B.S. Shapiro

Quantitative grading of a human blastocyst: optimal inner cell mass size and shape

OBJECTIVE To investigate the predictive value of quantitative measurements of blastocyst morphology on subsequent implantation rates after transfer. DESIGN Prospective observational study. SETTING Private assisted reproductive technology center. PATIENT(S) One hundred seventy-four IVF patients receiving transfers of expanded blastocyst-stage embryos on day 5 (n = 112) or day 6 (n = 62) after oocyte retrieval. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Blastocyst diameter, number of trophectoderm cells, inner cell mass (ICM) size, ICM shape, and implantation and pregnancy rates. RESULT(S) Blastocyst diameter and trophectoderm cell numbers were unrelated to implantation rates. Day 5 expanded blastocysts with ICMs of >4,500 microm(2) implanted at a higher rate than did those with smaller ICMs (55% vs. 31%). Day 5 expanded blastocysts with slightly oval ICMs implanted at a higher rate (58%) compared with those with either rounder ICMs (7%) or more elongated ICMs (33%). Implantation rates were highest (71%) for embryos with both optimal ICM size and shape. Pregnancy rates were higher for day 5 transfers of optimally shaped ICMs compared with day 5 transfers of optimally sized ICMs. CONCLUSION(S) Quantitative measurements of the inner cell mass are highly indicative of blastocyst implantation potential. Blastocysts with relatively large and/or slightly oval ICMs are more likely to implant than other blastocysts.

A comparison of day 5 and day 6 blastocyst transfers

OBJECTIVE To compare implantation and pregnancy rates according to the day of embryo transfer (day 5 or 6 after oocyte retrieval) when transfer was postponed until expanded blastocysts developed. DESIGN Retrospective clinical study. SETTING Private ART center. PATIENT(S) One-hundred and eighty-three women undergoing blastocyst-stage embryo transfer following in vitro fertilization. INTERVENTION(S) Bipronucleate oocytes were grown for up to 144 hours and subsequently transferred only when at least one embryo attained the expanded blastocyst stage. MAIN OUTCOME MEASURE(S) Implantation and pregnancy rates. RESULT(S) Blastocysts transferred on day 5 implanted at nearly twice the rate of blastocysts transferred on day 6 (36.3% vs. 19.0%). Pregnancy rates were also almost twice as high among the day 5 transfer patients (59.3% vs. 32.3%). In addition, more blastocysts developed (3.6 vs. 2.4), and more were transferred (2.7 vs. 2.3) to the day 5 transfer patients, although the proportion of expanded blastocysts among the blastocysts that were transferred was the same for the two groups (91.7% vs. 93.6%). CONCLUSION(S) Embryos that develop to the expanded blastocyst stage and are transferred on day 5 after retrieval are approximately twice as likely to implant compared to those for which expansion and transfer are delayed until day 6.

Clinical rationale for cryopreservation of entire embryo cohorts in lieu of fresh transfer

Recent dramatic increases in success rates with frozen-thawed embryo transfer (FET) are encouraging, as are numerous findings of several reduced risks with FET when compared with fresh transfer. These reduced risks include low birth weight and prematurity, among others. However, FET is also associated with increased risks of macrosomia and large for gestational age. There have been reports of greater implantation and pregnancy rates with FET than with fresh autologous embryo transfer, suggesting superior endometrial receptivity in the absence of ovarian stimulation. As cryo-technology evolves, there is potential for further increase in FET success rates, but for now it may be best to follow an individualized approach, balancing fresh transfer and embryo cohort cryopreservation options while considering patient characteristics, cycle parameters, and clinic success rates.

