Utilization of Cryopreserved Oocytes in Patients With Poor Ovarian Response After Planned Oocyte Cryopreservation.

Importance: Poor ovarian response (POR) to stimulation may impact patients' desire or need to utilize cryopreserved oocytes for family building in the future. These findings, captured by Society for Assisted Reproductive Technology (SART) national data, underscore the need for tailored counseling and further research into the decision-making processes influencing oocyte utilization. Objective: To examine the association of ovarian response to stimulation and the number of vitrified oocytes with the likelihood and timing of patients returning for oocyte utilization following planned oocyte cryopreservation (OC). Design, Setting, and Participants: This cohort study used data in the SART Clinical Outcome Reporting System for patients in US fertility clinics and data was used for eligible patients who underwent planned OC from January 2014 through December 2020. Data were analyzed from November 2022 to June 2023. Main outcomes and measures: The association between number of oocytes cryopreserved on return rate to utilize cryopreserved oocytes and the time from vitrification to warming. Results: A total of 67 893 autologous oocyte freezing cycles were performed in the US between 2014 and 2020, among 47 363 patients (mean [SD] age, 34.5 [4.7] years). Of these, 6421 (13.5%) were classified as patients with POR, with fewer than 5 oocytes vitrified across all ovarian stimulation cycles. A total of 1203 patients (2.5%) returned for oocyte warming and utilization. The rate of return was significantly higher in the POR group, with 260 (4.0%) returning compared with 943 (2.3%) in the normal responder group (P < .001). This trend was most notable in the age 30 to 34 years (warm cycle, 46 of 275 [16.7%] vs no warm cycle, 982 of 11 743 [8.4%]; P < .001) and age 35 to 39 years groups (warm cycle, 124 of 587 [21.1%] vs no warm cycle, 3433 of 23 012 [14.9%]; P < .001). The time elapsed from vitrification to warming was comparable between patients with POR (mean [SD], 716.1 [156.1] days) and normal responders (803.8 [160.7] days). A multivariate analysis adjusted for age, clinic region in the US, body mass index, and history of endometriosis was conducted to identify factors associated with the utilization of oocytes. The analysis revealed that having fewer than 5 oocytes vitrified was associated with higher odds of utilizing oocytes (OR, 1.52; 95% CI, 1.32-1.76). Conclusions and Relevance: This cohort study reveals a distinct pattern in the utilization of cryopreserved oocytes among patients undergoing planned OC in the US. Despite the increase in number of patients pursuing OC, there is a notably low rate of return to utilize previously vitrified oocytes; notably, patients with POR are more likely to return, although the time to return is similar to those with normal ovarian response.

Intra-patient analysis of individual weight gain or loss between IVF cycles: cycle now and transfer later.

