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. 2016 Oct;33(10):1311-1318.
doi: 10.1007/s10815-016-0764-7. Epub 2016 Jul 22.

Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience

C Yding Andersen  1   2 , R Fischer  3 , V Giorgione  4 , Thomas W Kelsey  5
Affiliations

Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience

C Yding Andersen et al. J Assist Reprod Genet. 2016 Oct.

Abstract

For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential advances and disadvantages. Based on the pharmacokinetic characteristics of hCG, the mathematical modelling of the concentration profiles of hCG during the luteal phase has been evaluated in connection with several different approaches for hCG administration as LPS. It is suggested that the currently employed LPS provided in connection with the GnRHa trigger (i.e. 1.500 IU) is too strong, and that daily micro-dose hCG administration is likely to provide an optimised LPS with the current available drugs. Initial clinical results with the micro-dose hCG approach are presented.

Keywords: Corpus luteum function; GnRH agonist trigger; Luteal phase support; hCG.

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Conflict of interest statement

The authors declare that they have no conflict of interest Ethical approval For this type of study, formal consent is not required.

Figures

Fig. 1
Fig. 1
hCG dose of 1500 IU or 2500 IU four times. The graph represents the circulatory concentrations of hCG after exogenous hCG administration of 10,000 IU hCG followed by four administrations of either 1500 or 2500 IU of hCG during the luteal phase. Data are calculated based on the information from exogenous administration of 250-μg recombinant hCG [17], fitted to represent a fit to a pharmacokinetic model with first-order absorption and linear elimination including a lag time
Fig. 2
Fig. 2
hCG doses of 100 IU, 125 IU or 150 IU daily. The graph represents the circulatory concentrations of hCG after use of the GnRHa trigger for the final maturation of follicles (devoid of hCG activity) followed by daily administration of either 100, 125 or 150 IU hCG throughout the luteal phase. The calculated concentration of hCG on day OPU + 7 is ≈6 IU/l, ≈8 IU/l, ≈9.5 IU/l. For data calculation, see legend to Fig. 1. Legend: OPU oocyte pick up
Fig. 3
Fig. 3
hCG doses of 5000 IU for the final maturation of follicle followed by 500 IU at OPU + 5 (156 h). The graph represents the circulatory concentrations of hCG after exogenous hCG administration of 5000 IU hCG for final maturation of follicles followed by 500 IU hCG on day OPU + 5. The calculated concentration of hCG on day OPU + 7 is 9.4 IU/l. For data calculation, see legend to Fig. 1. Legend: OPU oocyte pick up
Fig. 4
Fig. 4
hCG doses of 1500 IU at OPU (36 h) and 1.500 IU at OPU + 5 (156 h). The graph represents the circulatory concentrations of hCG after use of the GnRHa trigger for the final maturation of follicles (devoid of hCG activity) followed by administration of 1500 IU hCG at OPU and 1500 IU at day OPU + 5. The calculated concentration of hCG on day OPU + 7 is 23 IU/l. For data calculation, see legend to Fig. 1. Legend: OPU oocyte pick up
Fig. 5
Fig. 5
hCG doses of 1000 IU at OPU (36 h) and 500 IU at OPU + 5 (156 h). The graph represents the circulatory concentrations of hCG after use of the GnRHa trigger for the final maturation of follicles (devoid of hCG activity) followed by administration of 1000 IU hCG at OPU and 500 IU at day OPU + 5. The calculated concentration of hCG on day OPU + 7 is 8.2 IU/l. For data calculation, see legend to Fig. 1. Legend: OPU oocyte pick up
Fig. 6
Fig. 6
hCG doses of 500 IU at OPU (36 h), OPU + 2 (84 h) and OPU + 5 (156 h). The graph represents the circulatory concentrations of hCG after use of the GnRHa trigger for the final maturation of follicles (devoid of hCG activity) followed by administration of 500 IU hCG at OPU, 500 IU at OPU + 2 plus and 500 IU at day OPU + 5. The calculated concentration of hCG on day OPU + 7 is 9.1 IU/l. For data calculation, see legend to Fig. 1. Legend: OPU oocyte pick up
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