Fine-tuning blastocyst selection based on morphology: a multicentre analysis of 2461 single blastocyst transfers.

RESEARCH QUESTION: Which blastocyst morphology parameter is associated with live birth after controlling for female age and endometrial receptivity? DESIGN: Retrospective study including fresh single blastocyst transfers (n = 2461) where the value of serum progesterone on day of human chorionic gonadotrophin trigger (PdHCG) was available. Generalized estimating equation regression models evaluated the independent effects of developmental stage (DevSt), inner cell mass (ICM) and trophectoderm grade on live birth rates while controlling for the confounding effects of female age and PdHCG. RESULTS: DevSt was strongly associated with the probability of live birth (P < 0.0001) independently of female age (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.87-0.91) and PdHCG (OR 0.80, 95% CI 0.74-0.87). For full blastocysts, expanded blastocysts and hatching blastocysts, addition of ICM and trophectoderm grading in the multivariable analysis suggested that besides female age (OR 0.92, 95% CI 0.90-0.94) and PdHCG (OR 0.80, 95% CI 0.73-0.87), only DevSt (P = 0.001) and trophectoderm quality (P = 0.004) were independent predictors of live birth, while the predictive capacity of ICM was no longer significant. The mean probability of live birth was highest for AA blastocysts (35.0%), followed by BA blastocysts (31.2%) and AB blastocysts (27.7%). CONCLUSION: This large study analyses for the first time the independent role of blastocyst morphology in predicting live birth while controlling for female age and PdHCG. Its findings suggest that DevSt and then trophectoderm grade are stronger predictors of live birth over ICM grade when selecting a single blastocyst for transfer.

Is measurement of progesterone level prior to FSH stimulation useful in GnRH-antagonist cycles?

AIM: To reduce patient inconvenience during in vitro fertilization (IVF) cycles, some protocols delay intensive monitoring until mid-follicular stimulation. Others assess hormone levels prior to follicle-stimulating hormone (FSH) administration, not commencing stimulation until baseline progesterone (P4) levels (< 5 nmol/l) are achieved. Higher P4 levels (> 4.8 nmol/L) on the day of FSH trigger have been implicated in poorer pregnancy rates. This study evaluates the association of P4 levels at day 1-2 in gonadotrophin-releasing hormone (GnRH)-antagonist cycles with pre-trigger P4 levels and clinical pregnancy rates (CPRs). METHOD: All fresh GnRH-antagonist IVF cycles between June 2011 and June 2012, in which pre-FSH P4 levels were not routinely performed (group 1), were retrieved from the IVF Australia database and compared with controls (group 2). RESULTS: There were 163 cycles in each group. P4 levels on the day of trigger were significantly higher in group 1 (3.75 vs. 2.77, p < 0.05). The incidence of pre-trigger P4 levels >4.8 nmol/l was significantly higher in group 1 (30 vs. 16, p < 0.05). The number of oocytes retrieved was higher in group 1 (11.1 vs. 9, p < 0.05), however fertilization rates were significantly lower in that group (53.6% vs. 61.2%, p < 0.05); CPRs were similar between the two groups (27.8% vs. 31.8%, p = ns). Overall, pregnancy rates were lower in cycles with pre-trigger P4 level of > 4.8 nmol/L compared with those with lower levels (15% vs. 32.5%, p < 0.05). CONCLUSION: We found that measurement of P4 level at early follicular phase was associated with significantly lower pre-trigger levels. However, this did not translate into a difference in CPR between the monitored and unmonitored groups. We have confirmed that elevation in pre-trigger P4 level is associated with halving of the CPR, indicating that the most important P4 measurements are those in the late follicular/pre-trigger phase.

Predictive value of mid luteal progesterone concentration before luteal support in controlled ovarian hyperstimulation with intrauterine insemination.

BACKGROUND: There is no published data assessing whether higher mid luteal serum progesterone (P4) levels are associated with a higher cycle pregnancy rate (CPR) in controlled ovarian hyperstimulation (COH) with intrauterine insemination (IUI). AIMS: To assess whether the mid luteal serum P4 level is predictive of pregnancy in COH with IUI. METHODS: A retrospective cohort study of all women with unexplained, minimal endometriosis or mild male factor infertility who underwent COH with IUI between October 1999 and December 2000 at our department was analysed. The COH was achieved with follicle stimulating hormone injections. All cycles were triggered with human chorionic gonadotropin when at least one follicle > or =15 mm was visible on ultrasound and IUI performed the following day. A serum P4 and beta human chorionic gonadotropin level was measured at 7 and 14 days post-trigger, respectively. RESULTS: There were 33 pregnancies in the 188 cycles analysed, giving a CPR of 18%. The median (range) mid luteal P4 level for all cycles was 51 nmol/L (1.8-234). This did not differ between the pregnant (55 nmol/L) and non-pregnant (50 nmol/L) cycles (P=0.282, Mann-Whitney U-test). There was also no difference in CPR between cohorts below or above the cut-off levels of 33 nmol/L (25th percentile) (13.3 vs 18.9%; P=0.39), 51 nmol/L (50th percentile) (16.0 vs 19.1%; P=0.57), or 69 nmol/L (75th percentile) (16.3 vs 21.3%; P=0.44), respectively. CONCLUSIONS: Increased mid luteal serum P4 levels are not associated with a higher CPR in women undergoing COH with IUI. However, a low mid luteal P4 level < or =25 nmol/L may help predict treatment failure.