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Objective: To determine if transferring a lower-quality embryo with a good-quality blastocyst is detrimental, given that evidence suggests that embryos can signal the endometrium and that embryo quality may affect negatively endometrial receptivity., Design: Retrospective cohort study., Setting: In vitro fertilization center., Intervention(s): Single- versus double-embryo transfer., Patient(s): Patients with a double-embryo transfer of a good-quality blastocyst plus a lower-quality blastocyst, early blastocyst, or morula were compared with patients receiving a single good-quality blastocyst., Main Outcome Measure(s): Live birth, multiple gestation., Result(s): In this study, 4,640 in vitro fertilization cycles were analyzed. In none of the analyses did transferring a second lower-quality embryo negatively affect birth rate. In the primary analysis, transferring a second lower-quality embryo increased live birth by 10% and the multiple birth rate by 15%. The addition of a fair- or poor-quality blastocyst or early blastocyst markedly increased the twin birth rate by 22%-27% with an 8%-12% increase in live birth. The addition of a morula did not increase live birth but resulted in 12% more multiples. In women younger than 38 years, adding a lower-quality embryo increased the birth rate by 7% but resulted in 18% increase in multiples. In women 38 years or older, adding a lower-quality embryo increased the live birth rate by 9% with a 15% increase in multiples., Conclusion(s): Addition of a lower-quality embryo does not have a detrimental effect on a good-quality blastocyst and results in a small increase in live births. However, this is at the expense of a marked increase in the likelihood of multiple gestations., (Published by Elsevier Inc.)

Objective: To compare live birth and multiple gestation in patients diagnosed with unexplained infertility undergoing intrauterine insemination after ovarian stimulation (OS-IUI) with oral medications versus gonadotropins., Design: Systemic review and meta-analysis., Setting: Not applicable., Patient(s): Patients undergoing OS-IUI for treatment of unexplained infertility., Intervention(s): Clomiphene, letrozole, or gonadotropins for OS-IUI., Main Outcome Measure(s): Live birth and multiple gestation., Result(s): Eight total trials were identified that met the inclusion criteria and comprised 2,989 patients undergoing 6,590 cycles. One study reported a significant increase in both live births and multiple gestations with the use of gonadotropins, two studies found an increased likelihood of live birth with the use of gonadotropins, and two studies found an increased risk of twins with gonadotropins. The relative risk of live birth in subjects receiving gonadotropins was 1.09. The relative risk of multiple gestation in subjects receiving gonadotropins was 1.06. Clinical pregnancy was higher in protocols with lax cancellation policies or higher gonadotropin doses, with subsequent increased relative risks of multiple gestations of 1.20 and 1.15, respectively. Singleton births per subject were similar between the two groups. The results did not change in per-protocol, per cycle, or fixed-effect model sensitivity analyses., Conclusion(s): For every birth gained with the use of gonadotropins, a similar increased risk of multiple gestation occurs. The randomized data do not support the use of gonadotropin for OS-IUI in women with unexplained infertility., Clinical Trial Registration Number: Prospero CRD4201911998., (Published by Elsevier Inc.)

Context: Adequate luteal phase progesterone exposure is necessary to induce endometrial changes required for a successful pregnancy outcome. The relationship between low midluteal progesterone concentration and the outcome of live birth in ovarian stimulation with intrauterine insemination (OS-IUI) treatments is not defined., Objective: To determine the level of midluteal progesterone portending a low chance of live birth after OS-IUI in couples with unexplained infertility., Design and Setting: Secondary analyses of data from a prospective, randomized, multicenter clinical trial that determined pregnancy outcomes following OS-IUI with clomiphene citrate, letrozole, or gonadotropins for couples with unexplained infertility., Participants: Couples (n = 900) underwent 2376 OS-IUI cycles during the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation clinical trial., Main Outcome Measures: Live birth as it relates to midluteal progesterone level and thresholds below which no live births occur by treatment group., Results: Thresholds for non-live birth cycles were similar for clomiphene (14.4 ng/mL) and letrozole (13.1 ng/mL) yet were lower for gonadotropin (4.3 ng/mL) treatments. A midluteal progesterone level >10th percentile specific for each treatment group independently was associated with greater odds for a live birth in all OS-IUI cycles (adjusted OR: 2.17; 95% CI: 1.05, 4.48)., Conclusions: During OS-IUI, a low midluteal progesterone level was associated with a low probability of live birth. Thresholds differed by medication, with the lowest threshold for gonadotropin. Several pathophysiologic mechanisms may account for low progesterone levels. Refinement of the predictive range associated with particular ovarian stimulation medications during treatment of unexplained infertility may improve accuracy.

