Perinatal outcomes in children born after fresh or frozen embryo transfer using donated oocytes

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 (<37 weeks and <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 (<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.

Fetal Growth Velocity according to the Mode of Assisted Conception

“…Fourth, we were not able to adjust for the selected embryo transfer method (i.e., fresh vs. frozen) [12, 68, 69]. However, while in autologous cycles there is a demonstrated effect of the type of embryo transfer on birthweight [43], in oocyte donation such effect has not been consistently shown [70–72]. Fifth, although we adjusted for maternal age and the presence of comorbidities, we cannot completely rule out some remaining confounding effects on fetal growth secondary to differences in baseline characteristics among groups, such as infertility etiology [73], absence of corpus luteum (i.e., relaxin) [74, 75], different endometrial preparation protocols [76], number of transferred embryos [77, 78], the embryo transfer day (i.e., blastocyst-vs. cleavage-stage) [69, 79], the use of preimplantation genetic testing [80], nor the use of aspirin across gestation [81].…”

Elevated Sperm DNA Damage in IVF–ICSI Treatments Is Not Related to Pregnancy Complications and Adverse Neonatal Outcomes

“…Therefore, there is growing evidence of information regarding the safety of assisted reproductive technologies and the health of children born through them. Indeed, several studies have evaluated how ART-associated processes such as ovarian stimulation [48][49][50], embryo culture [14,48], and cryopreservation [12,13,51], as well as the type of preparation for ET [52,53] might influence obstetric and perinatal outcomes. However, there is a lack of information on the involvement of SDF at the time of conception beyond the usual clinical outcomes.…”

“…The different processes that currently involve infertility treatments have been studied separately. The application of different IVF techniques, such as the freezing and thawing of embryos, did not entail significant differences in gestational age, newborn weight, or neonatal morbidity when compared to pregnancies of the same women when donated oocytes were used [12,13]. Moreover, no adverse effects were found in children born from pregnancies obtained from embryos cultured using time-lapse technology [14], and a German historical cohort study after 21 years of follow-up of ART-conceived children found no increased risk of cancer compared to naturally conceived children [15].…”

Feasibility and impact of haplogroup matching for mitochondrial replacement treatment

“…The problem of finding haplogroup matched egg donors for women from diverse phylogeographical regions may in theory be alleviated by importing vitrified eggs from egg banks around the world. Whilst egg vitrification is a successful procedure (Rafael et al , 2022 ), the use of vitrified donor eggs for MRT is associated with increased carryover of mitochondria (Hyslop et al , 2016 ), which can result in elevated heteroplasmy for maternal mtDNA in babies born after MRT (Costa‐Borges et al , 2023 ). Thus, although, future advances in the use of vitrified donor eggs for MRT may enable import from international egg banks, current clinical practice relies largely on local egg donors, which are overwhelming of European maternal ancestry (HFEA, 2023 ).…”