{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "INVICTA Fertility Clinic, 80-850 Gdańsk, Poland",
    "Centre of Postgraduate Medical Education, 01-004 Warsaw, Poland",
    "INVICTA Research and Development Center, 81-740 Sopot, Poland",
    "Embryo Biology Team, InLife Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-683 Olsztyn, Poland",
    "Department of Reproductive Medicine and Gynecological Endocrinology, Medical University of Gdańsk, 80-210 Gdańsk, Poland"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Aron Łukaszuk"
    },
    {
      "affs": [
        2
      ],
      "name": "Jakub Łukaszuk"
    },
    {
      "affs": [
        3
      ],
      "name": "Izabela Wocławek-Potocka",
      "orcid": "0000-0002-1270-3438"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Grzegorz Jakiel",
      "orcid": "0000-0002-6094-2273"
    },
    {
      "affs": [
        2,
        4
      ],
      "name": "Krzysztof Łukaszuk",
      "orcid": "0000-0001-5996-6991"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/34psz428g7407.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27208944",
  "fulltext_url": "https://europepmc.org/articles/PMC13704441",
  "id": "34psz428g7407",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/20/8944",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2739|Reproductive Biology and Fertility"
    ]
  ],
  "openalex": "W7221164765",
  "pdf_url": "https://europepmc.org/articles/PMC13704441?pdf=render",
  "pmcid": "PMC13704441",
  "pmid": "42941721",
  "published": "2026-10-09",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/34psz428g7407.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:55Z",
      "native_id": "10.3390/ijms27208944",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/20/8944"
    },
    {
      "first_seen": "2026-10-30T12:22:24Z",
      "native_id": "MED:42941721",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42941721"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Reproductive Biology and Fertility",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Progesterone Beyond Pituitary Suppression in Assisted Reproduction: Peripheral Signalling, Gamete Biology, Endometrial Competence and Precision Therapeutic Use",
  "title_text": "Progesterone Beyond Pituitary Suppression in Assisted Reproduction: Peripheral Signalling, Gamete Biology, Endometrial Competence and Precision Therapeutic Use",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:24Z",
  "url": "https://research.draconitic.com/paper/34psz428g7407",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}