IMPACT OF TIME INTERVAL FROM CESAREAN DELIVERY TO FROZEN EMBRYO TRANSFER ON REPRODUCTIVE AND NEONATAL OUTCOMES.

OBJECTIVE: To evaluate differences in reproductive and neonatal outcomes based on the time interval from cesarean delivery to subsequent frozen embryo transfer (FET) DESIGN: Retrospective cohort SUBJECTS: Women undergoing autologous elective single embryo transfer (eSET) FET following prior cesarean delivery EXPOSURE: Time from prior cesarean delivery to subsequent FET MAIN OUTCOME MEASURES: Live birth RESULTS: A total of 6,556 autologous eSET FET cycles were included. FET cycles were divided into eight groups based on the time interval from prior cesarean delivery to subsequent FET in months. Time was also evaluated as a continuous variable. The proportion of live births did not differ significantly across all time interval groups and over continuous time (range: 40.0% - 45.6%, adjusted (adj) p = 0.572, continuous adj p = 0.599). Mean gestational age at the time of delivery did not significantly differ as the time between prior cesarean delivery and subsequent FET increased (range: 37.3 - 38.4 weeks, adj p = 0.87, continuous adj p = 0.06). When time was evaluated continuously, the proportion of preterm births was higher with a shorter time between cesarean delivery and subsequent FET (p = 0.02). Mean birth weight ranged from 3181 grams to 3470 grams, with a statistically significant increase over time (continuous adj p = 0.01). However, the proportions of extremely low birth weight, very low birth weight, and low birth weight did not significantly differ. CONCLUSION: There were no significant differences in reproductive outcomes based on the time interval from cesarean delivery to FET, including live birth. The proportion of preterm deliveries decreased with a longer time between cesarean delivery and FET. Differences in mean neonatal birth weight were not clinically significant, as the proportion of low-birth-weight neonates was not significantly different over time. While large, this sample cannot address all outcomes associated with short interpregnancy intervals, particularly rarer outcomes such as uterine rupture. When counseling patients, the timing of FET following cesarean delivery must be balanced against the risks of increasing maternal age on reproductive and neonatal outcomes.

High estradiol levels in fresh embryo transfer cycles are not associated with detrimental impact on birth outcomes.

PURPOSE: There is an unclear relationship between estradiol levels and fresh embryo transfer (ET) outcomes. We determined the relationship between estradiol on the day of trigger, in fresh ET cycles without premature progesterone elevation, and good birth outcomes (GBO). METHODS: We identified autologous fresh ET cycles from 2015 to 2021 at multiple clinics in the USA. Patients with recurrent pregnancy loss, uterine factor, and elevated progesterone on the day of trigger (progesterone > 2 ng/mL or 3-day area under the curve > 4.5 ng/mL) were excluded. The primary outcome was GBO (singleton, term, live birth with appropriate weight). Log-binomial generalized estimating equations determined the likelihood of outcomes. RESULTS: Of 17,608 fresh ET cycles, 5025 (29%) yielded GBO. Cycles with estradiol ≥ 4000 pg/mL had a greater likelihood of GBO compared to cycles < 1000 pg/mL (aRR = 1.32, 95% CI 1.13-1.54). Pairwise comparisons of estradiol between < 1000 pg/mL versus 1000-1999 pg/mL and 1000-1999 pg/mL versus 2000-2999 pg/mL revealed a higher likelihood of GBO with higher estradiol (aRR 0.83, 95% CI 0.73-0.95; aRR 0.91, 95% CI 0.85-0.97, respectively). Comparisons amongst more elevated estradiol levels revealed that the likelihood of GBO remained similar between groups (2000-2999 pg/mL versus 3000-3999 pg/mL, aRR 1.04, 95% CI 0.97-1.11; 3000-3999 pg/mL versus ≥ 4000 pg/mL, aRR 0.96, 95% CI 0.9-1.04). CONCLUSION: In fresh ET cycles, higher estradiol levels were associated with an increased prevalence of GBO until estradiol 2000-2999 pg/mL, thereafter plateauing. In fresh ET candidates, elevated estradiol levels should not preclude eligibility though premature progesterone rise, and risk of ovarian hyperstimulation syndrome must still be considered.

