Faculty Bibliography

PURPOSE/OBJECTIVE:Our aim was to describe the reproductive decisions and outcomes of BRCA-positive patients who used preimplantation genetic testing for monogenic disorders (PGT-M). METHODS:We performed a retrospective case series of all PGT-M cycles for BRCA variants between 2010-2021 at a large urban academic fertility center. All patients who underwent ≥ 1 cycle of IVF with PGT-M for BRCA1 or BRCA2 were included. The primary outcome was total number of BRCA-negative euploid embryos per patient. RESULTS:Sixty four patients underwent PGT-M for BRCA variants. Forty-five percent (29/64) were BRCA1-positive females, 27% (17/64) were BRCA2-positive females, 16% (10/64) were BRCA1-positive males, 11% (7/64) were BRCA2-positive males, and one was a BRCA1 and BRCA2-positive male. There were 125 retrieval cycles with PGT-M, and all cycles included PGT for aneuploidy (PGT-A). Eighty-six percent (55/64) of patients obtained at least one BRCA- negative euploid embryo, with median of 1 (range 0-10) BRCA-negative euploid embryo resulted per cycle and median 3 (range 0-10) BRCA-negative euploid embryos accumulated per patient after a median of 2 (range 1-7) oocyte retrievals. Sixty-four percent (41/64) of patients attempted at least one frozen embryo transfer (FET) with a total of 68 FET cycles. Fifty-nine percent (40/68) of embryos transferred resulted in live births. Subgroup analysis revealed different reproductive pathways for BRCA1-positive females, BRCA2-positive females, and BRCA1/2-positive males (p < 0.05). CONCLUSION/CONCLUSIONS:PGT-M is a viable option for BRCA-positive patients to avoid transmission while building their families. Most patients in our cohort achieved pregnancy with BRCA-negative euploid embryos.

STUDY QUESTION/OBJECTIVE:How often do patients undergoing frozen embryo transfer (FET) after preimplantation genetic testing for aneuploidy (PGT-A) choose to select for sex and do sex selection rates differ before and after successful delivery of a first baby? SUMMARY ANSWER/CONCLUSIONS:When a choice was available between male and female embryos, patients selected the sex more frequently when trying to conceive the second child (62%) as compared to the first child (32.4%) and most commonly selected for the opposite sex of the first child. WHAT IS KNOWN ALREADY/BACKGROUND:Sex selection is widely available in US fertility clinics. However, the rate of sex selection for patients undergoing FET after PGT-A is unknown. STUDY DESIGN, SIZE, DURATION/METHODS:This is a retrospective cohort study of 585 patients that took place between January 2013 and February 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS/METHODS:The study took place at a single, urban academic fertility center in the USA. Patients were included if they had a live birth after single euploid FET and returned for at least one subsequent euploid FET. The primary outcomes were the rates of sex selection for first versus second baby. Secondary outcomes were rate of selection for same versus opposite sex as first live birth and overall rate of selection for males versus females. MAIN RESULTS AND THE ROLE OF CHANCE/RESULTS:Five hundred and eighty-five patients underwent a total of 1560 single euploid FETs resulting in either one or two live births. A choice between male and female euploid embryos was available for 919 FETs (first child: 67.5% (519/769) versus second child: 50.6% (400/791), P < 0.01). When a choice was available, patients selected the sex more frequently when trying to conceive the second child (first child: 32.4% (168/519) versus second child: 62.0% (248/400), P < 0.01). When sex was selected after first live birth, the opposite sex of the first child was selected 81.8% (203/248 FETs) of the time. Of transfers that involved sex selection, rates of male and female selection were similar for the first child, but selection for females was greater for the second child (first child: 51.2% (86/168) male versus 48.9% (82/168) female, second child: 41.1% (102/248) male versus 58.9% (146/248) female, P < 0.04). LIMITATIONS, REASONS FOR CAUTION/CONCLUSIONS:The study was performed at one urban academic medical center in the Northeastern US, which may limit generalizability to other settings where PGT-A may be performed less frequently, or sex selection may be limited or not permitted. In addition, we could not reliably account for whether patients or their partners had prior children and if so, of what sex. WIDER IMPLICATIONS OF THE FINDINGS/CONCLUSIONS:Patients undergoing PGT-A with both male and female euploid embryos were more likely to select for sex when attempting a second child and usually selected for the opposite sex of their first child. These findings highlight the potential for family balancing for patients who undergo PGT-A in settings where sex selection is permitted. STUDY FUNDING/COMPETING INTEREST(S)/BACKGROUND:This study received no funding. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER/BACKGROUND:N/A.

