Ovarian stimulation with corifollitropin alfa followed by hp-hMG compared to hp-hMG in patients at risk of poor ovarian response undergoing ICSI: A randomized controlled trial.

OBJECTIVE: To compare the results of two ovarian stimulation protocols for IVF in patients at risk of poor ovarian response: corifollitropin alfa followed by hp-hMG versus daily administration of hp-hMG. We intended to demonstrate the non-inferiority of the protocol with corifollitropin alfa. STUDY DESIGN: This is a prospective, randomized, non-inferiority, controlled study. We compared two ovarian stimulation protocols for IVF in 234 patients, under 40 years of age and at risk of poor ovarian response. First protocol was a single injection of 150 µg corifollitropin alfa and the second, a daily injection of 300 IU of hp-hMG during the first week of ovarian stimulation. In both groups, if necessary, a daily injection of 300 IU of hp-hMG was dispensed until the criteria for hCG administration are met. For the primary and secondary outcomes, results were analysed by using a one-sided chi-square test or a Fisher exact test, as appropriate, with a level of significance of 0.05. For continuous variables, parametric (independent t-test) or non-parametric (Mann-Whitney test) tests were used depending on the normality of the distribution. Statistical significance was set at P < 0.05. RESULTS: The ongoing pregnancy rate, live birth rate (15.2 vs 20.2) (P = 0.33), and the cumulative live birth rate (15.2 vs 22.0) (P = 0.19) per started cycle did not show significant differences between the corifollitropin alfa and hp-hMG groups, and the difference estimated between treatments was -5% [95% CI: (-15.1, 5.0)]. CONCLUSIONS: It was not possible to probe non-inferiority of the protocol with corifollitropin alfa followed by hp-hMG compared to hp-hMG in patients at risk of poor ovarian response undergoing ICSI.

In vitro maturation, fertilization, embryo development & clinical outcome of human metaphase-I oocytes retrieved from stimulated intracytoplasmic sperm injection cycles.

BACKGROUND & OBJECTIVES: The major cause of fertilisation failure after ICSI is failure of the oocyte to initiate the biochemical processes necessary for activation. This inability could be ascribed to cytoplasmic immaturity of those gametes even if they had reached nuclear maturity. The activation of a mature oocyte is characterised by release from metaphase II (MII) arrest and extrusion of the second polar body, followed by pro-nuclear formation. The aim of this study was to evaluate the fate of in vitro matured (IVM) metaphase I (MI) oocytes subjected to intracytoplasmic sperm injection (ICSI) at different time intervals after extrusion of the first polar body (1PB) in in vitro fertilization (IVF) cycles. METHODS: A total of 8030 oocytes were collected from 1400 ICSI cycles, 5504 MII at the time of cumulus retrieval. Four hundred eight metaphase II (MII) (27.1%) matured to MII after in vitro culture for 2-26 h and 5389 sibling MII in the moment of oocyte denudation were injected. On the other hand, 49 ICSI cycles containing only MI oocytes at retrieval were injected at three different time intervals after reaching the MII. The intervals were as follows: 2-6 h (n=10), 8-11 h (n=4) and 23-26 h (n=10). Fertilization and development potential were evaluated in both studies. RESULTS: Fertilization, embryo cleavage and quality were significantly lower in IVM MI compared to MII at time of denudation. Pregnancy rate was higher in group MII. Pregnancy was achieved in three embryo transfers when ICSI was performed within 2-6 h (group I) and 8-11 h (group II) after PB extrusion. One pregnancy was obtained in group I and a healthy neonate was born. INTERPRETATION & CONCLUSIONS: Immature oocytes from women whose ovaries have been stimulated could be matured, fertilized by ICSI, cleaved in vitro and to give rise to a live birth. However, the developmental competence of embryos derived from immature oocytes is reduced, compared with sibling in vivo matured oocytes. Further, human IVM oocytes need between 2-6h after the 1PB extrusion to complete its maturation.

Zygote score and status 1 or 2 days after cleavage and assisted reproduction outcome.

OBJECTIVE: To determine whether pronuclear morphology is a useful additional criterion when selecting embryos for transfer. METHOD: A modified Tesarik and Greco scoring system was used in this retrospective study to assess the pronuclear morphology of 883 zygotes from 214 in vitro fertilization or intracytoplasmic sperm injection cycles. Pronucleus size and presence of cytoplasmic halo were also noted. Embryo selection was performed on Day 2 or 3 following oocyte retrieval. The chi2, analysis of variance, Kruskal-Wallis, and Fisher exact tests were used where appropriate. RESULTS: A stepwise logistic regression revealed that a better embryo quality was associated with both pattern 0 of the scoring system and pronuclei of equal size on Days 2 or 3. Higher pregnancy and multiple gestation rates were obtained when at least 1 embryo classified as pattern 0 was included in the set of embryos transferred. CONCLUSION: Combined with embryo morphology evaluation on Days 2 and 3, a scoring system based on pronuclear morphology seems to provide a good criterion when selecting embryos for transfer.