BACKGROUND
Although live birth rates were comparable between programmed and natural frozen-thawed
embryo transfer cycles, recent data showed that pregnancies after programmed cycle
were associated with an increased risk of adverse perinatal outcomes, such as hypertensive
disorders of pregnancy. Such a difference might be attributed to selection bias because
patients with ovulation disorders are more likely to receive programmed endometrial
preparation protocol than natural cycle.
OBJECTIVE
This study aimed to analyze whether programmed endometrial preparation protocol is
associated with an increased risk of adverse perinatal outcomes compared with natural
cycle during frozen embryo transfer in ovulatory women.
STUDY DESIGN
This regional multicenter retrospective cohort study was conducted in 5 reproductive
medical centers in Southeast China. Patients with regular cycles (21–35 days), who
underwent either programmed or natural cycle blastocyst frozen embryo transfer and
delivered singleton live birth babies after 28 weeks of gestation between 2016 and
2019 were analyzed. Each patient only contributed 1 cycle per cohort. The patients’
frozen embryo transfer treatment cycles were linked to their obstetrical medication
record, and a comprehensive medical record review was conducted to compare the maternal
and neonatal outcomes between natural cycle and programmed cycle. Crude and adjusted
odds ratios with 95% confidence intervals were calculated, and adjustment was made
for relevant confounders.
RESULTS
Study samples included 499 natural cycle frozen embryo transfer cases and 900 programmed
frozen embryo transfer cases. Pregnancies after programmed cycle were associated with
increased odds of hypertensive disorders of pregnancy (adjusted odds ratio, 2.71;
95% confidence interval, 1.59–4.91) and preeclampsia (adjusted odds ratio, 2.71; 95%
confidence interval, 1.17–6.23) compared with pregnancies after natural cycle. No
significant difference was detected regarding other adverse perinatal outcomes between
the 2 endometrial protocols. In subgroup analysis, both the subgroups of hormone replacement
therapy and hormone replacement therapy with gonadotrophin-releasing hormone analogue
pretreatment had increased odds of developing hypertensive disorders of pregnancy
than the natural cycle group. The risk of developing preeclampsia was higher in the
hormone replacement therapy with gonadotrophin-releasing hormone analogue pretreatment
subgroup than in the other 2 groups (adjusted odds ratio, 4.99; 95% confidence interval,
1.94–12.82) (aOR, 2.47; 95% CI, 1.17–5.18).
CONCLUSION
Pregnancies after programmed frozen embryo transfer were associated with higher risks
of hypertensive disorders of pregnancy in ovulatory women. The hormone replacement
therapy with gonadotrophin-releasing hormone analogue pretreatment cycle led to the
highest risk of preeclampsia among the 3 protocols.
Keywords
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Article info
Publication history
Published online: September 14, 2022
Accepted:
September 11,
2022
Received:
August 24,
2022
Footnotes
The authors consider that F.G., Y.W., and M.T. should be regarded as joint first authors.
This study was funded by the National Natural Science Foundation of China (grant number 82001499) and the Guangdong Basic and Applied Basic Research Foundation (grant number 2019A1515110623).
The authors report no conflict of interest.
Cite this article as: Gu F, Wu Y, Tan M, et al. Programmed frozen embryo transfer cycle increased risk of hypertensive disorders of pregnancy: a multicenter cohort study in ovulatory women. Am J Obstet Gynecol MFM 2022;XX:x.ex–x.ex.
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