Faculty Bibliography

OBJECTIVE: To define statistical thresholds for the number and morphological score of embryos transferred that would be predictive of reproductive success in an IVF program. DESIGN: A retrospective review of patient records. SETTING: The Mount Sinai Medical Center Assisted Reproductive Technologies Program. PARTICIPANTS: One hundred women who underwent IVF-ET for a diagnosis of tubal occlusion and later delivered viable infants. RESULTS: The mean number of embryos transferred before achieving live birth was 10.7 +/- 7.9 (mean +/- SD), with one half of patients achieving success within the first seven embryos transferred, and 95% achieving success within 25 embryos. For high quality embryos, the numbers were 7.5 +/- 6.3, 5, and 17, respectively, and, for the cumulative embryo score, a measure of both embryo morphology and metabolic activity, were 114.2 +/- 86.0, 83, and 280, respectively. Greater than 50% of live births occurred within the first two ET attempts. CONCLUSIONS: Although more than half of patients achieved reproductive success within the first two ETs and the first five high quality embryos transferred, after this threshold, fecundity declined rapidly. The calculation of cumulative embryo scores offered additional prognostic information. While all prior attempts to define IVF-ET failure have done so by including patients who did not become pregnant, we have found an analysis of our successes to be a useful adjunct in counseling patients

To determine the effect of cryopreservation on embryo quality and the pregnancy potential of embryos, donated oocytes from the same donor (n = 24) were randomly allocated, with subsequent transfer to two or more different ovum recipients resulting in at least one fresh and one frozen embryo transfer cycle from the same cohort of oocytes. Endometrial receptivity was controlled in all ovum recipients, and male factor patients were excluded. The number of embryos transferred, mean embryo grade transferred, number of high quality embryos (grade < or = 2.5, grade 1 being best) transferred and embryo implantation and live birth rates are reported. Significantly more embryos (4.4 +/- 1.2 versus 3.3 +/- 1.2, P < 0.00003) of higher quality (1.9 +/- 0.5 versus 2.1 +/- 0.5, P < 0.013) and of a more advanced cell stage (3.0 +/- 0.6 versus 2.6 +/- 0.7, P < 0.019) were transferred fresh than after cryopreservation respectively. Implantation rates/embryo [19/151 (12.6%) and 9/111 (8.1%)] and live birth rates/transfer [11/42 (26.2%) and 6/45 (13.3%)], from fresh and frozen transfers respectively, were not significantly different despite the larger number of high quality embryos transferred fresh. Embryo cryopreservation adversely affects embryo quality, but does not have detrimental effects on the implantation or pregnancy potential of high quality embryos. Because of the loss of embryos during freeze-thawing during frozen embryo cycles, every effort should be made to attempt a fresh transfer

Transforming growth factor-beta (TGF beta), a protein known to antagonize many of the functions of the epidermal growth factor-receptor system, was localized immunohistochemically in unruptured ectopic pregnancies (EP) removed by salpingectomy (n = 8), uterine decidua from EP (n = 4), and decidua and trophoblast from electively terminated first trimester pregnancies (ETP; n = 8). Two rabbit polyclonal antisera that recognize both TGF beta 1 and beta 2 were used. Immunostaining for TGF beta was identified in all three forms of trophoblast, cytotrophoblasts, intermediate trophoblasts, and syncytiotrophoblasts, which were differentiated histologically and immunohistochemically. Moderate cytoplasmic immunostaining was found in villous cytotrophoblasts in both EP and ETP. Nonvillous (anchoring) cytotrophoblasts in these same tissues demonstrated moderate immunostaining adjacent to the villous and light immunostaining distal to the villous. In intermediate trophoblasts, moderate to intense immunostaining was seen in EP and ETP. Syncytiotrophoblasts demonstrated moderate cytoplasmic immunostaining in EP and ETP as well as moderate to intense staining of plasma membranes and microvilli. Nuclear staining was not evident in any form of trophoblast. TGF beta immunostaining was demonstrated in both glands and stroma of decidua from both EP and ETP; however, staining was more intense in decidua from ETP. With the known presence of TGF beta receptors and mRNA in placenta, these results suggest an autocrine/paracrine role for TGF beta regulation of endometrial-trophoblast function during human implantation