Long-term reproductive outcomes in patients with unexplained infertility: follow-up of the Fast Track and Standard Treatment Trial participants.

OBJECTIVE: To evaluate long-term reproductive outcomes in couples who were enrolled in a large randomized controlled trial that studied optimal treatment for unexplained infertility. DESIGN: Telephone survey, administered between March 2019 and February 2020. SETTING: Large urban university-affiliated fertility center. PATIENT(S): Couples who enrolled in the Fast Track and Standard Treatment Trial (FASTT). INTERVENTION(S): None. MAIN OUTCOMES MEASURE(S): Number of live births, methods of conception, adoption, and satisfaction regarding family size. RESULT(S): Of the 503 couples enrolled in FASTT, 311 (61.8%) were contacted and 286 (56.9%) consented to participate. The mean age and follicle-stimulating hormone level at the time of enrollment in FASTT were 33.1 ± 3.2 years and 6.8 ± 2.2 mIU/mL, respectively, for those who participated in this study. The mean age at follow-up was 49.5 ± 3.4 years. Of the 286 women, 194 (67.8%) had a live birth during the trial and 225 (78.7%) continued to try to conceive after FASTT. Of those who tried to conceive without treatment, 101 of 157 (64.3%) had a successful live birth, whereas 12 (5.3%) women had a live birth via intrauterine insemination and 82 (36.4%) via autologous oocyte in vitro fertilization. Overall, 182 (80.9%) women achieved a live birth after FASTT. CONCLUSION(S): The majority of couples were able to achieve a live birth after FASTT. Only 19 (6.6%) never achieved a live birth during their reproductive years. Moving to treatment sooner allows the opportunity to achieve >1 live birth, which is associated with increased satisfaction regarding family size. This further supports access to care and insurance coverage for infertility treatment.

Dietary Energy Density and Fertility: Results from the Lifestyle and Fertility Study.

BACKGROUND: Diet is a modifiable lifestyle factor linked with fertility in a growing number of studies. OBJECTIVE: The objective of this study was to evaluate the association between dietary energy density (ED), a summary measure of diet quality that estimates the amount of energy per unit food (kcal/g) consumed, and conception and pregnancy outcomes. METHODS: A prospective cohort study of couples planning their first pregnancy was conducted in the Northeast region of the USA. Dietary data were collected prior to conception via 3 unannounced interviewer-administered 24-h dietary recalls. Multivariable-adjusted logistic regression (ORs and Cox proportional hazards models [RR] and 95% CIs) were estimated for continuous and categorical (tertile [T]) variables of dietary ED. RESULTS: The majority of women (n = 80; 61%) achieved clinical pregnancy. Median time to conception of a clincal pregnancy(TTC) for those who conceived was 4.64 mo with an IQR of 4.37 mo. ED modeled as a continuous variable was not associated with clinical pregnancy, live birth, or TTC after controlling for race, physical activity, and male partner's ED. When ED was categorized to consider nonlinear associations, 60%, 73%, and 50% of the participants in the tertiles (from lowest ED to highest) achieved clinical pregnancy. In multivariable logistic analyses with the middle group as the referent (ED = 1.37-1.60), membership in the highest ED group (ED >1.60) was associated with lower odds of clinical pregnancy (OR = 0.30; 95% CI: 0.11, 0.81, P = 0.02). In Cox proportional hazards analyses, membership in the highest ED group was associated with significantly longer TTC compared with the middle category (HR = 0.41; 95% CI: 0.21,0.82, P = 0.01). CONCLUSIONS: These results suggest that high dietary ED is associated with reduced fertility.This study evaluated associations between dietary energy density and the probability of conceiving clinical pregnancy, having a live birth, and the time to conception among couples planning pregnancy.

Dietary quality, as measured by the Alternative Healthy Eating Index for Pregnancy (AHEI-P), in couples planning their first pregnancy.

