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Brain parenchymal involvement by mantle cell lymphoma is rare and confers a grim prognosis. More commonly, patients with central nervous system manifestations of mantle cell lymphoma have leptomeningeal involvement on radiographic studies with malignant cells found in the cerebrospinal fluid. Risk factors for central nervous system involvement include a high proliferation index, bone marrow involvement, and blastoid morphology. We present an unusual case of a biopsy-proven mantle cell lymphoma mass lesion in the brain parenchyma as the presentation of relapse 6 months after diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To measure the change perceived by patients after endonasal rhinoplasty using a, septal extension graft (SEG), as measured by patient-reported outcome measures (PROMs). Methods: A retrospective review of patients with nasal obstruction underwent septoplasty, turbinoplasty, and SEG. PROMs were assessed to compare operative outcomes for breathing (Nose Obstruction Symptom Evaluation [NOSE], Sinonasal Outcome Test [SNOT]-22, Standardized Cosmesis and Health Nasal Outcomes Survey [SCHNOS]), and sleep quality (Epworth Sleepiness Scale [ESS]) Results: Of the 34 patients undergoing rhinoplasty with Endonasal SEG, the median patient age was 38.3 years (range 17-58) and mostly male ( n  = 18, 52.9%). Additional procedures performed on the patients included septoplasty ( n  = 34, 100%) and turbinate reduction ( n  = 34, 100%). Average follow-up was 126.6 days (range 28-573) for a majority of PROMs. There were no complications. The average change in NOSE score was 71.5 and -49.4 (standard deviation [SD] = 19.0, p  < 0.001). SNOT-22 change was 35.4 and -24.2 (SD = 14.5, p  < 0.001), and ESS scores averaged 6.7 and -3.4 (SD = 4.3, p  < 0.001). The average SCHNOS total, functional, and cosmetic scores were 40.6, 67.9, and 22.4, respectively, and -28.0 (SD = 19.8), -44.5 (SD = 22.9), and 17.1 (SD = 24.6) ( p  < 0.001). Conclusion: In this pilot study, patients reported improvement in nasal breathing after correcting a deviated caudal septum and applying an Endonasal SEG.

Introduction: Mandibular resection and reconstruction are common but complex procedures in head and neck surgery. Resection with adequate margins is critical to the success of the procedure but technical training is restricted to real case experience. Here we describe our experience in the development and evaluation of a mandibular resection and reconstruction simulation module., Methods: 3D printed (3DP) models of a mandible with a pathologic lesion were developed from imaging data from a patient with an ameloblastoma. During an educational conference, otolaryngology trainees participated in a simulation in which they reviewed a CT scan of the pathologic mandible and then planned their osteotomies before and after handling a 3DP model demonstrating the lesion. The adequacy of the osteotomy margins was assessed and components of the simulation were rated by participants with pre- and post-training surveys., Results: 52 participants met criteria. After reviewing the CT scan, 34 participants (65.3 %) proposed osteotomies clear of the lesion. This proportion improved to 48 (92.3 %, p = 0.001) after handling the 3D model. Among those with initially adequate margins (n = 33), 45.5 % decreased their margins closer to the ideal, 27.2 % made no revision, 21.2 % widened their margins. 92 % of participants found the simulation beneficial for surgical planning and technical training. After the exercise, the majority of participants had increased confidence in conceptualizing the boundaries of the lesion (69.2 %) and their abilities to ablate (76.5 %)., Conclusions: The structured mandibulectomy simulation using 3DP models was useful in the development of trainee experience in segmental mandible resection., Lay Summary: This study presents the first mandibulectomy simulation module for trainees with the use of 3DP models. The use of a 3DP model was also shown to improve the quality of surgical training., Competing Interests: Declaration of competing interest No funding or conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Preservation rhinoplasty is a re-emerging technique that lacks data on functional and aesthetic outcomes. Objective: To measure the change in patient-reported nasal aesthetic perception, nasal breathing, and sleep and compare outcomes between two different septal cartilage manipulation techniques among patients undergoing preservation rhinoplasty. Methods: Functional and aesthetic outcomes of a let down dorsal preservation rhinoplasty using either the modified subdorsal strip method (MSSM) or subdorsal Z-flap are assessed pre- and postoperatively using the validated assessment tools Nose Obstruction Symptom Evaluation (NOSE), Sinonasal Outcome Test (SNOT-22), Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS), and Epworth Sleepiness Scale (ESS). Results: Fifty-two patients, 40 women and 12 men ages 15-69 years, underwent dorsal preservation rhinoplasty and the majority reported at 1, 3, 6, and 12 months postoperatively significant improvement based on a paired t -test in NOSE, SNOT-22, SCHNOS, and ESS scores except for ESS scores at 6 and 12 months. No significant difference based on a two-sample t -test was observed between the MSSM and Z-flap techniques implemented. Conclusion: Let down dorsal preservation rhinoplasty with either the MSSM or Z-flap cartilage manipulation technique can achieve significant improvement in nasal aesthetics, nasal breathing, and sleep according to patient responses on validated assessment tools.

