Perinatal outcomes in children born after fresh or frozen embryo transfer using donated oocytes
Authors: Rafael Filipa , Robles Guillermo Mollá , Navarro Alfredo T , Garrido Nicolas , Garcia-Velasco Juan A , Bosch Ernesto , Nunes Sofia Gouveia , Soares Sérgio Reis , Santos-Ribeiro Samuel 
Published: April 2022

Abstract

STUDY QUESTION
Do children born after vitrified–thawed embryo transfers (ETs) using donated oocytes have worse perinatal outcomes when compared with fresh ET?

SUMMARY ANSWER
No significant difference in birthweight and prematurity rates between fresh or frozen embryo transfers (FETs) in newborns after oocyte donation was found.

WHAT IS KNOWN ALREADY
Autologous singletons born after fresh ET have been previously associated with higher rates of preterm birth and low birthweight, while FETs seem to confer a higher risk of hypertensive disorders during pregnancy and macrosomia. However, studies comparing these outcomes using autologous oocytes are unable to adequately disentangle the putative detrimental consequences of embryo vitrification from the possible effects that ovarian stimulation and endometrial preparation may have on endometrial receptivity prior to ET. The oocyte donation model is, for this reason, a more appropriate setting to study these hypotheses; however so far, the information available regarding neonatal outcomes in this patient population is limited to either small and/or heterogeneous studies.

STUDY DESIGN, SIZE, DURATION
We performed a multicentre retrospective cohort study including 5848 singletons born between 2009 and February 2020 following oocyte donation and single blastocyst transfer, subdivided according to whether a fresh ET or FET was performed. We also performed two additional sensitivity analyses, subgrouping the sample according to the type of endometrial preparation (natural versus artificial) and whether the donated oocytes had previously been vitrified or not.

PARTICIPANTS/MATERIALS, SETTING, METHODS
Patients with a first singleton livebirth after single blastocyst transfer were compared using multivariable regression analysis to account for potential confounding factors. The primary outcome was birthweight. Secondary outcomes were birthweight z-scores and percentiles, small/large for gestational age, gestational age at delivery, gender, prematurity (&lt;37 weeks and &lt;32 weeks), neonatal morbidity (Apgar scores and need for neonatal intensive care) and maternal morbidity (gestational hypertensive disorders, gestational diabetes and caesarean delivery).

MAIN RESULTS AND THE ROLE OF CHANCE
There was no significant difference between the fresh ET and FET groups in terms of mean birthweight (3215 g versus 3200 g) and birthweight z-scores (0.03 versus 0.1), in both the unadjusted and confounder-adjusted models. However, artificial endometrial preparation was associated with a higher birthweight (3220 g versus 3105 g) and birthweight z-scores (0.06 versus −0.13) when compared with a transfer in a natural cycle. Although a 1-day statistically significant difference in gestational age at birth (275 versus 274 days) was detected, premature birth rates (&lt;37 weeks) did not vary significantly between groups (9.9% and 11.2% for fresh ET and FET, respectively). No other statistically significant differences were found in the remaining neonatal and maternal outcomes studies between the fresh ET and FET groups.

LIMITATIONS, REASONS FOR CAUTION
This study is limited by its retrospective design and lack of information regarding congenital malformations. Moreover, the sample selection criteria that were used may limit the generalizability of our results.

WIDER IMPLICATIONS OF THE FINDINGS
Perinatal outcomes did not seem to be affected significantly by the embryo vitrification process in an oocyte donation model. Hence, other factors may contribute to the hindered perinatal outcomes described in ART, particularly the potential effect that ovarian stimulation and endometrial preparation may have on endometrial receptivity.

STUDY FUNDING/COMPETING INTEREST(S)
No specific funding was obtained for this study. All authors have no conflicts to declare.

TRIAL REGISTRATION NUMBER
N/A.