Purpose of Review: The purpose of the current review is to describe the common pitfalls in design and statistical analysis of reproductive medicine studies. It serves to guide both authors and reviewers toward reducing the incidence of spurious statistical results and erroneous conclusions., Recent Findings: The large amount of data gathered in IVF cycles leads to problems with multiplicity, multicollinearity, and over fitting of regression models. Furthermore, the use of the word 'trend' to describe nonsignificant results has increased in recent years. Finally, methods to accurately account for female age in infertility research models are becoming more common and necessary., Summary: The pitfalls of study design and analysis reviewed provide a framework for authors and reviewers to approach clinical research in the field of reproductive medicine. By providing a more rigorous approach to study design and analysis, the literature in reproductive medicine will have more reliable conclusions that can stand the test of time.

Objective: To evaluate the effect of progesterone (P) for luteal phase support after ovulation induction (OI) and intrauterine insemination (IUI)., Design: An updated systematic review and meta-analysis., Setting: Not applicable., Patient(s): Patients undergoing OI-IUI for infertility., Intervention(s): Exogenous P luteal support after OI-IUI., Main Outcome Measure(s): Live birth., Result(s): Eleven trials were identified that met inclusion criteria and constituted 2,842 patients undergoing 4,065 cycles, more than doubling the sample size from the previous meta-analysis. In patients receiving gonadotropins for OI, clinical pregnancy (relative risk [RR] 1.56, 95% confidence interval [CI] 1.21-2.02) and live birth (RR 1.77, 95% CI 1.30-2.42) were more likely in P supplemented patients. These findings persisted in analysis of live birth per IUI cycle (RR 1.59, 95% CI 1.24-2.04). There were no data on live birth in clomiphene citrate or clomiphene plus gonadotropin cycles. There was no benefit on clinical pregnancy with P support for patients who underwent OI with clomiphene (RR 0.85, 95% CI 0.52-1.41) or clomiphene plus gonadotropins (RR 1.26, 95% CI 0.90-1.76)., Conclusion(s): Progesterone luteal phase support is beneficial to patients undergoing ovulation induction with gonadotropins in IUI cycles. The number needed to treat is 11 patients to have one additional live birth. Progesterone support did not benefit patients undergoing ovulation induction with clomiphene citrate or clomiphene plus gonadotropins., (Published by Elsevier Inc.)

Objective: To critically evaluate the P to oocyte (O) ratio (P/O) in the prediction of live birth in assisted reproductive technology (ART) cycles., Design: Retrospective cohort study., Setting: Not applicable., Patient(s): A total of 7,608 fresh autologous ART ET cycles., Intervention(s): None., Main Outcome Measure(s): Live birth., Result(s): Generalized estimating equation (GEE) models and receiver operating characteristic curves assessed the ability of P, O, and the P/O ratio to predict live birth. In univariate GEE models, P, O, and P/O were each associated with live birth. However, in multivariate GEE models, the P/O ratio was not associated with live birth, but P alone was. This suggested that converting P and O into a ratio of P/O was not more helpful than the two independent variables themselves. Measures of overall model fit further suggested that P/O did not increase the predictive ability of the model over P and O alone. Receiver operating characteristic curves using incremental predictors further demonstrated that the P/O provided no incremental improvement in predicting live birth over P and O separately., Conclusion(s): These data suggest that P and O have utility in prediction modeling but demonstrate that additional oocytes were not protective from the negative association of P with live birth. There was no incremental improvement related to the P/O ratio specifically for predicting live birth over each variable independently., (Published by Elsevier Inc.)

