Genetic impact of external Targhee sires at the U.S. Sheep Experiment Station: a case study of introgression.

Sheep breeders requested that the U.S. Sheep Experiment Station (USSES) to participate in national genetic evaluation through the National Sheep Improvement Program (NSIP). The reasons included the need for (1) a comparison of the productivity of industry and United States Department of Agriculture (USDA) lines, (2) transparency of USDA flocks, (3) genetic ties for NSIP by sampling of industry flocks, and (4) development of premium genetic lines for public release. In response, USSES began to incorporate external sires from NSIP participating flocks into the USSES Targhee flock. Our objective, based on a pedigree analysis, was to test if introgression of external genetics into the flock was achieved. The pedigree included 13,189 animals with mean maximum generations, mean complete generations, and mean equivalent complete generations of 4.2, 1.8, and 2.6, respectively. The mean generation interval was 3.1 yr. The reference population was defined as lambs born from 2021 to 2023 (n = 792). Two additional populations were defined as the current mature ewe flock (n = 123) and the current mature rams (n = 14). The Genetic Conservation Index averaged 7.7 for the full population and 25.7 for the reference population. Overall inbreeding was 0.003 for the full population and 0.006 for the reference population. The rate of inbreeding was 0.0003 per generation. Average relatedness was 0.015 for the full population and 0.018 for the reference population. The effective number of founders, effective number of ancestors, and founder genome equivalents contributing to the reference population were 60, 39, and 19.1, respectively. The ratio of the effective number of founders to the effective number of ancestors was 1.5, indicating the presence of genetic bottlenecks. Measures of effective population size ranged from 102 to 547. Of the 704 offspring produced by external sires, 17 ram lambs and 132 ewe lambs were retained for breeding. The USSES sires produced 299 offspring with 2 ram lambs and 51 ewe lambs retained. Incorporating external sires resulted in a cumulative percentage of genetic variance of 48.8, 49.1, and 44.2 of external genetics for the reference population, current mature ewe flock, and current mature rams, respectively. Stakeholder needs were addressed by introgression of external sires and participation in NSIP, but future selection practices need to be modified to maintain a minimum of 50% USSES core genetics in the flock.

Assessing Population Structure and Genetic Diversity in US Suffolk Sheep to Define a Framework for Genomic Selection.

Long-term sustainability of breeds depends on having sufficient genetic diversity for adaptability to change, whether driven by climatic conditions or by priorities in breeding programs. Genetic diversity in Suffolk sheep in the United States was evaluated in four ways: 1) using genetic relationships from pedigree data [(n = 64 310 animals recorded in the US National Sheep Improvement Program (NSIP)]; 2) using molecular data (n = 304 Suffolk genotyped with the OvineHD BeadChip); 3) comparing Australian (n = 109) and Irish (n = 55) Suffolk sheep to those in the United States using molecular data; and 4) assessing genetic relationships (connectedness) among active Suffolk flocks (n = 18) in NSIP. By characterizing genetic diversity, a goal was to define the structure of a reference population for use for genomic selection strategies in this breed. Pedigree-based mean inbreeding level for the most recent year of available data was 5.5%. Ten animals defined 22.8% of the current gene pool. The effective population size (Ne) ranged from 27.5 to 244.2 based on pedigree and was 79.5 based on molecular data. Expected (HE) and observed (HO) heterozygosity were 0.317 and 0.306, respectively. Model-based population structure included 7 subpopulations. From Principal Component Analysis, countries separated into distinct populations. Within the US population, flocks formed genetically disconnected clusters. A decline in genetic diversity over time was observed from both pedigree and genomic-based derived measures with evidence of population substructure as measured by FST. Using these measures of genetic diversity, a framework for establishing a genomic reference population in US Suffolk sheep engaged in NSIP was proposed.

Concordance of Desired and Administered Postpartum Contraceptives among Emergency and Full Scope Medicaid Patients.

