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To evaluate potential variation in the euploid blastocyst rate and live birth rate (LBR) per single frozen euploid blastocyst transfer, among 4 unique United States reproductive genetics laboratories. Analyses were limited to blastocysts derived from vitrified donor oocytes, to minimize variation in oocyte quality.Retrospective cohort study from 2016 to 2020.Donor Egg Bank Database.Patients undergoing in vitro fertilization with donor oocytes. We excluded patients with uterine factor, male factor, or surgically extracted sperm. Only healthy women34 years old were accepted as oocyte donors.Next generation sequencing platforms for chromosomal analysis MAIN OUTCOME MEASURE(S): Euploid blastocyst rate and LBR per euploid transfer. Secondary outcomes included the rate of aneuploidy, mosaic calls, biochemical pregnancy loss, and miscarriage rate.A total of 2,633 embryos were included. Four laboratories had200 embryos tested. Euploid blastocyst rate was significantly higher in laboratory A (73.6%) vs. B (63.3%), C (60.9%), and D (52.3%). Mosaic rate was significantly lower for Laboratories B (2.8%) and C (5.5%) vs. Laboratories A (9.9%) and D (11.5). The LBR was significantly higher in laboratory A (58.73%) vs. laboratory D (47.3%). There were no significant differences in the implantation or miscarriage rate among laboratories.In this large study, controlling for oocyte quality, some preimplantation genetic testing for aneuploidy (PGT-A) laboratories report a significantly higher euploid blastocyst rate with concurrent higher LBR. This type of comparison is important as it provides insight into the role of the PGT-A process in outcomes. Further research is needed to evaluate the differences in laboratory techniques and bioinformatic algorithms accounting for variable outcomes across PGT-A laboratories.

Objective To determine whether follicle flushing during oocyte retrieval improves live birth or secondary outcomes in assisted reproductive technology (ART). Design Systematic review and meta-analysis. Setting Not applicable. Patient(s) Women undergoing ART using autologous gametes. Intervention(s) A systematic search of PubMed, EMBASE, Cochrane Database, and Web of Science for randomized controlled trials comparing follicle flushing to direct aspiration during oocyte retrieval published in English between 1989 to 2020. Main Outcome Measure(s) Live birth as primary outcome, and clinical and ongoing pregnancy, total and mature metaphase II (MII) oocytes retrieved, and operating time as secondary outcomes. Result(s) Eleven studies were included totaling 1,178 cases. No difference in live birth was demonstrated between follicle flushing and direct aspiration. Clinical pregnancy and ongoing pregnancy were not improved with flushing. Total oocyte and MII yield were lower with flushing compared with direct aspiration. Procedure time was increased with flushing by 2 minutes in poor responders and 9 minutes in normal responders. Other sensitivity analyses did not demonstrate any changes, except the difference in MII yield was no longer statistically significant. Conclusion(s) Follicle flushing during oocyte retrieval increases procedure time and does not improve live birth or secondary ART outcomes. Randomized data do not support the use of follicle flushing as an intervention in ART.

To compare clinical and ongoing pregnancy after natural cycle (NC) intrauterine insemination (IUI) versus ovarian stimulation (OS) IUI in ovulatory women undergoing therapeutic donor insemination (TDI).Retrospective cohort.Single infertility center.A total of 76,643 IUI cycles in patients treated with intrauterine insemination were examined. Women undergoing TDI in the absence of diagnosed female factor infertility were included.NC TDI or OS TDI with either clomiphene citrate or letrozole.Clinical and ongoing pregnancies were analyzed by generalized estimating equations adjusting for age, body mass index, total motile sperm at time of insemination and cycle number. Ongoing multiple gestations were examined as a secondary outcome.Six thousand one hundred ninety-two TDI cycles from 2,343 patients (711 patients without repeated IUI cycles) met inclusion criteria and were available for analysis (3,837 NC and 2,355 OS). There was no difference in mean age between the two groups (NC, 34.2 years vs. OS, 34.3 years). Probability of clinical and ongoing pregnancy was higher in the OS cohort compared with the NC cohort (OS, 22.4% vs. NC, 18.7% and OS, 15.4% vs. NC, 14.9%, respectively). However, OS significantly increased ongoing multiple gestations (OS, 10.8% vs. NC, 2.4%).Ovarian stimulation in TDI cycles resulted in a4% increase in clinical and1% increase in ongoing pregnancy, and more than fourfold increase in ongoing multiple gestations. Natural cycle IUI should be considered as a first-line treatment for ovulatory women who need donor insemination.

