P-754 Perinatal outcomes and congenital anomalies after clomiphene citrate based minimal ovarian stimulation in vitro fertilisation stratified by embryo transfer method: a 10-year cohort study
Authors: Onogi S , Ezoe K , Kawasaki N , Hiroko H , Kuroda T , Takeshima K , Tanoue K , Nishii S , Kato K 
Published: June 2022

Abstract

Study question
Is the embryo transfer method associated with perinatal outcomes and congenital anomalies after minimal ovarian stimulation in vitro fertilisation (IVF) with clomiphene citrate (CC)?

Summary answer
Single vitrified-warmed blastocyst transfers in natural cycles had a lower incidence of pregnancy complications compared to single fresh cleaved embryo transfers after CC-based ovarian stimulation.

What is known already
Pregnancies resulting from IVF are associated with a higher risk of adverse perinatal outcomes compared to spontaneous conception; therefore, the next focus in reproductive medicine is to assess whether the increased risks are attributable to the IVF. Perinatal outcomes and congenital anomalies should be considered in addition to pregnancy outcomes in selecting the embryo transfer method. However, studies describing the influence of transfer methods on perinatal and maternal outcomes are limited.

Study design, size, duration
This study retrospectively analysed a single centre 10-year cohort. A total of 82,491 clinical records of women who underwent oocyte retrieval during a CC-based minimal stimulation cycle followed by single fresh cleaved embryo transfer (SFCT), single vitrified-warmed cleaved embryo transfer (SVCT), or single vitrified-warmed blastocyst transfer (SVBT) at the Kato Ladies Clinic between January 2008 and December 2017 were retrospectively analysed.

Participants/materials, setting, methods
The oocyte retrievals were performed in CC-based minimal ovarian stimulation. The embryos were transferred 2–3 days after retrieval, or vitrified at the cleavage or blastocyst stages. The vitrified embryos were warmed and transferred within the natural cycles. Perinatal outcomes and congenital anomalies were stratified by the transfer method. Multivariate logistic regression analysis was performed to evaluate the effect of transfer methods on pregnancy complications and congenital anomalies.

Main results and the role of chance
The perinatal outcomes and congenital anomalies in 19,069 singleton pregnancies were analysed. Multivariate logistic regression analysis revealed that the incidence of hypertensive disorders of pregnancy was significantly lower in the SVBT group compared with the SFCT group (adjusted odds ratio [AOR], 0.628; P &lt; 0.0001). The incidence of low-lying placenta (AOR 0.359 P = 0.0483; AOR 0.452 P &lt; 0.0001, respectively) and placenta previa (AOR 0.300 P = 0.0021; AOR 0.542 P &lt; 0.0001, respectively) were lower in the SVCT and SVBT groups than in the SFCT group. The rate of preterm delivery was lower in SVBT compared with SFCT (AOR 0.732 P &lt; 0.0001). The rate of low birth weight was significantly lower after SVCT and SVBT, compared with the SFCT group (AOR 0.751; P = 0.0261: AOR, 0.560; P &lt; 0.0001: respectively). A lower incidence of small for gestational age (AOR 0.720 P = 0.0436; AOR 0.494 P &lt; 0.0001, respectively) and higher incidence of large for gestational age (AOR 1.287 P = 0.0332; AOR 1.706 P &lt; 0.0001, respectively) were observed in the SVCT and SVBT groups compared to the SFCT group. The incidence of each congenital anomaly was similar among the groups.

Limitations, reasons for caution
The data was collected through self-reported parental questionnaires on neonatal outcomes and congenital malformations. Furthermore, this study was retrospective in nature; further studies are necessary to ascertain the generalisability of these findings to other clinics with different protocols and/or patient demographics.

Wider implications of the findings
This study demonstrated reassuring outcomes for SVBT, in terms of a lower incidence of pregnancy complications compared with SFCT. Our findings provide valuable knowledge to improve perinatal outcomes in CC-based stimulation and to inform couples of the possible benefits and harms of each type of embryo transfer method.

Trial registration number
not applicable