How many days of progesterone before frozen embryo transfer?

This study looked at the number of days of progesterone treatment before frozen embryo transfer (FET) in hormone replacement cycles. It found that transfers after 7 days of progesterone may miscarry less, but the birth rate was the same as transfers after 6 days of progesterone.

In vitro fertilization (IVF) is an infertility treatment that stimulates multiple eggs and fertilizes them in the laboratory. The resulting embryos can be transferred to the uterus a few days later, or they can be frozen. Freezing embryos allows fewer embryos to be transferred at a time, reducing the risks of multiple pregnancies (twins or triplets). 

For a FET to be successful, the uterus (womb) must be receptive to embryo implantation at the transferral time. During a natural menstrual cycle, progesterone levels rise following ovulation and prepare the uterine lining. FET cycles can time the transfer to follow ovulation, or hormone replacement (HR) medications can prepare the uterine lining artificially. Some studies have found that FET after ovulation leads to lower rates of miscarriage than HR. However, HR is still commonly used, particularly for women who do not ovulate regularly. When using HR, it is not clear how many days of progesterone replacement before FET leads to optimal results.

This study used records from 619 patients undergoing HR-FET. All patients received estrogen for at least 13 days, followed by progesterone. 346 patients underwent FET on the 6th day of progesterone treatment (6-day group), and 273 patients underwent FET on the 7th day (7-day group). The thickness of the embryo lining on the day of FET was similar in both groups. Progesterone was continued after the FET.

Both groups had a birth rate of 36.6%. There was little difference even after adjusting for factors such as age, weight, and smoking. Significantly fewer FETs from the 7-day group ended in a clinical miscarriage (10.3% vs. 15.6%). A clinical miscarriage occurs after an ultrasound has confirmed pregnancy, and does not include very early losses after a positive pregnancy test.

The number of days after fertilization that an embryo is frozen can be meaningful. The study analyzed how the number of days of progesterone impacted FETs of embryos frozen six days after fertilization. For these FETs, 7-day progesterone cycles had significantly fewer miscarriages than 6-day (21.4% vs. 50%). There was also a trend toward more live births for 7-day cycles of these embryos (35.5% vs. 21.5%). For embryos frozen after five days, the number of days of progesterone did not affect miscarriage.

This study found that 7 days of progesterone may result in lower miscarriage for HR-FET, particularly with embryos frozen 6 days after fertilization.

Other studies have found that the number of days of progesterone did not impact HR-FET outcomes. Additional studies are needed, particularly studies where the number of days is randomly assigned.

If you will be using HR for a FET of embryos frozen six days after fertilization, talk to your doctor about the timing.