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PFC Poster at ASRM

Pacific Fertility Center presented a poster this October at the American Society for Reproductive Medicine (ASRM) annual meeting in San Diego. We shared our experience and success with elective single embryo transfer (eSET) and vitrification of blastocysts which has yielded high cumulative pregnancy and delivery rates for our patients, while at the same time reducing twin pregnancies.

Our high implantation rates from frozen embryos have encouraged patients to transfer fewer embryos in their fresh cycle with the confidence that their frozen embryos will perform well in the future. Patients also feel comfortable warming one embryo at a time in the frozen cycle, giving a high chance of pregnancy and still maintaining low multiple rates.

Between 2009 and 2012 frozen embryo implantation rates for PFC patients under 35 rose from 36% to 56% while the eSET rate went from 33% to 71% of patients. The percentage of twins fell from 22% to 16%. In 2010 the fresh transfer live birth rate per patient under 35 at PFC was 44%. The cumulative live birth rate, which includes patients who returned to use their frozen embryos following a negative fresh cycle, was 64%.

These trends were observed across all age groups of PFC patients. Implantation, pregnancy, and live birth rates continue to improve as we move forward with complete chromosome screening (CCS) of embryos in 2012.

The contents of the poster pictured to the right are posted below.

eSET and vitrification give high cumulative pregnancy and delivery rates, reducing the need for transfer of multiple embryos in good prognosis patients

By: Erin Fischer, BS and Joe Conaghan, PhD; Pacific Fertility Center, San Francisco, CA

Introduction

One approach to reducing IVF multiple pregnancy risk is to culture embryos to the blastocyst stage and then select the single best embryo for transfer. This approach can be used for all patients, but it relies on the ability of the laboratory to successfully cryopreserve surplus embryos for later use. Patients and physicians may not be willing to elect to transfer just a single embryo unless they have the insurance of a solid cryopreservation program that can provide high pregnancy rates. If implantation rates for embryos that that been frozen and thawed are as good as, or better than those with fresh embryos, then the incentive to transfer more than 1 embryo in the fresh cycle goes away.

The introduction of vitrification as a means of preserving blastocysts has allowed embryologists to reliably achieve high implantation rates with warmed embryos, leading to reduced numbers of embryos transferred in fresh cycles. Good prognosis patients, such as those using donor oocytes, or where the woman is under age 35, can be encouraged to transfer just a single embryo in their fresh cycle with the aim of avoiding a multiple pregnancy. Vitrification has been shown to work reliably with human blastocysts and patients that fail to establish a pregnancy in their fresh cycle can return quickly for another attempt at pregnancy with their vitrified embryos. Embryos can be warmed one at a time, and transferred individually even in the frozen cycle, giving patients a high chance of pregnancy while still maintaining low multiple rates.

In the present study, we present our experience with vitrification as an important part of our overall program that aims to reduce multiple pregnancy in high risk patients while still maintaining excellent fresh, frozen and cumulative pregnancy rates. Vitrification was introduced for preserving blastocysts in 2007 and since then patients with good quality oocytes (i.e. low maternal age) who were undertaking their first or second IVF cycle were asked to consider eSET in their fresh and frozen cycles. This program has been successful in delivering high cumulative live birth rates for patients doing one IVF cycle.

Materials and Methods

Good prognosis patients were informed at the initiation of their treatment that we would aim to transfer just a single embryo in their fresh, and if necessary, frozen cycles. The embryos from these patients were cultured to the blastocyst stage, and when the patient agreed to single embryo transfer, one embryo was selected based on morphologic criteria on Day 5 of development. Patients that elected to transfer 2 embryos (DET) were counseled on the risks of multiple pregnancy.

As part of our efforts to continually improve embryo survival and implantation rates after warming, from June 2009 artificial collapse (AC) of the blastocyst cavity was routinely applied to all embryos with a cavity > 50% of the volume of the embryo. From January of 2010, all warmed blastocysts underwent assisted hatching prior to transfer. These manipulations were achieved through the use of a single 450 µs laser pulse (Research Instruments, UK) applied at the junction of 2 trophectoderm cells (see Figure 2) for AC, or several pulses applied to the zona after warming to facilitate hatching.

Results

In the program overall, implantation rates following vitrification improved year after year through experience, and the introduction of AC and AH. Also, the number of twin gestations decreased over the past five years as confidence in our vitrification program grew and the percentage of patients transferring one embryo increased. From 2009 to 2012 frozen embryo implantation rates for patients under 35 rose from 36% to 56% while the eSET rate went from 33% to 71% of patients. The percentage of twins fell from 22% to 16% in this age category and we continue to see these trends as we move forward with complete chromosome screening (CCS) and vitrification of embryos in 2012. (See Figure 1)

In 2010, the fresh pregnancy rate for patients under 35 was 48%, with 56 of 123 (46%) patients opting for a single embryo transfer. For patients using donor oocytes the pregnancy rate was 60% with 85 of 140 (61%) cases being SETs. The live birth rate per patient was 44% and 50%, respectively. The cumulative live birth rate, which includes patients who returned to use their frozen embryos following a negative fresh cycle, was 64% for <35 and 73% for oocyte donor recipients. (See Figure 3)

In looking at the cumulative live birth rate, patients under 35 not achieving a fresh pregnancy had frozen pregnancy rates from warmed embryos of 66% (23/35); 11 (32%) which were SET resulting in 7 pregnancies (64%), and 24 patients transferring 2 embryos with 16 pregnancies (67%). There was one set of monozygotic twins from the SET group and 9 sets of twins following the transfer of 2 embryos (56%). (See Figure 4)

For oocyte donor recipients that did not have a live birth from their fresh pregnancy, 57 patients returned to use their vitrified embryos with a 54% pregnancy rate. 28 patients opted for an eSET with 13 pregnancies (46%) and no twins. 29 patients transferred 2 embryos with 18 pregnancies (62%), and 10 sets of twins (56%). (See Figure 4)

In 2011 the frozen embryo pregnancy rate for patients under 35 transferring one embryo was 55% with one set of monozygotic twins. The pregnancy rate transferring two embryos was 55% with 10 sets of twins (38%). For oocyte donor recipients transferring one embryo 51% became pregnant with three sets of monozygotic twins (7%). Patients transferring two embryos had a pregnancy rate of 46% and 9 sets of twins (39%) (See Figure 5)

Conclusions

The advent of vitrification for preservation of surplus blastocysts has facilitated the process of eSET in good prognosis patients. Vitrification of blastocysts is a relatively simple process that can be performed easily and quickly following embryo transfer. High recovery and survival rates for these embryos ensures good implantation and pregnancy rates after frozen embryo transfer. With experience, the rate of implantation for vitrified embryos increases and may surpass implantation rates seen with fresh embryos.

In this study, good prognosis patients that elected to transfer one embryo had slightly lower clinical pregnancy rates than patients transferring two. However, they had dramatically lower multiple pregnancy rates, and cumulative live birth rates were not different between patients transferring 1 or 2 embryos.

Conservative use of the embryos generated in a single IVF cycle with the aid of a highly successful vitrification program, gives patients access to high pregnancy and live birth rates without the dangers and complications of multiple pregnancy.

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