Ovarian volume and antral follicle count for the prediction of low and hyper responders with in vitro fertilization

BackgroundThe current study was designed to compare antral follicle count (AFC) and basal ovarian volume (BOV), the exogenous FSH ovarian reserve test (EFORT) and the clomiphene citrate challenge test (CCCT), with respect to their ability to predict poor and hyper responders.MethodsOne hundred and ten regularly menstruating patients, aged 18–39 years, participated in this prospective study, randomized, by a computer designed 4-blocks system study into two groups. Fifty six patients underwent a CCCT, and 54 patients underwent an EFORT. All patients underwent a transvaginal sonography to measure the basal ovarian volume and count of basal antral follicle. In all patients, the test was followed by a standard IVF treatment. The result of ovarian hyperstimulation during IVF treatment, expressed by the total number of follicles, was used as gold standard.ResultsThe best prediction of ovarian reserve (Y) was seen in a multiple regression prediction model that included, AFC, Inhibin B-increment in the EFORT and BOV simultaneously (Y = -3.161 + 0.805 × AFC (0.258-1.352) + 0.034 × Inh. B-incr. (0.007-0.601) + 0.511 BOV (0.480-0.974) (r = 0.848, p < 0.001). Univariate logistic regression showed that the best predictors for poor response were the CCCT (ROC-AUC = 0.87), the bFSH (ROC-AUC = 0.83) and the AFC (ROC-AUC = 0.83). Multiple logistic regression analysis did not produce a better model in terms of improving the prediction of poor response. For hyper response, univariate logistic regression showed that the best predictors were AFC (ROC-AUC = 0.92) and the inhibin B-increment in the EFORT (ROC-AUC = 0.92), but AFC had better test characteristics, namely a sensitivity of 82% and a specificity 89%. Multiple logistic regression analysis did not produce a better model in terms of predicting hyper response.ConclusionIn conclusion AFC performs well as a test for ovarian response being superior or at least similar to complex expensive and time consuming endocrine tests. It is therefore likely to be the test for general practise.

[1]  B. Fisch,et al.  A randomized, double-blind clinical trial using fixed daily doses of 100 or 200 IU of recombinant FSH in ICSI cycles. , 2001, Human reproduction.

[2]  B. Sundén,et al.  Ultrasound measurement of the ovarian volume , 1987, Acta obstetricia et gynecologica Scandinavica.

[3]  D. Seifer,et al.  Serum antimüllerian hormone/müllerian-inhibiting substance appears to be a more discriminatory marker of assisted reproductive technology outcome than follicle-stimulating hormone, inhibin B, or estradiol. , 2004, Fertility and sterility.

[4]  B. Fauser,et al.  Antimüllerian hormone serum levels: a putative marker for ovarian aging. , 2002, Fertility and sterility.

[5]  E. Block.  A quantitative morphological investigation of the follicular system in newborn female infants. , 1953, Acta Anatomica.

[6]  J. Balasch,et al.  Increasing the daily dose of recombinant follicle stimulating hormone (Puregon) does not compensate for the age-related decline in retrievable oocytes after ovarian stimulation. , 2000, Human reproduction.

[7]  M. Blankenstein,et al.  The number of antral follicles in normal women with proven fertility is the best reflection of reproductive age. , 2003, Human reproduction.

[8]  M. Faddy,et al.  Ovary and ovulation: A model conforming the decline in follicle numbers to the age of menopause in women , 1996 .

[9]  D. Seifer,et al.  Early follicular serum müllerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles. , 2002, Fertility and sterility.

[10]  J. Habbema,et al.  Predictors of poor ovarian response in in vitro fertilization: a prospective study comparing basal markers of ovarian reserve. , 2002, Fertility and sterility.

[11]  J. Skull,et al.  Measurement of ovarian volume by transvaginal sonography before ovulation induction with human menopausal gonadotrophin for in-vitro fertilization can predict poor response. , 1997, Human reproduction.

[12]  B. Mol,et al.  Antral follicle count in the prediction of poor ovarian response and pregnancy after in vitro fertilization: a meta-analysis and comparison with basal follicle-stimulating hormone level. , 2005, Fertility and sterility.

[13]  P. Pearson,et al.  The variability of female reproductive ageing. , 2002, Human reproduction update.

[14]  J. Habbema,et al.  Impact of repeated antral follicle counts on the prediction of poor ovarian response in women undergoing in vitro fertilization. , 2004, Fertility and sterility.