STUDY QUESTION: What is the impact of clinically significant weight change on outcomes related to IVF cycle performance? SUMMARY ANSWER: While individual weight loss did not significantly impact ovarian response to stimulation or other cycle outcome parameters in our study, some positive associations were found for individual weight gain. WHAT IS KNOWN ALREADY: The role of weight-change in patients undergoing IVF has been largely studied by comparing weight loss in different cohorts of patients stratified by a static BMI. Specifically, obesity has been extensively studied in relation to its negative effects on assisted or unassisted conception outcomes and ovulatory function. Previous research has shown conflicting results, while BMI, which is commonly used as a marker of obesity, may not accurately reflect the underlying factors affecting fertility in obese patients. STUDY DESIGN, SIZE, DURATION: This study utilized a retrospective within-patient repeated measurement analysis design to assess the impact of weight change on IVF outcomes in cycles where all embryos were cryopreserved at the blastocyst stage for transfer at a later date. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at an academically affiliated fertility center. The data included 961 women who underwent at least two IVF cycles between December 2014 and June 2020, with documented short-term weight gain (n = 607) or weight loss (n = 354) within 1 year from their initial IVF cycle. Multivariable generalized estimating equations (GEE) and generalized linear mixed models (GLMM) were employed to assess associations between weight change and outcomes across cycles. MAIN RESULTS AND THE ROLE OF CHANCE: The multivariable models indicated that weight loss did not show any significant associations with the numbers of oocytes retrieved, or mature oocytes, the fertilization rate or the blastulation rate. However, weight gain demonstrated a minor positive association with the number of oocytes retrieved in both GEE models (coefficient: 0.01, 95% CI: 0.00-0.01) and GLMM models (0.01, 95% CI: 0.01-0.00). There was also a potential increase in the fertilization rate with weight gain, as indicated by a positive coefficient in both GEE models (coefficient: 0.01, 95% CI: 0.00-0.02) and GLMM models (coefficient: 0.01, 95% CI: 0.00-0.01). However, the association between weight gain and the embryo blastulation rate was not statistically significant in any model. LIMITATIONS, REASONS FOR CAUTION: This study focused on cycle performance parameters instead of reproductive outcomes, which restricted our ability to evaluate the impact of weight change on cumulative live birth rates. Additionally, the study did not account for variables such as stimulation protocols, potentially introducing confounding factors and limiting the generalizability of the results. WIDER IMPLICATIONS OF THE FINDINGS: Although obesity is associated with adverse obstetrical risks, there is less evidence of adverse reproductive outcomes in IVF cycles. We therefore recommend that an IVF cycle should not be delayed due to weight, so that the patient is not adversely affected by increasing age. The IVF cycle should aim to freeze all embryos, so that embryo transfer can then occur after weight loss, so as to limit the recognized obstetrical risks. STUDY FUNDING/COMPETING INTEREST(S): The study was not funded and there were no competing interests. TRIAL REGISTRATION NUMBER: N/A.

From oocytes to a live birth: Are we improving the biological efficiency?

OBJECTIVE(S): The objectives of our study were to investigate the live birth rate (LBR) per oocyte retrieved during in vitro fertilization, in patients who had used all their embryos and to extrapolate the LBR in patients with remaining frozen embryos by calculating the expected LBR from these embryos. DESIGN: A retrospective cohort study. SETTING: A single academically affiliated fertility clinic. PATIENT(S): Autologous in vitro fertilization cycles from January 2014 to December 2020. Data on the number of oocytes retrieved, number of embryos obtained and transferred (at cleavage or blastocyst-stage), use of preimplantation genetic testing for aneuploidy (PGT-A), and number of live births were obtained. The expected LBR was estimated in patients with remaining frozen embryos according to nationally reported Society for Assisted Reproductive Technology LBR data. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth rate per oocyte retrieved. RESULT(S): A total of 12,717 patients met the inclusion criteria and underwent a total of 20,677 oocyte retrievals which yielded a total of 248,004 oocytes and 57,268 embryos (fresh and frozen). In patients who had fully utilized all their embryos the LBR per oocyte was 2.82% (ranging from 11.3% aged <35 years to 1.2% aged >42 years). Stratification of the population based on PGT-A utilization yielded similar results (with PGT-A: 2.88% and without PGT-A: 2.79%). When stratified by the Society for Assisted Reproductive Technology age groups, the addition of PGT-A in patients aged 35-37 and 38-40 years yielded higher LBR per oocyte compared with patients who did not add PGT-A (P<.05). In patients with remaining frozen embryos who had added PGT-A, the projected LBR per oocyte was 8.34%. Use of PGT-A in patients aged <35 and 35-37 years decreased LBR per oocyte (P<.001 and P=.03, respectively) but improved LBR per oocyte in patients aged 38-40 and 41-42 years (P=.006 and P=.005, respectively). Poisson regression analysis demonstrated an age threshold of 38.5, below which PGT-A lowers LBR per oocyte compared with no PGT-A. CONCLUSION(S): Despite clinical and scientific advances in Assisted Reproductive Technology, with the current protocols of ovarian stimulation, the LBR per oocyte remains low reflecting a biological barrier that has yet to be overcome. Overall, the addition of PGT-A did not demonstrate improved outcomes.

Acceptance of genetic editing and of whole genome sequencing of human embryos by patients with infertility before and after the onset of the COVID-19 pandemic.

