Use Of Preimplantation Genetic Testing Research Articles

Effect of Paternal Body Mass Index on Cumulative Live Birth Rates: Retrospective Analysis of 3048 Embryo Transfers in Couples Using Autologous Gametes

Obesity is a multifactorial disease present worldwide and correlated with hormonal alterations that may cause a decrease in reproductive outcomes and seminal quality. However, the specific mechanisms involved are unknown. This led us to examine the relationship between paternal body mass index (BMI) and clinical reproductive outcomes by evaluating the cumulative live birth rates (CLBRs) per number of embryo transfers (ETs), embryos replaced (EmbRs), and oocytes used (OUs) in consecutive treatments until achieving the first newborn. A retrospective study was performed, and Kaplan–Meier survival curves were created to observe CLBRs with regard to the paternal BMI, adjusted by relevant confounders through Cox regression models. The participants were couples undergoing intracytoplasmic sperm injection (ICSI) and ET in Spanish IVIRMA clinics using autologous gametes. The cohort was subdivided based on paternal BMI: normal (18.5–24.99 kg/m2) (N), overweight (25–29.99 kg/m2) (OV), or obese (≥30 kg/m2) (OB) patients. A total of 4750 ICSI cycles were included, encompassing 49,485 mature oocytes, 23,963 blastocysts, and 3048 ETs. When calculating CLBRs based on the number of ETs carried out until live birth was achieved, no statistically significant differences were found (p = 0.72). After adjusting for maternal age and BMI, female infertility diagnosis, the use of preimplantation genetic testing, and the number of ETs, Cox regression showed that there were no statistically significant differences between the BMI groups (HR: 0.94 [95% CI: 0.7–1.2]; p = 0.59). When calculating CLBRs considering EmbRs, there was a similarity between the BMI groups (p = 0.57). However, there were no statistically significant differences in the adjusted Cox regression (HR: 0.93 [95% CI: 0.7–1.2]; p = 0.51). Finally, when calculating CLBRs considering OUs, the results were comparable among BMI subgroups (p = 0.75), and there were no statistically significant differences with adjusted Cox regression (HR: 0.95 [95% CI: 0.8–1.2]; p = 0.66). In conclusion, paternal BMI was not associated with clinical reproductive outcomes when considering the ETs, EmbRs, or OUs needed to reach the first liveborn (LB).

Defining ethical criteria to guide the expanded use of Noninvasive Prenatal Screening (NIPS): Lessons about severity from preimplantation genetic testing.

We hypothesized that ethical criteria that guide the use of preimplantation genetic testing (PGT) could be used to inform policies about expanded use of non-invasive prenatal screening (NIPS). We used a systematic review of reasons approach to assess ethical criteria used to justify using (or not using) PGT for genetic conditions. Out of 1135 identified documents, we retained and analyzed 216 relevant documents. Results show a clear distinction in acceptability of PGT for medical vs. non-medical conditions. Criteria to decide on use of PGT for medical conditions are largely based on their severity, but there is no clear definition of "severity". Instead, characteristics of the condition that relate to severity are used as sub-criteria to assess severity. We found that characteristics that are used as sub-criteria for assessing severity include monogenic etiology, high penetrance, absence of treatment, early age of onset, shortened lifespan, and reduced quality of life. Consensus about the use of PGT is highest for conditions that meet most of these criteria. There is no consensus around the acceptability of using PGT to detect non-medical conditions. We propose that the same severity criteria could be used by policymakers to assess the acceptability of using other genetic tests in screening and practice, including for the use of NIPS for additional conditions as indications broaden.

Modern aspects of preimplantation genetic testing of embryos in assisted reproductive technology programs (literature review)

Background. The success of assisted reproductive technologies depends on many factors, the main ones being the quality and genetic status of the embryo and endometrial receptivity. Preimplantation genetic testing is a tool that aims to reduce the risk of selecting an aneuploid embryo for transfer. Disputes surrounding the use of preimplantation genetic testing are conducted in the context of older patients, with recurrent miscarriage, with genetic karyotype abnormalities in a married couple, as well as multiple unsuccessful attempts at ART in the anamnesis.Purpose of review. To summarize and analyze the available data on current trends in the use of preimplantation genetic testing (PGT-A).Materials and methods. The review includes published data over the past 10 years regarding the effectiveness of ART programs and pregnancy outcomes after the use of preimplantation genetic testing. The literature search was conducted in Medline, Scopus, Web of Science, Google Scholar, PubMed, Wiley and Cochrane Library databases.Results. According to most authors, preimplantation genetic testing does not improve live birth rates per patient in the general population, but it does improve live birth rates when performing PGT-A on blastocyst-stage embryos in women over 35 years of age, as well as in women with a history of pregnancy loss to reduce risk miscarriage of a subsequent pregnancy.Conclusion. Preimplantation genetic testing is a valid method for assessing euploidy and mosaicism of an embryo before transfer. The feasibility of use, according to research results, is more related to conditions in which the risk of embryonic aneuploidy may increase, and is justified in high-risk patients, while the use of this technique in patients with a good prognosis is still questionable. First, trophectoderm biopsies may not reflect the ploidy of the inner cell mass. Secondly, even if we assume that this is the case, we cannot be sure that the embryonic cell line will not self-correct. In other words, once a diagnosis of PGT-A is received suggesting mosaicism or aneuploidy, the likelihood of a false-positive diagnosis is high.

