory disturbances experience more negative changes in bone (approximately -0.9% per year). These cycles with silent estrogen/progesterone imbalance may be clinically important.