title: Live birth rates after modified natural cycle compared with high-dose FSH stimulation using GnRH antagonists in poor responders.
abstract: OBJECTIVE
  Do live birth rates differ between modified natural cycles (MNCs) and cycles using high-dose follicle stimulating hormone (HDFSH) with gonadotrophin-releasing hormone (GnRH) antagonist in poor responder patients?
  
  
  CONCLUSIONS
  Live birth rates are significantly higher in MNC compared with HDFSH GnRH antagonist cycles in poor responder patients.
  
  
  BACKGROUND
  Previous data on the efficiency of MNC in poor responders are very limited and suggest that MNC in vitro fertilization (IVF) does not offer a realistic solution for parenthood in these patients, since live birth rates are disappointingly low. To date, no studies exist comparing MNC with HDFSH stimulation protocols in poor responders.
  
  
  METHODS
  The present retrospective study included 161 MNCs (106 women in the MNC group) and 164 HDFSH antagonist cycles (136 women in the HDFSH group) performed between January 2008 and December 2013 at Eugonia Assisted Reproduction Unit. The patients included in the study had to fulfill the Bologna criteria for the definition of poor ovarian response.
  
  
  METHODS
  Irrespective of their age, poor responder patients should have a diminished ovarian reserve as shown by low antral follicle count (≤5) and increased basal FSH (>12 IU/l), and one or more previous failed IVF cycles in which ≤3 oocytes were retrieved using a high gonadotrophin dose. Analysis was performed by adjusting for the non-independence of the data.
  
  
  RESULTS
  The probability of live birth was significantly higher in the MNC when compared with the HDFSH group (OR: 4.01, 95% CI: 1.14-14.09), after adjusting for basal FSH, female age and cause of infertility, variables which were shown to be associated with the probability of live birth in univariable analysis. MNCs were characterized by significantly lower total gonadotrophin dose (490.0 ± 35.2 IU versus 2826.1 ± 93.4 IU, P < 0.001), lower estradiol concentrations (237.5 ± 12.3 pg/ml versus 487.3 ± 29.8 pg/ml, P < 0.001), fewer follicles present on the day of hCG (1.9 ± 0.1 versus 3.2 ± 0.2, P < 0.001), fewer oocytes retrieved (1.1 ± 0.01 versus 2.4 ± 0.1, P < 0.001), fewer oocytes fertilized (0.7 ± 0.1 versus 1.4 ± 0.1, P < 0.001), fewer embryos transferred (0.7 ± 0.1 versus 1.4 ± 0.1, P < 0.001), fewer good-quality embryos available (0.5 ± 0.1 versus 0.8 ± 0.1, P < 0.001) and fewer good-quality embryos transferred (0.5 ± 0.05 versus 0.8 ± 0.1, P < 0.001) compared with the HDFSH group. However, the proportion of cycles with at least one good-quality embryo transferred per started cycle was similar between the two groups compared (62.5, 95% CI: 52.7-72.3 versus 62.7, 95% CI: 53.0-72.5, respectively).
  
  
  CONCLUSIONS
  This is a retrospective comparison between MNC and HDFSH GnRH antagonist protocols in a large group of poor responder patients according to the Bologna criteria. Although the two groups compared were not imbalanced for all basic characteristics and multivariate analysis were performed to adjust for all known confounders, it cannot be excluded that non-apparent sources of bias might still be present. Future randomized controlled trials are necessary to verify the present findings.
  
  
  CONCLUSIONS
  Both MNC and HDFSH antagonist protocols offer very low chances of live birth in poor responder patients who fulfill the Bologna criteria. However, MNC-IVF is a more patient-friendly approach, with a higher probability of live birth compared with the HDFSH antagonist protocol. In this respect, the current data might be of help in counseling such patients, who do not wish to undergo oocyte donation, prior to abandoning treatment altogether and/or proceeding to adoption.
  
  
  BACKGROUND
  No funding was obtained. C.A.V. reports personal fees and non-financial support from Merck, Sharp and Dome, personal fees and non-financial support from Merck Serono, personal fees and non-financial support from IPSEN Hellas S.A. outside the submitted work. B.C.T. reports grants from Merck Serono, grants from Merck Sharp & Dohme, personal fees from IBSA, personal fees from Merck Sharp & Dohme and personal fees from Ovascience outside the submitted work .
authors: Eugonia Assisted Reproduction Unit, 7 Ventiri Street, Athens 11528, Greece.
authors: Trifon G
authors: TG
authors: Lainas
authors: Eugonia Assisted Reproduction Unit, 7 Ventiri Street, Athens 11528, Greece.
authors: Ioannis A
authors: IA
authors: Sfontouris
authors: Department of Women's and Children's Health, St George Hospital, School of Women's and Children's Health, University of New South Wales, Kogarah, NSW 2217, Australia.
authors: Christos A
authors: CA
authors: Venetis
authors: Eugonia Assisted Reproduction Unit, 7 Ventiri Street, Athens 11528, Greece.
authors: George T
authors: GT
authors: Lainas
authors: Eugonia Assisted Reproduction Unit, 7 Ventiri Street, Athens 11528, Greece.
authors: Ioannis Z
authors: IZ
authors: Zorzovilis
authors: Unit for Human Reproduction, 1st Department of Obstetrics & Gynaecology, Papageorgiou General Hospital, Medical School, Aristotle University of Thessaloniki, Ring Road, Nea Efkarpia, Thessaloniki 56429, Greece.
authors: Basil C
authors: BC
authors: Tarlatzis
authors: Unit for Human Reproduction, 1st Department of Obstetrics & Gynaecology, Papageorgiou General Hospital, Medical School, Aristotle University of Thessaloniki, Ring Road, Nea Efkarpia, Thessaloniki 56429, Greece stratis.kolibianakis@gmail.com.
authors: Efstratios M
authors: EM
authors: Kolibianakis
mesh_terms: D000328:Adult; D001723:Birth Rate; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D005640:Follicle Stimulating Hormone / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006062:Gonadotropins / Q000502:physiology; D006727:Hormone Antagonists / Q000627:therapeutic use; D006801:Humans; D050498:Live Birth; D009865:Oocytes / Q000166:cytology; D010053:Ovary / Q000502:physiology; D010062:Ovulation Induction / Q000379:methods; D011247:Pregnancy; D011256:Pregnancy Outcome; D018873:Pregnancy Rate; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D006062:Gonadotropins; D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone; D005640:Follicle Stimulating Hormone
keywords: Bologna criteria; GnRH antagonist protocol; live birth; modified natural cycle; poor responders