Evaluation of Ovarian Reserve Tests and Age in the Prediction of Poor Ovarian Response to Controlled Ovarian Stimulation-A Real-World Data Analysis of 89,002 Patients.

Aims: This study aimed to explore the value of ovarian reserve tests (ORTs) for predicting poor ovary response (POR) and whether an age cutoff could improve this forecasting, so as to facilitate clinical decision-making for women undergoing in vitro fertilization (IVF). Methods: A retrospective cohort study was conducted on poor ovary response (POR) patients using real-world data from five reproductive centers of university-affiliated hospitals or large academic hospitals in China. A total of 89,002 women with infertility undergoing their first traditional ovarian stimulation cycle for in vitro fertilization from January 2013 to December 2019 were included. The receiver operating characteristic (ROC) curve was performed to estimate the prediction value of POR by the following ORTs: anti-Mullerian hormone (AMH), antral follicle count (AFC), basal FSH (bFSH), as well as patient age. Results: In this retrospective cohort, the frequency of POR in the first IVF cycle was 14.8%. Age, AFC, AMH, and bFSH were used as predicting factors for POR, of which AMH and AFC were the best indicators when using a single factor for prediction (AUC 0.862 and 0.842, respectively). The predictive values of the multivariate model included age and AMH (AUC 0.865), age and AFC (AUC 0.850), age and all three ORTs (AUC 0.873). Compared with using a single factor alone, the combinations of ORTs and female age can increase the predictive value of POR. Adding age to single AMH model improved the prediction accuracy compared with AMH alone (AUC 0.865 vs. 0.862), but the improvement was not significant. The AFC with age model significantly improved the prediction accuracy of the single AFC model (AUC 0.846 vs. 0.837). To reach 90% specificity for POR prediction, the cutoff point for age was 38 years old with a sensitivity of 40.7%, 5 for AFC with a sensitivity of 55.9%, and 1.18 ng/ml for AMH with a sensitivity of 63.3%. Conclusion: AFC and AMH demonstrated a high accuracy when using ROC regression to predict POR. When testing is reliable, AMH can be used alone to forecast POR. When AFC is used as a prediction parameter, age is suggested to be considered as well. Based on the results of the cutoff threshold analysis, AFC ≤ 5 and AMH ≤ 1.18 ng/ml should be recommended to predict POR more accurately in IVF/ICSI patients.

Increased Likelihood of Pregnancy Using an App-Connected Ovulation Test System: A Randomized Controlled Trial.

Background: Women trying to conceive are increasingly using fertility-tracking software applications to time intercourse. This study evaluated the difference in conception rates between women trying to conceive using an application-connected ovulation test system, which measures urinary luteinizing hormone and an estrogen metabolite, versus those trying without using ovulation testing. Materials and Methods: This home-based study involved 844 volunteers aged 18-40 years seeking to conceive. Volunteers randomized to the test arm were required to use the test system for the duration of the study while those randomized to the control arm were instructed not to use ovulation testing. Pregnancy rate differences across one and two cycles between the two groups were examined. Results: Volunteers in the test (n = 382) and control arms (n = 403) had similar baseline demographics. The proportion of women pregnant after one cycle was significantly greater in the test arm (25.4%) compared with the control arm (14.7%; p < 0.001). After two cycles, there continued to be a greater proportion of women pregnant in the test arm compared with the control arm (36.2% vs. 28.6%; p = 0.026). In the test arm, volunteers had intercourse less frequently per cycle compared with those not using ovulation testing (9 [range: 1-60] vs. 10 [range: 1-50]; p = 0.027), but were more likely to target intercourse to a particular part of their cycle compared with those not using ovulation testing (88.5% vs. 57.8%; p < 0.001). Conclusion: Using the test system to time intercourse within the fertile window increases the likelihood of conceiving within two menstrual cycles.

Menstrual cyclicity is predictably unpredictable.

"Time moves slowly but passes quickly" - Alice Walker.