OBJECTIVE: To determine if concordance of contraceptive preference and uptake differ between postpartum recipients of emergency versus full scope Medicaid. STUDY DESIGN: We performed a historical cohort study of patients who delivered at a safety-net hospital in Denver, Colorado in 2016. In our public system, all patients had access to immediate postpartum tubal ligation and all forms of reversible contraception in outpatient clinics. We used data from electronic health records to compare contraceptive preferences and uptake between patients with full scope and emergency Medicaid at hospital discharge and by 12 weeks postpartum. We then compared contraceptive concordance (use of the same method as desired during delivery admission) between the groups at time of postpartum discharge and by 12 weeks postpartum. RESULTS: We examined 693 women; 349 (50.1%) had emergency Medicaid and 344 (49.9%) had full scope Medicaid. The mean age at delivery was 27.9 years, and most patients were Hispanic (74%). Women with emergency Medicaid were less likely to receive their desired method of postpartum contraception before hospital discharge (53.6% vs. 66.9%; p < .01). One-half of the patients with emergency Medicaid who did not receive their desired method of immediate postpartum contraception were unable to obtain it based on insurance ineligibility. By 12 weeks postpartum, the rates of concordance did not differ by insurance status: 52.4% of patients with emergency Medicaid and 55.2% of patients with full scope Medicaid received their desired method of contraception (p = .46). CONCLUSIONS: Emergency Medicaid recipients, largely recent and/or unauthorized immigrants, have high demand for highly effective postpartum contraceptives. Although emergency Medicaid recipients initially had lower rates of receipt of their desired contraceptive during the hospital stay compared with those with full scope Medicaid, they ultimately had similar concordance rates by 12 weeks postpartum. We suspect this finding was in part due to free access to all methods of contraception in our outpatient clinics during the postpartum course. Systemic barriers should be reduced to ensure better access to postpartum contraceptives for all patients, regardless of insurance coverage, to improve reproductive equity.

Maternal morbidity after preterm premature rupture of membranes at <24 weeks' gestation.

BACKGROUND: After preterm premature rupture of membranes at <24 weeks' gestation, pregnant women may choose continuation (expectant management) or termination of pregnancy, via either dilation and evacuation or labor induction. Neonatal outcomes after expectant management are well described. In contrast, limited research addresses maternal outcomes associated with expectant management compared to termination of pregnancy. OBJECTIVE: This study aimed to compare maternal morbidity after preterm premature rupture of membranes at <24 weeks' gestation in women who choose either expectant management or termination of pregnancy. STUDY DESIGN: This retrospective cohort study included women with preterm premature rupture of membranes between 14 0/7 and 23 6/7 weeks' gestation with singleton or twin pregnancies at 3 institutions from 2011 to 2018. We excluded pregnancies complicated by fetal anomalies, rupture of membranes immediately after obstetrical procedures (chorionic villus sampling, amniocentesis, cerclage placement, fetal reduction), spontaneous delivery <24 hours after membrane rupture, and contraindications to expectant management. Our primary outcome was the difference in composite maternal morbidity between women choosing expectant management and women choosing termination of pregnancy. We defined composite maternal morbidity as at least 1 of the following: chorioamnionitis, endometritis, sepsis, unplanned operative procedure after delivery (dilation and curettage, laparoscopy, or laparotomy), injury requiring repair, unplanned hysterectomy, unplanned hysterotomy (excluding cesarean delivery), uterine rupture, hemorrhage of >1000 mL, transfusion, admission to the maternal intensive care unit, acute renal insufficiency, venous thromboembolism, pulmonary embolism, and readmission to the hospital within 6 weeks. We compared the demographic and antenatal characteristics of women choosing expectant management with that of women choosing termination of pregnancy and used logistic regression to quantify the association between initial management decision and composite maternal morbidity. RESULTS: We identified 350 women with pregnancies complicated by preterm premature rupture of membranes at <24 weeks' gestation, and 208 women were eligible for the study. Of the 208 women, 108 (51.9%) chose expectant management as initial management, and 100 (48.1%) chose termination of pregnancy as initial management. Among women selecting termination of pregnancy, 67.0% underwent labor induction, and 33.0% underwent dilation and evacuation. Compared to women who chose termination of pregnancy, women who chose expectant management had 4.1 times the odds of developing chorioamnionitis (38.0% vs 13.0%; 95% confidence interval, 2.03-8.26) and 2.44 times the odds of postpartum hemorrhage (23.1% vs 11.0%; 95% confidence interval, 1.13-5.26). Admissions to the intensive care unit and unplanned hysterectomy only occurred after expectant management (2.8% vs 0.0% and 0.9% vs 0.0%). Of women who chose expectant management, 36.2% delivered via cesarean delivery with 56.4% non-low transverse uterine incisions. Composite maternal morbidity rates were 60.2% in the expectant management group and 33.0% in the termination of pregnancy group. After adjusting for gestational age at rupture, site, race and ethnicity, gestational age at entry to prenatal care, preterm premature rupture of membranes in a previous pregnancy, twin pregnancy, smoking, cerclage, and cervical examination at the time of presentation, expectant management was associated with 3.47 times the odds of composite maternal morbidity (95% confidence interval, 1.52-7.93), corresponding to an adjusted relative risk of 1.91 (95% confidence interval, 1.35-2.73). Among women who chose expectant management, 15.7% avoided morbidity and had a neonate who survived to discharge. CONCLUSION: Expectant management for preterm premature rupture of membranes at <24 weeks' gestation was associated with a significantly increased risk of maternal morbidity when compared to termination of pregnancy.

