Predictors of patients remaining anovulatory during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility

The diagnostic criteria used to identify patients suffering from polycystic ovary syndrome remain controversial. The present prospective longitudinal follow-up study was designed to identify whether certain criteria assessed during standardized initial screening could predict the response to ovulation induction with clomiphene citrate (CC) in 201 patients presenting with oligomenorrhea or amenorrhea and infertility. Serum FSH levels were within the normal range (1-10 IU/L), and all patients underwent spontaneous or progestin-induced withdrawal bleeding. Initial CC doses were 50 mg daily for 5 days starting on cycle day 3. In the case of an absent response, doses were increased to 100 and 150 mg daily in subsequent cycles. First ovulation with CC was used as the end point. After a complete follow-up (in the case of a nonresponse, at least 3 treatment cycles with daily CC doses up to 150 mg), 156 patients (78%) ovulated. The free androgen index (FAI = testosterone/sex hormone-binding globulin ratio), body mass index (BMI), cycle history (oligomenorrhea vs. amenorrhea), serum androgen (testosterone and/or androstenedione) levels, and mean ovarian volume assessed by transvaginal sonography were all significantly different (P < 0.01) in responders from those in nonresponders. FAI was chosen to be the best predictor in univariate analysis. The area under the receiver operating characteristics curve in a multivariate prediction model including FAI, BMI, cycle history, and mean ovarian volume was 0.82. Patients whose ovaries are less likely to respond to stimulation by FSH due to CC treatment can be predicted on the basis of initial screening characteristics, such as FAI, BMI, cycle history (oligomenorrhea or amenorrhea), and mean ovarian volume. These observations may add to ongoing discussion regarding etiological factors involved in ovarian dysfunction in these patients and classification of normogonadotropic anovulatory infertile women

Impact of repeated antral follicle counts on the prediction of poor ovarian response in women undergoing in vitro fertilization

Objective: To study the value of a single antral follicle count and the additional value of repeated counts in different cycles for the prediction of poor ovarian response in IVF. Design: Prospective. Setting: Tertiary fertility center. Patient(s): One hundred twenty women undergoing their first IVF cycle. Intervention(s): Measurement of the number of antral follicles on cycle day 3 in two spontaneous cycles. Main Outcome Measure(s): Ovarian response. Result(s): A single antral follicle count is clearly predictive of poor ovarian response and there is good agreement between repeated measurements in subsequent cycles (area under the receiver operating characteristic curve [ROCAUC]; cycle 1: 0.87, cycle 2: 0.85). In a logistic regression analysis, information obtained after the second cycle contributed significantly to the prediction of poor response by the antral follicle count of the first cycle. The predictive accuracy of the highest of two counts (ROCAUC 0.89) was slightly better than that of each single count. The predictive model with the highest count yielded slightly higher values of specificity and positive predictive value. Sensitivity, negative predictive value, and error rates were slightly lower. Conclusion(s): A single antral follicle count is a good predictor of poor ovarian response in IVF. Although the impact of a second antral follicle count on ovarian response predictions in IVF is statistically significant, clinical relevance is very limited. Repeating an antral follicle count in a subsequent cycle is not recommended

Predictors of chances to conceive in ovulatory patients during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility

The present prospective follow-up study was designed to identify whether clinical, endocrine, or ultrasound characteristics assessed by standardized initial screening of normogonadotropic oligo/amenorrheic infertile patients could predict conception in 160 women who reached ovulation after clomiphene citrate (CC) medication. Additional inclusion criteria were total motile sperm count of the partner above 1 million and a negative history for any tubal disease. Daily CC doses of 50 mg (increasing up to 150 mg in case of absent ovarian response) from cycle days 3-7 were used. First conception (defined as a positive urinary pregnancy test) was the end point for this study. A cumulative conception rate of 73% was reached within 9 CC-induced ovulatory cycles. Patients who did conceive presented more frequently with lower age (P < 0.0001) and amenorrhea (P < 0.05) upon initial screening. In a univariate analysis, patients with elevated initial serum LH concentrations (>7.0 IU/L) had a higher probability of conceiving (P < 0.01). In a multivariate analysis, age and cycle history (oligomenorrhea vs. amenorrhea) were identified as the only significant parameters for prediction of conception. These observations suggest that there is more to be gained from CC ovulation induction in younger women presenting with profound oligomenorrhea or amenorrhea. Screening characteristics involved in the prediction of ovulation after CC medication in normogonadotropic oligo/amenorrheic patients (body weight and hyperandrogenemia, as shown previously) are distinctly different from predictors of conception in ovulatory CC patients (age and the severity of cycle abnormality). This disparity suggests that the FSH threshold (magnitude of FSH required for stimulation of ongoing follicle growth and ovulation) and oocyte quality (chances for conception in ovulatory cycles) may be differentially regulated

Realizing a desired family size: When should couples start?