Identification and prediction of the fertile window with a new web-based medical device using a vaginal biosensor for measuring the circadian and circamensual core body temperature.

Fertility awareness-based (FAB) methods represent a term that includes all family planning methods that are based on the identification of the fertile window. They are based on the woman's observation of physiological signs of the fertile and infertile phases of the menstrual cycle. The first approach consists basically in symptothermal methods accompanied by cervical mucus measurements and clinical menstrual cycling data recording. The second most often used methods are the urinary measurement of E3G and luteinizing hormone (LH) with a personalized computer system. Hence these systems lack the efficacy of the continuous circadian and circamensual measurement of the core body temperature. Only this approach enables the accurate detection of the ovulation during the fertile window. A new medical device called OvulaRing has been developed to fill this gap. In the present study, the system and its first clinical results are presented. OvulaRing is a medical device used just like a tampon. The device is a vaginal ring of evatane that contains an integrated biosensor. This sensor measures continuously every 5 min the core body temperature throughout the entire cycle. This device allows a circadian and circamensual intravaginal exact measurement. With this system, 288 measurements are created per day. The system can detect retrospectively and predict prospectively the fertile window of the users. One hundred and fifty eight women aged between 18 and 45 years used this medical device in an open non-randomized clinical study for 15 months. A total of 470 cycles could be recorded and were able for analysis. By the same time in a subgroup of patients, hormonal assessments of LH, follicle-stimulating hormone, estradiol and progesterone as well as vaginal ultrasound were performed in parallel between the 9th and the 36th day of the cycle. The validation error due to software errors was 0.89% for the retrospective analysis; that means that the accuracy for the detection of the ovulation was 99.11%. Accuracy of 88.8% for a window of 3 days before ovulation, the day of ovulation and the 3 days after ovulation was achieved for the prospective analysis. In the subgroup of woman with recorded pregnancies, it could be shown that after 3.79 months of use (median) pregnancies were observed. In 67.72% in up to 3 months, in 16.36% between 3 and 6 months of use, in 7.27% between 7 and 9 months, in 5.45% between 10 and 12 months and in 1.82% between 13 and 15 months of use of the system. With this new web-based system, a precise determination of the fertile window even in women with ultralong cycles (>35 days) could be detected independently of their personal live circumstances. Exact determination of the fertile window is herewith possible so that OvulaRing represents an evolution in the FAB method for the cycle diagnosis of women with regular, irregular or anovulatory menstrual cycles.

Use of Bone Morphogenetic Protein 15 Polymorphisms to Predict Ovarian Stimulation Outcomes in Infertile Brazilian Women.

AIMS: Polymorphisms in the gene encoding bone morphogenetic protein 15 (BMP15) can result in inhibited secretion or lowered bioactivity of the BMP15 protein. BMP15 levels are associated with follicle-stimulating hormone receptor (FSHR) action on granulosa cells, wherein FSHR increases the sensitivity of ovarian follicles to follicle-stimulating hormone (FSH). In this study we evaluated the BMP15 polymorphisms A905 > G/rs3897937, C901 > T/rs17003221, and C-9 > G/rs3810682 in infertile Brazilian women in terms of anti-Mullerian hormone (AMH), FSH, and estradiol serum levels, as well as controlled ovarian hyperstimulation response and assisted reproduction outcomes. METHODS: A cross-sectional study comprising 186 infertile women who underwent the first cycle of high complexity assisted reproduction treatment was conducted using the TaqMan assay for quantitative polymerase chain reaction genotyping. Serum AMH, FSH, and estradiol levels were measured by enzyme-linked immunosorbent assay. RESULTS: For C901 > T (rs17003221) carriers, there was a statistically significant difference among carriers of a polymorphic BMP15 genotype (TT) and the estradiol concentration. These women had higher estradiol levels than women who had homozygous wild type or heterozygous genotypes. There was also a positive correlation between serum AMH and the C-9 > G (rs3810682) polymorphism, wherein women carrying both polymorphic alleles (homozygous, GG) had higher average AMH levels than heterozygous women. However, none of the three polymorphisms studied showed a statistically significant correlation with assisted reproduction outcome. DISCUSSION: Oocytes are known to secrete factors that regulate follicular development and oocyte maturation. Abnormal expression of these factors may thus be involved in follicular development disorders. A recent study highlighted the importance of BMP15 in regulating ovulation rates in sheep and that heterozygous deletions in the -9C > G polymorphism reduced BMP15 concentrations, increased granulosa cell FHSR mRNA levels, elevated estrogen secretion, and activated production of stem cell factors. In this study we found that BMP15 polymorphisms affected estrogen and AMH levels. CONCLUSION: BMP15 polymorphisms are not correlated with ovarian stimulation and assisted reproduction outcomes in infertile Brazilian women.

