Trophectoderm biopsy is associated with lower risks of moderate to extreme prematurity and low birthweights: a national registry cohort study of singleton livebirths from frozen-thawed blastocyst transfers.

BACKGROUND: Trophectoderm biopsy has become the mainstay assisted reproductive technique performed for preimplantation genetic testing, accounting for 43.8% of embryo transfer cycles in the United States in 2019 alone. Despite its prevalence, data on the obstetric and perinatal outcomes post-trophectoderm biopsy remains sparse and mixed. OBJECTIVE: This study aimed to examine the risks of adverse perinatal outcomes in birthweights and prematurity after transfers of the vitrified-thawed blastocyst with trophectoderm biopsy for preimplantation genetic testing. STUDY DESIGN: This was a retrospective observational cohort study of 45,712 singleton livebirths resulting from autologous vitrified-thawed blastocyst transfer cycles with or without trophectoderm biopsy for preimplantation genetic testing, reported by participating member clinics to the Society for Assisted Reproductive Technology national registry between 2014 and 2017. Adverse perinatal outcomes of preterm births and low birthweights were analyzed. Multivariable regression analyses were performed to control for covariates. Comparing the trophectoderm biopsy (n=21,584) and no trophectoderm biopsy (n=24,128) groups, adjusted odds ratios were calculated for the outcomes of small-for-gestational-age, large-for-gestational-age, low birthweight <2500 g, very low birthweight <1500 g, extremely low birthweight <1000 g, late preterm births <37 weeks, moderate preterm births <34 weeks, and extremely preterm births <28 weeks. RESULTS: Women in the trophectoderm biopsy group were older and more likely to have prior pregnancies, deliveries, and a history of spontaneous abortions. Tobacco use, diminished ovarian reserve, and recurrent pregnancy loss were also more prevalent in the trophectoderm biopsy group. Trophectoderm biopsy was not associated with small-for-gestational-age (adjusted odds ratio, 0.97; 95% confidence interval, 0.85-1.12; P=.72) or large-for-gestational-age newborns (adjusted odds ratio, 1.10; 95% confidence interval, 0.99-1.22; P=.09). Risks of preterm births <37 weeks gestation were similar between the biopsy and nonbiopsy groups (adjusted odds ratio, 0.93; 95% confidence interval, 0.85-1.02; P=.11). Trophectoderm biopsy was associated with a significantly lower risk of low birthweight <2500 g (adjusted odds ratio, 0.80; 95% confidence interval, 0.70-0.92; P<.001), very low birthweight <1500 g (adjusted odds ratio, 0.62; 95% confidence interval, 0.46-0.83; P<.001), extremely low birthweight <1000 g (adjusted odds ratio, 0.48; 95% confidence interval, 0.31-0.74; P<.001), moderate preterm birth <34 weeks (adjusted odds ratio, 0.76; 95% confidence interval, 0.64-0.91; P=.003), and extreme preterm birth <28 weeks (adjusted odds ratio, 0.63; 95% confidence interval, 0.43-0.92; P=.02). CONCLUSION: Trophectoderm biopsy is not associated with increased risks of small-for-gestational-age, large-for-gestational-age, or late preterm birth. Risks of low birthweight, very low birthweight, and extremely low birthweight from moderate and extreme preterm births are lower after trophectoderm biopsy, possibly by selecting against confined placental mosaicism or inducing placental epigenetic changes, the mechanisms of which warrant further investigation.

PGT-A is associated with reduced cumulative live birth rate in first reported IVF stimulation cycles age ≤ 40: an analysis of 133,494 autologous cycles reported to SART CORS.

PURPOSE: To evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on cumulative live birth rate (CLBR) in IVF cycles. METHODS: Retrospective cohort study of the SART CORS database, comparing CLBR for patients using autologous oocytes, with or without PGT-A. The first reported autologous ovarian stimulation cycle per patient between January 1, 2014, and December 31, 2015, and all linked embryo transfer cycles between January 1, 2014, and December 31, 2016, were included in the study. Exclusion criteria were donor oocyte cycles, donor embryo cycles, gestational carrier cycles, cycles which included both a fresh embryo transfer (ET) combined with a thawed embryo previously frozen (ET plus FET), or cycles with a fresh ET after PGT-A. RESULTS: A total of 133,494 autologous IVF cycles were analyzed. Amongst patients who had blastocysts available for either ET or PGT-A, including those without transferrable embryos, decreased CLBR was noted in the PGT-A group at all ages, except ages > 40 (p < 0.01). A subgroup analysis of only those patients who had PGT-A and a subsequent FET, excluding those without transferrable embryos, demonstrated a very high CLBR, ranging from 71.2% at age < 35 to 50.2% at age > 42. Rates of multiple gestations, preterm birth, early pregnancy loss, and low birth weight were all greater in the non-PGT-A group. CONCLUSIONS: PGT-A was associated with decreased CLBR amongst all patients who had blastocysts available for ET or PGT-A, except those aged > 40. The negative association of PGT-A use and CLBR per cycle start was especially pronounced at age < 35.

