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Background: Genomic insights in settings where tumour sample sizes are limited to just hundreds or even tens of cells hold great clinical potential, but also present significant technical challenges. We previously developed the DigiPico sequencing platform to accurately identify somatic mutations from such samples., Results: Here, we complete this genomic characterisation with copy number. We present a novel protocol, PicoCNV, to call allele-specific somatic copy number alterations from picogram quantities of tumour DNA. We find that PicoCNV provides exactly accurate copy number in 84% of the genome for even the smallest samples, and demonstrate its clinical potential in maintenance therapy., Conclusions: PicoCNV complements our existing platform, allowing for accurate and comprehensive genomic characterisations of cancers in settings where only microscopic samples are available., (© 2023. The Author(s).)

Hyperprolactinemia is common among infertile patients, with up to 15%-20% of women with oligomenorrhea having hyperprolactinemia. Suppression of the hypothalamic-pituitary-gonadal axis via inhibition of pulsatile gonadotropin releasing hormone because of hyperprolactinemia is a common endocrine etiology of infertility. There are 3 forms of human prolactin (PRL): monomeric PRL, dimeric PRL, and macro-PRL. Also known as big-big PRL, macro-PRL has a molecular weight >150 kDa and normally comprises 5%-10% of circulating PRL. When the predominant form of circulating PRL is macro-PRL, macroprolactinemia is diagnosed. Among patients with hyperprolactinemia, 10%-46% have macroprolactinemia. Patients with macroprolactinemia are at risk of unnecessary pituitary imaging and treatment with dopamine agonists if not correctly diagnosed. Given the high prevalence of macroprolactinemia among patients with elevated PRL levels and the different management of patients with macroprolactinemia vs true monomeric hyperprolactinemia, all patients with persistently elevated PRL levels should be screened for macro-PRL., (© 2023 The Authors.)

Purpose: The purpose of this study was to determine the impact of body mass index (BMI) on euploidy rates for in vitro fertilization (IVF) cycles with preimplantation genetic testing (PGT) utilizing primarily next-generation sequencing (NGS)., Methods: This retrospective cohort study included women aged ≤ 45 years who underwent IVF/PGT between September 2013 and September 2020 at a single university-affiliated fertility center. The primary outcome was euploidy rate. Secondary outcomes included peak serum estradiol (E2), number of oocytes retrieved, oocyte maturation rate, high-quality blastulation rate, clinical loss rate (CLR), clinical pregnancy rate (CPR), and ongoing pregnancy/live birth rate (OPR/LBR)., Results: The study included 1335 IVF cycles that were stratified according to BMI (normal, n = 648; overweight, n = 377; obese, n = 310). The obese group was significantly older with significantly lower baseline FSH, peak E2, high-quality blastulation rate, and number of embryos biopsied than the normal group. Overall euploidy rates were not significantly different between BMI groups (normal 36.4% ± 1.3; overweight 37.3% ± 1.8; obese 32.3% ± 1.8; p = 0.11), which persisted after controlling for covariates (p = 0.82) and after stratification of euploidy rate by age group and by number of oocytes retrieved per age group. There were no significant differences in CLR, CPR, and OPR/LBR across BMI groups., Conclusions: Despite a lower high quality blastulation rate with obesity, there is not a significant difference in euploidy rates across BMI groups in women undergoing IVF/PGT., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To evaluate and compare pregnancy outcomes between letrozole ovulation induction, natural, and programmed frozen-thawed embryo transfer (FET) cycles in a population based in the United States., Design: Retrospective cohort study., Setting: Single university-affiliated infertility practice., Patient(s): A total of 3,148 FET cycles consisting of patients aged ≤45 years transferring blastocysts that were created from autologous oocytes between January 2015 and July 2021., Intervention(s): None., Main Outcome Measure(s): The primary outcome was the ongoing pregnancy rate (OPR) or live birth rate (LBR). The secondary outcomes included clinical pregnancy and clinical loss rates (CLRs)., Result(s): The OPR/LBR was higher among letrozole FETs than among programmed FETs (adjusted risk ratio [aRR] 1.11, 95% confidence interval [CI] 1.02-1.21) but comparable to natural FETs (aRR 1.05, 95% CI 0.96-1.14). The OPR/LBR was comparable between natural and programmed FETs (aRR 1.06, 95% CI 0.99-1.13). The CLR was lower in the natural FET group than in the programmed FET group (aRR 0.62, 95% CI 0.46-0.84). There were no differences in CLRs between letrozole and programmed FETs and between letrozole and natural FETs. Among ovulatory women, the OPR/LBR among letrozole FETs was higher than that among programmed FETs (aRR 1.16, 95% CI 1.05-1.28). The CLR among ovulatory women was significantly lower in both letrozole FETs (aRR 0.44, 95% CI 0.22-0.87) and natural FETs (aRR 0.59, 95% CI 0.43-0.80) than in programmed FETs. Among anovulatory women, the OPR/LBR in the letrozole FET group was similar to that in the programmed FET group (aRR 0.95, 95% CI 0.79-1.13)., Conclusion(s): Letrozole and natural FET clinical outcomes were improved compared with programmed FET outcomes., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate embryologic outcomes among paired IVF cycles in which a microfluidics chip was utilized compared to density gradient centrifugation for sperm processing., Methods: This was a retrospective cohort study of 88 paired IVF cycles from patients aged 18-44 years at a university-affiliated IVF center. Fresh cycles from patients undergoing ICSI with sperm processed by a microfluidics chamber (microfluidics cycles) were compared to the same patients' previous ICSI cycles in which sperm was processed via density gradient centrifugation (control cycles). The primary outcome was the high-quality blastulation rate., Results: High-quality blastulation rate per oocyte retrieved was significantly higher in the microfluidics group compared to the control group (21.1% versus 14.5%, p < 0.01) as was the blastulation rate per 2PN (42.7% versus 30.8%, p < 0.01). Fertilization rates were significantly higher in the microfluidics group. The euploidy rate per oocyte retrieved was significantly higher in the microfluidics group compared with the control group (8.5% versus 4.3%, p = 0.04), while the euploidy rate per embryo biopsied was comparable (32.6% versus 21.8%, p = 0.09). In patients with male factor infertility, the high-quality blastulation rate was similar between the control and microfluidics cycles. There was a significantly higher blastulation rate among microfluidics cycles in patients without a diagnosis of male factor infertility (p < 0.01)., Conclusion: In this study, several embryologic outcomes, including fertilization rate, high-quality blastulation rate, and euploidy rate, were significantly higher in the microfluidics group compared to the control group. Microfluidics sperm processing may be a way to improve embryologic outcomes., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Genetic alterations of somatic cells can drive non-malignant clone formation and promote cancer initiation. However, the link between these processes remains unclear and hampers our understanding of tissue homeostasis and cancer development., Results: Here, we collect a literature-based repertoire of 3355 well-known or predicted drivers of cancer and non-cancer somatic evolution in 122 cancer types and 12 non-cancer tissues. Mapping the alterations of these genes in 7953 pan-cancer samples reveals that, despite the large size, the known compendium of drivers is still incomplete and biased towards frequently occurring coding mutations. High overlap exists between drivers of cancer and non-cancer somatic evolution, although significant differences emerge in their recurrence. We confirm and expand the unique properties of drivers and identify a core of evolutionarily conserved and essential genes whose germline variation is strongly counter-selected. Somatic alteration in even one of these genes is sufficient to drive clonal expansion but not malignant transformation., Conclusions: Our study offers a comprehensive overview of our current understanding of the genetic events initiating clone expansion and cancer revealing significant gaps and biases that still need to be addressed. The compendium of cancer and non-cancer somatic drivers, their literature support, and properties are accessible in the Network of Cancer Genes and Healthy Drivers resource at http://www.network-cancer-genes.org/ ., (© 2022. The Author(s).)