PURPOSE/OBJECTIVE:To design a replicable simulation curriculum collaboratively with the transgender and gender diverse community to improve clinician knowledge and comfort with providing reproductive care to this population. METHODS:This is a prospective, single arm pre-post analysis of obstetrics and gynecology residents at a single academic institution after completion of a novel simulation curriculum. The primary outcome was the change in resident comfort and knowledge in providing transgender and gender diverse patient care. A thematic analysis of learner and standardized patient free text responses was analyzed for insights on perceived learner experiences. RESULTS:This curriculum was created with iterative feedback from the transgender community and involved only transgender and gender diverse-identified standardized patients. Thirty residents participated, with 22 responding to both the pre-and post-curriculum surveys, and 11 responding to a 6-month post-curriculum survey. There were significant improvements in learner comfort and knowledge after participation that were found to persist at 6 months. Qualitative analysis demonstrated that this was a positive and powerful learning experience for both residents and standardized patients. CONCLUSIONS:This simulation curriculum may be an effective and impactful tool to increase trainee comfort and knowledge of transgender and gender diverse patient care, which is important given the lack of physician training in the care for these individuals. By building the foundation with resident learners, the ultimate goal is to enhance the pool of clinicians confident and capable of caring for transgender and gender diverse patients, to increase access to care, and to improve health outcomes in this vulnerable population.

Background: Preimplantation genetic testing for monogenic disorders (PGT-M) can be performed on embryos prior to transfer when a variant or mutation is identified in a single gene. PGT-M has historically been utilized to evaluate embryos for severe, highly penetrant and childhood-onset diseases.¹ However, the use of PGT-M has significantly increased due to increased genetic testing³ and expanded indications.^4-5 Objective: To investigate indications, trends and outcomes when PGT-M is performed for two or more monogenic disorders simultaneously.
Material(s) and Method(s): This is a case series in a single university-based fertility center. All PGT-M cases involving testing for two or more genes as well as preimplantation genetic testing for aneuploidy (PGT-A) between January 2010 and October 2021 were reviewed. Genes 1, 2 and 3 were defined as genes of interest discovered in chronological order respectively. Primary outcomes included indication for presentation to fertility center, PGT-M indication, type of condition, age of condition onset and PGT-M inheritance pattern. Secondary outcomes included genetic result of transferred embryo and ongoing pregnancy rates defined as pregnancies greater than 20 weeks gestation divided by total single thawed euploid embryo transfers (STEET).
Result(s): This study included 363 biopsied blastocysts from 49 retrievals, in 23 patients who had 24 STEET. 56%(13/23) of patients presented between 2019 and 2021,with 30%(7/23) presenting in 2021 alone.The majority initially presented for double PGT-M[44%(10/23)]. 39%(9/23) presented initially for single PGT-M,with a second gene identified later. 4%(1/23) presented for triple PGT-M. 13%(3/23) presented for infertility with no previous genetic testing.Across the 23 patients,47 genes were tested and 34 of those were unique.The most commonly tested genes were BRCA1/2[11%(5/47)],HLA[11%(5/47)], FMR1[6%(3/47)],GJB2[6%(3/47)],MSH2[4%(2/47)] and SLC26A4[4%(2/47)].The majority of genes tested cause childhood-onset diseases[68%(32/47)]. 23% were adult-onset and 8% were variable-onset.The majority were split between autosomal dominant(AD)[38%(18/47)] and autosomal recessive(AR)[(38%)18/47]. 13%(6/47) were X-linked and 10%(5/47) were for HLA matching.PGT-M indication for first gene identified included previous child affected[30%(7/23)], carrier screening[26%(6/23)], patient affected[22%(5/23)] and partner affected[22%(5/23)].PGT-M indication for second gene identified included carrier screening[43%(10/23)], previous child affected[26%(6/23)], patient affected[22%(5/23)] and partner affected[9%(2/23)].Patients underwent an average of 2.1 retrievals. 22%(11/49) of retrievals resulted in no embryos suitable for transfer requiring an average of 1.3 additional retrievals per patient. 13%(3/23) of patients had no embryos suitable for transfer.Of the 24 embryos transferred,12/24(50%) were euploid and non-carriers,11/24(46%) were euploid and autosomal recessive carriers of one gene and 1/24(4%) was euploid female and a premutation carrier of FMR1.There were no embryos transferred that were carriers of 2 mutations. 75%(18/24) of STEET resulted in ongoing pregnancies.
