RESUMO
BACKGROUND: The objective of this study is to evaluate artificial oocyte activation (AOA) with calcium ionophore (CaI) in a subsequent attempt at fertilisation in patients after extremely low or failed fertilisation. We assessed improvements in fertilisation, implantation and pregnancy rates as well as cancellation rates in these patients. Finally, was evaluated the result testing in addition to delivery rate and obstetric outcomes in children born after AOA. MATERIALS AND METHODS: This was a retrospective observational study conducted in an IVF laboratory of an IVI clinic (IVIRMA Valencia, Spain). One group (509 mature oocytes from 66 patients) received a first intracytoplasmic sperm injection (ICSI) without AOA, which resulted in either a failed fertilisation or very low values (<30%). This group was compared with a second group (616 mature oocytes from the same 66 patients) that used AOA. Outcome was compared by McNemar's test and the dependent t tests. RESULTS: AOA plus CaI resulted in enhanced fertilisation (51 vs. 13.1%), ongoing pregnancy (47 vs. 21.7%), and implantation (31.1 vs. 13.1%) rates, and less chances for cancelling the cycle (22.7 vs. 69.3%). There were no observed adverse effects in obstetric and perinatal outcomes after the use of AOA. CONCLUSION: Our findings support the use of AOA for a given population of patients where fertilisation was affected during previous attempts. After AOA, we observed a significant increase in reproductive success due to the increased number of embryos available for embryo selection and, therefore, enhanced chances for success. The use of this artificial technique is comforting after checking non-existence of detrimental effects on the offspring.
RESUMO
BACKGROUND: The use of ovarian stimulation, to stimulate a multi-follicular response for assisted reproduction treatments, may force the production of oocytes from follicles that do not reach optimal maturation, possibly yielding oocytes that are not fully competent. The present study aimed to define the follicular environment and oocyte competence of unstimulated pre-ovulatory follicles, to compare it with that of similar-sized stimulated follicles. For this purpose, we analyzed the follicular hormonal milieu, the oocyte meiotic spindle, the embryo development and the cumulus cells gene expression (GE) profiles. METHODS AND RESULTS: The study population was divided in two groups: (i) 42 oocyte donors undergoing unstimulated cycles and (ii) 18 oocyte donors undergoing controlled ovarian stimulation cycles (COS). Follicular fluid was analyzed to quantify the concentrations of estradiol (E2), progesterone (P), FSH, LH, testosterone (T) and androstendione (Δ4). T was higher in the COS group, while Δ4, E2 and LH were significantly higher in unstimulated cycles. The cumulus oophorus cells (CC) surrounding the oocyte were removed and their GE profiles were analyzed with microarrays. There were 18 differentially expressed genes in CC: 7 were up-regulated and 11 were down-regulated in the COS cycles. The microarray was validated by qRT-PCR. The analysis of spindle structure revealed no significant differences between the groups, except for the parameter of length which presented differences. The fertilization ability and embryo morphology on Days 2, 3 and 4 did not show any significant differences between groups. CONCLUSIONS: The use of ovarian stimulation induces changes in the follicular fluid and in CC GE that may affect immune processes, meiosis and ovulation pathways. Although these differences do not seem to relate to early-stage embryo morphology, the implications of some of the molecules, especially ALDH1A2, CTSL and ZNF33B at the CC level, deserve to be addressed in future studies.