Assessment of clinical pregnancies in up to eight ovarian stimulation with intrauterine insemination treatment cycles in those unable to proceed with in vitro fertilization.

OBJECTIVE: To study the primary objective of clinical pregnancy (CP) rate per ovarian stimulation with intrauterine insemination (OS-IUI) treatment cycle in patients with repetitive cycles up to a maximum of 8 cycles. DESIGN: Retrospective cohort. SETTING: Large fertility clinic. PATIENTS: A total of 37,565 consecutive OS-IUI cycles from 18,509 patients were included in this study. INTERVENTIONS: Those with anovulatory diagnoses, tubal factor infertility, male factor infertility, using donor sperm, canceled cycles, and those with missing data for either baseline characteristics or outcome were excluded. The CP rate was analyzed using generalized estimating equations and controlled for age, stimulation protocol, and body mass index. MAIN OUTCOMES MEASURES: Clinical pregnancy was defined as intrauterine gestation with fetal heartbeat visible on ultrasound. RESULTS: A total of 37,565 consecutive OS-IUI cycles from 2002 through 2019 at a private practice facility were evaluated. All cycles met inclusion criteria and were used in generalized estimating equation modeling. Patients aged <35 years comprised 47.6% of the cohort. After adjustment for confounders, the mean predicted probability of CP for cycles one to 8 was 15.7% per cycle. The mean predicted probability of CP in aggregated data from cycles 2 to 4 was only 1.7% lower compared with cycle 1 as the referent (16.7% vs. 15.0%, 95% confidence interval [CI] 2nd: 0.88 {0.82, 0.95}, 3rd: 0.86 {0.79, 0.93}, 4th: 0.88 {0.79, 0.98}). However, the 15.0% mean predicted probability of CP for the second through the fourth cycle was concordant with the mean for all included cycles (15.7%). The mean predicted probability of CP of cycles 5 to 8 was not significantly different compared with the referent (16.7% vs. 16.1%, 95% CI 5th: 0.97 [0.85, 1.11], 6th: 0.93 [0.79, 1.10], 7th: 1.01 [0.81, 1.26], 8th: 1.01 [0.76, 1.34]). The modeling of consecutive cycles suggested that the adjusted cumulative predicted probability of CP from OS-IUI continues to increase with each of the 8 successive cycles. CONCLUSION: Clinical pregnancy rates are satisfactory in up to 8 consecutive OS-IUI treatment cycles. These data are useful for counseling, especially in those patients for whom in vitro fertilization is not financially or ethically feasible.

Optimal antimüllerian hormone levels in oocyte donors: a national database analysis.