RESEARCH QUESTION: Has acceptance of heritable genome editing (HGE) and whole genome sequencing for preimplantation genetic testing (PGT-WGS) of human embryos changed after the onset of COVID-19 among infertility patients? DESIGN: A written survey conducted between April and June 2018 and July and December 2021 among patients at a university-affiliated infertility practice. The questionnaire ascertained the acceptance of HGE for specific therapeutic or genetic 'enhancement' indications and of PGT-WGS to prevent adult disease. RESULTS: In 2021 and 2018, 172 patients and 469 patients (response rates: 90% and 91%, respectively) completed the questionnaire. In 2021, significantly more participants reported a positive attitude towards HGE, for therapeutic and enhancement indications. In 2021 compared with 2018, respondents were more likely to use HGE to have healthy children with their own gametes (85% versus 77%), to reduce disease risk for adult-onset polygenic disorders (78% versus 67%), to increase life expectancy (55% versus 40%), intelligence (34% versus 26%) and creativity (33% versus 24%). Fifteen per cent of the 2021 group reported a more positive attitude towards HGE because of COVID-19 and less than 1% a more negative attitude. In contrast, support for PGT-WGS was similar in 2021 and 2018. CONCLUSIONS: A significantly increased acceptance of HGE was observed, but not of PGT-WGS, after the onset of COVID-19. Although the pandemic may have contributed to this change, the exact reasons remain unknown and warrant further investigation. Whether increased acceptability of HGE may indicate an increase in acceptability of emerging biomedical technologies in general needs further investigation.

Day after rescue ICSI: eliminating total fertilization failure after conventional IVF with high live birth rates following cryopreserved blastocyst transfer.

STUDY QUESTION: What is the impact of day after rescue ICSI (r-ICSI) on success of fresh and frozen embryo transfers? SUMMARY ANSWER: The use of r-ICSI can virtually allay fears of total fertilization failure (TFF) after conventional IVF (C-IVF) and achieve high live birth rates after frozen blastocyst transfer. WHAT IS KNOWN ALREADY: More infertility clinics have resorted to the use of ICSI in place of C-IVF in IVF treatment owing to fear of TFF or a low fertilization rate. r-ICSI has been attempted either on the day of IVF or the day after. Day after r-ICSI has proved unsuccessful in the past. STUDY DESIGN, SIZE, DURATION: A retrospective data analysis was performed of 16 608 qualifying cases between April 2010 and July 2021 conducted at a single private academically affiliated fertility clinic. PARTICIPANTS/MATERIALS, SETTING, METHODS: r-ICSI was performed principally on patients with >4 metaphase II oocytes, showing no signs of fertilization 18 h after C-IVF. C-IVF was performed on patients who had >4 million total motile sperm after preparation. r-ICSI was then performed 18-24 h after insemination, using the sperm sample from the previous day. r-ICSI fertilization rates, cryopreservation of cleavage and blastocysts embryos, and pregnancy rates after fresh or frozen transfer were then assessed. MAIN RESULTS AND THE ROLE OF CHANCE: r-ICSI was performed on 377 patients (2.3% of eligible retrieval cycles) who had a mean (±SD) female and male age of 35.9 ± 4.5 and 38.1 ± 9.1 years, respectively. A total of 5459 oocytes were initially retrieved. Of the oocytes undergoing r-ICSI, 2389 (49.5%) fertilized normally, and 205 (54.4%) patients underwent a fresh embryo transfer. The live birth rates were 23/186 (12.3%) for fresh cleavage and 5/19 (26.3%) for fresh blastocyst stage transfers. In 145 cycles a blastocyst was frozen, and 137 transfers were performed with a 64/137 (46.7%) live birth rate. Of the 377 cycles receiving r-ICSI only, 25 of the qualifying cases failed to have any fertilization, reducing TFF to 25/16 608 (0.15%). LIMITATIONS, REASONS FOR CAUTION: This was a single-center retrospective study on a specific subset of patients, which may limit its generalizability to other clinics. WIDER IMPLICATIONS OF THE FINDINGS: r-ICSI allows a second opportunity to fertilize oocytes despite poor initial outcomes. Patients who had a frozen blastocyst transfer achieved high live birth rates, indicating that a resynchronization of the embryo with the endometrium can optimize r-ICSI cases. r-ICSI allays fears of TFF when using C-IVF, providing evidence that the overuse of ICSI in patients without male factor may not be warranted. STUDY FUNDING/COMPETING INTEREST(S): The study was internally funded by Boston IVF. The authors declare that they have no conflict of interest in relation to the data published in the article. TRIAL REGISTRATION NUMBER: N/A.

