title: Antral Follicle Priming Before Intracytoplasmic Sperm Injection in Previously Diagnosed Low Responders: A Randomized Controlled Trial (FOLLPRIM).
abstract: BACKGROUND
  A low response to controlled ovarian hyperstimulation implies a reduced number of embryos and impaired pregnancy rate. Follicular priming with steroids before controlled ovarian hyperstimulation has been suggested to improve the subsequent ovarian response.
  
  
  OBJECTIVE
  The purpose of this study was to determine the best follicular priming protocol in low responders and to investigate the intrafollicular mechanisms triggered by steroid hormone priming.
  
  
  METHODS
  This was a single-center, randomized, parallel, open-label, controlled trial, in two phases.
  
  
  METHODS
  The setting was a university-based in vitro fertilization unit.
  
  
  METHODS
  Potential low responders (n = 99) underwent a first intracytoplasmic sperm injection cycle. Confirmed low responders (n = 66) were randomized to different priming protocols before a new intracytoplasmic sperm injection.
  
  
  METHODS
  Randomized patients underwent one of the following priming strategies: transdermal testosterone (20 μg/kg/d), transdermal estradiol (200 μg/d), or combined estrogens and oral contraceptive pills (30 μg of ethinyl estradiol plus 150 μg of desogestrel administered during the luteal phase of two consecutive cycles) and 4 mg/d of estradiol valerate during the follicular phase between them.
  
  
  METHODS
  Metaphase II (MII) oocytes were retrieved. Gene expression levels in the granulosa cells of steroidogenesis enzymes and FSH, LH, and androgen receptors were measured.
  
  
  RESULTS
  The number of retrieved MII oocytes did not differ between the interventional groups (testosterone, 2.2 ± 2.0; estrogen, 2.7 ± 1.7; and combined estrogens and oral contraceptive pills, 2.0 ± 1.3; not significant). Compared with those in nonprimed cycles, estradiol pretreatment yielded more MII oocytes (primed, 2.7 ± 1.7; nonprimed, 1.6 ± 1.2; P = .029) although the clinical pregnancy rate was higher in patients treated with testosterone (P = .003). Testosterone pretreatment increased androgen receptor expression (P = .028) compared with that for the previous cycle without priming.
  
  
  CONCLUSIONS
  The results of the present trial do not support the superiority of one priming strategy over the others.
authors.affiliation: Unidad de Reproducción Humana (A.M.E., C.D.-G., J.M.R., A.P.), Área de Salud de la Mujer, Hospital Universitario y Politécnico La Fe, Universidad de Valencia, 46010 Valencia, Spain; Grupo de Investigación de Medicina Reproductiva (A.M.E., C.D.-G., M.M., J.M.R., A.P.), Instituto de Investigación Sanitario La Fe, 46026 Valencia, Spain; and Instituto Valenciano de Infertilidad (A.M.E., A.P.), Instituto Universitario IVI, 46015 Valencia, Spain.
authors.forename: Alicia Marzal
authors.initials: AM
authors.lastname: Escriva
authors.affiliation: Unidad de Reproducción Humana (A.M.E., C.D.-G., J.M.R., A.P.), Área de Salud de la Mujer, Hospital Universitario y Politécnico La Fe, Universidad de Valencia, 46010 Valencia, Spain; Grupo de Investigación de Medicina Reproductiva (A.M.E., C.D.-G., M.M., J.M.R., A.P.), Instituto de Investigación Sanitario La Fe, 46026 Valencia, Spain; and Instituto Valenciano de Infertilidad (A.M.E., A.P.), Instituto Universitario IVI, 46015 Valencia, Spain.
authors.forename: Cesar
authors.initials: C
authors.lastname: Diaz-Garcia
authors.affiliation: Unidad de Reproducción Humana (A.M.E., C.D.-G., J.M.R., A.P.), Área de Salud de la Mujer, Hospital Universitario y Politécnico La Fe, Universidad de Valencia, 46010 Valencia, Spain; Grupo de Investigación de Medicina Reproductiva (A.M.E., C.D.-G., M.M., J.M.R., A.P.), Instituto de Investigación Sanitario La Fe, 46026 Valencia, Spain; and Instituto Valenciano de Infertilidad (A.M.E., A.P.), Instituto Universitario IVI, 46015 Valencia, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Monterde
authors.affiliation: Unidad de Reproducción Humana (A.M.E., C.D.-G., J.M.R., A.P.), Área de Salud de la Mujer, Hospital Universitario y Politécnico La Fe, Universidad de Valencia, 46010 Valencia, Spain; Grupo de Investigación de Medicina Reproductiva (A.M.E., C.D.-G., M.M., J.M.R., A.P.), Instituto de Investigación Sanitario La Fe, 46026 Valencia, Spain; and Instituto Valenciano de Infertilidad (A.M.E., A.P.), Instituto Universitario IVI, 46015 Valencia, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Rubio
authors.affiliation: Unidad de Reproducción Humana (A.M.E., C.D.-G., J.M.R., A.P.), Área de Salud de la Mujer, Hospital Universitario y Politécnico La Fe, Universidad de Valencia, 46010 Valencia, Spain; Grupo de Investigación de Medicina Reproductiva (A.M.E., C.D.-G., M.M., J.M.R., A.P.), Instituto de Investigación Sanitario La Fe, 46026 Valencia, Spain; and Instituto Valenciano de Infertilidad (A.M.E., A.P.), Instituto Universitario IVI, 46015 Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pellicer
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000453:epidemiology / Q000628:therapy*; D008183:Luteal Phase / Q000187:drug effects; D008297:Male; D054315:Oocyte Retrieval / Q000706:statistics & numerical data; D006080:Ovarian Follicle / Q000187:drug effects* / Q000502:physiology; D065851:Ovarian Reserve; D010062:Ovulation Induction / Q000379:methods*; D011247:Pregnancy; D018873:Pregnancy Rate; D020554:Sperm Injections, Intracytoplasmic / Q000379:methods*; D013739:Testosterone / Q000008:administration & dosage
chemical_list: D013739:Testosterone; D004958:Estradiol