Endometrial preparation methods for frozen-thawed embryo transfer are associated with altered risks of hypertensive disorders of pregnancy, placenta accreta, and gestational diabetes mellitus

Hum Reprod. 2019 Aug 1;34(8):1567-1575. doi: 10.1093/humrep/dez079.


Study question: What were the risks with regard to the pregnancy outcomes of patients who conceived by frozen-thawed embryo transfer (FET) during a hormone replacement cycle (HRC-FET)?

Summary answer: The patients who conceived by HRC-FET had increased risks of hypertensive disorders of pregnancy (HDP) and placenta accreta and a reduced risk of gestational diabetes mellitus (GDM) in comparison to those who conceived by FET during a natural ovulatory cycle (NC-FET).

What is known already: Previous studies have shown that pregnancy and live-birth rates after HRC-FET and NC-FET are comparable. Little has been clarified regarding the association between endometrium preparation and other pregnancy outcomes.

Study design, size, duration: A retrospective cohort study of patients who conceived after HRC-FET and those who conceived after NC-FET was performed based on the Japanese assisted reproductive technology registry in 2014.

Participants/materials, setting, methods: The pregnancy outcomes were compared between NC-FET (n = 29 760) and HRC-FET (n = 75 474) cycles. Multiple logistic regression analyses were performed to investigate the potential confounding factors.

Main results and the role of chance: The pregnancy rate (32.1% vs 36.1%) and the live birth rate among pregnancies (67.1% vs 71.9%) in HRC-FET cycles were significantly lower than those in NC-FET cycles. A multiple logistic regression analysis showed that pregnancies after HRC-FET had increased odds of HDPs [adjusted odds ratio, 1.43; 95% confidence interval (CI), 1.14-1.80] and placenta accreta (adjusted odds ratio, 6.91; 95% CI, 2.87-16.66) and decreased odds for GDM (adjusted odds ratio, 0.52; 95% CI, 0.40-0.68) in comparison to pregnancies after NC-FET.

Limitations, reasons for caution: Our study was retrospective in nature, and some cases were excluded due to missing data. The implication of bias and residual confounding factors such as body mass index, alcohol consumption, and smoking habits should be considered in other observational studies.

Wider implications of the findings: Pregnancies following HRC-FET are associated with higher risks of HDPs and placenta accreta and a lower risk of GDM. The association between the endometrium preparation method and obstetrical complication merits further attention.

Study funding/competing interest(s): No funding was obtained for this work. The authors declare no conflicts of interest in association with the present study.

Trial registration number: Not applicable.

Keywords: frozen-thawed embryo transfer; gestational diabetes mellitus; hormone replacement cycle; hypertensive disorders of pregnancy; placenta accreta.

MeSH terms

  • Adult
  • Birth Rate
  • Cryopreservation / methods
  • Diabetes, Gestational / epidemiology*
  • Diabetes, Gestational / etiology
  • Embryo Transfer / adverse effects*
  • Female
  • Humans
  • Hypertension, Pregnancy-Induced / epidemiology*
  • Hypertension, Pregnancy-Induced / etiology
  • Incidence
  • Live Birth
  • Placenta Accreta / epidemiology*
  • Placenta Accreta / etiology
  • Pregnancy
  • Pregnancy Outcome
  • Pregnancy Rate
  • Retrospective Studies
  • Risk