Psychological experience and coping strategies of patients in the Northeast US delaying care for infertility during the COVID-19 pandemic.

BACKGROUND: On March 17, 2020 an expert ASRM task force recommended the temporary suspension of new, non-urgent fertility treatments during an ongoing world-wide pandemic of Covid-19. We surveyed at the time of resumption of fertility care the psychological experience and coping strategies of patients pausing their care due to Covid-19 and examined which factors were associated and predictive of resilience, anxiety, stress and hopefulness. METHODS: Cross sectional cohort patient survey using an anonymous, self-reported, single time, web-based, HIPPA compliant platform (REDCap). Survey sampled two Northeast academic fertility practices (Yale Medicine Fertility Center in CT and Montefiore's Institute for Reproductive Medicine and Health in NY). Data from multiple choice and open response questions collected demographic, reproductive history, experience and attitudes about Covid-19, prior infertility treatment, sense of hopefulness and stress, coping strategies for mitigating stress and two validated psychological surveys to assess anxiety (six-item short-form State Trait Anxiety Inventory (STAl-6)) and resilience (10-item Connor-Davidson Resilience Scale, (CD-RISC-10). RESULTS: Seven hundred thirty-four patients were sent invitations to participate. Two hundred fourteen of 734 (29.2%) completed the survey. Patients reported their fertility journey had been delayed a mean of 10 weeks while 60% had been actively trying to conceive > 1.5 years. The top 5 ranked coping skills from a choice of 19 were establishing a daily routine, going outside regularly, exercising, maintaining social connection via phone, social media or Zoom and continuing to work. Having a history of anxiety (p < 0.0001) and having received oral medication as prior infertility treatment (p < 0.0001) were associated with lower resilience. Increased hopefulness about having a child at the time of completing the survey (p < 0.0001) and higher resilience scores (p < 0.0001) were associated with decreased anxiety. Higher reported stress scores (p < 0.0001) were associated with increased anxiety. Multiple multivariate regression showed being non-Hispanic black (p = 0.035) to be predictive of more resilience while variables predictive of less resilience were being a full-time homemaker (p = 0.03), having received oral medication as prior infertility treatment (p = 0.003) and having higher scores on the STAI-6 (< 0.0001). CONCLUSIONS: Prior to and in anticipation of further pauses in treatment the clinical staff should consider pretreatment screening for psychological distress and provide referral sources. In addition, utilization of a patient centered approach to care should be employed.

Fertility preservation for cancer patients: treatment gaps and considerations in patients' choices.

PURPOSE: Women with cancer may desire fertility preservation (FP) prior to initiating cancer treatment, but undergoing FP may result in treatment delays. This study sought to determine whether such delays existed in our population and which factors were associated with patients' decision to proceed with FP. METHODS: This was a historical cohort study performed at Montefiore Medical Center's Institute for Reproductive Medicine and Health. Reproductive age women diagnosed with cancer and consulted for FP were included. The main outcome measure was the number of days between FP consultation and cancer treatment initiation. Factors associated with patients' decisions to proceed with FP were also analyzed. RESULTS: Thirty out of 51 women in our study underwent FP including embryo cryopreservation, oocyte cryopreservation, ovarian tissue cryopreservation (OTC), both oocyte and embryo cryopreservation, or GnRH agonist treatment. The majority of women who underwent FP chose embryo cryopreservation (36.7%), followed by oocyte cryopreservation (33.3%). Of the 20 patients with partners who underwent FP, 13 (65%) froze embryos. Only 4 of the 30 women who underwent FP had all, or a portion of their services, covered by insurance. The mean treatment delay was 18 days (p = 0.007), with a mean consultation to oncologic treatment gap of 23 ± 16.8 and 41.4 ± 25.9 days in the non-FP and FP groups, respectively. CONCLUSION: Women with cancer diagnosis who underwent FP prior to initiating cancer treatment experienced a statistically significant delay in initiating cancer treatment. However, the clinical significance of this finding is unknown since FP treatments have not been associated with increased recurrence or mortality.

