Black recipients of oocyte donation experience lower live birth rates compared with White recipients.

RESEARCH QUESTION: Is minority race associated with worse oocyte donation outcomes? DESIGN: Retrospective analysis of 926 oocyte recipients who underwent a donor cycle with fresh embryo transfer at a single fertility centre between January 2009 and June 2015. Race was self-reported. To adjust for repeat donors within the sample, mixed models were used to analyse donor parameters and recipient outcomes. The recipient outcome models were adjusted for age, body mass index and primary infertility diagnosis. RESULTS: The study consisted of 767 (82.8%) White, 41 (4.4%) Black, 63 (6.8%) Asian and 55 (5.9%) Hispanic women. Compared with White recipients, the adjusted odds ratio (aOR) for clinical pregnancy was 0.39 (95% confidence interval [CI] 0.19-0.79) for Black, 0.55 (95% CI 0.31-0.98) for Hispanic and 0.88 (95% CI 0.51-1.53) for Asian recipients. The aOR for live birth was 0.47 (95% CI 0.23-0.98) for Black, 0.58 (95% CI 0.32-1.06) for Hispanic and 0.62 (95% 0.35-1.09) for Asian recipients. A subgroup analysis restricted to cycles with racially concordant donors and recipients showed that the odds of clinical pregnancy and live birth were further reduced among Black recipients, with aOR of 0.28 (95% CI 0.09-0.81) and 0.30 (95% CI 0.09-0.98), respectively. CONCLUSIONS: Black and Hispanic oocyte donation recipients experience lower clinical pregnancy rates and Black recipients experience lower live birth rates compared with White recipients. Racially discordant donor oocyte cycles involving donors and recipients of different races present an opportunity to further investigate the cause of disparity.

Diminished ovarian reserve is not observed in infertility patients with high normal CGG repeats on the fragile X mental retardation 1 (FMR1) gene.

STUDY QUESTION: Does an association exist between high normal numbers of CGG trinucleotide repeats on the fragile X mental retardation 1 (FMR1) gene and diminished ovarian reserve (DOR)? SUMMARY ANSWER: This large data set demonstrated that a high normal number of CGG repeats (35-54 repeats) on the FMR1 gene was not significantly correlated with DOR. WHAT IS KNOWN ALREADY: The FMR1 premutation (55-200 repeats) is a known cause of primary ovarian insufficiency. However, the relationship between high normal CGG repeat numbers (35-54 repeats) and ovarian reserve has yet to be conclusively demonstrated. STUDY DESIGN, SIZE, DURATION: This is a retrospective data analysis conducted between January 2012 and February 2014 that included 1287 women. Over 1140 women had complete data. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women, excluding oocyte donors, who presented to a large private practice specializing in reproductive endocrinology and infertility for treatment and who underwent both fragile X and ovarian reserve testing were included. All fragile X testing was performed using triplet repeat PCR, with confirmation of positives by Southern blot. CGG repeat numbers from both alleles were recorded, and the allele with the higher number of repeats was used for statistical calculations. We did not differentiate between patients with one or two high normal alleles. Women with >54 CGG repeats were excluded from the analysis. For our analysis, we considered both a 'high normal' number of CGG repeats (35-44) and an intermediate number of GCC repeats (45-54) as 'high normal'. Ovarian reserve testing was carried out on Cycle Day 2 or 3 and included measurements of FSH, anti-Müllerian hormone (AMH) and antral follicle count (AFC). A generalized linear regression model assuming gamma distribution and log link function that controlled for age was used to assess correlation between CGG repeat number and FSH, AMH and AFC. MAIN RESULTS AND THE ROLE OF CHANCE: As expected, there was a significant correlation between increasing age and increasing FSH and decreasing AFC and AMH for the patients in this study. For every 1-year increase in age, FSH increased by a factor of 1.04, AFC decreased by a factor of 0.93 and AMH decreased by a factor of 0.89. After controlling for age, there was no significant correlation between FMR1 CGG trinucleotide repeat number and FSH (P = 0.23), AFC (P = 0.14) or AMH (P = 0.53). Three subgroup analyses were also performed. We found a significant relationship between increasing CGG repeat number and decreasing AMH levels (P = 0.01) in women >44 years old. The second subgroup analysis included only Caucasian patients and found no significant correlation between CGG repeat number and DOR. In a subgroup analysis comparing women with at least one allele <26 repeats, at least one allele >35 and women with both alleles between 29 and 32, there were no significant associations regarding ovarian reserve in any of these groups. LIMITATIONS, REASONS FOR CAUTION: One limitation of this study is that it involved a heterogeneous population of infertile women with mixed diagnoses. Factors that could affect ovarian reserve, such as medical comorbidities, prior surgeries, family history and endometriosis, were not accounted for. Finally, there was a lack of racial diversity, with Caucasians representing 67.8% of the total population. WIDER IMPLICATIONS OF THE FINDINGS: The findings of this study are generalizable to an infertility population and are in line with several previously published studies. Women who are found to have high normal CGG repeat numbers can be counseled that this is not causative for DOR. Further studies are needed to investigate whether increasing CGG repeat numbers are associated with ovarian responsiveness to gonadotrophin stimulation or IVF outcome.

Racial disparities in in vitro fertilization outcomes.

OBJECTIVE: To evaluate the impact of race on in vitro fertilization (IVF) outcomes. DESIGN: Retrospective analysis. SETTING: Private practice. PATIENT(S): All women who underwent a first autologous IVF cycle at Fertility Centers of Illinois from January 2010 to December 2012. INTERVENTION(S): Information was collected on baseline characteristics, cycle parameters, and outcomes. Race was self-reported. MAIN OUTCOME MEASURE(S): Clinical intrauterine pregnancy and live birth rates. RESULT(S): A total of 4,045 women were included: 3,003 white (74.2%), 213 black (5.3%), 541 Asian (13.4%), and 288 Hispanic women (7.1%). A multivariable logistic regression was performed to control for confounders. Compared with white women, the adjusted odds ratio for clinical intrauterine pregnancy was 0.63 (95% confidence interval [CI] 0.44-0.88) in black women, 0.73 (95% CI 0.60-0.90) in Asian women, and 0.82 (95% CI 0.62-1.07) in Hispanic women. The adjusted odds ratio for live birth was 0.50 (95% CI 0.33-0.72) in black women, 0.64 (95% CI 0.51-0.80) in Asian women, and 0.80 (95% CI 0.60-1.06) in Hispanic women compared with white women. The spontaneous abortion rate was 14.6% in white women versus 28.9% in black women, 20.6% in Asian women, and 15.3% in Hispanic women. CONCLUSION(S): Black and Asian women had lower odds of clinical intrauterine pregnancy and live birth and higher rates of spontaneous abortion compared with white women. Further research is needed to better characterize the mechanisms associated with this racial disparity and to improve treatment options for black and Asian women.

Mechanism of protein splicing of the Pyrococcus abyssi lon protease intein.

Protein splicing is a post-translational process by which an intervening polypeptide, the intein, excises itself from the flanking polypeptides, the exteins, coupled to ligation of the exteins. The lon protease of Pyrococcus abyssi (Pab) is interrupted by an intein. When over-expressed as a fusion protein in Escherichia coli, the Pab lon protease intein can promote efficient protein splicing. Mutations that block individual steps of splicing generally do not lead to unproductive side reactions, suggesting that the intein tightly coordinates the splicing process. The intein can splice, although it has Lys in place of the highly conserved penultimate His, and mutants of the intein in the C-terminal region lead to the accumulation of stable branched-ester intermediate.