Randomized controlled pilot trial of natural versus hormone replacement therapy cycles in frozen embryo replacement in vitro fertilization

This randomized, controlled trial suggests that, for women with regular ovulatory cycles undergoing frozen embryo replacement in vitro fertilization, the live birth rate is similar whether the endometrium is prepared using a natural menstrual cycle or GnRH-agonist pituitary suppression and hormone replacement therapy.


Ginny Mounce, M.Sc., Enda McVeigh, F.R.C.O.G., Karen Turner, Ph.D., Tim J. Child, M.D.

Volume 104, Issue 4, Pages 915-920



To determine whether there is any difference between the outcomes of two standard treatment protocols for frozen embryo replacement (FER): natural and down-regulated hormone replacement treatment (HRT).


Prospective, open, single-center, randomized, controlled pilot trial.


Private fertility clinic.


Women (n = 159) planning an FER cycle at the Oxford Fertility Unit, aged <40 years at the time their embryos were frozen; with at least one blastocyst or two cleavage-stage embryos in storage; regular ovulatory cycles; and at most two previous FER cycles. Intervention(s):

Eligible participants were recruited and randomized between March 2010 and July 2012 into one of two standard FER treatment groups: natural (n = 80) menstrual (Natural) or GnRH agonist/HRT (n = 79) cycles.

Main Outcome Measure(s):

Live birth rate after replacement of frozen–thawed embryos, clinical pregnancy rate, implantation rate, and cycle cancellations.


A total of 159 women were randomized (80 Natural; 79 HRT), and 145 had ET and completed the study (72 Natural; 73 HRT). Pregnancy outcomes were not significantly different between the two groups. The live birth rates were 26.3% (Natural) and 31.7% (HRT) per randomized patient. Per ET/protocol the live birth rates were 29.2% and 34.2%. The implantation rates were 24.3% and 26.0%, and there were three twin births in the Natural and five in the HRT arms.


The findings of this pilot study support the suggestion that for women with ovulatory cycles undergoing FER, the outcomes are similar between natural and HRT protocols.

Clinical Trial Registration Number:

NCT00843570. Registered at www.clinicaltrials.gov.

Read the full text at: http://www.fertstert.org/article/S0015-0282(15)01642-8/fulltext

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