Three-dimensional sonography-based automated volume calculation (SonoAVC) versus two-dimensional manual follicular tracking in in vitro fertilization.

OBJECTIVE: To compare the predictive value of manual two-dimensional follicular monitoring with that of sonography-based automated volume calculation (SonoAVC) in routine follicular tracking in in vitro fertilization (IVF). METHODS: A prospective study was undertaken of women undergoing IVF with controlled ovarian hyperstimulation at a center in New Delhi, India, between October and November 2013. Follicular monitoring was performed both manually and in three dimensions with SonoAVC. On the day of oocyte retrieval, the follicular count and dimensions were calculated with both techniques and correlated with the number of oocytes retrieved. RESULTS: Overall, 46 patients and 91 ovaries were studied. The mean times taken to perform manual and SonoAVC measurements were 209.2 ± 47.4 s and 156.6 ± 38.6 s, respectively (P < 0.001). The mean follicular count was significantly lower when measured manually than with SonoAVC (8.46 ± 3.35 vs 9.91 ± 4.60; P = 0.016). However, the mean leading follicle diameter measured manually (19.45 ± 2.46 mm) was similar to both the mean diameter (21.12 ± 2.65 mm) and the volume-based diameter (19.56 ± 2.16 mm) measured with SonoAVC. CONCLUSION: Three-dimensional SonoAVC could be a useful adjunct for follicular monitoring, with a significant reduction in time and a good correlation with manual counts. However, further studies with larger sample sizes are required.

Timed intercourse for couples trying to conceive.

