Faculty Bibliography

PURPOSE/OBJECTIVE:To explore whether letrozole improved outcomes in subsequent controlled ovarian hyperstimulation (COH) cycles. METHODS:This was a retrospective repeated measures cohort study examining COH cycles. Patients were included if they underwent two cycles for unexplained infertility, male factor infertility, or planned oocyte/embryo cryopreservation. The first cycles for all patients implemented a non-letrozole, conventional gonadotropin protocol. Second cycles for the study group included letrozole (2.5-7.5 mg for 5 days) with no medication change to second cycles amongst controls. Our primary objective was to compare oocyte yield. Cohorts were then subdivided by pursuit of oocyte (OC) or embryo (IVF) cryopreservation. Secondary outcome amongst the OC subgroup was oocyte maturation index (metaphase II (MII)/total oocytes). Secondary outcomes amongst the IVF subgroup were normal fertilization rate (2-pronuclear zygotes (2PN)/oocytes exposed to sperm), blastocyst formation rate (blastocysts/2PNs), and embryo ploidy (%euploid and aneuploid). RESULTS:Fifty-four cycles (n = 27) were included in letrozole and 108 cycles (n = 54) were included in control. Oocyte yield was higher in second cycles (p < 0.008) in the letrozole group but similar in second cycles (p = 0.26) amongst controls. Addition of letrozole did not impact MII index (p = 0.90); however, MII index improved in second cycles amongst controls (p < 0.001). Both groups had similar rates of normal fertilization (letrozole: p = 0.52; control: p = 0.61), blast formation (letrozole: p = 0.61; control: p = 0.84), euploid (letrozole: p = 0.29; control: p = 0.47), and aneuploid embryos (letrozole: p = 0.17; control: p = 0.78) between cycles. CONCLUSIONS:Despite improved oocyte yield, letrozole did not yield any difference in oocyte maturation or embryo outcomes.

STUDY QUESTION/OBJECTIVE:What structural (logistical) and psychological challenges do patients who cryopreserve oocytes or embryos for medical reasons face, including possible barriers to using their frozen materials? SUMMARY ANSWER/CONCLUSIONS:The majority of women who underwent oocyte or embryo cryopreservation for medical reasons reported a desire to use their frozen oocytes or embryos but had been impeded by ongoing medical issues, the need for a gestational carrier, or the lack of a partner. WHAT IS KNOWN ALREADY/BACKGROUND:Current data suggest that many women who have frozen oocytes or embryos for medical indications are concerned about the prospect of infertility and have unique emotional and financial needs that differ from patients with infertility. Further, most patients have not returned to use their cryopreserved materials. STUDY DESIGN, SIZE, DURATION/METHODS:This is a qualitative interview study of 42 people who cryopreserved between January 2012 and December 2021. Interviews were conducted between March 2021 and March 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS/METHODS:All participants were cisgender women who had undergone oocyte or embryo cryopreservation for medical indications at an academic fertility center. Participants were invited to interview by email if they were younger than 40 years old when their oocytes or embryos were cryopreserved. Interviews were conducted over the internet and transcribed verbatim. Data were analyzed using thematic analysis with the constant comparison method. MAIN RESULTS AND THE ROLE OF CHANCE/RESULTS:Saturation was reached at 42 interviews. The median age of participants was 35 years old (range 28-43) at interview and 31 years old (range 25-39) at cryopreservation. Of the 42 women, 30 had a cancer diagnosis, while 7 had non-cancer chronic medical conditions, and 5 had hereditary cancer susceptibility syndromes. There were 12 women who banked embryos and 30 who banked oocytes. The majority of women indicated a desire to use their cryopreserved materials, but many were unsure about how or when. Four had already used their frozen oocytes or embryos, while another four had conceived without assisted reproduction. The cryopreservation experience was described by the majority as highly emotionally challenging because they felt out of place among couples receiving infertility treatment and, for cancer patients, overwhelmed by the complex decisions to be made in a short time period. Common reported barriers to using frozen materials included ongoing medical issues preventing pregnancy, the need for a gestational carrier, the lack of a partner, and the desire for unassisted conception. Some were glad to have frozen oocytes or embryos to allow more time to meet a partner or if they were considering becoming single parents. LIMITATIONS, REASONS FOR CAUTION/CONCLUSIONS:The majority of participants had their oocytes or embryos frozen at a single, urban, academic fertility center, which may limit generalizability. We also could not calculate a response rate because the snowball technique was used to identify additional participants, so did not know the total number of people invited to participate. Like other interview studies, our study may be subject to response bias because those who agreed to participate may have particularly positive or negative views about their experiences. Furthermore, the mean follow-up time since freezing was relatively short (3.3 years, median 2.7 years), which may not have been enough time for some patients to use their frozen materials. WIDER IMPLICATIONS OF THE FINDINGS/CONCLUSIONS:Learning about the experiences of patients undergoing medically indicated oocyte and embryo cryopreservation can help clinicians better counsel these patients regarding decisions and hurdles they may encounter. We found that most patients had not returned to use their frozen materials because of ongoing medical issues, the need for a gestational carrier, lack of a partner, or the desire to attempt unassisted reproduction. STUDY FUNDING/COMPETING INTEREST(S)/BACKGROUND:This study did not receive any funding. The authors of this study have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER/BACKGROUND:N/A.

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: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.

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.

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.