Gonadotropin-releasing hormone agonists (GnRHa) are used as an alternative to human chorionic gonadotropin (hCG) to trigger ovulation and decrease the risk of ovarian hyperstimulation syndrome. GnRHa is less potent at inducing ovarian vascular endothelial growth factor (VEGF), but may also affect endometrial angiogenesis and early placental development. In this study, we explore the effect of superovulation on endometrial angiogenesis during critical periods of gestation in a mouse model. We assigned female mice to three groups: natural mating or mating following injection with equine chorionic gonadotropin and trigger with GnRHa or hCG trigger. Females were killed prior to implantation (E3.5), post-implantation (E7.5), and at midgestation (E10.5), and maternal serum, uterus, and ovaries were collected. During peri-implantation, endometrial Vegfr1 and Vegfr2 mRNA were significantly increased in the GnRHa trigger group (P < 0.02) relative to the hCG group. Vegfr1 is highly expressed in the endometrial lining and secretory glands immediately prior to implantation. At E7.5, the ectoplacental cone expression of Vegfa and its receptor, Vegfr2, was significantly higher in the hCG trigger group compared to the GnRHa group (P < 0.05). Soluble VEGFR1 and free VEGFA were much higher in the serum of mice exposed to the hCG trigger compared to GnRHa group. At midgestation, there was significantly more local Vegfa expression in the placenta of mice triggered with hCG. GnRHa and hCG triggers differentially disrupt the endometrial expression of key angiogenic factors during critical periods of mouse gestation. These results may have significant implications for placental development and neonatal outcomes following human in vitro fertilization., (© The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To assess the reproductive and neonatal outcomes of cycles in which donor oocyte embryos were transferred to gestational carriers compared to intended parent recipients., Design: Retrospective cohort study., Setting: Not applicable., Patient(s): Intended parent recipients and gestational carriers receiving donor oocyte embryos in 2014 in the United States., Interventions(s): None., Main Outcomes Measure(s): Clinical pregnancy, live birth, miscarriage, plurality, prematurity, and birth weight from pregnancies conceived with donor oocyte embryos transferred to either a gestational carrier or an intended parent recipient., Result(s): The mean ages of intended parent recipients (N=18,317) and gestational carriers (N=1,927) were 41.6 and 31.6 years, respectively. Compared to an intended parent recipient, patients using a gestational carrier had significantly higher odds of a clinical pregnancy (65.2% vs. 56.3%, adjusted odds ratio (aOR) 1.33, 95% confidence interval (CI) 1.17-1.51) and live birth (57.1% vs. 46.4%, aOR 1.37, 95% CI 1.21-1.55) using fresh or frozen donor-oocyte embryos. Of the singletons born (n=716 using a gestational carrier and n=5,632 in intended parent recipients), the incidence of prematurity was significantly lower in gestational carriers compared to intended parent recipients (17.5% vs. 25.4%, aOR 0.78, 95% CI 0.61-0.99). The incidence of low birthweight among singletons was significantly reduced in gestational carrier cycles (6.4% vs. 12.1%, aOR 0.62, 95% CI 0.44-0.89)., Conclusion: Intended parent recipients had decreased pregnancy rates and poorer neonatal outcomes compared to a gestational carrier. This suggests that a history of infertility adversely affects the uterine microenvironment, independent of the oocyte., (Copyright © 2018 American Society for Reproductive Medicine. All rights reserved.)

