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Research Question: Can an empathic physician phone call in the interval between embryo transfer and first serum human chorionic gonadotrophin measurement decrease anxiety and distress amongst patients undergoing IVF?, Design: This was a randomized controlled trial at a single academically-affiliated fertility centre including patients aged 18-43 undergoing their first embryo transfer with autologous fresh or euploid cryopreserved embryos following preimplantation genetic testing for aneuploidies (frozen embryo transfer, FET/PGT-A). After embryo transfer, participants were randomized to a 5-minute scripted phone call (intervention) from a single physician 3-4 days after embryo transfer or to routine care. The primary and secondary outcomes included were change in State-Trait Anxiety Inventory (STAI) and Hospital Anxiety and Depression Scale (HADS) scores from the start of IVF stimulation to 8-9 days after embryo transfer, respectively., Results: A total of 231 participants (164 fresh, 67 FET/PGT-A) were randomized to intervention (n = 116) or routine care (n = 115). While mean STAI and HADS scores increased in both groups, the intervention group experienced lower mean increases than the routine care group for both the STAI (3.3 [0.97] versus 7.8 [1.10], respectively; P = 0.002) and the HADS (0.3 [0.44] versus 2.4 [0.53], respectively; P = 0.003). Most participants in the intervention group found the call helpful (91.4%) and reported that it decreased distress and anxiety (81%)., Conclusions: A brief empathic phone call from a physician during the waiting period resulted in significantly lower self-reported levels of patient anxiety and distress. As the intervention in this study averaged 5 min, implementing this in clinical practice would not be onerous and may ease the distress associated with the waiting period., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: To determine whether younger oocyte donor age is associated with better outcomes after in vitro fertilization (IVF) compared with older oocyte donor age., Design: A retrospective cohort study., Setting: Large academically affiliated infertility treatment center., Patients: We included all women ≥ 18 years who started their first fresh cycle using donor oocytes at our center from January 2002 through October 2017; only the first oocyte recipient cycle was analyzed., Intervention: Log-binomial regression was used to compare the incidence of clinical pregnancy and live birth among the following donor age groups: < 25 years, 25 to < 30 years, and 30 to <35 years., Main Outcome Measure: Incidence of clinical pregnancy and live birth among donor age groups., Results: We included 774 donor cycles; 269 (34.8%) used donors < 25 years, 399 (51.6%) used donors 25 to < 30 years, and 106 (13.7%) used donors 30 to < 35 years. Median donor age was 26 years (range 18-34.5), and median recipient age and partner age were both 42 years. Per cycle start, after adjusting for recipient age, cycles using donors < 25 years were not associated with a higher incidence of clinical pregnancy (RR 0.90; 95% CI 0.77-1.06) or live birth (RR 0.87; 95% CI 0.72-1.04) compared with donors age 25-< 30 years., Conclusions: Donor age < 25 was not associated with better outcomes after IVF. Under the age of 30, the prioritization of <25 year old donors may not be recommended given the lack of evidence for superior pregnancy or live birth outcomes.

Our objective was to determine if a correlation exists between endometrial thickness measured on the day of ovulation trigger during an in vitro fertilization (IVF) cycle and pregnancy outcomes among non-cancelled cycles. We performed a retrospective cohort study looking at 6331 women undergoing their first, fresh autologous IVF cycle from 1 May 2004 to 31 December 2012 at Boston IVF (Waltham, MA). Our primary outcome was the risk ratio (RR) of live birth and positive β-hCG. We found that thicker endometrial linings were associated with positive β-hCG and live birth rates. For each additional millimetre of endometrial thickness, we found a statistically significant increased risk of positive β-hCG (adjusted RR: 1.14; 95% CI: 1.09-1.18) and live birth (RR: 1.08; 95% CI: 1.05-1.11). There was no association between endometrial thickness and miscarriage (RR: 0.99; 95% CI: 0.91-1.07). Similar results were seen when categorizing endometrial thickness. Compared with an endometrial thickness >7 to <11 mm, the likelihood of a live birth was significantly higher for an endometrial thickness ≥11 mm (adjusted RR: 1.23; 95% CI: 1.11-1.37) and significantly lower for the ≤7 mm group (adjusted RR: 0.64; 95% CI: 0.45-0.90). In conclusion, thicker endometrial linings were associated with increased pregnancy and live birth rates.

