Objective: ART pregnancy rates have increased with improvements in technology. In spite of improvements in ovarian stimulation and embryo culture, implantation and pregnancy rates remain suboptimal. One variable that has received little attention is the role of the ET provider. This report describes our experience with multiple providers initiating US guidance for ET at different times. Design: Retrospective examination of clinical outcomes before and after the adoption of US guidance for ET as part of a quality assurance program. Materials/Methods: All patients who had an ET after undergoing IVF or ICSI without limitation of age were included. Laboratory culture conditions remained the same throughout the various time periods. Fertilization and early embryo growth were performed in HTF (Irvine Scientific) with Blastocyst Medium (Irvine Scientific) used for extended culture. ET was performed primarily with the Edwards-Wallace catheter. The Frydman TDT was used if the Edwards-Wallace failed to pass the cervix or if the ET was expected to be difficult on the basis of a mock ET done at time of retrieval. Trans-abdominal US with a full bladder was used to monitor placement of the catheter. Data was synchronized to the initiation of US guidance for each provider (this time varied over a 4 month period) to better examine the effect of this procedural change. Analysis was done of 40 sequential ET by each provider done immediately prior to the initiation of US guidance and of the first 40 ET done after initiation of US guidance. ET were sequentially grouped by 20 and pooled among the three providers, yielding 4 groups of 60 ET, 2 prior to US introduction (period 1 & 2) and 2 after (period 3 & 4). Patient characteristics and ET outcomes were compared among time groups, among providers, and overall with or without US. Continuous data were compared with analysis of variance while proportionate data were analyzed by chi-square. Results: Age, number of oocytes retrieved, fertilization rate, day of ET, number of embryos replaced and time to place the catheter did not vary among periods (table below). Pregnancy and implantation rates were higher and percent of ET with blood on the catheter was lower after the introduction of US guided embryo replacement. Significant differences were seen among providers with all providers having improved pregnancy rates after the adoption of US guidance (data not shown). Patient characteristics and clinical results for periods before and after the adoption of US guidance for ET. Tabled 1Without ultrasoundWith ultrasoundUSP-ValuePeriod 1Period 2Period 3Period 4Age (years)34.1 ± 4.634.0 ± 4.833.0 ± 5.034.3 ± 4.1NSOocytes10.8 ± 4.312.5 ± 6.713.1 ± 7.112.7 ± 7.1NSFertilized (%)55 ± 2353 ± 2456 ± 2659 ± 24NSDay of ET4.1 ± 1.23.6 ± 1.03.9 ± 1.13.7 ± 1.0NSEmbryos/ET2.9 ± 0.92.9 ± 1.02.7 ± 0.92.9 ± 1.0NSTime (seconds)62 ± 8056 ± 7280 ± 8162 ± 85NSBloody (%)202058P < 0.005Pregnant (%)22224260P < 0.005Implanted (%)14132128P < 0.005 Open table in a new tab Conclusions: Pregnancy and implantation rates vary among providers. Pregnancy rates improved for all providers with adoption of US guidance for ET. Routine use of US guidance is recommended for all ET. Supported by: Section of Reproductive Endocrinology and Infertility.
