P-784 Less obstetric and neonatal outcomes after natural versus artificial cycle frozen embryo transfer
Authors: Mol F , Zaat T , Showell M , Goddijn M , De Bruin J.P , Van Wely M 
Published: June 2022

Study question

Do obstetric and neonatal outcomes of women who conceived through natural cycle frozen embryo transfer (NC-FET) differ compared to an artificial cycle (AC-FET) method?

Summary answer

Fewer obstetric and neonatal complications after NC-FET were found compared with AC-FET.

What is known already

The number of FET has increased dramatically over the past decade, mainly due to improvement in laboratory techniques. Based on current evidence, there is no difference in pregnancy rates when NC-FET is compared to AC-FET in subfertile women with regular ovulatory cycles. However NC-FET seems to be associated with lower risk of adverse obstetric and neonatal outcomes compared with AC-FET cycles. The question of how to prepare the endometrium for FET, has now gained even more importance and taken on the dimension of safety into account as it should not simply be reduced to the basic question of effectiveness.

Study design, size, duration

Systematic review and meta-analysis. We registered the protocol prospectively with PROSPERO [CRD42020163086]. A literature search was performed using the following databases: EMBASE, CINAHL and MEDLINE from inception to December 2021. Inclusion criteria consisted of: (1) cohort or register based study and (2) study population of women who conceived after NC-FET and a control group of women who conceived after AC-FET. Studies including anovulatory women and women with polycystic ovary syndrome were excluded.

Participants/materials, setting, methods

Women who conceived after NC-FET and AC-FET. Main outcomes are birth weight, large for gestational age (LGA); macrosomia; low birth weight (LBW) and small for gestational age (SGA). Additional outcomes included: gestational diabetes (GDM), hypertensive-disorders-of-pregnancy (HDP), post-partum-hemorrhage (PPH), placenta praevia, preterm birth (PTB), very preterm birth (very PTB). We calculated pooled odds ratios (OR), adjusted ORs and prevalence estimates (95% CI) using a random effect model, while heterogeneity was assessed by the I2.

Main results and the role of chance

A total of 18 studies were included (NC-FET n = 45,170; AC-FET n = 50,902). Birthweight was lower following NC-FET versus AC-FET (mean difference 25.12 grams; 95% CI 10.58 – 39.96). Furthermore NC-FET compared to AC-FET resulted in a lower risk of LGA (odds ratio (OR) 0.90; 95% 0.87 – 0.94), macrosomia (OR 0.80; 95% CI 0.69 – 0.94), SGA (OR 0.92; 95% CI 0.86 – 0.99), LBW (OR 0.85; 95% CI 0.77 – 0.95), HDP (OR 0.58; 95% CI 0.48 – 0.70), PE (OR 0.45; 95% CI 0.40 – 0.51), PPH (OR 0.39; 95% CI 0.30 – 0.50), PTB (OR 0.79; 95% CI 0.72 – 0.88) and very PTB (OR 0.80; 95% CI 0.58 – 1.09). Pooled adjusted OR resulted in similar estimates. Heterogeneity was low and varied between 0% and 10%, quality of the evidence was low to moderate.

Limitations, reasons for caution

Protocols for per NC-FET and AC-FET varied. Several studies on NC-FET used luteal phase support (LPS) with progesterone supplementation until 10-12 weeks gestation, which could also have an effect on the obstetric and neonatal outcomes.

Wider implications of the findings

In combination with comparable effectiveness and considering lower risks of obstetric and neonatal complications after NC-FET: NC-FET is the preferred treatment in women with ovulatory cycles undergoing FET.

Trial registration number

International prospective register of systematic reviews PROSPERO CRD42020163086