Purpose: To evaluate the utilization of single-embryo transfer (SET) and preimplantation genetic testing (PGT) in gestational carrier IVF cycles in the USA with donor oocyte and examine the impact on live birth and multiple gestation., Methods: Retrospective cohort study using the Society of Assisted Reproductive Technology (SART) clinic database of 4776 donor oocyte-recipient IVF cycles in which a GC was used. The cycles were separated into 4 groups by use of PGT and number of embryos transferred as follows: (1) PGT and single-embryo transfer (PGT-SET); (2) PGT and multiple embryo transfer (PGT-MET); (3) no PGT and SET (NoPGT-SET); (4) no PGT and MET (NoPGT-MET). Primary outcomes were live birth rate (LBR) and multiple pregnancy rate (MPR)., Results: More than one blastocyst was transferred in 48.7% (2323/4774) of the cycles. When ≥1 blastocyst was transferred, with or without the use of PGT, the MPR was 45.5% and 42.0%, respectively. In comparison, in the PGT-SET and NoPGT-SET groups, the MPR was 1.4% (8/579) and 3.3% (29/883), respectively. Live birth rates increased with the use of PGT-A and with MET., Conclusion: This study shows that SET, with or without PGT, is associated with a significantly reduced MPR in donor oocyte-recipient GC IVF cycles while maintaining high LBR. It also demonstrates that many infertility centers in the USA are not adhering to ASRM embryo transfer guidelines. Our findings highlight an opportunity to increase GC safety, which ultimately may lead to widened access to this increasingly restricted service outside the USA.

Background: Identifying the complete repertoire of genes that drive cancer in individual patients is crucial for precision oncology. Most established methods identify driver genes that are recurrently altered across patient cohorts. However, mapping these genes back to patients leaves a sizeable fraction with few or no drivers, hindering our understanding of cancer mechanisms and limiting the choice of therapeutic interventions., Results: We present sysSVM2, a machine learning software that integrates cancer genetic alterations with gene systems-level properties to predict drivers in individual patients. Using simulated pan-cancer data, we optimise sysSVM2 for application to any cancer type. We benchmark its performance on real cancer data and validate its applicability to a rare cancer type with few known driver genes. We show that drivers predicted by sysSVM2 have a low false-positive rate, are stable and disrupt well-known cancer-related pathways., Conclusions: sysSVM2 can be used to identify driver alterations in patients lacking sufficient canonical drivers or belonging to rare cancer types for which assembling a large enough cohort is challenging, furthering the goals of precision oncology. As resources for the community, we provide the code to implement sysSVM2 and the pre-trained models in all TCGA cancer types ( https://github.com/ciccalab/sysSVM2 ).