BACKGROUND: Fertility problems are very common, as subfertility affects about 10% to 15% of couples trying to conceive. There are many factors that may impact a couple's ability to conceive and one of these may be incorrect timing of intercourse. Conception is only possible from approximately five days before up to several hours after ovulation. Therefore, to be effective, intercourse must take place during this fertile period. 'Timed intercourse' is the practice of prospectively identifying ovulation and, thus, the fertile period to increase the likelihood of conception. Whilst timed intercourse may increase conception rates and reduce unnecessary intervention and costs, there may be associated adverse aspects including time consumption and stress. Ovulation prediction methods used for timing intercourse include urinary hormone measurement (luteinizing hormone (LH), estrogen), tracking basal body temperatures, cervical mucus investigation, calendar charting and ultrasonography. This review considered the evidence from randomised controlled trials for the use of timed intercourse on positive pregnancy outcomes. OBJECTIVES: To assess the benefits and risks of ovulation prediction methods for timing intercourse on conception in couples trying to conceive. SEARCH METHODS: We searched the following sources to identify relevant randomised controlled trials, the Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, PubMed, LILACS, Web of Knowledge, the World Health Organization (WHO) Clinical Trials Register Platform and ClinicalTrials.gov. Furthermore, we manually searched the references of relevant articles. The search was not restricted by language or publication status. The last search was on 5 August 2014. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing timed intercourse versus intercourse without ovulation prediction or comparing different methods of ovulation prediction for timing intercourse against each other in couples trying to conceive. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and risk of bias and extracted the data. The primary review outcomes were cumulative live birth and adverse events (such as quality of life, depression and stress). Secondary outcomes were clinical pregnancy, pregnancy (clinical or self-reported pregnancy, not yet confirmed by ultrasound) and time to conception. We combined data to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I(2) statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods. MAIN RESULTS: We included five RCTs (2840 women or couples) comparing timed intercourse versus intercourse without ovulation prediction. Unfortunately one large study (n = 1453) reporting live birth and pregnancy had not published outcome data by randomised group and therefore could not be analysed. Consequently, four RCTs (n = 1387) were included in the meta-analysis. The evidence was of low to very low quality. Main limitations for downgrading the evidence included imprecision, lack of reporting clinically relevant outcomes and the high risk of publication bias.One study reported live birth, but the sample size was too small to draw any relevant conclusions on the effect of timed intercourse (RR 0.75, 95% CI 0.16 to 3.41, 1 RCT, n = 17, very low quality).One study reported stress as an adverse event. There was no evidence of a difference in levels of stress (mean difference 1.98, 95 CI% -0.87 to 4.83, 1 RCT, n = 77, low level evidence). No other studies reported adverse events.Two studies reported clinical pregnancy. There was no evidence of a difference in clinical pregnancy rates (RR 1.10, 95% CI 0.57 to 2.12, 2 RCTs, n = 177, I(2) = 0%, low level evidence). This suggested that if the chance of a clinical pregnancy following intercourse without ovulation prediction is assumed to be 16%, the chance of success following timed intercourse would be between 9% and 33%.Four studies reported pregnancy rate (clinical or self-reported pregnancy). Timed intercourse was associated with higher pregnancy rates compared to intercourse without ovulation prediction in couples trying to conceive (RR 1.35, 95% CI 1.06 to 1.71, 4 RCTs, n = 1387, I(2) = 0%, very low level evidence). This suggests that if the chance of a pregnancy following intercourse without ovulation prediction is assumed to be 13%, the chance following timed intercourse would be between 14% and 23%. Subgroup analysis by duration of subfertility showed no difference in effect between couples trying to conceive for < 12 months versus couples trying for ≥ 12 months. One trial reported time to conception data and showed no evidence of a difference in time to conception. AUTHORS' CONCLUSIONS: There are insufficient data available to draw conclusions on the effectiveness of timed intercourse for the outcomes of live birth, adverse events and clinical pregnancy. Timed intercourse may improve pregnancy rates (clinical or self-reported pregnancy, not yet confirmed by ultrasound) compared to intercourse without ovulation prediction. The quality of this evidence is low to very low and therefore findings should be regarded with caution. There is a high risk of publication bias, as one large study remains unpublished 8 years after recruitment finished. Further research is required, reporting clinically relevant outcomes (live birth, clinical pregnancy rates and adverse effects), to determine if timed intercourse is safe and effective in couples trying to conceive.

Accuracy of perception of ovulation day in women trying to conceive.

BACKGROUND: The likelihood of conception is increased if intercourse is timed to coincide with the fertile period (5 days up to ovulation). However, to be effective, this requires good awareness of the day of ovulation. The aim of this study was to examine the accuracy of women's perceived ovulation day, compared with actual fertile days, in a cohort of women trying to conceive. MAIN OUTCOME MEASURES: Comparison of women's estimated day of ovulation with their actual ovulation day (determined by detecting luteinising hormone). METHODS: This was a sample collection study and volunteer women were recruited via online advertising. At recruitment volunteers reported the cycle day they believed they ovulated. They then used a home urine fertility monitor to test their daily fertility status to time intercourse to try and achieve conception, in addition to collecting early morning urine samples for laboratory analysis. The main outcome measure was a comparison of women's estimated day of ovulation with their actual ovulation day, as determined by urine detection of luteinising hormone. RESULTS: Three hundred and thirty women were recruited onto the study and data was available for 102 volunteers who became pregnant. Thirteen women (12.7%) correctly estimated their ovulation day; median difference +2 days, range -10 to +27 days. The most common days for estimation of ovulation were day 14 (35.5%) and day 15 (15.7%). Only 55% of estimated ovulation days fell within the volunteers' fertile window; only 27% on days of peak fertility. CONCLUSIONS: Women trying to conceive may benefit from using a prospective method to identify their fertile phase, as a significant proportion could be incorrectly estimating their fertile days. These observations were made on women who were actively looking for knowledge on fertility and considered only cycles where conception occurred, inaccuracy could be greater if a broader population is considered.

