P-774 Conventional-IVF versus NC-IVF: unravelling the origins of fetal cardiac programming in ART
Authors: Barral Y , Casals G , Boutet M  L , Valenzuela-Alcaraz B , García-Otero L , Crovetto F , Agusti I , Goday A , Borras A , Civico M  S , Manau D , Gratacos E , Crispi F 
Published: July 2024

Abstract

Study question
Do fetuses from natural cycle IVF (NC-IVF) present signs of cardiac remodeling and suboptimal function similar to those observed in fetuses from conventional IVF (cIVF)?

Summary answer
Fetuses from both NC-IVF and cIVF present signs of fetal cardiac remodeling and suboptimal function as compared to spontaneously conceived fetuses (SC) from fertile couples.

What is known already
Previous publications have demonstrated that fetuses conceived by IVF present cardiac remodeling and suboptimal function. These fetuses show dilated atria, more globular and thicker ventricles, reduced longitudinal motion, and impaired relaxation. However, the pregnancies included in these studies were obtained following cIVF. In IVF cycles, ovarian stimulation has an impact on the oocyte quality and the endometrial milieu that may potentially affect perinatal results and fetal cardiovascular programming. Our aim was to compare cardiac morphometry and myocardial function in fetuses conceived by cIVF with those obtained after NC-IVF, without ovarian stimulation.

Study design, size, duration
This is a nested case-control study of 120 singleton pregnancies within a prospective cohort recruited from 2017 to 2021, including 40 SC from fertile couples, 40 following NC-IVF and 40 after cIVF with fresh embryo transfer, matched by maternal age, ethnicity, and gestational age at scan. IVF pregnancies were recruited from a single assisted reproduction center, ensuring homogeneity in ovarian stimulation protocols, laboratory procedures, and embryo culture conditions.

Participants/materials, setting, methods
The study protocol included prospective collection of parental demographics, reproductive and ART data, a fetal ultrasound scan at 28-34 weeks assessing biometry, feto-placental Doppler and morphological and functional echocardiography, and perinatal outcomes. Comparisons between groups were adjusted by gestational age and fetal weight at scan, and birthweight centile. Oocyte donation and PGT cycles were exclusion criteria. All the laboratory procedures including gamete manipulation, fertilization methods and embryo culture conditions were identical for NC-IVF and cIVF.

Main results and the role of chance
There were no significant differences in demographic data, perinatal outcomes, biometry and feto-placental Doppler parameters between the study groups. Reproductive data and IVF indications were also similar among the IVF groups. As compared to the SC, both IVF groups showed significant signs of fetal cardiac remodeling (higher cardio-thoracic ratio: cIVF mean 0.31 [SD 0.04]* versus NC-IVF 0.31 [0.03]* versus SC 0.28 [0.04], adjusted P-value &lt;0.001; larger right atria-to-heart ratio: cIVF 19.1% [3.0]*† versus NC-IVF 18.8% [3.3]* versus SC 17.4% [2.9], adjusted P-value &lt;0.001; increased relative wall thickness: c IVF 0.80 [0.2]* versus NC-IVF 0.85 [0.3]* versus SC 0.72 [0.3], adjusted P-value &lt;0.001) and suboptimal function (tricuspid ring displacement (mm): cIVF 7.1 [0.8]* versus NC-IVF 7.3 [0.9]* versus SC 7.5 [1.4], adjusted P-value 0.003; left myocardial performance index: cIVF 0.50 [0.06]* versus NC-IVF 0.49 [0.06]* versus SC 0.48 [0.08], adjusted P-value &lt;0.001).
* Adjusted P value &lt;0.05 as compared with SC.
† Adjusted P value &lt;0.05 as compared to NC- IVF.

Limitations, reasons for caution
The sample size was limited by the difficulty in recruiting viable pregnancies obtained by NC-IVF from a single center. The reported cardiac changes are subclinical and, although they are recognized as potential cardiovascular risk factors, their association with the long-term cardiovascular disease in these subjects remains to be proven.

Wider implications of the findings
Our findings contribute to assess the safety of different ART procedures in terms of cardiac performance in fetal life, before the influence of postnatal factors, in order to unravel the origins of fetal cardiac remodeling in ART. Studies evaluating the long-term health in this population are needed.

Trial registration number
Not applicable