P-421 Enhancing the success of frozen embryo transfer by human chorionic gonadotropin injection on the day of progesterone supplementation onset - a machine learning study

Abstract Study question Does subcutaneous injection of human chorionic gonadotropin (hCG) at the onset of progesterone supplementation affect clinical pregnancy rate in frozen embryo transfer cycles? Summary answer Clinical pregnancy rates are higher when hCG injection is administered at the onset of 300 mg/day progesterone in patients undergoing frozen embryo transfer. What is known already HCG and progesterone play crucial roles in embryo transfer and implantation during in vitro fertilization. Exisitng studies have demonstrated that pre-administration of hCG at the onset of progesterone supplementation for frozen embryo transfer increases clinical pregnancy rates in patients with endometriosis. However, the synergistic effects of hCG and progesterone co-supplementation in a broader range of patients remain unexplored and require further investigation. A multifactorial analysis of hormone replacement therapy, covering various patient-specific aspects, is necessary to understand the implications of this approach. Study design, size, duration This retrospective cohort study analyzed data from 2,251 single frozen embryo transfers performed between Jan 2019-Aug 2023 at the INVICTA Fertility Centre, Poland. The dataset was selected by the practitioner and included age, AMH, BMI, embryo morphology grade, total number of transfers, medical and embryological procedures, recurrent implantation failure, preimplantation genetic testing, endometrial thickness before transfer (≥ 7 mm), and the menstrual cycle day on which progesterone was started. Participants/materials, setting, methods Patients (21-47 years) receiving 300 or 600 mg/day progesterone for five days were divided into the control and hCG (6,500 IU hCG injection on progesterone onset) groups. A machine learning model was trained using a gradient boosting technique (100 decision trees, four leaves, maximum depth of two nodes, learning rate of 0.05) to identify factors affecting the clinical pregnancy rate. Statistical analysis was performed to compare clinical pregnancy rates between the groups. Main results and the role of chance Our machine-learning model revealed that hCG injection (512 processes vs. 1739 processes without it) at the onset of progesterone administration is an important feature for the clinical pregnancy rate. The performance accuracy of the model was approximately 70%. Of the 1,294 protocols where patients received 300 mg/day progesterone, 311 included hCG injection while 983 did not. The clinical pregnancy rate was significantly higher in the hCG group than that in the control group (54% vs. 46%, P < 0.05), with 167 clinical pregnancies observed in patients receiving hCG injections against 452 pregnancies without it. In contrast, among the 957 protocols where 600 mg/day progesterone was administered, the previously observed effect was not significant (P > 0.05). Comparing 201 processes with hCG injection to 756 processes without it, the incidence of clinical pregnancies was 46.8% and 47.2% (with 94 and 357 confirmed pregnancies), respectively. Other factors such as the morphology grade of the embryo used for transfer, patient’s age, AMH, BMI, total number of transfers performed on the patient, menstrual cycle day on which progesterone was started, occurrence of recurrent implantation failure, and the use of preimplantation genetic testing were not significantly different between the groups. Limitations, reasons for caution This study focused on frozen embryo transfers and validation across other protocols using fresh embryo transfers, and different doses or routes of hCG and progesterone administration are needed. The impact of hCG administration on patients with various causes of infertility should also be explored. Wider implications of the findings Pre-administration of hCG injection along with a daily dose of 300 mg/day progesterone enhanced clinical pregnancy rates for frozen embryo transfer. This holds the potential for the optimization of hormon supplementation protocols to increase overall success rates in assisted reproductive technologies. Trial registration number not applicable

Use of preimplantation genetic testing for monogenic adult-onset conditions: an Ethics Committee opinion

Preimplantation genetic testing for monogenic diseases for adult-onset conditions is ethically permissible for various conditions, including when the condition is fully penetrant or confers disease predisposition. The Committee strongly recommends that a genetic counselor experienced with both preimplantation genetic testing for monogenic diseases and assisted reproductive technology therapies counsel patients considering such procedures.

Is biochemical pregnancy loss associated with embryo or endometrium? A retrospective cohort study in frozen single embryo transfer of own and donated oocytes.