Predictive value of 72-hour blastomere cell number on blastocyst development and success of subsequent transfer based on the degree of blastocyst development

OBJECTIVE To determine the predictive value of 72-hour blastomere cell number on blastocyst development and to compare success rates of subsequent transfer based on the degree of blastocyst development. DESIGN Retrospective clinical study. SETTING Private assisted reproductive technology center. PATIENT(S) Ninety-three women aged 32.0 +/- 5.1 years undergoing oocyte retrieval for IVF. INTERVENTION(S) Bipronucleate oocytes obtained from IVF were grown for up to 168 hours after fertilization and subsequently transferred at the blastocyst stage. MAIN OUTCOME MEASURE(S) Percentages of embryos developing to blastocyst from 72-hour embryos by blastomere cell number and subsequent implantation and pregnancy rates of transferred blastocysts. RESULT(S) Rates of blastocyst formation and expansion increased as cell numbers at 72 hours increased. Implantation rates were 43% for embryos transferred to women receiving only expanded blastocysts and 17% for embryos transferred to women receiving one or more less developed blastocysts. Pregnancy rates were higher for women receiving only expanded blastocysts than for women receiving one or more less developed blastocysts, although the difference was not significant. CONCLUSION(S) More developed 72-hour embryos are more likely to become blastocysts and expand. Implantation rates are greater for the transfer of expanded rather than unexpanded blastocysts.

Comparison of “triggers” using leuprolide acetate alone or in combination with low-dose human chorionic gonadotropin

This retrospective study of fresh autologous blastocyst transfers in high responders compared ongoing pregnancy rates in cycles that followed trigger with GnRH agonist (GnRHa) alone with standard luteal support, GnRHa alone with enhanced luteal support, or GnRHa with concomitant low-dose hCG (dual trigger). Ongoing pregnancy rates were significantly increased with the dual trigger or with enhanced luteal support, whereas the incidence of clinically significant ovarian hyperstimulation syndrome was 0.0% in the groups receiving only GnRHa and 0.5% (1 of 182) in patients receiving GnRHa with concomitant low-dose hCG.

Embryo cryopreservation rescues cycles with premature luteinization

OBJECTIVE To determine whether embryo cryopreservation in cycles with elevated preovulatory P followed by thaw, extended culture, and transfer results in greater ongoing pregnancy rates than fresh blastocyst transfer. DESIGN Retrospective matched cohort study. SETTING Private fertility center. PATIENT(S) The study group consisted of 118 consecutive thaws of bipronucleate (2PN) oocytes derived from autologous cycles with elevated preovulatory P, resulting in 95 blastocyst transfers. The control group was selected by matching on the number of 2PN oocytes and patient age and consisted of 118 fresh cycles with elevated preovulatory P, including 108 fresh autologous blastocyst transfers. All patients were <41 years old at the time of stimulation. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Implantation and ongoing pregnancy rates. RESULT(S) The study group had significantly fewer blastocysts per 2PN oocyte than the control group (19.7% vs. 36.8%, respectively) and a significantly greater cancellation rate (19.5% vs. 8.5%, respectively). However, the ongoing pregnancy rate per cycle was significantly higher in the study group than in the control group (56.8% vs. 32.2%, respectively), resulting from greater rates of implantation (56.8% vs. 26.9%, respectively) and of ongoing pregnancy per transfer (70.5% vs. 35.2%, respectively). CONCLUSION(S) In cycles with elevated preovulatory P, the probabilities of implantation and ongoing pregnancy are increased if all 2PN oocytes are cryopreserved and subsequently thawed and cultured to the blastocyst stage before transfer.

Frozen-thawed embryo transfer is associated with a significantly reduced incidence of ectopic pregnancy.

OBJECTIVE To compare the incidence of ectopic pregnancy (EP) after fresh ET and thawed ET. DESIGN Retrospective cohort study. SETTING Private fertility center. PATIENT(S) This retrospective study included 2,150 blastocyst transfers, including all 1,460 fresh autologous blastocyst transfers and all 690 transfers of autologous blastocysts derived from post-thaw extended culture of thawed bipronuclear oocytes in the 8-year study period 2004-2011. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Visualized EP and treated persistent pregnancy of unknown location. RESULT(S) The rate of visualized EP was 1.5% in pregnancies in fresh autologous cycles, which was significantly more than the rate of 0 with autologous post-thaw extended culture. The rates of treated persistent pregnancy of unknown location were 2.5% and 0.3% in these two groups, respectively, a difference that was also statistically significant (relative risk 7.3, 95% confidence interval 1.7-31.0). CONCLUSION(S) Relative to fresh transfer, thawed ET was associated with significantly reduced incidence of EP. These findings are consistent with ovarian stimulation increasing the risk of EP.