Since the advent of ART, technology has continuously evolved to improve embryology and pregnancy outcomes. However, not all technologies that are integrated into practice have convincing evidence of clinical effectiveness, and they often increase the financial burden of fertility care. We discuss here a selection of commonly utilized IVF “add-ons” and discuss the existing evidence for their utility. The procedures included in this review are time-lapse imaging of embryos, assisted hatching, EmbryoGlue, sperm DNA testing, egg activation with calcium ionophore, endometrial receptivity array, and physiological intracytoplasmic sperm injection (PICSI). While there is rather limited supporting evidence for nearly all IVF add-ons that we reviewed, there is strong demand from patients, physicians, and the biotechnology industry to continue further research and development in this arena. We propose that all add-on procedures should provide true efficacy for the patient, and reproductive endocrinologists should inform patients of the costs and benefits of utilizing various technologies before they undergo treatment. In the future, add-ons that show clear evidence of efficacy and justifiable cost should be incorporated into routine practice, while others that do not meet these criteria should be phased out entirely.

A crisis is occurring in that reproductive endocrinologists are not doing the surgeries that are a part of their discipline. We list those procedures as a blueprint for training reproductive endocrinologists.

Research question Is ovulation suppression with progestins, requiring a freeze-all approach and subsequent frozen embryo transfer resulting from progestenic endometrial changes, cost-effective compared with gonadotropin releasing hormone analogues (GnRH) during assisted reproduction cycles. Design Cost-effectiveness analysis derived from a PubMed literature search of average US costs of GnRH agonist and antagonist IVF cycles. Results In all fresh IVF cycle models, progestin cycles were more expensive owing to the additional costs of increased gonadotropin use, embryo freezing and subsequent frozen embryo transfer (FET). The average cost per live birth with progestins ($32,466–$56,194) was higher than fresh IVF cycles with short (flare) GnRH agonist ($4,447–$12,797 higher) and GnRH antagonist ($1,542–$9,893 higher). When analyzing an initial embryo transfer plus additional FET in patients not initially pregnant, progestin cycles were still more expensive per live birth compared with conventional protocols. When planned freeze only cycles were analyzed, progestins became more cost-effective per live birth compared with antagonist cycles ($2,079 lower) but remained more expensive than short agonist cycles ($823 more expensive). Conclusions Ovulation inhibition in IVF using progestins requires a freeze-only approach of embryos, and thus progestin use was not cost-effective compared with fresh embryo transfer cycles. Progestins, however, may be cost-effective compared with GnRH antagonist in planned freeze only cycles such as in preimplantation genetic testing or fertility preservation.

Melvin Taymor's daughter, Julie Taymor, directed the musical version of The Lion King, which won six Tony Awards. Known for her revolutionary staging, she became the first woman to be awarded a Tony for Best Direction of a Musical.

Objective To determine whether subfertility in patients with endometriosis is due to impaired endometrial receptivity by comparing pregnancy and live-birth outcomes in women with endometriosis versus two control groups without suspected endometrial factors: noninfertile patients who underwent assisted reproduction to test embryos for a single-gene disorder and couples with isolated male factor infertility. Design Retrospective cohort. Setting Multicenter private practice. Patient(s) All patients aged 24 to 44 years undergoing euploid frozen blastocysts transfer from January 2016 through March 2018. Intervention(s) None. Main Outcome Measure(s) Live birth, clinical pregnancies, pregnancy losses, and aneuploid rates in preimplantation genetic testing for aneuploidy cycles. Result(s) The analysis included 459 euploid frozen embryo transfer cycles among 328 unique patients. There were no differences in clinical pregnancy, pregnancy loss, or live-birth rates in patients with endometriosis compared with both control groups. The aneuploidy rates were lowest in the preimplantation genetic testing for monogenic disorders cohort, and the endometriosis patients had aneuploidy rates similar to those of the male factor infertility patients. Conclusion(s) It is unclear whether endometriosis primarily affects in vitro fertilization outcomes via oocyte quality or the endometrium. By controlling for embryo quality using euploid frozen embryo transfer cycles, we found no difference in pregnancy outcomes in patients with endometriosis compared with patients undergoing treatment for male factor infertility and noninfertile patients.