Conclusion(s): From the preceding decade in our clinic, PGT-M for two or more genes increased by 43% in 2021. Over this time, there has been a shift towards more testing for AD over AR disorders due to an increase in BRCA1/2 testing. The majority of patients who attempt double or more PGT-M are able to obtain unaffected or autosomal recessive carrier euploid embryos with ongoing pregnancies despite requiring an often-increased number of cycles. We expect demand for multi-gene PGT-M to rise with increased and expanded utilization of preconception comprehensive genetic screening. Financial Support: Julia Buldo-Licciardi, M.D. - None Jacquelyn Shaw, M.D. - None Andria Besser, M.S. - None Jennifer Blakemore, M.D., M.Sc. - None REFERENCES: 1. ESHRE PGD Consortium Steering Committee. ESHRE Preimplantation Genetic Diagnosis Consortium data collection III (May 2001). Hum Reprod. 2002 Jan;17 (1) 233-46. 2. Besser AG, McCulloh D, McCaffrey C, Grifo JA. Trends in Preimplantation Genetic Testing for Monogenic Disorders (PGT-M). American Society for Reproductive Medicine Meeting 2021. Baltimore, MD. 3. Besser AG, Blakemore JK, Grifo JA, Mounts EL. Transfer of embryos with positive results following preimplantation genetic testing for monogenetic disorders (PGT-M): Experience of two high-volume fertility clinics. J Assist Reprod Genet. 2019 Sep; 36 (9) 1949-1955. 4. Baruch S, Kaufman D, Hudson KL. Preimplantation genetic screening: a survey of in vitro fertilization clinics. Fertil Steril. 2008. May; 89 (5): 1053-1058. 5. Mounts EL, Besser AG. Genetic Counseling for preimplantation genetic testing (PGT): Practical and Ethical Challenges. In Sills E, Palermo G, editors. Human Embryos and preimplantation genetic technologies. Academic Press; 2019. p 43-52.
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Objective: To systematically review and summarize the literaure on nongenetic risk factors that may contribute to the racial disparity in uterine fibroids (UF) that disproportionality impacts Black individuals at 2-3 times the rate of White individuals and how the racial disparity has been studied to date. Evidence Review: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol checklist guided the systematic review process. From January 1 to June 1, 2021, relevant articles were retrieved from PubMed, EMBASE, Web of Science, and Cochrane Library. Multiple investigators screened, assessed, extracted, and critically appraised the data. Results: A total of 44 articles examined the relationship among UFs, race/ethnicity, and nongenetic risk factors, including cardiometabolic features, comorbidities, diet, chemical exposures, vitamin D levels, reproductive characteristics and socioeconomic factors, and life experiences. Most studies reported on the same 3 cohort study populations, and there was inconsistent statistical reporting of the race/ethnicity, risk factors, and UF relationship. Conclusion: Many potential risk factors related to the racial disparity in UF have been studied thus far. There is still little conclusive evidence regarding which risk factors are the greatest contributors to racial disparities in UF. Promising areas of research deserve greater attention and a greater diversity of study populations and analytical methods.

Objective: Fragile X (FgX) is a recommended part of carrier screening with pre- and full mutations associated with a spectrum of disease including intellectual disability, tremor ataxia syndrome and premature ovarian insufficiency. Risk of expansion is categorized based on number of CGG repeats.¹ Testing for AGG interruptions can offer further risk assessment in some cases.¹ As these tests become more commonplace, our objective was to determine how often screened patients select PGT-M for FgX.
