Faculty Bibliography

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:To assess assisted reproductive technology (ART) outcomes in patients with one ovary compared to two ovaries. METHODS:We performed a retrospective cohort study of all patients with one ovary who underwent ≥ 1 ART cycle between 2012 and 2020 at a large university-affiliated fertility center. Patients were 3-to-1 matched with two ovary controls during the same period. Primary outcome was metaphase II oocytes (MIIs) retrieved per cycle. Secondary outcomes included ovarian reserve markers, laboratory outcomes, and live birth rates (LBRs). RESULTS:A total of 104 one ovary patients (158 cycles; median age 35.5 years) were matched to 312 two ovary patients (474 cycles; median age 35.0 years). In one ovary patients, anti-Mullerian hormone was lower (median 1.1 vs. 2.2, p < 0.01) and day 2 follicle-stimulating hormone was higher (median 7.4 vs. 6.2, p < 0.01). One ovary patients yielded median 7.5 MIIs and 10 oocytes per cycle, fewer than two ovary patients (11.0 and 14.5, respectively; p < 0.01). However, one ovary patients had ≥ 50% the MII and oocyte yield of two ovary patients (Z > 5.8, p < 0.01). Fertilization and blastocyst formation rates, euploidy rate, and rate of ≥ 1 embryo for transfer were equivalent between groups (p > 0.40). Among the one and two ovary groups, LBRs per transfer (45.8% vs. 46.6%, p = 1.00) and per patient who underwent transfer (68.3% vs. 73.9%, p = 0.55) were equivalent. CONCLUSION/CONCLUSIONS:One ovary patients yielded fewer MIIs and oocytes than two ovary patients, but had ≥ 50% the yield of two ovary patients, suggesting a compensatory mechanism in oocyte yield in the solitary ovary. One and two ovary patients had equivalent LBRs.

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.

The objective of this review is to provide an update on planned oocyte cryopreservation. This fertility preservation method increases reproductive autonomy by allowing women to postpone childbearing whilst maintaining the option of having a biological child. Oocyte cryopreservation is no longer considered experimental, and its use has increased dramatically in recent years as more women delay childbearing for personal, professional and financial reasons. Despite increased usage, most patients who have undergone oocyte cryopreservation have not yet warmed their oocytes. Most women who cryopreserve oocytes wait years to use them, and many never use them. Studies have demonstrated that oocyte cryopreservation results in live birth rates comparable with IVF treatment using fresh oocytes, and does not pose additional safety risks to offspring. Based on current evidence, cryopreserving ≥20 mature oocytes at <38 years of age provides a 70% chance of one live birth. However, larger studies from a variety of geographic locations and centre types are needed to confirm these findings. Additional research is also needed to determine the recommended age for oocyte cryopreservation, recommended number of oocytes to cryopreserve, return and discard/non-use rates, cost-effectiveness, and how best to distribute accurate and up-to-date information to potential patients.

OBJECTIVE:To determine how often a noneuploid result from a single trophectoderm (TE) biopsy tested with the next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) is concordant with rebiopsies tested with a single-nucleotide polymorphism (SNP) array-based PGT-A platform. DESIGN/METHODS:Blinded prospective cohort study. SETTING/METHODS:University-affiliated fertility center. PATIENT(S)/METHODS:One hundred blastocysts were chosen from donated samples; on TE biopsy with NGS-based PGT-A, 40 had at least one whole chromosome full copy number aneuploidy alone, 20 had a single whole chromosome intermediate copy number ("whole chromosome mosaic"), 20 had a single full segmental aneuploidy (segA), and 20 had a single segmental intermediate copy number ("segmental mosaic"). INTERVENTIONS/METHODS:Four rebiopsies were collected from each embryo: 3 TE biopsies and the remaining embryo. Each rebiopsy was randomized, blinded, and assessed with an SNP array-based PGT-A platform that combines copy number and allele ratio analyses, without mosaicism reporting. MAIN OUTCOME MEASURE(S)/METHODS:Concordance between the NGS result and rebiopsy results and within each embryo's blinded rebiopsy results. RESULT(S)/RESULTS:Next-generation sequencing-diagnosed whole chromosome aneuploidy (WCA) was reconfirmed in 95% (95% confidence interval [CI], 83%-99%) of embryos; 2 embryos with NGS-diagnosed WCA were called euploid on all conclusive rebiopsies. Among embryos with NGS-diagnosed whole chromosome mosaicism, 35% (95% CI, 15%-59%) were called euploid and 15% (95% CI, 3%-38%) were called whole chromosome aneuploid on all conclusive rebiopsies. A total of 30% (95% CI, 12%-54%) of embryos with NGS-diagnosed segA and 65% (95% CI, 41%-85%) of embryos with NGS-diagnosed segmental mosaicism were called euploid on all conclusive rebiopsies. In total, 13% (95% CI, 6%-25%) of embryos with NGS-diagnosed full copy number aneuploidy and 50% (95% CI, 34%-66%) of embryos with NGS-diagnosed mosaicism had uniformly euploid SNP results. Conversely, all embryos with at least one noneuploid SNP result (n = 72) either had SNP-diagnosed aneuploidy on another rebiopsy from the same embryo or NGS-diagnosed aneuploidy/mosaicism involving the same chromosome. CONCLUSION(S)/CONCLUSIONS:Next-generation sequencing-diagnosed WCA is highly concordant with rebiopsies tested with an SNP array-based PGT-A; however, whole chromosome mosaicism, segA, and segmental mosaicism are less concordant, reinforcing that embryos with these results may have reproductive potential and be suitable for transfer.