Study Question: Does trophectoderm biopsy for preimplantation genetic testing (PGT) increase the risk of obstetric or perinatal complications in frozen-thawed embryo transfer (FET) cycles?, Summary Answer: Trophectoderm biopsy may increase the risk of hypertensive disorders of pregnancy (HDP) in pregnancies following FET cycles., What Is Known Already: Trophectoderm biopsy has replaced blastomere biopsy as the standard of care to procure cells for PGT analysis. Recently, there has been concern that trophectoderm biopsy may adversely impact obstetric and perinatal outcomes. Previous studies examining this question are limited by use of inappropriate control groups, small sample size or reporting on data that no longer reflects current IVF practice., Study Design, Size, Duration: This was a retrospective cohort study conducted at a single university-affiliated fertility center. A total of 756 patients who underwent FET with transfer of previously vitrified blastocysts that had either trophectoderm biopsy or were unbiopsied and resulted in a singleton live birth between 2013 and 2019 were included., Participants/materials, Setting, Methods: Obstetric and perinatal outcomes for patients aged 20-44 years who underwent FET with transfer of previously vitrified blastocysts that were either biopsied (n = 241) or unbiopsied (n = 515) were analyzed. Primary outcome was odds of placentation disorders including HDP and rate of fetal growth restriction (FGR). Binary logistic regression was performed to control for potential covariates., Main Results and the Role of Chance: The biopsy group was significantly older, had fewer anovulatory patients, was more often nulliparous and had fewer embryos transferred compared to the unbiopsied group. After controlling for potential covariates, the probability of developing HDP was significantly higher in the biopsy group compared with unbiopsied group (adjusted odds ratio (aOR) 1.943, 95% CI 1.072-3.521; P = 0.029).There was no significant difference between groups in the probability of placenta previa or placenta accreta. There was also no significant difference in the rate of FGR (aOR 1.397; 95% CI, 0.815-2.395; P = 0.224) or the proportion of low (aOR 0.603; 95% CI, 0.336-1.084; P = 0.091) or very low (aOR 2.948; 95% CI, 0.613-14.177; P = 0.177) birthweight infants comparing biopsied to unbiopsied groups., Limitations, Reason for Caution: This was a retrospective study performed at a single fertility center, which may limit the generalizability of our findings., Wider Implications of the Findings: Trophectoderm biopsy may increase the risk of HDP in FET cycles, however, a prospective multicenter randomized trial should be performed to confirm these findings., Study Funding/competing Interest(s): No specific funding was obtained for this study. The authors declare no conflict of interest., Trial Registration Number: NA., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Research Question: Do maternal and perinatal outcomes differ between natural and programmed frozen embryo transfer (FET) cycles?, Design: Retrospective cohort study at a university-affiliated fertility centre including 775 patients who underwent programmed or natural FET cycles resulting in a singleton live birth using blastocysts vitrified between 2013 and 2018., Results: A total of 384 natural and 391 programmed FET singleton pregnancies were analysed. Programmed FET resulted in higher overall maternal complications (32.2% [126/391] versus 18.8% [72/384]; P < 0.01), including higher probability of hypertensive disorders of pregnancy (HDP) (15.3% [60/391] versus 6.3% [24/384]; P < 0.01), preterm premature rupture of membranes (2.6% [10/391] versus 0.3% [1/384]; P = 0.02) and caesarean delivery (53.2% [206/387] versus 42.8% [163/381]; P = 0.03) compared with natural FET. After controlling for potential confounders, including age, body mass index, parity, smoking status, history of diabetes or chronic hypertension, infertility diagnosis, number of embryos transferred and use of preimplantation genetic testing, the adjusted odds ratio for HDP was 2.39 (95% CI 1.37 to 4.17) and for overall maternal complications was 2.21 (95% CI 1.51 to 3.22) comparing programmed with natural FET groups. The groups did not significantly differ for any perinatal outcomes analysed, including birth weight (3357.9 ± 671.6 g versus 3318.4 ± 616.2 g; P = 0.40) or rate of birth defects (1.5% [6/391] versus 2.1% [8/384]; P = 0.57), respectively., Conclusion: Vitrified-warmed blastocyst transfer in a programmed cycle resulted in a twofold higher probability of HDP compared with transfer in a natural cycle. Natural FET cycle should, therefore, be recommended as first line for all eligible patients undergoing FET to reduce the risk of HDP., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: To assess whether GnRH agonist trigger impacts the implantation potential of euploid embryos., Methods: Retrospective cohort study done at an academic IVF center evaluating frozen-thawed embryo transfer (FET) cycles in which single-euploid blastocysts were transferred between 2014 and 2019. All embryos were generated in an IVF cycle which used GnRHa or hCG trigger and then were transferred in a programmed or natural FET cycle. Only the first FET cycle was included for each patient. Primary outcome was ongoing pregnancy rate or live birth rate (OPR/LBR). Secondary outcomes were implantation rate (IR), clinical pregnancy rate (CPR), clinical loss rate (CLR), and multiple pregnancy rate (MPR). Logistic regression was performed to control for confounding variables. A p value of < 0.05 was considered statistically significant., Results: Two hundred sixty-three FET cycles were included for analysis (GnRHa = 145; hCG = 118). The GnRHa group was significantly younger (35.2 vs. 37.5 years) and had higher AMH values (4.50 ng/ml vs. 2.03 ng/ml) than the hCG group, respectively (p < 0.05). There was no significant difference in OPR/LBR (64.1% (93/145) vs. 65.3% (77/118); p = 0.90) between the GnRHa and hCG groups, respectively. There was also no significant difference in IR, CPR, CLR, or MPR between groups. After controlling for confounding variables, the adjusted odds ratio for OPR/LBR was 0.941 (95% CI, 0.534-1.658); p = 0.83) comparing GnRHa to hCG. Pregnancy outcomes did not significantly differ when groups were stratified by age (< 35 vs. > 35 years old)., Conclusions: Our findings confirm that euploid embryos created after hCG or GnRHa trigger have the same potential for pregnancy.