This monograph, written by the pioneers of IVF and reproductive medicine, celebrates the history, achievements, and medical advancements made over the last 40 years in this rapidly growing field., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: The inferior turbinates are routinely examined by otolaryngologists on anterior rhinoscopy and nasal endoscopy. Most lesions of the inferior turbinate are benign but can often be confused with malignancy. This review highlights the broad differential of nonmalignant lesions of the inferior turbinates and their management., Recent Findings: A variety of infectious, inflammatory, neoplastic, and vascular lesions may affect the inferior turbinates. The most common nonmalignant lesions of the sinonasal region are nasal polyps, inverted papillomas, hemangiomas, and angiofibromas. Early lesions are often asymptomatic and discovered incidentally on routine examination. As these lesions grow they present with nonspecific signs that can be seen in benign, malignant, and infectious etiologies. The most common signs and symptoms are nasal obstruction, rhinorrhea, epistaxis, sinusitis, and hyposmia. Most nonmalignant lesions have characteristic appearances but definitive diagnosis is achieved with biopsy or culture. If the lesions are small the biopsy itself is often curative., Summary: Lesions of the inferior turbinates are rarely isolated to these structures alone. Careful examination can noninvasively assist in early diagnosis of extensive lesions. Once malignancy and processes such as invasive fungal sinusitis or inverted papillomas have been ruled out, treatment of these lesions is ordinarily noncomplicated and definitive.

Objective: To conduct the first and only systematic review of the existing literature on head and neck manifestations of eosinophilic granulomatosis with polyangiitis to guide clinical decision making for the otolaryngologist., Data Sources: PubMed, Cochrane Library, Scopus, and LILACS., Review Methods: A systematic review of the aforementioned sources was conducted per the PRISMA guidelines., Results: From an initial 574 studies, 28 trials and reports were included, accounting for a total of 1175 patients with eosinophilic granulomatosis with polyangiitis. Among clinical and cohort studies, 48.0% to 96.0% of all included patients presented with head and neck manifestations. In a distinct group of patients detailed in case reports describing patients presenting with head and neck manifestations, patients on average fulfilled 4.6 diagnostic criteria per the American College of Rheumatology. Furthermore, 95.8% of reported cases were responsive to steroids, and 60% required additional therapy., Conclusion: Otolaryngologists are in a unique position for the early diagnosis and prevention of late complications of eosinophilic granulomatosis with polyangiitis. The American College of Rheumatology criteria should be relied on in the diagnostic workup. Close surveillance of these patients in a multidisciplinary fashion and with baseline complete blood counts, chest radiographs, and autoimmune laboratory tests is often necessary. Such patients with head and neck manifestations of the disease are nearly always responsive to steroids and often require additional immunosuppressive therapy or surgical intervention in cases of cranial neuropathies, temporal bone involvement, and refractory symptoms., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.)