Anti-mullerian hormone as a predictive marker for the selection of women for oocyte in vitro maturation treatment.

PURPOSE: In oocyte in-vitro maturation (IVM) treatments, the chances to achieve a pregnancy are critically dependent on the retrieval of a suitable number of oocytes. In this study, we assessed the ability of circulating levels of anti-mullerian hormone (AMH) to identify normo-ovulatory women suitable for IVM treatment on the basis of the number of retrieved oocytes. METHOD: Serum AMH was quantified in normo-ovulatory women younger than 39 years undergoing IVM treatment. After immature oocyte retrieval and IVM, maximum 3 mature oocytes were used for treatment and all resulting embryos were transferred, as established by law. From 177 cycles, 991 oocytes were recovered. Following IVM, 484 mature oocytes were obtained (50.1%). RESULTS: The overall pregnancy rate per embryo transfer was 16.6% (25/151) and the implantation rate was 10.9% (30/278). Linear regression and receiver operating characteristic (ROC) analyses were applied to identify independent variables and quantify a cut-off AMH value able to identify patients suitable for IVM treatment. An AMH value of 1.28 ng/ml was identified as a threshold for the prediction of the retrieval of at least 5 oocytes, with a sensitivity of 93.4% and a specificity of 33.8%. Positive and negative predictive values were 67.6% and 75.0%, respectively. CONCLUSIONS: AMH can be adopted to identify women candidate for an IVM treatment from whom a suitable number of oocytes may be retrieved. This is of crucial significance during a non-stimulated cycle, in order to prevent an insufficient oocyte collection and rescue the treatment by implementing a conventional controlled ovarian stimulation.

Ovarian follicle diameter at timed insemination and estrous response influence likelihood of ovulation and pregnancy after estrous synchronization with progesterone or progestin-based protocols in suckled Bos indicus cows.

The objectives of the present study were to evaluate factors associated with estrous synchronization responses and pregnancy per insemination (P/AI) in Bos indicus beef cows submitted to progesterone-based fixed-time artificial insemination (FTAI) protocols. A total of 2388 cows (1869 Nellore and 519 crossbred NellorexAngus) from 10 commercial farms were evaluated to determine the relationships among breed, body condition score (BCS) on the first day of the FTAI protocol, the occurrence of estrus between progesterone device removal and FTAI, and diameter of largest ovarian follicle (LF) at FTAI on estrous synchronization responses and P/AI. Cows (n=412 primiparous; 1976 multiparous) received an intravaginal device containing progesterone or an ear implant containing norgestomet (a progestin), and an injection of estradiol at the beginning of the estrous synchronization protocol. Body condition was scored using a 1-5 scale on the first day of the FTAI protocol and at 30-60 days postpartum. Females received 300IU of equine chorionic gonadotropin (eCG) and PGF(2alpha) on the day the progesterone device/implant was removed and were inseminated 48-60h later. At insemination, cows (n=2388) were submitted to an ultrasonographic exam to determine the diameter of the LF. Follicles were classified into four categories based on mean and standard deviation (SD) of the LF (LF1=two SD below the mean; LF2=mean minus one SD; LF3=mean plus one SD; LF4=two SD above the mean). Ovulation rate was determined in a subset of cows (n=813) by three consecutive ultrasonographic exams: (1) at time of progesterone device/implant removal, (2) at time of FTAI and (3) 48h after FTAI. Ovulation was defined as the disappearance of a large follicle (>or=8.0mm) that was previously recorded. Estrus was determined in a subset of the cows (n=445) by the activation of a detection of estrous patch placed on the tail head on the day of progesterone device/implant removal. Pregnancy was diagnosed 30 days after FTAI. Pregnancy was influenced (P=0.001) by follicle diameter [LF1=27.5% (81/295), LF2=46.6% (328/705), LF3=57.9% (647/1118), LF4=63.3% (171/270)] and the occurrence of estrus [estrus=67.7% (174/257) and no estrus=36.2% (68/188)]. Follicle diameter at FTAI influenced ovulation rate [LF1=42.5% (34/80), LF2=73.9% (161/218), LF3=95.8% (407/425), LF4=97.8% (88/90)], the occurrence of estrus [LF1=54.8% (51/93), LF2=33.6% (43/128), LF3=68.9% (126/183), LF4=90.2% (37/41)] and P/AI among cows that had ovulations [LF1=32.4% (11/34), LF2=50.3% (81/161), LF3=60.0% (244/407), LF4=68.2% (60/88)]. Improving estrous responses between progesterone device withdrawal and FTAI and increasing the diameter of the LF at FTAI may be important aspects to achieve improved estrous synchronization responses and P/AI following progesterone/progestin and estradiol based FTAI protocols in suckled Bos indicus cows.