Objective: To study the reason(s) why insured patients discontinue in vitro fertilization (IVF) before achieving a live birth., Design: Cross-sectional study., Setting: Private academically affiliated infertility center., Patient(s): A total of 893 insured women who had completed one IVF cycle but did not return for treatment for at least 1 year and who had not achieved a live birth were identified; 312 eligible women completed the survey., Intervention(s): None., Main Outcome Measure(s): Reasons for treatment termination., Result(s): Two-thirds of the participants (65.2%) did not seek care elsewhere and discontinued treatment. When asked why they discontinued treatment, these women indicated that further treatment was too stressful (40.2%), they could not afford out-of-pocket costs (25.1%), they had lost insurance coverage (24.6%), or they had conceived spontaneously (24.1%). Among those citing stress as a reason for discontinuing treatment (n = 80), the top sources of stress included already having given IVF their best chance (65.0%), feeling too stressed to continue (47.5%), and infertility taking too much of a toll on their relationship (36.3%). When participants were asked what could have made their experience better, the most common suggestions were evening/weekend office hours (47.4%) and easy access to a mental health professional (39.4%). Of the 34.8% of women who sought care elsewhere, the most common reason given was wanting a second opinion (55.7%)., Conclusion(s): Psychologic burden was the most common reason why insured patients reported discontinuing IVF treatment. Stress reduction strategies are desired by patients and could affect the decision to terminate treatment., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to determine the effect of alcohol consumption on outcomes among women undergoing in vitro fertilization (IVF)., Design: This study is a retrospective cohort study., Setting: This study was performed in a private academically affiliated IVF center., Patients: Patients included women presenting for their first IVF cycle from July 2004 through October 2012., Intervention: Women completed self-administered questionnaires before their first IVF cycle, which included report of usual alcohol consumption. Women were categorized as non-drinkers, social drinkers, or daily drinkers, as well as by the number of drinks consumed per week. Competing risks analysis was used to calculate the cumulative incidence of live birth after 6 cycles stratified by alcohol consumption., Main Outcome Measures: Main outcome measures included spontaneous abortion, clinical pregnancy, and live birth following IVF., Results: There were 591 (27.7%) non-drinkers, 1466 (68.7%) social drinkers, and 77 (3.6%) daily drinkers (total n = 2134). In the first cycle, compared to non-drinkers, daily drinkers had a twofold increased risk of spontaneous abortion (adjusted risk ratio [aRR] 2.2; 95% confidence interval [CI] 1.1-4.5) among all cycle starts, and while their risk of live birth was 30% lower (aRR 0.7; 95% CI 0.4-1.3), the sample size was small, and it was not significantly lower. By the end of 6 cycles, social drinkers and daily drinkers did not differ from non-drinkers in their cumulative incidence of live birth (56.1, 50.6, and 52.1%, respectively; both P ≥ 0.28)., Conclusion: There was a trend towards lower risk of live birth among daily drinkers. Daily drinkers had an increased risk of spontaneous abortion in the first cycle, but the number of daily drinkers was small.

