Reproductive outcome of women 43 years and beyond undergoing ART treatment with their own oocytes in two Connecticut university programs.

PURPOSE: The aim of this study was to analyze the outcomes of IVF/ICSI cycles in women aged 43 and beyond. METHODS: Retrospective analysis of clinical pregnancy and live birth rates in 168 fresh, non donor, ART cycles performed in two Connecticut university IVF programs. RESULTS: In women of 43 and 44 years the overall clinical pregnancy and live birth rates were 8.3% and 5.3% per initiated cycle, respectively. There were no clinical pregnancies in women ≥45 years old. First cycle characteristics were not different from repeated cycles in terms of duration of ovulation induction, number of collected oocytes and transferred embryos (p > 0.05). CONCLUSIONS: Pregnancies can still be achieved with IVF/ICSI up to the age of 44. Since most pregnancies occurred within the first 3 cycles, another attempt may be a reasonable option before resorting to oocyte donation for patients who failed two previous cycles. Women 45 years and beyond do not benefit from ART procedures using their own oocytes.

Reproductive efficiency of women over the age of 40 and the low risk of multiple pregnancies.

Infertile patients over the age of 40 are generally considered to have a low chance of success with assisted cycles despite high numbers of embryos transferred. The risk of multiple pregnancy in this group of patients is not well established. The present study determined the rate of embryos that fail to produce a live birth and the rate of multiple pregnancies in a cohort of women over the age of 40 undergoing IVF/intracytoplasmic sperm injection cycles, utilizing Society for Assisted Reproductive Technology reported cycle outcomes from national summaries as well as from two university-based IVF centres. The rate of embryo wastage for women over the age of 40 is approximately 95% and these women have a correspondingly low rate of multiple pregnancy per cycle started (2.5% and 1.6% for women aged 41-42 years and 43-44 years, respectively). These data underscore the low reproductive efficiency of oocytes in women over the age of 40 and the very low probability of a multiple-gestation live birth despite the high number of embryos transferred. This information is an important additional counselling tool at the time of embryo transfer in this group of patients.

Meiotic arrest in human oocytes is maintained by a Gs signaling pathway.

In mammalian oocytes, the maintenance of meiotic prophase I arrest prior to the surge of LH that stimulates meiotic maturation depends on a high level of cAMP within the oocyte. In mouse and rat, the cAMP is generated in the oocyte, and this requires the activity of a constitutively active, Gs-linked receptor, GPR3 or GPR12, respectively. To examine if human oocyte meiotic arrest depends on a similar pathway, we used RT-PCR and Western blotting to look at whether human oocytes express the same components for maintaining arrest as rodent oocytes. RNA encoding GPR3, but not GPR12, was expressed. RNA encoding adenylate cyclase type 3, which is the major adenylate cyclase required for maintaining meiotic arrest in the mouse oocyte, was also expressed, as was Galphas protein. To determine if this pathway is functional in the human oocyte, we examined the effect of injecting a function-blocking antibody against Galphas on meiotic resumption. This antibody stimulated meiotic resumption of human oocytes that were maintained at the prophase I stage using a phosphodiesterase inhibitor. These results demonstrate that human oocytes maintain meiotic arrest prior to the LH surge using a signaling pathway similar to that of rodent oocytes.

Influence of embryo quality and number of previous cycles on pregnancy and multiple pregnancy rates in women aged 35 to 37 years who received two or three embryos.

Women aged 35-37 years undergoing IVF-ET with fresh embryos at a university infertility center were analyzed to evaluate factors useful in determining whether two or three embryos should be transferred in this age group. Embryo quality and number, but not number of previous failed cycles, were important in determining outcome, and all triplet pregnancies could have been avoided at our program in this age group by limiting the transfer to two good-quality embryos, without reducing pregnancy rates.