Palliative Benefits of Oral Mifepristone for the Treatment of Metastatic Fibroblastic Osteosarcoma.

BACKGROUND/AIM: It has been hypothesized that many, or even most cancers, utilize a unique immunomodulatory protein, called the progesterone induced blocking factor (PIBF) to allow spread of the cancer. Support for this concept has been provided by cancer cell line studies showing that PIBF is produced by these cancer cells and mifepristone suppresses this protein and inhibits proliferation of these cells. Furthermore, controlled murine studies with several spontaneous different types of cancer showed a clear beneficial effect of mifepristone over placebo control. Finally, there have been a variety of anecdotal reports showing efficacy of mifepristone in providing increased length and quality of life in patients with different types of advanced cancers. CASE REPORT: Single agent mifepristone was found to provide significant palliative benefit for a 51-year-old male whose metastatic advanced fibroblastic osteosarcoma progressed despite surgery, radiotherapy, multiagent chemotherapy, and targeted therapy. CONCLUSION: Thus, osteosarcoma can be added to the list of cancers, not necessarily associated with the classic nuclear progesterone receptor, that seem to respond to progesterone receptor antagonist therapy.

Influence of a values clarification workshop on residents training at Catholic Hospital programs.

OBJECTIVES: To evaluate if a values clarification workshop conducted at Catholic hospital training programs influenced obstetrics and gynecology residents' abortion attitudes. STUDY DESIGN: Between 2018 and 2019, we provided a values clarification workshop focused on abortion care to 47 obstetrics and gynecology residents at five Catholic programs that do not provide abortion training. Participants received a pre-survey eliciting participant characteristics, and training experiences. On pre- and post-surveys, we asked participants to respond to abortion scenarios using a five-point Likert scales (1 = strongly disagree, 2 = somewhat disagree 3 = neither agree nor disagree, 4 = somewhat agree, 5 = strongly agree). We calculated descriptive frequencies, report the proportions agreeing with the statements (Likert ≥ 4) before and after the workshop, and compared median Likert responses using Wilcoxon matched pair test. RESULTS: Forty-one participants (87%) completed both surveys. Twelve (29%) reported Catholic religion, six (15%) reported their personal reproductive care views were in line with their institution, and five (12%) selected their program based on its religious affiliation. Three (9%) had experience with first-trimester abortion for nonmedical reasons, and 20 (49%) planned to provide such care after graduation. Both before and after the workshop, all participants could think of a justification why a patient with an undesired pregnancy would choose abortion. After the workshop, more residents were able to think of a justifiable reason for the following abortion-related scenarios: (1) patients declining post-abortal contraception (51% vs. 78%, p < 0.001), (2) patients presenting for subsequent abortion (93% vs 95%, p = 0.01), and (3) patients presenting for second-trimester abortion (93% vs. 100%, p = 0.001). Many participants increased their Likert score when asked about acceptability of patients declining post-abortal contraception (n = 24, 59%), patients seeking a subsequent abortion (n = 15, 37%), and patients obtaining a second trimester abortion contraception (n = 11, 27%). Emotional and professional reactions to these scenarios were unchanged. After the workshop, residents were more likely to consider either financial inability (73% vs. 83%, p < 0.01) or disruption to career or education (71% vs 80%, p < 0.01) as morally acceptable reasons for requesting an