Can an ovulatory cycle improve the pregnancy outcomes of women undergoing frozen embryo transfer?

This review compared pregnancy outcomes following two methods of preparing the uterus for a frozen embryo transfer (FET). It found that natural cycle FET led to fewer pregnancy complications than artificial cycle FET.

Frozen embryo transfer (FET) is a common infertility treatment is related to in vitro fertilization (IVF). FET allows embryos to be transferred in a future menstrual cycle. Freezing embryos allows for multiple embryo transfers from the same IVF egg collection. It also reduces the risk of ovarian hyperstimulation syndrome (OHSS), which is a complication of IVF.

Prior to FET, the lining of the uterus is prepared so it is receptive to an embryo implanting. Artificial cycle (AC) uses synthetic hormones to thicken and mature the lining of the uterus. Alternately, natural cycle (NC) times the FET for after ovulation when the uterus is receptive.

During pregnancy, tissue from the embryo will grow into the lining of the uterus and forms the placenta. This organ exchanges nutrients between the woman’s blood and the embryo’s. A healthy uterine lining is needed for the placenta to form well. If not, it can increase complications during the pregnancy. This includes pre-eclampsia, which involves high blood pressure and the placenta not receiving enough blood.

It is not clear whether the type of preparation used for FET influences pregnancy outcomes.

This review included 13 studies of 93,201 cycles of FET overall. All of the studies used past medical records. Two of the studies were of large-scale registries, which included national records of FET in Sweden and Japan.

Four studies of 22,856 patients found that patients 53% fewer patients using NC-FET developed pre-eclampsia. There was a trend toward less pregnancy-related high blood pressure for patients using NC-FET.

Large birth weight (macrosomia) refers to an infant born over 4 kg (8.8 lbs). Large birth weight can increase childbirth complications and increases the chance the baby will develop obesity later in life. Pregnancies following NC-FET had large birth weight 18% less often than those following AC-FET. Patients using NC-FET also had a 16% lower chance of a Cesarean section delivery.

39% fewer patients using NC-FET had the placenta separate early (placental abruption). Also, 82% fewer patients using NC-FET had the placenta not separate normally following the birth (placenta accreta), which can cause dangerous bleeding.

This review found that pregnancies following NC-FET had less pre-eclampsia, less large birth weight, and fewer problems with the placenta than those following AC-FET.

Patients with health conditions that prevent ovulation, such as polycystic ovarian syndrome (PCOS), are more likely to use AC-FET. However, PCOS can also affect pregnancy outcomes including preterm delivery and large birth weight.