Prospective analysis of progesterone exposure in programmed single thawed euploid embryo transfer cycles and outcomes.

PURPOSE: In the era of personalized medicine and the increased use of frozen embryo transfer (FET), assay of the endometrium's receptivity prior to transfer has gained popularity, especially among patients. However, the optimal timing for single thawed euploid embryo transfers (STEET) in a programmed FET has yet to be determined Mackens et al. (Hum Reprod. 32(11):2234-42, 2017). We sought to examine the outcomes of euploid FETs by length of progesterone (P4) exposure. METHODS: Prospective cohort study of programmed FETs of single euploid embryos between June 1, 2018, and December, 18, 2018, at our center. Subjects reported the exact start time for initiating progesterone. The transfer time was noted to calculate the primary independent variable, duration of progesterone exposure. Statistical analysis included ANOVA and Spearman's rho correlation, with p < 0.05 considered significant. RESULTS: Inclusion criteria were met for 253 programmed STEET cycles in the analysis. There was no significant difference in P4 duration when comparing outcome groups (112.8 ± 3.1 ongoing pregnancy (OP), 112.4 ± 4.4 spontaneous abortion (SAB), 111.6 ± 1.7 biochemical pregnancy (BP), 113.9 ± 5.7 no pregnancy (NP), F 1.76, df 3, p = 0.16). An ROC curve assessing the ability of P4 duration to predict ongoing pregnancy (OP) had an area under the curve of 0.467 (p = 0.38). CONCLUSION: Duration of P4 was not associated with outcome. Of the cycles, 65.6% resulted in ongoing pregnancy with our center's instructions resulting in an average progesterone exposure of 112.8 h, with a range of 98.3-123.7 h. With growing popularity for individualized testing, these results provide evidence for patient counseling of the high likelihood of ongoing pregnancy without personalized testing.

mTORC1/2 inhibition preserves ovarian function and fertility during genotoxic chemotherapy.

The ovary contains oocytes within immature (primordial) follicles that are fixed in number at birth. Activation of follicles within this fixed pool causes an irreversible decline in reproductive capacity, known as the ovarian reserve, until menopause. Premenopausal women undergoing commonly used genotoxic (DNA-damaging) chemotherapy experience an accelerated loss of the ovarian reserve, leading to subfertility and infertility. Therefore, there is considerable interest but little effective progress in preserving ovarian function during chemotherapy. Here we show that blocking the kinase mammalian/mechanistic target of rapamycin (mTOR) with clinically available small-molecule inhibitors preserves ovarian function and fertility during chemotherapy. Using a clinically relevant mouse model of chemotherapy-induced gonadotoxicity by cyclophosphamide, and inhibition of mTOR complex 1 (mTORC1) with the clinically approved drug everolimus (RAD001) or inhibition of mTORC1/2 with the experimental drug INK128, we show that mTOR inhibition preserves the ovarian reserve, primordial follicle counts, serum anti-Mullerian hormone levels (a rigorous measure of the ovarian reserve), and fertility. Chemotherapy-treated animals had significantly fewer offspring compared with all other treatment groups, whereas cotreatment with mTOR inhibitors preserved normal fertility. Inhibition of mTORC1 or mTORC1/2 within ovaries was achieved during chemotherapy cotreatment, concomitant with preservation of primordial follicle counts. Importantly, our findings indicate that as little as a two- to fourfold reduction in mTOR activity preserves ovarian function and normal birth numbers. As everolimus is approved for tamoxifen-resistant or relapsing estrogen receptor-positive breast cancer, these findings represent a potentially effective and readily accessible pharmacologic approach to fertility preservation during conventional chemotherapy.

Beyond the biopsy: predictors of decision regret and anxiety following preimplantation genetic testing for aneuploidy.