abortion. For abortion for a patient who is financially unable to support their child, 12 (29%) increased their Likert score, 1 (2%) had a lower score and the remaining 28 (68%) had no change. For abortion for a patient whose career or education would be disrupted 13 (32%) increased their Likert score, one (2%) had a lower score and the remaining 27 (66%) had no change. CONCLUSION: Our values clarification workshop resulted in more residents at Catholic training programs endorsing accepting attitudes toward abortion patient scenarios. Values clarification exercises can be a useful tool for residents to discuss abortion care, especially when training is insufficient. IMPLICATIONS: Most obstetrics and gynecology residents at Catholic hospitals experience limited training in abortion care. A values clarification workshop conducted at such programs may result in increasing resident acceptance of abortion-related patient care scenarios and may help reduce abortion stigma.

Genomic Breed Composition of Selection Signatures in Brangus Beef Cattle.

Cattle breeding routinely uses crossbreeding between subspecies (Bos taurus taurus and Bos taurus indicus) to form composite breeds, such as Brangus. These composite breeds provide an opportunity to identify recent selection signatures formed in the new population and evaluate the genomic composition of these regions of the genome. Using high-density genotyping, we first identified runs of homozygosity (ROH) and calculated genomic inbreeding. Then, we evaluated the genomic composition of the regions identified as selected (selective sweeps) using a chromosome painting approach. The genomic inbreeding increased at approximately 1% per generation after composite breed formation, showing the need of inbreeding control even in composite breeds. Three selected regions in Brangus were also identified as Angus selection signatures. Two regions (chromosomes 14 and 21) were identified as signatures of selection in Brangus and both founder breeds. Five of the 10 homozygous regions in Brangus were predominantly Angus in origin (probability >80%), and the other five regions had a mixed origin but always with Brahman contributing less than 50%. Therefore, genetic events, such as drift, selection, and complementarity, are likely shaping the genetic composition of founder breeds in specific genomic regions. Such findings highlight a variety of opportunities to better control the selection process and explore heterosis and complementarity at the genomic level in composite breeds.

Long-term High-quality Survival with Single-agent Mifepristone Treatment Despite Advanced Cancer.

CASE REPORT: We show long-term high-quality survival following single-agent treatment with a progesterone receptor antagonist in two cases of advanced metastatic cancer. Because no biopsy was performed (patient refused) the exact type of lung cancer was not determined but the majority of oncologists who evaluated the patient thought that the rapid onset and syndrome of inappropriate anti-diuretic hormone was more consistent with small-cell lung cancer. The US Food and Drug Association granted a compassionate-use investigational new drug approval for use of single-agent 200 mg mifepristone orally/day to a moribund woman with never-treated metastatic lung cancer and a male with bilateral renal cell carcinoma who had undergone only a unilateral hemi-nephrectomy. Both had long-term high-quality survival (5 years for the patient with lung cancer with complete remission of all lung lesions, and 12 years for the male patient with kidney cancer). Neither patient had any side-effects from mifepristone therapy. CONCLUSION: These cases helped influence the US Food and Drug Association in granting an investigator-initiated investigational new drug study on advanced non-small cell lung cancer.