Objective: To compare the effect of P on live birth rate between hCG and GnRH agonist (GnRH-a) trigger cycles., Design: Retrospective cohort study., Setting: Large private assisted reproductive technology (ART) practice., Patient(s): A total of 3,326 fresh autologous ART cycles., Intervention(s): None., Main Outcome Measure(s): Live birth., Result(s): A total of 647 GnRH-a trigger cycles were compared with 2,679 hCG trigger cycles. Live birth was negatively associated with P in both the hCG trigger (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.52-0.76) and the agonist trigger cohorts (OR 0.56, 95% CI 0.45-0.69). Interaction testing evaluating P and trigger medication was not significant, indicating that P had a similar negative effect on live birth rates in both cohorts. Progesterone ≥2 ng/mL occurred more commonly in GnRH-a trigger cycles compared with hCG trigger cycles (5.5% vs. 3.1%) and was negatively associated with live birth in both the hCG trigger (OR 0.28, 95% CI 0.11-0.73) and agonist trigger cohorts (OR 0.35, 95% CI 0.14-0.90). When P ≥2 ng/mL, the live birth rates were poor and similar in the hCG and GnRH-a cohorts (5.9% vs. 14.2%), indicating that P ≥2 ng/mL had a similar negative effect on live birth in both cohorts., Conclusion(s): Elevated serum P on the day of hCG was negatively associated with live birth rates in both hCG and GnRH-a trigger cycles., (Published by Elsevier Inc.)

Objective: To evaluate whether intracytoplasmic sperm injection (ICSI) use and E2 on the final day of assisted reproductive technology (ART) stimulation are associated with adverse obstetric complications related to placentation., Design: Retrospective cohort study., Setting: Large private ART practice., Patient(s): A total of 383 women who underwent ART resulting in a singleton live birth., Intervention(s): None., Main Outcome Measure(s): Adverse placental outcomes composed of placenta accreta, placental abruption, placenta previa, intrauterine growth restriction, preeclampsia, gestational hypertension, and small for gestational age infants., Result(s): Patients with adverse placental outcomes had higher peak serum E2 levels and were three times more likely to have used ICSI. Adverse placental outcomes were associated with increasing E2 (odds ratio 1.36, 95% confidence interval 1.13-1.65) and ICSI (odds ratio 3.86, 95% confidence interval 1.61-9.27). Adverse outcomes increased when E2 was >3,000 pg/mL and continued to increase in a linear fashion until E2 was >5,000 pg/mL. The association of ICSI with adverse outcomes was independent of male factor infertility. Interaction testing suggested the adverse effect of E2 was primarily seen in ICSI cycles, but not in conventional IVF cycles. Estradiol >5,000 pg/mL was associated with adverse placental events in 36% of all ART cycles and 52% of ICSI cycles., Conclusion(s): ICSI and elevated E2 on the day of hCG trigger were associated with adverse obstetric outcomes related to placentation. The finding of a potential interaction of E2 and ICSI with adverse placental events is novel and warrants further investigation., (Published by Elsevier Inc.)

Objective: To compare the effect of progesterone (P) on the day of trigger in fresh assisted reproduction technology (ART) transfer cycles versus its effect on subsequent frozen embryo transfer (FET) cycles., Design: Retrospective cohort study., Setting: Large private ART practice., Patient(s): Fresh autologous and FET cycles from 2011-2013., Intervention(s): None., Main Outcome Measure(s): Live birth., Result(s): A paired analysis of patients who underwent both a fresh transfer and subsequent FET cycle and an unpaired analysis of data from all fresh transfer cycles and all FET cycles were performed. We analyzed 1,216 paired and 4,124 unpaired cycles, and P was negatively associated with birth in fresh but not FET cycles in all analyses. Interaction testing of P and cycle type indicated P had a different association with birth in fresh versus FET cycles. When P was ≥ 2 ng/mL at the time of trigger, live birth was more likely in FET versus fresh cycles in the paired analysis (47% vs. 10%), in the unpaired analysis (51% vs. 14%), and in unpaired, good blastocyst only transfer subgroup (51% vs. 29%). Live birth was similar in FET cycles, with P ≥ 2 ng/mL versus P < 2 ng/mL (51% vs. 49%). Conversely, live birth was lower in fresh cycles, with P ≥ 2 ng/mL versus P <2 ng/mL (15% vs. 45%)., Conclusion(s): Elevated P levels on the day of trigger during the initial fresh cycle were negatively associated with live birth in the fresh transfer cycles but not in subsequent FET cycles. Freezing embryos and performing a subsequent FET cycle ameliorates the effect of elevated P on live-birth rates., (Published by Elsevier Inc.)

