The evolving landscape of donor egg treatment: success, women's choice, and anonymity.

PURPOSE: To analyze donor oocyte (DE) data across 6 years for oocyte usage efficiency, trends, and whether changes impacted outcomes. METHODS: From 2014 to 2019, 323 DE embryo transfers were completed in 200 recipients using oocytes derived of 163 donors. We assessed data for oocytes being freshly retrieved (FRESH-EGG) vs. purchased frozen (FROZEN-EGG); embryos transferred fresh (FRESH-ET) vs. frozen (FROZEN-ET); cycles SHARED (two recipients) vs. SOLE (one recipient); single (SET) vs. double (DET) embryo transfers and usage of PGT-A. Primary outcome was ongoing pregnancy plus live birth (OP/LB) rate. RESULTS: A total of 229 FRESH-EGG (70%) and 94 FROZEN-EGG (30%) cycles were completed. Overall, the use of FRESH-EGG yielded a higher OP/LB compared to FROZEN-EGG (49% vs. 30%, p = 0.001); within the FRESH-EGG group, OP/LB was similar when comparing FRESH-ET vs. FROZEN-ET (58% vs. 45%, p = 0.07). Within the FRESH-ET group, those using FRESH-EGG had a higher OP/LB than those using FROZEN-EGG (58% vs. 27%, p < 0.001). SHARED vs. SOLE cycles (p = 0.6), donor age (21-32 years; p = 0.4), and age of intended parents (maternal p = 0.3, paternal p = 0.2) did not significantly impact OP/LB. Notably, the use of PGT-A did not improve odds for an OP/LB (p = 0.7). CONCLUSION: The use of FRESH-EGG with FRESH-ET without PGT-A remains superior to newer DE treatment combinations. Specifically, the use of FROZEN-EGG and PGT-A did not improve outcomes. Although changing DE practices may enhance experience and affordability, patients and providers must appreciate that choices do not always favorably impact success. Additionally, newly available genetic-ancestry testing may pose longer-term ramifications mandating change in treatment and/or counseling.

Clinical error rates of next generation sequencing and array comparative genomic hybridization with single thawed euploid embryo transfer.

We investigated clinical error rates with single thawed euploid embryo transfer (STEET) diagnosed by next generation sequencing (NGS) and array comparative genomic hybridization (aCGH). A total of 1997 STEET cycles after IVF with preimplantation genetic testing for aneuploidy (PGT-A) from 2010 to 2017 were identified; 1151 STEET cycles utilized NGS, and 846 STEET cycles utilized aCGH. Any abortions, spontaneous or elective, in which products of conception (POCs) were collected were reviewed. Discrepancies between chorionic villus sampling, amniocentesis, or live birth results and PGT-A diagnosis were also included. Primary outcomes were clinical error rate per: ET, pregnancy with gestational sac, live birth, and spontaneous abortion with POCs available for analysis. Secondary outcomes included implantation rate (IR), spontaneous abortion rate (SABR), and ongoing pregnancy/live birth rate (OPR/LBR). The clinical error rates in the NGS cohort were: 0.7% per embryo, 1% per pregnancy with gestational sac, and 0.1% rate per OP/LB. The error rate per SAB with POCs was 13.3%. The IR was 69.1%, the OPR/LBR was 61.6%, and the spontaneous abortion rate was 10.2%. The clinical error rates in the aCGH cohort were: 1.3% per embryo, 2% per pregnancy with gestational sac, and 0.4% rate per OP/LB. The error rate per SAB with POCs was 23.3%. The IR was 63.8%, the OPR/LBR was 54.6%, and the SAB rate was 12.4%. Our findings demonstrate that, although NGS and aCGH are sensitive platforms for PGT-A, errors still occur. Appropriate patient counseling and routine prenatal screening are recommended for all patients undergoing IVF/PGT-A.

Pregnancy Outcomes After Fertility Preservation in Transgender Men.

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.

Young Women's Attitudes Towards Modern Reproductive Practices: A Survey Study Assessing What Young Women Want.