Material(s) and Method(s): This is a retrospective case series at a single academic fertility center. Electronic medical records were queried to identify patients with a positive carrier screen for FgX from 2008-2022 and those undergoing PGT-M for FgX. Assisted reproductive treatments and outcomes were reviewed. Kruskal Wallis and Chi-square statistical tests were performed (p<0.05 significant).
Result(s): 393 positive FgX reports were identified including 20 prospective oocyte donors. 63% (247/393) had an intermediate (INT) number of CGG repeats (45-54), 34% (133/393) had a premutation (PRE) (55-200 repeats) and 0.8% (3/393) had a full mutation (FUL) (>200 repeats). 61% (238/393) underwent fertility treatment at our center. PRE patients were younger (INT: 36 (17-47) vs PRE: 33 (21-44) vs FUL: 37 (37-39) years (Y), p<0.01). Anti-mullerian hormone levels were similar (INT: 1.9 (0.03-14) vs PRE: 1.5 (0.01-8.7) vs FUL: 3 (0.1-5) ng/mL, p=0.08). Only 37% (49/133) of PRE carriers underwent AGG testing to further risk stratify expansion potential, as did 2% (4/247) of INT. 25% (13/53) had 0 AGGs: 4 declined fertility treatment, 4 cryopreserved oocytes, 5 underwent PGT-M. 12% (49/393) in total underwent PGT-M: 4% INT (2/49), 73% PRE (36/49), 6% FUL (3/49). 27% (13/49) of PGT-M patients underwent AGG testing: 38% (5/13) had 0 AGG, 38% (5/13) had 1 AGG, and 23% (3/13) had 2 AGGs. 8% (4/49) additional patients were offered but declined AGG testing. 18% (9/49) of PGT-M patients had terminated an affected pregnancy prior to PGT-M. 10% (5/49) had documented family members affected or PRE carriers. Patients underwent median 2 retrieval cycles (range 0-5) and 1 embryo transfer cycle (range 0-5). 31% (14/45) of patients with completed treatment did not achieved an autologous euploid unaffected embryo for transfer; two of these patients transferred non-euploid unaffected embryos and 71% (10/14) had AMH <0.8ng/mL. 1 INT and 2 PRE female embryos were also transferred. 46% (13/28) of transfers resulted in a live birth.
Conclusion(s): PGT-M is most commonly used for PRE carriers and with a history of prior affected pregnancy or family member, with varied use of AGG testing. Patients with low ovarian reserve are less likely to achieve an autologous live birth of an unaffected embryo from PGT-M. Impact Statement: FgX premutation carriers do not have uniform uptake of AGG testing or PGT-M and require individualized counseling due to differences in risk assessment and varied assisted reproductive technology outcomes. Support: None REFERENCES:: 1. Monaghan KG, Lyon E, Spector EB; American College of Medical Genetics and Genomics. ACMG Standards and Guidelines for fragile X testing: a revision to the disease-specific supplements to the Standards and Guidelines for Clinical Genetics Laboratories of the American College of Medical Genetics and Genomics. Genet Med. 2013 Jul;15(7):575-86.
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Objective: Infertility affects >100 million people worldwide; improving FC access is essential, especially for low socioeconomic and minority groups. In NYC's public hospital system, patients (pts) are referred to a fellow-led reproductive endocrinology and infertility (REI) clinic that provides consults, work-ups and ultrasound-monitored controlled ovarian hyperstimulation and ovulation induction (OI). REI referrals (REF) are in high demand limiting appointment (appt) availability¹ with new pts waiting >5 months. We developed a QIP to identify pts for OI counseling and initiation in GYN clinic.
Material(s) and Method(s): REI fellows screened all REFs, and scheduled eligible pts in GYN. QIP criteria: age <38 years (y); anti-Mullerian hormone (AMH) >2ng/mL; normal prolactin, thyroid function and hemoglobin A1C; no known reproductive issues/comorbidities requiring high risk obstetrics; <3 prior OI cycles. Eligible pts received early follicular letrozole 2.5mg for 5 days (d) in GYN and were then followed in REI's OI program. Non-eligible pts were scheduled in REI. To assess effectiveness, we retrospectively compared all REF outcomes from PRE-(3/1/21-5/31/21) to POST-(9/1/21-11/30/21) QIP as of 2/14/22. A transition period (6/1/21-8/31/21) was excluded. Primary outcome was time from REF to scheduled appt. Secondary outcomes included time from REF to OI prescription/cycle start. Statistics included Mann-Whitney, Chi-square, Fischer's exact and Two-sample t tests (p<0.05 significant).