Embryo selection in IVF

To optimize success rates of IVF, selection of the most viable embryo(s) for transfer has always been essential, as embryos that are cryopreserved are thought to have a reduced chance of implanting after thawing. Recent developments challenge this concept. Evidence is accumulating that all embryos can now be cryopreserved and transferred in subsequent cycles without impairing pregnancy rates or maybe even with an improvement in pregnancy rates. In such a scenario no selection method will ever lead to improved live birth rates, as, by definition, the live birth rate per stimulated IVF cycle can never be improved when all embryos are serially transferred. In fact, selection could then only lower the live birth rate after IVF. The only parameter that could possibly be improved by embryo selection would be time to pregnancy, if embryos with the highest implantation potential are transferred first.

Dramatic declines in implantation and pregnancy rates in patients who undergo repeated cycles of in vitro fertilization with blastocyst transfer after one or more failed attempts

OBJECTIVE To compare the outcome of second and third cycles of in vitro fertilization with blastocyst transfer to the outcome of first attempts at IVF with blastocyst transfer. DESIGN Retrospective study. SETTING Private ART center. PATIENT(S) Three hundred and four patients undergoing treatment with in vitro fertilization with blastocyst transfer, 87 of which underwent at least one cycle of re-treatment after failing to achieve pregnancy in their first cycle. INTERVENTION(S) Bipronucleate oocytes were grown for up to 144 hours and subsequently transferred when at least one embryo attained the expanded blastocyst stage. MAIN OUTCOME MEASURE(S) Pregnancy and implantation rates. RESULT(S) Pregnancy rates per retrieval were significantly higher for patients undergoing their first cycle of in vitro fertilization with blastocyst transfer (36%) compared to those undergoing their second (19%) or their third (9%) cycles of treatment. Implantation rates per embryo were also higher for first cycles of in vitro fertilization with blastocyst transfer (30%) compared to second (18%) or third cycles (8%). CONCLUSION(S) Pregnancy and implantation rates decline dramatically in repeated cycles of in vitro fertilization with blastocyst transfer following one or more unsuccessful cycles of in vitro fertilization with blastocyst transfer.

Influence of patient age on the growth and transfer of blastocyst-stage embryos

OBJECTIVE To examine the effects of patient age on the growth and transfer of blastocyst-stage embryos. DESIGN Retrospective clinical study. SETTING Private assisted reproductive technologies center. PATIENT(S) Three hundred patients between the ages of 18 and 45 undergoing in vitro fertilization. INTERVENTION(S) Bipronucleate oocytes were grown for up to 144 hours and subsequently transferred when at least one embryo attained the expanded blastocyst stage. MAIN OUTCOME MEASURE(S) Oocytes retrieved and fertilized, blastocyst formation rates, implantation rates, and pregnancy rates per retrieval and transfer. RESULT(S) The rate of cycle cancellation before oocyte retrieval increased significantly with age, and the average number of oocytes per retrieval declined significantly with age. Fertilization rates were unrelated to patient age. The proportion of cycles with expanded blastocysts declined significantly with age. Pregnancy rates per stimulation declined with age, but pregnancy rates per transfer were approximately 50% across the entire age range studied. CONCLUSION(S) The decline in female fertility with age appears to be the result of reduced numbers of oocytes and the inability of fertilized oocytes to develop to the blastocyst stage. Implantation and pregnancy rates appear to be unaffected by age when blastocysts do form.