Walking the tightrope: Fertility preservation among hereditary breast and ovarian Cancer syndrome Previvors.

INTRODUCTION: Fertility-related concerns cause significant anxiety among patients with Hereditary Breast and Ovarian Cancer Syndrome (HBOC). The Society of Gynecologic Oncology and the American Society for Reproductive Medicine recommend patients diagnosed with HBOC receive early referral to a reproductive endocrinologist. However, evidence about fertility trends in this patient population are limited and guidelines are scarce. The aim of this study is to compare fertility preservation among patients with HBOC to control patients undergoing fertility treatment without a diagnosis of infertility. METHODS: This retrospective study included patients who presented to a single academic institution for fertility preservation in the setting of diagnosis of HBOC. In this study, HBOC patients are referred to as those who had tested positive for pathogenic mutations in BRCA1, BRCA2 or were at high-risk for HBOC based on a strong family history (defined as >3 family members diagnosed with HBOC) without a genetic mutation. HBOC patients were matched in a 1:1 fashion to a control group undergoing fertility preservation without a diagnosis of infertility or HBOC. All analysis was done using SPSS version 9.4 (SAS Institute, Cary, NC). RESULTS: Between August 1st, 2016 and August 1st, 2022, 81 patients presented to the study center for consultation in the setting of HBOC. Of those who presented, 48 (59.2%) ultimately underwent oocyte cryopreservation and 33 (40.7%) underwent embryo cryopreservation. Patients who underwent oocyte cryopreservation due to BRCA1 status were more likely to present for fertility consultation at a younger age compared to control patients (32.6 vs. 34.7 years, p = 0.03) and were more likely to undergo oocyte cryopreservation at a younger age (32.1 vs. 34.6 years, p = 0.007). There was no difference in age at initial consultation or age at procedure for patients with BRCA2 or patients with a strong family history compared to control patients (p > 0.05). There was no difference in the mean age of patients with HBOC at presentation for consultation for embryo cryopreservation or the mean age the patient with HBOC underwent embryo cryopreservation compared to control patients (p > 0.05). Patients with BRCA1 or BRCA2 did not have expedited time from consultation to first cycle start (p > 0.05). After adjusting for factors including anti-Müllerian hormone (AMH) level and age, patients considered in the HBOC group due to family history had less time between consultation and oocyte cryopreservation cycle compared to control patients. (179 vs. 317 days, p = 0.045). There was no difference in time from consultation to starting cycle for embryo cryopreservation for patients with HBOC compared to controls (p > 0.05). CONCLUSION: Patients with HBOC did not undergo expedited fertility treatment compared to control patients undergoing oocyte and embryo cryopreservation for non-infertility reasons. Patients diagnosed with BRCA1 had more oocytes retrieved compared to the control population which is possibly due to earlier age of presentation in the setting of recommended age of risk reducing surgery being age 35-40. When age matched, cycle outcomes did not differ between HBOC and control patients. Given the known cancer prevention benefit and recommendations for risk-reducing surgery, future studies should focus on guidelines for fertility preservation for patients with HBOC.

Effect of postthaw change in embryo score on single euploid embryo transfer success rates.

OBJECTIVE: To assess whether the change in embryo morphology from precryopreservation to postthaw is associated with the embryo transfer success rates in single euploid embryo transfer cycles. DESIGN: Retrospective cohort study. SETTING: Academic affiliated fertility clinic. PATIENT(S): Patients who underwent a single euploid embryo transfer cycle from September 2016 to April 2022 were included. A decision support tool was used to assign each embryo a reproductive potential score on the basis of the day of biopsy, expansion, and grade of trophectoderm and inner cell mass at the time of cryopreservation and after thaw. Embryos were divided into 4 groups: group 1 included embryos with the same score after thaw (reference); group 2 included those with a higher score; group 3 included those with a lower score; and group 4 included those that did not re-expand after thaw. INTERVENTION(S): No interventions administered. MAIN OUTCOME MEASURE(S): The primary outcome was the live birth rates (LBRs) per embryo transfer. The secondary outcomes included the chemical pregnancy, clinical pregnancy, and clinical pregnancy loss rates. Comparative statistics and univariate analyses were performed using the Kruskal-Wallis and χ2tests. Multivariate logistic regression fitted with generalized estimating equation was performed to compare the odds of live birth between groups. RESULT(S): A total of 7,750 embryo transfers performed for 4,613 patients met inclusion criteria: 5,331 in group 1; 486 in group 2; 1,726 in group 3; and 207 in group 4. In the univariate analysis, there was a statistically significant difference in the LBR between groups 1, 2, 3, and 4 (55.8% vs. 51.4%, 47.5%, and 26.6%). Logistic regression controlling for oocyte age, antimüllerian hormone, body mass index, endometrial thickness, year of embryo transfer, time from thaw to final grading, and embryo score before cryopreservation showed significantly lower odds of live birth when the embryo was downgraded (odds ratio [OR], 0.70; confidence interval [CI], 0.62-0.79) or did not re-expand (OR, 0.36; CI, 0.26-0.51) than those with no change in score. When controlling for all variables, there was a significant increase in the odds of live birth between embryos that had a higher score after thaw and those without a change (OR, 1.42; CI, 1.14-1.76). There was no significant difference in the clinical pregnancy loss rate among the 4 groups. CONCLUSION(S): The change in the quality of the embryo after thaw is an important factor in embryo transfer success. In an adjusted analysis, the chemical and clinical pregnancy rates and LBR per embryo transfer all significantly decrease in embryos that were downgraded or did not expand on the day of single euploid embryo transfer. Embryos that re-expand and have improved quality after thaw have the highest odds of live birth.