Does the use of preimplantation genetic testing for aneuploidies (PGT-A), personalized embryo transfer with endometrial receptivity assay (pET-ERA), or the use of donated oocytes modify the incidence of biochemical pregnancy loss (BPL) in frozen single embryo transfer (FSET)? Following FSET, BPL incidence does not differ between own and donated oocytes, and the use of PGT-A with euploid embryo transfer or pET-ERA results in a similar incidence of BPL compared to cycles without embryo or endometrial analysis. BPL occurs frequently after IVF, and many factors have been associated with its incidence. The etiology of BPL is not well known, but the most probable cause seems to be either a low-quality embryo or impaired endometrial maintenance. The impact of techniques diagnosing embryonic ploidy or endometrial receptivity on BPL incidence and the BPL incidence between own and donated oocytes have not been analyzed. This is a retrospective cohort study analyzing the incidence of BPL over 3741 cycles of FSET derived from own (2399 cycles) and donated (1342 cycles) oocytes between January 2013 and January 2022 in 1736 of which PGT-A, pET-ERA, or both were applied. We defined BPL as a pregnancy diagnosed only by serum β-hCG > 10 UI/l followed by a decrease that does not result in a clinical pregnancy. Clinical pregnancy was defined as the presence of gestational sac on transvaginal ultrasound. We compared BPL rates among patients undergoing 2399 FSETs from own oocytes, which comprised 1310 cycles of embryos analyzed by PGT-A, 950 cycles of untested embryos, 30 cycles of untested embryos with pET-ERA, and a subgroup of 109 cycles analyzed by both PGT-A and pET-ERA. We also included a total of 1342 FSET cycles from donated oocytes comprising 132, 1055, 140, and 15 cycles in the same groups, respectively. In FSET from own oocytes, the overall BPL rate per embryo transfer was 8.2% (95% CI [7.09-9.33]). In untested embryo transfers, the BPL rate was 7.5% [5.91-9.37]. In the PGT-A group, the BPL rate was 8.8% [7.32-10.47]. In the pET-ERA group, the rate was 6.7% [0.82-22.07]. In the PGT-A+ERA group, the rate was 6.5% [2.65-12.90]. No significant differences were found (P = 0.626). A multivariate analysis considering clinically meaningful variables that were significantly different among groups, taking the untested embryos/endometrium group as a reference, showed comparable incidences among groups. For PGT-A, the adjusted odds ratio (AdjOR) was 1.154 [0.768-1.735] (P = 0.49) and for PGT-A+ERA 0.885 [0.330-2.375] (P = 0.808). Because of a low number of registered cases in the pET-ERA group, and to prevent statistical errors and convergence issues, this group was excluded from further analysis. In FSET of donated oocytes, the overall BPL rate per embryo transfer was 4.9% [3.76-6.14]. In the PGT-A group, the BPL rate was 6.8% [3.16-12.55]. In the pET-ERA group, the rate was 5.0% [2.03-10.03]. In untested embryo transfers, the rate was 4.7% [3.46-6.10]. No cases occurred in the PGT-A+ERA group, and no significant differences were found (P = 0.578). The multivariate analysis showed comparable incidences among groups. For PGT-A the AdjOR was 1.669 [0.702-3.972] (P = 0.247) and for pET-ERA 1.189 [0.433-3.265] (P = 0.737). The PGT-A+ERA group was eliminated from the model to prevent statistical errors and convergence issues because no BPL cases were registered in this group. In the multivariate analysis, when the sources of oocytes were compared, own versus donated, no significant differences were found in the incidence of BPL. This was a retrospective cohort study with potential biases. In addition, we were unable to control differences among groups due to modifications in medical or laboratory protocols during this long time period, which may modify the relationships being addressed. Factors previously associated with BPL, such as immunological conditions other than thyroid autoimmunity, were not considered in this study. Limited sample sizes of some groups may limit the statistical power for finding differences that can be present in the general population. BPL may be related to a mechanism not associated with the chromosomal constitution of the embryo or the transcriptome of the endometrium. More studies are needed to explore the factors associated with this reproductive issue. No specific funding was available for this study. None of the authors have a conflict of interest to declare with regard to this study. This trial was registered at clinicaltrials.gov (NCT04549909).