Objective: To characterize corpora lutea (CL) function after gonadotropin-releasing hormone agonist (GnRHa) trigger with the use of adjuvant human chorionic gonadotropin (hCG)., Design: Secondary analysis of serum from prospective randomized clinical trial., Setting: University-based fertility center., Patient(s): Women under 40 years of age at risk of ovarian hyperstimulation syndrome (OHSS) with serum E 2 level <4,000 pg/mL., Interventions(s): All subjects underwent ovarian stimulation with the use of a GnRH antagonist protocol. Within a larger study, subjects were randomized to receive 1,000 IU hCG at the time of GnRHa trigger and placebo at the time of vaginal oocyte retrieval (VOR) or placebo at the time of GnRHa trigger and 1,500 IU hCG at the time of VOR., Main Outcome Measure(s): Luteal phase and early pregnancy curves of serum prorenin and 17α-hydroxyprogesterone (17OH-P)., Result(s): Thirty subjects enrolled in this secondary analysis. Serum 17OH-P peaked in the early luteal phase, 5 days after GnRHa trigger, with a nadir in the mid-luteal phase 9 days after trigger. Serum prorenin peaked in the luteal phase 2 days after GnRHa trigger, independently from adjuvant hCG timing, and reached a nadir at 9 days after trigger. CL function appears higher when adjuvant hCG is given at VOR compared with adjuvant hCG given at the time of trigger., Conclusion(s): CL function, as interpreted by proxy measures of serum prorenin and 17OH-P with pregnancy, continues despite GnRHa trigger. Both options for adjuvant hCG timing are sufficient for CL rescue and successful pregnancy, so the potential for OHSS risk with increased CL activity after hCG at VOR should be considered., Clinical Trial Registration Number: NCT01815138., (Copyright © 2019 American Society for Reproductive Medicine. All rights reserved.)

Objective: To evaluate differences in euploidy rates between IVF cycles triggered with either GnRH agonist (GnRHa) or hCG., Design: Retrospective cohort study., Setting: University-affiliated fertility center., Patient(s): A total of 366 patients performing 539 IVF cycles utilizing preimplantation genetic testing for aneuploidy (PGT-A)., Intervention(s): Gonadotropin-releasing hormone agonist or hCG trigger of oocyte maturation during IVF cycles., Main Outcome Measure(s): Rate of euploid embryos., Result(s): Patients in the GnRHa trigger arm were younger, with a lower body mass index and higher antimüllerian hormone level, and they had a higher number of oocytes retrieved and embryos biopsied. Euploid rate per embryo biopsied was higher after GnRHa trigger than after hCG trigger (37.8% ± 2.1% vs. 30.3% ± 1.8%), but multivariate regression analysis controlling for potential confounding factors did not show any differences between the two groups. Moreover, the euploid rate per oocyte retrieved was not significantly different overall (GnRHa vs. hCG: 33.9% ± 2.2% vs. 28.0% ± 1.9%). The anticipated decline in the rate of euploid embryos per oocyte retrieved went from 15.8% ± 1.2% for age <35 years to 4.3% ± 0.9% for patients aged ≥41 years. There were no significant differences between the two groups after stratifying by age and controlling for PGT-A testing modality., Conclusion(s): Both GnRHa and hCG trigger result in comparable euploid rates. Trigger with GnRHa should therefore be considered a valid option for trigger modality in freeze-all PGT-A cycles, in view of its demonstrated effectiveness and known safety enhancement., (Copyright © 2019. Published by Elsevier Inc.)