Length of ovarian stimulation does not impact live birth rate in fresh donor oocyte cycles: a SART CORS study.

PURPOSE: To evaluate the effect of controlled ovarian hyperstimulation length and total gonadotropin (GN) dose on recipient live birth rate (LBR) in fresh donor oocyte cycles. METHODS: Data was obtained from SART CORS on all fresh donor oocyte GnRH antagonist cycles (n = 1049) between 2014 and 2015 which resulted in a single embryo transferred. Donor and recipient demographic information and cycle characteristics were extracted. Binomial regression was used to estimate LBR with respect to days of stimulation (DOS) and total GN dose. Multivariate analysis was performed to evaluate these relationships after controlling for confounders. RESULTS: Overall LBR in fresh donor oocyte cycles was 57%. Average stimulation length was 14.3 ± 4.9 days, and total GN dose was 2464 ± 1062 IU. On univariate analysis, neither days of stimulation (p = 0.5) nor total GN dose (p = 0.57) was independently correlated with LBR. However, in prolonged stimulations (> 15 days) with high total GN dose (> 3000 IU), as both the cycle length and total GN dose increased, LBR significantly decreased from 63.81 to 48.15% (p = 0.02) and from 67.61 to 48.15% (p = 0.01), respectively. Multivariate analysis showed no significant effect of either DOS or total GN dose on LBR. CONCLUSIONS: LBR is significantly decreased in fresh donor oocyte cycles when cycles are prolonged with high total GN dose. However, after controlling for confounders neither DOS nor total GN dose significantly affects LBR.

Counseling patients on reproductive aging and elective fertility preservation-a survey of obstetricians and gynecologists' experience, approach, and knowledge.

PURPOSE: What are the experience, approach, and knowledge of US Obstetricians and Gynecologists' (ob-gyn) towards counseling patients on reproductive aging (RA) and elective fertility preservation (EFP). METHODS: A cross-sectional survey emailed by the American College of Obstetricians and Gynecologists (ACOG) to 5000 ACOG fellows consisting of 9 demographic and 28 questions relating to counseling patients on RA and EFP. RESULTS: Seven hundred and eighty-four responders completed the survey. Although 82.8% agreed that conversations relating to RA should take place with patients desiring future childbearing and delaying due to social reasons, only 27.6% stated that they frequently counsel these women aged 18-34 years old, compared to 75.8% aged 35-44 years old (P < 0.01). Limited time (75.8%) and limited knowledge (41.4%) were amongst the most frequent reported barriers towards counseling patients on RA. Fifty-eight percent stated that they have been asked about EFP by patients. Although 74.8% agreed that conversations should take place related to EFP in women desiring future childbearing and delaying due to social reasons, only 27.6% stated that they frequently counsel these patients on EFP (P < 0.01). Limited time (75%) and limited knowledge (59.9%) were amongst the most frequent barriers towards counseling on EFP. CONCLUSIONS: In the USA, methods to improve patient counseling and provider knowledge on RA and EFP are warranted and further studies are needed to address optimal methods to improve counseling and knowledge related to these topics.

Obesity adversely affects serum anti-müllerian hormone (AMH) levels in Caucasian women.

OBJECTIVE: Previous studies regarding the effect of obesity on serum anti-müllerian hormone (AMH) levels have been conflicting. Our aim was to determine the effect of obesity on serum AMH levels among women from different racial backgrounds. METHODS: The medical records of 350 women (159 Caucasian, 99 African-American, 58 Hispanic, 34 Asian with ages 16-46) evaluated for infertility at an academic-affiliated center and who had AMH levels measured as part of their evaluation were reviewed. Age, AMH, body mass index (BMI), self-reported race, etiology of infertility, smoking history, maximum serum early follicular follicle-stimulating hormone (FSH) levels, antral follicle count (AFC), and history of ovarian surgery, chemotherapy, or radiotherapy were recorded. RESULTS: Age correlated negatively with AMH and antral follicle count across all races (p < 0.05). After adjusting for age, polycystic ovary syndrome diagnosis, and smoking, elevated BMI had a negative correlation with AMH in Caucasian women (ß = 0.17, p = 0.01) but not in African-American, Hispanic, or Asian women. CONCLUSION: Elevated BMI correlates negatively with AMH in Caucasian women but not in African-American, Hispanic, or Asian women. Additional studies are needed to elucidate further the effect of race on the interaction between obesity and ovarian reserve.