Purpose: This retrospective cohort study aimed to determine whether age influences treatment discontinuation among insured patients undergoing in vitro fertilization (IVF). We hypothesized that the youngest patients would be the least likely to discontinue treatment., Methods: All women age 18-42 who underwent their first fresh, non-donor IVF cycle from 2002 to 2013 were followed until a live birth was achieved, until they discontinued treatment at our center (not presenting for treatment for a one-year period), or until they completed six fresh or frozen embryo transfer cycles, whichever occurred first., Results: Of 11,361 women included, 4336 (38.2 %) discontinued treatment at our center before achieving a live birth or undergoing six IVF cycles. Discontinuation differed by age for cycles 2-4 (all P ≤ 0.004), with the proportion among women age 40-42 averaging 6-7 % higher than the other groups; discontinuation per cycle was similar among women <30 compared to women age 30-<35 and 35-<40. This continued in cycles 5 and 6, and in the sixth, 35.2, 32.0, 32.3, and 40.2 % of women among the four age groups discontinued treatment, respectively (P = 0.17). In cycles 2-5, women in the oldest two age groups with secondary infertility consistently discontinued treatment more frequently than those with primary infertility., Conclusions: We found that women in the oldest age group were more likely to discontinue IVF treatment than younger women. Surprisingly, we found that the youngest women discontinued treatment in a similar fashion to women age 30-<40.

Background: It is unknown whether certain factors are associated with the success of in vitro fertilization (IVF) in women with inflammatory bowel disease (IBD)., Aim: This study assessed whether certain characteristics are associated with greater success of live birth following IVF., Methods: In a cohort study of 8684 women with IBD seen at two tertiary care centers, we identified 121 women with IBD who underwent IVF. We assessed the effect of numerous factors on likelihood of achieving live birth after IVF., Results: Seventy-one patients with ulcerative colitis (UC) and 49 patients with Crohn's disease (CD) were analyzed. Patients with UC who achieved a live birth were younger (p = 0.03), had a shorter duration of disease (p = 0.01), and were more likely to be in remission (p = 0.03) versus those who did not achieve live birth. Patients with CD who achieved live birth were younger (p < 0.001), had lower body mass index (BMI) (p = 0.02), and had lower cycle day 3 follicle-stimulating hormone levels (p = 0.02). There was no difference in likelihood of achieving live birth among patients in remission and those with mild or unknown disease status (p = 0.69), though most CD patients (79.5 %) were in remission. Prior surgery was not associated with live birth in patients with UC (p = 0.31) or CD (p = 0.62)., Conclusions: As in the general infertility population, younger patients and those with lower BMI were more likely to achieve live birth. History of surgery was not associated with live birth among IBD patients. This is important information for practitioners counseling IBD patients.

Background: Evidence from both animal and human studies suggests that exposure to phthalates may be associated with adverse female reproductive outcomes., Objective: We evaluated the associations between urinary concentrations of phthalate metabolites and outcomes of assisted reproductive technologies (ART)., Methods: This analysis included 256 women enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2004-2012) who provided one to two urine samples per cycle before oocyte retrieval. We measured 11 urinary phthalate metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), monocarboxyisooctyl phthalate (MCOP), monocarboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate (MCPP)]. We used generalized linear mixed models to evaluate the association of urinary phthalate metabolites with in vitro fertilization (IVF) outcomes, accounting for multiple IVF cycles per woman., Results: In multivariate models, women in the highest as compared with lowest quartile of MEHP, MEHHP, MEOHP, MECPP, ΣDEHP (MEHP + MEHHP + MEOHP + MECPP), and MCNP had lower oocyte yield. Similarly, the number of mature (MII) oocytes retrieved was lower in the highest versus lowest quartile for these same phthalate metabolites. The adjusted differences (95% CI) in proportion of cycles resulting in clinical pregnancy and live birth between women in the fourth versus first quartile of ΣDEHP were -0.19 (-0.29, -0.08) and -0.19 (-0.28, -0.08), respectively, and there was also a lower proportion of cycles resulting in clinical pregnancy and live birth for individual DEHP metabolites., Conclusions: Urinary concentrations of DEHP metabolites were inversely associated with oocyte yield, clinical pregnancy, and live birth following ART., Citation: Hauser R, Gaskins AJ, Souter I, Smith KW, Dodge LE, Ehrlich S, Meeker JD, Calafat AM, Williams PL, for the EARTH Study Team. 2016. Urinary phthalate metabolite concentrations and reproductive outcomes among women undergoing in vitro fertilization: results from the EARTH study. Environ Health Perspect 124:831-839; http://dx.doi.org/10.1289/ehp.1509760.