Objective: To assess young women's preferences and attitudes towards various options to create families at a time when women are increasingly postponing childbearing due to greater career focus and widespread availability of contraceptives. Study Design: Reported data were obtained from an electronic survey distributed over 6 months to approximately 7,000 females enrolled in American universities. Results: Most respondents ranked preferable childbearing modalities as follows: natural conception, assisted reproductive technologies, adoption, anonymous oocyte donation, and directed oocyte donation. The majority would consider using autologous oocyte cryopreservation for childbearing, but only a minority saw oocyte donation as a viable option. When queried about donating oocytes, 61% said they would donate to a sibling/friend, 51% to research, and 40% for clinical usage. Most would prefer to receive donation outcome information and would be comfortable being contacted by offspring. Most believed selecting recipient characteristics would increase their likelihood of donation, and 43% felt donors should receive additional compensation for desirable characteristics. Conclusion: Reproductive autonomy and fertility preservation are important to young educated females, a population sought-after for oocyte donation. Potential donors' desires for additional rights merit consideration as oocyte demand increases and frozen-oocyte banks emerge.

Successful Oocyte Cryopreservation in Reproductive-Aged Cancer Survivors.

OBJECTIVE: To demonstrate that oocyte cryopreservation is a feasible reproductive option for patients with cancer of childbearing age who require gonadotoxic therapies. METHODS: This study is a university-based retrospective review of reproductive-aged cancer patient treatment cycles that included ovarian stimulation, transvaginal oocyte retrieval, oocyte cryopreservation, and, in some cases, subsequent oocyte thaw, in vitro fertilization, and embryo transfer. Outcome measures included ovarian stimulation response, number of oocytes retrieved, cryopreserved, and thawed, and pregnancy data. RESULTS: From 2005 to 2014, 176 reproductive-aged patients with cancer (median age 31 years, interquartile range 24-36) completed 182 oocyte cryopreservation cycles. Median time between consult request and oocyte retrieval was 12 days (interquartile range 10-14). Median peak stimulation estradiol was 1,446 pg/mL (interquartile range 730-2,687); 15 (interquartile range 9-23) oocytes were retrieved and 10 (interquartile range 5-18) metaphase II oocytes were cryopreserved per cycle. Ten patients (11 cycles) have returned to attempt pregnancy with their cryopreserved oocytes. Among thawed oocytes, the cryopreservation survival rate was 86% (confidence interval [CI] 78-94%). Nine of 11 thaw cycles resulted in embryos suitable for transfer. The embryo implantation rate was 27% (CI 8-46%) and the live birth rate was 44% (CI 12-77%) per embryo transfer. Chance for live birth with embryos created from cryopreserved oocytes was similar between the patients with cancer in this study and noncancer patients who underwent the same treatment at our center (44% [CI 12-77%] compared with 33% [CI 22-44%] per embryo transfer). CONCLUSION: Oocyte cryopreservation is now a feasible fertility preservation option for reproductive-aged patients with cancer who require gonadotoxic therapies.

Heterotopic Gestation with Twin Intrauterine Implantation Following Transfer of Three Developmentally-delayed Embryos from Cryopreserved Oocytes: A Case Report.

BACKGROUND: In vitro fertilization (IVF) data suggest improved live birth rates for embryos transferred at the blastocyst versus the cleavage stage. Embryos that have not reached the blastocyst stage by day 5 postthaw have diminished potential for implantation and live birth. Few data exist regarding embryogenesis and optimal timing of transfer for embryos derived from previously cryopreserved oocytes, but we report the case of 100% implantation following transfer of 3 developmentally-delayed embryos derived from cryopreserved oocytes. CASE: A 38-year-old woman cryopreserved 20 oocytes for the purpose of future childbearing. At age 42 she returned to thaw and fertilize 8 oocytes using donor sperm. Embryos were cultured to day 5 postthaw, at which time 1 morula and 2 cleavage-stage embryos were available for transfer. Three-embryo transfer resulted in a heterotopic tubal pregnancy and twin intrauterine gestation. Laparoscopic salpingectomy was performed for the ectopic gestation. The twin intrauterine pregnancy spontaneously reduced to singleton, and the patient delivered a live-born infant. CONCLUSION: While heterotopic and multifetal pregnancy are known risks of multiembryo transfer, 3 lesser-quality embryos derived from cryopreserved oocytes would be unlikely to have high implantation potential. Future studies are needed to delineate timing of embryogenesis events in previously cryopreserved oocytes.