Comparing reproductive outcomes between conventional in vitro fertilization and nonindicated intracytoplasmic sperm injection in autologous embryo transfer cycles: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System Study.

Objective: To compare clinical outcomes between nonindicated intracytoplasmic sperm injection (ICSI) and conventional insemination. Design: Autologous cycles performed from 2014-2017 were identified, excluding frozen oocyte cycles. Outcomes were compared between conventional insemination (in vitro fertilization [IVF]) and nonindiated ICSI and analyzed separately for fresh, frozen-thawed preimplantation genetic testing (PGT) and frozen-thawed non-PGT cycles. Setting: US-based fertility clinics reporting to the Society for Assisted Reproductive Technology. Participants: A total of 187,520 patients underwent 318,930 cycles, 57,516 (18.0%) using conventional IVF and 261,414 ICSI (82.0%). Interventions: Intracytoplasmic sperm injection, with or without indications (male factor, prior fertilization failure or any PGT [2012 recommendations]/single-gene PGT [2020 recommendations]). Main Outcome Measures: Odds ratios (ORs) for live birth rates and clinical pregnancy rates were calculated after multivariable adjustment for maternal age, body mass index, infertility etiologies, prior IVF births, and number oocytes retrieved. Results: Intracytoplasmic sperm injection was indicated in 151,627 (58.0%) of cycles according to 2012 American Society for Reproductive Medicine Practice Committee recommendations, and 108,895 (41.7%) according to 2020 recommendations. In multivariable models, nonindicated ICSI among fresh cycles was associated with reduced odds of completing a blastocyst-stage transfer (OR, 0.72; 95% confidence interval [CI] [0.7, 0.75]; P<.001), resulting in reduced odds of live birth (OR, 0.80; 95% CI [0.78, 0.83]; P<.001). Among completed fresh transfers, clinical pregnancy and live birth rates were comparable between nonindicated ICSI and IVF. Nonindicated ICSI in frozen-thawed cycles with PGT and without PGT was associated with comparable live birth and clinical pregnancy rates with IVF in multivariable models. Conclusion: Nonindicated ICSI was associated with reduced blastocyst availability in fresh cycles compared with IVF, leading to lower live birth rates. Outcomes from completed transfers were clinically comparable.

A retrospective comparison of the impact of industry payments on assisted reproductive technology practice and outcomes.

OBJECTIVE: To determine whether industry payments to physicians are associated with a difference in assisted reproductive technology practices and outcomes. DESIGN: Retrospective cohort. SETTING: Assisted reproductive technology centers. PATIENT(S): Patients undergoing asissted reproduction. INTERVENTION(S): Industry payments reported to the Open Payments 2020 database. MAIN OUTCOME MEASURE(S): The live birth rate, frozen embryo transfer (FET) rate, intracytoplasmic sperm injection (ICSI) rate, preimplantation genetic testing (PGT) rate, and percentage of patients aged >40 years were obtained from the Centers for Disease Control and Prevention 2020 database. Linear regression analysis was performed comparing the percentage of physicians per center receiving industry payments to clinic-level outcomes. RESULT(S): A total of 873 reproductive endocrinology and infertility physicians received payments in the 2020 database. At least one physician received a payment in 80.5% (437/543) of in vitro fertilization centers. Of 1,724 reproductive endocrinology and infertility physicians, 873 (50.6%) received at least one payment in 2020. The live birth, ICSI, FET, and PGT rates and percentage of patients aged >40 years did not significantly differ between centers by percentage of physicians receiving industry payments. However, in the subanalysis of 99 large centers (defined as ≥5 physicians), each increase in the percentage of physicians receiving industry payments was associated with increases of 0.20% (95% confidence interval, 0.02-0.39) and 0.14% (95% confidence interval, 0.05-0.24) in the PGT and FET rates, respectively. The live birth, ICSI rates and percentage of patients aged >40 years were not associated with increased industry payment rates to physicians. CONCLUSION(S): Industry payments were not associated with differences in in vitro fertilization center outcomes overall. However, large centers with more physicians receiving industry payments may be more likely to use additional procedures such as PGT and FET, without improvement in the final outcomes such as the live birth rate. Further research is needed to determine whether these differences reflect the industry payment influence vs. individual center/provider practice habits in larger practices.

Placental site nodules and reproductive outcomes: a clinicopathologic case series.

