PMID- 33792685 OWN - NLM STAT- MEDLINE DCOM- 20210528 LR - 20210528 IS - 1460-2350 (Electronic) IS - 0268-1161 (Print) IS - 0268-1161 (Linking) VI - 36 IP - 6 DP - 2021 May 17 TI - Reduced FSH and LH action: implications for medically assisted reproduction. PG - 1469-1480 LID - 10.1093/humrep/deab065 [doi] AB - Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) play complementary roles in follicle development and ovulation via a complex interaction in the hypothalamus, anterior pituitary gland, reproductive organs, and oocytes. Impairment of the production or action of gonadotropins causes relative or absolute LH and FSH deficiency that compromises gametogenesis and gonadal steroid production, thereby reducing fertility. In women, LH and FSH deficiency is a spectrum of conditions with different functional or organic causes that are characterized by low or normal gonadotropin levels and low oestradiol levels. While the causes and effects of reduced LH and FSH production are very well known, the notion of reduced action has received less attention by researchers. Recent evidence shows that molecular characteristics, signalling as well as ageing, and some polymorphisms negatively affect gonadotropin action. These findings have important clinical implications, in particular for medically assisted reproduction in which diminished action determined by the afore-mentioned factors, combined with reduced endogenous gonadotropin production caused by GnRH analogue protocols, may lead to resistance to gonadotropins and, thus, to an unexpected hypo-response to ovarian stimulation. Indeed, the importance of LH and FSH action has been highlighted by the International Committee for Monitoring Assisted Reproduction Technologies (ICMART) in their definition of hypogonadotropic hypogonadism as gonadal failure associated with reduced gametogenesis and gonadal steroid production due to reduced gonadotropin production or action. The aim of this review is to provide an overview of determinants of reduced FSH and LH action that are associated with a reduced response to ovarian stimulation. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. FAU - Bosch, E AU - Bosch E AUID- ORCID: 0000-0003-2212-5931 AD - IVI-RMA, Valencia, Spain. FAU - Alviggi, C AU - Alviggi C AD - Department of Neuroscience, Reproductive Science and Odontostomatology, University Federico II, Naples, Italy. FAU - Lispi, M AU - Lispi M AD - Global Medical Affairs Fertility, Merck KGaA, Darmstadt, Germany. AD - International PhD School in Clinical and Experimental Medicine (CEM), University of Modena and Reggio Emilia, Modena, Italy. FAU - Conforti, A AU - Conforti A AUID- ORCID: 0000-0002-5676-0055 AD - Department of Neuroscience, Reproductive Science and Odontostomatology, University Federico II, Naples, Italy. FAU - Hanyaloglu, A C AU - Hanyaloglu AC AD - Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. FAU - Chuderland, D AU - Chuderland D AD - Global Medical Affairs Fertility, Merck KGaA, Darmstadt, Germany. FAU - Simoni, M AU - Simoni M AUID- ORCID: 0000-0002-2133-4304 AD - Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy. FAU - Raine-Fenning, N AU - Raine-Fenning N AD - Department of Child Health, Obstetrics and Gynaecology, School of Medicine, University of Nottingham, Nottingham, UK. FAU - Crepieux, P AU - Crepieux P AD - Physiologie de la Reproduction et des Comportements, UMR INRA 085, CNRS 7247, Universite de Tours, Nouzilly, France. FAU - Kol, S AU - Kol S AD - IVF Unit, Elisha Hospital, Haifa, Israel. FAU - Rochira, V AU - Rochira V AD - Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. AD - Unit of Endocrinology, Azienda Ospedaliero-Universitaria of Modena, Ospedale Civile di Baggiovara, Modena, Italy. FAU - D'Hooghe, T AU - D'Hooghe T AUID- ORCID: 0000-0002-2373-8257 AD - Global Medical Affairs Fertility, Merck KGaA, Darmstadt, Germany. AD - Department of Development & Regeneration, University of Leuven (KU Leuven), Leuven, Belgium. AD - Department of Obstetrics and Gynecology, Yale University, New Haven, CT, USA. FAU - Humaidan, P AU - Humaidan P AUID- ORCID: 0000-0001-6884-5366 AD - Fertility Clinic, Skive Regional Hospital, and the Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - England TA - Hum Reprod JT - Human reproduction (Oxford, England) JID - 8701199 RN - 0 (Gonadotropins) RN - 33515-09-2 (Gonadotropin-Releasing Hormone) RN - 4TI98Z838E (Estradiol) RN - 9002-67-9 (Luteinizing Hormone) RN - 9002-68-0 (Follicle Stimulating Hormone) SB - IM MH - Estradiol MH - Female MH - *Follicle Stimulating Hormone MH - *Gonadotropin-Releasing Hormone MH - Gonadotropins MH - Humans MH - Luteinizing Hormone MH - Reproduction PMC - PMC8129594 OTO - NOTNLM OT - LH / FSH / gonadotropins / LH and FSH deficiency / polymorphisms / recombinant LH / recombinant FSH / hypo-response / ovarian stimulation EDAT- 2021/04/02 06:00 MHDA- 2021/05/29 06:00 PMCR- 2021/04/01 CRDT- 2021/04/01 12:33 PHST- 2020/08/06 00:00 [received] PHST- 2020/12/18 00:00 [revised] PHST- 2021/04/02 06:00 [pubmed] PHST- 2021/05/29 06:00 [medline] PHST- 2021/04/01 12:33 [entrez] PHST- 2021/04/01 00:00 [pmc-release] AID - 6207798 [pii] AID - deab065 [pii] AID - 10.1093/humrep/deab065 [doi] PST - ppublish SO - Hum Reprod. 2021 May 17;36(6):1469-1480. doi: 10.1093/humrep/deab065.