Baby budgeting: oocyte cryopreservation in women delaying reproduction can reduce cost per live birth.

OBJECTIVE: To determine whether oocyte cryopreservation for deferred reproduction is cost effective per live birth using a model constructed from observed clinical practice. DESIGN: Decision-tree mathematical model with sensitivity analyses. SETTING: Not applicable. PATIENT(S): A simulated cohort of women wishing to delay childbearing until age 40 years. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Cost per live birth. RESULT(S): Our primary model predicted that oocyte cryopreservation at age 35 years by women planning to defer pregnancy attempts until age 40 years would decrease cost per live birth from $55,060 to $39,946 (and increase the odds of live birth from 42% to 62% by the end of the model), indicating that oocyte cryopreservation is a cost-effective strategy relative to forgoing it. If fresh autologous assisted reproductive technology (ART) was added at age 40 years, before thawing oocytes, 74% obtained a live birth, and cost per live birth increased to $61,887. Separate sensitivity analyses demonstrated that oocyte cryopreservation remained cost effective as long as performed before age 38 years, and more than 49% of those women not obtaining a spontaneously conceived live birth returned to thaw oocytes. CONCLUSION(S): In women who plan to delay childbearing until age 40 years, oocyte cryopreservation before 38 years of age reduces the cost to obtain a live birth.

Long-term cryopreservation of human oocytes does not increase embryonic aneuploidy.

OBJECTIVE: To determine if long-term cryopreservation of human oocytes affects oocyte developmental competence, blastocyst euploidy, or live-birth rates. DESIGN: Retrospective cohort study. SETTING: University-based fertility center. PATIENT(S): A total of 33 patients with cryopreserved oocytes underwent oocyte thaw, blastocyst culture, trophectoderm biopsy, and 24-chromosome preimplantation genetic screening (PGS) with array comparative genomic hybridization between December 2011 and July 2014; subjects were compared with 2:1 age-matched controls with fresh oocytes whose embryos underwent trophectoderm biopsy and PGS during the same period. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rates of fertilization, blastulation, euploidy, implantation, and live birth. RESULT(S): Thirty-three patients (mean age 36.2 ± 3.8 y) thawed 475 oocytes that had been cryopreserved for a median of 3.5 years. Compared with 66 age-matched controls who underwent in vitro fertilization and PGS with fresh oocytes, embryos derived from cryopreserved oocytes demonstrated compromised blastocyst formation (54.5% vs. 66.2%) despite no impairment in fertilization (72.8% vs. 73.2%). Results showed no difference in the number of euploid blastocysts (1.7 ± 1.9 vs. 2 ± 2.5), percentage of euploid blastocysts (44.5% vs. 47.6%), rate of implantation (65% vs. 65%), or rate of live birth and ongoing pregnancy (62.5% vs. 55%) after 24-chromosome PGS with cryopreserved or fresh oocytes. CONCLUSION(S): Embryos derived from cryopreserved oocytes demonstrate impaired blastulation but equivalent rates of euploidy, implantation, and live birth compared with blastocysts derived from fresh oocytes, supporting the safety and efficacy of oocyte cryopreservation.

Assessing morphokinetic parameters via time lapse microscopy (TLM) to predict euploidy: are aneuploidy risk classification models universal?

PURPOSE: To determine if Aneuploidy Risk Classification Models are predictive of euploidy/aneuploidy amongst IVF facilities. METHODS: We retrospectively applied key time lapse imaging events of embryos (Campbell et al.[5, 6]) to stratify embryos into 3 groups: low, medium and high risk of aneuploidy. The actual ploidy results (from array comparative genomic hybridization) were compared with expectations [5, 6]. Sources of variability in morphokinetic parameters were determined using Analysis of Variance (ANOVA). RESULTS: The model failed to segregate euploid embryos from aneuploid embryos cultured at our facility. Further analysis indicated that the variability of embryos among patients was too great to allow selection of euploid embryos based on simple morphokinetic thresholds. Clinical selection of embryos based on morphokinetics alone is unlikely to identify euploid embryos accurately for transfer or yield higher rates of live delivery. CONCLUSIONS: The use of non-invasive morphokinetics is unlikely to discriminate aneuploid from euploid embryos. Further, it does not approach the accuracy of preimplantation genetic screening with array comparative genomic hybridization.

