Daily low-dose hCG stimulation during the luteal phase combined with GnRHa triggered IVF cycles without exogenous progesterone: a proof of concept trial.Hum Reprod. 2015 Oct; 30(10):2387-95.HR
Can the luteal phase support be improved in terms of efficacy, hormonal profiles and convenience as compared with today's standard care?
Daily low-dose rhCG supplementation in GnRHa triggered IVF cycles can replace the traditional used luteal phase support with exogenous progesterone.
WHAT IS KNOWN ALREADY
A bolus of hCG for final maturation of follicles in connection with COS may induce the risk of OHSS and the luteal phase progesterone levels rise very abruptly in the early luteal phase.
STUDY DESIGN, SIZE, DURATION
This is a proof-of-concept study conducted as a three arm RCT with a total of 93 patients. First patient enrolled in January 2012 and the study finished in January 2014.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Normal responder women undergoing IVF/ICSI treatment in a university hospital. One arm served as control, where women followed a standard antagonist protocol. Two study arms were included both having 125 IU hCG daily for luteal phase support without exogenous progesterone after using a GnRHa trigger for ovulation induction. In both study arms exogenous FSH was stopped on stimulation day 6 and replaced by exogenous hCG that was initiated on either stimulation day 2 or day 6. Blood samples were obtained on the day of ovulation induction, on the day of oocyte pickup (OPU) and day OPU + 7.
MAIN RESULTS AND THE ROLE OF CHANCE
The mean serum levels of hCG did not exceeded the normal physiological range of LH activity in any samples. Mid-luteal progesterone levels were significantly higher in the two study groups receiving daily low-dose hCG for luteal phase support as compared with the control group (control group: 177 ± 27 nmol/l; study group 1: 334 ± 42 nmol/l; study group 2: 277 ± 27 nmol/l; (mean ± SEM). No differences in reproductive outcome were seen between groups.
LIMITATIONS, REASONS FOR CAUTION
The number of patients included is limited and conclusions need to be verified in a larger RCT.
WIDER IMPLICATIONS OF THE FINDINGS
Endogenous production of progesterone may become more attractive as the luteal phase support with levels of LH-like activity only in the physiological range and may, from the patients' point of view, replace inconvenient exogenous progesterone preparation. Further hCG may reduce the cost of stimulation and may collectively be used for stimulation of the follicular phase, ovulation induction and for luteal phase support.
STUDY FUNDING/COMPETING INTERESTS
An unrestricted grant from ARTS Biologics made this study possible. None of the authors has any competing interests to declare.
TRIAL REGISTRATION NUMBER
ClinicalTrial.gov number: NCT01504139.
TRIAL REGISTRATION DATE
28 December 2011.