OBJECTIVE: To study the relationship between high antimüllerian hormone (AMH) levels in oocyte donors and embryo development and pregnancy outcomes among donor oocyte recipients. DESIGN: Retrospective cohort study. SETTING: Donor Egg Bank Database. PATIENTS: Patients undergoing in vitro fertilization using vitrified donor oocytes from 35 in vitro fertilization centers in the United States between 2013 and 2021. For each recipient, the first oocyte lot that was received with a planned insemination and embryo transfer (ET) was included. INTERVENTION: Oocyte donor-recipient cycles. MAIN OUTCOME MEASURES: Ongoing pregnancy rate (OPR) per ET. RESULTS: A total of 3,871 donor oocyte-recipient thaw cycles were analyzed. On the basis of donor AMH serum concentration, cycles were stratified into the high AMH group (AMH ≥5 ng/mL; n = 1,821) and the referent group (AMH <5 ng/mL; n = 2,050). Generalized estimating equation models were used to account for donors that contributed more than one lot of oocytes. The number of usable embryos per lot (median [interquartile range]) was significantly increased in the high AMH group (2 [2-4]) compared with the referent group (2 [1-3]) (relative risk [RR] 1.06; confidence interval [CI] 1.01-1.12). Among recipients with a planned ET, there was no difference in OPR between the high AMH group (45.4%) and the referent group (43.5%) (RR 1.04; 95% CI 0.94-1.15). Among preimplantation genetic testing for aneuploidy cycles, the embryo euploidy rate per biopsy was similar at 66.7% (50%-100%) in both groups (RR 1.04; CI 0.92-1.17). The OPR per euploid ET among patients who used preimplantation genetic testing for aneuploidy was also comparable, at 52% in the high AMH group and 54.1% in the referent group (RR 0.95; CI 0.74-1.23). CONCLUSION: This large national database study observed that there was no association between a high level of AMH (≥5 ng/mL) in oocyte donors and an OPR in the recipient after the first ET. On the basis of these findings, recipients and physicians can be reassured that oocyte donors with a high AMH level can be expected to produce outcomes that are at least as good as donors with an AMH level (<5 ng/mL).

Examining reasons that patients discard cryopreserved oocytes.

PURPOSE: Assess the rate, rationale, and characteristics of patients who cryopreserved and subsequently discarded their oocytes, and compare their characteristics to patients with continued cryopreservation of oocytes. METHODS: All patients who disposed of cryopreserved oocytes between 2009 and 2022 reported their reason for discarding their oocytes. This was a retrospective cohort study. RESULTS: Of 5,010 patients who underwent oocyte cryopreservation (OC) cycles, 201 (4%) patients elected to discard their oocytes and 751 (15%) thawed oocytes for clinical use. The average ages of OC and disposal were 35 and 39 years old, respectively. Of the 201 patients who discarded their oocytes, 71 patients (35%) requested disposal after having a child. Twenty-six (13%) discarded oocytes because of worsening cancer and three (1.4%) discarded because of death. 16 (8%) discarded oocytes due to cost of cryopreservation and eight (4%) due to low oocyte yield. Ten (5%) patients underwent new IVF cycles and discarded previously stored oocytes. Sixty-seven patients (33%) discarded oocytes for unspecified reasons. When comparing patients who discarded oocytes with those who did not, the former had lower AMH (2.7 vs 3.5 ng/ml, p < 0.001) but otherwise comparable age and number of cryopreserved oocytes. The mean age for those with continued cryopreservation was 35.4 years at time of OC and 40 years at time of data collection in June 2023. CONCLUSION: Childbirth was the most common reason to dispose of oocytes followed by unspecified reasons. Larger studies of oocyte disposal may better define clinical characteristics of patients most likely to use, maintain or discard their oocytes.

Preimplantation genetic testing for sickle cell disease: a cost-effectiveness analysis.

Objective: To evaluate the cost-effectiveness of in vitro fertilization with preimplantation genetic testing for monogenic disease (IVF + PGT-M) in the conception of a nonsickle cell disease (non-SCD) individual compared with standard of care treatment for a naturally conceived, sickle cell disease (SCD)-affected individual. Design: A Markov simulation model was constructed to evaluate a one-time IVF + PGT-M treatment compared with the lifetime standard of care costs of treatment for an individual potentially born with SCD. Using an annual discount rate of 3% for cost and outcome measures, quality-adjusted life years were constructed from utility weights and life expectancy values and then used as the effectiveness measurement. An incremental cost-effectiveness ratio was calculated for both treatment arms, and a willingness-to-pay threshold of $50,000 per quality-adjusted life year was assumed. Setting: Tertiary care or university medical center. Patients: A hypothetical cohort of 10,000 patients was analzyed over a lifetime horizon using yearly cycles. Interventions: In vitro fertilization with preimplantation genetic testing for monogenic disease use in conception of a non-SCD individual. Main Outcome Measures: The primary outcomes of interest were the incremental cost and effectiveness of an IVF+PGT-M conception compared with the SOC treatment of an SCD-affected individual. Results: In vitro fertilization with preimplantation genetic testing for monogenic disease was the optimal strategy in 93.17% of the iterations. An incremental savings of $137,594 was demonstrated with a gain of 1.96 QALYs and 3.69 life years over a lifetime. Sensitivity analysis demonstrated that SOC treatment never met equivalent cost-effectiveness. Conclusions: Our model demonstrates that IVF + PGT-M for selection against SCD, compared with lifetime SOC treatment for those affected, is the most cost-effective strategy within the United States healthcare sector.