STUDY QUESTION: What factors are associated with decision regret and anxiety following preimplantation genetic testing for aneuploidy (PGT-A)? SUMMARY ANSWER: The majority of patients viewed PGT-A favourably regardless of their outcome; although patients with negative outcomes expressed greater decision regret and anxiety. WHAT IS KNOWN ALREADY: PGT-A is increasingly utilized in in vitro fertilization (IVF) cycles to aid in embryo selection. Despite the increasing use of PGT-A technology, little is known about patients' experiences and the possible unintended consequences of decision regret and anxiety related to PGT-A outcome. STUDY DESIGN, SIZE, DURATION: Anonymous surveys were distributed to 395 patients who underwent their first cycle of autologous PGT-A between January 2014 and March 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: There were 69 respondents who underwent PGT-A at a university-affiliated fertility centre, completed the survey and met inclusion criteria. Respondents completed three validated questionnaires including the Brehaut Decision Regret (DR) Scale, short-form State-Trait Anxiety Inventory (STAI-6) and a health literacy scale. The surveys also assessed demographics, fertility history, IVF and frozen embryo transfer cycle data. MAIN RESULTS AND THE ROLE OF CHANCE: The majority of respondents were Caucasian, >35 years of age and educated beyond an undergraduate degree. The majority utilized PGT-A on their first IVF cycle, most commonly to 'maximize the efficiency of IVF' or reduce per-transfer miscarriage risk. The overall median DR score was low, but 39% of respondents expressed some degree of regret. Multiple regression confirmed a relationship between embryo ploidy and decision regret, with a lower number of euploid embryos associated with a greater degree of regret. Patients who conceived following euploid transfer reported less regret than those who miscarried or failed to conceive (P < 0.005). Decision regret was inversely associated with number of living children but not associated with age, education, race, insurance coverage, religion, marital status or indication for IVF/PGT-A. Anxiety was greater following a negative pregnancy test or miscarriage compared to successful conception (P < 0.0001). Anxiety was negatively associated with age, time since oocyte retrieval and number of living children, and a relationship was observed between anxiety and religious affiliation. Overall, decision regret was low, and 94% of all respondents reported satisfaction with their decision to pursue PGT-A; however, patients with a negative outcome were more likely to express decision regret and anxiety. LIMITATIONS, REASON FOR CAUTION: This survey was performed at a single centre with a relatively homogenous population, and the findings may not be generalizable. Reasons for caution include the possibility of response bias and unmeasured differences among those who did and did not respond to the survey, as well as the possibility of recall bias given the retrospective nature of the survey. Few studies have examined patient perceptions of PGT-A, and our findings should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: Overall decision regret was low following PGT-A, and the vast majority deemed the information gained valuable for reproductive planning regardless of outcome. However, more than one-third of the respondents expressed some degree of regret. Respondents with no euploid embryos were more likely to express regret, and those with a negative outcome following euploid embryo transfer expressed both higher regret and anxiety. These data identify unanticipated consequences of PGT-A and suggest opportunities for additional counselling and support surrounding IVF with PGT-A. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. D.H.M. reports personal fees, honorarium, and travel expenses from Ferring Pharmaceuticals, personal fees and travel expenses from Granata Bio, and personal fees from Biogenetics Corporation, The Sperm and Embryo Bank of New York, and ReproART: Georgian American Center for Reproductive Medicine. All conflicts are outside the submitted work.

Evaluating genetic ancestry and self-reported ethnicity in the context of carrier screening.

BACKGROUND: Current professional society guidelines recommend genetic carrier screening be offered on the basis of ethnicity, or when using expanded carrier screening panels, they recommend to compute residual risk based on ethnicity. We investigated the reliability of self-reported ethnicity in 9138 subjects referred to carrier screening. Self-reported ethnicity gathered from test requisition forms and during post-test genetic counseling, and genetic ancestry predicted by a statistical model, were compared for concordance. RESULTS: We identified several discrepancies between the two sources of self-reported ethnicity and genetic ancestry. Only 30.3% of individuals who indicated Mediterranean ancestry during consultation self-reported this on requisition forms. Additionally, the proportion of individuals who reported Southeast Asian but were estimated to have a different genetic ancestry was found to depend on the source of self-report. Finally, individuals who reported Latin American demonstrated a high degree of ancestral admixture. As a result, carrier rates and residual risks provided for patient decision-making are impacted if using self-reported ethnicity. CONCLUSION: Our analysis highlights the unreliability of ethnicity classification based on patient self-reports. We recommend the routine use of pan-ethnic carrier screening panels in reproductive medicine. Furthermore, the use of an ancestry model would allow better estimation of carrier rates and residual risks.

