Frozen Embryo Transfer Vs Fresh Embryo Transfer after IVF

Frozen Embryo Transfer Vs Fresh Embryo Transfer after IVF

Frozen Embryo Transfer Vs Fresh Embryo Transfer after IVF

After embryos are created with in vitro fertilization, should you have your embryos transfer 3 to 5 days later or should embryos be frozen and transferred later in frozen-thaw cycle (FET)? This question became viable after improvement in freezing technology (vitrification) to the extent that the vast majority of embryos (>95%) frozen in The US survive thaw and has high implantation potential.

There are indications to freeze all embryos after IVF i. avoiding ovarian hyperstimulation syndrome,ii. unfavorable uterine lining (thin, fluid..) iii. allow more time for PGD / PGS, iv.personal reasons related to patients.

The aim here is to discuss the merits for and against elective embryo freezing to transfer the embryo or embryos in a thaw cycle. A thaw cycle involves preparation of the uterine lining, embryo thaw and embryo transfer (no stimulation or egg retrieval). Preparation of the lining of the uterus can be accomplished through one of two main methods

a. Natural Cycle FET  :  Natural ovulation is monitored using ultrasound and blood work. The time of ovulation need to be accurately defined. Embryos are thawed 3 or 5 days later and transferred. It requires minimal medications but require regular ovulation.

b. Synthetic Cycle FET  :  Estrogen is administered (patches, pills..etc) till the lining of the uterus reach the desired thickness and pattern. Progesterone is then administered (injections, vaginal tablets) and embryos are thawed and transferred few days later. It does not require ovulation and allows more flexibility in timing of embryo transfer.

There is some evidence that both methods are equivalent with regards to implantation and pregnancy.

On The Advantages of Elective Frozen Embryo transfer

Fresh embryos vs Frozen Embryos

Fresh embryos vs Frozen Embryos

In the US frozen cycles result in equivalent number of pregnancies and deliveries as fresh embryos.

Should Elective Frozen Embryo Transfer be Recommended to The General Fertility Population Undergoing IVF?

In other words, do we have enough data to recommend freezing all embryos created after IVF and transfer later?

The possible advantages cited for performing frozen embryos transfer originates from two sources

1. Physiological information: excessive exposure of the lining of the uterus to estrogen may lead to abnormal development of the placenta and

2. Observational studies: when compared to fresh embryo transfer, pregnancies resulting from frozen transfer are less affected by bleeding and are associated with heavier babies with lower odds for low birth weight.

Conclusions resulting from non controlled studies and physiologic interpretation are not always accurate due to differences between the two groups and cannot be relied upon for definitive conclusions. A definitive study will need to be prospective and patients can be randomly allocated to fresh transfer or elective frozen transfer. This study does not exist at this time

Can Elective Frozen Embryo Transfer Improve Pregnancy & Delivery Rates?

Three studies showed a trend to improve in pregnancy rates following frozen transfer when compared to fresh IVF transfer. The studies should be interpreted with caution as it included young high or normal responders and not low responders and older women. The studies did show an improve in delivery rate, did not track perinatal outcomes and did not include economic analysis of cost and benefits. So a larger and more comprehensive study is still needed.

New Ideas in reproductive medicine, though exciting, still require the scientific rigorous study to ensure that the conclusions are correct and define which group will benefit most from freeze all strategy before its general application to women undergoing IVF.

If you need to freeze your embryos after IVF to avoid ovarian hyperstimulation syndrome, because of unfavorable uterine lining or other reasons, please do so especially if the clinic has a robust freezing program. Freezing of embryos (especially with vitrification) is unlikely to affect your chance to get pregnant. On the other hand if you want to freeze all your embryos to improve your chance of getting pregnant, know that this strategy is debatable and not backed by solid scientific evidence.

When undergoing a frozen transfer cycle and if you have regular ovulation and a favorable lining, consider natural cycle FET over synthetic (medicated) cycle as there is evidence that they are equivalent. Natural cycle avoid external medications and excessive exposure to estrogen


Frozen Embryo Transfers (FET)

Frozen Embryo Transfer

Following IVF, excess embryos are frozen for use with second attempts if no pregnancy takes place or to conceive a second child. With improvement of the freezing and thaw techniques: the majority of frozen embryos survive thawing, the implantation potential of a thawed embryo is comparable to a fresh embryo, less embryos or single embryo can be transferred in the fresh cycle and selection of the best embryo for fresh transfer became less important.

Frozen embryo transfer: blastocysts and cleavage embryos can be vitrified after IVF

Frozen embryo transfer (FET)

Freezing of embryos allow ample time for genetic testing of embryos if needed, transferring embryos to a different locale, delaying transfer due to medical problem, the emergence of an abnormality in the lining of the uterus e.g thin  endometrium, polyp, fluid.. or till a gestational carrier is found.

Benefits of Frozen Embryo Transfer

1. Pregnancy rate after frozen embryo transfer is comparable to fresh transfer and may even be higher than fresh transfer in some studies. More work is needed to confirm higher live birth rate.

2. Complications: frozen embryo transfer minimize some of the complications related to IVF. Ovarian hyperstimulation syndrome (OHSS) and possibly ectopic pregnancy (pregnancy in the fallopian tube)

3. Lower risk for pregnancy complications and better quality baby: frozen transfer appear to reduce the risk for preterm delivery, bleeding in pregnancy and low birth weight, possibly due to better placental function.

How is the lining of the uterus prepared for frozen embryo transfer?

1. Natural cycle: in ovulating women, the follicle in the ovary is monitored till the point of ovulation is accurately identified. The follicle will internally produce the estrogen required to build the lining. When ovulation takes place, the embryos are thawed and transferred in a day comparable to its age e.g a day 5 embryo is transferred 5 days after ovulation. This process require only ultrasound and blood work monitoring

2. Estrogen replacement cycle: ovulation is stopped and estrogen is supplemented externally (patches,oral or vaginal) till the desired thickness and pattern of the uterine lining. Progesterone is then started (injection or vaginal) then embryos are transferred.

Timing of thaw and transfer is a complicated question and it depends on the type of cycle and age of embryos. Sometimes embryos are thawed and cultured for few days before transfer

All method for endometrium preparation yield similar pregnancy rate. At NYCIVF we prefer natural cycle with luteal phase support using vaginal estrogen.

What makes a frozen embryo transfer cycle successful?

Embryo quality: one or more top quality embryo morphology observed at any stage of culture improves the outcome even if high-quality characteristics disappeared before transfer. Transferring more than one embryo increases the pregnancy rate but also multiple pregnancy.

Conclusion: should you intentionally delay transfer to frozen cycle? no but if you need to freeze the embryos, expect similar pregnancy rate as in the fresh cycle.