Original Research
Obstetrics
Neonatal and maternal outcome after blastocyst transfer: a population-based registry study

Presented orally at the 36th Society for Maternal-Fetal Medicine Annual Pregnancy Meeting, Atlanta, GA, Feb. 1-6, 2016.
https://doi.org/10.1016/j.ajog.2015.12.040Get rights and content

Background

Previous studies have shown a higher risk of birth defects and preterm birth (PTB) in singletons born after blastocyst transfer as compared to singletons born after cleavage-stage transfer. Few studies have investigated the maternal outcomes.

Objective

We sought to analyze the neonatal and maternal outcome after blastocyst transfer (day 5-6) compared to transfer of cleavage-stage embryos (day 2-3) and spontaneous conception.

Study Design

This was a population-based retrospective registry study including all singleton deliveries after blastocyst transfer in Sweden from 2002 through 2013. The in vitro fertilization register was cross-linked with the Swedish Medical Birth Register, the Register of Birth Defects, and the National Patient Register. Deliveries after blastocyst transfer were compared with deliveries after cleavage-stage transfer and deliveries after spontaneous conception. Outcome measures included birth defects, PTB, low birthweight, small for gestational age, large for gestational age, perinatal mortality, placenta previa, placental abruption, and preeclampsia. Crude and adjusted odds ratios (AOR) with 95% confidence interval (CI) were calculated. Adjustment was made for year of birth of child, maternal age, parity, smoking, body mass index, years of involuntary childlessness, and child’s sex and, for cleavage stage, also for number of oocytes retrieved, number of embryos transferred, and fresh/frozen embryo transfer.

Results

There were 4819 singletons born after blastocyst transfer, 25,747 after cleavage-stage transfer, and 1,196,394 after spontaneous conception. Singletons born after blastocyst transfer had no increased risk of birth defects compared to singletons born after cleavage-stage transfer (AOR, 0.94; 95% CI, 0.79–1.13) or spontaneous conception (AOR, 1.09; 95% CI, 0.92–1.28). Perinatal mortality was higher in the blastocyst vs the cleavage-stage group (AOR, 1.61; 95% CI, 1.14–2.29). When comparing singletons born after blastocyst transfer to singletons born after spontaneous conception, a higher risk of PTB (<37 weeks) was seen (AOR, 1.17; 95% CI, 1.05–1.31). Singletons born after blastocyst transfer had a lower rate of low birthweight (AOR, 0.83; 95% CI, 0.71–0.97) as compared to cleavage-stage transfer. The rate of being small for gestational age was lower in singletons born after blastocyst transfer as compared to both cleavage-stage and spontaneous conception (AOR, 0.71; 95% CI, 0.56–0.88 and AOR, 0.70; 95% CI, 0.57–0.87, respectively). The risk of placenta previa and placental abruption was higher in pregnancies after blastocyst transfer as compared to pregnancies after cleavage-stage (AOR, 2.08; 95% CI, 1.70–2.55 and AOR, 1.62; 95% CI, 1.15–2.29, respectively) and spontaneous conception (AOR, 6.38; 95% CI, 5.31–7.66 and AOR, 2.31; 95% CI, 1.70–3.13, respectively).

Conclusion

No increased risk of birth defects was found in singletons born after blastocyst transfer. Perinatal mortality and risk of placental complications were higher in the blastocyst group as compared to the cleavage-stage group, observations that need further investigations.

Introduction

Worldwide, the use of assisted reproductive therapy (ART) is expanding, and the number of children born through ART has passed 6 million. In Sweden, around 4000 children are born through ART each year and they comprise today 3.6% of the total national birth cohort in Sweden.1

In vitro fertilization (IVF) is associated with an increased risk of preterm birth (PTB) and low birthweight (LBW) as compared to spontaneous conception, which mainly can be explained by the higher incidence of multiple pregnancies.2, 3, 4 However, an increased risk of PTB, LBW, and birth defects has also been demonstrated in singleton pregnancies after IVF.4, 5, 6, 7, 8, 9

