Frozen embryo transfer or FET is a highly effective method for conceiving a pregnancy. In fact, recent studies show that the chances for pregnancy are higher when embryos are frozen and placed into the uterus at a time after the stimulation of the ovaries.

Frozen embryo transfers are most commonly performed by preparing the uterine lining with hormones. Estrogen is used first to thicken the lining and progesterone is used next to produce the changes necessary for an embryo to implant.

So what can go wrong with a frozen embryo transfer?

Frozen Embryo Transfer Problem 1 – A thin uterine lining

Many studies have demonstrated that not as many women get pregnant if their uterine lining, as measured on ultrasound, does not thicken enough. In most women, it isn’t clear why this happens and there isn’t a sure fire treatment that will always get the lining thicker. Fertility experts will try a number of different approaches such as increasing the dose of estrogen or changing how the estrogen is given. In other cases, supplemental medications can be tried. In some women, however, the problem will persist.

What is done if the problem persists?

One approach is to cancel the embryo transfer and try again at a later time, perhaps with a different treatment method. A second option is to go ahead with the transfer. A thin lining does not necessarily mean that it is impossible to get pregnant but the efficiency may be reduced. One other option is to use the opportunity to do additional testing to assess the “receptivity” or ability of the uterus to allow embryos to implant.

Read more: Endometrial receptivity testing

Frozen Embryo Transfer Problem 2 – Unexpected ovulation

In order for embryos to implant into the uterus, they must be placed at precisely the correct time. This is known as the window of implantation. The timing is based on the length of time since progesterone reaches the uterine lining.

When your doctor has you start taking progesterone supplements, he or she knows the correct time to place the embryos. However, if you were to ovulate – you would start producing progesterone earlier than expected and this would shift the window of implantation. Since it is nearly impossible to identify the exact time of ovulation, this will introduce some uncertainty into the timing.

For this reason, many doctors will use medications to try to prevent unexpected ovulation. The medications most commonly used for this are called GnRH antagonists. In the USA, two brands of GnRH-a medications are Ganirelix and Cetrotide

Frozen Embryo Transfer Problem 3 – Inappropriate timing for the embryo transfer

This problem is related to the early ovulation problem. However, in some cases, the window of implantation is shifted even then the timing of the transfer is accurate. Previously, doctors believed that the timing of the window of implantation was the same in all women. Studies using molecular markers to identify the correct “window of implantation” have shown that a small percentage of women may have a window of implantation that is earlier or later than usual.

Tests such as the Endometrial Receptivity Array were performed for many years in the hopes that it could help identify patients that has a shift in their window of receptivity and therefore allow the doctor t make adjustments. Unfortunately, several studies in the last few years have failed to show a benefit in making these adjustments Therefore, the ERA is no longer recommended.

Frozen Embryo Transfer Problem 4 – Fluid in the uterine cavity

Fluid in the uterine cavity
Fluid in the uterine cavity

The cells of the uterine lining are constantly producing fluid. Some of this fluid is reabsorbed by cells in the uterine lining, some of the fluid leaks out of the uterus through the cervix into the vagina and some leaks out thought the fallopian tubes into the abdomen. In some cases, however, extra fluid may accumulate in the cavity and this can be seen on ultrasound. Doctors do not want to transfer embryos into a uterine cavity that is filled with fluid as this will lessen the chances that the embryos will implant.

In some patients, fluid accumulation in the uterine cavity may be a sign that the ends of the fallopian tubes are blocked causing the tubes to fill with fluid. This is called a hydrosalpinx. Women who have a hydrosalpinx have much lower pregnancy rates with IVF or FET cycles. The treatment to fix this cause for fluid is to perform surgery and remove the fallopian tubes. This is known as a salpingectomy. This is a well-studied treatment that is found to double the chances for pregnancy.

In the absence of a hydrosalpinx, getting rid of fluid in the uterine cavity is more challenging. If the fluid is present during the time that estrogen is being taken, then starting progesterone will often cause the excess fluid to be reabsorbed and an embryo transfer can proceed normally.

Some doctors will put a catheter inside the uterus and try to aspirate the fluid. There is little evidence that this is an effective treatment.

Finally, it may be prudent to cancel the FET cycle, induce a period and try again on a different month.

Frozen Embryo Transfer Problems: Unknown factors

The uterine lining and the embryo have many complex interactions that are poorly understood. Even when none of the problems described in this article are present, embryos may still fail to implant. With continued research, new problems and new therapies will hopefully be discovered. IVF1 is currently conducting clinical research studies of a new treatment that we hope may help some women with recurrent implantation failure achieve a pregnancy.

Learn more about IVF1 clinical trials

Conclusion

Frozen embryo transfer is an effective means for achieving pregnancy. Problems can occur while preparing a woman for an FET. These problems include a failure to adequately thicken the uterine lining, premature ovulation, fluid accumulation in the uterine cavity and incorrect timing of a transfer. There may be other problems that scientists have not yet discovered.