P–382 Association of extended culture to blastocyst and gestational trophoblastic disease risk following IVF/ICSI assisted reproduction cycles: An analysis of large UK National database
Authors: Bambaranda I , Bomiriya R , Choudhary M 
Published: August 2021

Abstract

Study question
Is there any association between stage of embryo at transfer based on extended in vitro culture and gestational trophoblastic disease risk during assisted reproduction?

Summary answer
No significant association between stages of embryo transfer from zygote stage to blastocyst stage was found after analysing 540376 cycles of IVF and ICSI.

What is known already
Gestational trophoblastic disease (GTD), commonly referred to as molar pregnancy, results from abnormal proliferation of the trophoblast with a reported incidence of ∼1 in 700 in the UK. Despite technological advances such as ICSI, PGT and selection of normally fertilised (2PN) embryos, there are reported cases of GTD following assisted reproduction. Blastocyst transfer is associated with higher pregnancy and live birth rates but evidence is lacking whether extended embryo culture to blastocyst stage influences implantation of an abnormal embryo or abnormal trophoblastic proliferation leading to GTD.

Study design, size, duration
A retrospective study was carried out using Human Fertilisation and Embryology Authority (HFEA) anonymised register data from 1999 to 2016. HFEA holds the longest running register for fertility treatment data in the world and is the national database for fertility treatment data in UK. A total of 540376 fresh IVF or ICSI assisted reproduction cycles were analysed.

Participants/materials, setting, methods
There were 1033588 treatment cycles during the study period but only 540376 cycles met the inclusion criteria of fresh IVF or ICSI. Cycles with incomplete data, frozen embryo transfers, donor treatment or surrogacy were excluded. A subgroup analysis of those with primary subfertility was performed after excluding subjects with secondary infertility in order to exclude an effect of a previous molar pregnancy. Multivariate regression analysis was used to adjust for possible confounders.

Main results and the role of chance
78 molar pregnancies were reported in the original sample giving a prevalence of 4/10000 live births (78/228461), much lower than the prevalence given with natural pregnancies. Prevalence of molar pregnancy amongst the study population after meeting exclusion criteria was 4 /10000 livebirths (53/156683). Incidence of molar pregnancy was not statistically different between treatment type (0.0001 vs 0.00009). Significantly higher incidence of GTD was seen in the 40 to 42 age category compared to 18–34 category(OR 1.86(95% CI 8.7–3.75)),in par with known higher GTD risk in women above 40 in the general population. Of interesting note, although the incidence of molar pregnancy was significantly lower in women undergoing assisted reproduction increased risk with advancing age is not totally eliminated with treatment. There was no significant association between the occurrence of molar pregnancy with the type and cause for infertility and number of embryos transferred. Crude (1.06 (95% CI 0.852–1.31)) and adjusted odds ratios (1.07 (95% CI (0.857–1.32)) did not show any association between day of embryo transfer and molar pregnancy even after adjusting for age and excluding secondary infertility. Selection of blastocyst stage embryo after extended culture did not alter the likelihood of having a GTD compared to cleavage stage embryo.

Limitations, reasons for caution
The retrospective analysis of anonymised HFEA data limited adjustments for confounders such as smoking, previous history of GTD, ethnicity etc that predispose to GTD. Caution needs to be exercised for under-reporting of GTD to HFEA and lack of information on type of GTD identified.
Wider implications of the findings: Though GTD cannot be prevented by IVF/ICSI, the incidence is significantly low and extended culture is not associated with higher risk of abnormal trophoblastic proliferation or GTD occurrence with IVF/ ICSI treatment. These findings would aid informed implications counselling and reassurance of patients during assisted reproduction treatments.

Trial registration number
Not applicable