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Planned oocyte cryopreservation-10-15-year follow-up: return rates and cycle outcomes

Blakemore, Jennifer K; Grifo, James A; DeVore, Shannon M; Hodes-Wertz, Brooke; Berkeley, Alan S
OBJECTIVE:To evaluate the outcomes of planned oocyte cryopreservation patients most likely to have a final disposition. DESIGN/METHODS:Retrospective cohort study of all patients who underwent at least 1 cycle of planned oocyte cryopreservation between Jan 2005 and December 2009. SETTING/METHODS:Large urban University-affiliated fertility center PATIENT(S): All patients who underwent ≥1 cycle of planned oocyte cryopreservation in the study period. INTERVENTION(S)/METHODS:None MAIN OUTCOME MEASURE(S): Primary outcome was the disposition of oocytes at 10-15 years. Secondary outcomes included thaw/warming types, laboratory outcomes, and live birth rates. Outcomes and variables treated per patient. RESULT(S)/RESULTS:A total of 231 patients with 280 cycles were included. The mean age at the first retrieval was 38.2 years (range 23-45). A total of 3,250 oocytes were retrieved, with an average of 10 metaphase II frozen/retrieval. To date, the oocytes of 88 patients (38.1%) have been thawed/warmed, 109 (47.2%) remain in storage, 27 (11.7%) have been discarded, and 7 (3.0%) have been transported elsewhere. The return rate (patients who thawed/warmed oocytes) was similar by Society for Assisted Reproductive Technology age group. The mean age of patients discarding oocytes was 47.4 years (range, 40-57). Of the 88 patients who thawed/warmed oocytes, the mean age at the time of thaw/warming was 43.9 years (range, 38-50) with a mean of 5.9 years frozen (range, 1-12). Nine patients (10.2%) thawed/warmed for secondary infertility. A total of 62.5% of patients created embryos with a partner, and 37.5% used donor sperm. On average, 14.3 oocytes were thawed/warmed per patient, with 74.2% survival (range, 0%-100%) and a mean fertilization rate of 68.8% of surviving oocytes. Of 88 patients, 39 (44.3%) planned a fresh embryo transfer (ET); 36 of 39 patients had at least 1 embryo for fresh ET, and 11 had a total of 14 infants. Forty-nine of 88 patients (55.7%) planned for preimplantation genetic testing for aneuploidy, with a mean of 4.2 embryos biopsied (range, 0-14) and a euploidy rate of 28.9%. Of the 49 patients, 17 (34.7%) had all aneuploidy or no embryos biopsied. Twenty-four patients underwent a total of 36 single euploid ET with 18 live births from 16 patients. Notably, 8 PGT-A patients had a euploid embryo but no ET, affecting the future cumulative pregnancy rate. Overall, 80 patients with thaw/warming embryos had a final outcome. Of these, 20 had nothing for ET (arrested/aneuploid), and of the 60 who had ≥1 ET, 27 had a total of 32 infants, with a live birth rate of 33.8% (27/80). CONCLUSION(S)/CONCLUSIONS:We report the final outcomes of patients most likely to have returned, which is useful for patient counseling: a utilization rate of 38.1% and a no-use rate of 58.9%, similar across age groups. Further studies with larger cohorts as well as epidemiologic comparisons to patients currently cryopreserving are needed.
PMID: 33712289
ISSN: 1556-5653
CID: 4817192


Blakemore, Jennifer K.; Grifo, James A.; Devore, Shannon; Hodes-Wertz, Brooke; Berkeley, Alan S.
ISSN: 0015-0282
CID: 4685162

Achieving the "ideal" family size at advanced reproductive ages through oocyte cryopreservation

DeVore, Shannon; Noyes, Nicole; Grifo, James A; Berkeley, Alan S; Licciardi, Frederick; Goldman, Kara N
PMID: 30194616
ISSN: 1573-7330
CID: 3274882

PGS: Does this expensive technology improve outcomes in donor oocyte thaw cycles (DOT)? [Meeting Abstract]