BACKGROUND: Placental site nodules (PSNs) are benign tumor-like growths that develop from chorionic-type intermediate trophoblastic cells. Their clinical significance is unknown. This study aims to determine the risk factors associated with PSNs, with focus on possible reproductive impact. METHODS: We performed a retrospective case series of all patients with a pathology diagnosis of PSN in a large urban hospital system from 2018 to 2022. We collected clinical variables such as pathology diagnosis/description, presenting symptoms, method of prior delivery, and prior history of infertility, pregnancy loss, and uterine instrumentation. RESULTS: A total of 32 patients were included in this case series. The most common presenting symptom was abnormal uterine bleeding (40.6%, 13/32). Recurrent pregnancy loss (RPL) (15.6%, 5/32) and infertility (15.6%, 5/32) were common presenting symptoms as well. 62.5% (20/32) patients had a history of prior uterine instrumentation. Coexisting chronic endometritis was identified in 9.4% (3/32) of cases. Of the 5 RPL/infertility patients who underwent hysteroscopic resection of a PSN, 1 achieved a live birth. CONCLUSION: PSNs may be associated with abnormal uterine bleeding, recurrent pregnancy loss, infertility, history of prior uterine instrumentation, and chronic endometritis. Although a rare diagnosis, the presence of a PSN should be considered in patients presenting for infertility or recurrent pregnancy loss workup.

Higher live birth rates are associated with a normal body mass index in preimplantation genetic testing for aneuploidy frozen embryo transfer cycles: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System study.

OBJECTIVE: To determine whether body mass index (BMI) was associated with live birth in patients undergoing transfer of frozen-thawed preimplantation genetic testing for aneuploidy (PGT-A) embryos. DESIGN: Retrospective cohort study of cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. SUBJECTS: All autologous and donor recipient PGT-A-tested cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System from 2014 to 2017. INTERVENTION(S): Body mass index. MAIN OUTCOME MEASURE(S): The primary outcome measure was the live birth rate, and the secondary outcome measures were the clinical pregnancy and biochemical pregnancy rates. Multivariable generalized additive mixed models and log-binomial models were used to model the relationship between BMI and outcome measures. RESULT(S): A total of 77,018 PGT-A cycles from 55,888 patients were analyzed. Of these cycles, 70,752 were autologous, and 6,266 were donor recipient. In autologous cycles, a statistically significant and clear nonlinear relationship was observed between the BMI and live birth rates, with the highest birth rates observed for the BMI range of 23-24.99 kg/m2. When using 23-24.99 kg/m2 as the referent, other BMI ranges demonstrated a lower probability of live birth and clinical pregnancy that continued to decrease as the BMI moved further from the reference value. Patients with a BMI of <18.5 kg/m2 had a 11% lower probability of live birth, whereas those with a BMI of ≥40 kg/m2 had a 27% lower probability than the referent. CONCLUSION(S): A normal-weight BMI range of 23-24.99 kg/m2 was associated with the highest probability of clinical pregnancy and live birth after a frozen-thawed PGT-A-tested blastocyst transfer in both autologous and donor recipient cycles. A BMI outside the range of 23-24.99 kg/m2 is likely associated with a malfunction in the implantation process, which is presumed to be related to a uterine factor and not an oocyte factor, as both autologous and donor recipient cycle outcomes were associated similarly with the BMI of the intended parent.

Obstetric and Neonatal Outcomes After Transferring More Than One Embryo in Patients With Preimplantation Genetic Testing.

