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

METHODS:

• Retrospective cohort study
• Participants
  • Women with PCOS undergoing FET from 2010 to 2018
• Exposure
  • Letrozole-stimulated cycle FET
  • Artificial cycle FET (estrogen and progesterone are used to mimic the natural cycle)
• Study design
  • Multivariable logistic regression analysis was performed with control for potential confounders
• Primary outcome
  • Incidence of hypertensive disorders of pregnancy

RESULTS:

• 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
  • Gestational diabetes
  • Abnormal placentation
  • Preterm premature rupture of membranes
• Prevalence of the following birth outcomes were similar between groups
  • Preterm birth
  • Perinatal death
  • Birthweight outcomes
• 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)

CONCLUSION:

• 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

Learn More – Primary Sources:

Letrozole-induced frozen embryo transfer cycles are associated with a lower risk of hypertensive disorders of pregnancy among women with polycystic ovary syndrome

Related ObG Topics:

Does Endometrial Scratching Improve IVF Outcomes?

Are Adverse Birth Outcomes Following Medically Assisted Reproduction a Result of Treatment or Underlying Issues?

Cochrane Review: Letrozole vs Clomiphene Citrate for the Treatment of infertility in Women with PCOS