Druckenmiller, S; Lee, H -L; Berkeley, A; Fino, M E; Devore, S; Noyes, N
Objective Improvements in oocyte cryopreservation(OC) have led to successful oocyte banking and more readily available cryopreserved donor oocytes(DO). Simultaneously, preimplantation genetic screening(PGS) has increased, even with DO. Using OC, DO, and PGS together is less common, but now occurs. Reservations include increased technological and financial cost ($1,100/oocyte). Our goal was to determine whether adding PGS increases implantation and live birth rates in DOT. Design Retrospective cohort study. Material and Methods We conducted a retrospective analysis of DOT performed 10/2004-1/2017 at a university-based fertility center. To remove bias, we conducted a sub-analysis of single embryo transfers(SET). Data was mined for: number of oocytes thawed/survived/fertilized, embryo development/transfer/implantation, and ongoing pregnancy/live birth. Mood's median and Fischer's exact tests were used for statistical analysis. Results Within the 130 non-PGS DOT (118 pts, median age:26y), 1138 oocytes (median:8/cycle) were thawed. Within the 15 PGS DOT (15 pts, median age:24y), 180 oocytes (median:11/cycle) were thawed a mean of 3 blastocysts(BL) were biopsied. Oocyte survival, 2-PN fertilization, BL formation, implantation, and ongoing pregnancy/live birth rates were not significantly different between the groups. The multiple birth rate in the non-PGS group was 6% (5/84 births). When controlling for SET, no differences were found in implantation or ongoing pregnancy/live birth rates with and without PGS (p>.1). When comparing embryo quality in the non-PGS group, a higher ongoing pregnancy/live birth rate was noted among SETs with excellent-quality Gardner's >2Bb (62% 50 births/81 transfers) when compared with SETs with poor-quality Gardner's <2Bb (35% 8 births/23 transfers p=.03). Conclusions Due to this study's small sample size, it is difficult to conclude whether PGS improves implantation/live birth rates in a young donor population. In DO cycles with excellent-quality BL for transfer, morphology alone predicts a high live birth rate. Given the financial and technological burden of PGS, larger studies are needed to determine whether the costs of PGS outweigh the benefits in DO cycles
ISSN: 1573-7330
CID: 3549382


McCulloh, DH; McCaffrey, C; Lee, H; Noyes, N; Berkeley, AS; Grifo, J
ISSN: 1556-5653
CID: 2713622

Pregnancy Outcomes After Fertility Preservation in Transgender Men

Maxwell, Susan; Noyes, Nicole; Keefe, David; Berkeley, Alan S; Goldman, Kara N
BACKGROUND: Transgender individuals, individuals whose gender identity does not align with their sex assigned at birth, undergoing gender-affirming hormonal or surgical therapies may experience loss of fertility. Assisted reproductive technologies have expanded family-building options for transgender men who were assigned female at birth. CASES: Three transgender men underwent oocyte cryopreservation before gender-affirming hormonal therapy. One patient underwent fertility preservation as an adolescent. Two adult patients had children using their cryopreserved oocytes, with the pregnancies carried by their sexually intimate partners. CONCLUSION: Transgender men with cryopreserved gametes can build families in a way that affirms their gender identity. Obstetrician-gynecologists should be familiar with the fertility needs of transgender patients so appropriate discussions and referrals can be made.
PMID: 28486372
ISSN: 1873-233x
CID: 2548972

Preimplantation Genetic Diagnosis (PGD) for Monogenic Disorders: the Value of Concurrent Aneuploidy Screening