Single Euploid Embryo Transfer Outcomes After Uterine Septum Resection.

STUDY OBJECTIVE: To study pregnancy outcomes after single euploid embryo transfer (SEET) in patients who underwent prior uterine septum resection to those with uteri of normal contour, without Müllerian anomalies or uterine abnormalities including polyps or fibroids, and without a history of prior uterine surgeries. DESIGN: Retrospective cohort study. SETTING: Single academic affiliated center. PATIENTS: 60 cycles of patients with prior hysteroscopic uterine septum resection who underwent an autologous SEET between 2012 and 2020 were used as the investigational cohort. A 3:1 ratio propensity score matched control cohort of 180 single euploid embryo transfer cycles from patients without a history of uterine septa were used as the control group. INTERVENTIONS: No interventions administered. MEASUREMENTS AND MAIN RESULTS: Pregnancy, clinical pregnancy loss, ongoing clinical pregnancy, and live birth rates in patients with a history of uterine septum resection compared with matched patients without Müllerian anomalies or uterine surgeries. Patients with a prior uterine septum had significantly lower rates of chemical pregnancy (58.33% vs 77.2%, p = .004), implantation (41.67% vs 65.6%, p = .001), and live birth (33.33% vs 57.8%, p = .001) per transfer. No statistical difference in clinical pregnancy loss rates was found when comparing septum patients with controls (8.33% vs 7.8%, p = .89). CONCLUSION: Patients with a history of hysteroscopic resection who undergo in vitro fertilization are more susceptible to suboptimal clinical outcomes compared with patients with normal uteri. Early pregnancy loss rates in patients with a uterine septum are higher than in those without; however, after resection, the rates are comparable. Patients born with septate uteri require assessment of surgical intervention prior to SEET, and to optimize their reproductive outcomes.

Family Building in Transgender Patients: Modern Strategies with Assisted Reproductive Technology Treatment.

Purpose: Transgender and gender diverse (TGD) individuals continue to face adversity, stigma, and inequality, especially in health care. This study aimed to characterize the experience of TGD people and partners of TGD people with regard to fertility treatment. Methods: All TGD patients presenting to a single academic center between 2013 and 2021 were included. Baseline demographics collected included patient age, body mass index, anti-Mullerian hormone, basal antral follicle count, history of gender-affirming surgery, and/or gender-affirming hormone therapy. Outcomes included total patients who progressed to treatment, cycle type(s), and clinical outcomes. Results: In total, 82 patients who identified as TGD or had a partner who identified as TGD presented to care seeking fertility treatment. Of the 141 planned cycles, 106 (75.2%) progressed to treatment. Of the 15 in vitro fertilization (IVF) and co-IVF cycles, 12 achieved live birth. Of the 76 intrauterine inseminations 7 patients were discharged with ongoing pregnancies and one achieved live birth. Conclusion: These findings reaffirm that TGD individuals utilize the entire array of fertility services. With recent advances in access to care and modern medicine, assisted reproductive technology treatment has the power to support TGD patients in building contemporary family structures.

Assessing the clinical viability of micro 3 pronuclei zygotes.

