Ovarian sensitivity index is strongly related to circulating AMH and may be used to predict ovarian response to exogenous gonadotropins in IVF

<p>Abstract</p> <p>Background</p> <p>Serum anti-Mullerian hormone (AMH) is currently considered the best marker of ovarian reserve and of ovarian responsiveness to gonadotropins in in-vitro fertilization (IVF). AMH assay, however, is not available in all IVF Units and is quite expensive, a reason that limits its use in developing countries. The aim of this study is to assess whether the "ovarian sensitivity index" precisely reflects AMH so that this index may be used as a surrogate for AMH in prediction of ovarian response during an IVF cycle.</p> <p>Methods</p> <p>AMH serum levels were measured in 61 patients undergoing IVF with a "long" stimulation protocol including the GnRH agonist buserelin and recombinant follicle-stimulating hormone (rFSH). Patients were divided into four subgroups according to the percentile of serum AMH and their ovarian stimulation was prospectively followed. Ovarian sensitivity index (OSI) was calculated dividing the total administered FSH dose by the number of retrieved oocytes.</p> <p>Results</p> <p>AMH and OSI show a highly significant negative correlation (r = -0.67; <it>p </it>= 0.0001) that is stronger than the one between AMH and the total number of retrieved oocytes and than the one between AMH and the total FSH dose.</p> <p>Conclusions</p> <p>OSI reflects quite satisfactory the AMH level and may be proposed as a surrogate of AMH assay in predicting ovarian responsiveness to FSH in IVF. Being very easy to calculate and costless, its use could be proposed where AMH measurement is not available or in developing countries where limiting costs is of primary importance.</p

IVF results in patients with very low serum AMH are significantly affected by chronological age

PURPOSE: The aims of this study were to assess the outcome of in vitro fertilization (IVF) in women with very low circulating anti-müllerian hormone (AMH) and to investigate factors affecting their probability of pregnancy. METHODS: The outcome of 448 IVF cycles in 361 women with circulating AMH <0.5 ng/ml was retrospectively analyzed. RESULTS: Cycle cancellation rate was 14.5 %; patients whose cycle was cancelled had significantly lower AMH than women who reached oocyte pickup (OPU). Among those who reached OPU, age significantly affected the success rate: despite comparable AMH levels, patients below 35 years obtained significantly more oocytes and a better clinical pregnancy rate (CPR)/OPU than patients aged 35–39 or 40–43 (31 % vs. 23.2 % vs. 10.2 %, respectively; p = 0.001). Differently, comparable IVF results were observed stratifying patients for AMH levels in the range 0.14–0.49 ng/ml. Multivariable logistic regression analysis confirmed that the probability of pregnancy was significantly affected by age, but not by small differences in AMH level. CONCLUSIONS: Women with very low (<0.5 ng/ml) AMH levels undergoing IVF still have reasonable chances of achieving a pregnancy, but their prognosis is significantly affected by chronological age. Very low AMH levels are associated with a relevant risk of cycle cancellation but should not be considered a reason to exclude a couple from IVF

The Ovarian Sensitivity Index (OSI) Significantly Correlates with Ovarian Reserve Biomarkers, Is More Predictive of Clinical Pregnancy than the Total Number of Oocytes, and Is Consistent in Consecutive IVF Cycles

Background and Objectives: Some biomarkers of ovarian responsiveness to gonadotropins and the total number of retrieved oocytes are known to affect the success rate after controlled ovarian stimulation (COS) and in vitro fertilization (IVF). The aim of this study was to study another putative marker, the Ovarian Sensitivity Index (OSI: (number of retrieved oocytes/total gonadotropin dose) &times; 1000), assessing whether (a) it correlates with ovarian responsiveness biomarkers, (b) it is an independent predictor of clinical pregnancy, (c) it predicts clinical pregnancy comparably to the number of retrieved oocytes, and (d) it is consistent in the repeated COS cycles of the same woman. Design: retrospective analysis. Setting: public IVF Unit in University Hospital. Cases and Measurements: 1612 patients submitted to 3353 IVF cycles were included, their OSI was calculated and it was correlated with the ovarian responsiveness biomarkers (age, BMI, anti-Mullerian hormone, antral follicle count). The OSI and the total number of oocytes were compared for their value in predicting clinical pregnancy. The inter-cycle consistency of the OSI was estimated in 209 patients who underwent two consecutive cycles in which the ovarian stimulation regimen was changed from the Gonadotropin-releasing Hormone (GnRH)-agonist long protocol to the GnRH-antagonist protocol or vice-versa. Results: The OSI turned out to be significantly related to age and BMI (inversely), the anti-Mullerian hormone (AMH) and the antral follicle count (AFC) (directly), to be an independent predictor of clinical pregnancy, and to correlate with clinical pregnancy better than the total number of oocytes (p &lt; 0.0001 vs. &lt;0.002). In patients who underwent two consecutive COS cycles changing stimulation regimen, the OSI showed 82% consistency. Conclusion(s): The OSI significantly correlates to the currently used biomarkers of ovarian responsiveness; it is an independent predictor of clinical pregnancy; it is more predictive of clinical pregnancy than the total number of oocytes, and is highly consistent in repeated IVF cycles even when the COS protocol changes. These characteristics make the OSI quite suitable to be incorporated into more complex prediction models of IVF outcome

Oocyte polarized light microscopy, assay of specific follicular fluid metabolites, and gene expression in cumulus cells as different approaches to predict fertilization efficiency after ICSI

Background: The complex relationship between oocyte morphology, specific follicular fluid metabolites, gene expression in cumulus granulosa cells, and oocyte competence toward fertilization and embryo development still needs further clarification. Methods: Forty-six oocytes retrieved from the largest pre-ovulatory follicle of patients undergoing intra-cytoplasmic sperm injection (ICSI) were considered assessing: (a) oocyte morphological characteristics at polarized light microscopy (PLM), (b) specific follicular fluid (FF) metabolites previously suggested to influence oocyte competence (AMH, markers of redox status and of cytotoxicity), (c) transcription of AMH and AMH type II receptor genes in cumulus cells. Data were analyzed using mono-parametric tests and multivariable logistic analysis in order to correlate morphological and biochemical data with fertilization. Results: Comparing normally fertilized oocytes (n = 29, F group) with unfertilized (n = 17, nF group) we observed that: (a) the meiotic spindle area and major axis were significantly higher in nF group and in fertilized oocytes undergoing an early embryo development arrest; (b) AMH level in FF was comparable in F and nF groups; (c) the FF of nF group contained significantly higher levels of cytotoxicity (lactate dehydrogenase) and oxidative stress (Cu,Zn-superoxide dismutase, catalase, 4-hydroxynonenal-protein conjugates) markers; (d) cumulus cells of nF group showed significantly higher AMH receptor type II gene expression. Conclusions: Taken together, these observations suggest that an excessive cytotoxicity level can alter AMH signal transduction within cumulus cells, in turn leading to partial inhibition of aromatase activity, altered cytoplasmic maturation and increased oxidative stress, factors able to impair oocyte fertilization competence and embryo growth

Additional file 1: of Oocyte polarized light microscopy, assay of specific follicular fluid metabolites, and gene expression in cumulus cells as different approaches to predict fertilization efficiency after ICSI

Figure S1. Scheme of how material from individual first/largest follicle was evaluated in the enrolled patients’ population