Science, propelled forward by noble aspirations and, at times, human hubris, has the capacity to affect lives and alter the world in unanticipated ways. Even seemingly minor discoveries have repeatedly proven to have far reaching implications that experts within their respective fields could not have predicted. Nuclear technology is both a source of energy and a potential means of annihilation. The internet has both seamlessly connected the world but has also opened society to the misuse and manipulation of information. Both exemplify how new technologies have the potential for positive and negative outcomes that often go beyond what was initially intended. This is not a fault of science and innovation but rather an inherent occupational hazard as new discoveries exist within a gray zone between ignorance and comprehension. These gaps in our knowledge can only be filled over time as our knowledge expands. Innovations that were once seen as fringe, over time, become mainstream and that which was once revolutionary becomes a part of everyday life. Occasionally, a scientific advancement comes along that challenges societal norms and causes us to question what is feasible, acceptable, and ethical. Nowhere in the twenty-first century has this been more evident than within the fields of genetics and genetic engineering. As we gain a deeper understanding of the source code of life, from individual base pairs to epigenetic influences, the implications of new discoveries will go far beyond curing genetic diseases, and the possibilities will be endless. Reproductive endocrinology and infertility (REI) specialists utilize many tools including expanded carrier screening, preimplantation genetic testing, and embryo selection and have become some of the experts at the forefront of the ongoing genetic revolution. Now more than ever, there is a need for REIs to be trained in the fundamentals of genetics, exposed to novel gene sequencing and editing techniques, and involved in the coming ethical discussions in order to be prepared for the genetically engineered future.

Premature progesterone (P) elevation was commonly seen in IVF prior to the utilization of GnRH analogues for suppression of endogenous gonadotropin release. The cause and effect of premature P elevation has finally been better elucidated in the past decade. Although still occurring in 5-38% of all IVF cycles, the adverse effects of premature P elevation on pregnancy outcomes are now well known.

PURPOSE: To describe controlled ovarian stimulation (COS) in a population of women with GATA2 deficiency, a genetic bone marrow failure syndrome, prior to allogeneic hematopoietic stem cell transplant METHODS: This is a retrospective case series of nine women with GATA2 deficiency who underwent oocyte preservation at a research institution. Main outcomes measured include baseline fertility characteristics ((antimullerian hormone (AMH) and day 3 follicle-stimulating hormone (FSH) and estradiol (E2)) and total doses of FSH and human menopausal gonadotropins (HMG), E2 on day of trigger, and total number of metaphase II oocytes retrieved. RESULTS: The mean age was 24 years [16–32], mean AMH was 5.2 ng/mL [0.7–10], and day 3 mean FSH was 5.1 U/L [0.7–8.1], and E2 was 31.5 pg/mL [