Gestational carrier cycles: embryology trends, national guideline compliance, and resultant perinatal outcomes in the United States, 2014–2020

The increased use of gestational carriers has expanded family-building opportunities for people and couples unable to carry pregnancies on their own. National American Society of Reproductive Medicine guidelines for gestational carriers have changed over time to reflect advances in reproductive technology and mounting evidence supporting the medical benefits associated with singleton gestations. Assess changes in gestational carrier cycle practice patterns and resultant pregnancy outcomes in the United States in relation to changing national American Society of Reproductive Medicine guidelines, which changed in 2013 and2017. This retrospective study used data from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System and included all cycles that were reported from 2014-2020 involving an embryo transfer to a gestational carrier. Binomial regression models evaluated trends in preimplantation genetic testing for aneuploidy, American Society of Reproductive Medicine guideline adherence, number of embryos transferred, and pregnancy outcomes over time. Of the 40,177 gestational carrier transfer cycles from 2014-2020, there was a significant increase in frozen-thawed cycles (41.3% increase), use of assisted hatching (53.4% increase), intracytoplasmic sperm injection (50.0% increase), and preimplantation genetic testing for aneuploidy (155.7% increase). The likelihood of preimplantation genetic testing for aneuploidy was higher in 2020 than in 2014 for autologous oocyte transfers to gestational carriers, both for those aged ≥38 years (adjusted relative risk, 2.38 [95% confidence interval, 2.11-2.70]) and than those aged <38 years (adjusted relative risk, 2.85 [95% confidence interval, 2.58-3.15]). As preimplantation genetic testing for aneuploidy usage increased, single embryo transfer rose for both autologous (adjusted relative risk, 2.22 [95% confidence interval, 1.94-2.50]) and donor cycles (relative risk, 1.91 [95% confidence interval, 1.81-2.02]). This shift toward single embryo transfer corresponded with a decrease in multiple embryo transfer by 79.2% and subsequent decreases in multiple gestations by 68.8% in donor and 73.6% in autologous oocyte cycles from 2014-2020. Gestational carrier cycles remained highly adherent to changing American Society of Reproductive Medicine guidelines throughout the study period. Among live births, there was a 19.4% and 7.9% increase in term deliveries among donor and autologous oocyte cycles, respectively, from 2014 to2020. Practice patterns have drastically changed throughout the study period, with major increases in the use of preimplantation genetic testing for aneuploidy, intracytoplasmic sperm injection, assisted hatching, and frozen transfers. In response to changing American Society of Reproductive Medicine guidelines, the use of multiple embryo transfers has decreased for gestational carrier cycles with subsequent decreases in multiple gestations and miscarriages and slight increases in live birth rates.

The use of preimplantation genetic testing for aneuploidy: a committee opinion

The use of preimplantation genetic testing for aneuploidy (PGT-A) in the United States has been increasing steadily. Moreover, the underlying technology used for 24-chromosome analysis continues to evolve rapidly. The value of PGT-A as a routine screening test for all patients undergoing invitro fertilization has not been demonstrated. Although some earlier single-center studies reported higher live-birth rates after PGT-A in favorable-prognosis patients, recent multicenter, randomized control trials in women with available blastocysts concluded that the overall pregnancy outcomes via frozen embryo transfer were similar between PGT-A and conventional invitro fertilization. The value of PGT-A to lower the risk of clinical miscarriage is also unclear, although these studies have important limitations. This document replaces the document of the same name, last published in2018.

Comparing the advantages, disadvantages and diagnostic power of different non-invasive pre-implantation genetic testing: A literature review.

To improve embryo transfer success and increase the chances of live birth in assisted reproductive methods, there is a growing demand for the use of pre-implantation genetic testing (PGT). However, the invasive approaches used in PGT have led to in vitrofertilization failure and abortions, increasing anxiety levels for parents. To address this, non-invasive PGT methods have been introduced, such as the detection of DNA in blastocoel fluid of blastocysts and spent culture media (SCM). These methods have proven to be minimally invasive and effective in detecting aneuploidy in the chromosomes of human embryos. This review aims to explore the different approaches to pre-implantation diagnosis, including invasive and non-invasive methods, with a particular focus on non-invasive PGT (niPGT). The search strategy involved gathering data from scientific databases such as PubMed, Google Scholar, and Science Direct using relevant keywords. The search was conducted until January 2023. In total, 22 studies have successfully reported the detection and amplification of cell-free DNA in the embryonic SCM. It is important to note that niPGT has some limitations, which include differences in indicators such as cell-free DNA amplification rate, concordance, level of maternal DNA contamination, sensitivity, and specificity between SCM samples and biopsied cells. Therefore, more extensive and detailed research is needed to fully understand niPGT's potential for clinical applications.

