S Santos-Ribeiro1, N P Polyzos2, P Haentjens2, J Smitz2, M Camus2, H Tournaye2, C Blockeel2. 1. Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, Brussels 1090, Belgium Department of Obstetrics, Gynaecology and Reproductive Medicine, Hospital Universitário de Santa Maria, Avenida Professor Egas Moniz, Lisboa 1649-035, Portugal samueldsribeiro@gmail.com. 2. Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, Brussels 1090, Belgium.
Abstract
STUDY QUESTION: Are low serum progesterone levels on the day of human chorionic gonadotrophin (hCG) administration detrimental for live birth delivery rates during in vitro fertilization (IVF)? SUMMARY ANSWER: Progesterone levels ≤0.5 ng/ml on the day of hCG administration hinder live birth rates. WHAT IS KNOWN ALREADY: Fundamental research has shown that the presence of late follicular phase progesterone is essential for follicular development, ovulation and endometrial receptivity. However, previous studies in patients undergoing ovarian stimulation have only assessed if progesterone levels in the higher range are detrimental for pregnancy or not. That said, information on the effect of the full range of late follicular progesterone on IVF outcomes is still lacking. STUDY DESIGN, SIZE, DURATION: This was a retrospective, single-centre cohort study with 2723 cycles performed in patients aged between 19 and 36 and undergoing controlled ovarian stimulation between January 2006 and March 2012 for their first or second attempt of IVF followed by a fresh embryo transfer (ET). PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent ovarian stimulation using a gonadotrophin-releasing hormone (GnRH) antagonist for pituitary down-regulation. Final oocyte maturation was triggered with hCG 36 h before oocyte retrieval. On the day of hCG administration, serum progesterone evaluation was performed. Live birth delivery rates were compared amongst various ordinal and regular progesterone intervals (≤0.50, 0.50-0.75, 0.75-1.00, 1.00-1.25, 1.25-1.50, >1.50 ng/ml) using logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of our sample was 30.5 years. Almost 82% of all embryo transfers were of a single embryo and 51.8% were performed with a Day 5 embryo. The average value (±standard deviation) of progesterone on the day of hCG administration was 1.02 ± 0.50 ng/ml and the live birth rate was 23.4%. The live birth rates (according to the above-described ordinal serum progesterone intervals) were 17.1, 25.1, 26.7, 25.5, 21.9 and 16.6%, respectively. The live birth rates were significantly lower in patients with both low (≤0.5 ng/ml) and high (>1.5 ng/ml) late follicular progesterone levels (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: The main limitation of our study was its retrospective nature. Furthermore, our study was restricted to patients under GnRH antagonist pituitary suppression and requires confirmation in a GnRH agonist setting. WIDER IMPLICATIONS OF THE FINDINGS: This study comprehensively assessed the relationship between live birth delivery rates and progesterone levels on the day of hCG administration during ovarian stimulation for IVF. Clinically relevant lower (≤0.5 ng/ml) and higher (>1.5 ng/ml) progesterone level limits were determined. STUDY FUNDING/COMPETING INTERESTS: No funding was received for this study and the authors have no conflicts of interest to declare.
STUDY QUESTION: Are low serum progesterone levels on the day of human chorionic gonadotrophin (hCG) administration detrimental for live birth delivery rates during in vitro fertilization (IVF)? SUMMARY ANSWER: Progesterone levels ≤0.5 ng/ml on the day of hCG administration hinder live birth rates. WHAT IS KNOWN ALREADY: Fundamental research has shown that the presence of late follicular phase progesterone is essential for follicular development, ovulation and endometrial receptivity. However, previous studies in patients undergoing ovarian stimulation have only assessed if progesterone levels in the higher range are detrimental for pregnancy or not. That said, information on the effect of the full range of late follicular progesterone on IVF outcomes is still lacking. STUDY DESIGN, SIZE, DURATION: This was a retrospective, single-centre cohort study with 2723 cycles performed in patients aged between 19 and 36 and undergoing controlled ovarian stimulation between January 2006 and March 2012 for their first or second attempt of IVF followed by a fresh embryo transfer (ET). PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent ovarian stimulation using a gonadotrophin-releasing hormone (GnRH) antagonist for pituitary down-regulation. Final oocyte maturation was triggered with hCG 36 h before oocyte retrieval. On the day of hCG administration, serum progesterone evaluation was performed. Live birth delivery rates were compared amongst various ordinal and regular progesterone intervals (≤0.50, 0.50-0.75, 0.75-1.00, 1.00-1.25, 1.25-1.50, >1.50 ng/ml) using logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of our sample was 30.5 years. Almost 82% of all embryo transfers were of a single embryo and 51.8% were performed with a Day 5 embryo. The average value (±standard deviation) of progesterone on the day of hCG administration was 1.02 ± 0.50 ng/ml and the live birth rate was 23.4%. The live birth rates (according to the above-described ordinal serum progesterone intervals) were 17.1, 25.1, 26.7, 25.5, 21.9 and 16.6%, respectively. The live birth rates were significantly lower in patients with both low (≤0.5 ng/ml) and high (>1.5 ng/ml) late follicular progesterone levels (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: The main limitation of our study was its retrospective nature. Furthermore, our study was restricted to patients under GnRH antagonist pituitary suppression and requires confirmation in a GnRH agonist setting. WIDER IMPLICATIONS OF THE FINDINGS: This study comprehensively assessed the relationship between live birth delivery rates and progesterone levels on the day of hCG administration during ovarian stimulation for IVF. Clinically relevant lower (≤0.5 ng/ml) and higher (>1.5 ng/ml) progesterone level limits were determined. STUDY FUNDING/COMPETING INTERESTS: No funding was received for this study and the authors have no conflicts of interest to declare.
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