OBJECTIVE: Dietary quality (DQ), as assessed by the Alternative Healthy Eating Index for Pregnancy (AHEI-P), and conception and pregnancy outcomes were evaluated. DESIGN: In this prospective cohort study on couples planning their first pregnancy. Cox proportional hazards regression assessed the relationship between AHEI-P score and clinical pregnancy, live birth and pregnancy loss. SETTING: Participants were recruited from the Northeast region of the USA.Participants: Healthy, nulliparous couples (females, n 132; males, n 131; one male did not enrol). RESULTS: There were eighty clinical pregnancies, of which sixty-nine resulted in live births and eleven were pregnancy losses. Mean (sd) female AHEI-P was 71·0 (13·7). Of those who achieved pregnancy, those in the highest tertile of AHEI-P had the greatest proportion of clinical pregnancies; however, this association was not statistically significant (P = 0·41). When the time it took to conceive was considered, females with the highest AHEI-P scores were 20 % and 14 % more likely to achieve clinical pregnancy (model 1: hazard ratio (HR) = 1·20; 95 % CI 0·66, 2·17) and live birth (model 1: HR = 1·14; 95 % CI 0·59, 2·20), respectively. Likelihood of achieving clinical pregnancy and live birth increased when the fully adjusted model, including male AHEI-P score, was examined (clinical pregnancy model 4: HR = 1·55; 95 % CI 0·71, 3·39; live birth model 4: HR = 1·36; 95 % CI 0·59, 3·13). CONCLUSIONS: The present study is the first to examine AHEI-P score and achievement of clinical pregnancy. DQ was not significantly related to pregnancy outcomes, even after adjustments for covariates.

Prophylactic Negative Pressure Wound Therapy and Wound Complication After Cesarean Delivery in Women With Class II or III Obesity: A Randomized Controlled Trial.

OBJECTIVE: To compare the occurrence of superficial surgical site infections in obese women using prophylactic negative pressure therapy with standard dressings after cesarean delivery. METHODS: We conducted a randomized controlled, nonblinded, two-center study of prophylactic negative pressure therapy compared with standard surgical dressings placed at the time of primary closure at cesarean delivery in obese women with body mass indexes (BMI) of 35 or higher (ie, class II and III obesity). Our primary outcome was occurrence of a superficial surgical site infection. We assumed a superficial surgical site infection occurrence rate of 20% and intended to recruit 400 women. However, after low enrollment of 166 women over 24 months, an interim analysis for futility was conducted and the decision was made to halt the study. RESULTS: Women were recruited between January 5, 2015, and January 7, 2017, from two sites. The mean BMI on admission was 44.9 (±8) for the prophylactic negative wound therapy group and 43.4 (±7) for the standard dressing group. There were no differences in the occurrence of observed superficial surgical site infections between women using prophylactic negative pressure wound therapy (12/80 [15%]) compared with women who received the standard dressing (8/81 [10%], P=.35, relative risk 1.52, 95% CI 0.66-3.52). There were no differences in the occurrence of composite wound complications between women using prophylactic negative pressure wound therapy (25/80 [31%]) compared with women who received the standard dressing (24/81 [30%], P=.87). CONCLUSION: In this randomized controlled trial that did not achieve full anticipated enrollment, we did not observe a decrease in superficial surgical site infections after cesarean delivery in obese women with the use of prophylactic negative pressure wound therapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02390401.

Association of vitamin D intake and serum levels with fertility: results from the Lifestyle and Fertility Study.

OBJECTIVE: To evaluate the role of vitamin D intake and serum levels on conception of clinical pregnancy and live birth. DESIGN: Prospective cohort study. SETTING: Academic medical centers. PATIENT(S): Healthy, nulliparous women, age 18-39 years, and their male partners. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy and live birth were compared between those who did or did not meet the vitamin D estimated average requirement (EAR) intake (10 µg/d) and with serum 25-hydroxyvitamin D (25(OH)D) considered at risk for inadequacy or deficiency (<50 nmol/L) or sufficient (≥50 nmol/L). RESULT(S): Among 132 women, 37.1% did not meet the vitamin D EAR and 13.9% had serum levels at risk for inadequacy or deficiency. Clinical pregnancies were significantly higher among women who met the vitamin D EAR (67.5% vs. 49.0%) and with sufficient serum 25(OH)D (64.3% vs. 38.9%) compared with those who did not. Live births were higher among those who met the vitamin D EAR (59.0% vs. 40.0%). The adjusted odds ratio (AOR) of conceiving a clinical pregnancy was significantly higher among those who met the EAR (AOR = 2.26; 95% confidence interval [CI], 1.05-4.86) and had sufficient serum 25(OH)D (AOR = 3.37; 95% CI, 1.06-10.70). The associations were not significant after controlling for selected nutrients and dietary quality. CONCLUSION(S): Women with vitamin D intake below EAR and serum 25(OH)D levels at risk for inadequacy or deficiency may be less likely to conceive and might benefit from increased vitamin D intake to achieve adequacy. CLINICAL TRIAL REGISTRATION NUMBER: NCT00642590.

A randomized controlled trial comparing two types of retractors at caesarean delivery.