U.S. Gestational Carrier Embryo Transfer Trends, 2014–2020 [ID 2683526

INTRODUCTION: Multiple embryo transfers (METs) are common among gestational carriers (GCs) despite increased obstetric risks of multiple gestations and strong recommendations from American Society for Reproductive Medicine (ASRM) for single-embryo transfers. This study assessed GC embryo transfer trends from 2014–2020 to evaluate compliance with national guidelines. METHODS: This retrospective, population-based cohort study used data from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. All cycles from 2014 to 2020 involving an embryo transfer to a GC were analyzed. The number of GC embryo transfers, use of preimplantation genetic testing (PGT), and outcome (singleton versus multiple gestation) were assessed. Poisson and linear regression models evaluated trends in number and proportion of cycles over time. Institutional review board approval was obtained. RESULTS: Of the 40,177 GC transfer cycles from 2014 to 2020, 11,081 (27.6%) involved transfer of two or more embryos. Both the number (n=2,001 in 2014; n=814 in 2020) and proportion of METs (56.6% of all transfers in 2014; 11.8% in 2020) (P&lt;.05 for both) decreased. The use of PGT among MET GC cycles increased from 23.9% in 2014 to 61.4% in 2020. Among live births, there was a 71.0% reduction in the proportion of multiple gestations from 2014 (25.5%) to 2020 (7.4%) (P&lt;.05). Among double-embryo transfers, the majority were performed at the blastocyst stage with an increase from 2014 (76.7%) to 2020 (88.1%) (P&lt;.05). CONCLUSION: With increased use of PGT and extended blastocyst culture, MET and subsequent multiple gestation pregnancies have decreased amongst U.S. GCs. These trends suggest increased compliance with ASRM national guidelines.

Modified natural cycle allows a window of 7 days for frozen embryo transfer planning

Research questionShould ovulation be triggered in a modified natural cycle (mNC) with recombinant human chorionic gonadotrophin (rHCG) as soon as a mean follicle diameter of 17 mm is visible, or is more flexible planning possible? DesignThis multicentre, retrospective, observational study of 3087 single frozen blastocyst transfers in mNC was carried out between January 2020 and September 2022. The inclusion criteria included endometrial thickness ≥7 mm and serum progesterone <1.5 ng/ml. The main outcome was ongoing pregnancy rate. Secondary end-points were pregnancy rate, implantation rate, clinical pregnancy rate and miscarriage rate. The mean follicle size at triggering was stratified into three groups (13.0–15.9, 16.0–18.9 and 19.0–22 mm). ResultsThe baseline characteristics between the groups did not vary significantly for age, body mass index and the donor's age for egg donation. No differences were found in pregnancy rate (64.5%, 60.2% and 57.4%; P = 0.19), clinical pregnancy rate (60.5%, 52.8% and 50.6%; P = 0.10), implantation rate (62.10%, 52.9% and 51.0%; P = 0.05) or miscarriage rate (15.0%, 22.2%; and 25.0%; P = 0.11). Although ongoing pregnancy rate (54.9%, 46.8% and 43.1%; P = 0.02) varied significantly in the univariable analysis, it was no longer significant after adjustment for the use of preimplantation genetic testing for aneuploidies and egg donation. ConclusionsThe findings showed rHCG could be flexibly administered with a mean follicle size between 13 and 22 mm as long as adequate endometrial characteristics are met, and serum progesterone is <1.5 ng/ml. Considering the follicular growth rate of 1–1.5 mm/day, this approach could allow a flexibility for FET scheduling of 6–7 days, simplifying mNC FET planning in clinical practice.

Sex ratio of offspring is not statistically altered following pre-implantation genetic testing under a specific sex selection policy.

To determine whether the use of pre-implantation genetic testing (PGT) under a specific sex selection policy is associated with alterations in offspring sex ratio. This was a single-center retrospective cohort study of singleton live births from January 2018-December 2020 achieved via single blastocyst non-PGT or PGT frozen embryo transfer (FET). Per institutional policy, sex may be disclosed following PGT. If both sexes are available and morphologic grade is similar, patients may select the sex of the embryo to be transferred. Demographics and cycle characteristics were compared between non-PGT vs. PGT cycles with Mann-Whitney U or χ2. Poisson regression with robust variance estimates was used to model the probability of female vs. male offspring among non-PGT vs. PGT cycles, reported as risk ratio (RR) and 95% confidence interval (CI). Among 541 live births, 350 (64.7%) were achieved with PGT and 191 (35.3%) without PGT. In both groups, female sex was more common, representing 59.4% of PGT-offspring and 55.0% of non-PGT offspring. After adjusting for potential confounders, the use of PGT was not significantly associated with an increased likelihood of female offspring (RR 1.04, 95% CI 0.98-1.11, p = 0.22). Singletons born following FET had a higher rate of female sex than male. Allowing sex selection per institutional policy did not increase this ratio. These results contrast with those of prior publications and should motivate individual centers to monitor their own sex ratios. As utilization of PGT increases, local, regional, and national monitoring will become increasingly important.

