Background
Frozen embryo transfer is associated with better perinatal outcome regarding preterm
birth and low birthweight, yet higher risk of large for gestational age and macrosomia
compared to fresh transfer. Further, higher rates of hypertensive disorders in pregnancy
are noted after frozen embryo transfer. Whether these differences are due to the protocol
used in frozen cycles remains unknown.
Objective
To analyze the obstetric outcome after frozen embryo transfer depending on protocol
used. Comparison was also made for frozen vs fresh transfer and for frozen transfer
vs spontaneous conception.
Study Design
A population-based retrospective registry study including all singletons born after
frozen embryo transfer in Sweden from 2005 to 2015. The in vitro fertilization register
was cross-linked with the Medical Birth Register, the Register of Birth Defects, the
National Patient Register, the Swedish Neonatal Quality Register, and the Prescribed
Drug Register. Singletons after frozen embryo transfer were compared depending on
the presence of a corpus luteum in the actual cycle. All frozen transfer singletons
were also compared with fresh transfer and spontaneous conception singletons. Primary
outcomes were preterm birth (<37 w), low birthweight (<2500 g), hypertensive disorders
in pregnancy, and postpartum hemorrhage (>1000 mL). Crude and adjusted odds ratio
with 95% confidence interval were calculated and adjustment made for relevant confounders.
Results
A total of 9726 singletons were born after frozen embryo transfer (natural cycles,
n = 6297; stimulated cycles, n = 1983; programmed cycles, n = 1446), 24,365 after
fresh transfer, and 1,127,566 after spontaneous conception. No significant differences
were noticed for preterm birth and low birthweight between the different protocols
used in frozen embryo transfer. Compared to natural and stimulated frozen cycles,
programmed frozen cycles were associated with a higher risk of hypertensive disorders
in pregnancy (adjusted odds ratio, 1.78; 95% confidence interval, 1.43–2.21 and adjusted
odds ratio, 1.61; 95% confidence interval, 1.22–2,10, respectively) and postpartum
hemorrhage (adjusted odds ratio, 2.63; 95% confidence interval, 2.20–3.13 and adjusted
odds ratio, 2.87; 95% confidence interval, 2.29–2.60, respectively). Moreover, higher
risks for postterm birth (adjusted odds ratio, 1.59; 95% confidence interval, 1.27–2.01
and adjusted odds ratio, 1.98; 95% confidence interval, 1.47–2.68) and macrosomia
(adjusted odds ratio, 1.62; 95% confidence interval, 1.26–2.09 and adjusted odds ratio,
1.40; 95% confidence interval, 1.03–1.90) were detected. There were no significant
differences in any outcomes between stimulated and natural cycles. Frozen cycles in
general compared to fresh cycles and compared to spontaneous conceptions showed neonatal
and maternal outcomes in agreement with earlier studies.
Conclusion
No significant difference could be seen regarding preterm birth and low birthweight
between the different protocols. However, higher rates of hypertensive disorders in
pregnancy, postpartum hemorrhage, postterm birth, and macrosomia were detected in
programmed cycles. Stimulated cycles had outcomes similar to natural cycles. These
findings are important in view of the increasing use of frozen cycles and the new
policy of freeze-all cycles in in vitro fertilization. The results suggest a link
between the absence of corpus luteum and adverse obstetric outcomes.
Key words
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Article info
Publication history
Published online: March 22, 2019
Accepted:
March 18,
2019
Received in revised form:
March 5,
2019
Received:
November 16,
2018
Footnotes
The authors report no conflicts of interest.
The study was financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (LUA/ALF 70940).
Reprints will not be available.
Cite this article as: Ginström Ernstad E, Wennerholm U-B, Khatibi A, et al. Neonatal and maternal outcome after frozen embryo transfer: Increased risks in programmed cycles. Am J Obstet Gynecol 2019;221:126.e1-18.
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© 2019 Elsevier Inc. All rights reserved.