ART outcomes in lean compared to obese phenotypes of polycystic ovarian syndrome.

RESEARCH QUESTION: To investigate differences in reproductive outcomes among IVF patients with lean compared to obese polycystic ovarian syndrome (PCOS) phenotypes. DESIGN: A retrospective cohort study of patients with PCOS who underwent IVF in a single, academically affiliated infertility center in the USA between December 2014 and July 2020. The diagnosis of PCOS was assigned based on Rotterdam criteria. Patients were designated as lean (< 25) or overweight/obese (≥ 25) PCOS phenotype based on BMI (kg/m2) at cycle start. Baseline clinical and endocrinologic laboratory panel, cycle characteristics, and reproductive outcomes were analyzed. The cumulative live birth rate included up to 6 consecutives cycles. A Cox proportional hazards model and Kaplan-Meier curve for estimating live birth rates were used to compare the two phenotypes. RESULTS: A total of 1395 patients who underwent 2348 IVF cycles were included. The mean (SD) BMI was 22.7 (2.4) in the lean and 33.8 (6.0) in the obese group (p < 0.001). A number of endocrinological parameters were similar between lean and obese phenotypes: total testosterone 30.8 ng/dl (19.5) vs 34.1 (21.9), p > 0.02 and pre-cycle hemoglobin A1C 5.33% (0.38) vs 5.51% (0.51) p > 0.001, respectively. The CLBR was higher in those with a lean PCOS phenotype: 61.7% (373/604) vs 54.0% (764/1414) respectively. Miscarriage rates were significantly higher for O-PCOS patients (19.7% (214/1084) vs 14.5% (82/563) p < 0.001) and the rate of aneuploids was similar (43.5%, 43.8%, p = 0.8). A Kaplan-Meier curve estimating the proportion of patients with a live birth was higher in the lean group (log-rank test p = 0.013). After adjusting for potential confounders, the lean phenotype was associated with an increased hazard ratio for live birth: HR = 1.38 p < 0.001. CONCLUSIONS: Lean PCOS phenotype is associated with a significantly higher CLBR compared to their obese counterparts. Miscarriage rates were significantly higher among obese patients, despite comparable pre-cycle HBA1C and similar aneuploidy rates in patients who underwent PGT-A.

Compared with conventional insemination, intracytoplasmic sperm injection provides no benefit in cases of nonmale factor infertility as evidenced by comparable euploidy rate.

OBJECTIVE: To evaluate whether differences in euploidy rates exist between intracytoplasmic sperm injection (ICSI) and conventional insemination (CI) in nonmale factor infertility cases. DESIGN: Retrospective cohort study. SETTING: A single, academically affiliated infertility center in the United States. PATIENTS: A total of 3554 patients who underwent in vitro fertilization cycles from January 2014 to December 2021. All cycles that had preimplantation testing for aneuploidy (PGT-A) performed by trophectoderm biopsy and had a postpreparation sperm concentration >4 million total motile sperm per milliliter were included. MAIN OUTCOME MEASURES: The primary outcome was the embryo euploidy rate per embryo biopsied in the ICSI vs. CI group. Secondary outcomes included the fertilization rate and number of embryos biopsied. Generalized estimating equations with a Poisson distribution were used to estimate the euploid rate ratio (with total embryos biopsied as an offset), while accounting for multiple retrievals per patient. To adjust for confounding, a propensity score model was fit for ICSI using 14 baseline female and male characteristics. RESULTS: Oocytes retrieved and the number of embryos biopsied were similar in both groups, while the fertilization rate per oocyte retrieved was significantly lower with ICSI (0.64 vs. 0.66). The proportion of euploid embryos in the ICSI group was significantly lower when compared with CI (0.47 vs. 0.52), with a euploid rate ratio of 0.89. Interestingly, when accounting for the variation in PGT reference laboratories over the study time period, adjusting for the date of procedure did not change the relationship between ICSI and euploid rate (rate ratio = 0.89); however, after adjusting for the PGT reference laboratory, the relationship between ICSI and euploid rate was no longer significant (rate ratio = 0.97). CONCLUSIONS: In the setting of nonmale factor infertility, ICSI resulted in a lower fertilization rate and an 11% lower embryo euploid rate compared with CI. Although the data are not statistically significant when adjusted for the PGT reference laboratory, we still can conclude that ICSI does not provide any benefit. These data support the recommendation that CI should be the preferred methodology for fertilization in nonmale factor infertility cases.