Suppressor of sable [Su(s)] and Wdr82 down-regulate RNA from heat-shock-inducible repetitive elements by a mechanism that involves transcription termination.

Although RNA polymerase II (Pol II) productively transcribes very long genes in vivo, transcription through extragenic sequences often terminates in the promoter-proximal region and the nascent RNA is degraded. Mechanisms that induce early termination and RNA degradation are not well understood in multicellular organisms. Here, we present evidence that the suppressor of sable [su(s)] regulatory pathway of Drosophila melanogaster plays a role in this process. We previously showed that Su(s) promotes exosome-mediated degradation of transcripts from endogenous repeated elements at an Hsp70 locus (Hsp70-αß elements). In this report, we identify Wdr82 as a component of this process and show that it works with Su(s) to inhibit Pol II elongation through Hsp70-αß elements. Furthermore, we show that the unstable transcripts produced during this process are polyadenylated at heterogeneous sites that lack canonical polyadenylation signals. We define two distinct regions that mediate this regulation. These results indicate that the Su(s) pathway promotes RNA degradation and transcription termination through a novel mechanism.

Evidence that Mifepristone, a progesterone receptor antagonist, can cross the blood brain barrier and provide palliative benefits for glioblastoma multiforme grade IV.

BACKGROUND: Mifepristone, a progesterone receptor antagonist, has been found to provide palliative benefits for various types of spontaneous murine cancer in randomized controlled trials and in anecdotal reports from a variety of advanced metastatic human cancer not known to be associated with progesterone receptors. The theory of its mechanism is that it prevents the secretion of a progesterone-induced immunomodulatory protein in the tumor microenvironment, or in the tumor cell itself, called the progesterone-induced blocking factor, which inhibits natural killer cells from attacking the cancer cell. Many anticancer chemotherapeutic agents fail to cross the blood-brain barrier and thus prove ineffective for brain cancer. The objective of the present study was to determine if mifepristone could provide palliative benefits to a patient with end-stage stage IV glioblastoma multiforme. CASE REPORT: A 43-year-old male with end-stage stage IV glioblastoma multiforme was exclusively treated with mifepristone 200 mg orally daily. RESULTS: The patient showed definite palliative effects for several weeks and his life was significantly extended beyond pre-treatment predictors. CONCLUSION: It appears that mifepristone does cross the blood-brain barrier and could be considered for palliative therapy of other patients with chemotherapy-resistant brain cancer.

Progesterone receptor antagonist therapy has therapeutic potential even in cancer restricted to males as evidenced from murine testicular and prostate cancer studies.

BACKGROUND: Treatment with the progesterone receptor antagonist mifepristone has been shown to improve the length and quality of life in mice with spontaneous leukemia, breast cancer, and lung cancer. The present study evaluated the efficacy of mifepristone therapy in murine tumors restricted to males, i.e. testicular and prostate cancer. MATERIALS AND METHODS: Eight-week-old mice with a strong predisposition to testicular or prostate cancer were gavaged with mifepristone. Olive oil was used in place of mifepristone in order to provide a control. Survival rates and body conditioning scores were compared after one year of treatment. RESULTS: Non-significant trends in survival rates were found in both types of murine cancers. Mifepristone significantly reduced the number of sick days in mice with testicular cancer. There was a significant reduction of adverse events (i.e. a tumor >1 cm or bleeding from the penis) in those with prostate cancer treated with mifepristone. CONCLUSION: These data support the hypothesis that various cancers may utilize a mechanism that is present in normal pregnancy that involves secretion of a progesterone-induced protein that blocks natural killer cell activity. The hypothesis that the cancer cells have the capacity to direct local progesterone production is supported by demonstrating the benefit of a progesterone receptor antagonist in tumors restricted to males.

Efficacy of the progesterone receptor antagonist mifepristone for palliative therapy of patients with a variety of advanced cancer types.