OBJECTIVE: To compare obstetric and neonatal outcomes after single embryo transfer (SET) compared with multiple embryo transfer (MET) from frozen-thawed transfer cycles of embryos that underwent preimplantation genetic testing for aneuploidies (PGT-A). METHODS: We conducted a retrospective cohort study from the SART CORS (Society for Assisted Reproductive Technology Clinic Outcome Reporting System) national database. Clinical and demographic data were obtained from the SART CORS database for all autologous and donor egg frozen-thawed transfer cycles of embryos that underwent PGT-A between 2014 and 2016, after excluding cycles that used frozen oocytes, fresh embryo transfer, and transfers of embryos from more than one stimulation cycle. Multivariable linear and log-binomial regression models were used to estimate the relative and absolute difference in live-birth rate, multiple pregnancy rate, gestational age at delivery, and birth weight between SET compared with MET. RESULTS: In total, 15,638 autologous egg transfer cycles and 944 donor egg transfer cycles were analyzed. Although the live-birth rate was higher with MET compared with SET in the autologous oocyte cycles (64.7% vs 53.2%, relative risk [RR] 1.24, 95% CI, 1.20-1.28), the multiple pregnancy rate was markedly greater (46.2% vs 1.4%, RR 32.56, 95% CI, 26.55-39.92). Donor oocyte cycles showed similar trends with an increased live-birth rate (62.0% vs 49.7%, RR 1.26, 95% CI, 1.11-1.46) and multiple pregnancy rate (54.0% vs 0.8%) seen with MET compared with SET. Preterm delivery rates and rates of low birth weight were significantly higher in MET compared with SET in both autologous and donor oocyte cycles and were also higher in the subanalysis of singleton deliveries that resulted from MET compared with SET. CONCLUSION: Despite some improvement in live-birth rate, nearly half of the pregnancies that resulted from MET of embryos that underwent PGT-A were multiples. Compared with SET, MET is associated with significantly higher rates of neonatal morbidity, including preterm delivery and low birth weight. The transfer of more than one embryo that underwent PGT-A should continue to be strongly discouraged, and patients should be counseled on the significant potential for adverse outcomes.

Preimplantation genetic testing for aneuploidy is associated with reduced live birth rates in fresh but not frozen donor oocyte in vitro fertilization cycles: an analysis of 18,562 donor cycles reported to Society for Assisted Reproductive Technology Clinic Outcome Reporting System.

OBJECTIVE: To evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on first transfer live birth rate (LBR) and cumulative LBR (CLBR) in donor oocyte in vitro fertilization (IVF) cycles. DESIGN: Retrospective cohort study of the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database. SETTING: Fertility centers reporting to Society for Assisted Reproductive Technology. PATIENT(S): A total of 11,348 fresh and 7,214 frozen-thawed donor oocyte IVF cycles were analyzed. INTERVENTION(S): The first reported donor stimulation cycle per patient between January 1, 2014, and December 31, 2015, and all linked embryo transfer cycles between January 1, 2014, and December 31, 2016, were included in the study. MAIN OUTCOME MEASURE(S): Live birth rate was compared for patients using fresh and frozen-thawed donor oocytes, with or without PGT-A. Logistic regression models were adjusted for age, body mass index, gravidity, infertility etiology, and prior IVF cycles. RESULT(S): Among patients who had blastocysts available for transfer or PGT-A, the use of PGT-A was associated with a decreased first transfer LBR (46.9 vs. 53.2%) and CLBR (58.4 vs. 66.6%) in fresh oocyte donor cycles compared with no PGT-A. Live birth rate in frozen-thawed oocyte donor cycles with PGT-A were nominally higher than those without PGT-A (48.3% vs. 40.5%) but were not statistically significant in multivariable logistic regression models. Early pregnancy loss was not significantly different with and without PGT-A. Multiple gestation, preterm birth, and low birth weight infants were all reduced with the addition of PGT-A in fresh donor oocyte cycles, although these outcomes were not significantly different when comparing single embryo transfers in fresh oocyte cycles and also not significantly different among frozen-thawed donor oocyte cycles. CONCLUSION(S): Preimplantation genetic testing for aneuploidy in fresh oocyte donor cycles was associated with decreased LBR and CLBR, whereas effects on frozen-thawed oocyte donor cycles were clinically negligible. Obstetric benefits associated with PGT-A in fresh donor cycles appear linked to increased single embryo transfer.

The promise and peril of using a large language model to obtain clinical information: ChatGPT performs strongly as a fertility counseling tool with limitations.