Objective: Use of frozen sperm in non-male factor infertility is often needed in donor cycles. Most studies to date examining outcomes of fresh vs frozen sperm are unable to control for oocyte quality. Studies examining sibling oocytes represent a unique model to control for oocyte quality. A recent small study using this model found worse outcomes in the frozen group. We sought to evaluate, in a large cohort, if fresh and frozen ejaculated sperm are associated with similar pregnancy outcomes by analyzing paired donor egg recipient (DER) cycles. Materials and Methods: Retrospective cohort study from 2016-2019 at a large fertility center. Patients who underwent DER cycles where oocytes were split between two couples and one couple used fresh sperm and the other used frozen sperm were included. All patients with uterine factor, male factor or surgically obtained sperm were excluded. Primary outcome was Ongoing pregnancy/Live birth rate (OPR). Secondary outcome included clinical pregnancy rate (CPR) and miscarriage rate. GEE analysis was performed to control for confounding factors and donors providing oocytes to both study cohorts. Results: 1255 donor oocytes cycles were screened. A total of 205 unique oocytes donors were identified with oocytes inseminated with discrepant sperm in different recipient cycles. There were 698 recipient transfer cycles, 405 fresh and 293 frozen. Cohorts were similar in baseline characteristics (table 1). There were no differences in OPR/LBR with fresh vs frozen sperm (53.6% vs 55.6%, p=0.7) or clinical pregnancies (66.4% vs 63.5%, p=0.4). Spontaneous miscarriage (

STUDY QUESTION Do donor oocyte recipients benefit from preimplantation genetic testing for aneuploidy (PGT-A)? SUMMARY ANSWER PGT-A did not improve the likelihood of live birth for recipients of vitrified donor oocytes, but it did avoid embryo transfer in cycles with no euploid embryos. WHAT IS KNOWN ALREADY Relative to slow freeze, oocyte vitrification has led to increased live birth from cryopreserved oocytes and has led to widespread use of this technology in donor egg IVF programs. However, oocyte cryopreservation has the potential to disrupt the meiotic spindle leading to abnormal segregation of chromosome during meiosis II and ultimately increased aneuploidy in resultant embryos. Therefore, PGT-A might have benefits in vitrified donor egg cycles. In contrast, embryos derived from young donor oocytes are expected to be predominantly euploid, and trophectoderm biopsy may have a negative effect relative to transfer without biopsy. STUDY DESIGN, SIZE, DURATION This is a paired cohort study analyzing donor oocyte-recipient cycles with or without PGT-A performed from 2012 to 2018 at 47 US IVF centers. PARTICIPANTS/MATERIALS, SETTING, METHODS Vitrified donor oocyte cycles were analyzed for live birth as the main outcome measure. Outcomes from donors whose oocytes were used by at least two separate recipient couples, one couple using PGT-A (study group) and one using embryos without PGT-A (control group), were compared. Generalized estimating equation models controlled for confounders and nested for individual donors contributing to both PGT-A and non-PGT-A cohorts, enabling a single donor to serve as her own control. MAIN RESULTS AND THE ROLE OF CHANCE In total, 1291 initiated recipient cycles from 223 donors were analyzed, including 262 cycles with and 1029 without PGT-A. The median aneuploidy rate per recipient was 25%. Forty-three percent of PGT-A cycles had only euploid embryos, whereas only 12.7% of cycles had no euploid embryos. On average 1.09 embryos were transferred in the PGT-A group compared to 1.38 in the group without PGT-A (P LIMITATIONS, REASONS FOR CAUTION Pooled clinical data from 47 IVF clinics introduced PGT-A heterogeneity as genetic testing were performed using different embryology laboratories, PGT-A companies and testing platforms. WIDER IMPLICATIONS OF THE FINDINGS PGT-A testing in donor oocyte-recipient cycles does not improve the chance for live birth nor decrease the risk for miscarriage in the first transfer cycle but does increase cost and time for the patient. Further studies are required to test if our findings can be applied to the young infertility patient population using autologous oocytes. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