The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy.

Systemic lupus erythematosus carries an increased risk of pregnancy complications, including preeclampsia and fetal adverse outcomes. To identify the underlying molecular mechanisms, we longitudinally profiled the blood transcriptome of 92 lupus patients and 43 healthy women during pregnancy and postpartum and performed multicolor flow cytometry in a subset of them. We also profiled 25 healthy women undergoing assisted reproductive technology to monitor transcriptional changes around embryo implantation. Sustained down-regulation of multiple immune signatures, including interferon and plasma cells, was observed during healthy pregnancy. These changes appeared early after embryo implantation and were mirrored in uncomplicated lupus pregnancies. Patients with preeclampsia displayed early up-regulation of neutrophil signatures that correlated with expansion of immature neutrophils. Lupus pregnancies with fetal complications carried the highest interferon and plasma cell signatures as well as activated CD4 + T cell counts. Thus, blood immunomonitoring reveals that both healthy and uncomplicated lupus pregnancies exhibit early and sustained transcriptional modulation of lupus-related signatures, and a lack thereof associates with adverse outcomes., (© 2019 Hong et al.)

The Network of Cancer Genes (NCG) is a manually curated repository of 2372 genes whose somatic modifications have known or predicted cancer driver roles. These genes were collected from 275 publications, including two sources of known cancer genes and 273 cancer sequencing screens of more than 100 cancer types from 34,905 cancer donors and multiple primary sites. This represents a more than 1.5-fold content increase compared to the previous version. NCG also annotates properties of cancer genes, such as duplicability, evolutionary origin, RNA and protein expression, miRNA and protein interactions, and protein function and essentiality. NCG is accessible at http://ncg.kcl.ac.uk/ .

Purpose: The aim of this study is to analyze clinical pregnancy rates (CPR) and ongoing pregnancy rates (OPR) for frozen embryo transfers (FET) performed with blastocysts in the cycle immediately after GnRH agonist (GnRHa) versus human chorionic gonadotropin (hCG) triggers, with outcomes of delayed FET for comparison., Methods: Retrospective cohort study at a university-affiliated in vitro fertilization (IVF) clinic, including patients undergoing IVF between 2013-16 with a blastocyst FET performed within two menstrual cycles of a previous stimulation cycle and vaginal oocyte retrieval (VOR). FETs included programmed and natural endometrial preparation. Outcome measures were clinical and ongoing pregnancy rates., Results: CPR and OPR for 344 FET cycles were similar when comparing immediate and delayed transfer overall (crude CPR 67.5 versus 76.5%, p = 0.11; OPR 57.5 versus 66.7%, p = 0.13), and after stratifying by cycles following hCG trigger (OPR 62.5 versus 66.3%, p = 0.61) and GnRHa trigger (OPR 55.6 versus 64.5%, p = 0.17). When considering a number of predictors for OPR, an adjusted odds ratio (OR) of 1.74 [95% CI 1.00-3.03] approached significance in favor of delayed FET., Conclusions: Regardless of trigger modality, patients can be reassured that pregnancy rates with FET are high in immediate and delayed cycles. However, our study suggests a potential benefit in delaying a cycle before proceeding with FET.

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of controlled ovarian stimulation. The use of gonadotropin releasing hormone (GnRH) agonist for the trigger of oocyte maturation is effective in the prevention of OHSS although it may result in a lower pregnancy rate. The use of adjuvant low dose human chorionic gonadotropin (hCG) at the time of trigger or at the time of oocyte retrieval may improve pregnancy rates. The goal of this dual trigger study is to evaluate the safety and efficacy of the use of low dose hCG administered at the time of GnRH agonist trigger or 35 h later as well as the potential impact on pregnancy rates. The population will consist of 82 women undergoing IVF treatment who are at risk of developing OHSS. This study will be a single center prospective randomized double-blind placebo controlled trial. The randomization schedule will be administered by the Investigational Drug Services of the University. After controlled ovarian stimulation, induction of oocyte maturation will be achieved using a GnRH agonist and patients will be randomized to receive either low dose hCG 1000 IU at the time of trigger and placebo at oocyte retrieval (Study group) or placebo at the time of trigger and hCG 1500 IU at the time of oocyte retrieval (Control group). The main outcomes will be live birth rates and incidence of OHSS. Two ancillary studies will include a quality of life survey and serum assessment of independent corpus luteum function.