Objective: To analyze donor oocyte cycles in the Society for Assisted Reproductive Technology (SART) registry to determine: 1) how many cycles complied with the 2009 American Society for Reproductive Medicine/SART embryo transfer guidelines; and 2) cycle outcomes according to the number of embryos transferred. For donor oocyte IVF with donor age <35 years, the consideration of single-embryo transfer was strongly recommended., Design: Retrospective cohort study of United States national registry information., Setting: Not applicable., Patient(s): A total of 13,393 donor-recipient cycles from 2011 to 2012., Intervention(s): Embryos transferred in donor IVF cycles., Main Outcome Measure(s): Percentage of compliant cycles, multiple pregnancy rate., Result(s): There were 3,157 donor cleavage-stage transfers and 10,236 donor blastocyst transfers. In the cleavage-stage cycles, 88% met compliance criteria. The multiple pregnancy rate (MPR) was significantly higher in the noncompliant cycles. In a subanalysis of compliant cleavage-stage cycles, 91% transferred two embryos and only 9% single embryos. In those patients transferring two embryos, the MPR was significantly higher (33% vs. 1%). In blastocyst transfers, only 28% of the cycles met compliance criteria. The MPR was significantly higher in the noncompliant blastocyst cohort at 53% (compared with 2% in compliant cycles)., Conclusion(s): The majority of donor cleavage-stage transfers are compliant with current guidelines, but the transfer of two embryos results in a significantly higher MPR compared with single-embryo transfer. The majority of donor blastocyst cycles are noncompliant, which appears to be driving an unacceptably high MPR in these cycles., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether IVF clinics are compliant with American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology (SART) (ASRM/SART) guidelines and assess the multiple pregnancy outcomes according to the number of embryos transferred., Design: Retrospective cohort study., Setting: Not applicable., Patient(s): Data from 59,689 fresh first autologous IVF cycles from the 2011-2012 SART registry., Intervention(s): None., Main Outcome Measure(s): Percentage of compliant cycles, multiple pregnancy rate (PR)., Result(s): Between 2011 and 2012, a total of 59,689 fresh first autologous cycles were analyzed. Among cleavage-stage ET cycles, the noncompliance rate ranged from 10%-27.4% depending on the age group. The multiple PR was significantly increased in noncompliant cycles involving patients <35 years (38.1% vs. 28.7%) and 35-37 years (35.4% vs. 24.5%) compared with compliant cycles. Among blastocyst-stage ET cycles, the highest rate of noncompliance was seen in patients <35 years old (71%), which resulted in a statistically higher multiple PR (48.3% vs. 2.8%) compared with compliant cycles. Far fewer cycles were noncompliant in patients 35-40 years of age. In a subanalysis of compliant cycles, transferring two blastocyst embryos in patients 35-37 years and 38-40 years resulted in a higher live birth rate compared with the transfer of one embryo (50.4% vs. 40.9% and 42.1% vs. 30.0%, respectively) but the multiple PR was also significantly higher (40.5% vs. 1.7% and 34.0% vs. 2.0%, respectively)., Conclusion(s): Most first fresh autologous IVF cycles performed from 2011-2012 were compliant with ASRM/SART guidelines, except those that involved a blastocyst ET in patients <35 years. Despite compliance, cycles that involved the transfer of >1 embryo resulted in a high multiple PR, whereas noncompliant cycles resulted in an even more remarkable multiple PR for both cleavage and blastocyst-stage embryos. Clinics need to be more compliant with ET limits and ASRM/SART need to consider revising their guidelines to limit the number of blastocyst transfer to one in patients ≤40 years of age undergoing their first IVF cycle. Furthermore, decreasing the number of cleavage-stage embryos transferred in patients ≤40 years of age should also be considered., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the effect of body mass index (BMI) on IVF outcomes in fresh autologous cycles., Design: Retrospective cohort study., Setting: Not applicable., Patient(s): A total of 239,127 fresh IVF cycles from the 2008-2010 Society for Assisted Reproductive Technology registry were stratified into cohorts based on World Health Organization BMI guidelines. Cycles reporting normal BMI (18.5-24.9 kg/m(2)) were used as the reference group (REF). Subanalyses were performed on cycles reporting purely polycystic ovary syndrome (PCOS)-related infertility and those with purely male-factor infertility (34,137 and 89,354 cycles, respectively)., Intervention(s): None., Main Outcome Measure(s): Implantation rate, clinical pregnancy rate, pregnancy loss rate, and live birth rate., Result(s): Success rates and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for all pregnancy outcomes were most favorable in cohorts with low and normal BMIs and progressively worsened as BMI increased. Obesity also had a negative impact on IVF outcomes in cycles performed for PCOS and male-factor infertility, although it did not always reach statistical significance., Conclusion(s): Success rates in fresh autologous cycles, including those done for specifically PCOS or male-factor infertility, are highest in those with low and normal BMIs. Furthermore, there is a progressive and statistically significant worsening of outcomes in groups with higher BMIs. More research is needed to determine the causes and extent of the influence of BMI on IVF success rates in other patient