Efeito da frequência de amamentação sobre a taxa de ovulação após tratamento com desmame temporário + GnRH, sobre a incidência de luteólise prematura no primeiro ciclo estral pós-parto e sobre o desempenho da progênie de vacas Nelore / Effect of suckling frequency on ovulation rate after temporary weaning + GnRH treatment, incidence of premature luteolysis in the first postpartum estrous cycle, and performance of calves from Nelore cows

Avaliou-se o efeito da restrição na frequência de amamentação sobre o diâmetro folicular no dia 0 (DFOL), sobre a taxa de ovulação (TO), e sobre a incidência de luteólise prematura no primeiro ciclo estral pós-parto (ILP) de vacas Nelore multíparas, em anestro, submetidas à amamentação ad libitum (controle; n= 115) ou amamentação uma vez ao dia (restrito; n= 109), entre os dias -14 e 9 do experimento, e estudou-se o efeito desses tratamentos sobre o peso à desmama da progênie dessas vacas. Induziu-se ovulação com remoção de bezerros entre os dias -2 e 0 e aplicação de 100μg de GnRH no dia 0. Somente animais que ovularam foram mantidos no experimento (n= 125). A ocorrência de luteólise prematura foi avaliada por meio da dosagem da concentração sérica de progesterona nos dias 5 e 9. A TO não foi influenciada pelos tratamentos (55,8 por cento; P>0,1), e as vacas do tratamento restrito apresentaram maior DFOL (10,90±0,26 vs. 10,18±0,21mm; P<0,05) e menor ILP (21,4 por cento vs. 43,5 por cento; P<0,05). Os bezerros do tratamento controle foram mais pesados (162,32±2,08 vs. 155,91±4,12kg; P<0,05). Conclui-se que a restrição na frequência de amamentação em vacas Nelore reduz a ILP, porém com possível efeito negativo no desenvolvimento dos bezerros.

The effects of restricted suckling on follicular diameter at day 0 (FDDO), ovulation rate (OR), and incidence of premature luteolysis in the first post partum estrous cycle (PLI) of Nelore cows and the effects on weight at weaning (WW) of progenie of these cows were evaluated. Multiparous anestrous postpartum Nelore cows were submitted to ad libitum suckling (control; n= 115) or once-a-day suckling (restricted; n= 109) from days -14 to 9 of the experiment. For both treatments, a temporary calf removal was performed from days -2 to 0, and on day 0 cows received 100μg of GnRH. Only animals that ovulated after GnRH treatment were used in the experiment (n= 125). The occurrence of premature luteolysis was evaluated by dosage of serum progesterone concentrations on days 5th and 9th. The OR was not affected by treatments (55.8 percent; P>0.1), but cows from restricted treatment had larger FDDO at time of GnRH treatment (10.90±0.26 vs. 10.18±0.21mm; P<0.05) and lower PLI (21.4 percent vs. 43.5 percent; P<0.05) than cows from control treatment. Calves from control treatment had higher WW than calves from restricted treatment (162.32±2.08 vs. 155.91±4.12kg; P<0.05). These results indicate that the restriction in frequency of suckling in Nelore cows may decrease the incidence of premature luteolysis in the first postpartum estrous cycle; however, with possible negative effects on calves development.