Modified natural and optimized programmed frozen embryo transfers have equivalent live birth rates: an analysis of 6,682 cycles.

OBJECTIVE: To compare the live birth rates (LBRs) in modified natural and programmed single blastocyst frozen embryo transfer (FET) cycles. DESIGN: Retrospective cohort study. SETTING: University-affiliated fertility practice. PATIENT(S): Patients who underwent single blastocyst FETs between January 2014 and December 2019. A total of 15,034 FET cycles from 9,092 patients were reviewed; 1,186 modified natural and 5,496 programmed FET cycles from 4,532 patients met the inclusion criteria for analysis. INTERVENTION(S): No intervention. MAIN OUTCOME MEASURE(S): The primary outcome measure was the LBR. RESULT(S): There was no difference in live birth after programmed cycles using intramuscular (IM) progesterone or a combination of vaginal progesterone and IM progesterone compared with that after modified natural cycles (adjusted relative risks, 0.94 [95% confidence interval {CI}, 0.85-1.04] and 0.91 [95% CI, 0.82-1.02], respectively). The relative risk of live birth decreased in programmed cycles that used exclusively vaginal progesterone compared with that in modified natural cycles (adjusted relative risk, 0.77 [95% CI, 0.69-0.86]). CONCLUSION(S): The LBR decreased in programmed cycles that used only vaginal progesterone. However, no difference in the LBRs existed between modified natural and programmed cycles if programmed cycles used either IM progesterone or a combination of IM and vaginal progesterone protocols. This study demonstrates that modified natural FET cycles and optimized programmed FET cycles have equivalent LBRs.

A diagnosis of diminished ovarian reserve does not impact embryo aneuploidy or live birth rates compared to patients with normal ovarian reserve.

OBJECTIVE: To estimate the aneuploidy rates in young women with diminished ovarian reserve (DOR) before treatment and poor ovarian response (POR) postretrieval. DESIGN: Retrospective cohort study. SETTING: A single academically-affiliated fertility clinic. PATIENT(S): Autologous frozen embryo transfer cycles from December 2014 to June 2020 were reviewed. Demographic and clinical factors that impact outcomes were used for propensity score matching (PSM) in a ratio of 2:1 and 4:1 for preimplantation genetic testing for aneuploidy pre-cycle DOR and POR after stimulation, respectively. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Aneuploid rates, defined as the number of aneuploid blastocysts divided by the number of biopsied blastocysts per cycle. No euploid embryos to transfer, defined as all cohorts of embryos being aneuploid. RESULT(S): A total of 383 women diagnosed with DOR were compared with matched controls. Aneuploid rates did not differ significantly between the two groups (42.2% vs. 41.7%; RR = 1.06; 95% CI, 0.95-1.06). No differences were identified in live birth rates per transfer between women with and without DOR after euploid single-embryo transfers (56.0% and 60.5%, respectively). An additional PSM analysis to assess aneuploidy rates for patients with POR (<5 oocytes) vs. those without it, resulted in similar rates of aneuploidy between the two comparison groups (41.1% vs. 44%, R = 1.02; 95% CI, 0.91-1.14). The prevalence of cycles with "no euploid embryos" in the POR cohort was higher (26% vs. 13%); however, rates of cases with a single embryo available for biopsy were lower in the DOR group, relative to controls (11% vs. 31%). CONCLUSION(S): Young women diagnosed with DOR or POR exhibited equivalent aneuploidy rates and live birth rates per euploid embryo transfer in a large matched population, based on age, body mass index, and IVF cycle initiation. The lower percentage of cycles with no euploid embryo available for transfer in DOR and POR patients is because of the decreased total number of oocytes/developing embryos and not because of increased aneuploidy rates in these groups.

