Is the progesterone to oocyte ratio a better predictive tool for ART success than progesterone alone?

OBJECTIVE: To describe trends and investigate predictors of live birth in women ages 40 and older starting in vitro fertilization (IVF) cycles with autologous oocytes. DESIGN: Retrospective cohort study using data from the National Assisted Reproductive Technology Surveillance System. MATERIALS AND METHODS: Linear regression analysis was used to assess trends in number of fresh and frozen IVF cycles and live births among women >40 and proportion of cycles in women >40 among cycles in all ages using autologous oocytes during 2007-2013. Log binomial regression was performed to determine predictors of live birth in fresh IVF cycles resulting in transfer using autologous oocytes during 2007-2013. RESULTS: From 2007 to 2013, the number of total cycles (fresh and frozen) among women >40 years increased significantly from 24,529 to 28,883 (p¼0.0009); the number of frozen cycles more than doubled from 2,968 to 7,632 over the study period. The proportion of cycles in women >40 among cycles in all ages did not significantly increase (19.82% to 20.95%; p¼0.059). The number of live births among women >40 years increased from 2,902 in 2007 to 4,217 in 2013 (p<0.0001). In women >40 years starting fresh cycles during 2007-2013, the cancellation rate was 17.1% and the live birth rate following transfer was 16.1%. Among fresh cycles resulting in transfer, the following variables were predictive of higher live birth rates: higher parity, no prior IVF cycles, use of an antagonist stimulation, lower gonadotropin dose, higher number of oocytes retrieved, ovarian hyperstimulation, use of pre-implantation genetic diagnosis/ screening, transferring a higher number of embryos and blastocyst stage embryos, and cryopreservation of more embryos. The diagnoses of ovulatory dysfunction, tubal factor, and uterine factor were predictive of lower live birth rates. CONCLUSIONS: The total number of cycles and live births to women >40 years using autologous oocytes has increased from 2007 to 2013, though the proportion of cycles amongst women in all ages remained stable. Although there is a high cycle cancellation rate, certain predictors of live birth can be identified to facilitate treatment option counseling. P-207 Tuesday, October 18, 2016 HCG LEVELS AT DIFFERENT TIME POINTS DURING OVARIAN STIMULATION ARE NOT ASSOCIATED WITH OUTCOME IN ICSI CYCLES. F. Shararaa,b M. R. Goodwin.a aVirginia Center for Reproductive Medicine, Reston, VA; bOb/gyn, George Washington University, Washington, DC. OBJECTIVE: HP-hMG (MenopurÒ) has 75 IU of FSH and 75 IU of hCGderived LH activity. It contains 9.9 IU/vial of hCG and 0.4 IU/vial of LH, making > 90% of its LH activity hCG-derived. Only one study has addressed the hCG levels during ovarian stimulation (Platteau 2004). In that study, hCG levels were assessed on day 6 in 121 IVF and 237 ICSI cycles using HP-hMG. Day 6 hCG > 2.0 IU/L was associated with the highest live birth rate in ICSI but not in IVF cycles. It is unclear why this would be the case on day 6 and for only ICSI cycles. We therefore decided to compare hCG levels at several time points during ovarian stimulation with success rate in our program. DESIGN: Retrospective analysis. MATERIALS AND METHODS: A total of 159 ICSI cycles using HP-hMG and fresh transfer at day 5 or 6 were evaluated: 105 HP-hMGonly cycles (mono-hMG group) and 54 mixed FSH-HP-hMG cycles at 1:1 ratio (mixed group). FSH used was uFSH (BravelleÒ) or recFSH (GonalFÒ or FollistimÒ). All patients received HP-hMG (MenopurÒ) from day one of stimulation. Levels of hCG were assessed on day 5-6, day 7-9, and day of hCG administration. Ongoing pregnancy was assessed by ultrasound at 6-7 weeks gestation. RESULTS: Levels of hCG increased steadily during ovarian stimulation in both groups but were significantly higher in the mono-hMG group than the mixed group at all time points: 3.41  1.40 vs 1.59  0.87 IU/L, respectively, (P<0.001) on day 5-6; 3.88  1.61 vs 2.14  2.50 IU/L, (P<0.001) on day 7-9; and 3.69  1.55 vs 1.98  0.92 IU/L, (P<0.001) on day of hCG administration. Ongoing/delivered PR was 63.8% (67/105) in the mono-hMG group and 57.4% (31/54) in the mixed group (P¼NS). At all time points studied, hCG levels were not different between pregnant and non-pregnant cycles: 2.90 + 1.43 vs 2.76 + 1.55 IU/L, respectively, (P¼0.64) on day 5-6; 3.15 + 1.60 vs 3.19 + 2.80 IU/L (P¼0.94) on day 7-9; and 3.10 + 1.48 vs 2.79 + 1.37 IU/L (P¼0.25) on day of hCG administration. Subgroups of hCG (hCG < 1.0, 1-1.9, or > 2.0 IU/L) were also assessed at all 3 time points in both pregnant and non-pregnant cycles. Unlike the Platteau study, no differences in cycle outcome were detected.