Objective: To compare implantation and ongoing pregnancy rates in freeze-only versus fresh transfer cycles., Design: Retrospective matched cohort study., Setting: Not applicable., Patient(s): Women selected using a matching algorithm for similar distributions of clinical characteristics for a total of 2,910 cycles (1,455 fresh cohort and 1,455 freeze-only cohort)., Intervention(s): None., Main Outcome Measure(s): Implantation and ongoing pregnancy rates., Result(s): Implantation and ongoing pregnancy rates were statistically significantly higher in the freeze-only transfer cohort than in the matched fresh transfer cohort: ongoing pregnancy rate for freeze-only was 52.0% (95% confidence interval [CI], 49.4-54.6) and for fresh was 45.3% (95% CI, 42.7-47.9), odds ratio (OR) 1.31 (95% CI, 1.13-1.51). In a stratified analysis, the odds of ongoing pregnancy after freeze-only transfer were statistically significantly higher for women both above and below age 35 with progesterone concentration >1.0 ng/mL (age ≤35: OR 1.38 [1.11-1.71]; age >35: OR 1.73 [1.34-2.24]). For women with progesterone concentration ≤1.0 ng/mL, no statistically significant difference in freeze-only odds of ongoing pregnancy was observed in either age group. The sensitivity analysis revealed that increasing maternal age alone (regardless of progesterone) trended toward a more beneficial effect of freeze-only cycles. A lower progesterone concentration was associated with statistically significantly higher ongoing pregnancy odds for fresh but not freeze-only cycles., Conclusion(s): Freeze-only transfer protocols are associated with statistically significantly higher ongoing implantation and pregnancy rates compared with fresh transfer cycles. This effect is most pronounced for cycles with progesterone >1.0 ng/mL at trigger and may also be stronger for older patients., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to compare clinical and ongoing pregnancy rates in cycles with single embryo transfer (SET) of blastocysts cryopreserved on day 5 or day 6. Our aim was to determine whether day 6 blastocysts perform adequately to recommend SET., Methods: Retrospective cohort study including 468 transfer cycles for 392 women younger than age 38 undergoing SET at a university-affiliated IVF clinic in the USA. A total of 261 day 5 blastocysts and 207 day 6 blastocysts for frozen-thawed SET between 2010 and 2016 were analyzed. Data included cryopreservation by both a slow freeze method and vitrification., Results: In total, 59.0% of day 5 SET cycles resulted in a clinical pregnancy compared to 54.1% of day 6 blastocysts (p = 0.54). Ongoing pregnancy rates from day 5 frozen-thawed blastocysts (51.7%) were comparable to day 6 (44.9%, p = 0.14). When looking at vitrified blastocysts only, there were no significant differences between day 5 and day 6 blastocysts, with a clinical pregnancy rate of 69.2% for day 5 and 72.5% for day 6 (p = 0.68)., Conclusions: SETs of day 6 cryopreserved blastocysts resulted in similar clinical and ongoing pregnancy rates compared to day 5, particularly after vitrification.