What makes them split? Identifying risk factors that lead to monozygotic twins after in vitro fertilization.

OBJECTIVE: To identify the incidence, risk factors, and obstetric/perinatal outcomes associated with monozygotic twins (MZTs) after IVF. DESIGN: Nested case-control. SETTING: University-based center. PATIENT(S): The IVF cycles eventuating in pregnancy from 2000-2009. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The MZT incidence, chorionicity/zygosity, pregnancy/neonatal outcome. RESULT(S): Of 6,223 gestations, 131 MZTs were diagnosed (2.1% incidence; 2.0% in autologous and 2.7% in donor IVF cycles), 10 were dichorionic, and 121 were monochorionic. Controlling for all risk factors, young oocyte age, extended culture (noncleavage embryos transferred on/after day 4), and year of IVF treatment cycle were significantly associated with MZT. When assessing factors associated with specific MZT placentation, day 3 assisted hatching correlated more with dichorionic MZT, whereas extended culture and advanced day 5 embryonic stage correlated with monochorionic MZT. Comparing monozygotic to dizygotic multigestation outcomes, MZT fared worse; however, once controlling for triplet gestation, only gestational age at delivery remained significantly compromised in the monozygotic group. CONCLUSION(S): After IVF the incidence of MZT is high, with young oocyte age, year of treatment, and extended culture (or embryo stage at transfer) conferring greatest risk. Regarding MZT type, assisted reproductive technology (ART) procedures may influence the timing of embryonic splitting (i.e., division in early embryonic development may be influenced by zona pellucida [ZP] manipulation whereas later splitting may occur during delayed implantation). Poor obstetric/perinatal outcome is significantly impacted by the presence of an "extra" fetus, as high-order multiple gestation concurrent with an MZT conveyed the worst prognosis.

WITHDRAWN: What makes them split? Identifying risk factors that lead to monozygotic twins after in vitro fertilization.

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What do reproductive-age women who undergo oocyte cryopreservation think about the process as a means to preserve fertility?

OBJECTIVE: To better understand women's beliefs, priorities, and attitudes toward oocyte cryopreservation, to appreciate the extent of their reproductive education, and to track the reproductive paths of women who chose to undergo oocyte cryopreservation treatment. DESIGN: An anonymous 30-question survey. SETTING: Not applicable. PATIENT(S): From 2005-2011, 478 women completed ≥1 oocyte cryopreservation treatment cycle at our center to defer reproduction. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Demographics, motivations, desires, fertility knowledge, and outcomes related to oocyte cryopreservation. RESULT(S): A total of 183 patients (38%) completed the survey with >80% being aged ≥35 years; white; having no partner at time of oocyte cryopreservation; undergoing oocyte cryopreservation after an optimal reproductive age; feeling they had improved their reproductive future after oocyte cryopreservation and being empowered by the process; aware of age-related infertility; sensing popular media falsely portrayed the upper age limit for natural conception; and recorded lack of partner as the primary rationale for not yet starting a family. Nineteen percent of respondents added that workplace inflexibility contributed to their reproductive dilemma. Half stated they learned about oocyte cryopreservation from a friend; others became aware through a medical provider, the media, and the internet. Most patients (93%) have not yet returned to use their frozen oocytes; 11 stated they had. Overall, 20% reported a successful conception after oocyte cryopreservation. CONCLUSION(S): Surveying oocyte cryopreservation patients provides a glimpse into the knowledge base and motivations surrounding current female reproductive practices. Oocyte cryopreservation technology may prove to bridge the gap between reproductive prime and when a woman is realistically "ready" to have children.

Experiences in fertility preservation: lessons learned to ensure that fertility and reproductive autonomy remain options for cancer survivors.