Urinary hormone analysis assists reproductive monitoring and sex identification of bell frogs (Litoria raniformis).

With the world currently facing a global amphibian extinction crisis, the development of techniques to help meet the needs of conservation managers and researchers studying the reproductive biology of amphibians is needed. Here, we developed enzyme immunoassays to measure estrone, testosterone, and progesterone hormone metabolites in the urine of Litoria raniformis, the southern bell frog. Concentrations of urinary estrone, testosterone, and progesterone increased during the breeding season for females (P<0.05). Concentrations of urinary testosterone and progesterone increased for males during the breeding season compared with that for months where no reproductive behaviors were observed (P<0.05). Furthermore, urinary estrone concentrations proved to be a reliable sexing tool for adult frogs, with no overlap between the sexes in 98% of cases, regardless of season. There was no difference in estrone (P=0.204) or testosterone (P=0.485) metabolite concentrations between samples taken immediately upon capture and those taken 12 to 24h later from the same individual. Progesterone metabolite concentrations were lower on Day 2 than upon collection (P=0.004). This is the first study to show that urinary hormone analysis can be a useful technique for reproductive monitoring in an amphibian. Additionally, hormone metabolite measures offer promise as sex identification tools for monomorphic species and for those whose secondary sex characteristics are visible only during the breeding season.

Resonancia magnética en la respuesta al tratamiento del síndrome de hiperestimulación ovárica: comparación de modelos farmacocinéticos / Magnetic resonance for evaluating the response to treatment for ovarian hyperstimulation syndrome: comparison of pharmokinetic models

Objetivo Valorar el efecto del tratamiento con cabergolina en el síndrome de hiperestimulación ovárica (SHO) mediante la aplicación de modelos mono y bicompartimentales en resonancia magnética (RM). Material y métodosSe estudiaron 20 mujeres donantes de óvulos con riesgo de desarrollar SHO, divididas en 2 grupos (placebo y tratamiento). Se realizaron 2 estudios de RM de perfusión, antes y tras el inicio del tratamiento. Se comparó el modelo monocompartimental, con parámetros de permeabilidad vascular (Ktrans), ratio de extracción (kep) y fracción de espacio extravascular extracelular (ve), y el bicompartimental, que añade la fracción de espacio intravascular (vp). El análisis de las diferencias entre grupos (placebo frente a tratamiento) para los 2 estudios de RM y para cada modelo farmacocinético se realizó con una prueba t para muestras independientes. El coeficiente de correlación intraclase (CCI) analizó la variabilidad de las medidas. ResultadosEn el grupo placebo se observó un incremento significativo de Ktrans para ambos modelos (p=0,021 para un compartimiento, y p<0,001 para 2 compartimientos). En las pacientes tratadas no hubo diferencias en ningún parámetro para ninguno de los modelos. Por diferencias entre grupos, para 2 compartimentos Ktrans aumentó un 168,6±151,9% para placebo y un 43,3±54,5% para tratamiento (p=0,04). Para un único compartimiento no hubo diferencias significativas. En el análisis de variabilidad se obtuvo un CCI >0,95 para todos los parámetros, excepto vp (CCI=0,89). ConclusionesLa permeabilidad capilar calculada empleando modelos farmacocinéticos bicompartimentales tras la administración de un contraste en RM es un biomarcador del efecto del tratamiento en pacientes con SHO (AU)

