Kim L. Thornton

A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial

OBJECTIVE To determine the value of gonadotropin/intrauterine insemination (FSH/IUI) therapy for infertile women aged 21-39 years. DESIGN Randomized controlled trial. SETTING Academic medical center associated with a private infertility center. PATIENT(S) Couples with unexplained infertility. INTERVENTION(S) Couples were randomized to receive either conventional treatment (n=247) with three cycles of clomiphene citrate (CC)/IUI, three cycles of FSH/IUI, and up to six cycles of IVF or an accelerated treatment (n=256) that omitted the three cycles of FSH/IUI. MAIN OUTCOME MEASURE(S) The time it took to establish a pregnancy that led to a live birth and cost-effectiveness, defined as the ratio of the sum of all health insurance charges between randomization and delivery divided by the number of couples delivering at least one live-born baby. RESULT(S) An increased rate of pregnancy was observed in the accelerated arm (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.00-1.56) compared with the conventional arm. Median time to pregnancy was 8 and 11 months in the accelerated and conventional arms, respectively. Per cycle pregnancy rates for CC/IUI, FSH/IUI, and IVF were 7.6%, 9.8%, and 30.7%, respectively. Average charges per delivery were

Race matters: a systematic review of racial/ethnic disparity in Society for Assisted Reproductive Technology reported outcomes.

9,800 lower (95% CI,

Increased frequency of occult fragile X-associated primary ovarian insufficiency in infertile women with evidence of impaired ovarian function

25,100 lower to

Evaluation of leuprolide acetate treatment on histopathology of uterine myomata

3,900 higher) in the accelerated arm compared to conventional treatment. The observed incremental difference was a savings of

A randomized clinical trial to determine optimal infertility treatment in older couples: the Forty and Over Treatment Trial (FORT-T)

2,624 per couple for accelerated treatment and 0.06 more deliveries. CONCLUSION(S) A randomized clinical trial demonstrated that FSH/IUI treatment was of no added value.

Assessment of day-3 morphology and euploidy for individual chromosomes in embryos that develop to the blastocyst stage.

OBJECTIVE To systematically review the reporting of race/ethnicity in Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System (CORS) publications. DESIGN Systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology of literature published in PubMed on race/ethnicity that includes data from SART CORS. SETTING Not applicable. PATIENT(S) Not applicable. INTERVENTION(S) In vitro fertilization cycles reported to SART. MAIN OUTCOME MEASURE(S) Any outcomes reported in SART CORS. RESULT(S) Seven publications were identified that assessed racial/ethnic disparities in IVF outcomes using SART data. All reported a racial/ethnic disparity. However, more than 35% of cycles were excluded from analysis because of missing race/ethnicity data. CONCLUSION(S) Review of current publications of SART data suggests significant racial/ethnic disparities in IVF outcomes. However, the potential for selection bias limits confidence in these findings, given that fewer than 65% of SART reported cycles include race/ethnicity. Our understanding of how race/ethnicity influences ART outcome could be greatly improved if information on race/ethnicity was available for all reported cycles.

Contraceptive Counseling for Women Who Undergo Bariatric Surgery

BACKGROUND The FMR1 premutation is associated with overt primary ovarian insufficiency (POI). However, its prevalence in women with occult POI (i.e. menstrual cycles, but impaired ovarian response) has not been examined. We hypothesized that both the FMR1 premutation and intermediate allele is more frequent in infertile women with occult POI than in controls, and that a repeat length cutoff might predict occult POI. METHODS All subjects were menstruating women <42 years old and with no family history of unexplained mental retardation, autism or fragile X syndrome. Cases had occult POI defined by elevated FSH or poor response to gonadotrophin therapy (n = 535). Control subjects (n = 521) had infertility from other causes or were oocyte donors. Prevalence of the FMR1 premutation and intermediate alleles was examined and allele length was compared between controls and women with occult POI. RESULTS The frequency of the premutation (7/535 versus 1/521; P< 0.05) and intermediate alleles (17/535 versus 7/521; P< 0.05) was higher in women with occult POI than in controls. The allele with the greatest number of CGG repeats was longer in women with occult POI compared with controls (32.7 ± 7.1 versus 31.6 ± 4.3; P < 0.01). A receiver operating characteristic curve examining repeat length as a test for occult POI had an area of 0.56 ± 0.02 (P < 0.01). A repeat cutoff of 45 had a specificity of 98%, but a sensitivity of only 5% to identify occult POI. The positive predictive value was only 21% for a fertility population that has ∼ 22% of its patients with occult POI. CONCLUSIONS The data suggest that FMR1 premutations and intermediate alleles are increased in women with occult POI. Thus, FMR1 testing should be performed in these women as some will have fragileX-associated POI. Although the FMR1 repeat lengths were longer in women with occult POI, the data do not support the use of a repeat length cutoff to predict occult POI.