Objective: To summarize the available published randomized controlled trial data regarding timing of P supplementation during the luteal phase of patients undergoing assisted reproductive technology (ART)., Design: A systematic review., Setting: Not applicable., Patient(s): Undergoing IVF., Intervention(s): Different starting times of P for luteal support., Main Outcome Measure(s): Clinical pregnancy (PR) and live birth rates., Result(s): Five randomized controlled trials were identified that met inclusion criteria with a total of 872 patients. A planned meta-analysis was not performed because of a high degree of clinical heterogeneity with regard to the timing, dose, and route of P. Two studies compared P initiated before oocyte retrieval versus the day of oocyte retrieval and PRs were 5%-12% higher when starting P on the day of oocyte retrieval. One study compared starting P on day 6 after retrieval versus day 3, reporting a 16% decrease in pregnancy in the day 6 group. Trials comparing P start times on the day of oocyte retrieval versus 2 or 3 days after retrieval showed no significant differences in pregnancy., Conclusion(s): There appears to be a window for P start time between the evening of oocyte retrieval and day 3 after oocyte retrieval. Although some studies have suggested a potential benefit in delaying vaginal P start time to 2 days after oocyte retrieval, this review could not find randomized controlled trials to adequately assess this. Further randomized clinical trials are needed to better define P start time for luteal support after ART., (Published by Elsevier Inc.)

Oocyte retrieval is most safely accomplished with conscious sedation via a transvaginal approach under ultrasound guidance with low-pressure aspiration. Follicle flushing has not been shown to improve outcomes. The type of vaginal surgical preparation and the use of antibiotics have not been demonstrated to affect outcomes. As the final step in a rigorous assisted reproductive technology (ART) cycle, precise technique in embryo transfer is essential. Based on current findings, the recommended embryo transfer technique includes the use of an ultrasound-guided transcervical approach with a full bladder using a soft catheter. The transfer depth of the embryo should be in the mid-portion of the uterus with a quick steady insertion followed by pressure on the syringe during withdrawal of the catheter. It is acceptable to encourage immediate ambulation after embryo transfer., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To evaluate the effect of luteal phase P support after ovulation induction IUI., Design: A systematic review and meta-analysis., Setting: Not applicable., Patient(s): Undergoing ovulation induction IUI., Intervention(s): Any form of exogenous P in ovulation induction IUI cycles., Main Outcome Measure(s): Clinical pregnancy and live birth., Result(s): Five trials were identified that met inclusion criteria and comprised 1,298 patients undergoing 1,938 cycles. Clinical pregnancy (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.15-1.98) and live birth (OR 2.11, 95% CI 1.21-3.67) were more likely in P-supplemented patients. These findings persisted in analyses evaluating per IUI cycle, per patient, and first cycle only data. In subgroup analysis, patients receiving gonadotropins for ovulation induction had the most increase in clinical pregnancy with P support (OR 1.77, 95% CI 1.20-2.6). Conversely, patients receiving clomiphene citrate (CC) for ovulation induction showed no difference in clinical pregnancy with P support (OR 0.89, 95% CI 0.47-1.67)., Conclusion(s): Progesterone luteal phase support may be of benefit to patients undergoing ovulation induction with gonadotropins in IUI cycles. Progesterone support did not benefit patients undergoing ovulation induction with CC, suggesting a potential difference in endogenous luteal phase function depending on the method of ovulation induction., (Published by Elsevier Inc.)