PURPOSE: What is the rate of euploidy and clinical viability of embryos resulting from micro 3 pronuclei zygotes? METHODS: Retrospective cohort analysis in a single, academic in vitro fertilization (IVF) center from March 2018 to June 2021. Cohorts were separated by fertilization as either a 2 pronuclear zygote (2PN) or micro 3 pronuclear zygote (micro 3PN). PGT-A was performed to identify embryonic ploidy rates in embryos created from micro 3PN zygotes. The clinical outcomes of all transferred euploid micro 3PN zygotes were evaluated from frozen embryo transfer (FET) cycles. RESULTS: During the designated study period, 75,903 mature oocytes were retrieved and underwent ICSI. Of these, 60,161 were fertilized as 2PN zygotes (79.3%) and 183 fertilized as micro 3PN zygotes (0.24%). Of the micro 3PN-derived embryos that underwent biopsy, 27.5% (n=11/42) were deemed euploid by PGT-A, compared to 51.4% (n=12,301/23,923) of 2PN-derived embryos, p=0.06. Four micro 3PN-derived embryos were transferred in subsequent single euploid FET cycles, which includes one live birth and one ongoing pregnancy. CONCLUSION: Micro 3PN zygotes that develop to the blastocyst stage and meet the criteria for embryo biopsy have the potential to be euploid by preimplantation genetic testing for aneuploidy (PGT-A) and if selected for transfer can achieve a live birth. Although there are a significantly lower number of micro 3PN embryos that make it to blastocyst biopsy, the potential to continue to culture abnormally fertilized oocytes may give these patients a chance at pregnancy that they previously did not have.

Fertility treatment outcomes in transgender men with a history of testosterone therapy.

Objective: To evaluate fertility treatment outcomes among transgender (TG) men with a history of gender-affirming hormone therapy with exogenous testosterone. Design: Descriptive, retrospective cohort study. Patients: Transgender men with a history of gender-affirming hormone therapy with exogenous testosterone underwent fertility treatments, including embryo cryopreservation, in vitro fertilization (IVF), co-IVF, oocyte cryopreservation, and intrauterine insemination (IUI), between 2013 and 2021. Intervention: Gender-affirming hormone therapy with testosterone. Main Outcome Measures: Live births (LBs), number of frozen embryos, and number of frozen oocytes. Other outcome measures included total gonadotropin used, peak estradiol levels, oocytes retrieved, oocyte maturity rate, fertilization rate, and embryo grade. Results: A total of 77 TG men self-presented or were referred to care at a single academic fertility center, of which 46 (59.7%) TG men underwent fertility preservation and/or family-building counseling, with 16 (20.8%) patients proceeding to fertility treatment. Of those patients who underwent treatment, 11 (68.8%) had a history of gender-affirming hormone therapy with exogenous testosterone use. Cohort 1 included IVF (n = 1), co-IVF (n = 1), embryo cryopreservation (n = 2), cohort 2 included oocyte cryopreservation (n = 4), and cohort 3 included IUI (n = 3). In cohort 1, both the patients who underwent IVF and the patients who underwent co-IVF achieved LBs. All embryo cryopreservation cycles froze three or more embryos. In cohort 2, the average number of frozen mature oocytes was 19.3 ± 16.2 (range 6-43). All patients who underwent IUI cycles achieved LB. Conclusion: In this study, no correlation existed between patient age, time on or off gender-affirming hormone therapy with exogenous testosterone, total gonadotropin used, and number of oocytes retrieved. All patients who completed IVF or embryo cryopreservation produced high-quality blastocytes, and this is the first study to show successful IUI cycles in patients with a history of gender-affirming hormone therapy with exogenous testosterone. This study demonstrates that TG men who have used gender-affirming hormone therapy previously can successfully undergo fertility treatments to attain oocyte and embryo cryopreservation, pregnancy, and LBs.

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

Objective: To explore the cycle characteristics and outcomes of single and coupled intended fathers (SCIFs) using assisted reproductive technology. Design: Cross-sectional study. Setting: Multicenter, fertility practices from 2016 to 2020. Patients: In this study, cycles among SCIFs with access to fertility coverage from 2016 to 2020 were included. Interventions: None. Main Outcome Measures: Our primary outcome was live birth rate. The secondary outcomes included the number of embryos transferred, miscarriage rate, and incidence of multifetal birth. Results: Five single and 39 coupled intended fathers completed an in vitro 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). Conclusions: 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.

An interpretable machine learning model for individualized gonadotrophin starting dose selection during ovarian stimulation.