Serum progesterone trend after day of transfer predicts live birth in fresh IVF cycles.

PURPOSE: Our objective was to determine if a change in serum P4 from day of transfer (defined as day 19) to day 28 could predict live birth outcome in patients undergoing IVF. METHODS: This study was a retrospective analysis of fresh IVF cycles from 2010 to 2013 at a single center. Primary outcomes include raw and percent change in serum P4, live birth rate, missed abortion, and biochemical pregnancies. RESULTS: Our results showed an association between live birth rate and percent change in P4. Patients with a 10% or greater drop in serum P4 from day 19 to day 28 had a lower live birth rate, at 26 versus 63%. Interestingly, both groups had "normal" serum P4 levels on day 19, but patients with a 10% or greater drop had lower P4 levels than their counterparts. There was no association between percent P4 change and spontaneous abortion or biochemical pregnancy. CONCLUSIONS: This is the first study to show that percent drop in serum P4 from day of transfer to day 28 is associated with decreased rates of live birth and ongoing pregnancy in fresh IVF cycles, even despite "high or normal" P4 levels on day of transfer.

The why, the how and the when of PGS 2.0: current practices and expert opinions of fertility specialists, molecular biologists, and embryologists.

STUDY QUESTION: We wanted to probe the opinions and current practices on preimplantation genetic screening (PGS), and more specifically on PGS in its newest form: PGS 2.0? STUDY FINDING: Consensus is lacking on which patient groups, if any at all, can benefit from PGS 2.0 and, a fortiori, whether all IVF patients should be offered PGS. WHAT IS KNOWN ALREADY: It is clear from all experts that PGS 2.0 can be defined as biopsy at the blastocyst stage followed by comprehensive chromosome screening and possibly combined with vitrification. Most agree that mosaicism is less of an issue at the blastocyst stage than at the cleavage stage but whether mosaicism is no issue at all at the blastocyst stage is currently called into question. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: A questionnaire was developed on the three major aspects of PGS 2.0: the Why, with general questions such as PGS 2.0 indications; the How, specifically on genetic analysis methods; the When, on the ideal method and timing of embryo biopsy. Thirty-five colleagues have been selected to address these questions on the basis of their experience with PGS, and demonstrated by peer-reviewed publications, presentations at meetings and participation in the discussion. The first group of experts who were asked about 'The Why' comprised fertility experts, the second group of molecular biologists were asked about 'The How' and the third group of embryologists were asked about 'The When'. Furthermore, the geographical distribution of the experts has been taken into account. Thirty have filled in the questionnaire as well as actively participated in the redaction of the current paper. MAIN RESULTS AND THE ROLE OF CHANCE: The 30 participants were from Europe (Belgium, Germany, Greece, Italy, Netherlands, Spain, UK) and the USA. Array comparative genome hybridization is the most widely used method amongst the participants, but it is slowly being replaced by massive parallel sequencing. Most participants offering PGS 2.0 to their patients prefer blastocyst biopsy. The high efficiency of vitrification of blastocysts has added a layer of complexity to the discussion, and it is not clear whether PGS in combination with vitrification, PGS alone, or vitrification alone, followed by serial thawing and eSET will be the favoured approach. The opinions range from in favour of the introduction of PGS 2.0 for all IVF patients, over the proposal to use PGS as a tool to rank embryos according to their implantation potential, to scepticism towards PGS pending a positive outcome of robust, reliable and large-scale RCTs in distinct patient groups. LIMITATIONS, REASONS FOR CAUTION: Care was taken to obtain a wide spectrum of views from carefully chosen experts. However, not all invited experts agreed to participate, which explains a lack of geographical coverage in some areas, for example China. This paper is a collation of current practices and opinions, and it was outside the scope of this study to bring a scientific, once-and-for-all solution to the ongoing debate. WIDER IMPLICATIONS OF THE FINDINGS: This paper is unique in that it brings together opinions on PGS 2.0 from all different perspectives and gives an overview of currently applied technologies as well as potential future developments. It will be a useful reference for fertility specialists with an expertise outside reproductive genetics. LARGE SCALE DATA: none. STUDY FUNDING AND COMPETING INTERESTS: No specific funding was obtained to conduct this questionnaire.