The aim of this study was to determine if the use of a self-retaining, symmetrical retractor (OB/Mobius®) during caesarean delivery is associated with differences in post-operative pain experience. Consenting women undergoing caesarean delivery were randomly assigned to OB/Mobius® versus conventional retraction instruments. Women were blinded to retractor type and filled out surgical pain surveys each post-operative day. Additional outcome variables were collected through a provider survey and chart review. Of the 154 randomised women, 144 completed the study. There was no difference in the symmetry, quality or intensity of postoperative pain based on the method of retraction. The OB/Mobius® retractor did not confer an improvement in the quality or intensity of post-caesarean discomfort in the first three days following delivery. Nor did the groups differ in operative times, blood loss or pain medication usage. However, the retractor may offer improved visualisation and retraction in obese women. Impact statement Use of a plastic sheath self-retaining retractor has been minimally studied in caesarean deliveries. Recently it was found that the use of such a retractor reduced wound infection, but another study in obese women did not show improved rates of infection (Hinkson et al. 2016 ; Scolari Childress et al. 2016 ). The study of sheath self-retaining retractors to decrease post-operative pain has not been reported previously. This study offers an investigation into a generalisable population of parturients who undergo caesarean delivery and if the primary use of a self-retaining retractor versus sole use of traditional hand-held retractors decreased post-operative pain while in the hospital. Although this study did not show an improvement in post-operative pain, provider experience reports demonstrated some improvement in visualisation, particularly in the obese population with the use of this novel retractor, thus making it an option for providers who do caesarean deliveries without an assistant and find hand-held retractors inadequate.

When is clomiphene or gonadotropin intrauterine insemination futile? Results of the Fast Track and Standard Treatment Trial and the Forty and Over Treatment Trial, two prospective randomized controlled trials.

OBJECTIVE: To determine whether day 3 FSH and E2 levels at the upper limits of normal affect live-birth rates and treatment trajectory in a conventional versus "fast track" treatment program for IVF. DESIGN: Secondary analysis of two randomized controlled trials, FASTT and FORT-T. SETTING: Not applicable. PATIENT(S): Infertile women ages 21-42 years randomized to conventional or accelerated treatment with controlled ovarian hyperstimulation (COH)-IUI and/or IVF (n=603 patients contributing 2,717 total cycles). INTERVENTION(S): Patients were stratified according to basal FSH and E2: FSH<10 mIU/mL and E2<40 pg/mL (group 1A), FSH<10 mIU/mL and E2≥40 pg/mL (group 1B), FSH, 10-15 mIU/mL and E2<40 pg/mL (group 2A), and FSH, 10-15 mIU/mL and E2≥40 pg/mL (group 2B). MAIN OUTCOME MEASURE(S): Number of cancelled cycles, disenrollment for poor response, and cumulative live-birth rates per couple. RESULT(S): Women in groups 2A and 2B were more likely to have cancelled cycles and be disenrolled for poor response. While no live births occurred in group 2B during COH-IUI (0/19 couples, 0/58 cycles), IVF still afforded these patients a reasonable chance of success (6/18 couples, 6/40 cycles, 33.3% live-birth rate per couple). The specificity and positive predictive value of basal FSH of 10-15 mIU/mL and E2≥40 pg/mL for no live birth during COH-IUI treatment were both 100%. CONCLUSION(S): Women who initiated infertility treatment with FSH of 10-15 mIU/mL and E2≥40 pg/mL on day 3 testing were unlikely to achieve live birth after COH-IUI treatment.

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

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.

Female dietary antioxidant intake and time to pregnancy among couples treated for unexplained infertility.

OBJECTIVE: To determine whether increased antioxidant intake in women is associated with shorter time to pregnancy (TTP) among a cohort of couples being treated for unexplained infertility. DESIGN: Secondary data analysis of a randomized controlled trial. SETTING: Academic medical center associated with a private infertility center. PATIENTS: Females with unexplained infertility. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): The time it took to establish a pregnancy that led to a live birth. RESULT(S): Mean nutrient intake exceeded the estimated average requirement (EAR) for vitamins C and E. No differences in mean intake of any of the antioxidants were noted between women who delivered a live-born infant during the study period vs. those who did not. In multivariable models, intake of ß-carotene from dietary supplements was associated with shorter TTP among women with body mass index (BMI) ≥25 kg/m(2) (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.09-1.53) and women <35 y (HR 1.19, 95% CI 1.01-1.41). Intake of vitamin C from dietary supplements was associated with shorter TTP among women with BMI <25 kg/m(2) (HR 1.09, 95% CI 1.03-1.15) and women <35 y (HR 1.10, 95% CI 1.02-1.18). Intake of vitamin E from dietary supplements among women ≥35 y also was associated with shorter TTP (HR 1.07, 95% CI 1.01-1.13). CONCLUSION(S): Shorter TTP was observed among women with BMI <25 kg/m(2) with increasing vitamin C, women with BMI ≥25 kg/m(2) with increasing ß-carotene, women <35 y with increasing ß-carotene and vitamin C, and women ≥35 y with increasing vitamin E. CLINICAL TRIAL REGISTRATION NUMBER: NCT00260091.