The field of reproductive endocrinology and infertility (REI) is at a crossroads; there is a mismatch between demand for reproductive endocrinology, infertility and assisted reproductive technology (ART) services, and availability of care. This document's focus is to provide data justifying the critical need for increased provision of fertility services in the United States now and into the future, offer approaches to rectify the developing physician shortage problem, and suggest a framework for the discussion on how to meet that increase in demand. The Society of REI recommend the following: 1. Our field should aggressively explore and implement courses of action to increase the number of qualified, highly trained REI physicians trained annually. We recommend efforts to increase the number of REI fellowships and the size complement of existing fellowships be prioritized where possible. These courses of action include: a. Increase the number of REI fellowship training programs. b. Increase the number of fellows trained at current REI fellowship programs. c. The pros and cons of a 2-year focused clinical fellowship track for fellows interested primarily in ART practice were extensively explored. We do not recommend shortening the REI fellowship to 2 years at this time, because efforts should be focused on increasing the number of fellowship training slots (1a and b). 2. It is recommended that the field aggressively implements courses of action to increase the number of and appropriate usage of non-REI providers to increase clinical efficiency under appropriate board-certified REI physician supervision. 3. Automating processes through technologic improvements can free providers at all levels to practice at the top of their license. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the correlation of preretrieval quantitative serum hCG level with oocyte maturity. Design: Retrospective cohort study. Setting: Military assisted reproductive technology (ART) program. Patient(s): Fresh autologous ART cycles. Intervention(s): Serum hCG level the day before oocyte retrieval. Main Outcome Measure(s): Linear regression was used to correlate serum hCG levels and oocyte maturity rates. Normal oocyte maturity was defined as ≥75% and the Wilcoxon rank sum test was used to compare serum hCG levels in patients with normal and low oocyte maturity. Threshold analysis was performed to determine hCG levels that could predict oocyte maturity. Result(s): A total of 468 ART cycles were analyzed. Serum hCG level was not correlated with hCG dose; however, it was negatively correlated with body mass index (BMI). Serum hCG levels did not differ between patients with oocyte maturity of <75% and ≥75%. Serum hCG levels did not correlate with oocyte maturity rates. Receiver operator characteristic and less than efficiency curves failed to demonstrate thresholds at which hCG could predict oocyte maturity. Conclusion(s): Serum hCG levels were not correlated with oocyte maturity. Although a positive hCG was reassuring that mature oocytes would be retrieved for most patients, the specific value was not helpful. [Copyright &y& Elsevier]

Gonadotrophin-releasing hormone (GnRH) antagonist rescue is performed by replacing a GnRH agonist with a GnRH antagonist in patients with rapidly rising serum oestradiol who are at risk of ovarian hyperstimulation syndrome (OHSS) during stimulation. It results in a rapid reduction in serum oestradiol, allowing for the avoidance of cycle cancellation and the continuation of exogenous gonadotrophin administration. A total of 387 patients who underwent GnRH antagonist rescue for ovarian hyperresponse were compared with 271 patients who did not receive GnRH antagonist rescue and had oestradiol concentrations >4000 pg/ml on the day of human chorionic gonadotrophin (HCG) administration. GnRH antagonist rescue decreased the mean oestradiol concentration by 35% on the first day of use. There was no difference in oocyte maturity (82% versus 83%) or fertilization rate (69% versus 67%) between the antagonist rescue and comparison groups, respectively. The percentage of high-grade embryos on day 3 and the blastocyst development rate were also similar between groups. The live-birth rate was 41.9% in the antagonist rescue group and 36.9% in the comparison group. GnRH antagonist rescue enabled cycle completion with high live-birth rates in patients at risk for OHSS. GnRH antagonist was associated with high oocyte quality, blastocyst development and pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To determine whether a mandatory single-blastocyst transfer (mSBT) algorithm reduced multiple gestation rates without sacrificing clinical pregnancy rates.Design: Retrospective review.Setting: U.S. university-based assisted reproductive technology (ART) program.Patient(s): All women younger than 38 years undergoing their first ART cycle from 2009 to 2010 with ≥4 high-grade embryos on day 3 after oocyte retrieval (patients from 2009 were the "before" group, and patients completing ART under the mSBT policy in 2010 were the "after" group).Intervention(s): mSBT algorithm.Main Outcome Measure(s): Multiple gestation and clinical pregnancy rates.Result(s): Of the qualified patients, 136 women met inclusion criteria (62 from 2009, 74 from 2010). The baseline demographics were similar between the groups. Statistically significantly fewer blastocysts were transferred per patient in 2010 compared with 2009 (1.5 vs. 1.9). The clinical pregnancy rates before (67.7%) or after (63.5%) the mSBT policy were not statistically significantly different. Multiple gestation rates were statistically significantly reduced, from 43.8% (2009) to 14.6% (2010) after the mSBT policy was instituted. More patients from 2010 had ≥1 blastocyst cryopreserved compared with 2009 (52.9% vs. 30.6%).Conclusion(s): A novel single-blastocyst transfer algorithm reduced multiple gestation rates and improved cryopreservation rates without compromising clinical pregnancy rates in good-prognosis patients. [ABSTRACT FROM AUTHOR]