In spontaneous conception the implantation occurs 5-7 days after fertilization. In conventional IVF, the cleavage-stage embryos (day-2 to -3 embryos) are replaced in the uterus. Modern technology has made it possible to wait until the blastocyst stage (day 5-6 embryos) and then replace the embryo in the uterus. Blastocyst transfer has been shown to increase delivery rates in fresh cycles, although not cumulatively.10

Conflicting results have been reported concerning neonatal and maternal outcomes after blastocyst vs cleavage-stage transfers. A systematic review and metaanalysis showed an increased risk of PTB (<37 gestational weeks) (4 studies) and birth defects (2 studies) when using blastocyst transfer.11 Other recent studies from Australia and Japan showed no significant differences in PTB or LBW between singletons from blastocyst and cleavage-stage transfers.12, 13 A previous Swedish study including 1311 singletons and multiples born after fresh and frozen blastocyst transfers, covering the years 2002 through 2006 and partially overlapping the present study, showed a significantly increased risk of birth defects as compared to children born after cleavage-stage transfer.14 However, in a Canadian study covering the years 2001 through 2009 including 3206 singletons after fresh blastocyst transfer there was no increased risk of birth defects after blastocyst transfer.15

Few studies have reported on maternal outcomes after blastocyst vs cleavage-stage transfers. A Swedish registry study, covering the years 2002 through 2006 and partially overlapping the present study, showed increased risk of placenta previa in singleton pregnancies from fresh blastocyst vs fresh day-2 to day-3 transfers.16 However, other studies have shown no significant differences in placental complications.13, 17, 18

The aim of this study was to examine neonatal and maternal outcomes in singleton deliveries after blastocyst transfer in Sweden from 2002 through 2013, and compare these deliveries with all singleton deliveries after cleavage-stage transfer and after spontaneous conception during the same period of time.

Section snippets

Study design

This study was a population-based retrospective registry study carried out in Sweden. We collected data from all IVF clinics, both public and private, in Sweden on IVF treatments performed from 2002 through 2013. The IVF clinics reported data on deliveries to the Swedish National Board of Health and Welfare for years 2002 through 2006, and for years 2007 through 2013, to the National Registry of Assisted Reproduction.1 All reported IVF singleton and twin deliveries with autologous oocytes were

Results

In total, 4819 singletons were born after blastocyst transfer, 62.8% after fresh and 37.2% after frozen embryo transfer. There were 25,747 singletons born after cleavage-stage transfer, 76.7% after fresh and 23.3% after frozen embryo transfer.

There were 295 multiple births after blastocyst transfer (76.6% fresh, 23.4% frozen) and 1937 after cleavage-stage transfer (78.0% fresh, 22.0% frozen), giving a multiple birth rate of 5.8% (295/5114) and 7.0% (1937/27,684), respectively.

In the general

Principal findings

The main finding of this large retrospective population-based registry study was that no significant difference in the rate of birth defects was found between singletons born after blastocyst transfers and singletons born after cleavage-stage transfers. Perinatal mortality and rates of placental complications were significantly higher in singletons born after blastocyst transfers as compared with singletons born after cleavage-stage transfer.

Meaning of the findings in relation to other studies

The finding of no increase in birth defects differ

Acknowledgment

The authors want to express their thanks to all in vitro fertilization clinics in Sweden that provided in vitro fertilization data.

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      However, a number of studies have drawn conflicting conclusions. These studies found that in fresh embryo transfer cycles, blastocyst transfer increased the risk of PTB, very preterm birth (VPTB) and LBW, but decreased the risk of SGA [13–15]. A meta-analysis published recently by Zeng et al. found that blastocyst transfer had no adverse effects on pregnancy outcomes in FET cycles compared with cleavage-stage embryo transfer [16].

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    This study was supported by grants from Swedish Association of Local Authorities and Regions and the University of Gothenburg/Sahlgrenska University Hospital (LUA/ALF 70940).

    The authors report no conflict of interest.

    Cite this article as: Ginström Ernstad E, Bergh C, Khatibi A, et al. Neonatal and maternal outcome after blastocyst transfer: a population-based registry study. Am J Obstet Gynecol 2016;214:378.e1-10.

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