Result(s): PRE (n=121) and POST (n=102) REFs had similar median ages [36 (interquartile range (IQR): 32-39) PRE vs 35y (IQR: 31-40) POST, p=0.73], ethnic/racial identity [56.2% (68/121) PRE vs 53.9% (55/102) POST Hispanic (p=0.79); 34.7% (42/121) PRE vs 30.4% (31/102) POST Black (p=0.59)], and rates of no prior FC [88.4% (107/121) PRE vs 93.1% (95/102) POST, p=0.15]. QIP identified pts for GYN who were younger [median age 29 (IQR: 27-33) vs 38y (IQR: 33-41), p<0.01], had higher AMHs [median 3.065 (IQR: 2.315-4.883) vs 1.230 ng/mL (IQR: 0.513-3.630), p<0.01], and had fewer comorbidities [100% (19/19) vs 72.5% (50/69), p<0.01] compared to REI. After QIP implementation, median time from REF to scheduled appt decreased from PRE 151 (IQR: 125-173) to POST 98d (IQR: 73-137) (p<0.01). For pts seen in clinic thus far, median time from REF to OI prescription decreased from 150 (IQR: 122-173) to 82d (IQR: 63-119) (p<0.01) and to 1st follicle check from 202 (IQR: 159-221) to 107d (IQR: 98-115) (p<0.04). In the POST cohort, 86.3% (88/102) of REFs had visits scheduled, with 21.6% (19/88) in GYN and 78.4% (69/88) in REI. OI was started at initial visit for 61.5% (8/13) of GYN pts vs 25.8% (8/31) of REI pts (p<0.04). 38.5% (5/13) of GYN pts met criteria for QIP, but were pending >1 blood test, while 51.6% (16/31) of REI pts were pending further work-up.
Conclusion(s): Our QIP expedited FC for all pts by reducing the time from REF to scheduled fertility appt by 35% (median of 53d) and to OI prescription/cycle start by nearly 45% (medians of 68d/95d). Impact Statement: Similar OI pathways could improve access to FC for underserved populations in broader practice settings. REFERENCES: 1 Blakemore JK, Maxwell SM, Hodes-Wertz B, Goldman KN. Access to infertility care in a low-resource setting: bridging the gap through resident and fellow education in a New York City public hospital. J Assist Reprod Genet. 2020 Jul;37(7):1545-1552.
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Objective: E2P is a technique for IVF protocols in poor responders to reduce cycle cancelation due to elevated FSH as well as increase stimulation response. Yet data is inconsistent on the impact on clinical pregnancy rates.¹ We sought to evaluate if E2P increases euploidy rates in IVF with PGTA.
Material(s) and Method(s): This is a retrospective cohort study of IVF cycles with PGTA from 3/2020-12/2021 at a single academic fertility center. E2P cycles were compared to age and AMH matched controls (CON) (1:2 ratio). The primary outcome was number of euploid embryos. Secondary outcomes were cycle start follicle stimulation hormone level (FSH), total gonadotrophin (GND) dose, number oocytes, mature oocytes (MII), fertilization rate (2PN), and number of embryos biopsied (BX). Mann Whitney and Chi-square tests were performed (p<0.05 significant). Data is reported in median (range) and percentages.
Result(s): 337 E2P cycles were compared to 674 CON. There were fewer microdose lupron (MCD) cycles in E2P patients (E2P: 88% antagonist (ANT), 12% MCD vs CON: 76% ANT, 24% MCD, p<0.01). Similar cancelation rates [E2P: 14% (47/337) vs CON: 12% (82/674), p=0.42] and poor blast formation (defined as nothing for biopsy) [E2P: 18% (60/337) vs CON: 15% (103/674), p=0.24] were seen between groups. Number of euploid embryos were similar across all SART age groups except for 38-40 years (y), with fewer euploids in E2P (Table). Cycle start FSH was lower and total GND dose was higher for E2P (p<0.05). Other cycle outcomes were not different.