Objective: To determine whether frozen-thawed blastocyst transfer pregnancy rates (PR) are lower in African-American compared with white women.Design: Retrospective review of frozen blastocyst cycles.Setting: University-based assisted reproductive technology (ART) program.Patient(s): All patients who underwent a frozen blastocyst transfer between 2003 and 2008.Intervention: None.Main Outcome Measure(s): Live birth rate.Result(s): One hundred sixty-nine patients underwent transfer of a frozen-thawed blastocyst. African-American women had a higher incidence of leiomyoma (40% vs. 10%) and tubal and uterine factor infertility. There was no difference in the live birth rate for African-American patients (28.0%) compared with white patients (30.2%). Of the patients who underwent a frozen-thawed blastocyst transfer, 58% (n=98) had their fresh, autologous IVF cycle, which produced the cryopreserved blastocyst, at Walter Reed Medical Center. A higher peak serum E2 level was noted in African-American patients (5,355 pg/mL) compared with white patients (4,541 pg/mL). During the fresh cycle, the live birth rates between African-American and white patients were significantly different at 16.7% versus 39.7%, respectively.Conclusion(s): Live birth rates after frozen blastocyst transfer are not different between African-American and white women despite a fourfold higher incidence of leiomyomas in African-American women. [ABSTRACT FROM AUTHOR]

Objective: To analyze the sex ratio of infants born after blastocyst-stage transfer of embryos with normal preimplantation FISH genetic screening.Design: Retrospective cohort analysis.Setting: Large academic assisted reproductive technology center.Patient(s): Two hundred twenty-eight patients undergoing fresh IVF cycle with blastocyst transfer.Intervention(s): Preimplantation genetic screening for sex complement.Main Outcome Measure(s): Sex ratio in liveborn infants following blastocyst transfer.Result(s): One thousand thirteen embryos were normal by preimplantation genetic screening of chromosomes 13, 15, 16, 17, 18, 21, 22, X, and Y. Four hundred ninety-eight normal embryos were transferred to 228 patients with an overall live birth rate of 41.7%. Transferred blastocysts were selected based upon morphologic assessment. When controlling for the sex of the blastocyst embryo, there was no difference in the male-to-female delivery rate per embryo transferred (27.3% vs. 21.4%) (relative risk =1.28, confidence interval 0.93-1.74). Of the live births 51.7% were male and 48.3% were female (P=.61). Subanalysis revealed no difference in male-to-female delivery rates in groups with a 1:1 ratio of male:female embryos transferred, a non 1:1 ratio transferred, or single-sex transfers.Conclusion(s): Blastocyst-stage embryo transfer does not influence the live birth sex ratio of embryos with normal preimplantation FISH genetic screening. [ABSTRACT FROM AUTHOR]