Race, ovarian responsiveness, and live birth after in vitro fertilization

To determine if ovarian responsiveness to gonadotropin stimulation differs by race/ethnicity and whether this predicts live birth rates (LBRs) in non-White patients undergoing invitro fertilization (IVF). Retrospective cohort study. Academic infertility center. White, Asian, Black, and Hispanic patients undergoing ovarian stimulation for IVF. Self-reported race and ethnicity. The primary outcome was ovarian sensitivity index (OSI), defined as (the number of oocytes retrieved ÷ total gonadotropin dose) × 1,000 as a measure of ovarian responsiveness, adjusting for age, body mass index, infertility diagnosis, and cycle number. Secondary outcomes included live birth and clinical pregnancy after first retrievals, adjusting for age, infertility diagnosis, and history of fibroids, as well as miscarriage rate per clinical pregnancy, adjusting for age, body mass index, infertility diagnosis, duration of infertility, history of fibroids, and use of preimplantation genetic testing for aneuploidy. The primary analysis of OSI included 3,360 (70.2%) retrievals from White patients, 704 (14.7%) retrievals from Asian patients, 553 (11.6%) retrievals from Black patients, and 168 (3.5%) retrievals from Hispanic patients. Black and Hispanic patients had higher OSIs than White patients after accounting for those with multiple retrievals and adjusting for confounders (6.08 in Black and 6.27 in Hispanic, compared with 5.25 in White). There was no difference in OSI between Asian and White patients. The pregnancy outcomes analyses included 2,299 retrievals. Despite greater ovarian responsiveness, Black and Hispanic patients had lower LBRs compared with White patients, although these differences were not statistically significant after adjusting for confounders (adjusted odds ratio, 0.83; 95% confidence interval [CI], 0.63-1.09, for Black; adjusted odds ratio, 0.93; 95% CI, 0.61-1.43, for Hispanic). Ovarian sensitivity index was modestly predictive of live birth in White and Asian patients but not in Black (area under the curve, 0.51; 95% CI, 0.38-0.64) and Hispanic (area under the curve, 0.50; 95% CI, 0.37-0.63) patients. Black and Hispanic patients have higher ovarian responsiveness to stimulation during IVF but do not experience a consequent increase in LBR. Factors beyond differences in responsiveness to ovarian stimulation need to be explored to address the racial/ethnic disparity established in prior literature.

Effect of state insurance mandates on racial/ethnic disparities in the utilization and outcomes of donor oocyte–assisted reproductive technologies

To characterize racial/ethnic disparities in donor oocyte-assisted reproductive technology (ART) nationwide and examine the impact of state insurance mandates on disparities in utilization and outcomes. Retrospective cohort study. Donor oocyte ART cycles in the United States (US). Women who underwent donor oocyte ART in 2014-2016, as reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. Race/ethnicity of oocyte recipients. Live birth through 1 or more donor oocyte ART cycles in 2014-2016 per recipient. We analyzed 44,033 donor ART cycles performed for 28,157 oocyte recipients, 99.2% (27,919/28,157) of whom were aged 25-54 years. Race/ethnicity data were reported for 61.4% (17,281/28,157) of the recipients. Among recipients aged 25-54 years with race data, 65.8% (11,264/17,128) identified as non-Hispanic White, whereas 58.9% were White among women aged 25-54 in the 2016 US census. In contrast, Black recipients comprised 8.3% of those aged 25-54 years with race data, compared with 13.7% nationwide. Among White recipients, 7.0% (791/11,356) lived in states with donor ART mandates (Massachusetts/New Jersey), compared with 6.5% (93/1,439) of Black recipients, 8.1% (108/1,335) of Hispanic recipients, and 5.8% (184/3,151) of Asian recipients. Black recipients had a higher median age and body mass index and were more likely to have uterine factor infertility. White recipients had the highest cumulative probability of live birth in the nonmandate (64.6%, 6,820/10,565) and mandate (69.5%, 550/791) states, followed by Asian recipients (nonmandate, 63.4% [1,881/2,967]; mandate, 65.2% [120/184]), Hispanic recipients (nonmandate, 60.5% [742/1,227]; mandate, 68.5% [74/108]), and Black recipients (nonmandate, 48.7% [655/1,346]; mandate, 48.4% [45/93]). The multivariable Poisson regression adjusting for donor's age and recipient's age, body mass index, nulliparity, history of recurrent pregnancy loss, diminished ovarian reserve, tubal factor and uterine factor infertility, prior ART treatment, use of preimplantation genetic testing, cumulative number of embryos transferred, use of blastocysts, and frozen-thawed transfers, demonstrated that Black recipients had a lower cumulative probability of a live birth than White recipients (relative risk [RR], 0.82; 95% confidence interval [CI], 0.77-0.87), as were Hispanic recipients (RR, 0.93; 95% CI, 0.89-0.99) and Asian recipients (RR, 0.96; 95% CI, 0.93-0.99). These disparities were not modified by state mandate for donor ART. State mandates for donor oocyte ART in their current forms are insufficient in decreasing racial/ethnic disparities.