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.

Objective: Data regarding the chance of more than one LB from oocyte cryopreservation (OC) is lacking. We reviewed outcomes from patients (pts) with >=1 LB from thawed autologous oocytes (AOs) to examine: 1) how many have inventory (AOs or resultant euploid/untested/no result embryos), and 2) embryo transfer (ET) outcomes after 1^st LB.
Material(s) and Method(s): We reviewed all pts who thawed AOs at our center in 2006-2021 and had >=1 resultant LB. Pts were excluded if OC was performed for a medical reason, as research, due to lack of sperm or a natural disaster, with embryo banking or for gestational carrier use.
Result(s): 191 pts had >=1 LB (median # OC cycles 1, median age at 1^st OC 37 years (y), median # cryopreserved AOs 18, median # AOs thawed before 1^st LB 15). After LB, 61% of pts (n=117) had inventory and 39% (n=74) did not; see table. Among pts with inventory, 12% (n=14) discarded or donated, 3% (n=4) transported out and 10% (n=12) consumed all inventory as of 1/2022. 22% of pts with inventory (n=26) had >=1 ET after LB. Among these pts, 21 thawed embryos (median # thawed 1, range 1-2), 4 thawed AOs (median # thawed 11, range 5-40) and 1 thawed both AOs + embryos (15 AOs + 4 embryos). Median time from the ET that led to 1^st LB and next ET was 26 months (range 15-57) and median age at next ET was 44y (range 37-53). This ET resulted in: implantation rate of 63% (19/30), spontaneous abortion rate of 16% (3/19) and ongoing pregnancy (OP) + LB rate of 58% (15/26); 1 pregnancy was terminated for monozygotic twins. Among pts who had a LB from this ET, 66% (10/15) had remaining inventory and 33% (5/15) did not. Among pts who did not have a LB from this ET, 45% (5/11) had remaining inventory and 54% (6/11) did not; 5 of these unsuccessful pts returned for another ET and 2 had a LB. In total, 16 pts had 2 ETs result in OP/LB and 1 pt had 3 ETs result in LB. 10 more pts had >=2 children from a single ET (9 twins, 1 triplet); thus, we report 27 pts with >=2 children from OC. Among pts with >=2 children, median # OC cycles was 1 (range 1-8), median age at 1^st OC was 37y (range 34-41), median # cryopreserved AOs was 20 (range 5-102) and median # thawed AOs was 19 (range 5-58).
Conclusion(s): Most pts (61%) had inventory after their 1^st LB from OC, and most pts (65%) who returned for ET after LB achieved another OP/LB. Further research must explore pts' thoughts regarding OC inventory after LB and its associated storage fees. Impact Statement: OC can help pts achieve their ideal family size, even if >1 child. [Formula presented] Support: None.
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Objective: Planned OC is increasing; yet, there is a lack of thaw data to provide an accurate estimate of CLBR.¹ We reviewed our AO thaws to determine CLBR by age and #AOs.
Material(s) and Method(s): We reviewed AO thaws at our academic center from 2004-2021. Inclusion criteria: 1) >=1 live birth (LB)/ongoing pregnancy (OP) >12 weeks, or 2) all AOs + embryos from OC consumed. Exclusion criteria: 1) OC for a medical reason, as research, due to lack of sperm or a natural disaster, combined with embryos or for gestational carrier use, or 2) AOs/embryos from OC transported out before a LB. Primary outcome was CLBR (LB + OP). Patients (pts) were stratified by age and #AOs or metaphase II oocytes (M2s) thawed. If pts had >=1 OC cycle, we calculated a weighted age: [SIGMA (#AOs thawed x age at OC)] / [#AOs thawed]. Statistics included multiple logistic regression (MLR), Fischer's exact test, and chi-squared test (p<0.05 significant).
