Predictive performance of peritoneal fluid in the pouch of Douglas measured five days after oocyte pick-up in predicting severe late-onset OHSS: A secondary analysis of a randomized trial.

OBJECTIVES: To investigate if the amount of peritoneal fluid (PF) in the Pouch of Douglas at oocyte pick-up (OPU) or OPU + 5 days predict severe late-onset ovarian hyperstimulation syndrome (OHSS) in women undergoing ovarian stimulation for assisted reproductive technology (ART). STUDY DESIGN: A secondary analysis of a dual-centre RCT on 1050 women referred for their first ART treatment in two public fertility clinics in Denmark and randomized 1:1 to GnRH-antagonist or GnRH-agonist protocol. All women from the two arms who were examined on day of OPU and OPU + 5 days were included in this study (n = 940). The ability of PF in the pouch of Douglas to predict severe late-onset OHSS was assessed by multivariate logistic regression analyses and receiver operator characteristics (ROC) curve analyses and compared with other known predictors of OHSS. The final models were cross-validated by the leave-one-out method to assess the models' generalizability. RESULTS: A total of 28 (3%) women developed severe late-onset OHSS. PF in the pouch of Douglas measured on OPU + 5 days predicted severe late-onset OHSS. The optimal cut-off value was 17.5 mm at OPU + 5 days with a 61% sensitivity and 71% specificity (Area under the curve = 0.70 95% CI 0.61-0.80). PF on the day of OPU was not predictive of late on-set OHSS as the adjusted multivariate logistic regression analyses showed insignificant results. CONCLUSION: Although PF in the pouch of Douglas could predict late-onset severe OHSS, the low sensitivity underlines that it is not useful as a sole marker to decide whether to perform blastocyst transfer or to use a freeze-all strategy.

Prediction of the lower serum anti-Müllerian hormone threshold for ovarian stimulation prior to in-vitro fertilization using the Elecsys® AMH assay: a prospective observational study.

BACKGROUND: In assisted reproductive technology, prediction of treatment failure remains a great challenge. The development of more sensitive assays for measuring anti-Müllerian hormone (AMH) has allowed for the possibility to investigate if a lower threshold of AMH can be established predicting very limited or no response to maximal ovarian stimulation. METHODS: A prospective observational multicenter study of 107 women, < 40 years of age with regular menstrual cycle and serum AMH levels ≤ 12 pmol/L, treated with 300 IU/day of HP-hMG in a GnRH-antagonist protocol. AMH was measured before treatment start using the Elecsys® AMH assay by Roche Diagnostics. The ability of AMH to predict follicular development and ovarian response was assessed by receiver operating characteristics (ROC). Furthermore, the relationship between AMH at start of stimulation and cycle outcome was investigated using multivariate logistic regression analysis. RESULTS: Five out of 107 cycles (4.7%) were cancelled due to lack of follicular development and 60/107 (56%) women did not reach the classical hCG criteria for ovulation induction (≥ 3 follicles of ≥17 mm). An AMH threshold of 4 pmol/L predicted failure to reach the classical hCG criteria with 89% specificity and 53% sensitivity and an area under the curve (AUC) of 0.76 (95% CI 0.66-0.85). AMH predicted cycle cancellation due to lack of follicular development, using a cut-off value of 1.5 pmol/L, with a specificity of 96% and sensitivity of 80% (AUC = 0.92, 95% CI 0.79-1.00). A single-unit increase in AMH was associated with a 29% decrease in odds of failure to reach the classical hCG criteria (OR 0.71 95% CI 0.59-0.85, p < 0.01). The lowest AMH value compatible with a live birth was 1.3 pmol/L. CONCLUSIONS: Among women with a limited ovarian reserve, pre-treatment serum AMH levels significantly predicted failure to reach the classical hCG triggering criteria and predicted lack of follicular development using a new sensitive assay, but AMH was not suitable for withholding fertility treatment, as even very low levels were associated with live births. TRIAL REGISTRATION: Not relevant.

Concentration of soluble urokinase plasminogen activator receptor (suPAR) in the pre-ovulatory follicular fluid is associated with development of ovarian hyperstimulation syndrome during ovarian stimulation.

PURPOSE: Investigating whether pre-ovulatory follicular fluid (FF) levels of selected proteins differ between women who do or do not develop severe ovarian hyperstimulation syndrome (OHSS) and evaluate whether they potentially could guide a "freeze-all" strategy. METHODS: FF was collected during a randomized controlled trial comparing OHSS in antagonist versus agonist protocol including 1050 women in their first assisted reproductive technology (ART) cycle during year 2009-2013. The present sub-study is a matched case-control study comparing FF levels of soluble urokinase plasminogen activator receptor (suPAR), C-reactive protein, placental growth factor, vascular endothelial growth factor, and angiopoietins 1 and 2 in OHSS cases (n = 25, severe OHSS, and ≥ 15 oocytes), high-risk controls (n = 25, no OHSS, and ≥ 15 oocytes), and low-risk controls (n = 25, no OHSS, and 5-8 oocytes). RESULTS: FF level of suPAR differed significantly between the three groups (p = 0.018) with mean (SD) levels of 2.3 (0.4) µg/L, 2.6 (0.8) µg/L, and 2.8 (0.6) µg/L in OHSS cases, high-risk controls, and low-risk controls, respectively. Receiver operating characteristic curve analysis demonstrated that suPAR levels could predict severe OHSS (AUC 0.678; 95% CI 0.553-0.803) with a sensitivity of 64% and a specificity of 66%. None of the other investigated proteins differed between the three groups or between OHSS cases and combined controls. CONCLUSION: The pre-ovulatory FF level of suPAR was significantly lower in women developing severe OHSS, indicating that the plasminogen activator system could be involved in the pathophysiology of OHSS. However, suPAR did not provide a satisfying predictive value for the prediction of OHSS.