Abstract P6-05-47: Preimplantation genetic testing for BRCA gene mutation carriers - the future of health care in Poland?

Abstract Introduction Genetic background is rarely the cause of breast cancer incidence. Mutations in genes that increase the risk of breast cancer (most commonly BRCA1/2) are diagnosed in about 5-10% of patients. The lifetime risk of breast cancer in BRCA1/2 gene mutation carriers is 80%, and for ovarian cancer from 40-60%, while the chance of passing the mutation to offspring is 50%. The use of pre-implantation genetic testing (PGT-M) of the embryo during in vitro treatment prevents the transfer of mutated gene associated with an increased risk of cancer to the child. The significantly limited availability and high cost of PGT-M in Poland prevent its widespread use. The aim of the survey was to assess interest in PGT-M by female carriers of mutations in genes that increase cancer risk in Poland. Material and Methods The survey covered 103 persons, 102 with diagnosed mutations in genes that increase cancer risk. The questionnaire consisted of 22 questions regarding: age and gender of the patients, carriage of mutations in genes that increase the risk of cancer (age of mutation diagnosis, type of mutation, preventive measures taken, carriage of mutations in the family, incidence of cancer among relatives, and care of relatives during illness), and knowledge of pre-implantation diagnosis and attitudes regarding the use of PGT-M to avoid passing the defective gene to offspring. Results The study included 101 women (98.1%) and 2 men (1.9%), with a median age of 38 years (22-74). Fifty-two (50.5%) were diagnosed with cancer: 50 with breast cancer and 2 with ovarian cancer. Eighty-one subjects (78.6%) were diagnosed with a mutation in the BRCA1 gene, seventeen (16.5%) in the BRCA2 gene, three (2.9%) in the CHEK2 gene, two (1.9%) in the TP53 gene and one (1%) in the PALB gene. The median age of mutation diagnosis was 34 years (18-66). A significant proportion of patients took prophylactic measures, sixty-one (59.2%) underwent risk-reducing mastectomy (RRM), and forty-six (44.7%) risk-reducing salphingo-oophorectomy (RRSO). Ninety-five subjects (92.2%) declared regular visits to a genetic counseling center. Thirty-two persons (31.1%) had a family history of cancer (1-5 members in the family), mainly in 1st degree relatives – parents and siblings (about 60% of cases), the predominant cancers were breast cancer (106 cases), ovarian cancer (38 cases) and prostate cancer (7 cases); eighty-two family members died of cancer, seventy-five (72.8%) respondents accompanied family members in the dying process. Twenty-six individuals (25.2%) knew what PGT-M was, information was obtained from an oncologist (11), gynecologist (7), geneticist (6), other patients (6) and most often from the Internet (17). Seventy-four respondents (71.8%) had children. Thirty-three (32%) declared that information about carrying a mutation in a gene that increases cancer risk influenced their decision to have offspring. Sixty-eight (64.1%) of the respondents, with prior knowledge of PGT-M and with the availability of the method, would have used the diagnosis in combination with in vitro fertilization to avoid passing the defective gene to offspring. Fifty subjects (48.5%) were willing to cover the costs of this procedure. Conclusions PGT-M in combination with in vitro fertilization is a safe and effective method of preventing the transfer of a defective gene to offspring. Due to the lack of availability and high cost of the procedure, it is not available in daily clinical practice among carriers of mutations in genes that increase the risk of cancer in Poland. Their own incidence of cancer, multiple incidences in family members and involvement in the dying process may influence patients’ decisions to have offspring and motivate them to seek out centers offering PGT-M. The results of this survey indicate the need to offer pre-implantation testing to patients despite the lack of reimbursement and to increase its availability in Poland. Citation Format: Joanna Kufel-Grabowska, Amira Podolak, Mikołaj Bartoszkiewicz, Daniel Maliszewski, Dominika Ossowska, Robert Spaczynski. Preimplantation genetic testing for BRCA gene mutation carriers - the future of health care in Poland? [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-47.

PATIENT DECISION-MAKING PROCESS FOR DISPOSITION OF CRYOPRESERVED EMBRYOS

At our institution, cryopreserved embryos remain in onsite storage for up to three years, after which point patients are given the option to transfer embryos to an offsite storage facility, donate them to research, or discard them. This study aimed to assess factors influencing patient decision-making regarding embryo disposition, primarily the use of preimplantation genetic testing (PGT) and donor gametes, and secondarily household income. It was hypothesized that patients using PGT or donor gametes will be more likely to maintain embryos in storage.

RACIAL DISPARITIES IN PREIMPLANTATION GENETIC TESTING (PGT)

To determine whether there are racial/ethnic differences in the use of preimplantation genetic testing (PGT) over time.

Freeze all-first versus biopsy-first: A retrospective analysis of frozen blastocyst transfer cycles with preimplantation genetic testing for aneuploidy.