populations., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the effect of recipient body mass index (BMI) on IVF outcomes in fresh donor oocyte cycles., Design: Retrospective cohort study., Setting: Not applicable., Patient(s): A total of 22,317 donor oocyte cycles from the 2008-2010 Society for Assisted Reproductive Technology Clinic Outcome Reporting System registry were stratified into cohorts based on World Health Organization BMI guidelines. Cycles reporting normal recipient BMI (18.5-24.9) were used as the reference group., Intervention(s): None., Main Outcome Measure(s): Implantation rate, clinical pregnancy rate (PR), pregnancy loss rate, live birth rate., Result(s): Success rates and adjusted odds ratios with 95% confidence intervals for all pregnancy outcomes were most favorable in cohorts of recipients with low and normal BMI, but progressively worsened as BMI increased., Conclusion(s): Success rates in recipient cycles are highest in those with low and normal BMI. Furthermore, there is a progressive and statistically significant worsening of outcomes in groups with higher BMI with respect to clinical pregnancy and live birth rate., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To use a large US IVF database and compare pregnancy outcomes in fresh donor oocyte versus autologous IVF cycles in women age 20-30 years., Design: Retrospective cohort study., Setting: Not applicable., Patient(s): Women undergoing fresh autologous ovarian stimulation, and oocyte donors and recipients in the United States between 2008 and 2010., Intervention(s): None., Main Outcome Measure(s): Implantation, clinical pregnancy (CP), and live birth (LB) rates., Result(s): Despite similar demographics, stimulation, and embryo parameters, donor oocyte recipients had significantly higher rates of implantation, CP, and LB compared to those undergoing fresh autologous cycles. Odds ratios for implantation, CP, and LB significantly favored the donor oocyte group in all comparisons, including those limited to intracytoplasmic sperm injection cycles, intracytoplasmic sperm injection with male factor, unexplained infertility, cleavage stage embryo transfer, blastocyst transfer, elective single blastocyst transfer, and autologous patients with prior tubal ligation., Conclusion(s): Recent US data suggest that the hormonal environment resulting from autologous ovarian stimulation lowers IVF success rates. Further research is needed to determine when to avoid fresh embryo transfer in autologous patients., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To use a large and recent national registry to provide an updated report on the effect of recipient age on the outcome of donor oocyte in vitro fertilization (IVF) cycles., Design: Retrospective cohort study., Setting: United States national registry for assisted reproductive technology., Patient(s): Recipients of donor oocyte treatment cycles between 2008 and 2010, with cycles segregated into five age cohorts: ≤34, 35 to 39, 40 to 44, 45 to 49, and ≥50 years., Intervention(s): None., Main Outcome Measure(s): Implantation, clinical pregnancy, live-birth, and miscarriage rates., Result(s): In donor oocyte IVF cycles, all age cohorts ≤39 years had similar rates of implantation, clinical pregnancy, and live birth when compared with the 40- to 44-year-old reference group. Patients in the two oldest age groups (45 to 49, ≥50 years) experienced statistically significantly lower rates of implantation, clinical pregnancy, and live birth compared with the reference group. Additionally, all outcomes in the ≥50-year-old group were statistically significantly worse than the 45- to 49-year-old group, demonstrating progressive decline with advancing age., Conclusion(s): Recent national registry data suggest that donor oocyte recipients have stable rates of pregnancy outcomes before age 45, after which there is a small but steady and significant decline., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the association between oocyte number and the rates of ovarian hyperstimulation syndrome (OHSS) and live birth (LB) in fresh autologous in vitro fertilization (IVF) cycles., Design: Retrospective cohort study., Setting: An academic reproductive medicine practice., Patient(s): We analyzed data from 256,381 IVF cycles using the 2008-2010 Society for Assisted Reproductive Technology national registry. Patients were divided into five groups based on retrieved oocyte number., Main Outcome Measure(s): Rates of OHSS and LB were calculated for each group. A generalized estimating equation (GEE) was used to assess differences in OHSS and LB between groups. Receiver operating characteristic (ROC) curves were used to evaluate oocyte number as a predictor of OHSS and LB., Intervention(s): None., Result(s): The LB rate increased up to 15 oocytes, then plateaued (0-5: 17%, 6-10: 31.7%; 11-15: 39.3%; 16-20: 42.7%; 21-25: 43.8%; and >25 oocytes: 41.8%). However, the rate of OHSS became much more clinically significant after 15 oocytes (0-5: 0.09%; 6-10: 0.37%; 11-15: 0.93%; 16-20: 1.67%; 21-25: 3.03%; and >25 oocytes: 6.34%). These trends remained after adjustment with the use of GEE. ROC curves revealed that although oocyte number is not useful in the prediction of LB, 15 retrieved oocytes is the number that best predicts OHSS risk., Conclusion(s): Retrieval of >15 oocytes significantly increases OHSS risk without improving LB rate in fresh autologous IVF cycles. In general, less aggressive stimulation protocols should be considered, especially in high-responders, to optimize outcomes., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