Gonadotropin therapy: a 20th century relic.

Gonadotropin therapy has been a cornerstone of infertility therapy for half a century. From the very beginning, its use has been associated with a high rate of multiple births, particularly high order multiples, and ovarian hyperstimulation syndrome. Initially, success rates seemed acceptable when used for superovulation (SO)/IUI therapy. However, as data from RCTs have emerged, reported outcomes suggest that we question the use of injectible gonadotropins. This manuscript examines the studies that have challenged gonadotropin use for SO/IUI and other research that supports reduced doses of gonadotropins for IVF. We examine the challenges for its continued use for SO/IUI and for moving to lower doses worldwide for IVF. We propose a future that views gonadotropins as a relic of the twentieth century.

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 $9,800 lower (95% CI, $25,100 lower to $3,900 higher) in the accelerated arm compared to conventional treatment. The observed incremental difference was a savings of $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.

Impact of oxidative stress on female fertility.

PURPOSE OF REVIEW: To review the role of oxidative stress in the context of female fertility. RECENT FINDINGS: Oxidative stress is associated with decreased female fertility in animal and in-vitro models, but no studies to date have directly assessed the relationship in women. Exposures associated with oxidative stress and with evidence to influence the timing and maintenance of a viable pregnancy include pregnancy complications (e.g. preeclampsia), extremes of body weight, alcohol, tobacco, and caffeine intake. Intake of antioxidant nutrients, including use of multivitamins, impacts the generation of reactive oxygen species and may play a beneficial role in female fertility. SUMMARY: Infertility is a significant public health problem and diagnosis and treatment are stressful, invasive, and costly. The role of oxidative stress in female fertility is an understudied and compelling area for investigation. Identifying modifiable factors to decrease oxidative stress in the gynecologic environment may be an inexpensive and noninvasive therapy for increasing fertility.

Optimizing the number of blastocyst stage embryos to transfer on day 5 or 6 in women 38 years of age and older: a Society for Assisted Reproductive Technology database study.

OBJECTIVE: To develop evidence-based recommendations for the optimum numbers of blastocyst stage embryos to transfer in women >or=38 years old. DESIGN: Retrospective analysis of national Society for Assisted Reproductive Technology data from 2000 to 2004. SETTING: National writing group. PATIENT(S): Five thousand five hundred sixty-nine day 5 and day 6 ETs in women >or=38 years of age undergoing their first assisted reproductive technology cycle. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Logistic regression was used to model the probability of a delivery, twins, and high-order multiples based on patient characteristics. RESULT(S): In 38- and 39-year-old women there was an increase in delivery rates up to transfer of two embryos. Beyond that, number transferred increased multiple rates but not delivery rates. Transfer of three embryos in 40-year-old women increased delivery but not multiple rate. For 41- to 42-year-olds delivery rate was level after transfer of three, but twin rate continued to increase. Multivariate analysis showed that age, embryo cryopreservation, and use of intracytoplasmic sperm injection influence delivery rate. Increasing numbers of oocytes retrieved showed a trend but was not an independent predictor. CONCLUSION(S): Optimal numbers of blastocyst stage embryos to transfer in first cycles for women 38 to 39 years old differ from those in women >or=40 years. Number transferred should be modified as determined by a model that includes availability of excess embryos to cryopreserve, use of intracytoplasmic sperm injection, and, possibly, number of oocytes retrieved.

Optimizing the number of cleavage stage embryos to transfer on day 3 in women 38 years of age and older: a Society for Assisted Reproductive Technology database study.

OBJECTIVE: To determine the optimal number of day 3 embryos to transfer in women >or=38 years by conducting an evidence-based evaluation. DESIGN: Retrospective analysis of 2000-2004 national SART data. SETTING: National writing group. PATIENT(S): A total of 36,103 day 3 embryo transfers in women >or=38 years undergoing their first assisted reproductive technology cycle. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Logistic regression was used to model the probability of pregnancy, delivery, and multiple births (twin or high order) based on age- and cycle-specific parameters. RESULT(S): Pregnancy rates, delivery rates, and multiple rates increased up to transfer of three embryos in 38-year-olds and four in 39-year-olds; beyond this number, only multiple rates increased. In women >or=40 years, delivery rates and multiple rates climbed steadily with increasing numbers transferred. Multivariate analysis confirmed the statistically significant effect of age, number of oocytes retrieved, and embryo cryopreservation on delivery and multiple rates. Maximum FSH level was not an independent predictor by multivariate analysis. Use of intracytoplasmic sperm injection was associated with lowered delivery rate. CONCLUSION(S): No more than three or four embryos should be transferred in 38- and 39-year-olds, respectively, whereas up to five embryos could be transferred in >or=40-year-olds. Numbers of embryos to transfer should be adjusted according to number of oocytes retrieved and availability of excess embryos for cryopreservation.