Introduction: Limited evidence suggests that male exposure to ubiquitous environmental phthalates may result in poor reproductive outcomes among female partners., Methods: This analysis included male-female couples undergoing in vitro fertilization (IVF) and/or intrauterine insemination (IUI). We evaluated associations between the geometric mean of paternal specific gravity-adjusted urinary phthalate concentrations prior to the female partners' cycle and fertilization, embryo quality, implantation, and live birth using generalized linear mixed models., Results: Two-hundred eighteen couples underwent 211 IVF and 195 IUI cycles. Trends were observed between paternal urinary mono-3-carboxypropyl phthalate (MCPP; P=0.01) and mono(carboxyoctyl) phthalate (MCOP; P=0.01) and decreased odds of implantation. MCPP and MCOP were also associated with decreased odds of live birth following IVF (P=0.01 and P=0.04, respectively), and monobutyl phthalate above the first quartile was significantly associated with decreased odds of live birth following IUI (P=0.04). However, most urinary phthalate metabolites were not associated with these reproductive outcomes., Conclusion: Selected phthalates were associated with decreased odds of implantation and live birth., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study is to evaluate the outcomes of in vitro fertilization (IVF), including cumulative live birth rate, among women <25 years, 25 to <30 years, and 30 to <35 years., Methods: A retrospective cohort study of all women 18 to <35 years of age at their first fresh-embryo, non-donor IVF cycle from January 1995 through December 2012 at a single center was conducted. A competing-risk regression model was used to estimate the cumulative probability and 95 % confidence interval (CI) of the first live birth in up to 6 cycles during the study period with IVF cycle number as the time metric., Results: Among 7243 women who underwent 16,792 cycles, there were 163 (2.3 %) women <25 years, 1691 (23.3 %) women 25 to <30 years, and 5389 (74.4 %) women 30 to <35 years. Women <25 years had the lowest cumulative live birth rate after each cycle, followed by women 30 to <35 years. In both groups, the cumulative live birth rate after 6 cycles was significantly lower than that of women 25 to <30 years; these rates were 58 % (95 % CI 0.51-0.66) among women <25 years, 69 % (95 % CI 0.67-0.71) among women 25 to <30 years, and 64 % (95 % CI 0.63-0.65) among women 30 to <35 years., Conclusions: Our findings are consistent with other reports of less favorable IVF treatment outcomes in women <25 years of age following their first IVF cycle. This indicates that there are underlying factors in couples with a female <25 years of age that should lead to different treatment counseling when they attempt IVF.

Background & Aims: Inflammatory bowel disease (IBD) affects women of reproductive age, so there are concerns about its effects on fertility. We investigated the success of in vitro fertilization (IVF) in patients with IBD compared with the general (non-IBD) IVF population., Methods: We conducted a matched retrospective cohort study of female patients with IBD who underwent IVF from 1998 through 2011 at 2 tertiary care centers. Patients were matched 4:1 to those without IBD (controls). The primary outcome was the cumulative rate of live births after up to 6 cycles of IVF. Secondary outcomes included the proportion of patients who became pregnant and the rate of live births for each cycle., Results: Forty-nine patients with Crohn's disease (CD), 71 patients with ulcerative colitis (UC), 1 patient with IBD-unclassified, and 470 controls underwent IVF during the study period. The cumulative rate of live births was 53% for controls, 69% for patients with UC (P = .08 compared with controls), and 57% for patients with CD (P = .87 compared with controls). The incidence of pregnancy after the first cycle of IVF was similar among controls (40.9%), patients with UC (49.3%; P = .18), and patients with CD (42.9%; P = .79). Similarly, the incidence of live births after the first cycle of IVF was similar among controls (30.2%), patients with UC (33.8%; P = .54), and patients with CD (30.6%; P = .95)., Conclusions: Based on a matched cohort study, infertile women with IBD achieve a rate of live births after IVF that is comparable with those of infertile women without IBD., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Women with ulcerative colitis (UC), who require ileal pouch anal anastomosis (IPAA), have up to a threefold increased incidence