Pregnancy derived from human zygote pronuclear transfer in a patient who had arrested embryos after IVF.

Nuclear transfer of an oocyte into the cytoplasm of another enucleated oocyte has shown that embryogenesis and implantation are influenced by cytoplasmic factors. We report a case of a 30-year-old nulligravida woman who had two failed IVF cycles characterized by all her embryos arresting at the two-cell stage and ultimately had pronuclear transfer using donor oocytes. After her third IVF cycle, eight out of 12 patient oocytes and 12 out of 15 donor oocytes were fertilized. The patient's pronuclei were transferred subzonally into an enucleated donor cytoplasm resulting in seven reconstructed zygotes. Five viable reconstructed embryos were transferred into the patient's uterus resulting in a triplet pregnancy with fetal heartbeats, normal karyotypes and nuclear genetic fingerprinting matching the mother's genetic fingerprinting. Fetal mitochondrial DNA profiles were identical to those from donor cytoplasm with no detection of patient's mitochondrial DNA. This report suggests that a potentially viable pregnancy with normal karyotype can be achieved through pronuclear transfer. Ongoing work to establish the efficacy and safety of pronuclear transfer will result in its use as an aid for human reproduction.

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

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.

Is it the egg or the endometrium? Elevated progesterone on day of trigger is not associated with embryo ploidy nor decreased success rates in subsequent embryo transfer cycles.

PURPOSE: The purpose of our study was to determine if progesterone (P4) values on day of trigger affect certain cycle outcome parameters, ploidy status of embryos, as well as pregnancy outcomes in the subsequent first frozen embryo transfer cycle. METHODS: Two hundred thirty-eight patients undergoing pre-gestational screening and freeze all protocol at our fertility center from 2013 to 2014 were included. Excluded patients were those whom had cancelled cycles prior to egg retrieval as well as cycles utilizing donor eggs. Once patients were identified as eligible for this study, frozen serum from the day of trigger was identified and analyzed using the Siemens Immulite 2000. Number of eggs retrieved, number of available embryos for biopsy, and number of euploid/aneuploid embryos were analyzed. The first frozen embryo transfer cycle was linked to the initial egg retrieval and outcomes including pregnancy rates, and live birth/ongoing pregnancy rates were calculated and analyzed. A discriminatory P4 value of 1.5 ng/ml was set. Group A had P4 values of less than 1.5 ng/ml and group B had P4 values greater than or equal to 1.5 ng/ml. T tests and chi-squared tests were used for statistical analysis. RESULTS: Group A had an average trigger P4 value of 0.87 +/- 0.3 and group B had an average trigger P4 of 2.1 +/- 0.8. Table 1 shows the baseline characteristics of both group A and group B. The only significant difference between the two groups was total gonadotropin dosage (IU) with a p value of 0.02 and estradiol (pg/ml) at trigger, also with a p value of 0.02 (Table 1). Number of eggs retrieved, number of embryos biopsied, number euploid/aneuploid, and non-diagnosis embryos were all non-significant. Chi-square analysis was used to compare pregnancy rates between the two groups after the first frozen embryo transfer cycle. Group A had a pregnancy rate of 72 % and Group B had a pregnancy rate of 66.7 %, which was not significant. Ongoing pregnancy/live birth rates were 65.6 % in group A and 66.67 % in group B, also not significant (Table 2). CONCLUSIONS: P4 values on day of trigger do not affect number of eggs retrieved and number of chromosomally normal embryos available for transfer in a subsequent embryo transfer cycle. Elevated P4 values (≥1.5 ng/ml) also do not affect pregnancy rates or live birth/ongoing pregnancy rates in the first subsequent frozen embryo transfer cycle.

