Faculty Bibliography

Many transgender and gender diverse (TGD) individuals will be considering gender-affirming treatments during their reproductive lifespan. These medically necessary treatments have a negative impact on reproductive potential. All TGD individuals should be counseled regarding fertility. Options for fertility preservation for individuals who have undergone puberty include mature oocyte, embryo, and sperm cryopreservation. In prepubertal individuals, ovarian tissue cryopreservation may be considered, but testicular tissue cryopreservation remains experimental only. While there have been advances in the technology and standardization of reproductive health care for this population, many gaps remain in our knowledge which require further research.

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.

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.

Objective: Several patient populations prefer to avoid TV monitoring for comfort or to prevent dysphoria. The purpose of this study is to compare TA and TV ultrasound as a means of determining cycle trigger timing and predicting oocyte maturity based on scans performed during ART cycles in this patient population.
Material(s) and Method(s): This was a retrospective cohort study of 59 patients who underwent >= 1 ART cycle at a single academic center. The study group consisted of patients who preferred TA monitoring based on any of 3 following inclusion criteria: 1) if they were virginal, 2) identified as transgender or 3) had a diagnosis of vaginismus. The control group included patients within this cohort that had no preference for TA imaging and thus underwent exclusive TV imaging. Demographics and variables included age, body mass index (BMI), antral follicle count (AFC) and anti-mullerian hormone (AMH), day 2 estradiol (D2 E2) and follicle-stimulating hormone (FSH) levels, # scans per cycle, # stimulation days per cycle, estimated # follicles and follicle sizes at trigger, # eggs retrieved, and oocyte maturity rate. Primary outcomes were 1) % difference between estimated # follicles at trigger and # oocytes retrieved, 2) # oocytes retrieved, and 3) % maturity. Secondary outcomes included % difference between AFC and # oocytes retrieved. Kolmogorov-Smirnov test was used to determine normality with independent sample t-tests and Mann Whitney U-Tests were used where appropriate with p<0.05 considered significant.
Result(s): 59 patients (n=18 TA; n= 41 TV) were included in the analysis. 27.1% (n=9 TA; 7 TV) were virginal, 50.8% (6 TA; 24 TV) had vaginismus and 37.3% (10 TA; 12 TV) identified as transgender. Some patients met 2 criteria (virginal + vaginismus, transgender + virginal, or transgender + vaginismus). Patients in the TA group were significantly younger than those in the TV group (26.2 TA v 37.8 years TV, p<0.001). Median BMI (22.4 TA v 23.7 kg/m² TV, p=0.26) and AMH (2.9 TA v 2.7 ng/mL TV, p=0.99) were similar. There was no statistical significance in mean AFC (12.8 +/- 9.2 TA, 13.6 +/- 8.2 TV, p=0.18). Patients in both groups had similar median D2 E2 (32.0 TA v 41.1 TV pg/mL, p=0.23) and FSH (5.6 TA v 7.2 mIU/mL TV, p=0.23), # scans per cycle (5 TA v 5 TV, p=0.88), and # stimulation days (11 TA v 11 TV, p=0.74). The TA group had higher mean E2 at trigger (3488.5 +/- 1087.0 TA, 2566.1 +/- 1416.1 pg/mL TV, p<0.002). There was no significant difference between estimated # follicles at trigger and # oocytes retrieved (17.7 +/- 31.4% TA, 6.7 +/- 38.0% TV; p= 0.29). Mean # oocytes (21.3 +/- 10.8 TA, 15.9 +/- 8.8 TV, p= 0.05) and median % mature oocytes (0.89 TA, 0.83 TV; p= 0.12) were also similar. Median % difference between AFC and # oocytes retrieved was not significantly different (0.68 TA, 0.82 TV; p= 0.18).
Conclusion(s): TA and TV imaging do not differ in their ability to predict FP cycle characteristics, oocytes retrieved or oocyte maturity rate. TA imaging may offer an acceptable alternative for patients uncomfortable with TV imaging during FP. Impact Statement: TA monitoring for oocyte cryopreservation does not adversely affect oocyte yield in patients with preference against TV imaging.
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Objective: To evaluate differences in oocyte cryopreservation (OC) in BRCA 1/2 patients with and without cancer diagnoses compared to controls who underwent elective cryopreservation.
Material(s) and Method(s): This was a single-center retrospective cohort study of BRCA mutation carriers who presented for fertility preservation. A data query was performed to identify all patients who were referred to our academic center from 2006-2022 to discuss fertility preservation in the setting of known BRCA 1/2-carrier status with or without cancer diagnosis. BRCA 1/2 carriers without cancer (Group A), with cancer (Group B) and controls (Group C) were included in the study. Patient demographic information, gynecologic history, antral follicle count (AFC) and cycle characteristics were reviewed. The control group consisted of 308 patients who underwent elective OC in 2021, with a 1:10 ratio of study to control group. Primary outcomes included 1) median number of oocytes retrieved, 2) oocyte maturity rate and 3) rate of M1 or GV oocytes amongst BRCA 1/2 carriers who underwent oocyte cryopreservation compared to the control group. Secondary outcomes included 1) mean anti-mullerian hormone levels (AMH), 2) median number of stimulation days and 3) cumulative dose of exogenous FSH and hMG administered during stimulation. Data was analyzed using Kruskal-Wallis analysis and Mann Whitney U-tests. A P-value of < 0.05 was considered statistically significant.
Result(s): Of 242 BRCA 1/2 carriers who were referred to our center for fertility consultation, 103 underwent ART cycles, of which 38 completed at least 1 OC cycle (21 BRCA1, 17 BRCA2), with a total of 49 OC cycles within the study group. 7 BRCA 1/2 carriers had breast cancer at time of OC (2 BRCA1, 5 BRCA2). There was no significant difference between median numbers of oocytes retrieved amongst groups (A: 18, B: 20, C: 16, p = 0.93). Oocyte maturity also did not vary significantly between groups (A: 74.4 +/- 13.5%, B: 57.3 +/- 24.8%, C: 73.4 +/- 18.1%; p=0.3). BRCA 1/2 carriers without cancer had a higher rate of M1 oocytes compared to cancer and control groups (A: 8.9 +/- 10.4%, B: 4.5 +/- 4.8%, C: 4.7 +/- 8.9%; p=0.02). Furthermore, BRCA1/2 carriers with and without cancer had a significantly higher percent of GV oocytes (A: 8.6 +/- 11.6%, B: 10.8 +/- 11.4%, C: 0.02 +/- 0.48%; p=0.001) compared to controls. Mean AMH was significantly lower in BRCA 1/2 patients with cancer compared to those without and controls (A: 3.8 +/- 2.4, B: 1.5 +/- 1.9, C: 3.2 +/- 2.6 ng/mL; p=0.04). There was no significant difference in median number of stimulation days and cumulative dose of exogenous FSH or hMG between groups.
Conclusion(s): BRCA1/2 carrier status does not compromise stimulation cycle characteristics or oocyte maturity rates. Although BRCA1/2 carriers with and without cancer at time of cycle had higher rates of M1 and GV oocytes per OC cycle, they had similar maturity rates overall compared to controls. Impact Statement: BRCA1/2 carriers should be encouraged to pursue fertility preservation if they are interested. BRCA status and/or active breast cancer diagnosis do not negatively impact cycle characteristics or oocyte maturity potential.
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OBJECTIVE:To review the outcomes of patients who underwent autologous oocyte thaw after planned oocyte cryopreservation. DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Large urban university-affiliated fertility center. PATIENT(S)/METHODS:All patients who underwent ≥1 autologous oocyte thaw before December 31, 2020. INTERVENTION(S)/METHODS:None. MAIN OUTCOME MEASURE(S)/METHODS:The primary outcome was the final live birth rate (FLBR) per patient, and only patients who had a live birth (LB) or consumed all remaining inventory (cryopreserved oocytes and resultant euploid/untested/no result embryos) were included. The secondary outcomes were laboratory outcomes and LB rates per transfer. RESULT(S)/RESULTS:A total of 543 patients underwent 800 oocyte cryopreservations, 605 thaws, and 436 transfers. The median age at the first cryopreservation was 38.3 years. The median time between the first cryopreservation and thaw was 4.2 years. The median numbers of oocytes and metaphase II oocytes (M2s) thawed per patient were 14 and 12, respectively. Overall survival of all thawed oocytes was 79%. Of all patients, 61% underwent ≥1 transfer. Among euploid (n = 262) and nonbiopsied (n = 158) transfers, the LB rates per transfer were 55% and 31%, respectively. The FLBR per patient was 39%. Age at cryopreservation and the number of M2s thawed were predictive of LB; the FLBR per patient was >50% for patients aged <38 years at cryopreservation or who thawed ≥20 M2s. A total of 173 patients (32%) have remaining inventory. CONCLUSION(S)/CONCLUSIONS:Autologous oocyte thaw resulted in a 39% FLBR per patient, which is comparable with age-matched in vitro fertilization outcomes. Studies with larger cohorts are necessary.

