Both high and low HCG day progesterone concentrations negatively affect live birth rates in IVF/ICSI cycles


      Research question

      Can previous reports of a decreased probability of success in stimulated IVF cycles with premature rise of progesterone, as determined by progesterone concentration on HCG day (PHCG), be confirmed?


      Retrospective, observational, single-centre cohort study conducted on 5447 IVF and intracytoplasmic (ICSI) cycles carried out among 2192 patients between 2009 and 2015, with conventional ovarian stimulation. This large database was used to develop a non-linear mixed prognosis model of live birth rate (LBR) incorporating PHCG as a predictor.


      In addition to known predictors (age, body mass index, anti-Müllerian hormone, type of infertility), PHCG was associated with a linear effect (OR 0.78 per Log[PHCG]ng/ml, 95% CI 0.611 to 0.997, P = 0.047) combined with a strong quadratic effect (OR 0.585 per Log2(PHCG)ng/ml, 95% CI 0.444 to 0.775, P < 0.001) resulting into a parabolic reverse-U curve. A significant interaction (P = 0.038) was found between PHCG and number of oocytes if three or less, but the effect of PHCG remains modest. For higher oocyte numbers, LBR rapidly increases with number of retrieved oocytes; however, LBR becomes more sensitive to PHCG as the number of oocytes increases. Higher live birth prognoses occur for optimal PHCG but are sharply reduced for lower or higher PHCG.


      Evidence is provided of an important negative effect of PHCG at lower and higher values, independent of oocyte number, thus defining appropriate ranges for fresh embryo transfer or freeze-all strategy. In poor responders, premature progesterone rise may be ignored, thus avoiding unnecessary cancellations or embryo freezing. Conversely, in higher responders, the negative effect of progesterone elevation is more pronounced, suggesting that freeze-all policy should be applied more widely.


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      Dr Philippe ARVIS obtained his medical training (MBBS) in 1974 and MD in Obstetrics and Gynaecology in 1984. He further specialized in Reproductive Medicine at the University Hospital, Rennes, France, and has been working as an infertility and reproductive medicine consultant in the ART unit of Clinique La Sagesse, Rennes, France.
      Key message
      Progesterone concentration at HCG administration (PHCG) negatively affects live birth rate at lower and higher values. In poor responders, the effect of PHCG elevation is minimal so cancellations or embryo freezing are unnecessary. In higher responders, the negative effect is more pronounced, and freeze-all policy should be widely applied.