Meeting the demand for fertility services: the present and future of reproductive endocrinology and infertility in the United States.

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.

Live birth per embryo transfer with next generation sequencing preimplantation genetic testing: an analysis of 26,107 cycles.

The technique and platform used for preimplantation genetic testing for aneuploidy (PGT-A) have undergone significant changes over time. The contemporary technique utilizes trophectoderm biopsy followed by next-generation sequencing (NGS). The goal of this study was to explore the role of PGT-A using NGS technique exclusively in contemporary in vitro fertilization (IVF) practice. For this, we performed a retrospective analysis of a large dataset collected from the Shady Grove Fertility (SGF) multicentre practice. All autologous IVF cycles which were followed by at least one single embryo transfer (ET) (fresh and/or frozen) between January 2017 to July 2020, were included. Our study group included patients who had PGT-A and the control group included patients who did not proceed with PGT-A. The primary outcome was the live birth rate (LBR) per transfer. All age-adjusted LBR was higher in the PGT-A group than the non-PGT-A group (48.9% vs. 42.7%, p < 0.001), except in women <35 years old among single embryo frozen ETs. Similarly, LBR in the PGT-A group was higher in all ages except in women <35 years old (48.7% vs. 41.7%, p < 0.001) when all single embryos fresh and frozen ETs were included. In patients of decreased ovarian reserve, transfer of euploid embryo was associated with higher LBR (46.7% vs. 26.7%, p < 0.001) whereas miscarriages were lower in patients with unexplained infertility (9.3% vs. 11.3%, p = 0.007 and endometriosis (8.9% vs. 11.6%, p < 0.001) following euploid embryo transfer. To conclude, the transfer of euploid embryos tested via NGS PGT-A was associated with improved LBR per transfer in women ≥35 years old.

Recurrent implantation failure: reality or a statistical mirage?: Consensus statement from the July 1, 2022 Lugano Workshop on recurrent implantation failure.

IMPORTANCE: To date, recurrent implantation failure (RIF) has no clear definition and no clearly identified impaired function. Hence, the term RIF is currently used somewhat haphazardly, on the basis of clinicians' judgment. OBJECTIVE: International experts in reproductive medicine met on July 1, 2022, in Lugano, Switzerland, to review the different facets of RIF and define the diagnosis and its appropriate management. EVIDENCE REVIEW: A systematic review without meta-analysis of studies published in English from January 2015 to May 2022. FINDINGS: Data indicated that RIF has been largely overevaluated, overdiagnosed, and overtreated without sufficient critical assessment of its true nature. Our analyses show that true RIF is extremely uncommon-occurring in <5% of couples with infertility-and that reassurance and continued conventional therapies are warranted in most cases of assisted reproductive technology (ART) failure. Although the true biologic determinants of RIF may exist in a small subset of people with infertility, they elude the currently available tools for assessment. Without identification of the true underlying etiology(ies), it is reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid blastocyst transfers (or the equivalent number of unscreened embryo transfers, adjusted to the patient's age and corresponding euploidy rate). In addition, other factors should be ruled out that may contribute to her reduced odds of sustained implantation. In such cases, implantation failure should not be the only issue considered in case of ART failure because this may result from multiple other factors that are not necessarily repetitive or persistent. In reality, RIF impacting the probability of further ART success is a very rare occurrence. CONCLUSION: True RIF is extremely uncommon, occurring in <5% of couples with infertility. Reassurance and continued conventional therapies are warranted in most cases. It would seem reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid embryo transfers (or the equivalent number of unscreened embryos, adjusted to her age). RELEVANCE: Given the number of internationally recognized experts in the field present at the Lugano meeting 2022, our publication constitutes a consensus statement.