This analysis explores the impact of modifying the Smokefree Women Facebook social media strategy, from primarily promoting resources to encouraging participation in communications about smoking cessation by posting user-generated content. Analyses were performed using data from the Smokefree Women Facebook page to assess the impact of the revised strategy on reach and engagement. Fan engagement increased 430%, and a strong and statistically significant correlation (P < .05) between the frequency of moderator posts and community engagement was observed. The reach of the page also increased by 420%. Our findings indicate that the strategy shift had a statistically significant and positive effect on the frequency of interactions on the Facebook page, providing an example of an approach that may prove useful for reaching and engaging users in online communities. Additional research is needed to assess the association between engagement in virtual communities and health behavior outcomes.

Objective: To describe our Partnership for Families Program, which was established to provide second in vitro fertilization (IVF) cycles for couples who pay for one IVF cycle, do not get pregnant and cannot afford a second IVF cycle. In addition, this program provides funding for fertility-sparing procedures for financially needy cancer patients., Study Design: Retrospective description of the Partnership for Families' first 5 years of operation., Results: In its 5 years of operation, the Partnership for Families Program has provided 137 infertile couples with a second IVF cycle, resulting in 68 ongoing or delivered pregnancies. It has also provided funding for 19 fertility-sparing procedures for cancer patients., Conclusion: Because of the high costs of IVF, alternative funding sources, specifically philanthropy, must be explored to provide increased access to IVF. The Partnership for Families Program, started by patients in a single practice, has in 5 years provided over 151 infertile and cancer patients IVF or egg-freezing cycles that they otherwise could not have afforded. This is a program that can be emulated by other fertility centers.

Objective: To compare the efficacy of recombinant FSH and urinary-derived hMG for ovarian stimulation during IVF., Design: Retrospective analysis of data from IVF cycles conducted over 15 months., Setting: University hospital IVF unit., Patient(s): Three hundred twenty-four women undergoing their first to sixth IVF cycle., Intervention(s): After pituitary down-regulation, patients received recombinant FSH or hMG, according to personal choice. After hCG administration, patients underwent oocyte retrieval, oocyte fertilization, and embryo transfer., Main Outcome Measure(s): Implantation rate and clinical ongoing pregnancy rate per oocyte retrieval., Result(s): Patients who chose recombinant FSH were slightly younger than those who chose hMG (34.1 vs. 35.1 years, respectively). Although more embryos were transferred in the hMG group (3.6 vs. 3.2), the ongoing pregnancy and implantation rates were significantly higher in the recombinant FSH group (ongoing pregnancy rate, 50.0% vs. 36.2%)., Conclusion(s): Recombinant FSH is more effective than hMG for ovarian stimulation in IVF cycles. This increased efficacy, which is achieved with fewer ampoules, is likely to offset the higher acquisition costs of recombinant FSH.

A scoring system specific for day 3 embryos has not been extensively explored. Most IVF laboratories continue to grade embryos solely on the basis of cell number and percentage fragmentation as was traditionally done for day 2 embryos. Additional morphological features, some unique to day 3 embryos, may be useful in selecting embryos most likely to blastulate and implant. The objective of this study was to derive an embryo scoring system for day 3 transfers which is predictive of positive pregnancy outcomes. A total of 316 transferred embryos from 93 patients was recorded on videotape and evaluated. The following parameters were used to grade the embryos: cell number, fragmentation pattern (FP), cytoplasmic pitting, compaction, equal sized blastomeres, blastomere expansion and absence of vacuoles. The clinical pregnancy rate was 41.9%, with an implantation rate of 18% per embryo transferred. The mean number of embryos transferred per patient was 3.4. Three formulae were derived to score embryo quality in each transfer based on the average score of individual embryos transferred. In the first scoring system, cell number alone was used to predict pregnancy outcome. The second scoring system was based on blastomere number and the observed FP. The third scoring system utilized both blastomere number and FP but also combined this with five morphological criteria to yield a final day 3 embryo quality (D3EQ) score. We found the D3EQ score to be prognostic of pregnancy outcome. This study suggests that although cell number and FP are certainly predictors of positive pregnancy outcomes, additional parameters specific to day 3 embryos should be used to stratify a cohort of embryos further.

Objective: To describe two cases of subclavian deep vein thrombosis (DVT) associated with the use of recombinant gonadotropins and mild ovarian hyperstimulation syndrome (OHSS) and review the literature associated with this condition., Design: Retrospective study (case report)., Setting: Tertiary academic IVF program., Patient(s): Two women undergoing IVF with intracytoplasmic sperm injection due to male factor infertility., Intervention(s): Ovaluation induction with recombinant FSH, IVF, and therapeutic heparinization., Main Outcome Measure(s): Coagulation studies, resolution of DVT, delivery at term., Result(s): Mild OHSS with left subclavian thrombosis occurred in two patients. Laboratory evaluation revealed normal protein C, protein S, antinuclear antibodies (ANA), and absence of antiphospholipid (APA) and anticardiolipin antibodies (ACA). Antithrombin III levels and coagulation studies were also within normal limits. Both patients tested negative for a factor V Leiden mutation and delivered healthy infants at term., Conclusion(s): Arm swelling associated with the use of gonadotropins during controlled ovarian hyperstimulation should be promptly evaluated and treated. Subclavian vein thrombosis is a rare complication of ovulation induction, and the possibility that recombinant gonadotropins increase the risk for this complication should be further studied.

