Faculty Bibliography

PURPOSE/OBJECTIVE:To evaluate live birth rates (LBRs) for in vitro fertilization (IVF) cycles with ≤5 follicles at trigger, with the goal of helping patients with low follicle counts decide whether to proceed to retrieval. METHODS:This is a retrospective cohort study from an urban, university-affiliated fertility center. All IVF cycles that yielded <10 oocytes between 2016 and 2020 were reviewed. Cycles were included if <5 follicles measuring >14 mm were verified on trigger day. The primary outcome was LBR per retrieval after fresh or frozen transfer. Secondary outcomes were number of oocytes, mature oocytes, 2-pronuclear zygotes (2-PNs), blastocysts for transfer/biopsy, and euploid blastocysts (if preimplantation genetic testing for aneuploidy (PGT-A) was used). RESULTS:1502 cycles (900 with PGT-A) from 972 patients were included. Mean number of oocytes, mature oocytes, 2-PNs, blastocysts for transfer/biopsy, and euploid blastocysts differed by follicle number (p < 0.001). Across all age groups, there were differences in LBR associated with follicle number (p < 0.001). However, within age groups, not all results were significant. For example, for patients <35 years, LBR did not differ by follicle number and among patients 35-37 years; LBR with two or three follicles was lower than with five (p < 0.02). LBR for patients 35-40 years was <20% with 1-3 follicles and 25-40% with 4-5 follicles. LBR for patients >41 years was <5% with 1-3 follicles and <15% with 4-5 follicles. CONCLUSION/CONCLUSIONS:As expected, LBR is higher with more follicles. Providing patients with <5 follicles with specific data can help them weigh the emotional, physical, and financial costs of retrieval.

PURPOSE/OBJECTIVE:To evaluate pre-implantation genetic testing for aneuploidy (PGT-A) outcomes in patients without infertility compared to infertile patients. METHODS:We performed a retrospective cohort study of all patients without an infertility diagnosis ("fertile" patients) who utilized PGT-A at a large university-affiliated fertility center between 2016 and 2021. Fertile patients were 1-to-3 matched to infertile controls by age and number of oocytes retrieved. The primary outcome was blastocyst aneuploidy rate. Secondary outcomes included ovarian reserve markers, laboratory outcomes, and other PGT-A outcomes [rates of euploidy, mosaicism, and potentially transferrable (euploid + mosaic) embryos]. RESULTS:283 fertile and 849 infertile patients were included. Median age, anti-Mullerian hormone, and day 2 estradiol levels were equivalent among groups; day 2 follicle-stimulating hormone levels were higher in fertile patients (6.9 vs. 6.5 IU/mL, p < 0.01). The aneuploidy rate was similar among fertile and infertile patients (33.7% vs. 31.8%, p = 0.11); the euploidy rate was higher (50.8% vs. 47.0%, p < 0.01), and the mosaicism rate was lower in fertile patients (13.3% vs. 19.2%, p < 0.01). The rate of transferrable embryos was similar among groups (64.0% vs. 66.3%, p = 0.07), as was the percentage of patients yielding ≥ 1 euploid embryo (90.1% vs. 87.3%, p = 0.25). When controlling for significant covariates, multiple linear regression showed that aneuploidy rate was equivalent in both cohorts. CONCLUSION/CONCLUSIONS:Aneuploidy rate was similar in fertile and infertile patients. Fertile patients had slightly higher euploidy and lower mosaicism than infertile patients. Still, compared to fertile patients, infertile patients had equivalent rates of transferrable embryos and were just as likely to yield ≥ 1 euploid embryo.

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.

The goal of fertility-sparing treatment (FST) for patients desiring future fertility with EMCA, and its precursor EH, is to clear the affected tissue and revert to normal endometrial function. Approximately 15% of patients treated with FST will have a live birth without the need for assisted reproductive technology (ART). Despite this low number, little information exists on the pregnancy outcomes of patients who utilize ART. The purpose of this study was to evaluate pregnancy outcomes following embryo transfer in patients with EMCA or EH who elected for FST. This retrospective cohort study at a large urban university-affiliated fertility center included all patients who underwent embryo transfer after fertility-sparing treatment for EMCA or EH between January 2003 and December 2018. Primary outcomes included embryo transfer results and a live birth rate (defined as the number of live births per number of transfers). There were 14 patients, three with EMCA and 11 with EH, who met the criteria for inclusion with a combined total of 40 embryo transfers. An analysis of observed outcomes by sub-group, compared to the expected outcomes at our center (patients without EMCA/EH matched for age, embryo transfer type and number, and utilization of PGT-A) showed that patients with EMCA/EH after FST had a significantly lower live birth rate than expected (Z = −5.04, df = 39, p < 0.01). A sub-group analysis of the 14 euploid embryo transfers resulted in a live birth rate of 21.4% compared to an expected rate of 62.8% (Z = −3.32, df = 13, p < 0.001). Among patients with EMCA/EH who required assisted reproductive technology, live birth rates were lower than expected following embryo transfer when compared to patients without EMCA/EH at our center. Further evaluation of the impact of the diagnosis, treatment, and repeated cavity instrumentation for FST is necessary to create an individualized and optimized approach for this unique patient population.