Objective: To evaluate clinical pregnancy rates in embryo transfer (ET) cycles with and without peri-implantation corticosteroid and oral antibiotic administration., Design: Retrospective cohort study., Setting: University-affiliated in vitro fertilization (IVF) clinic., Patient(s): Eight hundred and seventy-six ETs with or without the routine use of methylprednisolone and doxycycline., Intervention(s): Embryo transfer procedures., Main Outcome Measure(s): Clinical pregnancy rates (CPR)., Result(s): The CPR with the routine use of methylprednisolone and doxycycline was 56.1% compared with 61.5% after discontinuation of these medications. Ongoing pregnancy rates were 49.5% with medications versus 53.2% without medications. Of the cleavage-stage embryos, 79% underwent assisted hatching; among these, the CPR was 28.7% when treated with corticosteroids and antibiotics compared with 47.4% without medications., Conclusion(s): No statistically significant difference in overall IVF outcomes was noted after the discontinuation of routine peri-implantation corticosteroids and antibiotics. The use of these medications varies across the country and may be a result of habit rather than evidence-based medicine., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess medical students' and house staff's knowledge and personal and professional perceptions of age-related fertility and fertility preservation before and after an educational intervention., Design: Pre-/post intervention survey., Setting: University-based medical center., Patient(s): Medical students and house staff., Intervention(s): An educational session on age-related fertility decline and elective fertility preservation., Main Outcome Measure(s): Knowledge scores and perceptions assessed immediately before and after the intervention., Result(s): Sixty-five surveys were administered. Of the 53 respondents, 71.7% were married or in a committed relationship; 89.4% reported that they were delaying childbearing, with career and/or education being the most frequently listed reason (85.7%); 39.5% indicated that they had both personal and professional interest in fertility preservation but identified finances (62.5%) and time (59.4%) as barriers; 86.9% indicated previous exposure, with formal education (80.0%) and social media (40.0%) being the most common sources. Mean scores on a six-question knowledge-based assessment improved significantly following the presentation (54.6 ± 19.0% vs. 78.1 ± 16.0%), as did the number of participants who indicated that they might now recommend elective oocyte cryopreservation to others (71.1% vs. 54.3%). After the intervention, 97.8% thought that it was important for medical professionals to be informed about age-related fertility decline and elective oocyte cryopreservation., Conclusion(s): Despite professional and personal interest, knowledge of age-related fertility decline and elective fertility preservation is limited among medical students and house staff. This study highlights the need for formal education across all levels of training and specialties, with even brief interventions being of potential benefit., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To describe intentions and outcomes of lesbian couples requesting reproductive assistance; and report number of cycles needed to achieve a live birth., Design: Retrospective chart review., Setting: University-based fertility center., Patient(s): A total of 306 lesbian couples who sought reproductive assistance between 2004 and 2015., Intervention(s): Intrauterine insemination or IVF using donor sperm., Main Outcome Measure(s): Mean age, relationship status, family size, preconception goals, conception attempts, number of cycles to achieve a live birth., Result(s): Preconception plans were available for 233 couples: 76.4% planned for one partner to conceive and carry (single partner conception); 23.6% planned for both partners to eventually conceive and carry (dual partner conception). Of 306 couples who presented, 85.1% attempted single partner conception, and 68% of these achieved a live birth. Dual partner conception was attempted by 14.9% of couples, and 88.9% achieved a live birth. Of those who conceived with IUI, a mean (±SD) of 3 ± 1.1 cycles were completed. Of those who conceived with IVF, a mean of 6 ± 1.4 IUI and 1.7 ± 0.3 IVF cycles were completed., Conclusion(s): Lesbian couples may improve their likelihood of a live birth if both partners attempt conception. Further studies are needed to understand why one-fifth of patients did not pursue treatment., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine what assisted reproductive technologies (ART) policies, if any, have been instituted in response to an increasingly overweight and obese patient population., Design: Cross-sectional survey., Setting: University-affiliated IVF clinic., Patient(s): Women in the overweight and obese body mass index (BMI) categories seeking ART treatments., Intervention(s): Anonymous survey sent to medical directors at 395 IVF centers listed in Society for Assisted Reproductive Technology database., Main Outcome Measure(s): Assessment of recommendations, policies, and restrictions for patients who are overweight/obese and who desire treatment for infertility, including in IVF, IUI, and donor egg cycles., Result(s): Seventy-seven anonymous responses were received (19.5% response rate): 64.9% of centers have a formal policy for obesity, and 84% of those have a maximum BMI at which they will perform IVF, while 38% of those have a maximum BMI for performing IUI; 64.6% of respondents reported anesthesia requirements/concerns as the primary criteria for patient exclusion. Other primary considerations included safety during ongoing pregnancy and ART outcomes., Conclusion(s): Centers that have policies regarding obesity and access to ART consider efficacy, procedural safety, safety in pregnancy, and overall health status. Policies vary widely. The patient's autonomy must be balanced with nonmaleficence and the avoidance of interventions that may be unsafe both immediately and long term., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To compare in vitro fertilization (IVF) outcomes in low responders stimulated with microdose leuprolide protocol (ML) following pretreatment with either oral contraceptive pill (OCP) or luteal estradiol (E2) + GnRH antagonist (E2 + antag) for follicular synchronization prior to controlled ovarian hyperstimulation (COH)., Study Design: This was a retrospective study of 130 women, who were poor responders, undergoing IVF with either OCP/ML or E2+ antag/ML protocols. The main outcome measures were ongoing pregnancy rates, number of oocytes retrieved, and cancellation rate., Results: Both groups were similar in baseline characteristics. There were no significant differences in gonadotropin requirement, cancellation rate, and number of embryos transferred. Ongoing pregnancy rates (40% vs. 15%) were significantly higher in the OCP/ML group. Trends toward greater number of oocytes retrieved (7.7 ± 3.4 vs. 5.9 ± 4.2) and improved implantation rates (20% vs. 12%) were also noted, but these did not reach statistical significance., Conclusion: E2+antag pretreatment does not appear to improve IVF outcomes in ML protocol when compared to the standard OCP in poor responders. Randomized trials with adequate power to study the optimal method of steroid pretreatments appear justified.

