A randomized double-blinded controlled trial of hCG as luteal phase support in natural cycle frozen embryo transfer

Abstract

Study question: Does the use of hCG as luteal phase support in natural cycle frozen embryo transfer (FET) increase the ongoing pregnancy rate?

Study answer: The use of hCG in natural cycle FET did not improve the ongoing pregnancy rate.

What is known already: The use of luteal phase support in stimulated cycles has been associated with higher live-birth rates and the results are similar when using hCG or progesterone.

Study design size, duration: This is a randomized double-blinded controlled trial of 450 women recruited between August 2013 and October 2015.

Participants/materials setting methods: Women with regular cycles undergoing natural cycle FET were recruited. Serial serum hormonal concentrations were used to time natural ovulation and at least Day 2 cleavage embryos were replaced. Patients were randomized into either: (i) the treatment group, receiving 1500 IU hCG on the day of FET and 6 days after FET, or (ii) the control group, receiving normal saline on these 2 days.

Main results and the role of chance: The ongoing pregnancy rate [60/225 (26.7%) in the treatment group vs 70/225 (31.3%) in the control group, odds ratio 1.242 (95% CI 0.825-1.869)], implantation rate and miscarriage rate were comparable between the two groups. In the treatment group, there were significantly more cycles with top quality embryos transferred and a significantly higher serum oestradiol level, but a comparable serum progesterone level, 6 days after FET. However, no significant differences were observed in serum oestradiol and progesterone levels 6 days after FET between the pregnant and non-pregnant women. In the multivariate logistic regression, the number of embryos transferred was the only significant factor predictive of the ongoing pregnancy rate after natural cycle FET.

Limitations reason for caution: This study only included FET with cleavage stage embryos and only hCG, not vaginal progesterone, was used as luteal phase support.

Wider implantations of the findings: The findings in this study do not support the use of hCG for luteal phase support in natural cycle FET.

Study funding/competing interests: No external funding was used and there were no competing interests.

Trial registration number: clinicaltrial.gov identifier: NCT01931384.

Trial registration date: 23/8/2013.

Date of first patient's enrolment: 30/8/2013.

Keywords: frozen embryo transfer; hCG; luteal phase support; natural cycle; randomized controlled trial.