Result(s): 548 pts (median age at OC 38y, range 28-45y; 151 weighted ages used) underwent 767 OC (location: 90% our center, 9% elsewhere, 2% both; method: 77% vitrification, 4% slow cooling, 19% both), 604 thaw and 465 transfer cycles. 40% (n=218) of pts had >=1 LB/OP, resulting in 221 babies + 30 OPs. See table for CLBRs. In pts of all ages and <38y, CLBR increased as #AO/M2s thawed increased from 0-10 to 11-20 to >20 (p<0.03). In pts 38-39y, CLBR was lower if 0-10 vs. 11-20 or >20 AOs were thawed (p<0.01), but was similar if 11-20 vs. >20 AOs (p=0.34) or M2s (p=0.13) were thawed. In pts >=40y, CLBR did not differ based on #AOs (p=0.81) or M2s thawed (p=0.17). For pts with any # or >20 AO/M2s thawed, CLBR was higher in pts <38y and 38-39y vs. pts >=40y (p<0.04). In a MLR model adjusting for effect of age on #AOs, age and age-independent #AOs were predictive of LB.
Conclusion(s): CLBR increases as more AO/M2s are thawed. OC at <38y has a CLBR of ~50%, a reasonable rate in younger pts at an ideal age for OC. Impact Statement: Pts who freeze >20 AOs at <38y can expect >=70% CLBR based on actual outcomes. This is the largest report to date of AO thaw outcomes from a single U.S. center. [Formula presented] REFERENCES:: 1 Practice Committee of the American Society for Reproductive Medicine. Evidence-based outcomes after oocyte cryopreservation for donor oocyte in vitro fertilization and planned oocyte cryopreservation: a guideline. Fertil Steril. 2021 Jul;116(1):36-47.
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OBJECTIVE: Oocyte cryo is widely used for fertility preservation, but the value of M1 cryo remains unclear. We evaluated the utility and efficiency of M1 compared to M2 cryo. MATERIALS AND METHODS: Patients (pts) who thawed autologous oocytes at our academic center from 2004-2020 were reviewed. Pts were excluded if cryo was performed for a medical indication, as research, due to no sperm or a natural disaster, in combination with embryos or for use with a gestational carrier. At our center, all M1s retrieved from 2004-2015 were cryopreserved; after 2015, M1s were only cryopreserved if <15 M2s were retrieved during the same cryo cycle. Outcomes included survival rate, useable embryo rate and embryo transfer (ET) results.Auseable embryo was defined as an embryo that was transferred, biopsied or cryopreserved for future use. Statistics included Fisher's exact test.
RESULT(S): 543 pts (median age at 1st cryo 38y, interquartile range 37-40y) underwent 800 cryo, 605 thaw and 416 ET cycles. Cryo was performed with vitrification for 72%, slow freezing for 4% and both technologies for 24% of pts. In total, 8511 oocytes (1019M1s + 7492 M2s)were thawed.All pts thawed >=1 M2, and 60% (n=327) thawed >=1 M1. See table for thaw outcomes of M1s vs. M2s. For 30 pts, >=1 M1 led to a useable embryo (n=32 useable embryos). Vitrification was used for 69% of these M1s (n=22) and slow freezing was used for 31% (n=10). Of the 32 useable embryos from M1s, 69% (n=22) underwent PGTand 4were euploid (17 aneuploid, 1 mosaic). Therewere 3 single ETs of euploid embryos from M1s, which led to 1 spontaneous abortion (SAB) and 2 biochemical pregnancies. Therewere 3 single ETs of untested embryos from M1s, which led to 1 negative result, 1 SAB and 1 singleton ongoing pregnancy. The ongoing pregnancy is from an ETof a day 5 morula and is now in the third trimester. There were 6 ETs in which untested embryos from M1s were transferred alongwith untested embryos fromM2s, resulting in 3 negative results, 1 SAB, 1 singleton live birth and 1 unknown outcome (ongoing singleton pregnancy at last contact).
CONCLUSION(S): Cryopreserved M1s can result in useable embryos and pregnancies, but are less likely to survive or form useable embryos than cryopreserved M2s. To our knowledge, this is the first report of an ongoing third trimester pregnancy from a cryopreserved M1. This information may be helpful for pt counselling and designing oocyte cryo protocols for embryology labs. IMPACT STATEMENT: Cryopreserved M1s may be a viable option for pts with a low M2 yield. (Table Presented)