OBJECTIVE: To compare the responses of the large language model-based "ChatGPT" to reputable sources when given fertility-related clinical prompts. DESIGN: The "Feb 13" version of ChatGPT by OpenAI was tested against established sources relating to patient-oriented clinical information: 17 "frequently asked questions (FAQs)" about infertility on the Centers for Disease Control (CDC) Website, 2 validated fertility knowledge surveys, the Cardiff Fertility Knowledge Scale and the Fertility and Infertility Treatment Knowledge Score, as well as the American Society for Reproductive Medicine committee opinion "optimizing natural fertility." SETTING: Academic medical center. PATIENT(S): Online AI Chatbot. INTERVENTION(S): Frequently asked questions, survey questions and rephrased summary statements were entered as prompts in the chatbot over a 1-week period in February 2023. MAIN OUTCOME MEASURE(S): For FAQs from CDC: words/response, sentiment analysis polarity and objectivity, total factual statements, rate of statements that were incorrect, referenced a source, or noted the value of consulting providers. FOR FERTILITY KNOWLEDGE SURVEYS: Percentile according to published population data. FOR COMMITTEE OPINION: Whether response to conclusions rephrased as questions identified missing facts. RESULT(S): When administered the CDC's 17 infertility FAQ's, ChatGPT produced responses of similar length (207.8 ChatGPT vs. 181.0 CDC words/response), factual content (8.65 factual statements/response vs. 10.41), sentiment polarity (mean 0.11 vs. 0.11 on a scale of -1 (negative) to 1 (positive)), and subjectivity (mean 0.42 vs. 0.35 on a scale of 0 (objective) to 1 (subjective)). In total, 9 (6.12%) of 147 ChatGPT factual statements were categorized as incorrect, and only 1 (0.68%) statement cited a reference. ChatGPT would have been at the 87th percentile of Bunting's 2013 international cohort for the Cardiff Fertility Knowledge Scale and at the 95th percentile on the basis of Kudesia's 2017 cohort for the Fertility and Infertility Treatment Knowledge Score. ChatGPT reproduced the missing facts for all 7 summary statements from "optimizing natural fertility." CONCLUSION(S): A February 2023 version of "ChatGPT" demonstrates the ability of generative artificial intelligence to produce relevant, meaningful responses to fertility-related clinical queries comparable to established sources. Although performance may improve with medical domain-specific training, limitations such as the inability to reliably cite sources and the unpredictable possibility of fabricated information may limit its clinical use.

Adherence to embryo transfer guidelines in favorable-prognosis patients aged less than 35 years using autologous oocytes and in recipients using donor oocytes: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System study.

OBJECTIVE: To measure the consequences of nonadherence with the 2013 American Society for Reproductive Medicine elective single embryo transfer (eSET) guidelines for favorable-prognosis patients. DESIGN: Retrospective cohort. SETTING: In vitro fertilization clinics. PATIENT(S): A total of 28,311 fresh autologous, 2,500 frozen-thawed autologous, and 3,534 fresh oocyte-donor in vitro fertilization cycles in 2014-2016 at Society for Assisted Reproductive Technology-reporting centers. INTERVENTION(S): Patients aged <35 years or using donors aged <35 years underwent first blastocyst transfer. MAIN OUTCOME MEASURE(S): Singleton birth rate, gestational age at delivery, and birth weight were compared between the eSET and non-eSET groups using the chi-square or Fisher's exact test or t-tests. RESULT(S): Among fresh transfers, 15,643 (55%) underwent eSET. Live births after non-eSETs were less likely singletons (38.0% vs. 96.5%; adjusted relative risk [aRR], 0.56) and more likely complicated by preterm delivery (55.0% vs. 20.1%; aRR, 2.39) and low birth weight (<2,500 g) (40.1% vs. 10.6%; aRR, 3.4) compared with those after eSET. Among frozen-thawed transfers, 1,439 (58%) underwent eSET. Live births after non-eSETs were less likely singletons (41.9% vs. 95.2%; aRR, 0.69; 95% confidence interval, 0.66-0.73) and more likely complicated by preterm delivery (56.4% vs. 19.5%; aRR, 2.6; 95% confidence interval, 2.2-3.1) and low birth weight (38.0% vs. 8.9%; aRR, 3.9) compared with those after eSET. Among fresh donor oocyte transfers, 1,946 (55%) underwent eSET. Live births after non-eSETs were less likely singletons (31.3% vs. 97.3%; aRR, 0.48) and more likely complicated by preterm delivery (61.1% vs. 25.7%; aRR, 2.09) and low birth weight (44.3% vs. 11.7%; aRR, 3.39) compared with those after eSET. CONCLUSION(S): Nonadherence with transfer guidelines was associated with dramatically increased multiple pregnancies, preterm births, and low birth weights.

Presence of endometrial nucleolar channel systems at the time of frozen embryo transfer in hormone replacement cycles with successful implantation.