Background: Pregnancy loss prediction based on routinely measured ultrasound characteristics is generally aimed toward distinguishing nonviability. Physicians also use ultrasound indicators for patient counseling, and in some cases to decide upon the frequency of follow-up sonograms. To improve clinical utility, allocation of cut-points should be based on clinical data for multiple sonographic characteristics, be specific to gestational week, and be determined by methods that optimize prediction.Objectives: To identify routinely measured features of the early first trimester ultrasound and the gestational age-specific cut-points that are most predictive of pregnancy loss.Materials and Methods: This was a secondary analysis of 617 pregnant women enrolled in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial; all women had 1-2 previous pregnancy losses and no documented infertility. Each participant had a single ultrasound with a detectable fetal heartbeat between 6 weeks 0 days and 8 weeks 6 days. Cut-points for low fetal heart rate and small crown-rump length were separately defined for gestational weeks 6, 7, and 8 to optimize prediction. Identity and log-binomial regression models were used to estimate absolute and relative risks, respectively, and 95% confidence intervals between jointly categorized low fetal heart rate, small crown-rump length, and clinical pregnancy loss. Adjusted models accounted for gestational age at ultrasound in weeks. Missing data were addressed using multiple imputation.Results: A total of 64 women experienced a clinical pregnancy loss following the first ultrasound (10.4%), 7 were lost to follow-up (1.1%), and 546 women (88.5%) had a live birth. Low fetal heart rate and small crown-rump length (≤122, 123, and 158 bpm; ≤6.0, 8.5, and 10.9 mm for gestational weeks 6, 7, and 8, respectively) were independent predictors of clinical pregnancy loss, with greatest risks observed for pregnancies having both characteristics (relative risk, 2.08; 95% confidence interval, 1.24-2.91). The combination of low fetal heart rate and small crown-rump length was linked to a 16% (95% confidence interval, 9.1-23%) adjusted absolute increase in risk of subsequent loss, from 5.0% (95% confidence interval, 1.5-8.5%) to 21% (95% confidence interval, 15-27%). Abnormal yolk sac diameter or the presence of a subchorionic hemmhorage did not improve prediction of clinical pregnancy loss.Conclusion: Identified cut-points can be used by physicians for patient counseling, and in some cases to decide upon the frequency of follow-up sonograms. The specified criteria should not be used to diagnose nonviability. [ABSTRACT FROM AUTHOR]

Background: Inflammation and elevated blood lipids are associated with infertility. Aspirin and statin therapy may improve infertility treatment outcomes among overweight and obese women with systemic inflammation, but little is known about the short-term effects of statins in this population. We conducted a pilot study of aspirin, pravastatin, or combined treatment among a group of overweight and obese, reproductive-aged women. Our goal was to characterize short-term changes in inflammatory and lipid biomarkers during and after treatment. Methods: In this open-label trial, women aged 18–40 years with a body mass index ≥25 kg/m2 were randomized to receive either 162 mg aspirin, 40 mg pravastatin, or both. The study medication was taken daily for 2 weeks, and participants were then followed for a two-week washout period. Participants provided blood samples at baseline, after the intervention period, and after the washout period. The outcomes were changes in biomarkers of inflammation and lipids measured in blood components at each timepoint. Results: Nine, 8, and 8 women were randomized to the aspirin, pravastatin, and combined arms, respectively. Analyses were conducted among 8, 7, and 7 women in the aspirin, pravastatin, and combined arms for whom biomarker data was available at baseline. High-sensitivity C-reactive protein (hsCRP) levels were lower after treatment in all arms and continued to decrease after washout in the pravastatin and combined arms. Results were consistent between the whole sample and women with baseline hsCRP between 2 and 10 mg/L. Low-density lipoprotein (LDL) cholesterol was lower after treatment in the pravastatin and combined arms and rose slightly after washout. Conclusions: Our results provide preliminary evidence that short-term aspirin and pravastatin therapy reduces hsCRP and LDL cholesterol among overweight and obese women of reproductive age, including those with low-grade inflammation. Because of these short-term effects, these drugs may improve infertility treatment outcomes in this population, which we will assess in a future randomized trial. [ABSTRACT FROM AUTHOR]