Live birth associated with peak serum estradiol levels in letrozole intrauterine insemination cycles.

OBJECTIVE: To identify whether the serum estradiol (E2) level on the day of human chorionic gonadotropin (hCG) trigger or luteinizing hormone (LH) surge (hCG-LH) was associated with the live birth rate (LBR) during ovulation induction (OI) or controlled ovarian hyperstimulation with letrozole followed by intrauterine insemination (IUI). DESIGN: Retrospective cohort study. SETTING: Large, multicenter private practice. PATIENT(S): A total of 2,368 OI-IUI cycles in patients treated with letrozole followed by IUI were evaluated from January 1, 2014, to July 31, 2019. INTERVENTION(S): Ovulation induction with letrozole, followed by autologous IUI. MAIN OUTCOME MEASURE(S): The primary outcome measure was the LBR as a function of the serum E2 level at the time of hCG administration or LH surge, adjusting for age, body mass index, the largest follicle diameter, and the number of follicles ≥14 mm in diameter. The clinical pregnancy rate as a function of the E2 level, pregnancy rate as a function of the lead follicle diameter, and pregnancy loss rates were the secondary outcome variables. RESULT(S): A total of 2,368 cycles met the inclusion criteria. Outcomes were evaluated at the 25th (E2 level, 110 pg/mL), 50th (157 pg/mL), 75th (225 pg/mL), and 90th (319 pg/mL) percentiles. The LBRs ranged from 9.4% to 11.1% in the lower E2 cohorts and from 12.5% to 13.5% in the higher E2 cohorts. The LBR was significantly greater in the cohort of women with higher E2 levels in all percentile comparisons except for the 90th percentile. The mean periovulatory follicle diameter of ≥20 or <20 mm was not independently associated with the LBR or clinical pregnancy rate, despite a significantly higher mean E2 level in the larger follicle group. CONCLUSION(S): In letrozole OI cycles followed by IUI, lower LBRs and clinical pregnancy rates were found in women with lower E2 levels than in those with higher E2 levels at the 25th, 50th, and 75th percentile E2 level quartiles. Where possible, delaying hCG trigger until the E2 level increases after aromatase inhibition and approaches the physiologic periovulatory level may improve the pregnancy rates with letrozole followed by IUI.

AKAP13 Enhances CREB1 Activation by FSH in Granulosa Cells.

Granulosa cells (GCs) must respond appropriately to follicle-stimulating hormone (FSH) for proper follicle maturation. FSH activates protein kinase A (PKA) leading to phosphorylation of the cyclic AMP response element binding protein-1 (CREB1). We identified a unique A-kinase anchoring protein (AKAP13) containing a Rho guanine nucleotide exchange factor (RhoGEF) region that was induced in GCs during folliculogenesis. AKAPs are known to coordinate signaling cascades, and we sought to evaluate the role of AKAP13 in GCs in response to FSH. Aromatase reporter activity was increased in COV434 human GCs overexpressing AKAP13. Addition of FSH, or the PKA activator forskolin, significantly enhanced this activity by 1.5- to 2.5-fold, respectively (p < 0.001). Treatment with the PKA inhibitor H89 significantly reduced AKAP13-dependent activation of an aromatase reporter (p = 0.0067). AKAP13 physically interacted with CREB1 in co-immunoprecipitation experiments and increased the phosphorylation of CREB1. CREB1 phosphorylation increased after FSH treatment in a time-specific manner, and this effect was reduced by siRNA directed against AKAP13 (p = 0.05). CREB1 activation increased by 18.5-fold with co-expression of AKAP13 in the presence of FSH (p < 0.001). Aromatase reporter activity was reduced by inhibitors of the RhoGEF region, C3 transferase and A13, and greatly enhanced by the RhoGEF activator, A02. In primary murine and COV43 GCs, siRNA knockdown of Akap13/AKAP13 decreased aromatase and luteinizing hormone receptor transcripts in cells treated with FSH, compared with controls. Collectively, these findings suggest that AKAP13 may function as a scaffolding protein in FSH signal transduction via an interaction with CREB, resulting in phosphorylation of CREB.