The effect of interpregnancy interval on preterm birth and low birth weight in singleton pregnancies conceived without assistance or by infertility treatments.

OBJECTIVE: To determine the association of interpregnancy interval on perinatal outcomes and whether this was influenced by mode of conception. DESIGN: Retrospective cohort. SETTING: Centers for Disease Control and Prevention's natality national database. PATIENT(S): Patients who had an index singleton live birth with a preceding live birth. Index pregnancies from 2016 to 2019 were conceived with in vitro fertilization (IVF) (n = 32,829) or ovulation induction/intrauterine insemination (OI/IUI) (n = 23,016) or without assistance (n = 7,564,042). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcomes evaluated were preterm birth (<37 weeks) and low birth weight (<2,500 g). Multivariable logistic regression was performed to evaluate the association of interpregnancy intervals with perinatal outcomes stratified by mode of conception. Adjusted odds ratios and 95% confidence intervals (CIs) were presented. RESULT(S): Compared with the interpregnancy interval reference group of 12 to <18 months, a <12 month interpregnancy interval was associated with an increase in preterm birth (<37 weeks) for pregnancies conceived with OI/IUI or without assistance (aOR, 1.42; 95% CI, 1.16-1.74, and aOR, 1.14; 95% CI, 1.13-1.15, respectively), whereas IVF was not associated with an increase (aOR, 0.90; 95% CI, 0.77-1.04). A <12 month interpregnancy interval was associated with an increase in low birth weight for pregnancies conceived with IVF or OI/IUI or without assistance (aOR, 1.34; 95% CI, 1.09-1.64; aOR, 1.33; 95% CI, 1.01-1.76; and aOR, 1.26; 95% CI, 1.24-1.27, respectively). CONCLUSION(S): An interpregnancy interval of at least 12 months reduces adverse perinatal outcomes for pregnancies conceived with and without infertility treatment.

Impact of empathic physician contact on patient anxiety and distress during the waiting period after embryo transfer: a randomized controlled trial.

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.

Endometrial compaction does not predict live birth in single euploid frozen embryo transfers: a prospective study.

STUDY QUESTION: Is there a relationship between endometrial compaction and live birth in euploid frozen embryo transfer (FET) cycles? SUMMARY ANSWER: Live birth rates (LBRs) were similar in both patients that demonstrated endometrial compaction or no compaction in single euploid FETs. WHAT IS KNOWN ALREADY: There has been increasing interest in the correlation between endometrial compaction and clinical outcomes but there has been conflicting evidence from prior investigations. STUDY DESIGN, SIZE, DURATION: This was a prospective observational study from 1 September 2020 to 9 April 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was performed at a single, academically affiliated fertility center in which patients who had an autologous single euploid FET using a programmed or modified natural cycle protocol were included. All embryos had trophectoderm biopsy for preimplantation genetic testing for aneuploidy followed by vitrification at the blastocyst stage. Two ultrasound measurements of endometrial thickness (EMT) were obtained. The first measurement (T1) was measured transvaginally within 1 day of initiation of progesterone or ovulation trigger injection, and a second EMT (T2) was measured transabdominally at the time of embryo transfer (ET). The primary outcome (LBR) was based on the presence and proportion of compaction (percentage difference in EMT between T1 and T2). MAIN RESULTS AND THE ROLE OF CHANCE: Of the 186 participants included, 54%, 45%, 35%, 28% and 21% of women exhibited >0%, ≥5%, ≥10%, ≥15% and ≥20% endometrial compaction, respectively. Endometrial compaction was not predictive of live birth at any of the defined cutoffs. A sub-analysis stratified by FET protocol type (n = 89 programmed; n = 97 modified natural) showed similar results. LIMITATIONS, REASONS FOR CAUTION: There was the potential for measurement error in the recorded EMTs. The T2 measurement was performed transabdominally, which may cause potential measurement error, as it is generally accepted that transvaginal measurements of EMT are more accurate, though, any bias is expected to be non-differential. The sub-analysis performed looking at FET protocol type was underpowered and should be interpreted with caution. Our study, however, represents a pragmatic approach, as it allowed patients to avoid having to come in for an extra transvaginal ultrasound the day before or on the day of ET. WIDER IMPLICATIONS OF THE FINDINGS: Assessing endometrial compaction may lead to unnecessary cycle cancellation. However, further studies are needed to determine if routine screening for endometrial compaction would improve clinical outcomes. STUDY FUNDING/COMPETING INTEREST(S): No authors report conflicts of interest or disclosures. There was no study funding. TRIAL REGISTRATION NUMBER: NCT04330066.

