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.

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.

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.

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.

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.

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.

Fertility considerations in the management of gynecologic malignancies.

GOALS: Gynecologic cancers represent a significant proportion of malignancies affecting women. Historically, cancer treatment focused primarily on eradicating disease, irrespective of the impact on fertility. The implementation of early detection protocols and advanced treatment regimens has resulted in improved prognosis for gynecologic cancer patients. With this improvement, more attention is now paid to quality-of-life issues. Fertility preservation (FP) has become an integral component in the selection and execution of gynecological cancer management. In this report we address gynecologic malignancies as they relate to future fertility potential. METHODS: We review reproductive principles such as ovarian reserve, uterine function, cervical competence, and early obstetrical management, as well as available FP methods. In addition, we discuss the potential damage that cancer and cancer treatments can impart on the female reproductive system. We offer general recommendations regarding baseline screening tests useful in assessing the feasibility of FP. Lastly, cancer-specific FP methods are presented. RESULTS: Oocyte quantity and quality naturally decline with advancing age. In most patients, the slope of decline steepens significantly after the age of 35. Reliable ovarian reserve measures exist and should be utilized to assess and triage potential candidates for FP. Advancements in FP, particularly in oocyte cryopreservation (OC), have improved the success rates associated with the techniques available to cancer patients. Currently, where successfully available, OC appears to be the preferred method for single women diagnosed with a gynecologic malignancy as it affords reproductive autonomy, whereas embryo cryopreservation using a donor gamete remains an alternative. CONCLUSIONS: In gynecologic oncology, effective treatments to achieve cancer survival can compromise the ability to subsequently conceive and/or carry a child. Therefore, as the field of oncofertility continues to expand, a discussion regarding FP should be initiated when tailoring a cancer treatment protocol.

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 .

Retrospective analysis of outcomes following transfer of previously cryopreserved oocytes, pronuclear zygotes and supernumerary blastocysts.

Oocyte cryopreservation still bears the experimental label. Remarkable innovation in this field has led to immense improvement in clinical outcomes and has even resulted in outcomes comparable to those achieved following fresh embryo transfers. Such success has prompted this centre to investigate outcomes of cryopreservation options (oocyte versus pronuclear zygote versus supernumerary day-5 blastocyst after fresh embryo transfer). This study retrospectively analysed 200 cryopreservation cycles which were divided into three groups according to cryopreservation option, which were all cultured to blastocyst-stage post thaw/warming from January 2005 to December 2008, and compared them with 400 fresh embryo transfer cycles from the same time period. When compared with fresh embryo transfer, frozen embryo transfers originating from previously cryopreserved oocytes or pronuclear zygotes resulted in similar implantation, pregnancy and live-birth rates; however, frozen embryo transfers originating from supernumerary day-5 blastocysts resulted in lower outcomes. Thus, oocyte and/or pronuclear zygote cryopreservation appear to be the most viable options for women desiring fertility preservation. Cryopreservation of supernumerary blastocysts may lead to a slightly lower live-birth rate since the best-quality blastocysts are generally transferred during the fresh embryo transfer attempt.

Treatment outcomes and quality-of-life assessment in a university-based fertility preservation program: results of a registry of female cancer patients at 2 years.

PURPOSE: To explore patient goals and quality of life (QOL) via a prospective registry and compare fertility preservation (FP) outcomes before, during, and after cancer therapy. METHODS: Of 35 patients entering the registry from 3/2008 to 3/2010, 29/35 completed the study survey and agreed to follow-up, and 31/35 completed treatment. Survey results and FP outcomes were analyzed. RESULTS: Most patients rated the impact of cancer treatment on fertility of highest importance at baseline and 1-year follow-up. QOL scores were overall positive at both intervals. Patients naïve to any cancer treatment (n = 12) had more gametes frozen than patients with prior cancer treatment (n = 19) with no difference in age or gonadotropin dosage. For patients awaiting cancer treatment, the median time from consultation to oocyte retrieval was 25 days. Cancer treatment sequalae posed challenges to optimal FP outcomes. CONCLUSIONS: Fertility preservation remains a significant issue for cancer patients. With early reproductive endocrinologist referral, cancer treatment delay is minimized and FP outcomes are optimized.

Surviving childhood and reproductive-age malignancy: effects on fertility and future parenthood.

Annually, more than 50,000 cancer diagnoses are made in the USA in patients under the age of 35 years. Despite this staggering statistic, medical advancements have substantially improved survival rates. Thus, for both male and female patients with cancer, quality-of-life issues, such as fertility preservation and parenthood, have become an essential component of treatment. Unfortunately, many of the treatments to eradicate malignant processes can also compromise reproductive function. In these cases, fertility preservation should be discussed and initiated with early treatment planning, to allow the best chance for future parenthood, when appropriate. The effects of cancer and cancer treatments on fertility and future parenthood, including health risks for patients, their gametes, and offspring are discussed.

Oocyte cryopreservation: is it time to remove its experimental label?