Reproductive genetics laboratory may impact euploid blastocyst and live birth rates: a comparison of 4 national laboratories' PGT-A results from vitrified donor oocytes.

OBJECTIVE: To evaluate potential variation in the euploid blastocyst rate and live birth rate (LBR) per single frozen euploid blastocyst transfer, among 4 unique United States reproductive genetics laboratories. Analyses were limited to blastocysts derived from vitrified donor oocytes, to minimize variation in oocyte quality. DESIGN: Retrospective cohort study from 2016 to 2020. SETTING: Donor Egg Bank Database. PATIENT(S): Patients undergoing in vitro fertilization with donor oocytes. We excluded patients with uterine factor, male factor, or surgically extracted sperm. Only healthy women <34 years old were accepted as oocyte donors. INTERVENTION(S): Next generation sequencing platforms for chromosomal analysis MAIN OUTCOME MEASURE(S): Euploid blastocyst rate and LBR per euploid transfer. Secondary outcomes included the rate of aneuploidy, mosaic calls, biochemical pregnancy loss, and miscarriage rate. RESULT(S): A total of 2,633 embryos were included. Four laboratories had >200 embryos tested. Euploid blastocyst rate was significantly higher in laboratory A (73.6%) vs. B (63.3%), C (60.9%), and D (52.3%). Mosaic rate was significantly lower for Laboratories B (2.8%) and C (5.5%) vs. Laboratories A (9.9%) and D (11.5). The LBR was significantly higher in laboratory A (58.73%) vs. laboratory D (47.3%). There were no significant differences in the implantation or miscarriage rate among laboratories. CONCLUSION(S): In this large study, controlling for oocyte quality, some preimplantation genetic testing for aneuploidy (PGT-A) laboratories report a significantly higher euploid blastocyst rate with concurrent higher LBR. This type of comparison is important as it provides insight into the role of the PGT-A process in outcomes. Further research is needed to evaluate the differences in laboratory techniques and bioinformatic algorithms accounting for variable outcomes across PGT-A laboratories.

Effect of Timing by Endometrial Receptivity Testing vs Standard Timing of Frozen Embryo Transfer on Live Birth in Patients Undergoing In Vitro Fertilization: A Randomized Clinical Trial.