FERTILITY & STERILITYÒ

CONCLUSIONS: hCG levels steadily increased during ovarian stimulation, and were higher in mono-HP-hMG cycles compared to mixed FSHHP-hMG cycles. In contrast to the only published paper associating day 6 hCG level with ICSI cycle outcome, we found no association between pregnancy rate and hCG levels on days 5-6, 7-9, or day of hCG administration. Our study is ongoing. References: 1. Platteau PP, Smitz J, Albano C, et al. Fertil Steril 81;5:1401-4, 2004.

P-208 Tuesday, October 18, 2016 IS THE PROGESTERONE TO OOCYTE RATIO A BETTER PREDICTIVE TOOL FOR ART SUCCESS THAN PROGESTERONE B. W. Whitcomb,b G. Patounakis,a ALONE?. M. W. Healy,a c a c E. Levens, A. DeCherney, E. A. Widra, K. S. Richter,c M. J. Hill.a a National Institutes of Health- NICHD, Bethesda, MD; bBiostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, MA; cShady Grove Fertility Reproductive Science Center, Rockville, MD. OBJECTIVE: Recent studies have suggested that the progesterone:oocyte (P:O) ratio may be more effective for predicting ART outcomes than P alone on the day of ovulation trigger. This study was designed to critically evaluate how to best incorporate P and O in prediction models of ART outcomes. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: 7,608 fresh autologous ART embryo transfer cycles were analyzed. GEE models and ROC curves were utilized to assess the predictive value of P, number of oocytes (O) retrieved, age of patient, and the P:O ratio on ART outcomes. In addition to the ratio P:O, 1/oocytes (1/O) was evaluated to allow statistical prediction models to separately estimate discriminatory ability of P and 1/O. Sequential models were evaluated to assess the incremental probability of variables to predict the primary outcome of live birth. Predictive ability of models was assessed using area under the curve (AUC). RESULTS: In single predictor models, O was a stronger predictor than P; however, age was the strongest predictor of live birth (Table 1). Once age was included in models, the incremental predictive ability of either P or 1/O to age is similar and small. When considering models using 3 predictors, the highest predictive ability was observed for a model including age, P, and 1/O. P:O again did provide incremental value over the model with just P or just 1/O.

Table 1:

Predictors 1 Predictor Model Age O 1/O P 2 Predictor Model Age Age Age P:O 3 Predictor Model Age Age Age

AUC 0.617 0.582 0.582 0.533 1/O O P P P:O P

0.628 0.623 0.622 0.597 1/O O

0.637 0.636 0.630

CONCLUSIONS: Prior studies have suggested the P:O ratio to be a better predictor of ART outcomes than P alone. Our results confirm that addition of O to models improves prediction over P alone. However, use of the P:O ratio per se places constraints on statistical models, and may not optimize predictive ability using this information. Regardless of the physiological underpinnings of the P:O ratio, P exerts its negative effect on the endometrium in ART and it is plausible that P over specific thresholds would result in negative outcomes regardless of how many follicles are secreting the serum P.

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