As more reproductive-age women survive cancer at the expense of gonadotoxic therapy, the need for viable fertility preservation options has become paramount. Embryo cryopreservation, often using donor sperm, has been the standard offered these women over the past 20 years. Preservation of unfertilized oocytes now represents an acceptable and often equally viable alternative, particularly for single women, due to technologic advances made in the past decade. Given such, oocyte cryopreservation's experimental designation and need for IRB approval should thus be revisited.

Laboratory evaluation in oocyte cryopreservation suggests retrieved oocytes are comparable whether frozen for medical indications, deferred reproduction or oocyte donation.

PURPOSE: to compare pre-cryo data from oocyte cryopreservation (OC) cycles performed for malignancy (MED) vs. elective deferment of reproduction (DR) or oocyte donation (OD). METHODS: all patients were ≤40 y and underwent standard ovarian stimulation and retrieval. Prior to OC, meiotic spindle (MS) and zona pellucida (ZP) retardance was measured using digital polarized light microscopy (DPLM). RESULTS: of 130 OC cycles, 49 were for MED, 73 for DR, and 8 for OD. Cycles completed for MED had an average of 9 ±1 spindle-positive oocytes with a mean MS retardance of 1.2 ± 02 nm and ZP retardance of 2.1 ± .06 nm, which was clinically comparable to the other groups. CONCLUSIONS: women with malignancy can achieve adequate ovarian response and similar oocyte parameters to those of women undergoing fertility preservation for non-cancer indications. Such information, coupled with the ability to noninvasively study oocyte dynamics, may improve the counseling of cancer patients seeking fertility preservation.

Oocyte cryopreservation: a feasible fertility preservation option for reproductive age cancer survivors.

PURPOSE: To compare oocyte cryopreservation cycles performed in cancer patients to those of infertile women. METHODS: Cancer patients referred for fertility preservation underwent counseling in compliance with the ASRM; those electing oocyte cryopreservation were included. Ovarian stimulation was achieved with injectable gonadotropins and freezing was performed using slow-cooling and vitrification methods. RESULTS: Fifty cancer patients (mean age 31 y) underwent oocyte cryopreservation; adequate ovarian stimulation was achieved in 10 ± 0.3 days. The outcome from these cycles included a mean peak estradiol of 2,376 pg/ml and an average of 19 oocytes retrieved (15 mature oocytes were cryopreserved/cycle). All patients tolerated ovarian hyperstimulation. There were no significant differences noted between cryopreservation cycles performed in cancer patients and in women without malignancy. CONCLUSIONS: Oocyte cryopreservation appears to be a feasible fertility preservation method for reproductive-age women diagnosed with cancer. This modality is not only effective but also, providing a multidiscipline effort, can be completed in timely fashion.

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.

Impact of developmental stage at cryopreservation and transfer on clinical outcome of frozen embryo cycles.

Although several early IVF successes were achieved after transferring fully formed blastocysts, the majority of embryos replaced worldwide over the past 30 years have been at the cleavage stage. The programme at this study centre has previously found that delaying an embryo transfer to day 5 can reduce the chance for a high-order multiple gestation without compromising the pregnancy rate because fewer embryos can be replaced. To evaluate the impact of transfer day and embryonic stage at cryopreservation on cycle outcome, 6069 fresh and 706 frozen transfers from 2000-2006 performed at this study centre were retrospectively analysed. Approximately half of the fresh transfers were performed on day 3, with a shift to day-5 transfer over the study period with no change in cryopreservation incidence. Implantation, clinical pregnancy and live birth rates were significantly higher following day-5 transfer. When frozen-thawed embryos (2-cell to day-6 blastocysts) were transferred, acceptable pregnancy and live birth rates were achieved at all stages but thawed embryos transferred as day-5 blastocysts generated consistently higher clinical pregnancy and live birth rates. Transfer of embryos frozen on day 6 had the highest miscarriage and lowest live birth rates. Barring government regulation, an IVF programme's day for cryopreservation generally depends on its management of and success with fresh embryo transfer.

Embryo biopsy: the fate of abnormal pronuclear embryos.

This study assessed 1908 embryos, including those with abnormal numbers of pronuclei, in IVF cycles from July 2001 to December 2006 in which preimplantation genetic screening (PGS) was performed on day 3 post-retrieval and 'euploid' embryos transferred the following day. PGS-intracytoplasmic sperm injection and PGS-translocation cycles were excluded. At 18 h post-insemination, the zygote distribution was 19% 0PN, 4% 1PN, 69% 2PN and 8% 3PN. No pregnancy occurred following 0PN or 1PN embryo transfers. A retrospective, blinded morphological ranking of all embryos on day 3 was performed and the results compared with PGS; no 0PN or 1PN embryo would have been chosen for transfer based on morphological superiority alone. Blastocyst formation occurred in 1PN embryos (29%) but not in 0PN embryos when evaluated on day 5. Euploid karyotypes were reported for biopsies of 0PN (3%), 1PN (5%) and 2PN (19%) embryos (P = 0.015, 1PN versus 2PN). A Y chromosome was observed in 0PN (17%) and 1PN (32%) embryos; surprisingly, 91% of these Y chromosome-bearing embryos were aneuploid. Many different meiotic and fertilization errors can result in 0PN or 1PN zygotes; these results indicate that the resultant embryos should not be transferred, especially when normally fertilized embryos are available.

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.