Objective: To evaluate the percentage (%) of mature oocytes retrieved in patients with a previous history of >25% immature oocytes retrieved who were triggered with gonadotropin-releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG) to induce oocyte maturation., Design: Retrospective cohort study., Setting: A university-based tertiary fertility center., Patient(s): Patients with a history of >25% immature oocytes retrieved in a prior in vitro fertilization cycle who were triggered with GnRH-a and hCG 5,000 IU or 10,000 IU in a subsequent cycle from January 2008 through February 2012., Intervention(s): Dual trigger of GnRH-a and hCG 5,000 or 10,000 IU., Main Outcome Measure(s): Percent of mature oocytes retrieved and fertilization rate., Result(s): The proportion of mature oocytes retrieved was significantly higher with a dual trigger compared with the subject's previous cycle (75.0%, interquartile range 55.6%-80.0% vs. 38.5%, interquartile range 16.7%-55.6%). The odds of a mature oocyte retrieved for patients who received a dual trigger was 2.51 times higher after controlling for stimulation protocol, hCG dose, gonadotropin dose, and oocyte retrieval time interval (odds ratio 2.51; confidence interval 1.06-5.96). The implantation, clinical, and ongoing pregnancy rates for the dual trigger were 11.8%, 26.1%, and 17.4%, respectively., Conclusion(s): In patients with a low percentage of mature oocytes retrieved who are triggered with a combination of GnRH-a and hCG, the % of mature oocytes retrieved improved. in vitro fertilization outcomes, however, remain poor, suggesting an underlying oocyte dysfunction., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the outcome of a newly established oocyte vitrification program in women undergoing in vitro fertilization (IVF) within a short timeframe by simultaneously evaluating embryos derived from vitrified and fresh oocytes from the same stimulated cycle., Design: Cohort prospective controlled trial and case-control study., Setting: University-based tertiary fertility center., Patient(s): Fourteen women who fulfilled the inclusion criteria underwent controlled ovarian hyperstimulation and Intracytoplasmic sperm injection (ICSI) treatment., Intervention(s): Oocyte vitrification., Main Outcome Measure(s): The primary outcome measures were oocyte survival, fertilization and cleavage rate, and subsequent embryo development, compared between vitrified and fresh oocytes. Secondary outcomes were implantation, clinical pregnancy, miscarriage and live birth rates using embryos derived from the vitrified oocytes for transfer. This was compared with age-matched controls who met similar inclusion criteria as the study patients and who underwent IVF during the same time period. Neonatal data on all newborns was also collected., Results: From October 2009 until November 2010, a total of 17 patients were enrolled in this study (mean age 31.9 +/- 2.9 years). Three subjects withdrew prior to retrieval and one subject did not have a transfer from vitrified oocytes. A total of 164 metaphase II (MII) oocytes were retrieved (mean 11.7 +/- 3.7), 83 were vitrified with 86.7% survival. Fertilization rate was similar between vitrified and fresh oocytes (69.4 vs 78.2%, P = 0.8). Cleavage on day two, however, was lowerin the vitrified oocytes (88% vs 100%, P = 0.004). Implantation rate (IR) was 25% (7/28) with a mean number of 2.0 +/- 0.5 embryos transferred. Live birth rate/embryo transfer (ET) was 46.1% (6/13) after transferring embryos derived only from vitrified oocytes, (six live births, seven babies,one set of twins). One additional ongoing pregnancy has been established after transfer of a cryopreserved blastocyst derived from a vitrified oocyte (combined pregnancy rate/ ET: 50%; 7/14)., Conclusions: This study provides a viable model to quickly assess the efficacy of a newly established egg vitrification program following American Society for Reproductive Medicine (ASRM) guidelines in an investigational protocol. Embryos resulting from oocyte vitrification resulted in optimal live birth and implantation rate. The lower cleavage rate noted in this study may indicate a possible detrimental effect of the vitrification process, which may be overcome with additional experience and refinement of the technique.

Study Question: Are there factors predicting the number of total and mature oocytes retrieved after controlled ovarian hyperstimulation (COH) utilizing a gonadotropin-releasing hormone (GnRH) antagonist protocol and a GnRH agonist (GnRHa) to induce oocyte maturation?, Summary Answer: Peak estradiol (E₂) level, post-trigger LH and progesterone and the magnitude of LH rise are independent predictors of the total number of oocytes and mature oocytes retrieved., What Is Known Already: Despite multiple follicular development in high responders, oocyte retrieval after a GnRHa trigger in a small subset of patients fails to obtain a substantial number of total oocytes or mature oocytes., Study Design, Size and Duration: A retrospective chart review of all autologous and oocyte donation cycles utilizing a GnRHa antagonist protocol where GnRHa was used for the induction of oocyte maturation between 1 April 2003 and 31 December 2011., Participants/materials, Setting and Methods: A total of 508 autologous and donor IVF/ICSI cycles utilizing a GnRH antagonist protocol for COH and GnRHa for the induction of oocyte maturation at a university-based tertiary fertility center., Main Results and the Role of Chance: Peak E₂ on the day of trigger (r = 0.19, P < 0.001), post-trigger LH (r = 0.12, P = 0.009) and progesterone (r = 0.47, P < 001) and LH rise (r = 0.18, P < 0.001) all positively correlated with the number of total and mature oocytes retrieved. The true incidence of empty follicle syndrome was 1.4% (7/508). There was no post-trigger LH or progesterone cut-off value for the prediction of oocyte yield. However, all cases of empty follicle syndrome occurred in patients with post-trigger LH <15 IU/l and P ≤ 3.5 ng/ml. The findings of this study may also be due to chance since it was a retrospective study and not prospectively designed., Limitation, Reasons for Caution: This is a retrospective chart review and therefore subject to bias. Serum hormone measurements were performed between 8 and 12 h after GnRHa trigger rather than a standardized time period following trigger administration. Therefore, peak levels of LH may have been missed due to the short ascending limb of LH rise lasting approximately 4 h after GnRHa trigger., Wider Implications of the Findings: The results of this study can be generalized to high responders utilizing a GnRH antagonist protocol for COH and a GnRHa for the induction of oocyte maturation. The use of alternative stimulation regimens or medications will limit the ability to generalize the results of this study to other populations., Study Funding/competing Interest(s): This study was not funded, and there are no conflicts of interest., Trial Registration Number: n/a.