RESEARCH QUESTION: Can we develop an interpretable machine learning model that optimizes starting gonadotrophin dose selection in terms of mature oocytes (metaphase II [MII]), fertilized oocytes (2 pronuclear [2PN]) and usable blastocysts? DESIGN: This was a retrospective study of patients undergoing autologous IVF cycles from 2014 to 2020 (n = 18,591) in three assisted reproductive technology centres in the USA. For each patient cycle, an individual dose-response curve was generated from the 100 most similar patients identified using a K-nearest neighbours model. Patients were labelled as dose-responsive if their dose-response curve showed a region that maximized MII oocytes, and flat-responsive otherwise. RESULTS: Analysis of the dose-response curves showed that 30% of cycles were dose-responsive and 64% were flat-responsive. After propensity score matching, patients in the dose-responsive group who received an optimal starting dose of FSH had on average 1.5 more MII oocytes, 1.2 more 2PN embryos and 0.6 more usable blastocysts using 10 IU less of starting FSH and 195 IU less of total FSH compared with patients given non-optimal doses. In the flat-responsive group, patients who received a low starting dose of FSH had on average 0.3 more MII oocytes, 0.3 more 2PN embryos and 0.2 more usable blastocysts using 149 IU less of starting FSH and 1375 IU less of total FSH compared with patients with a high starting dose. CONCLUSIONS: This study demonstrates retrospectively that using a machine learning model for selecting starting FSH can achieve optimal laboratory outcomes while reducing the amount of starting and total FSH used.

Improving preeclampsia risk prediction by modeling pregnancy trajectories from routinely collected electronic medical record data.

Preeclampsia is a heterogeneous and complex disease associated with rising morbidity and mortality in pregnant women and newborns in the US. Early recognition of patients at risk is a pressing clinical need to reduce the risk of adverse outcomes. We assessed whether information routinely collected in electronic medical records (EMR) could enhance the prediction of preeclampsia risk beyond what is achieved in standard of care assessments. We developed a digital phenotyping algorithm to curate 108,557 pregnancies from EMRs across the Mount Sinai Health System, accurately reconstructing pregnancy journeys and normalizing these journeys across different hospital EMR systems. We then applied machine learning approaches to a training dataset (N = 60,879) to construct predictive models of preeclampsia across three major pregnancy time periods (ante-, intra-, and postpartum). The resulting models predicted preeclampsia with high accuracy across the different pregnancy periods, with areas under the receiver operating characteristic curves (AUC) of 0.92, 0.82, and 0.89 at 37 gestational weeks, intrapartum and postpartum, respectively. We observed comparable performance in two independent patient cohorts. While our machine learning approach identified known risk factors of preeclampsia (such as blood pressure, weight, and maternal age), it also identified other potential risk factors, such as complete blood count related characteristics for the antepartum period. Our model not only has utility for earlier identification of patients at risk for preeclampsia, but given the prediction accuracy exceeds what is currently achieved in clinical practice, our model provides a path for promoting personalized precision therapeutic strategies for patients at risk.

An interpretable machine learning model for predicting the optimal day of trigger during ovarian stimulation.

OBJECTIVE: To develop an interpretable machine learning model for optimizing the day of trigger in terms of mature oocytes (MII), fertilized oocytes (2PNs), and usable blastocysts. DESIGN: Retrospective study. SETTING: A group of three assisted reproductive technology centers in the United States. PATIENT(S): Patients undergoing autologous in vitro fertilization cycles from 2014 to 2020 (n = 30,278). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Average number of MII oocytes, 2PNs, and usable blastocysts. RESULT(S): A set of interpretable machine learning models were developed using linear regression with follicle counts and estradiol levels. When using the model to make day-by-day predictions of trigger or continuing stimulation, possible early and late triggers were identified in 48.7% and 13.8% of cycles, respectively. After propensity score matching, patients with early triggers had on average 2.3 fewer MII oocytes, 1.8 fewer 2PNs, and 1.0 fewer usable blastocysts compared with matched patients with on-time triggers, and patients with late triggers had on average 2.7 fewer MII oocytes, 2.0 fewer 2PNs, and 0.7 fewer usable blastocysts compared with matched patients with on-time triggers. CONCLUSION(S): This study demonstrates that it is possible to develop an interpretable machine learning model for optimizing the day of trigger. Using our model has the potential to improve outcomes for many in vitro fertilization patients.

Elevated Body Mass Index in Donor Oocyte Recipients Does Not Affect Implantation of Euploid Embryos.