PURPOSE: Assess fertility preservation (FP) measures chosen by patients newly diagnosed with malignancy and their outcomes. METHODS: Reproductive-age patients referred for FP underwent counseling and elected cryopreservation vs. no treatment. Outcome measures included ovarian stimulation, FP choice, oocytes/zygotes retrieved/cryopreserved and pregnancy outcome. RESULTS: From 2005 to 2012, 136 patients were counseled with 124 electing treatment: 83 oocyte-only, 21 oocyte + zygote and 20 zygote-only cryopreservation. Age, partnership and financial status factored into FP choice. Treatment was completed in 12 ± 2 days with 14 ± 11 metaphase-II oocytes harvested and cryopreserved/cycle. Eight patients returned to attempt pregnancy; three succeeded. CONCLUSIONS: Our data demonstrate that oocyte and/or zygote banking are feasible FP options for women with malignancy; given the choice, the majority elected oocyte cryopreservation, highlighting desire for reproductive autonomy. Continued growth and research, combined with interdisciplinary communication, will ensure that appropriate candidates are offered FP and the potential for future parenthood, an important quality-of-life marker for survivors.

Oocyte efficiency: does live birth rate differ when analyzing cryopreserved and fresh oocytes on a per-oocyte basis?

OBJECTIVE: To compare the efficiency of oocyte cryopreservation (OC) and IVF using the metric "live births per mature oocyte retrieved." DESIGN: Retrospective analysis. SETTING: University-based fertility center. PATIENT(S): Forty women who underwent OC with thaw attempt between 2004 and 2010; 25 autologous and 15 donor-oocyte treatments were included. One thousand nine hundred eight women underwent their first, fresh conventional IVF treatment between 2004 and 2010; 1,392 used autologous oocytes, and 516 used donor oocytes. Autologous and donor-oocyte cycles were analyzed separately. All oocytes were obtained from women

Is intracytoplasmic sperm injection overused?

PURPOSE: We determined whether the use of intracytoplasmic sperm injection in couples who previously underwent intracytoplasmic sperm injection cycles elsewhere could be decreased without compromising the pregnancy rate. MATERIALS AND METHODS: At our university in vitro fertilization-embryo transfer center we retrospectively analyzed the records of 149 fresh, in vitro fertilization-embryo transfer cycles in patients who underwent intracytoplasmic sperm injection elsewhere and subsequent fertilization by insemination only (all insemination group) or half insemination and half intracytoplasmic sperm injection at our center. We compared fertilization, implantation, clinical pregnancy and live birth rates. RESULTS: The fertilization rate was 74% and 73% for the all insemination and the half intracytoplasmic sperm injection groups, respectively. In the latter group 69% of inseminated and 78% of intracytoplasmic sperm injected oocytes were fertilized. No cycle showed complete fertilization failure. No statistically significant difference in the live birth rate was found between the 2 groups. CONCLUSIONS: More stringent criteria for intracytoplasmic sperm injection do not compromise the clinical outcome and reasonable fertilization can be achieved whether or not intracytoplasmic sperm injection is performed. Thus, although intracytoplasmic sperm injection is one of the greatest advances in our field, it is overused and should only be done for clinically proven indications.

Oocyte cryopreservation as a fertility preservation measure for cancer patients.

Advances in cancer treatment have allowed women to live longer, fuller lives. However, gonadotoxic therapies used to effect cancer 'cures' often significantly impair a woman's reproductive potential. Thus, in accordance with improved survival rates,there is an increase in demand for fertility preservation. Initially, fertility preservation was limited to embryo cryopreservation;therefore, the number of patients enrolling was relatively low. Recently, substantial improvements have increased available options, specifically oocyte cryopreservation, thereby expanding and altering the make-up of the patient population under going treatment for fertility preservation. Patient diversity requires the treating physician(s) to be cognizant of issues specific to cancer type and stage. Furthermore, patients often have comorbidities which must be attended to and addressed. Although not all patients will be candidates for, or will elect to pursue, fertility preservation, all should receive counselling regarding their options. This practice will ensure that the reproductive rights of those patients facing impending sterility are maintained. Here, fertility preservation protocols, practices and special considerations, categorized by most frequently encountered cancer types, are reviewed to guide reproductive endocrinologists in the management of fertility preservation in such patients. The formation of a multidisciplinary patient-structured team will ensure a successful, yet safe, fertility-preservation outcome .