Potential use of preimplantation genetic testing for aneuploidy (PGT-A) is increasing. Patients who have excess embryos cryopreserved at the blastocyst stage may desire PGT-A but there is little data available on options for these patients. We compared the efficacy and safety of the timing on the cryopreservation and trophectoderm(TE) biopsy for preimplantation genetic testing for aneuploidy (PGT-A) program associated with the better outcomes after frozen blastocyst transfer. Retrospective analysis of patients who underwent PGT-A cycles from January 2016 to December 2019 was carried out. 2684 blastocysts from cycles were subjected to TE biopsy for performing array comparative genomic hybridization test and Next-generation sequencing. All cycles were divided into two according to the timing of biopsy: biopsy-first (n = 211 cases/ 232 transfers) versus freeze all-first (n = 327 cases/ 415 transfers). In the biopsy-first group, embryos were cultured to expanded blastocyst and proceed to TE biopsy on day 5 or day 6 followed by cryopreservation. In the freeze all-first, blastocysts were vitrified and warmed before biopsy. Rates of clinical pregnancy (52.3% vs. 38.7%, P = 0.09) and ongoing pregnancy (44.3% vs. 34.5%, P = 0.07) in biopsy-first were significantly higher than those in freeze all-first. Biopsy-first showed comparable miscarriage rate with freeze all-first (15.2% (33/217) vs.11.1% (10/90), respectively). Rate ratio (RR) for clinical pregnancy was lower in freeze all-first group (adjusted RR = 0.78, 95% confidence interval: 0.65, 0.93). The RRs for miscarriage and live birth was also lower but it did not reach statistical significance. Our result supported performing TE biopsy of blastocyst for PGT-A before vitrification and warming. This finding would contribute to more evidence-based decision in PGT-A cycles.

Prednisolone and enoxaparin (clexane) therapy ('the Bondi protocol') for repeated IVF failure.

What is the impact of an empirical immune therapy protocol of prednisolone and enoxaparin (clexane) (the 'Bondi protocol') on women with repeated in vitro fertilization (IVF) failure? This was a retrospective review of live birth outcomes conducted on all transfer cycles performed by a single clinician (GS) at IVFAustralia between February 2016 and April 2020. This study consisted of 1786 transfer cycles, including 460 cycles treated with the Bondi protocol and 1326 without. Women with repeated IVF failure were given the Bondi protocol based on blood NK cell activity. Primary outcome was live birth and statistical analysis was performed with GraphPad Prism software with significance for P-values<.05. Overall 'Bondi' and 'normal' protocol cycles had similar rates of IVF/ICSI, fresh/frozen transfers and use of preimplantation genetic testing (PGT). Women given the Bondi protocol were older, had more previous cycles and had higher blood NK cell activity. There was no significant difference in live birth rates (Bondi 26%, normal 28%). Bondi protocol live birth rates per transfer cycle were as high as 40% in patients under 38 years old. The Bondi protocol was more effective as NK activity increased from 'normal' to 'borderline' to 'high'. For high NK cell activity levels, live birth rates were over four times higher for women on the Bondi protocol (28%) than those on normal protocols (6%, P=.0007). This study describes a simple and relatively safe immune therapy protocol that may improve IVF success rates in women with evidence of immune dysfunction.

Pathways to fatherhood: clinical experiences with assisted reproductive technology in single and coupled intended fathers

To explore the cycle characteristics and outcomes of single and coupled intended fathers (SCIFs) using assisted reproductive technology. Cross-sectional study. Multicenter, fertility practices from 2016 to2020. In this study, cycles among SCIFs with access to fertility coverage from 2016 to 2020 were included. None. Our primary outcome was live birth rate. The secondary outcomes included the number of embryos transferred, miscarriage rate, and incidence of multifetal birth. Five single and 39 coupled intended fathers completed an invitro fertilization cycle with a majority using egg donation and an agency-based gestational carrier (69.7%, 83/119). In most couples, both partners wanted to serve as the sperm source (64.4%, 29/45). The vast majority (97.7%, 43/44) also used preimplantation genetic testing for aneuploidy. Among the embryo transfer (ET) cycles (n = 27), most consisted of a single euploid ET (74.07%, 20/27), whereas the remaining consisted of a double euploid ET (25.92%, 7/27). The SCIFs had high rates of success, with a live birth rate of 85.19% (23/27). A mean of 1.26 ± 0.44 embryos were transferred, with a majority resulting in singleton birth (70.37%, 19/27). Our study of SCIFs using assisted reproductive technology in the United States demonstrates that this population shares similar preferences for sperm source and the use of preimplantation genetic testing. Clinical outcomes suggest that this population is successful at achieving a live birth when using egg donation and a gestational carrier.