Goldman, Kara N; Nazem, Taraneh; Berkeley, Alan; Palter, Steven; Grifo, Jamie A
Pre-implantation genetic diagnosis (PGD) has changed the landscape of clinical genetics by helping families reduce the transmission of monogenic disorders. However, given the high prevalence of embryonic aneuploidy, particularly in patients of advanced reproductive age, unaffected embryos remain at high risk of implantation failure or pregnancy loss due to aneuploidy. 24-chromosome aneuploidy screening has become widely utilized in routine in vitro fertilization (IVF) to pre-select embryos with greater pregnancy potential, but concurrent 24-chromosome aneuploidy screening has not become standard practice in embryos biopsied for PGD. We performed a retrospective cohort study of patients who underwent PGD with or without 24-chromosome aneuploidy screening to explore the value of concurrent screening. Among the PGD + aneuploidy-screened group (n = 355 blastocysts), only 25.6 % of embryos were both Single Gene Disorder (SGD)-negative (or carriers) and euploid; thus the majority of embryos were ineligible for transfer due to the high prevalence of aneuploidy. Despite a young mean age (32.4 +/- 5.9y), 49.9 % of Blastocysts were aneuploid. The majority of patients (53.2 %) had >/=1 blastocyst that was Single Gene Disorder (SGD)-unaffected but aneuploid; without screening, these unaffected but aneuploid embryos would likely have been transferred resulting in implantation failure, pregnancy loss, or a pregnancy affected by chromosomal aneuploidy. Despite the transfer of nearly half the number of embryos in the aneuploidy-screened group (1.1 +/- 0.3 vs. 1.9 +/- 0.6, p < 0.0001), the implantation rate was higher (75 % vs. 53.3 %) and miscarriage rate lower (20 % vs. 40 %) (although not statistically significant). 24-chromosome aneuploidy screening when performed concurrently with PGD provides valuable information for embryo selection, and notably improves single embryo transfer rates.
PMID: 27277129
ISSN: 1573-3599
CID: 2136452

Translocations and sex-does sizematter? [Meeting Abstract]

Escudero, T; Armenti, E M; Berkeley, A S; Norian, J M; Shapiro, D; Chantilis, S J; Racowsky, C; Ribustello, L; Liu, E
OBJECTIVE: Determine if the gender of the translocation carrier and the size of chromosome fragments involved in a translocation impact the segregation pattern during meiosis. DESIGN: Retrospective analysis of PGS results for embryos analyzed for reciprocal translocations (RT). MATERIALS AND METHODS: Results obtained from PGD lab internal data. Fragment sizes (FS) calculated using the UCSC Genome Browser and calculating the distance from the breakpoint of the translocation to the telomere and centromere. FS over 6 megabases (Mb) in size were considered "large"; those under 6Mb were considered "small." Segregation patterns were classified as: alternate, adjacent I, adjacent II, 3:1, 4:0 and atypical configurations (AC). An AC is characterized as one that cannot be explained by the standard segregation patterns and involves the breakage of the chromosomes involved in the RT. RESULTS: We review segregation patterns for 1,159 embryos (640 from female carriers, 519 from male carriers) for RT via array comparative genome hybridization (a CGH). Of the embryos, 58.2% involved RT where all FS were classified as large and 41.8% involved RT where one or more FS were classified as small. Embryos with one or more small FS were significantly more likely (p<0.001) to segregate in ACs than those with all large FS. When sorted by the gender of the parent with the RT, a significant increase in occurrence of 3:1 segregation was seen in female carriers (p<0.001); when divided by FS, female carriers of translocations with at least one small FS were more likely to have 3:1 configurations (p<0.001) (table 1). CONCLUSIONS: Patients with RT presenting for PGD testing are anxious to know the likelihood of identifying an embryo suitable for transfer and often inquire about numbers specific to their RT. As the almost endless permutations of RT make such numbers difficult to generate, this data suggests trends that may provided additional information for these patients. Those with small FS are more likely to produce embryos with ACs. Further, female carriers of RT, particularly those with small FS, are more likely to produce embryos with 3:1 segregations, and thus, may be more likely to produce unbalanced embryos than male carriers. This data will help manage expectations of RT patients presenting for PGD. (Table Presented)
ISSN: 1556-5653
CID: 2294402

Use of single nucleotide polymorphism (SNP) arrays and next generation sequencing (NGS) to study the incidence, type and origin of aneuploidy in the human preimplantation embryo [Meeting Abstract]