No change in live birthweight of IVF singleton deliveries over an 18-year period despite significant clinical and laboratory changes.

OBJECTIVE To determine if short-term, preoperative leuprolide acetate (LA) therapy alters the histologic appearance of uterine leiomyomata. DESIGN Retrospective evaluation by a pathologist (who was blinded to patient history) of the histologic features of leiomyomata excised from 36 women, 12 who received preoperative LA and 24 age-matched controls. SETTING Yale-New Haven Hospital, New Haven, Connecticut, from September 1989 to September 1990. MAIN OUTCOME MEASURE The histologic specimens were evaluated for the presence of mitotic activity, cellular atypia, cellularity, and secondary changes including edema, fibrosis, calcification, hemorrhage, infarction, hyalinization, and vascular appearance. RESULTS Of the 12 patients treated with LA, 10 (84%) demonstrated a reduction in uterine volume after 3 to 6 months of LA therapy. There was no difference in any of the histopathologic parameters evaluated between the LA-treated group and the untreated group. Exclusion of leiomyoma, which did not have a reduction in size during LA therapy, did not alter the analysis. Among patients treated with LA, those leiomyoma that did not respond to LA had a greater degree of hyalinization than those that responded. CONCLUSION Reduction in uterine size by short-term LA therapy did not detectably alter histologic appearance of leiomyoma.

Follicular Fluid-Specific Distribution of Vascular Endothelial Growth Factor Isoforms and sFlt-1 in Patients Undergoing IVF and Their Correlation With Treatment Outcomes

OBJECTIVE To determine the optimal infertility therapy for women at the end of their reproductive potential. DESIGN Randomized clinical trial. SETTING Academic medical centers and private infertility center in a state with mandated insurance coverage. PATIENT(S) Couples with ≥ 6 months of unexplained infertility; female partner aged 38-42 years. INTERVENTION(S) Randomized to treatment with two cycles of clomiphene citrate (CC) and intrauterine insemination (IUI), follicle stimulating hormone (FSH)/IUI, or immediate IVF, followed by IVF if not pregnant. MAIN OUTCOME MEASURE(S) Proportion with a clinically recognized pregnancy, number of treatment cycles, and time to conception after two treatment cycles and at the end of treatment. RESULT(S) We randomized 154 couples to receive CC/IUI (N = 51), FSH/IUI (N = 52), or immediate IVF (N = 51); 140 (90.9%) couples initiated treatment. The cumulative clinical pregnancy rates per couple after the first two cycles of CC/IUI, FSH/IUI, or immediate IVF were 21.6%, 17.3%, and 49.0%, respectively. After all treatments, 110 (71.4%) of 154 couples had conceived a clinically recognized pregnancy, and 46.1% had delivered at least one live-born baby; 84.2% of all live-born infants resulting from treatment were achieved via IVF. There were 36% fewer treatment cycles in the IVF arm compared with either COH/IUI arm, and the couples conceived a pregnancy leading to a live birth after fewer treatment cycles. CONCLUSION(S) A randomized controlled trial in older women with unexplained infertility to compare treatment initiated with two cycles of controlled ovarian hyperstimulation/IUI versus immediate IVF demonstrated superior pregnancy rates with fewer treatment cycles in the immediate IVF group. CLINICAL TRIAL REGISTRATION NUMBER NCT00246506.

Influence of embryo sex on development to the blastocyst stage and euploidy.

OBJECTIVE To examine the relationship between day-3 morphology and euploidy for individual chromosomes in embryos that develop to the blastocyst stage by day 5. DESIGN Retrospective cohort study. SETTING Boston IVF, a large university-affiliated reproductive medicine practice. PATIENT(S) Ninety-nine patients undergoing their first preimplantation genetic screening (PGS) cycle between January 1 and December 31, 2006. INTERVENTION(S) In vitro fertilization (IVF) and preimplantation genetic screening (PGS). MAIN OUTCOME MEASURE(S) Prevalence of euploidy for chromosomes X, Y, 8, 13, 14, 15, 16, 17, 18, 20, 21, and 22 in day-3 high implantation potential (HIP) versus non-HIP embryos that grew to day-5 blastocysts. RESULT(S) Seven hundred three embryos from 99 cycles in 99 patients underwent PGS. Three hundred sixty-four (52%) embryos from 88 cycles in 88 patients developed to the blastocyst stage by day 5. High implantation potential embryos were more likely to be euploid for chromosomes X/Y, 8, 15, 16, 18, and 22 compared with non-HIP embryos, with similar trends for chromosomes 14 and 17. There were no statistically significant differences between HIP and non-HIP embryos in euploidy prevalence for chromosomes 13, 20, and 21. CONCLUSION(S) Our data suggest that PGS may detect potentially viable but detrimental chromosomal abnormalities that are not detected by embryo morphology alone.