Objective: To evaluate similarities and differences in clinical and laboratory practices among high-performing fertility clinics.Design: Cross-sectional questionnaire study of selected programs.Setting: Academic and private fertility practices performing in vitro fertilization (IVF).Patient(s): Not applicable.Intervention(s): A comprehensive survey was conducted of 13 IVF programs performing at least 100 cycles a year and having high cumulative singleton delivery rates for 2 years.Main Outcome Measure(s): Clinical and laboratory IVF practices.Result(s): Although many areas of clinical practice varied among top programs, some commonalities were observed. All programs used a combination of follicle-stimulating hormone and luteinizing hormone for IVF stimulation, intramuscular progesterone in frozen embryo transfer cycles, ultrasound-guided embryo transfers, and a required semen analysis before starting the IVF cycle. Common laboratory practices included vitrification of embryos at the blastocyst stage, air quality control with positive air pressure and high-efficiency particulate air filtration, use of incubator gas filters, working on heated microscope stages, and incubating embryos in a low-oxygen environment, most often in benchtop incubators.Conclusion(s): Some areas of consistency in clinical and laboratory practices were noted among high-performing IVF programs that are likely contributing to their success. High-performing programs focused on singleton deliveries. As the field of IVF is rapidly evolving, it is imperative that we share best practices in an effort to improve outcomes from all clinics for the good of our patients. [ABSTRACT FROM AUTHOR]

Objective: To compare clinical and ongoing pregnancy after natural cycle (NC) intrauterine insemination (IUI) versus ovarian stimulation (OS) IUI in ovulatory women undergoing therapeutic donor insemination (TDI).Design: Retrospective cohort.Setting: Single infertility center.Patient(s): A total of 76,643 IUI cycles in patients treated with intrauterine insemination were examined. Women undergoing TDI in the absence of diagnosed female factor infertility were included.Intervention(s): NC TDI or OS TDI with either clomiphene citrate or letrozole.Main Outcome Measure(s): Clinical and ongoing pregnancies were analyzed by generalized estimating equations adjusting for age, body mass index, total motile sperm at time of insemination and cycle number. Ongoing multiple gestations were examined as a secondary outcome.Result(s): Six thousand one hundred ninety-two TDI cycles from 2,343 patients (711 patients without repeated IUI cycles) met inclusion criteria and were available for analysis (3,837 NC and 2,355 OS). There was no difference in mean age between the two groups (NC, 34.2 years vs. OS, 34.3 years). Probability of clinical and ongoing pregnancy was higher in the OS cohort compared with the NC cohort (OS, 22.4% vs. NC, 18.7% and OS, 15.4% vs. NC, 14.9%, respectively). However, OS significantly increased ongoing multiple gestations (OS, 10.8% vs. NC, 2.4%).Conclusion(s): Ovarian stimulation in TDI cycles resulted in a <4% increase in clinical and <1% increase in ongoing pregnancy, and more than fourfold increase in ongoing multiple gestations. Natural cycle IUI should be considered as a first-line treatment for ovulatory women who need donor insemination. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether intracytoplasmic sperm injection (ICSI) use and E2 on the final day of assisted reproductive technology (ART) stimulation are associated with adverse obstetric complications related to placentation.Design: Retrospective cohort study.Setting: Large private ART practice.Patient(s): A total of 383 women who underwent ART resulting in a singleton live birth.Intervention(s): None.Main Outcome Measure(s): Adverse placental outcomes composed of placenta accreta, placental abruption, placenta previa, intrauterine growth restriction, preeclampsia, gestational hypertension, and small for gestational age infants.Result(s): Patients with adverse placental outcomes had higher peak serum E2 levels and were three times more likely to have used ICSI. Adverse placental outcomes were associated with increasing E2 (odds ratio 1.36, 95% confidence interval 1.13-1.65) and ICSI (odds ratio 3.86, 95% confidence interval 1.61-9.27). Adverse outcomes increased when E2 was >3,000 pg/mL and continued to increase in a linear fashion until E2 was >5,000 pg/mL. The association of ICSI with adverse outcomes was independent of male factor infertility. Interaction testing suggested the adverse effect of E2 was primarily seen in ICSI cycles, but not in conventional IVF cycles. Estradiol >5,000 pg/mL was associated with adverse placental events in 36% of all ART cycles and 52% of ICSI cycles.Conclusion(s): ICSI and elevated E2 on the day of hCG trigger were associated with adverse obstetric outcomes related to placentation. The finding of a potential interaction of E2 and ICSI with adverse placental events is novel and warrants further investigation. [ABSTRACT FROM AUTHOR]