The psychological impact of the coronavirus disease 2019 pandemic on women who become pregnant after receiving treatment for infertility: a longitudinal study.

OBJECTIVE: To compare the impact of the coronavirus disease 2019 (COVID-19) pandemic on the psychological health of patients with infertility who have become pregnant with that of women who have not. DESIGN: Prospective cohort study conducted from April 2020 to June 2020. The participants completed three questionnaires over this period. SETTING: A single large, university-affiliated infertility practice. PATIENTS: A total of 443 pregnant women and 1,476 women still experiencing infertility who completed all three questionnaires. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Patient-reported primary stressor over three months of the first major COVID-19 surge; further data on self-reported sadness, anxiety, loneliness, and the use of personal coping strategies. RESULTS: Pregnant participants were significantly less likely to report taking an antidepressant or anxiolytic medication, were less likely to have a prior diagnosis of depression, were more likely to cite COVID-19 as a top stressor, and overall were less likely to practice stress-relieving activities during the first surge. CONCLUSIONS: Women who became pregnant after receiving treatment for infertility cited the pandemic as their top stressor and were more distressed about the pandemic than their nonpregnant counterparts but were less likely to be engaging in stress-relieving activities. Given the ongoing impact of the pandemic, patients with infertility who become pregnant after receiving treatment should be counseled and encouraged to practice specific stress-reduction strategies.

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.

Clinical outcomes and utilization from over a decade of planned oocyte cryopreservation.

RESEARCH QUESTION: What is the clinical experience of patients who have undergone planned oocyte cryopreservation and oocyte thawing and warming? DESIGN: Retrospective observational cohort study. All women who completed planned oocyte cryopreservation at a single large university-affiliated fertility centre between June 2006 and October 2020 were identified, including the subset who returned to use their oocytes. Patients who underwent oocyte cryopreservation for medical reasons were excluded. Baseline demographics, oocyte cryopreservation and thawing-warming cycle parameters, and clinical outcomes, were extracted from the electronic medical record. The primary outcome was cumulative live birth rate (LBR), and secondary outcomes were cumulative clinical pregnancy rate (CPR), and CPR and LBR per transfer. Results were stratified by age at time of cryopreservation (<38 and ≥38 years). RESULTS: Of 921 patients who underwent planned oocyte cryopreservation, 68 (7.4%) returned to use their oocytes. Forty-six patients (67.6%) completed at least one embryo transfer. The CPR per transfer was 47.5% and LBR was 39.3%. The cumulative LBR per patient who initiated thawing-warming was 32.4%. Cycle outcomes were not significantly different in patients aged younger than 38 years and those aged 38 years or over. No patient aged 40 years or older (n = 6) was successful with their cryopreserved oocytes. Ten patients (14.7%) who were unsuccessful with their cryopreserved oocytes achieved a live birth using donor oocytes, with most (7/10) of these patients aged 38 years and older. CONCLUSION: Only a small percentage of patients returned to use their oocytes, and 32% of those were able to achieve a live birth.

Routine ketorolac at oocyte retrieval decreases postoperative narcotic use by more than 50.

