Higher exogenous gonadotrophin doses increase the risk of small for gestational age singletons after fresh embryo transfers

Published:November 30, 2021DOI:


      Research question

      A negative relationship has been reported between exogenous gonadotrophin dosage and the live birth rate in IVF. It is unclear whether total gonadotrophin dosage is associated with neonatal outcomes. The effect of exogenous gonadotrophin dosage on neonatal outcomes of singletons after fresh embryo transfer (FET) was investigated.


      A retrospective cohort study of 2020 live singletons evaluating neonatal outcomes. All patients underwent autologous IVF cycles between 1 August 2016 and 30 April 2020 and delivered a live singleton birth after FET. Patients with polycystic ovary syndrome were excluded. Patients were divided according to total gonadotrophin dose: group 1: ≤1800 IU; group 2: 1801–2500 IU; and group 3: >2500 IU.


      After adjusting for confounding factors by multiple regression models, the adjusted rate of small for gestational age (SGA) was significantly higher in group 3 (adjusted [a]OR 2.25, 95% CI 1.24 to 4.08). The risk of SGA increased 2.25 times when total gonadotrophin dose exceeded 2500 IU versus gonadotrophin doses below 1800 IU. The hierarchical analysis showed that an increased rate of SGA infants occurred in the GnRH agonist long protocol (aOR 2.09, 95% CI 1.02 to 5.17) and in the antagonist protocol (aOR 2.75, 95% CI 1.05 to 7.22).


      For patients without polycystic ovary syndrome, an excessive total gonadotrophin dose during ovarian stimulation, i.e. more than 2500 IU, may negatively affect neonatal outcomes by increasing the SGA rate of singletons after FET. Therefore, total gonadotrophin dose administered during ovarian stimulation should preferably not exceed 2500 IU.


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      Jing Wu has worked in the Air Force Military Medical University-affiliated Reproductive Medicine Center in Xi'an, China, since 2012. She is now an attending doctor focusing on the treatment of female infertility, particularly maternal and fetal safety in IVF.
      Key message
      In patients without polycystic ovary syndrome, a higher exogenous gonadotrophin dosage administered in the process of ovarian stimulation, particularly a dose of over 2500 IU, has an adverse effect on neonatal outcomes, by increasing the risk of small for gestational age singletons after fresh embryo transfers.