Interpretation
Until now, it remains unclear if estradiol valerate and progesterone
harm endometrial receptivity and embryo development. The adverse
clinical outcome of AC might be caused by supraphysiological hormone
levels during early trophoblast invasion, which could lead to abnormal
pregnancy18-20. Estradiol is essential for endometrial
and placental development. One historical cohort study indicated
elevated serum estradiol levels in AC cycles are associated with lower
ongoing pregnancy rate and live birth rate21. Excess
estradiol levels in the early stages of pregnancy can have adverse
effects on placentation and may in turn cause miscarriage. In vitro
study has shown estradiol can cause cell death and inhibit trophoblast
invasion in both first-trimester human cytotrophoblast cell line and
placental explants22. Studies have indicated
preeclampsia in pregnancy is associated with FET23,24.
Unfortunately, we have no data on pre-eclampsia. One retrospective study
suggested a higher risk of hypertension disorder in women of both
singletons and multiples after AC than NC7. The
adverse obstetric outcomes of AC for endometrial preparation indicate a
possible link between endometrial preparation and placenta-related
diseases, which might be caused by supraphysiological hormone levels
during early trophoblast invasion. In natural cycles, corpus luteum (CL)
is derived from the ovulated follicle. The formation of CL is
indispensable for steroid hormone production required to support
endometrial receptivity for successful implantation and maintenance of
early pregnancy. However, women in the AC cycle do not have CL to
produce hormone that is necessary to sustain early pregnancy. Instead,
women in the AC cycle were given exogenous estradiol and progesterone
and maybe too much or less for individual need. Exogenous endometrial
preparation may decrease the ability of embryos selecting the
endometrium, which could, in turn, lead to abnormal embryos implantation
and miscarriage.
Although we did not find a difference in the live birth rate between two
protocols, we did demonstrate a higher miscarriage rate in AC cycles.
Miscarriage is a heartbreaking experience for patients and may lead to
intrauterine infection or adhesion which could, in turn, have a negative
effect on embryo implantation for the next cycle of embryo transfer.
Even though AC is convenient for both doctors and patients, a higher
miscarriage rate should be considered before making decisions.