title: Natural cycle IVF reduces the risk of low birthweight infants compared with conventional stimulated IVF.
abstract: OBJECTIVE
  Are perinatal outcomes improved in singleton pregnancies resulting from fresh embryo transfers performed following unstimulated/natural cycle IVF (NCIVF) compared with stimulated IVF?
  
  
  CONCLUSIONS
  Infants conceived by unstimulated/NCIVF have a lower risk of being low birthweight than infants conceived by stimulated IVF; however, this risk did not remain significant after adjusting for gestation age.
  
  
  BACKGROUND
  Previous studies have shown that infants born after modified NCIVF have a higher average birthweight and are less likely to be low birthweight than those infants conceived with conventional stimulated IVF.
  
  
  METHODS
  Retrospective cohort study of singleton live births in non-smoking women undergoing fresh IVF-embryo transfer cycles from 2007 to 2013 in a single IVF center. The women were stratified by stimulated (n = 174) or unstimulated (n = 190) IVF exposure status. Unstimulated/NCIVF is defined as IVF without the use of exogenous gonadotrophins, and only includes the use of HCG to time oocyte retrieval.
  
  
  METHODS
  Demographic data including maternal age, BMI, infertility diagnosis and IVF cycle characteristics were collected. The perinatal outcomes used for comparison between the two study groups were length of gestation, birthweight, preterm delivery, very preterm delivery, low birthweight, small for gestational age and large for gestational age.
  
  
  RESULTS
  Although women in the NCIVF group were older than those in the stimulated group (35.0 versus 34.2 years, P < 0.05), parity and history of prior ART cycles were comparable between the groups. The mean birthweight was significantly higher in the NCIVF group by 163 g than in the stimulated group (3436 ± 420 g versus 3273 ± 574 g, P < 0.05). Consistent with this finding, there were also less low birthweight (<2500 g) infants in the NCIVF group versus stimulated group (1 versus 8.6%, P < 0.005). The reduction in risk for low birthweight in the NCIVF group remained significant after adjustment for maternal age, infertility diagnosis, ICSI, number of embryos transferred and blastocyst transfer (odds ratio (OR) 0.07; 95% CI 0.014-0.35). As NCIVF group had less preterm infants, additional adjustment for gestational age was performed and this showed a tendency towards lower risk of low birthweight in NCIVF (OR 0.11; 95% CI 0.01-1.0). While gestational age at delivery was comparable between the groups, both preterm births (<37 weeks gestation) (31 versus 42%, P < 0.05) and very preterm births (<32 weeks gestation) (0.52 versus 6.3%, P < 0.005) were significantly reduced in the NCIVF group. However, after adjustment for potential confounders, the reduction in risk of preterm and very preterm delivery associated with the NCIVF group was no longer significant (OR 1.1; 95% CI 0.48-2.5).
  
  
  CONCLUSIONS
  Limitations of this study are the retrospective nature of the data collection and the lack of information about parental characteristics associated with birthweight.
  
  
  CONCLUSIONS
  The improved perinatal outcomes following successful unstimulated/NCIVF suggest that this treatment should be considered as a viable option for infertile couples. NCIVF could reduce potential adverse perinatal outcomes such as low birthweight related to fresh embryo transfers performed following ovarian stimulation. The etiology of the improved perinatal outcomes following NCIVF needs to be explored further to determine if the improvement is derived from endometrial factors versus follicular/oocyte factors.
  
  
  BACKGROUND
  The study was supported by the following grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD K12HD047018 (W.M.), NICHD K12HD001271 (L.A.K.). The authors have no competing interests.
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Yale School of Medicine, FMB 329, 333 Cedar Street, New haven, CT 06511, USA winifred.mak@yale.edu.
authors.forename: Winifred
authors.initials: W
authors.lastname: Mak
authors.affiliation: Colorado Center for Reproductive Medicine, Denver, CO, USA Reproductive Endocrinology and Infertility, University of Colorado, Denver, CO, USA.
authors.forename: Laxmi A
authors.initials: LA
authors.lastname: Kondapalli
authors.affiliation: Dominion Fertility, Arlington, VA, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Celia
authors.affiliation: Dominion Fertility, Arlington, VA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Gordon
authors.affiliation: Dominion Fertility, Arlington, VA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: DiMattina
authors.affiliation: Dominion Fertility, Arlington, VA, USA Inova Fairfax Hospital Women's Center, Falls Church, VA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Payson
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004624:Embryo Transfer; D005191:Family Characteristics; D005260:Female; D005300:Fertility Agents, Female / Q000009:adverse effects; D005307:Fertilization in Vitro; D005317:Fetal Growth Retardation / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D007230:Infant, Low Birth Weight; D007247:Infertility, Female / Q000503:physiopathology / Q000628:therapy; D007248:Infertility, Male; D008297:Male; D008597:Menstrual Cycle; D010062:Ovulation Induction / Q000009:adverse effects*; D047928:Premature Birth / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D012189:Retrospective Studies; D012306:Risk; D012720:Severity of Illness Index; D014481:United States / Q000453:epidemiology
chemical_list: D005300:Fertility Agents, Female
keywords: in vitro fertilization; low birthweight; natural cycle; neonatal; obstetric; outcomes; preterm birth; stimulated; unstimulated