Importance: Endometrial receptivity testing is purported to improve live birth following frozen embryo transfer by identifying the optimal embryo transfer time for an individual patient; however, data are conflicting. Objective: To compare live birth from single euploid frozen embryo transfer according to endometrial receptivity testing vs standardized timing. Design, Setting, and Participants: Double-blind, randomized clinical trial at 30 sites within a multicenter private fertility practice in the Eastern US. Enrollment was from May 2018 to September 2020; follow-up concluded in August 2021. Participants underwent in vitro fertilization, preimplantation genetic testing for aneuploidy, endometrial receptivity testing, and frozen embryo transfer. Those with euploid blastocyst(s) and an informative receptivity result were randomized. Exclusion criteria included recurrent pregnancy loss, recurrent implantation failure, surgically aspirated sperm, donor egg(s), and unmitigated anatomic uterine cavity defects. Interventions: The intervention group (n = 381) underwent receptivity-timed frozen embryo transfer, with adjusted duration of progesterone exposure prior to transfer, if indicated by receptivity testing. The control group (n = 386) underwent transfer at standard timing, regardless of receptivity test results. Main Outcomes and Measures: The primary outcome was live birth. There were 3 secondary outcomes, including biochemical pregnancy and clinical pregnancy. Results: Among 767 participants who were randomized (mean age, 35 years), 755 (98%) completed the trial. All randomized participants were analyzed. The primary outcome of live birth occurred in 58.5% of transfers (223 of 381) in the intervention group vs 61.9% of transfers (239 of 386) in the control group (difference, -3.4% [95% CI, -10.3% to 3.5%]; rate ratio [RR], 0.95 [95% CI, 0.79 to 1.13]; P = .38). There were no significant differences in the intervention vs the control group for the prespecified secondary outcomes, including biochemical pregnancy rate (77.2% vs 79.5%, respectively; difference, -2.3% [95% CI, -8.2% to 3.5%]; RR, 0.97 [95% CI, 0.83 to 1.14]; P = .48) and clinical pregnancy rate (68.8% vs 72.8%, respectively; difference, -4.0% [95% CI, -10.4% to 2.4%]; RR, 0.94 [95% CI, 0.80 to 1.12]; P = .25). There were no reported adverse events. Conclusions and Relevance: Among patients for whom in vitro fertilization yielded a euploid blastocyst, the use of receptivity testing to guide the timing of frozen embryo transfer, compared with standard timing for transfer, did not significantly improve the rate of live birth. The findings do not support routine use of receptivity testing to guide the timing of embryo transfer during in vitro fertilization. Trial Registration: ClinicalTrials.gov Identifier: NCT03558399.

Modern assessment of the uterine cavity and fallopian tubes in the era of high-efficacy assisted reproductive technology.

The high efficacy of modern assisted reproductive technology (ART) and increase in the number of noninfertile patients who are using ART for family building in the United States call into question the relevance of the standard, one-size-fits-all infertility evaluation. Here, we explore whether all patients presenting for ART need uterine cavity and tubal assessment and what tests are most appropriate, efficient, and cost-effective in current times.

Live birth after transfer of a single euploid vitrified-warmed blastocyst according to standard timing vs. timing as recommended by endometrial receptivity analysis.

OBJECTIVE: To determine whether endometrial receptivity analysis (ERA) improves live births in patients with and without a history of unsuccessful frozen embryo transfers (FETs). DESIGN: Retrospective cohort study. SETTING: Large reproductive center. PATIENT(S): Patients with and without ERA before euploid single FET were included in the analysis. INTERVENTION(S): Subjects in the exposed group underwent ERA and ERA-timed FETs. Subjects in the unexposed group followed a standard protocol FET without ERA. Outcomes were compared between nonreceptive and receptive subjects undergoing an ERA-timed FET and between ERA-timed vs. standard protocol FETs. MAIN OUTCOME MEASURE(S): The primary outcome was a live birth; secondary outcomes were biochemical and clinical pregnancy rates. RESULT(S): A total of 307 ERA-timed FETs and 2,284 standard protocol FETs were analyzed. One hundred twenty-five patients (40.7%) were ERA receptive, and 182 (59.3%) were ERA nonreceptive. After adjusting for the number of the previously failed FETs, there was no difference in the proportion of receptive and nonreceptive ERA results. There were no statistically significant differences in live births in patients with ERA-receptive vs. ERA-nonreceptive results (48.8% and 41.7%, respectively; adjusted odds ratio 1.17; 95% CI, 0.97-1.40). There were no statistically significant differences in live births in patients with or without ERA testing results before FET (44.6% and 51.3%, respectively; adjusted odds ratio 0.87; 95% CI, 0.73-1.04). CONCLUSION(S): Patients with an increasing number of previous failed euploid FET cycles are not at an increased risk of a displaced window of implantation. Patients categorized as receptive vs. nonreceptive and those without ERA testing results have comparable FET success rates.