STUDY QUESTION Until what age can couples wait to start a family without compromising their chances of realizing the desired number of children? SUMMARY ANSWER The latest female age at which a couple should start trying to become pregnant strongly depends on the importance attached to achieving a desired family size and on whether or not IVF is an acceptable option in case no natural pregnancy occurs. WHAT IS KNOWN ALREADY It is well established that the treatment-independent and treatment-dependent chances of pregnancy decline with female age. However, research on the effect of age has focused on the chance of a first pregnancy and not on realizing more than one child. STUDY DESIGN, SIZE, DURATION An established computer simulation model of fertility, updated with recent IVF success rates, was used to simulate a cohort of 10 000 couples in order to assess the chances of realizing a one-, two- or three-child family, for different female ages at which the couple starts trying to conceive. PARTICIPANTS/MATERIALS, SETTING, METHODS The model uses treatment-independent pregnancy chances and pregnancy chances after IVF/ICSI. In order to focus the discussion, we single out three levels of importance that couples could attach to realizing a desired family size: (i) Very important (equated with aiming for at least a 90% success chance). (ii) Important but not at all costs (equated with a 75% success chance) (iii) Good to have children, but a life without children is also fine (equated with a 50% success chance). MAIN RESULTS AND THE ROLE OF CHANCE In order to have a chance of at least 90% to realize a one-child family, couples should start trying to conceive when the female partner is 35 years of age or younger, in case IVF is an acceptable option. For two children, the latest starting age is 31 years, and for three children 28 years. Without IVF, couples should start no later than age 32 years for a one-child family, at 27 years for a two-child family, and at 23 years for three children. When couples accept 75% or lower chances of family completion, they can start 4-11 years later. The results appeared to be robust for plausible changes in model assumptions. LIMITATIONS, REASONS FOR CAUTION Our conclusions would have been more persuasive if derived directly from large-scale prospective studies. An evidence-based simulation study (as we did) is the next best option. We recommend that the simulations should be updated every 5-10 years with new evidence because, owing to improvements in IVF technology, the assumptions on IVF success chances in particular run the risk of becoming outdated. WIDER IMPLICATIONS OF THE FINDINGS Information on the chance of family completion at different starting ages is important for prospective parents in planning their family, for preconception counselling, for inclusion in educational courses in human biology, and for increasing public awareness on human reproductive possibilities and limitations

Serum antimüllerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: A longitudinal study

Objective: The aim of this study was to assess which of the basal ovarian reserve markers provides the best reflection of the changes occurring in ovarian function over time (i.e., reproductive aging). Design: Prospective longitudinal study. Setting: Healthy volunteers in an academic research center. Patient(s): Eighty-one women with normal reproductive performance during the course of their lives were longitudinally assessed. In this select group of women, becoming chronologically older was considered as a proxy variable for becoming older from a reproductive point of view. Intervention(s): The women were assessed twice, with on average a 4-year interval (T 1 and T 2). The number of antral follicles on ultrasound (AFC) and blood levels of antimüllerian hormone (AMH), FSH, inhibin B, and E 2 were assessed. Main Outcome Measure(s): Longitudinal changes of the markers mentioned and the consistency of these parameters over time. Result(s): The mean ages at T 1 and T 2 were 39.6 and 43.6 years, respectively. Although AFC was strongly associated with age in a cross-sectional fashion, it did not change over time. The AMH, FSH, and inhibin B levels showed a significant change over time, in contrast to E 2 levels. The AMH and AFC were highly correlated with age both at T 1 and T 2, whereas FSH and inhibin B predominantly changed in women more than 40 years of age. To assess the consistency of these parameters over time, we investigated whether a woman's individual level above or below the mean of her age group at T 1 remained above or below the mean of her age group at T 2. Serum AMH concentrations showed the best consistency, with AFC as second best. The FSH and inhibin B showed only modest consistency, whereas E 2 showed no consistency at all. Conclusion(s): These results indicate that serum AMH represents the best endocrine marker to assess the age-related decline of reproductive capacity

The future of motherhood: conclusion and discussion

We suppose that there are not many reasons to believe that the age at first birth will soon lower by itself. More likely, if nothing happens from the outside, the age at birth will continue to rise further up until a certain ceiling. A significant share of the future western first babies will be born to mothers in their 30s. From a health perspective that is beyond ideal but only if health costs will rise alarmingly the age at first birth may lower. More awareness of unhealthy fertility boundaries may have some toning down effect.But we believe that a coherent package of fundamental supportive arrangements, making society more child and gender friendly, would have much more impact, not only on the age at first birth but on the wellbeing in general

Introduction

With late fertility as the main trigger and focal point, this book discusses the future of motherhood in western societies: to what extent and under what conditions are motherhood and emancipation (still) compatible? Is it possible to define an optimal time path or optimal conditions? Earlier discussions in the Netherlands on late motherhood/parenthood and the dilemma of health issues versus personal and socio-economic motives revealed that adressing this general question, immediately brings up a series of related questions in which many scientific dimensions are involved.That is why we brought together an international team of scolars and scientists from various disciplines to present and discuss their view on the relation between motherhood and emancipation and the dilemmas around late parenthood. This book consists of several chapters resulting from these consultations

Two new prediction rules for spontaneous pregnancy leading to live birth among subfertile couples, based on the synthesis of three previous models.

BACKGROUND: Several models have been published for the prediction of spontaneous pregnancy among subfertile patients. The aim of this study was to broaden the empirical basis for these predictions by making a synthesis of three previously published models. METHODS: We used the original data from the studies of Eimers et al. (1994), Collins et al. (1995) and Snick et al. (1997) on couples consulting for various forms of subfertility. We developed a so-called three-sample synthesis model for predicting spontaneous conception leading to live birth within 1 year after intake based on the three data sets. The predictors used are duration of subfertility, women's age, primary or secondary infertility, percentage of motile sperm, and whether the couple was referred by a general practitioner or by a gynaecologist (referral status). The performance of this model was assessed according to a 'jack-knife' analysis. Because the post-coital test (PCT) was not assessed in one of the samples, a synthesis model including the PCT was based on two samples only. RESULTS: The ability of the synthesis models to distinguish between women who became pregnant and those who did not was comparable to the ability of the one-sample models when applied in the other samples. The reliability of the predictions by the three-sample synthesis model was somewhat better. Predictions improved considerably by including the PCT. CONCLUSIONS: The synthesis models performed better and had a broader empirical basis than the original models. They are therefore better suitable for application in other centres