of infertility. To better counsel patients who require colectomy, we examined the success rates of in vitro fertilization (IVF) among women who have undergone IPAA., Methods: This was a retrospective cohort study conducted at the Brigham and Women's Hospital and Beth Israel Deaconess Medical Center. Female patients with UC were identified via ICD-9 codes and cross-referenced with those presenting for IVF from 1998 through 2011. UC patients with IPAA were compared with the following two unexposed groups that underwent IVF: (1) patients with UC, who had not undergone IPAA, and (2) patients without inflammatory bowel disease (IBD). The primary outcome was the cumulative live birth rate. Secondary outcomes included number of oocytes retrieved, proportion of patients who underwent embryo transfer, pregnancy rate, and live birth rate at first cycle., Results: There were 22 patients with UC and IPAA, 49 patients with UC and without IPAA, and 470 patients without IBD. The cumulative live birth rate after six cycles in the UC and IPAA groups was 64% (95% confidence interval (CI): 44-83%). This rate did not differ from the cumulative live birth rate in the UC without IPAA group (71%, 95% CI: 59-83%; P=0.63) or the group without IBD (53%, 95% CI: 48-57%; P=0.57)., Conclusions: This study demonstrates that in our cohort, women who undergo IPAA achieve live births following IVF at comparable rates to women with UC without IPAA and to women without IBD.

Objective: To estimate the cumulative probability of liveborn multiples after IVF to improve patient counseling regarding this significant morbidity., Design: Retrospective cohort study., Setting: Large academic-affiliated infertility practice., Patient(s): A total of 10,169 women were followed from their first fresh, nondonor IVF cycle through up to six fresh and frozen IVF cycles from 2000-2010., Intervention(s): None., Main Outcome Measure(s): Delivery of a liveborn infant(s)., Result(s): After three IVF cycles the cumulative live birth rate (CLBR) was 53.2%. The singleton, twin, and triplet CLBRs were 38.0%, 14.5%, and 0.7%. After six IVF cycles the CLBR was 73.8%, with 52.8%, 19.8%, 1.3% for singletons, twins, and triplets. Of the 5,433 live births, 71.4% were singletons, 27.1% were twins, and 1.5% were triplets. Women more than 39 years had the lowest incidence of liveborn multiples with CLBRs of 5.2% after three cycles and 9.5% after six cycles. The twin CLBR doubled from cycles 1 through 3 with the rate of increase slowing from cycles 3 through 6. Although very low in absolute terms, the triplet CLBR also doubled from cycles 1 through 3 and doubled again from cycles 3 through 6. Of the 1,970 pregnancies that began as multifetal on ultrasound, 77.4% resulted in liveborn multiples., Conclusion(s): Providers should be aware of the cumulative probability of liveborn multiples to effectively counsel patients on this important issue. With nearly three-quarters of all women having live birth after up to six IVF cycles, it is encouraging to report a low incidence of liveborn multiples., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To report and evaluate the performance and utility of an approach to predicting IVF-double embryo transfer (DET) multiple birth risks that is evidence-based, clinic-specific, and considers each patient's clinical profile., Design: Retrospective prediction modeling., Setting: An outpatient university-affiliated IVF clinic., Patient(s): We used boosted tree methods to analyze 2,413 independent IVF-DET treatment cycles that resulted in live births. The IVF cycles were retrieved from a database that comprised more than 33,000 IVF cycles., Intervention(s): None., Main Outcome Measure(s): The performance of this prediction model, MBP-BIVF, was validated by an independent data set, to evaluate predictive power, discrimination, dynamic range, and reclassification., Result(s): Multiple birth probabilities ranging from 11.8% to 54.8% were predicted by the model and were significantly different from control predictions in more than half of the patients. The prediction model showed an improvement of 146% in predictive power and 16.0% in discrimination over control. The population standard error was 1.8%., Conclusion(s): We showed that IVF patients have inherently different risks of multiple birth, even when DET is specified, and this risk can be predicted before ET. The use of clinic-specific prediction models provides an evidence-based and personalized method to counsel patients., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)