Objective To estimate the effect of daily 81 mg low-dose aspirin (LDA) on menstrual cycle length and hormone profiles. Design Secondary analysis of a trial evaluating the effect of daily LDA or placebo on live birth among women with one or two previous pregnancy losses. Setting University medical centers. Patient(s) A total of 915 regularly menstruating women who had at least one menstrual cycle (3,190 total cycles) in which pregnancy did not occur. Intervention(s) Randomized allocation to LDA versus placebo. Main Outcome Measure(s) Menstrual cycle length and follicular and luteal phases were measured. Urinary pregnanediol glucuronide, follicle-stimulating hormone, luteinizing hormone, and estrone-3-glucuronide were assessed up to six times during the first two cycles. Generalized estimating equations estimated relative risk of short ( 75th percentile: ≥32 days) versus normal cycle length. Linear mixed models estimated mean hormone level differences with weights used to account for multiple cycles contributed per participant. Result(s) There were no significant differences in total menstrual cycle, follicular phase, or luteal phase length between LDA and placebo groups. LDA posed no greater risk of having a short versus normal-length or long versus normal-length follicular phase, or having a short versus normal-length or long versus normal-length luteal phase. There were no significant differences in hormone levels across the menstrual cycle between the LDA and placebo groups. Conclusion(s) Daily LDA use did not result in any changes to menstrual cycle, follicular phase, or luteal phase length or hormone levels across the menstrual cycle compared with placebo. Clinical Trial Registration Number NCT00467363

Objectives To identify uterine measurements that are reliable and accurate to distinguish between T-shaped and normal/arcuate uterus, and define T-shaped uterus, using Congenital Uterine Malformation by Experts (CUME) methodology, which uses as reference standard the decision made most often by several independent experts. Methods This was a prospectively planned multirater reliability/agreement and diagnostic accuracy study, performed between November 2017 and December 2018, using a sample of 100 three-dimensional (3D) datasets of different uteri with lateral uterine cavity indentations, acquired from consecutive women between 2014 and 2016. Fifteen representative experts (five clinicians, five surgeons and five sonologists), blinded to each others' opinions, examined anonymized images of the coronal plane of each uterus and provided their independent opinion as to whether it was T-shaped or normal/arcuate; this formed the basis of the CUME reference standard, with the decision made most often (i.e. that chosen by eight or more of the 15 experts) for each uterus being considered the correct diagnosis for that uterus. Two other experienced observers, also blinded to the opinions of the other experts, then performed independently 15 sonographic measurements, using the original 3D datasets of each uterus. Agreement between the diagnoses made by the 15 experts was assessed using kappa and percent agreement. The interobserver reliability of measurements was assessed using the concordance correlation coefficient (CCC). The diagnostic test accuracy was assessed using the area under the receiver-operating-characteristics curve (AUC) and the best cut-off value was assessed by calculating Youden's index, according to the CUME reference standard. Sensitivity, specificity, negative and positive likelihood ratios (LR- and LR+) and post-test probability were calculated. Results According to the CUME reference standard, there were 20 T-shaped and 80 normal/arcuate uteri. Individual experts recognized between 5 and 35 (median, 19) T-shaped uteri on subjective judgment. The agreement among experts was 82% (kappa = 0.43). Three of the 15 sonographic measurements were identified as having good diagnostic test accuracy, according to the CUME reference standard: lateral indentation angle (AUC = 0.95), lateral internal indentation depth (AUC = 0.92) and T-angle (AUC = 0.87). Of these, T-angle had the best interobserver reproducibility (CCC = 0.87 vs 0.82 vs 0.62 for T-angle vs lateral indentation depth vs lateral indentation angle). The best cut-off values for these measurements were: lateral indentation angle = 7 mm (sensitivity, 95%; specificity, 77.5%; LR+, 4.2; LR-, 0.06) and T-angle = 7 mm, lateral indentation angle

Objective To determine if transferring a lower-quality embryo with a good-quality blastocyst is detrimental, given that evidence suggests that embryos can signal the endometrium and that embryo quality may affect negatively endometrial receptivity. Design Retrospective cohort study. Setting In vitro fertilization center. Intervention(s) Single- versus double-embryo transfer. Patient(s) Patients with a double-embryo transfer of a good-quality blastocyst plus a lower-quality blastocyst, early blastocyst, or morula were compared with patients receiving a single good-quality blastocyst. Main Outcome Measure(s) Live birth, multiple gestation. Result(s) In this study, 4,640 in vitro fertilization cycles were analyzed. In none of the analyses did transferring a second lower-quality embryo negatively affect birth rate. In the primary analysis, transferring a second lower-quality embryo increased live birth by 10% and the multiple birth rate by 15%. The addition of a fair- or poor-quality blastocyst or early blastocyst markedly increased the twin birth rate by 22%–27% with an 8%–12% increase in live birth. The addition of a morula did not increase live birth but resulted in 12% more multiples. In women younger than 38 years, adding a lower-quality embryo increased the birth rate by 7% but resulted in 18% increase in multiples. In women 38 years or older, adding a lower-quality embryo increased the live birth rate by 9% with a 15% increase in multiples. Conclusion(s) Addition of a lower-quality embryo does not have a detrimental effect on a good-quality blastocyst and results in a small increase in live births. However, this is at the expense of a marked increase in the likelihood of multiple gestations.

