P-683 Live birth rate following medicated frozen-thawed embryo transfer with or without GnRH-antagonist (Cetrotide) pituitary suppression. A randomised, controlled pilot trial
Authors: Noble M , Mounce G , Child T 
Published: June 2023

Abstract

Study question
Does the administration of GnRH-antagonist (Cetrotide) in medicated frozen-thawed embryo transfer (FET) cycles improve live birth (LBR) or cycle cancellation rate?

Summary answer
Live birth and cycle cancellation were similar with or without Cetrotide. However, cancellation for threatened ovulation was statistically significantly lower when Cetrotide was administered.

What is known already
During medicated FET, embryo and endometrial development must be synchronized, with endometrial window of implantation dependent on duration of progesterone. Suppression of spontaneous ovulation is key to maintaining synchrony. There are insufficient data regarding the use of supplementary pituitary suppression in medicated FET.
A recent Cochrane review identified one small RCT comparing live birth rate between medicated FET with or without GnRH-agonist pretreatment. The study suggested benefit to GnRH-agonist, but cycles were not monitored for ovulation. One RCT compared GnRH-antagonist with agonist showing better clinical pregnancy rate with GnRH-antagonist. No published RCT has compared medicated FET with versus without GnRH-antagonist.

Study design, size, duration
We conducted an open, two-arm, single-centre, randomised, controlled trial comparing medicated FET with or without Cetrotide. Target recruitment was 300. However, the study was stopped due to the Covid-19 pandemic. Recruitment occurred between 23rd January 2019 and 11th March 2020 and ended at 161 participants. Analysis was undertaken on an intention-to-treat basis, with live birth rate (LBR) as the primary outcome.

Participants/materials, setting, methods
Patients were given oestradiol 2mg orally TDS. Once the endometrium was ≥7mm, vaginal progesterone was commenced, with FET on the sixth day of progesterone. The Cetrotide group were given Cetrotide 0.25mg SC OD from days 1-7. Urine pregnancy test was done 11 days following FET, with oestradiol and progestogen continued to 10 weeks gestation. Cycles were cancelled for “threatened ovulation” if daily urinary LH-surge testing was positive or an ovarian follicle (≥12mm) was growing.

Main results and the role of chance
161 patients were randomised (Cetrotide: 76, no Cetrotide: 85). Six were withdrawn after randomisation (three withdrew consent, two did not start, one natural pregnancy). 155 participants started treatment (Cetrotide: 73, no Cetrotide: 82) and 140 had embryo transfer (Cetrotide: 68, no Cetrotide: 72).
The LBR was similar between groups (Cetrotide: 39% (30/76), no Cetrotide (29/85): 34%; OR 0.79, 95% CI 0.42 - 1.51), as were pregnancy rate (42% versus 38%; OR 0.87; 95% CI 0.47-1.63), clinical pregnancy rate (52% versus 49%; OR 0.83; 95% CI 0.44 – 1.56), biochemical pregnancy rate (20% versus 24%; OR 1.25; 95% CI 0.44 - 3.58) and miscarriage rate (7% versus 10%; OR 1.55; 95% CI 0.24 – 9.97).
In the Cetrotide group, 7% of cycles were cancelled, compared to 12% in the no Cetrotide group (NS). However, cancellation due to threatened ovulation was statistically significantly lower in the Cetrotide group, with 0% of cycles cancelled compared to 5% in the no Cetrotide group (OR 1.05; 95% CI 1.001 – 1.105).
Baseline characteristics (age at oocyte retrieval, age at FET, parity, subfertility diagnosis, number of oocytes retrieved, number of viable blastocysts, proportion of IVF/ICSI, endometrial thickness, number of embryos transferred, embryo quality) were similar between groups.

Limitations, reasons for caution
The study is limited by the fact it was unblinded, undertaken at a single site and was underpowered for live birth due to early trial cessation.

Wider implications of the findings
Results suggest no effect of Cetrotide on LBR in medicated FET. There was a significantly higher risk of cycle cancellation due to risk of ovulation in patients not taking Cetrotide. This is clinically significant and requires further study, as cancelled cycles increase costs and duration to birth.

Trial registration number
EudraCT Number: 2018-001915-63