title: Detrimental effects of high-dose gonadotropin on outcome of IVF: making a case for gentle ovarian stimulation strategies.
abstract: OBJECTIVE
  Limited data identify detrimental influences of aggressive use of gonadotropins (G) for controlled ovarian hyperstimulation (COH); the underlying mechanisms however remain unclear. We report on the relationship between G dose and in vitro fertilization (IVF) cycle parameters (ovarian response, endometrial thickness [EMT]) and cycle outcome (implantation rate [IR] and clinical pregnancy [CP] rate) in a cohort of women undergoing IVF.
  
  
  METHODS
  Retrospective analysis of fresh embryo transfer (ET) cycles. Univariate and multivariable regression analyses assessed relationship between G dose and outcomes of interest.
  
  
  RESULTS
  Higher G dose related positively with advancing age (P < .001) and inversely with EMT (P < .001). The overall CP rate was 30%. Significantly lower IR (.003) and CP rate (.002) were observed across increasing tertiles of G dose. Increasing G dose was identified as an independent negative predictor of EMT after adjusting for age, COH protocol and duration, infertility diagnosis, and ovarian response (P = .016). Adjusting for age, suppression protocol (gonadotropin-releasing hormone agonist vs antagonist), infertility diagnoses, EMT, quality, and cleavage of ET, lower G dose was an independent positive predictor of CP rate (odds ratio for CP rate was 1.57 for G dose in middle compared to the highest G dose quartile (95% confidence interval 1.09-2.24). Stratified analyses identified detrimental associations of higher G dose with CP rate to be relevant in women aged 35 years and younger.
  
  
  CONCLUSIONS
  Our analyses suggest detrimental influences of higher G dose on the endometrium and confirm the previously reported adverse association between higher G dose and IVF outcome. Gentler COH regimens may be of particular benefit in women aged ≤35 years.
authors.affiliation: Kaali Institute IVF Center, Budapest, Hungary. peterkovacs1970@hotmail.com
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.forename: Attila
authors.initials: A
authors.lastname: Sajgo
authors.forename: Steven G
authors.initials: SG
authors.lastname: Kaali
authors.forename: Lubna
authors.initials: L
authors.lastname: Pal
mesh_terms: D000328:Adult; D000367:Age Factors; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000187:drug effects; D004624:Embryo Transfer; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects; D005307:Fertilization in Vitro; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000819:agonists / Q000037:antagonists & inhibitors; D006062:Gonadotropins / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D007247:Infertility, Female / Q000473:pathology / Q000628:therapy*; D010062:Ovulation Induction / Q000379:methods*; D011247:Pregnancy; D018873:Pregnancy Rate; D012189:Retrospective Studies
chemical_list: D005300:Fertility Agents, Female; D006062:Gonadotropins; D007987:Gonadotropin-Releasing Hormone