Does Using Letrozole-Induced Frozen Embryo Transfer Cycles Reduce the Risk of Hypertensive Disorders in Women with PCOS?
BACKGROUND AND PURPOSE:
Zhang et al. (AJOG, 2021) assessed the impact of letrozole (an aromatase inhibitor) during frozen embryo transfer (FET) on obstetrical and perinatal outcomes of singleton and twin pregnancies compared with artificial cycle FET among women with polycystic ovary syndrome
Retrospective cohort study
Women with PCOS undergoing FET from 2010 to 2018
Letrozole-stimulated cycle FET
Artificial cycle FET (estrogen and progesterone are used to mimic the natural cycle)
Multivariable logistic regression analysis was performed with control for potential confounders
Incidence of hypertensive disorders of pregnancy
2427 women with PCOS
Artificial cycles: 1168 women
Letrozole-stim cycles: 1259
Letrozole alone: 25%
Letrozole plus gonadotropins: 75%
There was no significant difference between the groups for the following
Preterm premature rupture of membranes
Prevalence of the following birth outcomes were similar between groups
Singleton pregnancies resulting from letrozole-stimulated cycles had a lower risk of hypertensive disorder of pregnancy than those conceived by artificial cycle
Adjusted odds ratio (aOR) 0.63 (95% CI, 0.40 to 0.98)
There was also a decreased risk of hypertensive disorders of pregnancy in women with twin pregnancies resulting from letrozole-stimulated cycles, compared to those from artificial cycles
aOR 0.52 (95% CI, 0.30 to 0.87)
The cesarean delivery rate was significantly lower for singletons but not for twins in the letrozole group compared with pregnancies from the artificial cycle group
Singletons: aOR 0.63 (95% CI, 0.50 to 0.78)
Twins: aOR 1.20 (95% CI, 0.65 to 2.23)
It is postulated that pregnancies conceived using artificial cycle FET do not have a corpus luteum and this may contribute to a higher incidence of hypertensive disorders of pregnancy
Incorporating letrozole into frozen embryo transfer (FET) protocols would lead to the development of a corpus luteum and therefore reduce the risk for hypertensive disorders of pregnancy in patients with PCOS
For women with PCOS undergoing FET, the use of letrozole for endometrial preparation was associated with fewer hypertensive disorders of pregnancy, compared with women who underwent artificial cycle FET
The authors conclude
Our findings provided a foundation that the increased risk of hypertensive disorder of pregnancy associated with frozen embryo transfer might be mitigated by utilizing physiological endometrial preparation protocols that lead to the development of a corpus luteum, such as a mild ovarian stimulation cycle for oligo- or anovulatory women
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