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

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.

Clinical utilisation of a rapid low-pass whole genome sequencing technique for the diagnosis of aneuploidy in human embryos prior to implantation.

BACKGROUND: The majority of human embryos created using in vitro fertilisation (IVF) techniques are aneuploid. Comprehensive chromosome screening methods, applicable to single cells biopsied from preimplantation embryos, allow reliable identification and transfer of euploid embryos. Recently, randomised trials using such methods have indicated that aneuploidy screening improves IVF success rates. However, the high cost of testing has restricted the availability of this potentially beneficial strategy. This study aimed to harness next-generation sequencing (NGS) technology, with the intention of lowering the costs of preimplantation aneuploidy screening. METHODS: Embryo biopsy, whole genome amplification and semiconductor sequencing. RESULTS: A rapid (<15 h) NGS protocol was developed, with consumable cost only two-thirds that of the most widely used method for embryo aneuploidy detection. Validation involved blinded analysis of 54 cells from cell lines or biopsies from human embryos. Sensitivity and specificity were 100%. The method was applied clinically, assisting in the selection of euploid embryos in two IVF cycles, producing healthy children in both cases. The NGS approach was also able to reveal specified mutations in the nuclear or mitochondrial genomes in parallel with chromosome assessment. Interestingly, elevated mitochondrial DNA content was associated with aneuploidy (p<0.05), a finding suggestive of a link between mitochondria and chromosomal malsegregation. CONCLUSIONS: This study demonstrates that NGS provides highly accurate, low-cost diagnosis of aneuploidy in cells from human preimplantation embryos and is rapid enough to allow testing without embryo cryopreservation. The method described also has the potential to shed light on other aspects of embryo genetics of relevance to health and viability.

Serum progesterone levels greater than 20 ng/dl on day of embryo transfer are associated with lower live birth and higher pregnancy loss rates.

BACKGROUND: Progesterone (P4) is essential for support of the endometrium and implantation of an embryo in the normal menstrual cycle. In programed frozen embryo transfer cycles using exogenous P4 is necessary, as the endogenous production of P4 requires a functioning corpus luteum that is not present in programed cycles. To date, there is continuing debate about ideal serum estradiol and P4 values in frozen embryo transfer cycles. METHODS: Patients underwent single euploid embryo frozen transfer cycles from 2010 to 2013 at a single large academic center. Patients using donor oocytes and patients with changes in progesterone dose during the cycles in question were excluded. All cycles were programed and intramuscular P4 was used exclusively. Only patients administering the same daily dose of P4 throughout the cycle were included (N = 213 patients). Main outcomes were ongoing pregnancy/live birth rates (OPR/LBR), clinical pregnancy rates (CPR), and spontaneous abortions/biochemical pregnancies. CPR was defined by the presence of a sac on 1st trimester ultrasound. Missed abortions were calculated per pregnancy with a sac. Receiver operator characteristic curves (ROC curves) and chi-squared tests were performed for statistical analysis. RESULTS: Two groups based on day 19 P4 levels were compared (group A, P4 < 20 ng/ml; group B, P4 > 20 ng/ml). OPR/LBRs were 65 vs. 49 %, group A vs. B, p value = 0.02, RR = 1.33 (1.1-1.7). Missed abortion and biochemical rates were higher in group B as opposed to group A, 27 vs. 12 %, p = 0.01, RR = 0.45(0.24-0.86). When P4 was stratified into five groups based on nanogram per milliliter of progesterone on day 19 (10-15, 15-20, 20-30, 30-40, and >40), there was a trend downward in OPR/LBR (70, 62, 52, 50, and 33 %, respectively). There was also an increase in missed abortion/biochemical rates (7, 15, 27, 32, and 20 %, respectively). Multiple logistic regression showed an increase in OPR/LBR when accounting for age, day 2 FSH, weight, number of embryos biopsied, and number of euploid embryos. CONCLUSION: P4 levels >20 ng/ml on the day of transfer (during frozen single euploid embryo transfer cycles) were associated with decreased OPR/LBR.