The purpose of our study was to review and evaluate retrospectively the experience of an in-vitro fertilization (IVF) surrogate gestational programme in a tertiary care and academic centre. In a 15 year period from 1984 to 1999, a total of 180 cycles of IVF surrogate gestational pregnancy was started in 112 couples. On average, the women were 34.4 +/- 4.4 years of age, had 11.1 +/- 0.72 oocytes obtained per retrieval, 7.1 +/- 0.5 oocytes fertilized and 5. 8 +/- 0.4 embryos subsequently cleaved. Sixteen cycles (8.9%) were cancelled due to poor stimulation. Except for six cycles (3.3%) where there were no embryos available, an average of 3.2 +/- 0.1 embryos was transferred to each individual recipient. The overall pregnancy rate per cycle after IVF surrogacy was 24% (38 of 158), with a clinical pregnancy rate of 19% (30 of 158), and a live birth rate of 15.8% (25 of 158). When compared to patients who underwent a hysterectomy, individuals with congenital absence of the uterus had significantly more oocytes retrieved (P < 0.006), fertilized, cleaved and more embryos available for transfer despite being of comparable age. IVF surrogate gestation is an established, yet still controversial, approach to the care of infertile couples. Take-home baby rates are comparable to conventional IVF over the same 15 year span in our programme. Patients with congenital absence of the uterus responded to ovulation induction better than patients who underwent a hysterectomy, perhaps due in part to ovarian compromise from previous surgical procedures.

The objective of this study was to analyze follicular fluid active renin and its relationship to steroid hormones throughout the normal and gonadotropin-stimulated menstrual cycle. Active renin was measured in the follicular fluid of patients undergoing tubal sterilization (n = 16) and in vitro fertilization (IVF) (n = 25); IVF patients were either in a natural cycle (n = 7) or undergoing controlled ovarian hyperstimulation (n = 18). The largest visible follicle was aspirated at the time of laparoscopic tubal sterilization; ultrasound guided transvaginal follicular aspiration was used in the IVF group. Follicular fluid active renin, estradiol and progesterone levels were measured with immunoradiometric and fluoroimmunoassays. The cycle day was correlated with the spontaneous luteinizing hormone (LH) surge or human chorionic gonadotropin (hCG) administration, as well as active renin, estradiol, progesterone levels and the estradiol/progesterone ratio using simple and multiple regression and analysis of variance (ANOVA). Cycle day independently influenced active renin, progesterone and the estradiol/progesterone ratio in a statistically significant manner (p < 0.0001). The active renin and progesterone levels were highest during the periovulatory period (p < 0.0001 and p < 0.002, respectively) and the estradiol/progesterone ratio correlated inversely with cycle day (p < 0.003). Although the follicular fluid active renin, estradiol and progesterone levels were higher after controlled ovarian hyperstimulation when compared to natural cycles, this difference did not reach statistical significance. Our findings suggest that active renin levels in follicular fluid increase in the follicular phase of the menstrual cycle, reaching peak levels in the periovulatory period following the LH surge or hCG administration, providing indirect support for the hypothesis that the ovarian renin-angiotensin system (RAS) is under gonadotropin control.

Problem: The effects of exogenous gonadotropin administration and steroid levels on the release of various cytokines into the human follicular fluid (FF) were studied., Method of Study: Forty patients were included in two groups, those undergoing controlled ovarian hyperstimulation (COH) (n = 33) and natural cycles (n = 7). FF transvaginal aspirations were performed 36 hr after administration of human chorionic gonadotropin or a spontaneous surge of luteinizing hormone, respectively. FF cytokine measurements were performed with sensitive immunoassays., Results: FF cytokine levels were higher after COH [interleukin (IL)-1 beta, 6.6 +/- 0.32 pg/ml; IL-6, 18.7 +/- 2.1 pg/ml; and tumor necrosis factor (TNF)-alpha, 32.5 +/- 4.9 pg/ml] than in natural unstimulated cycles (0.52 +/- 0.1 pg/ml, P < 0.001; 8.9 +/- 1.2 pg/ml, P < 0.01; and 13.2 +/- 2.6 pg/ml, P < 0.001, respectively). FF estradiol (E2) and progesterone levels were not statistically different between groups, despite the higher serum E2 levels observed in patients after COH., Conclusions: Gonadotropins might regulate ovarian secretion of cytokines, because FF IL-1 beta, IL-6, and TNF-alpha levels after COH were higher than during natural cycles.