BACKGROUND: Mifepristone has been demonstrated to improve longevity and quality of life in mice with spontaneous murine cancer without progesterone receptors and in human colon cancer. The present study evaluated the palliative effect of mifepristone in a variety of different types of human cancer. PATIENTS AND METHODS: Mifepristone was given at 200 mg daily orally with permission from the Food and Drug Administration to people with widely metastatic human cancer no longer responsive to other chemotherapy regimens. RESULTS: Improvement in pain and energy and/or length of life was found in thymic epithelial cell carcinoma, transitional cell carcinoma of the renal pelvis, leiomyosarcoma, pancreatic carcinoma, malignant fibrous histiocytoma and another case of adenocarcinoma of the colon. CONCLUSION: Our data demonstrate a palliative role for the use of mifepristone in cancer therapy. Progesterone receptor antagonists should be given a therapeutic trial in larger controlled studies of various malignancies in humans.

A cost-effectiveness comparison of embryo donation with oocyte donation.

OBJECTIVE: To compare the cost-effectiveness of embryo donation (ED) to that of oocyte donation (OD). DESIGN: Calculation of cost-effectiveness ratios (costs per outcome achieved) using data derived from clinical practices. SETTING: In vitro fertilization centers and embryo donation programs. PATIENT(S): Infertile couples undergoing oocyte donation or embryo donation. INTERVENTION(S): Oocyte donation or embryo donation cycles. MAIN OUTCOME MEASURE(S): Cost-effectiveness ratios. RESULT(S): For a single cycle, ED is approximately twice as cost-effective as OD, with a cost-effectiveness ratio of $21,990 per live delivery compared to 40,600 dollars. When strategies of up to three cycles (to achieve one live delivery) are used, ED costs 13,505 dollars per live delivery compared to 31,349 dollars for OD. CONCLUSION(S): Cost-effectiveness is a compelling reason for infertile couples to consider embryo donation.

Drosophila suppressor of sable protein [Su(s)] promotes degradation of aberrant and transposon-derived RNAs.

RNA-binding proteins act at various stages of gene expression to regulate and fine-tune patterns of mRNA accumulation. One protein in this class is Drosophila Su(s), a nuclear protein that has been previously shown to inhibit the accumulation of mutant transcripts by an unknown mechanism. Here, we have identified several additional RNAs that are downregulated by Su(s). These Su(s) targets include cryptic wild-type transcripts from the developmentally regulated Sgs4 and ng1 genes, noncoding RNAs derived from tandemly repeated alphabeta/alphagamma elements within an Hsp70 locus, and aberrant transcripts induced by Hsp70 promoter transgenes inserted at ectopic sites. We used the alphabeta RNAs to investigate the mechanism of Su(s) function and obtained evidence that these transcripts are degraded by the nuclear exosome and that Su(s) promotes this process. Furthermore, we showed that the RNA binding domains of Su(s) are important for this effect and mapped the sequences involved to a 267-nucleotide region of an alphabeta element. Taken together, these results suggest that Su(s) binds to certain nascent transcripts and stimulates their degradation by the nuclear exosome.

A retrospective comparison of pregnancy outcome following conventional oocyte insemination vs intracytoplasmic sperm injection for isolated abnormalities in sperm morphology using strict criteria.

Initial in vitro fertilization (IVF)-embryo transfer studies found poor fertilization and pregnancy rates following conventional fertilization of oocytes when using sperm with <4% normal morphology using strict criteria. Some consider today that sperm with only < or =5% normal morphology using strict criteria are associated with infertility. However, other studies have disputed the diagnostic potential of low strict morphology in identifying subnormal male fertility. Based on the original studies most IVF centers perform intracytoplasmic sperm injection (ICSI) when the sperm shows low morphology using strict criteria to allow selection of normal sperm. However, ICSI adds extra time for the embryologist and extra expense for the infertile couple. The present study retrospectively compared fertilization, pregnancy, and implantation rates according to the 2 methods of oocyte fertilization with sperm having normal morphology using strict criteria of < or =5% in women < or =39 years. All fresh embryo transfers were performed on day 3. There was a significantly higher fertilization rate with ICSI. However, there were significantly higher clinical and delivered pregnancy and implantation rates following conventional insemination. The rate of canceled transfers due to no available embryo was 1.9% with conventional insemination vs 1.5% for ICSI in women with adequate egg reserve. Hopefully, this retrospective study will generate interest in a prospective study.