OBJECTIVE: To detect nucleolar channel systems (NCSs) in cells in endometrial aspirations obtained immediately before embryo transfer during blastocyst hormone replacement therapy-frozen embryo transfer (HRT-FET) cycles without affecting implantation. DESIGN: Prospective case series. SETTING: University-affiliated fertility clinic. PATIENTS: Five patients who underwent an HRT-FET cycle consented to lower uterine segment aspiration using an open-tip embryo transfer catheter during a routine mock transfer performed immediately before embryo transfer. INTERVENTIONS: Exfoliated cells in the aspirated endometrial secretions were analyzed for the presence of NCSs using indirect immunofluorescence and, in one case, electron microscopy for unambiguous identification. MAIN OUTCOME MEASURES: On the basis of a previous study, positive NCS status was defined as the presence of NCSs in at least 3 endometrial epithelial cells (EECs). The effect of endometrial aspiration on implantation and pregnancy outcomes was assessed. RESULTS: Biochemical pregnancy, as evidenced by positive ß-human chorionic gonadotropin, was seen in 5 of 5 patients, and clinical pregnancy was seen in 2 of 5 patients. NCSs were detected in exfoliated EECs of uterine secretions in 4 of 5 patient samples and could not be unequivocally identified in 1 of 5 patient samples, which was designated as indeterminate. CONCLUSIONS: This is the first report of NCS detection in HRT-FET cycles in the absence of follicular development and ovulation. NCS status can be determined in exfoliated EECs of uterine secretions obtained at the time of embryo transfer while maintaining implantation. Our study furthers the goal of establishing whether individualized point of care testing of NCS status in HRT-FET cycles can determine optimal endometrial receptivity and improve pregnancy outcomes.

Early experience with universal SARS-CoV-2 testing in a New York-based reproductive endocrinology practice.

The SARS-CoV-2 pandemic peak around March 2020 led to temporary closures of most fertility clinics. Many clinics reopened but required universal SARS-CoV-2 screening. However, the rate of positive results and the necessity for such testing is unknown. We report here on early results from asingle-center academic NewYork fertility practice utilizing universal SARS-CoV-2 screening. This mixed prospective retrospective cohort included 164 patients who underwent at least one SARS-CoV-2 screening test for fertility treatment between May and July2020. Patients completed 1 to 3 nasopharyngeal SARS-CoV-2 tests per cycle and remained symptom-free to continue fertility treatments. SARS-CoV-2 test results, past results, history of Covid-19 infection, and patient/cycle characteristics were recorded and tabulated through October2020. Outcomes included positive SARS-CoV-2 RNA tests, rate of prior Covid-19 infections, and clinical courses of patients testing positive. Patients underwent 263 cycles entailing 460 total SARS-CoV-2 screening tests. Fifteen patients reported astrong prior clinical history of Covid-19. Six patients experienced apositive SARS-CoV-2 test (2.3% of all cycles). Among 77 cycles (n = 58 patients) entailing one SARS-CoV-2 test, 2 cases (2.6%) were noted. Among 173 cycles (n = 121 patients) entailing two SARS-CoV-2 tests, 4 cycles (2.3%) were noted. Zero (0%) of 13 cycles (n = 13 patients) entailing 3 SARS-CoV-2 tests were positive. All patients were cleared to resume treatment within one month. Overall, anew asymptomatic infection was identified in 2 cycles (0.8%), while 4 of the 6 positive SARS-CoV-2 tests were among patients with aprior history of Covid-19. 3 of 4 also had adocumented prior positive RNA test. Our data suggest that universal SARS-CoV-2 screening among fertility patients is feasible, with an approximately 2% positive rate per cycle among the patients of this study. Most positive patients had aprior remote infection, but their infectiousness while being screened remains unclear.Abbreviations: REI: reproductive endocrinology and infertility; IUI: intrauterine insemination; IVF: in vitro fertilization; sono: sonography; cryo: cryopreservation; FET: frozen embryo transfer.

Prolonged gonadotropin stimulation is associated with decreased ART success.

PURPOSE: to evaluate whether the duration of gonadotropin stimulation predicts the likelihood of live birth after ART. METHODS: all IVF or ICSI cycles using fresh autologous oocytes at our institution between January 2004 and December 2007 were analyzed. RESULTS: out of 699 cycles resulting in oocyte retrieval, 193 produced a live birth (27.6%). Women who achieved a live birth had a significantly shorter stimulation phase (11.1 vs. 11.5 days, respectively). Multivariable analysis suggested that 13 days or longer of stimulation decreased the likelihood of a live birth by 53% as compared to cycles that were 10-12 days long (odds ratio [OR] 0.47; 95% confidence interval [CI]: 0.30-0.75) after adjustment for female age, maximum historical FSH, total dose of gonadotropin received, oocytes retrieved, embryos transferred, antagonist suppression and PCOS diagnosis. CONCLUSIONS: prolonged duration of gonadotropin stimulation is an independent negative predictor of ART success in our cohort.