A greater number of euploid blastocysts in a given cohort predicts excellent outcomes in single embryo transfer cycles.

PURPOSE: This multicentered retrospective study analyzed whether the quantity of euploid blastocysts in a given cohort after comprehensive chromosomal screening can be used to identify candidates for single embryo transfer. METHODS: Blastocysts from 437 patients underwent trophectoderm biopsy followed by array comparative genomic hybridization. Embryos were then selected for single or double embryo transfer. The number of euploid blastocysts produced and transferred for each patient was recorded, as was clinical pregnancy rate and multiple gestation rate. RESULTS: In patients with ≤ 3 euploid blastocysts, clinical pregnancy rate was higher in double, compared to single embryo transfers. However, in patients with ≥ 4 euploid blastocysts, clinical pregnancy rate was not reduced with single embryo transfer was performed, whereas the multiple gestation rate was greatly reduced. CONCLUSIONS: Size of the euploid embryo cohort is a marker for success in single embryo transfer cycles. Patients who produce at least four euploid blastocysts are outstanding candidates for single embryo transer.

Single thawed euploid embryo transfer improves IVF pregnancy, miscarriage, and multiple gestation outcomes and has similar implantation rates as egg donation.

PURPOSE: The objective of our study was to determine if trophectoderm biopsy, vitrification, array-comparative genomic hybridization and single thawed euploid embryo transfer (STEET) can reduce multiple gestations and yield high pregnancy and low miscarriage rates. METHODS: We performed a retrospective observational study comparing single thawed euploid embryo to routine age matched in vitro fertilization (IVF) patients that underwent blastocyst transfer from 2008 to 2011 and to our best prognosis group donor oocyte recipients (Donor). Our main outcome measures were implantation rate, clinical pregnancy rate, spontaneous abortion rate and multiple gestation rate. RESULTS: The STEET group had a significantly higher implantation rate (58 %, 53/91) than the routine IVF group (39 %, 237/613) while the Donor group (57 %, 387/684) had a similar implantation rate. The clinical pregnancy rates were not statistically different between the STEET and IVF groups. However, the multiple gestation rate was significantly lower in the STEET group (STEET 2 % versus IVF 34 %, Donor 47 %). CONCLUSIONS: STEET results in a high pregnancy rate, low multiple gestation rate and miscarriage rates. Despite the older age of STEET patients and transfer of twice as many embryos, the implantation rate for STEET was indistinguishable from that for egg donation. STEET offers an improvement to IVF, lowering risks without compromising pregnancy rate.

Validation of array comparative genome hybridization for diagnosis of translocations in preimplantation human embryos.

Fluorescent in-situ hybridization (FISH) for preimplantation genetic diagnosis (PGD) of structural chromosome abnormalities has limitations, including carrier testing, inconclusive results and limited aneuploidy screening. Array comparative genome hybridization (CGH) was used in PGD cases for translocations. Unbalances could be identified if three fragments were detectable. Smallest detectable fragments were ∼6 Mbp and ∼5 Mbp for blastomeres and trophectoderm, respectively. Cases in which three or more fragments were detectable by array CGH underwent PGD by FISH and concordance was obtained in 53/54 (98.1%). The error rate for array CGH was 1.9% (1/54). Of 402 embryos analysed, 81 were normal or balanced, 92 unbalanced but euploid, 123 unbalanced and aneuploid and 106 balanced but aneuploid. FISH with additional probes to detect other aneuploidies would have missed 28 abnormal embryos in the reciprocal group and 10 in the Robertsonian group. PGD cases (926) were retrospectively reviewed for reciprocal translocations performed by FISH to identify which could have been analysed by array CGH. This study validates array CGH in PGD for translocations and shows that it can identify all embryos with unbalanced reciprocal and Robertsonian translocations. Array CGH is a better approach than FISH since it allows simultaneous screening of all chromosomes for aneuploidy.