[15]  J. Kline,et al.  Predictors of antral follicle count during the reproductive years. , 2005, Human reproduction.

[16]  P. Bezemer,et al.  Comparison of endocrine tests with respect to their predictive value on the outcome of ovarian hyperstimulation in IVF treatment: results of a prospective randomized study. , 2003, Human reproduction.

[17]  Y. Soong,et al.  Use of the antral follicle count to predict the outcome of assisted reproductive technologies. , 1998, Fertility and sterility.

[18]  J. Nelson,et al.  Follicular depletion during the menopausal transition: evidence for accelerated loss and ultimate exhaustion. , 1988, The Journal of clinical endocrinology and metabolism.

[19]  H. Martikainen,et al.  Pretreatment transvaginal ultrasound examination predicts ovarian responsiveness to gonadotrophins in in-vitro fertilization. , 1997, Human reproduction.

[20]  J. Henk.  A double-blind clinical trial comparing a fixed daily dose of 150 and 250 IU of recombinant follicle-stimulating hormone in women undergoing in vitro fertilization. , 2001, Fertility and sterility.

[21]  M. Faddy,et al.  Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. , 1992, Human reproduction.

[22]  F. Broekmans,et al.  Repeated clomiphene citrate challenge testing in the prediction of outcome in IVF: a comparison with basal markers for ovarian reserve. , 2005, Human reproduction.

[23]  J. McDonnell,et al.  Ovarian response to standard gonadotrophin stimulation for IVF is decreased not only in older but also in younger women in couples with idiopathic and male subfertility. , 2005, Human reproduction.

[24]  D. Cahill,et al.  The Practical Implications of a Raised Serum FSH and Age on the Risk of IVF Treatment Cancellation Due to a Poor Ovarian Response , 2004, Journal of Assisted Reproduction and Genetics.

[25]  S. Campbell,et al.  REAL-TIME ULTRASONOGRAPHY FOR DETERMINATION OF OVARIAN MORPHOLOGY AND VOLUME A Possible Early Screening Test for Ovarian Cancer? , 1982, The Lancet.

[26]  C. Lambalk,et al.  The clomiphene citrate challenge test versus the exogenous follicle-stimulating hormone ovarian reserve test as a single test for identification of low responders and hyperresponders to in vitro fertilization. , 2006, Fertility and sterility.

[27]  A. Templeton,et al.  Reducing the risk of multiple births by transfer of two embryos after in vitro fertilization. , 1998, The New England journal of medicine.

[28]  M. Faddy,et al.  Ovarian aging, follicular depletion, and steroidogenesis , 1994, Experimental Gerontology.

[29]  J. Habbema,et al.  Antral follicle counts by transvaginal ultrasonography are related to age in women with proven natural fertility. , 1999, Fertility and sterility.

[30]  E. Block,et al.  Quantitative morphological investigations of the follicular system in women; variations at different ages. , 1952, Acta anatomica.

[31]  F. Broekmans,et al.  Anti-müllerian hormone is a promising predictor for the occurrence of the menopausal transition , 2004, Menopause.

[32]  B. Mol,et al.  A systematic review of tests predicting ovarian reserve and IVF outcome. , 2006, Human reproduction update.

[33]  R. Kryscio,et al.  Interobserver variation in ovarian measurements using transvaginal sonography. , 1990, Gynecologic oncology.

[34]  A. Gougeon.  Ovarian follicular growth in humans: ovarian ageing and population of growing follicles. , 1998, Maturitas.

[35]  F. Broekmans,et al.  Age at menopause as a marker of reproductive ageing. , 1998, Maturitas.

[36]  S. Ivarsson,et al.  Ultrasonography of the pelvic organs in prepubertal and postpubertal girls. , 1983, Archives of disease in childhood.

[37]  J. Schoemaker,et al.  Cohort size rather than follicle-stimulating hormone threshold level determines ovarian sensitivity in polycystic ovary syndrome. , 1998, The Journal of clinical endocrinology and metabolism.

[38]  M. Eijkemans,et al.  Women with regular menstrual cycles and a poor response to ovarian hyperstimulation for in vitro fertilization exhibit follicular phase characteristics suggestive of ovarian aging. , 2002, Fertility and sterility.

[39]  J. Nelson,et al.  Follicular Depletion during the Menopausal Transition , 1990, Annals of the New York Academy of Sciences.

[40]  B. V. Van Voorhis,et al.  Ovarian volume: a novel outcome predictor for assisted reproduction. , 1995, Fertility and sterility.