Background: Obesity is a worldwide epidemic that has been shown to have serious implications on health outcomes. Regarding reproductive health, increased body mass index (BMI) reduces fertility and increases the time to conceive. It is unclear how excess weight in females affects the development of oocytes and embryos or the impact of implantation. Materials and Methods: This retrospective single-center study aimed to determine if overweight and obese oocyte recipients had similar pregnancy outcomes compared with healthy weight controls after the transfer of a single euploid frozen-thawed embryo transfer (FET). Five hundred twenty-eight patients who underwent a transfer from 2016 to 2021 were included. The primary outcome studied was the clinical pregnancy (CP) rate. Secondary outcomes included live birth (LB) rate, biochemical pregnancy loss (BPL) rate, and clinical pregnancy loss (CPL) rate. Results: The overall CP rate was 54.9% and did not differ significantly among normal weight (n = 318), overweight (n = 129), and obese (n = 81) BMI categories (0.56 vs. 0.56 vs. 0.49, p = 0.56). There were no significant differences in LB rate (0.47 vs. 0.43 vs. 0.38, p = 0.33), BPL rate (0.14 vs. 0.09 vs. 0.11, p = 0.59), and CPL rate (0.15 vs. 0.21 vs. 0.18, p = 0.38) among BMI groups. Conclusions: Our findings provide support that BMI alone does not adversely alter endometrial receptivity and is not the cause of poor in vitro fertilization (IVF) outcomes in patients with increased BMI. These deleterious IVF outcomes might be to the result of diminished oocyte and/or embryo quality or other factors that have not yet been elucidated.

In Vitro Fertilization and Early Pregnancy Outcomes After Coronavirus Disease 2019 (COVID-19) Vaccination.

OBJECTIVE: To assess whether coronavirus disease 2019 (COVID-19) mRNA vaccination is associated with controlled ovarian hyperstimulation or early pregnancy outcomes. METHODS: This retrospective cohort study included patients who underwent controlled ovarian hyperstimulation or single euploid frozen-thawed embryo transfer at a single academic center. Patients fully vaccinated with a COVID-19 mRNA vaccine were compared with unvaccinated patients who cycled during the same time period. The primary outcome was the fertilization rate for controlled ovarian hyperstimulation and the clinical pregnancy rate for frozen-thawed embryo transfer. Secondary outcomes for controlled ovarian hyperstimulation included eggs retrieved, mature oocytes retrieved, mature oocytes ratio, blastulation rate, and euploid rate. Secondary outcomes for frozen-thawed embryo transfer included pregnancy rate, ongoing pregnancy rate, biochemical pregnancy loss rate, and clinical pregnancy loss rate. RESULTS: Among 222 vaccinated patients and 983 unvaccinated patients who underwent controlled ovarian hyperstimulation cycles between February and September 2021, there was no association on adjusted analysis between COVID-19 vaccination and fertilization rate (ß=0.02±0.02, P=.20) or any of the secondary outcomes assessed: eggs retrieved (ß=0.01±0.57, P=.99), mature oocytes retrieved (ß=0.26±0.47, P=.58), mature oocytes ratio (ß=0.02±0.01, P=.12), blastulation rate (ß=0.02±0.02, P=.27), or euploid rate (ß=0.05±0.03, P=.08). Among 214 vaccinated patients and 733 unvaccinated patients undergoing single euploid frozen-thawed embryo transfer, adjusted analysis demonstrated no significant association between vaccination and clinical pregnancy (adjusted odds ratio [aOR] 0.79, 95% CI 0.54-1.16) or any of the secondary outcomes: pregnancy (aOR 0.88, 95% CI 0.58-1.33), ongoing pregnancy (aOR 0.90, 95% CI 0.61-1.31), biochemical pregnancy loss (aOR 1.21, 95% CI 0.69-2.14), or clinical pregnancy loss (aOR 1.02, 95% CI 0.51-2.06). CONCLUSION: Administration of COVID-19 mRNA vaccines was not associated with an adverse effect on stimulation or early pregnancy outcomes after IVF. Our findings contribute to the growing body of evidence regarding the safety of COVID-19 vaccination in women who are trying to conceive.

The Impact of the Coronavirus Disease 19 Pandemic on Early Pregnancy Outcomes Among Patients Undergoing In Vitro Fertilization Treatment.

Objective: To determine if pregnancy rates (PRs) or pregnancy loss rates (PLRs) were altered in patients undergoing single, euploid frozen-thawed embryo transfer (FET) during the initial peak of the Coronavirus Disease 19 (COVID-19) pandemic. Materials and Methods: This was a retrospective cohort study performed in a single academic center. Patients undergoing single, euploid FET cycles from January to May 2017-2020 were included. Cycles with FET performed in January-May of 2020 ("COVID-surge cohort") were compared to cycles with FET performed in January-May of 2017-2019 ("pre-COVID cohort"). Pregnancy rate (PR), clinical pregnancy rate (CPR), pregnancy loss rate (PLR), and clinical pregnancy loss rate (CLR) were compared between the cohorts. Results: A total of 2629 single, euploid FET cycles were included: 2070 from January to May, 2017-2019 and 559 from January to May 2020. PR was similar when comparing FET performed from January to May 2020 (COVID-surge) to those performed from January to May, 2017-2019 (pre-COVID) (77.6% vs. 73.7%, p = 0.06), while CPR was higher among the COVID-surge compared to the pre-COVID cohort (65.5% vs. 60.0%, p = 0.02). No differences were seen in PLR and CLR among the COVID-surge and pre-COVID cohorts (28.3% vs. 32.0%, p = 0.08; 15.0% vs. 16.5%, p = 0.50). PR, CPR, PLR, and CLR were similar when comparing individual months between the cohorts. Adjusted analysis showed no differences in PR, CPR, PLR, or CLR when comparing the cohorts overall or when comparing corresponding individual months in the two time periods. Conclusion: PRs and PLRs were not decreased when SARS-CoV-2 transmission was widespread in our geographic area, suggesting that high COVID-19 transmission does not compromise early pregnancy outcomes.