Characteristics of chromosomal abnormalities diagnosed after spontaneous abortions in an infertile population.

PURPOSE: To estimate the prevalence of chromosomally abnormal related miscarriages in an infertile population. METHODS: Retrospective analysis of cytogenetics obtained by chorionic villi harvesting of the first miscarriage cycle of infertile patients at our center from 2001-2010 were reviewed. Abnormal results were characterized as trisomy, monosomy X, structural, or other. Age, # of eggs, #2PN, # embryos transferred, day of transfer, and performance of intracytoplasmic sperm injection (ICSI) were recorded. RESULTS: In a study population of 299 patients with a mean age of 38.0 ± 4.5 y, 276(92 %) patients had some form of assisted reproductive technologies (ART), and 244(82 %) had IVF. Of all results, 71.6 % had an abnormal karyotype. Patients with abnormal cytogenetics were older (38.6 ± 4.1 vs. 36.3 ± 4.9, p < 0.001), and more likely to have a day 3 transfer (age < 38 ( 20.7 %) vs. age 38 (46.3 %), p = <0.001) with more embryos transferred (3.0 ± 1.2, vs. 2.3 ± 0.9, p < 0.001). The performance of ICSI did not affect the rate of cytogenetically abnormal products of conception (ICSI 68.3 % vs. no ICSI 70.7 %). In comparing patients, monosomy X was more common in <38 y. Rates of trisomy, although not statistically significant, were higher in older patients. CONCLUSIONS: The classic associations between advancing age and chromosomal abnormalities, and younger age and monosomy X, are affirmed in our infertile population. There was no increase in chromosomal abnormalities in cycles where ICSI was performed. Older patients are more likely to have day 3 transfers and more embryos transferred. Our chromosomal abnormality rates are higher than classic estimates but comparable to recent studies. The limitation of this study was a lack in uniformity among practitioners in recommending all patients have a Dilation and Curettage (D&C) at time of diagnosis. Such information may serve to improve the counseling of patients after miscarriage.

Supernumerary blastocyst cryopreservation: a key prognostic indicator for patients opting for an elective single blastocyst transfer (eSBT).

OBJECTIVE: To determine if patients, less than 40 years of age with or without day 5 cryopreservation (d5 cryo), compromise their pregnancy rate (PR) by choosing an eSBT. DESIGN: Retrospective analysis SETTING: University IVF center PATIENTS: 2,203 non-donor fresh IVF cycles in women <40 years of age from January 2004 to January 2010. INTERVENTIONS: None MAIN OUTCOME MEASURE(S): Eggs retrieved, Embryos cryopreserved, Implantation Rates, Clinical Pregnancy Rates, Live Birth Rates, Spontaneous Abortion Rates RESULTS: Pregnancy outcomes in women <40 years with or without d5 cryo were compared according to whether patients underwent an eSBT versus a 2BT in non-donor fresh IVF cycles. Overall, eSBT was associated with elimination of twinning while maintaining a high clinical pregnancy rate in both groups with d5 cryo (75 % eSBT versus 72 % 2BT) and groups without d5 cryo (48 % eSBT versus 56 % 2BT). CONCLUSIONS: In this study, patients <40 years of age have eliminated twinning by electively choosing to transfer a single blastocyst without compromising their PR if embryos are available for d5 cryo, and suffer only a non-statistically significant drop in their PR if there are no embryos available for d5 cryo in exchange for the benefit of eliminating the obstetrical risk of twinning.

Disaster preparedness in assisted reproductive technology.

The American Society for Reproductive Medicine compels centers providing reproductive medicine care to develop and implement an emergency preparedness plan in the event of a disaster. Reproductive care is vulnerable to disruptions in energy, transportation, and supply chains as well as may have potential destructive impacts on infrastructure. With the relentless progression of events related to climate change, centers can expect a growing number of such disruptive events and must prepare to deal with them. This article provides a case study of the impact of Hurricane Sandy on one center in New York City and proposes recommendations for future preparedness and mitigation.