Use Of Preimplantation Genetic Testing Research Articles

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).

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.

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.

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<.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<.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<.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.

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.

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.

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.

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.

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.

Fertility preservation practices for female oncofertility differ significantly across the USA: results of a survey of SREI members.

The field of oncofertility has maintained an important focus on improving access, yet standardized practices are lacking. To assess how female cancer patients are provided oncofertility care, we sought to determine provider-level differences and whether there are physician or practice characteristics that predict these variations. A cross-sectional survey was sent to SREI members. The survey included fifteen questions about physician practice characteristics and oncofertility cryopreservation protocols. Topics included ovarian stimulation protocols, fertilization techniques, stage of embryo cryopreservation, routine use of pre-implantation genetic testing for aneuploidy (PGT-A), and ovarian tissue cryopreservation (OTC). Statistical analyses assessed whether practice setting, geographic region, time in practice, and mandatory state insurance coverage had effects on cryopreservation protocols. A total of 141 (17%) from diverse REI practice backgrounds completed the survey. The median number of new female oncofertility consults per year was 30 (range 1 to 300). Providers in academic settings treated more patients (median 40 vs. 15, p < 0.001). Providers in academic settings more often use gonadotropin-releasing hormone agonists (85% vs. 52%, p < 0.001) and perform OTC (41% vs. 4%, p < 0.001). Providers in academic practices were less likely to perform intracytoplasmic sperm injection in every cycle (37% vs. 55%, p = 0.032) and less likely to usually advise PGT-A (21% vs. 36%, p = 0.001). Mandated state insurance coverage had no effect on oncofertility practices. Oncofertility practices vary among providers. Factors such as practice setting and region may affect the services provided. We do not yet know the best practices in oncofertility patients, and future research is needed.

The death of Roe and the future of ex vivo embryos

This article examines the possible effects of the end of a federal constitutional right to abortion on clinical practice and research involving ex vivo human embryos. It first analyzes the likely outcomes of Dobbs v. Mississippi, concluding the Supreme Court will either overrule the federal constitutional abortion right or restrict it in a way that leads to its rapid disappearance. Next, the article discusses a possible increase in use of preimplantation genetic testing as one result. It then forecasts the likely ramifications of such a court decision on state legislation affecting ex vivo human embryos in two ways. It examines the possibility that victory over Roe will inspire embryo support groups to push for limitations on in vitro fertilization, perhaps on its destruction of embryos and more likely on permissible grounds for prospective parents to use in choosing embryos for transfer. It ends by discussing the prospects of new laws in some states banning or limiting research with human embryos.

Use of preimplantation genetic testing for monogenic disorders and subsequent prenatal care and diagnostic testing.

The goal of preimplantation genetic testing for monogenic or single gene defects (PGT-M) is to identify inherited pathogenic variants in the embryo prior to embryo transfer, increasing the likelihood of an unaffected child. Prenatal diagnostic testing is recommended to confirm the results of PGT-M. The purpose of this study was to characterize the population undergoing PGT-M over time. This retrospective study examined patients who had a positive pregnancy test after PGT-M from 2012 to 2019. A query of the internal assisted reproductive technology database and chart review were used. One hundred and 42 patients completed IVF cycles for PGT-M during this time period and progressed past 10weeks gestation. There were more PGT-M cycles over time with 46 cycles between 2012 and 2015 and 96 cycles between 2016 and 2019. Patients varied on the decision to pursue prenatal diagnostic testing after PGT-M. For those with known follow-up (130/142), 16 patients underwent diagnostic testing (12%) and 114 did not. As PGT-M is increasingly utilized prior to pregnancy, it is important for genetic counselors and OB/GYNs to understand the characteristics and outcomes of the population of patients undergoing PGT-M, including how to counsel about the residual risk of an affected pregnancy after PGT-M.