Factors associated with vitrification-warming survival in 6167 euploid blastocysts.

PURPOSE: To understand the clinical factors associated with embryo survival after vitrification in a cohort of human blastocysts screened by preimplantation genetic testing for aneuploidy (PGT-A). METHODS: Patient demographic, embryo, and cycle characteristics associated with failed euploid blastocyst survival were compared in a cohort of women (n = 6167) who underwent IVF-PGT-A. RESULTS: Compared to those that survived warming, vitrified euploid embryos that failed to survive after warming came from IVF cycles with significantly higher estradiol levels at time of surge (2754.8 ± 1390.2 vs. 2523.1 ± 1190.6 pg/mL, p = 0.03), number of oocytes retrieved (19.6 ± 10.7 vs. 17.5 ± 9.8, p = 0.005), and basal antral follicle count (BAFC) (15.3 ± 8.5 vs. 13.9 ± 7.2, p = 0.05). Euploid embryos were less likely to survive warming if they came from cycles before 2015 (24.6% vs. 13.2%, p < 0.001), were cryopreserved on day 7 versus day 5 or 6 (9.1% vs. 3.0%, p < 0.001), underwent two trophectoderm biopsies (6.9% vs. 2.3%, p < 0.001), had a grade C inner cell mass (15.4% vs. 7.7%, p < 0.001), or were fully hatched (41.1% vs. 12.2%, p < 0.001). In the multivariate model, which controlled for relevant confounders, the association between decreased survival and increased BAFC, year of IVF cycle, double trophectoderm biopsy, and fully hatched blastocysts remained statistically significant. CONCLUSION: Euploid embryos that are fully hatched at time of vitrification, come from patients with high ovarian reserve, or require repeat trophectoderm biopsy are less likely to survive vitrification-warming. Our results provide a framework for reproductive counseling and offer realistic expectations to patients about the number of embryos needed to achieve family building goals.

Parental chromosomal heteromorphisms are not associated with an increased risk of embryo aneuploidy.

OBJECTIVE: Although chromosomal heteromorphisms are commonly found in the general population, some researchers have suggested a correlation with higher rates of embryo aneuploidy. This study aimed to assess the rates of embryo aneuploidy in couples who carry a chromosome heteromorphism. METHODS: The study included couples who had G-banding karyotype testing and underwent an IVF/PGT-A cycle between January 2012 and March 2018. The participants were classified by couple karyotype: Group A: ≥1 patient reported to be a heterochromatic variant carrier; Group B: both partners reported to be "normal". We assessed the rates of aneuploidy among the groups. We ran a multivariate regression analysis to assess the relationship between heterochromatic variants and the rates of embryo aneuploidy. RESULTS: Of the 946 couples analyzed, 48 (5.0%) reported being a carrier of ≥1 heterochromatic variant. We had 869 IVF/PGT-A cycles included in the analysis (Group A: n=48; Group B: n=82). There were no significant differences in embryo ploidy rates among the groups. The heterochromatic chromosome variant was not associated with increased likelihoods of aneuploidy (OR=1.04, CI:95% 0.85- 1.07; p=0.46). Finally, the gender of the heterochromatic variant carrier had no association with increased likelihood of aneuploidy (OR 1.02, CI 95% 0.81-1.28, p=0.82). CONCLUSIONS: Our study showed no association between parental heterochromatic chromosome variants and subsequent embryo aneuploidy rates. Ploidy rates do not appear to be negatively associated with couples when at least one patient is reported to be a carrier of a heterochromatic variant on the karyotype.

Evaluating in vitro fertilization outcomes of patients with low body mass index following frozen-thawed embryo transfer.