PURPOSE/OBJECTIVE:Characterize outcomes among adolescents and young adults (AYAs) with sex chromosome disorders (SCDs) after oocyte cryopreservation (OC) consultation. METHODS:Retrospective case series of all AYA (< 25 years) patients with SCDs seen for OC consultation from 2011 to 2019 at a large, urban, academic fertility center. All AYA patients with an SCD seen for OC consult in the study time period were reviewed and included. Data collected included patient age, SCD type, number of patients who attempted OC, number of cycles attempted, and cycle outcomes. RESULTS:Twenty-two patients were included: 9 with Turner syndrome, 12 with mosaic Turner syndrome, and 1 with 47,XXX. Mean age at consult was 14.7 ± 3.5 years. Fourteen patients elected for OC: 5 with Turner syndrome, 8 with mosaic Turner syndrome, and 1 47,XXX who pursued 31 OC cycles total. Of those 14 patients, 10 underwent retrieval, 9 froze oocytes, and 8 froze mature (MII) oocytes. Seven patients underwent > 1 cycle and 7 had ≥ 1 cancelation. 3/3 patients who pursued cycles after 1st cancelation never got to retrieval. Age, SCD type, and baseline FSH did not predict ability to freeze MIIs. One patient returned after OC and attempted 4 ovulation induction cycles and 2 IVF cycles; all were canceled for low response. CONCLUSIONS:AYA patients with SCDs have a high risk of poor response and cycle cancelation but the majority froze MIIs. Thus, setting expectations is important. A larger sample size is needed to evaluate possible clinical predictors of success.

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.