Effect of embryo quality on pregnancy outcome following single embryo transfer in women with a diminished egg reserve.

OBJECTIVE: To evaluate independently the effect of blastomere number and degree of fragmentation on pregnancy outcome following single ETs in women with a decreased egg reserve. DESIGN: Retrospective cohort analysis. SETTING: In vitro fertilization center of a university-based practice. PATIENT(S): Women having a single ET related to a decreased egg reserve. A requirement for inclusion was a day 3 serum FSH >12 mIU/mL and < or =3 antral follicles on ultrasound. INTERVENTION(S): Patients received no or minimal stimulation with gonadotropins. MAIN OUTCOME MEASURE(S): Pregnancy rates (PRs) following single ETs were evaluated according to blastomere number (group 1, < or =4 cells; group 2, 5 cells; group 3, 6 cells; group 4, 7 cells; and group 5, > or =8 cells) and fragmentation index (A, no fragmentation; B, 1-25% fragmentation; and C, >25% fragmentation). Embryo transfers and morphologic evaluation were performed on day 3. RESULT(S): The clinical and delivered PRs according to blastomere number showed that 6-8-cell embryos were six times more likely to implant than 4-5-cell embryos (6.6% versus 40.4% clinical). Degree of fragmentation did not predict outcome nearly as well as blastomere number. The overall clinical and delivered PRs per transfer were 27.8% and 24.1%, respectively, and were 14.8% and 12.8% per retrieval, respectively, and were 9.0% and 7.3% per initiated cycle, respectively. CONCLUSION(S): Six, seven, or eight-cell embryos have equal chances of implanting in women with day 3 elevated serum FSH. The key finding is that these embryos do better than those with <6 blastomeres. These data may be helpful in women with a diminished ovarian reserve in attempting IVF with their own eggs or when choosing donor oocytes.

Antagonism of CRF receptors prevents the deficit in brain reward function associated with precipitated nicotine withdrawal in rats.

Nicotine dependence is a chronic mental illness that is characterized by a negative affective state upon tobacco smoking cessation and relapse after periods of abstinence. It has been hypothesized that cessation of nicotine administration results in the activation of brain corticotropin-releasing factor (CRF) systems that leads to the negative affective state of withdrawal. The aim of our experiments was to investigate the role of brain CRF systems in the deficit in brain reward function associated with the cessation of nicotine administration in rats. The intracranial self-stimulation procedure was used to assess to negative affective aspects of nicotine withdrawal as this procedure can provide a quantitative measure of emotional distress in rats. In the first experiment, mecamylamine induced a dose-dependent elevation in brain reward thresholds in nicotine-treated rats. In the follow-up experiment, it was shown that pretreatment with the corticotropin-receptor antagonist D-Phe CRF((12-41)) prevents the elevations in brain reward thresholds associated with precipitated nicotine withdrawal. In the third experiment, the effect of D-Phe CRF((12-41)) on the elevations in brain reward thresholds associated with spontaneous nicotine withdrawal was investigated. Administration of D-Phe CRF((12-41)) 6 h after the explantation of the nicotine pumps, did not result in a lowering of the brain reward thresholds. These findings indicate that antagonism of CRF receptors prevents, but not reverses, the deficit in brain associated with nicotine withdrawal. These data provide support for the hypothesis that a hyperactivity of brain CRF systems may at least partly mediate the initiation of the negative affective aspects of nicotine withdrawal.

The feasibility of embryo donation.

Transfer of donated frozen embryos of various quality to recipients resulted in a delivered pregnancy rate of 36.8% per transfer. Hopefully these data will encourage other in vitro fertilization programs to set up similar programs.