How does the uterine lining thickness affect pregnancy in each IVF protocol?

This study compared how the thickness of the uterine lining affected outcomes from two protocols for in vitro fertilization (IVF). It found that the GnRH antagonist protocol had better outcomes when the lining was of medium thickness. The long GnRH agonist protocol had better outcomes when there was a thick lining.

IVF is one of the most common and established infertility treatments. There are several medication protocols in use for IVF. In the natural menstrual cycle, gonadotropin hormones stimulate the ovaries and trigger ovulation. Gonadotropin-releasing hormone (GnRH) directs the pituitary gland to release these hormones. 

To prevent unpredictable early ovulation, the body’s own gonadotropin hormones are downregulated (reduced) during IVF. The classic method is the long GnRH agonist (GnRH-a) protocol. This floods the body with so much GnRH that the pituitary gland stops responding to it. A more recent method is the GnRH antagonist (GnRH-ant), which directly blocks the pituitary from sensing GnRH.

The long GnRH-a and GnRH-ant protocols are both effective. GnRH-a can have more side effects, such as hot flashes, and also requires the use of more ovarian stimulation medications. However, an early study suggests fresh embryos may implant in the uterus at a lower rate when using the GnRH-ant protocol. It is not clear whether the type of protocol affects how receptive the lining of the uterus is to implantation.

This study used records from 4,631 patients who were undergoing IVF or a related technique, intracytoplasmic sperm injection (ICSI). 1,527 patients used the GnRH-ant protocol, while 3,104 used the long GnRH-a protocol. The women in the GnRH-ant group had a significantly lower ovarian reserve (AMH 1.81 vs. 2.71 ng/mL), and had been trying to conceive for a longer time (38 vs. 36 months). Ultrasound was used to measure the lining of the uterus on the same day as an injection was given to trigger ovulation.

For the long GnRH-a group, pregnancy and birth rates increased with a thicker lining. The birth rate was at least 50% in the long GnRH-a group when the lining was at least 9.5 mm. However, there was a difference in how the thickness of the lining affected outcomes between the two protocols.

For the GnRH-ant group, the birth rate was over 50% when the lining was between 9.5 and 15.5 mm. The birth rate was highest (70%) in the GnRH-ant group when the lining was 12 mm. Over that thickness, the birth rate decreased sharply as the lining became thicker.

GnRH-ant protocol had a significantly higher pregnancy rate when the lining was of medium (7 to 10 mm) thickness (61.81% vs. 55.58%). This is not adjusted for age, ovarian reserve, or other factors. The long GnRH-a protocol had a higher pregnancy rate when the lining was thick (over 14 mm).

This study found that the thickness of the uterine lining affected IVF pregnancies depending on whether the long GnRH-a or GnRH-ant protocol was used.

This study assumes that the thickness of the lining is separate from the protocol. However, which hormonal medications are used may affect the uterine lining thickness.