Conclusion(s): E2P is a viable tool for PGTA freeze all cycles, but does not improve euploidy rate; larger studies are necessary to determine if E2P produces fewer euploids in >38y. Impact Statement: E2P cycles require higher GND dose without increased yield in euploid embryos. [Formula presented] Support: None REFERENCES: 1. Orvieto R. Pretreatment: Does it improve quantity or quality? Fertil Steril. 2022 Apr;117(4):657-663. Epub 2022 Mar 5. PMID:.
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Background/UNASSIGNED:The opportunity for fertility preservation in adolescent and young adult (AYA) transmen is growing. Many AYA transmen desire future biologic children and are interested in ways to preserve fertility through oocyte cryopreservation prior to full gender affirmation, yet utilization of oocyte cryopreservation remains low. Additionally, standard practice guidelines currently do not exist for the provision of oocyte cryopreservation to AYA transmen. Our objective was to review our experience with oocyte cryopreservation in adolescent and young adult transmen in order to synthesize lessons regarding referral patterns, utilization, and oocyte cryopreservation outcomes as well as best practices to establish treatment guidance. Methods/UNASSIGNED:This is a case series of all AYA transmen (aged 10 to 25 years) who contacted, consulted or underwent oocyte cryopreservation at a single high volume New York City based academic fertility center between 2009 and 2021. Results/UNASSIGNED:Forty-four adolescent and young adult transmen made contact to the fertility center over the study period. Eighty percent (35/44) had a consultation with a Reproductive and Endocrinology specialist, with a median age of 16 years (range 10 to 24 years) at consultation. The majority were testosterone-naive (71%, 25/35), and had not pursued gender affirming surgery (86%, 30/35). Expedited initiation of testosterone remained the most commonly cited goal (86%, 30/35). Fifty-seven percent (20/35) pursued oocyte cryopreservation. Ninety-five percent (19/20) underwent successful transvaginal oocyte aspiration, with a median of 22 oocytes retrieved and 15 mature oocytes cryopreserved. There were no significant adverse events. At time of review, no patient has returned to utilize their cryopreserved oocytes. Conclusions/UNASSIGNED:Oocyte cryopreservation is a safe fertility preservation option in AYA transmen and is an important aspect of providing comprehensive transgender care. Insights from referral patterns, utilization, and oocyte cryopreservation outcomes from a single center's experience with adolescent and young adult transmen can be integrated to identify lessons learned with the goal of providing transparency surrounding the oocyte cryopreservation process, improving the education and comfort of patients and providers with fertility preservation, and easing the decision to pursue an oocyte cryopreservation cycle in parallel to gender-affirmatory care.

OBJECTIVE:To evaluate the prevalence of coronavirus disease 2019 (COVID-19) and efficacy of a universal screening program in patients undergoing controlled ovarian stimulation (COS). DESIGN:Single-center retrospective cohort study. SETTING:Academic fertility center in an epicenter of the COVID-19 pandemic. PATIENT(S):All patients undergoing COS from June 17, 2019, to February 28, 2021. INTERVENTION(S):Universal COVID-19 screening starting June 17, 2020, with SARS-CoV-2 polymerase chain reaction testing within 5 days of oocyte retrieval, patient-reported symptom screening, and temperature monitoring. MAIN OUTCOMES MEASURE(S):The primary outcome was the number of positive COVID-19 cases in patients undergoing COS cycles. The secondary outcomes were cycle outcomes compared with before COVID-19 COS cycles, adverse outcomes in COVID-canceled cycles, and center-specific COVID-19 detection rates compared with New York City cases. RESULT(S):From June 17, 2020, to February 28, 2021, 1,696 COS cycles were initiated with only seven positive COVID-19 cases for an overall positivity rate of 0.4%. When compared with before COVID cycles from June 17, 2019, to February 28, 2020, the volume of COS cycles were higher, while the overall cycle cancelation rate was lower during COVID-19. Cycle outcomes including oocyte yield and blast utilization rates were unchanged from pre-COVID cycles. Cases of COVID-19, while very low, occurred more frequently during surges in New York City rates. CONCLUSION(S):Assisted reproductive technology can be performed during the COVID-19 pandemic utilizing frequent universal screening and safe practices with low SARS-CoV-2 positivity, low cycle cancelation rates, and positive patient outcomes.