Konstantinidis, M; Milligan, K; Berkeley, A S; Kennedy, J; Maxson, W; Racowsky, C; Wells, D; Munne, S
OBJECTIVE: To perform a thorough investigation using a combination of the most advanced technologies available in an effort to decipher the aneuploidy 'code' in the human preimplantation embryo. DESIGN: Quantitative assessment and genotyping were undertaken concurrently for human blastocysts using SNP arrays and NGS. MATERIALS AND METHODS: Single trophectoderm biopsies were obtained from blastocysts of couples undergoing in vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD) for single gene disorders (SGD) and aneuploidy screening. Karyomapping SNP array (Illumina, USA) was used for PGD of SGD while, NGS via the VeriSeq PGS assay (Illumina) was utilized for comprehensive chromosome screening. Fisher's exact test (GraphPad Software, USA) was used for statistical analysis. RESULTS: In total, over 19,000 chromosomes were screened in 417 embryos from 75 couples [maternal age: 34.1+/-0.5 years (mean +/- SE)]. At least one chromosomal abnormality was detected in 49.2% (205/417) of the embryos assessed, with 48.3% of the embryos exhibiting only abnormalities of meiotic origin, 40% having only mitotic abnormalities and the remainder of the embryos presenting both types of abnormalities. Notably, maternal meiosis was associated with an equal number of events leading to gain vs. loss of chromosomal material (74 gains vs. 75 losses) and prevailed over paternal meiosis which consisted of events mainly involving loss of chromosomal material (27 losses vs. 1 gain) with almost half of the losses (40.7%) being partial. Of the overall number of aneuploidies detected, 15.7% were determined to be partial with the size of segments gained or lost ranging from 7.8 to 145.6 megabases. Incidences of maternally-derived meiotic errors and overall mitotic errors detected are presented in the table below in relation to maternal age: CONCLUSIONS: The incidence of maternal meiotic abnormalities was associated with increasing age, consistent with the higher rates of implantation failure and miscarriage experienced by older women. Mitotic errors, potentially producing mosaicism, were also common. Interestingly, aneuploidy of male meiotic origin was characterized by a predominance of monosomies compared with that of female origin, suggesting a sex-specific difference in the mechanism underlying segregation errors. (Table Presented)
ISSN: 1556-5653
CID: 2294452

Deliveries from trophectoderm biopsied, fresh and vitrified blastocysts derived from polar body biopsied, vitrified oocytes

Grifo, Jamie; Adler, Alexis; Lee, Hsiao Ling; Morin, Scott J; Smith, Meghan; Lu, Lucy; Hodes-Wertz, Brooke; McCaffrey, Caroline; Berkeley, Alan; Munne, Santiago
This longitudinal study reports preliminary findings of six patients who underwent first polar body biopsy followed by oocyte vitrification. All oocytes were warmed, inseminated by intracytoplasmic sperm injection and cultured to blastocyst. All suitable blastocysts underwent trophectoderm biopsy for aneuploidy screening, and supernumerary blastocysts were vitrified. Euploid blastocysts were transferred either fresh or in a subsequent programmed cycle. Of the 91 metaphase II oocytes, 30 had euploid first polar bodies. Development to blastocyst was more likely in oocytes with a euploid first polar body (66.7% versus 24.6%; P < 0.001). Nineteen euploid blastocysts were produced: 10 from oocytes with a euploid first polar body and nine from oocytes with an aneuploid first polar body. Five out of six patients (83%) had a live birth or ongoing pregnancy at the time of analysis. Eleven euploid blastocysts have been transferred and seven implanted (64%). Although the chromosomal status of the first polar body was poorly predictive of embryonic ploidy, an association was found between chromosomal status of the first polar body and development to blastocyst. Further study is required to characterize these relationships, but proof of concept is provided that twice biopsied, twice cryopreserved oocytes and embryos can lead to viable pregnancies.
PMID: 26096028
ISSN: 1472-6491
CID: 1640752