{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:42:15Z","timestamp":1793130135007,"version":"4.5.0"},"reference-count":108,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T00:00:00Z","timestamp":1626825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>One of the most widely used types of assisted reproduction technology is the <jats:italic>in vitro<\/jats:italic> fertilization (IVF), in which women undergo controlled ovarian stimulation through the administration of the appropriate hormones to produce as many mature follicles, as possible. The most common hormone combination is the co-administration of gonadotropin-releasing hormone (GnRH) analogues with recombinant or urinary-derived follicle-stimulating hormone (FSH). In the last few years, scientists have begun to explore the effect that different gonadotropin preparations have on granulosa cells\u2019 maturation and apoptosis, aiming to identify new predictive markers of oocyte quality and successful fertilization. Two major pathways that control the ovarian development, as well as the oocyte\u2013granulosa cell communication and the follicular growth, are the PI3K\/Akt\/mTOR and the Hippo signaling. The purpose of this article is to briefly review the current knowledge about the effects that the different gonadotropins, used for ovulation induction, may exert in the biology of granulosa cells, focusing on the importance of these two pathways, which are crucial for follicular maturation. We believe that a better understanding of the influence that the various ovarian stimulation protocols have on these critical molecular cascades will be invaluable in choosing the best approach for a given patient, thereby avoiding cancelled cycles, reducing frustration and potential treatment-related complications, and increasing the pregnancy rate. Moreover, individualizing the treatment plan will help clinicians to better coordinate assisted reproductive technology (ART) programs, discuss the specific options with the couples undergoing IVF, and alleviate stress, thus making the IVF experience easier.<\/jats:p>","DOI":"10.3389\/fendo.2021.702446","type":"journal-article","created":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T12:03:24Z","timestamp":1626869004000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Interplay Between mTOR and Hippo Signaling in the Ovary: Clinical Choice Guidance Between Different Gonadotropin Preparations for Better IVF"],"prefix":"10.3389","volume":"12","author":[{"given":"Kyriaki","family":"Papageorgiou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirini","family":"Mastora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Zikopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria E.","family":"Grigoriou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Georgiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theologos M.","family":"Michaelidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1748-1716.1960.tb01823.x","article-title":"Site of Production of Estrogen in Rat Ovary as Studied in Micro-Transplants","volume":"163","author":"Falck","year":"1959","journal-title":"Acta Phvsiol Stand"},{"key":"B2","article-title":"Review of the 35th European Society of Human Reproduction and Embryology (ESHRE)","volume":"5","year":"2019","journal-title":"Congress EMJ Repro Health"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-016-0225-2.3","article-title":"Systematic Review of Worldwide Trends in Assisted Reproductive Technology 2004-2013","volume":"15","author":"Kushnir","year":"2017","journal-title":"Reprod Biol Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"79","DOI":"10.22074\/ijfs.2017.4759","article-title":"A Comparison of Outcomes From In Vitro Fertilization Cycles Stimulated with Follicle Stimulating Hormone Plus Either Recombinant Luteinizing Hormone or Human Menopausal Gonadotropins in Subjects Treated with Long Gonadotropin Releasing Hormone Agonist Protocols","volume":"1","author":"Bleau","year":"2017","journal-title":"Int J Fertil Steril"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00282","article-title":"An Observational Retrospective Cohort Trial on 4,828 IVF Cycles Evaluating Different Low Prognosis Patients Following the POSEIDON Criteria","volume":"10","author":"Levi-Setti","year":"2019","journal-title":"Front Endocrinol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2019.08.010","article-title":"HMG Versus Recombinant FSH Plus Recombinant LH in Ovarian Stimulation for IVF: Does the Source of LH Preparation Matter","volume":"6","author":"Orvieto","year":"2019","journal-title":"Reprod BioMed Online"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e15512","DOI":"10.1097\/MD.0000000000015512","article-title":"A Cohort Study of Both Human Menopausal Gonadotropin (HMG) and Recombinant Luteinizing Hormone Addition at Early Follicular Stage in In Vitro Fertilization Outcome: A STROBE-Compliant Study","volume":"98","author":"Xia","year":"2019","journal-title":"Med (Baltimore)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.03.029","article-title":"Menopur in GnRH Antagonist Cycles With Single Embryo Transfer \u2013 High Responder (MEGASET-HR) Trial Group. 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