ObjectiveTo evaluate the response to treatment with cabergoline for ovarian hyperstimulation syndrome (OHS) using mono- and bi-compartmental MRI models. Material and methodsWe studied 20 ovum donors with a high risk of developing OHS, divided in two groups (placebo vs. treatment). MRI perfusion studies were performed before and after the beginning of treatment. We compared the monocompartmental model, with the parameters vascular permeability (Ktrans), extraction ratio (kep), and extravascular extracellular space fraction (ve), against the bicompartmental model, with the same parameters as in the monocompartmental model and the additional parameter vascular space fraction (vp). The differences between groups (placebo vs. treatment) on the two MRI studies and for each pharmacokinetic model were analyzed using t-tests for independent samples. The intraclass correlation coefficient (ICC) was used to assess the variability of the measurements. ResultsIn the placebo group, a significant increase in Ktrans was observed with both models (p=0.021 for one compartment; and p<0.001 for two compartments). In the treatment group, no statistically significant differences were found for any parameter in either model. Regarding differences between groups, in the bicompartmental model Ktrans increased 168.6%±151.9% in the placebo group versus 43.3%±54.5% in the treatment group, p=0.04). In the monocompartmental model, no differences were found between groups. In the variability analysis, the ICC was higher than 0.95 for all parameters except vp (ICC=0.89). ConclusionsCapillary permeability calculated with bicompartmental pharmacokinetic models after MRI contrast administration is a biomarker of the treatment effect in OHS patients (AU)

Interpretation of the BBT chart: using the "Gap" technique compared to the Coverline technique.

OBJECTIVE: The aim of the study was to compare the accuracy of the Gap and Coverline techniques of interpreting the basal body temperature chart. METHODS: We compared the proportion of menstrual cycles for which the Gap and Coverline techniques accurately identified the post-ovulatory final fertile phase (FFP) and the initial infertile phase (IIP) and the median number of days each overestimated the fertile period, using urinary LH testing as the gold standard. RESULTS: The Gap and Coverline techniques identified the FFP within +/-1 day of that identified by LH testing in 13/33 (39%) and 10/33 (30%) cycles (chi2=0.6; p=.44), respectively, and the IIP within +1 day of that of LH testing in 13/33 (55%) and 4/33 (12%) cycles, respectively (chi2=13.4; p<.001). The Gap and Coverline techniques overestimated the fertile period by 1 and 4 days, respectively (p=.0002). CONCLUSION: Based on this small study, the Gap technique appears to be more accurate than the Coverline technique in identifying the post-ovulatory IIP.

Urinary follicle-stimulating hormone peak as a biomarker for estimating the day of ovulation.

OBJECTIVE: To evaluate urinary follicle-stimulating hormone (FSH) as a biomarker for the day of ovulation. DESIGN: Prospective observational study. SETTING: Clinical research center. PATIENT(S): Thirteen women were monitored with measurements of serum and urinary hormones and ovarian ultrasonography during 20 menstrual cycles. Data on urinary hormones and ultrasound evaluations from a total of 65 menstrual cycles from 42 women were analyzed. INTERVENTION(S): Blood and/or urine samples were collected daily. Daily transvaginal ultrasonography was used to detect follicular collapse. MAIN OUTCOME MEASURE(S): LH, FSH, and E(2) were measured in serum. FSH, estrone conjugates (E1C), and pregnanediol-3-glucuronide (PdG) were analyzed in urine. The day of luteal transition (DLT) was calculated using two algorithms. RESULT(S): In 20 cycles, the urinary FSH peak was closer to the day of follicular collapse (-0.85 days) than was the peak day of serum E(2) and the day of luteal transition, as calculated by one algorithm. The FSH peak was not closer to the day of follicular collapse than the peak values of urinary LH, serum FSH, or the day of luteal transition as calculated by a second algorithm. The most consistent correspondence between a hormone peak and ovulation was for serum E(2), serum FSH, serum LH, and urinary FSH. In 65 cycles for which urinary hormone data and ultrasound evaluations were available, the urinary FSH peak occurred within 1 day of follicular collapse in 97% of cycles. CONCLUSION(S): Urinary FSH is a useful biomarker for estimating the day of ovulation in population-based studies.