The objective of this study was to investigate the utility of using serum gonadotropin levels to predict optimal luteinizing hormone (LH) response to gonadotropin releasing hormone agonist (GnRHa) trigger. A retrospective cohort study was performed of all GnRH-antagonist controlled ovarian hyperstimulation (COH) cycles at an academic fertility center from 2017-2020. Cycles that utilized GnRHa alone or in combination with human chorionic gonadotropin (hCG) for trigger were included. Patient and cycle characteristics were collected from the electronic medical record. Optimal LH response was defined as a serum LH ≥ 40 mIU/mL on the morning after trigger. Total sample size was 3865 antagonist COH cycles, of which 91% had an optimal response to GnRHa trigger. Baseline FSH (B-FSH) and earliest in-cycle LH (EIC-LH) were significantly higher in those with optimal response. Multivariable logistic regression affirmed association of optimal response with EIC-LH, total gonadotropin dosage, age, BMI and Asian race. There was no difference in the number of oocytes retrieved (p = 0.14), maturity rate (p = 0.40) or fertilization rates (p = 0.49) based on LH response. There was no difference in LH response based on use of combination vs. GnRHa alone trigger (p = 0.21) or GnRHa trigger dose (p = 0.46). The EIC-LH was more predictive of LH trigger response than B-FSH (p < 0.005).The optimal B-FSH and EIC-LH values to yield an optimal LH response was ≥ 5.5 mIU/mL and ≥ 1.62 mIU/mL, respectively. In an era of personalized medicine, utilizing cycle and patient characteristics, such as early gonadotropin levels, may improve cycle outcomes and provide further individualized care.

PURPOSE/UNASSIGNED:Our objective was to analyse information and sentiments posted regarding the COVID-19 vaccine on fertility-related social media. MATERIALS AND METHODS/UNASSIGNED:The first fifty accounts on Instagram and Twitter were identified with the terms: fertility doctor, fertility, OBGYN, infertility, TTC, IVF. Accounts were categorised as physician (PH), individual (ID), or fertility center/organisation (FCO). The vaccine was approved on 12/11/2020 and Instagram and Twitter posts dated 12/1/2020 - 2/28/2021 were reviewed. Posts were analysed for sentiment, mention of research studies (RS), national guidelines (NG), personal experience (PE), side effects (SE), reproductive related (RR) content and activity, including likes and comments. RESULTS/UNASSIGNED:A total of 276 accounts were included. Sentiments towards the vaccine were largely positive (PH 90.3%, ID 71.4%, FCO 70%), or neutral (PH 9.7%, ID 28.6%, FCO 30%). Instagram accounts showed an increase in activity on vaccine posts compared to baseline by likes (PH 4.86% v 3.76%*, ID 7.5% v 6.37%*, FCO 2.49% v 0.52%*) and comments (PH 0.35% v 0.28%, ID 0.90% v 0.69%,* FCO 0.10% v 0.02%*). CONCLUSION/UNASSIGNED:Most posts expressed positive sentiments towards the vaccine. Evaluating the sentiment of the COVID-19 vaccine as it relates to fertility on social media represents an opportunity for understanding both the patient's and health care professional's opinion on the subject. Given the potential devastating effects of misinformation on public health parameters, like vaccination, social media offers one avenue for healthcare professionals to engage online and work to make their presences more effective and influential.SHORT CONDENSATIONThis article analyses content and sentiments posted regarding the COVID-19 vaccine on fertility-related social media in order to offer a deeper understanding of available information and beliefs.

KEY WORDS/BACKGROUND:postpartum hemorrhage, thromboelastography, coagulopathy, fibrinogen, massive transfusion. OBJECTIVE:Thromboelastography, a point-of-care test that measures blood's dynamic viscoelastic properties, is routinely used to guide resuscitation in surgical specialties with high hemorrhage risk. Patients with ongoing postpartum hemorrhage often develop coagulopathy and hypofibrinogenemia. Timely assessment of fibrinogen is crucial because cryoprecipitate for repletion requires thawing prior to administration. Thromboelastography may provide rapid assessment of coagulopathy in ongoing hemorrhage but this has not been thoroughly studied. Our objective was to determine if thromboelastography accurately reflects coagulopathy in ongoing postpartum hemorrhage when compared to standard assays. STUDY DESIGN/METHODS:This was a retrospective cohort study of people with ongoing postpartum hemorrhage (quantified blood loss >1000 mL), from 1/1/16-12/31/19. Thromboelastography variables and standard coagulation parameters were compared in patients who had both assays drawn simultaneously. As a secondary analysis, patients who had thromboelastography were compared to those who did not. Mann-Whitney, Fisher's Exact, Kruskal-Wallis, Spearman's Rho, and logistic regression tests were used for analysis. Significance was set at p < 0.05. RESULTS:A total of 680 patients were included. 69 had thromboelastography and coagulation parameters drawn simultaneously and were included in the primary analysis. The remainder were included in the secondary analysis. Thromboelastography variables and coagulation assays correlated significantly - prolonged R with increased PTT (rho 0.25, p=0.04), prolonged K and decreased alpha angle with decreased fibrinogen (rho -0.61, p<0.001; rho 0.24, p<0.001), and decreased maximum amplitude with decreased platelets (rho 0.62, p<0.001). Those who had thromboelastographic assays had higher blood loss and need for interventions to manage hemorrhage than those who did not. CONCLUSION/CONCLUSIONS:Thromboelastography correlated significantly with standard laboratory assays in ongoing postpartum hemorrhage, including for patients with hypofibrinogenemia Given the point-of-care nature and rapid turnaround time, thromboelastography should be considered for timely hemorrhage evaluation and directed resuscitation of coagulopathy.

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.
Copyright