Oxidative stress and antioxidants: exposure and impact on female fertility.

BACKGROUND: Reproductive failure is a significant public health concern. Although relatively little is known about factors affecting fertility and early pregnancy loss, a growing body of literature suggests that environmental and lifestyle factors play an important role. There is sufficient evidence to hypothesize that diet, particularly its constituent antioxidants, and oxidative stress (OS) may influence the timing and maintenance of a viable pregnancy. We hypothesize that conditions leading to OS in the female affect time-to-pregnancy and early pregnancy loss. METHODS: We review the epidemiology of female infertility related to antioxidant defenses and oxidation and examine potential sources of OS from the ovarian germ cell through the stages of human pregnancy and pregnancy complications related to infertility. Articles were identified through a search of the PubMed database. RESULTS: Female OS is a likely mediator of conception and threshold levels for OS exist, dependent on anatomic location and stage of preconception. CONCLUSIONS: Prospective pregnancy studies with dietary assessment and collection of biological samples prior to conception with endpoints of time-to-pregnancy and early pregnancy loss are needed.

Urodynamic leak point pressures weakly correlate with subjective urinary incontinence severity.

OBJECTIVE: To evaluate preoperative abdominal leak point pressures (ALPP) with pre- and postoperative Incontinence Severity Index (ISI) scores. METHODS: A review of women who underwent a midurethral sling procedure between August 2004 and April 2006 was conducted. Eligible women completed preoperative urodynamic testing with ALPP determination and subjective incontinence severity assessment using the ISI before and 6 weeks after surgery. The ISI and ALPP relationship was analyzed using a Spearman rank correlation (Rho). RESULTS: Ninety-nine women met the inclusion criteria. Mean ALPP was 77.7 (25-172 cm H2O). Mean improvement in ISI following surgery was 4 (-8 to 12). ALPP correlated with preoperative ISI (Spearman Rho -0.28, P=0.01), preoperative leakage frequency (ISI question 1) (Spearman Rho -0.32, P=0.001), and the ISI change 6 weeks postoperatively (ISI-delta) (Spearman Rho -0.23, P=0.002). CONCLUSION: ALPP is associated with subjective incontinence severity. Women with the lowest ALPP improved most following a midurethral sling procedure.

Effects of teamwork training on adverse outcomes and process of care in labor and delivery: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of teamwork training on the occurrence of adverse outcomes and process of care in labor and delivery. METHODS: A cluster-randomized controlled trial was conducted at seven intervention and eight control hospitals. The intervention was a standardized teamwork training curriculum based on crew resource management that emphasized communication and team structure. The primary outcome was the proportion of deliveries at 20 weeks or more of gestation in which one or more adverse maternal or neonatal outcomes or both occurred (Adverse Outcome Index). Additional outcomes included 11 clinical process measures. RESULTS: A total of 1,307 personnel were trained and 28,536 deliveries analyzed. At baseline, there were no differences in demographic or delivery characteristics between the groups. The mean Adverse Outcome Index prevalence was similar in the control and intervention groups, both at baseline and after implementation of teamwork training (9.4% versus 9.0% and 7.2% versus 8.3%, respectively). The intracluster correlation coefficient was 0.015, with a resultant wide confidence interval for the difference in mean Adverse Outcome Index between groups (-5.6% to 3.2%). One process measure, the time from the decision to perform an immediate cesarean delivery to the incision, differed significantly after team training (33.3 minutes versus 21.2 minutes, P=.03). CONCLUSION: Training, as was conducted and implemented, did not transfer to a detectable impact in this study. The Adverse Outcome Index could be an important tool for comparing obstetric outcomes within and between institutions to help guide quality improvement. CLINICAL TRIAL REGISTRATION: (www.ClinicalTrials.gov), NCT00381056 LEVEL OF EVIDENCE: I.

Impact of subgroup analysis on estimates of infertility.

Conclusions regarding estimates of infertility may reflect study bias based on the definition of infertility used. Careful consideration of how the infertile population is defined, as well its use in subgroup analysis that may not be generalizable to the population of infertile women as a whole, is needed.