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.

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.