Objective: Despite many improvements in assisted reproductive technology pregnancy rates remain sub-optimal. This study examined the utility of early cleavage as a predictor of embryonic developmental potential. Design: Retrospective analysis of the relationship between the occurrence of early embryo cleavage and embryonic development and implantation. Materials/Methods: Patients undergoing IVF with or without ICSI without regard to age were included (n = 171). Fertilization and early culture were performed in HTF (Irvine Scientific) with 5% Serum Substitute Supplement (Irvine Scientific). All zygotes (n = 1153) were re-examined at 26 hr post insemination (≅68 hr post HCG). Zygotes were classified as either containing 2PN, having no visible PN remaining, or as having cleaved. For analysis, patients were grouped based on the number of zygotes that showed progression (either loss of visible PN or occurrence of cleavage) at the time of observation. Results: At the time of observation 607 (52.7%) of the zygotes still showed 2PN, while 299 (25.9%) showed no PN and 247 (21.4%) had cleaved. When patients were grouped based on the number of zygotes showing progression there was an increase in cell number and number of 8-cell embryos at 72 hr as well as increases in pregnancy and implantation (see table below). Characteristics of patients classified by number of zygotes showing progression at 26 hours. Tabled 1Number of zygotes showing progressionP-value01–23–45+Patients24544642Age34.8 ± 4.233.6 ± 4.433.1 ± 3.932.9 ± 4.5NSEmbryo total6.1 ± 3.05.5 ± 2.46.8 ± 2.48.7 ± 2.0P < 0.0001Day 3-cell number5.5 ± 1.46.7 ± 1.37.1 ± 1.07.0 ± 0.9P < 0.0001Day 3-fragments16 ± 812 ± 811 ± 511 ± 6P < 0.0117# 8-cells (day 3)1.4 ± 1.62.4 ± 1.93.8 ± 1.95.0 ± 2.1P < 0.0001Embryos/ET3.2 ± 0.82.9 ± 0.82.6 ± 1.02.5 ± 0.9P < 0.013Pregnant (%)6 (25)17 (31)22 (48)29 (69)P < 0.0001Implanted (%)7 (9)19 (12)36 (29)45 (41)P < 0.0001 Open table in a new tab Conclusions: Early cleavage of zygotes appears to be highly correlated with embryo development and implantation potential. Since prepackaged maternal mRNA controls early cleavage, the developmental potential of the oocyte is established during follicular growth, prior to aspiration and culture. These results suggest that the outcome of an ART cycle may be determined prior to oocyte retrieval or fertilization Supported by: Section of Reproductive Endocrinology and Infertility.
Objective: Multiple embryos are routinely transferred in order to increase the likelihood of attaining a successful pregnancy. Any variable that allows more accurate assessment of which embryos have the best implantation potential is of clinical utility. The goal of this study was to determine if the presence of polar body (PB) fragmentation at the time ICSI was predictive of subsequent fertilization or development. Design: Retrospective evaluation of the relationship between PB morphology at the time of ICSI and subsequent embryo development. Materials/Methods: Oocytes (n = 639) were denuded in preparation for ICSI by hyaluronidase exposure and gentle aspiration in graduated pipets. At the time of ICSI (≅42 hr post HCG) the PB was examined and oocytes classified as having either an intact or fragmented PB. Fertilization and embryo development were determined for each type of oocyte. For analysis, patients were grouped based on the percentage of their mature oocytes that had an intact PB at the time of ICSI. Pregnancy and implantation were determined after transfer of embryos selected solely on the basis of embryo quality (cell number and fragmentation) without regard to previous PB morphology. Data were analyzed either by analysis of variance or chi-square. Results: Outcome of ICSI did not differ between oocytes with different PB morphology. Intact PB—322 injected—221 (69%) 2PN, 32 (10%) 1PN, 13 (4%) 3PN, 35 (11%) unfert, 21 (6) degen. Fragmented PB—184 injected—126 (68%) 2PN, 13 (7%) 1PN, 9 (5%) 3PN, 23 (13%) unfert, 13 (7) degen. Development of embryos on day 3 was similar between groups (data not shown). Results when patients were grouped by percentage of fragmented PB at the time of ICSI are shown in the table below. Characteristics of patients classified by percentage of mature oocytes with fragmented PB. Tabled 1Percentage with a fragmented polar bodyP-value<20%20–49%50+%Number142314Age (years)34.1 ± 4.732.4 ± 4.833.5 ± 4.8NSTotal oocytes10.6 ± 6.513.5 ± 6.312.0 ± 4.3NSPeak estradiol1980 ± 10292188 ± 9042067 ± 853NSEmbryo/ET2.8 ± 1.02.8 ± 0.63.2 ± 1.0NSDay 3-cell number5.6 ± 1.36.2 ± 1.36.3 ± 0.9NSDay 3-fragments14 ± 713 ± 814 ± 6NSImplanted (%)3 (8)14 (22)10 (22)P < 0.05Pregnant (%)2 (14)8 (35)6 (43)P < 0.09 Open table in a new tab Conclusions: There were no detectable differences in fertilization or early embryo development in association with a fragmented PB on a per oocyte basis. However, there was an association of fragmentation within a cohort with increased pregnancy and implantation. Increased fragmentation of the PB may reflect the length of time since PB extrusion, which may in turn be responsible for the variation in developmental potential after ICSI. Supported by: Section of Reproductive Endocrinology and Infertility.