Progesterone Beyond Pituitary Suppression in Assisted Reproduction: Peripheral Signalling, Gamete Biology, Endometrial Competence and Precision Therapeutic Use
5 affiliations
- 1INVICTA Fertility Clinic, 80-850 Gdańsk, Poland
- 2Centre of Postgraduate Medical Education, 01-004 Warsaw, Poland
- 3INVICTA Research and Development Center, 81-740 Sopot, Poland
- 4Embryo Biology Team, InLife Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-683 Olsztyn, Poland
- 5Department of Reproductive Medicine and Gynecological Endocrinology, Medical University of Gdańsk, 80-210 Gdańsk, Poland
Abstract
Progesterone is indispensable to assisted reproduction, yet the phrase “progesterone effect” collapses non-equivalent biological processes. Classical progesterone receptors (PGR-A and PGR-B), progestin and adipoQ receptor-family proteins, progesterone receptor membrane components 1 and 2 (PGRMC1/2), and an unresolved proximal sensor upstream of sperm CatSper operate over different timescales and with unequal evidence for direct ligand binding. In the ovary, PGRMC-associated complexes regulate granulosa-cell survival, mitosis and oocyte competence, although much causal evidence is non-human. In sperm, progesterone-evoked CatSper activation is robust, whereas the influential ABHD2 hydrolase model was challenged by human data in 2026. In endometrium, receptivity emerges from temporally ordered PGR-dependent epithelial–stromal, immune, metabolic and vascular programmes; “progesterone resistance” is therefore better treated as a family of molecular states than as a single diagnosis. Oral, vaginal, subcutaneous and intramuscular regimens generate different systemic and uterine exposures, and serum progesterone is an exposure marker rather than a direct assay of tissue response. We integrate these levels into an exposure–target engagement–tissue state–outcome framework. This framework explains why universal serum thresholds and unselected rescue strategies remain uncertain and defines the experiments and trials needed for mechanism-informed luteal support and frozen embryo transfer.
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BibTeX
@article{lukaszuk2026progesterone,
title = {{Progesterone Beyond Pituitary Suppression in Assisted Reproduction: Peripheral Signalling, Gamete Biology, Endometrial Competence and Precision Therapeutic Use}},
author = {Aron Łukaszuk and Jakub Łukaszuk and Izabela Wocławek-Potocka and Grzegorz Jakiel and Krzysztof Łukaszuk},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27208944},
url = {https://www.mdpi.com/1422-0067/27/20/8944},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Progesterone Beyond Pituitary Suppression in Assisted Reproduction: Peripheral Signalling, Gamete Biology, Endometrial Competence and Precision Therapeutic Use
AU - Aron Łukaszuk
AU - Jakub Łukaszuk
AU - Izabela Wocławek-Potocka
AU - Grzegorz Jakiel
AU - Krzysztof Łukaszuk
PY - 2026
DA - 2026/10/09
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27208944
UR - https://www.mdpi.com/1422-0067/27/20/8944
AB - Progesterone is indispensable to assisted reproduction, yet the phrase “progesterone effect” collapses non-equivalent biological processes. Classical progesterone receptors (PGR-A and PGR-B), progestin and adipoQ receptor-family proteins, progesterone receptor membrane components 1 and 2 (PGRMC1/2), and an unresolved proximal sensor upstream of sperm CatSper operate over different timescales and with unequal evidence for direct ligand binding. In the ovary, PGRMC-associated complexes regulate granulosa-cell survival, mitosis and oocyte competence, although much causal evidence is non-human. In sperm, progesterone-evoked CatSper activation is robust, whereas the influential ABHD2 hydrolase model was challenged by human data in 2026. In endometrium, receptivity emerges from temporally ordered PGR-dependent epithelial–stromal, immune, metabolic and vascular programmes; “progesterone resistance” is therefore better treated as a family of molecular states than as a single diagnosis. Oral, vaginal, subcutaneous and intramuscular regimens generate different systemic and uterine exposures, and serum progesterone is an exposure marker rather than a direct assay of tissue response. We integrate these levels into an exposure–target engagement–tissue state–outcome framework. This framework explains why universal serum thresholds and unselected rescue strategies remain uncertain and defines the experiments and trials needed for mechanism-informed luteal support and frozen embryo transfer.
SN - 1422-0067
ER -