PURPOSE: The purpose of the study was to evaluate whether routinely collected clinical factors can predict in vitro fertilization (IVF) failure among young, good prognosis patients predominantly with secondary infertility who are less than 35 years of age. METHODS: Using de-identified clinic records, 414 women <35 years undergoing their first autologous IVF cycle were identified. Logistic regression was used to identify patient-driven clinical factors routinely collected during fertility treatment that could be used to model predicted probability of cycle failure. RESULTS: One hundred ninety-seven patients with both primary and secondary infertility had a failed IVF cycle, and 217 with secondary infertility had a successful live birth. None of the women with primary infertility had a successful live birth. The significant predictors for IVF cycle failure among young patients were fewer previous live births, history of biochemical pregnancies or spontaneous abortions, lower baseline antral follicle count, higher total gonadotropin dose, unknown infertility diagnosis, and lack of at least one fair to good quality embryo. The full model showed good predictive value (c = 0.885) for estimating risk of cycle failure; at ≥80 % predicted probability of failure, sensitivity = 55.4 %, specificity = 97.5 %, positive predictive value = 95.4 %, and negative predictive value = 69.8 %. CONCLUSION: If this predictive model is validated in future studies, it could be beneficial for predicting IVF failure in good prognosis women under the age of 35 years.

Objective

To study the effects of ibuprofen on androgen production, gene expression, and cell viability in rat theca-interstitial cells exposed to the proinflammatory stimuli interleukin-1β (IL-1β) and lipopolysaccharide (LPS).

Design

Animal study.

Setting

University-based research laboratory.

Patients/animals

Theca-interstitial cells were isolated from 30 day old female Sprague Dawley rats.

Interventions

Theca cells were cultured with pro-inflammatory media containing IL-1β and LPS and compared with cells cultured in control media.

Main outcome measures

Androstenedione quantification was performed on conditioned cell culture medium using liquid chromatography-mass spectrometry. Theca cell viability was assessed using PrestoBlue cell viability assay. The gene expression of Cyp17a1, Cyp11a1, and Hsd3b was analyzed using quantitative polymerase chain reaction.

Results

Both proinflammatory stimuli IL-1β and LPS increased androstenedione concentration in cell culture medium, and these effects were mitigated with ibuprofen. Both inflammatory agents in addition increased the expression of key genes involved in androgen synthesis: Cyp17a1, Cyp11a1, and Hsd3b; the addition of ibuprofen to the culture medium inhibited these effects. Theca cell viability increased with IL-1β and LPS. Ibuprofen inhibited the IL-1β-mediated increase in cell viability but did not reverse the effects of LPS.

Conclusions

In conclusion, our findings support the hypothesis that many of the alterations induced by inflammatory stimuli in theca-interstitial cells are abrogated by the addition of ibuprofen.

Abstract: Embryo implantation in humans is remarkably inefficient for reasons that remain largely unexplained, and high rates of implantation failure remain one of the greatest obstacles in treating infertility. The volume of gene expression data available from human embryos has rapidly accumulated in recent years. However, prioritization of these data to identify the subset of genes that determine successful implantation remains a challenge, in part, because comprehensive analyses cannot be performed on the same embryos that are transferred. Here, we leverage clinical morphologic grading—known for decades to correlate with implantation potential—and transcriptome analyses of matched embryonic and abembryonic samples to identify genes and cell-cell interactions enriched and depleted in human blastocysts of good and poor morphology, genome-wide. Unexpectedly, we discovered that the greatest molecular difference was in the state of the extraembryonic primitive endoderm (PrE), with relative deficiencies in PrE development in embryos of poor morphology at the time of embryo transfer. Together, our results support a model in which implantation success is most strongly reflected by factors and signals from the embryonic compartment and suggest that deficiencies in PrE development, in particular, are common among embryos with reduced implantation potential. Our study provides a valuable resource for those investigating the markers and mechanisms of human embryo implantation.