OBJECTIVE: To determine the relationship between patients with a low body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) and in vitro fertilization (IVF) outcomes following frozen-thawed embryo transfer (FET). METHODS: Retrospective cohort study including 12 618 women aged 20-46 years with an underweight (<18.5) or normal weight (18.5-24.9) BMI who underwent controlled ovarian stimulation for IVF in a private and academic IVF center between August 2002 and December 2019. RESULTS: Anti-Müllerian hormone, peak estradiol levels, number of MII oocytes, and fertilized oocytes were greater in the underweight group compared with the normal weight group. The total required gonadotropin dose was lower in the underweight patients compared with the normal weight patients. MII, fertilization, blastulation, and euploid rates did not differ before and after adjusting for confounders between BMI groups. In a cohort of 316 patients who underwent preimplantation genetic testing for aneuploidy and single euploid FET, pregnancy loss, pregnancy, clinical pregnancy, and live birth rates before and after controlling for covariates were similar between groups. CONCLUSION: Although there are known fetal growth or obstetrical issues associated in patients with a low BMI, it is reassuring that these risks do not extend to embryologic or clinical outcomes from IVF treatment.

A multi-centre international study of salivary hormone oestradiol and progesterone measurements in ART monitoring.

RESEARCH QUESTION: Ovarian stimulation during IVF cycles involves close monitoring of oestradiol, progesterone and ultrasound measurements of follicle growth. In contrast to blood draws, sampling saliva is less invasive. Here, a blind validation is presented of a novel saliva-based oestradiol and progesterone assay carried out in samples collected in independent IVF clinics. DESIGN: Concurrent serum and saliva samples were collected from 324 patients at six large independent IVF laboratories. Saliva samples were frozen and run blinded. A further 18 patients had samples collected more frequently around the time of HCG trigger. Saliva samples were analysed using an immunoassay developed with Salimetrics LLC. RESULTS: In total, 652 pairs of saliva and serum oestradiol were evaluated, with correlation coefficients ranging from 0.68 to 0.91. In the European clinics, a further 237 of saliva and serum progesterone samples were evaluated; however, the correlations were generally poorer, ranging from -0.02 to 0.22. In the patients collected more frequently, five out of 18 patients (27.8%) showed an immediate decrease in oestradiol after trigger. When progesterone samples were assessed after trigger, eight out of 18 (44.4%) showed a continued rise. CONCLUSIONS: Salivary oestradiol hormone testing correlates well to serum-based assessment, whereas progesterone values, around the time of trigger, are not consistent from patient to patient.

Late follicular phase progesterone elevation during ovarian stimulation is not associated with decreased implantation of chromosomally screened embryos in thaw cycles.

STUDY QUESTION: What is the impact of a late follicular phase progesterone elevation (LFPE) during controlled ovarian hyperstimulation (COH) on embryonic competence and reproductive potential in thaw cycles of preimplantation genetic testing for aneuploidy (PGT-A) screened embryos? SUMMARY ANSWER: Our study findings suggest that LFPE, utilizing a progesterone cutoff value of 2.0 ng/ml, is neither associated with impaired embryonic development, increased rate of embryonic aneuploidy, nor compromised implantation and pregnancy outcomes following a euploid frozen embryo transfer (FET) cycle. WHAT IS KNOWN ALREADY: Premature progesterone elevation during COH has been associated with lower pregnancy rates due to altered endometrial receptivity in fresh IVF cycles. Also, increased levels of progesterone (P) have been suggested to be a marker for ovarian dysfunction, with some evidence to show an association between LFPE and suboptimal embryonic development. However, the effect of LFPE on embryonic competence is still controversial. STUDY DESIGN, SIZE, DURATION: Retrospective cohort analysis in a single, academic ART center from September 2016 to March 2020. In total, 5244 COH cycles for IVF/PGT-A were analyzed, of those 5141 were included in the analysis. A total of 23 991 blastocysts underwent trophectoderm biopsy and PGT analysis. Additionally, the clinical IVF outcomes of 5806 single euploid FET cycles were evaluated. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohorts were separated in two groups: Group 1: oocytes retrieved from cycles with normal P levels during ovulation trigger (P ≤ 2.0 ng/ml); Group 2: oocytes retrieved after cycles in which LFPE was noted (P > 2.0 ng/ml). Extended culture and PGT-A was performed. Secondly, IVF outcomes after a single euploid FET were evaluated for each cohort. MAIN RESULTS AND THE ROLE OF CHANCE: Four thousand nine hundred and twenty-five cycles in Group 1 were compared with 216 cycles on Group 2. Oocyte maturity rates, fertilization rates and blastulation rates were comparable among groups. A 65.3% (n = 22 654) rate of utilizable blastocysts was found in patients with normal P levels and were comparable to the 62.4% (n = 1337) observed in those with LFPE (P = 0.19). The euploidy rates were 52.8% (n = 11 964) and 53.4% (n = 714), respectively, albeit this difference was not statistically significant (P = 0.81). Our multivariate analysis was fitted with a generalized estimating equation (GEE) and no association was found with LFPE and an increased odds of embryo aneuploidy (adjusted odds ratio 1.04 95% CI 0.86-1.27, P = 0.62). A sub-analysis of subsequent 5806 euploid FET cycles (normal P: n = 5617 cycles and elevated P: n = 189 cycles) showed no differences among groups in patient's BMI, Anti-Müllerian hormone (AMH), endometrial thickness at FET and number of prior IVF cycles. However, a significant difference was found in patient's age and oocyte age. The number of good quality embryos transferred, implantation rate, clinical pregnancy rate, ongoing pregnancy rate, multiple pregnancy rate and clinical pregnancy loss rates were comparable among groups. Of the registered live births (normal P group: n = 2198; elevated P group: n = 52), there were no significant differences in gestational age weeks (39.0 ± 1.89 versus 39.24 ± 1.53, P = 0.25) and birth weight (3317 ± 571.9 versus 3 266 ± 455.8 g, P = 0.26) at delivery, respectively. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study and probable variability in the study center's laboratory protocol(s), selected progesterone cutoff value and progesterone assay techniques compared to other ART centers may limit the external validity of our findings. WIDER IMPLICATIONS OF THE FINDINGS: Based on robust sequencing data from a large cohort of embryos, we conclude that premature P elevation during IVF stimulation does not predict embryonic competence. Our study results show that LFPE is neither associated with impaired embryonic development nor increased rates of aneuploidy. Embryos obtained from cycles with LFPE can be selected for transfer, and patients can be reassured that the odds of achieving a healthy pregnancy are similar to the embryos exposed during COH cycles to physiologically normal P levels. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for the realization of this study. Dr A.B.C. is advisor and/or board member of Sema 4 (Stakeholder in data), Progyny and Celmatix. The other authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NA.