The current treatment for Asherman syndrome is limited and not very effective. The aim of this review is to summarize the most recent evidence for stem cells in the treatment of Asherman syndrome. The advent of stem cell therapy has propagated experimentation on mice and humans as a novel treatment. The consensus is that the regenerative capacity of stem cells has demonstrated improved outcomes in terms of fertility and fibrosis in both mice and humans with Asherman syndrome. Stem cells have effects on tissue repair by homing to the injured site, recruiting other cells by secreting chemokines, modulating the immune system, differentiating into other types of cells, proliferating into daughter cells, and potentially having antimicrobial activity. The studies reviewed examine different origins and administration modalities of stem cells. In preclinical models, therapeutic systemic injection of stem cells is more effective than direct intrauterine injection in regenerating the endometrium. In conjunction, bone marrow-derived stem cells have a stronger effect on uterine regeneration than uterine-derived stem cells, likely due to their broader differentiation potency. Clinical trials have demonstrated the initial safety and effectiveness profiles of menstrual, bone marrow, umbilical cord, and adipose tissue-derived stem cells in resumption of menstruation, fertility outcomes, and endometrial regeneration.

"An object in motion tends to remain in motion along a straight line unless acted upon by an outside force." —Isaac Newton

Since Barker's publication of “The fetal and infant origins of adult disease” in 1990, significant emphasis has been placed on the intrauterine environment and its effect on adult disease. Historical events such as the Dutch Famine and the 1918 Flu Pandemic have provided organic data about the epigenetic changes that can result from famine, infection, and stress. Mechanisms that allow for intrauterine survival may predispose to adult disease states when the fetus enters a world of abundance. As the field of in vitro fertilization (IVF) has developed and evolved, little attention has been paid to subtle yet significant differences in IVF offspring. Offspring of assisted reproductive technology (ART) have been reported to have higher rates of preterm birth, abnormal fetal size, and birth defects. It is clear that epigenetic modifications may begin as early as pre-pregnancy. These differences are likely not attributable to one factor in the IVF process. Each variable likely plays a subtle role in the epigenetic manipulation of the embryo. Thus, moving forward, physicians should practice with heightened determination to follow the long-term outcomes of the offspring of ART in an effort to further modify and perfect the field.

The aim of this study was to evaluate if premature progesterone elevation on the last day of assisted reproduction technique stimulation contributes to racial disparities in IVF outcome. A total of 3289 assisted reproduction technique cycles were evaluated in Latino, Asian, African American, and white women. Live birth was more likely in white women (42.6%) compared with Asian (34.8%) and African American women (36.3%), but was similar to Latino women (40.7%). In all racial groups, progesterone was negatively associated with live birth and the negative effect of progesterone persisted when adjusting for confounders. Although the effect of elevated progesterone was similar in all racial groups, the prevalence of elevated progesterone differed. Progesterone > 1.5 ng/ml occurred in only 10.6% of cycles in white women compared with 18.0% in Latino and 20.2% in Asian women. Progesterone > 2 ng/ml occurred in only 2.3% of cycles in white women compared with 6.3% in Latino, 5.9% in Asian and 4.4% in African American women. The increased prevalence of premature elevated progesterone persisted when controlling for IVF stimulation parameters. In conclusion, premature progesterone elevation had a negative effect on live birth in all racial groups studied. The prevalence of elevated progesterone was higher in racial minorities.