OBJECTIVE: To study the impact of routine ketorolac administration during oocyte retrieval on the proportion of patients who require postoperative narcotics for analgesia. DESIGN: Retrospective cohort study. SETTING: Single, university-affiliated infertility clinic. PATIENTS: All women undergoing oocyte retrieval between July and November 2016 (non-ketorolac group [NKG]; n = 826) and April-August 2017 (ketorolac group, KG; n = 1780). INTERVENTIONS: A single 30 mg intravenous dose of ketorolac was administered after the oocyte retrieval procedure. MAIN OUTCOME MEASURES: The number of patients who required postoperative narcotic analgesia, postoperative complication rate, and fresh embryo transfer pregnancy outcomes were examined. RESULTS: In the KG, we found a significant decrease in the patients who required narcotics after oocyte retrieval compared with the NKG (12% KG vs. 25.5% NKG). We found no significant change in the clinical pregnancy rate (CPR) resulting from fresh embryo transfer after our intervention (NKG CPR 32.6%, KG CPR 32.4%). Furthermore, there was no increase in postoperative bleeding complications in the KG. CONCLUSIONS: Routine use of ketorolac at the time of oocyte retrieval may decrease the rate of postoperative opioid use without adversely impacting pregnancy and complication rates.

Perinatal outcomes in singleton pregnancies after in vitro fertilization cycles over 24 years.

OBJECTIVE: To determine how a shift in clinical practice along with laboratory changes has impacted singleton perinatal outcomes after autologous in vitro fertilization (IVF) cycles. DESIGN: Retrospective cohort. SETTING: Single academic fertility clinic. PATIENT(S): Singleton live births resulting from all IVF cycles (n = 14,424) from August 1, 1995 to October 31, 2019. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth weight, large for gestational age (GA), small for GA, and preterm birth. RESULT(S): The entire cohort consisted of 9,280 fresh and 5,144 frozen IVF cycles. Maternal age, parity, body mass index, neonatal sex, and GA at delivery were similar in both groups. There was a decrease in adjusted birth weight per year over the study period for the entire cohort of IVF cycles (-4.42g, 95% confidence interval [CI]: -6.63g to -2.22g). Rates of large for GA newborns decreased by 1.7% (95% CI: 2.9% to 0.6%) annually across the entire cohort of IVF cycles. Furthermore, there was a decrease in annual rates of preterm birth before 32 weeks by 3.2% (95% CI: 5.9% to 0.5%) across the entire cohort of IVF cycles. Trends were also seen in annual reduction of rates of preterm birth before 37 and 28 weeks. CONCLUSION(S): With the gradual evolution of clinical and IVF laboratory practices, there has been a decrease in birth weight over 24 years for the entire cohort of IVF cycles. Concurrently, noteworthy practice changes have resulted in an improvement in IVF outcomes with decreased rates of large for GA newborns and preterm birth before 32 weeks for the entire cohort of IVF cycles.

The use of propensity score matching to assess the benefit of the endometrial receptivity analysis in frozen embryo transfers.

OBJECTIVE: To study the impact of the endometrial receptivity analysis (ERA) on live birth rates in frozen embryo transfer (FET) cycles. DESIGN: Retrospective cohort study. SETTING: A single, large, university-affiliated infertility practice. PATIENT(S): Autologous FET cycles between January 1, 2014, and June 30, 2019, were reviewed. Multiple covariates that impact outcomes were used for propensity score matching; 133 ERA patients were matched to 353 non-ERA patients. Patients were assigned to the ERA group if they had an ERA during treatment and underwent at least one "personalized" FET based on the ERA recommendations. INTERVENTION(S): No interventions administered. MAIN OUTCOME MEASURE(S): Live birth rates per cycle in the FET cycle after ERA compared with that of matched non-ERA patients. RESULT(S): The live birth rates for the ERA group, 49.62%, and the matched non-ERA group, 54.96%, (odds ratio 0.8074; 95% confidence interval, 0.5424-1.2018) were not significantly different, nor was a difference seen in subanalyses based on prior number of FETs or receptivity status. CONCLUSION(S): The ERA identifies a patient's putative window of implantation with the goal of improving synchrony with the embryo, thereby achieving higher live birth rates. This study used propensity score matching to control for multiple covariates in a heterogenous group of patients to compare live birth rates. There was no difference in the live birth rate in patients who underwent the ERA compared with that of those who did not.