Expanded carrier screening for preconception reproductive risk assessment: Prevalence of carrier status in a Mexican population.

OBJECTIVE: Genetic carrier screening has the potential to identify couples at risk of having a child affected with an autosomal recessive or X-linked disorder. However, the current prevalence of carrier status for these conditions in developing countries is not well defined. This study assesses the prevalence of carrier status of selected genetic conditions utilizing an expanded, pan-ethnic genetic carrier screening panel (ECS) in a large population of Mexican patients. METHODS: Retrospective chart review of all patients tested with a single ECS panel at an international infertility center from 2012 to 2018 were included, and the prevalence of positive carrier status in a Mexican population was evaluated. RESULTS: Eight hundred five individuals were analyzed with ECS testing for 283 genetic conditions. Three hundred fifty-two carriers (43.7%) were identified with 503 pathogenic variants in 145 different genes. Seventeen of the 391 participating couples (4.34%) were identified as being at-risk couples. The most prevalent alleles found were associated with alpha thalassemia, cystic fibrosis, GJB2 nonsyndromic hearing loss, biotinidase deficiency, and familial Mediterranean fever. CONCLUSION: Based on the prevalence and severity of Mendelian disorders, we recommend that couples who wish to conceive regardless of their ethnicity background explore carrier screening and genetic counseling prior to reproductive medical treatment.

Conservative treatment versus surgical excision of ovarian dermoid cysts: Impact on ovarian stimulation and IVF cycle success.

OBJECTIVE: To analyze outcomes of IVF treatment among women diagnosed with an ovarian dermoid cyst (DC). METHODS: Retrospective analysis of women with an ovarian DC who underwent IVF with fresh blastocyst transfer at a single center in New York from January 2010 to March 2018. Outcomes were compared between women with conservative treatment and those with surgical excision of the DC. Multivariate logistic regression was used to assess associations between variables and the presence of a DC during treatment. RESULTS: Overall, 119 women with a DC were included. No differences were found in demographic characteristics, controlled ovarian hyperstimulation parameters, and IVF outcomes between women with an intact DC (n=65, 54.6%) and those who underwent cystectomy (n=54, 45.4%) (all P<0.05). Similarly, there was no difference in anti-Mϋllerian hormone and basal antral follicle count among women with a DC (respectively, ß=-0.1, P=0.8, and ß=-1.0, P=0.28) or resected DC (respectively, ß=0.9, P=0.07, and ß=1.5, P=0.08) as compared with control women with no DC (n=352). CONCLUSION: Ovarian reserve, embryo implantation and IVF success rates were not lower in the presence of an ovarian DC. Surgical therapy, if indicated, can be safely postponed until family planning goals have been achieved.