Background This large prospective, randomized study was designed to compare the "mild" protocol with clomiphene citrate, low-dose gonadotropins and a GnRH-antagonist (CC/Gn/GnRH-ant protocol) with the "long" protocol with a GnRH-agonist and high-dose Gn for the controlled ovarian hyperstimulation (COH) of patients with expected poor ovarian responsiveness undergoing IVF. Materials and Methods A total of 695 women with clinical, endocrine and ultrasound characteristics suggesting a low ovarian reserve and a poor responsiveness to COH were recruited and randomly assigned to receive the CC/Gn/ GnRH-ant "mild" protocol (mild group, n=355) or the "long" protocol with high-dose Gn (long group, n=340). Results The "mild" stimulation led to significantly shorter follicular phase, lower consumption of exogenous Gn and lower peak estradiol level than the "long" regimen. With the "long" protocol, significantly less cycles were cancelled due to the lack of ovarian response; further, it obtained significantly more oocytes, more mature oocytes, more embryos, and a thicker endometrium. As for the final IVF outcome, however, the two stimulation regimens obtained comparable implantation rate, clinical pregnancy rate, and ongoing pregnancy rate at 12 weeks. Conclusions In conclusion, the "mild" CC/Gn/GnRH-ant stimulation protocol is a valid alternative to the long protocol with high Gn dose as it obtains a comparable success rate and requires significantly less medications, with an obvious economical advantage.

Purpose To clarify if birefringent structures of human oocytes and embryos, measurable by polarized light microscopy, have any value in predicting the chance of pregnancy in human in vitro fertilization and may halp to identify the most competent oocytes and embryos. Methods The inner layer of the zona pellucida (IL-ZP) and the meiotic spindle (MS) were analyzed by polarized light microscopy in 258 oocytes and in the 209 embryos deriving from them. Data obtained from 102 ICSI cycles with conception were compared with those obtained in 156 cycles without conception. The retardance and area of the IL-ZP, as well as the retardance, length of the major axis, and area of the MS were measured. Furthermore, polarized light microscopy parameters were related to the embryo morphological score by multiple regression analysis. Result(s) The mean area of the IL-ZP of both oocytes and embryos was significantly lower in conception than in nonconception cycles (p00.0001 for oocytes and p00.002 for embryos). The area of the IL-ZP in embryos was significantly, inversely related to the embryo morphological score (p00.011). The area, the major axis length and the retarcance of the MS, as well as the retardance of the IL-ZP in oocytes and embryos were comparable in conception and non-conception cycles. ConclusionThe area of the IL-ZP of the human oocytes may represent a marker of oocyte competence, as oocytes with a low IL-ZP area are more frequently obtained in conception cycles. When measured in embryos, a low IL-ZP area identifies embryos with a high chance of implantation.

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) × 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 < 0.0001 vs. <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.

No abstract

The interplay between oocyte and surrounding cumulus cells (CCs) during follicular growth influences oocyte competence to undergo fertilization and sustain embryo development. The expression of many genes and proteins in CCs has been suggested as potential biomarker of oocyte competence in human in vitro fertilization (IVF). In the present study, we analyzed 90 human cumulus-oocyte complexes obtained during IVF procedure: 30 CCs were analyzed using quantitative real-time polymerase chain reaction and 60 CCs using Western blotting analysis to detect gene and protein expression of some enzymes related to oxidative stress, that is, the 3 nitric oxide synthase (NOS) isoforms and heme oxygenase 1 (HO-1). In the group of 60 CCs, we also investigated the expression and phosphorylation of IkBα, a known inhibitor of the nuclear factor κB (NF-κB) pathway, which controls several redox-sensitive genes. The expression of the messenger RNAs (mRNAs) was related to the oocyte morphological analysis performed by polarized light microscopy and to the occurrence of normal fertilization after intracytoplasmic sperm injection. We observed that the amount of iNOS and HO-1 mRNAs and proteins is significantly higher, and that in the meanwhile the NF-κB pathway is activated, in CCs corresponding to oocytes that were not fertilized in comparison to CCs whose corresponding oocyte showed normal fertilization. Instead, no correlation between the fertilization and the oocytes' morphological data was observed. These results suggest that the increase in iNOS and HO-1 mRNAs expression in CCs is a negative index of oocyte fertilizability and might be an useful tool for oocyte selection.