Daily low-dose hCG stimulation during the luteal phase combined with GnRHa triggered IVF cycles without exogenous progesterone: a proof of concept trial

TY - JOUR

T1 - Daily low-dose hCG stimulation during the luteal phase combined with GnRHa triggered IVF cycles without exogenous progesterone

T2 - a proof of concept trial

AU - Andersen, Claus Yding

AU - Elbaek, Helle Olesen

AU - Alsbjerg, Birgit

AU - Laursen, Rita Jakubcionyte

AU - Povlsen, Betina Boel

AU - Thomsen, Lise

AU - Humaidan, Peter

N1 - © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: [email protected].

PY - 2015/10

Y1 - 2015/10

N2 - STUDY QUESTION Can the luteal phase support be improved in terms of efficacy, hormonal profiles and convenience as compared with today's standard care? SUMMARY ANSWER 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.

AB - STUDY QUESTION Can the luteal phase support be improved in terms of efficacy, hormonal profiles and convenience as compared with today's standard care? SUMMARY ANSWER 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.

U2 - 10.1093/humrep/dev184

DO - 10.1093/humrep/dev184

M3 - Journal article

C2 - 26209535

SN - 0268-1161

VL - 30

SP - 2387

EP - 2395

JO - Human Reproduction

JF - Human Reproduction

IS - 10

ER -