Purpose: Our purpose was to analyze factors for their predictability of multiple pregnancies in patients treated with a combination of human menopausal gonadotropins (hMG) and intrauterine insemination (IUI)., Methods: The records of all patients conceiving through treatment with hMG/IUI were reviewed for factors predictive of multiple pregnancy., Results: Ninety-one pregnancies reviewed included 78 singleton (86%), 8 twin (9%), and 5 higher-order pregnancies (5%). The total number of follicles > 10 mm was greater in the multiple-pregnancy group and there was a decreased number of postwash sperm in the multiple-pregnancy group. Otherwise there was no significant difference in the factors analyzed., Conclusions: No factor or combination of factors predicts multiple pregnancies to a degree that it would be helpful in managing or counseling patients.

Objective: To estimate the cost per woman delivered of a shared oocyte in an in vitro fertilization (IVF) program, and to compare these costs with those of a routine IVF program., Methods: The cost of 23 shared oocyte cycles was analyzed retrospectively and compared with the cost of routine IVF., Results: The cost per woman delivered in the shared oocyte program was approximately $22,000, compared with $66,000 in the routine IVF program., Conclusion: Shared IVF is a very cost-effective program and others donors and recipients an otherwise unavailable opportunity.

Objective: Our goal was to identify and quantitate growth factors and cytokines actively secreted by a permanent human endometrial cell line with embryotrophic properties and to determine if cell lines enhancing embryo development secrete common growth factors and/or cytokines., Design: Culture medium conditioned by this human endometrial cell line was screened for platelet-derived growth factor (PDGF), leukemia inhibitory factor (LIF), interleukin-6 (IL-6), epidermal growth factor (EGF), and transforming growth factor-beta (TGF-beta) by enzyme-linked immunoassay (ELISA). Comparisons were made to the African Green monkey kidney epithelial cell line (Vero), which has been well documented to be embryotrophic., Setting: This study was conducted in a university-based research laboratory associated with a clinical IVF program., Results: The monkey Vero cell line and our permanent human endometrial cell line produced several common growth factors and cytokines, such as IL-6, PDGF, and LIF. IL-6 was secreted in substantial amounts by both Vero cells (400 pg/ml per 100,000 cells) and endometrial cells (100 pg/ml). PDGF levels in culture supernatant were measured to be 72 and 35 pg/ml, respectively, for Vero and endometrial cells. LIF could not be assayed in our human cell line by ELISA but its presence was evidenced by immunocytochemistry. EGF and active TGF-beta were not detectable in conditioned medium from either cell line., Conclusions: The two embryotrophic cell lines analyzed in this investigation synthesized several common growth factors and cytokines. Identification of factors being secreted by cell lines which positively influence embryo development may aid us in understanding the basic growth requirements of the preimplantation embryo.

Purpose: Our purpose was to assess how the number of embryos transferred can be adjusted to limit multiple gestations., Methods: A retrospective analysis of 535 consecutive embryo transfers for the years 1991-1993 was conducted., Results: Fewer than three embryos were associated with a low pregnancy rate. Pregnancy rates were highest in women less than 35 when four or more embryos were transferred. With four or more embryos, multiple gestation pregnancy correlated with the number of high-quality embryos transferred. The risk of triplets and quadruplets was greatest for women less than 40., Conclusions: Multiple-embryo transfer carries a risk of plural gestation. The risk of multiple pregnancy cannot be eliminated without decreasing the pregnancy rate. The risk of high-order multiple pregnancy was best correlated with the number of good-quality embryos transferred. While all are at risk, patients younger than 40 were at highest risk.

The pathogenesis of the ovarian hyperstimulation syndrome (OHSS) is poorly understood. Since significant elevations in cytokines are found in OHSS, our objective was to conduct a prospective case-controlled study to assess if pre-ovulatory cytokine serum concentrations can predict its occurrence. The study group was selected from in-vitro fertilization patients who subsequently developed severe OHSS, along with a matched group who did not develop this complication (n = 20), and a healthy normal control group (n = 10). Interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1RA) and tumour necrosis factor-alpha (TNFalpha) measurements were performed with sensitive immunoassays and confirmed with bioassays. Serum IL-6 (mean concentrations +/- SEM: 4. 38 +/- 0.36 pg/ml), IL-1RA (829 +/- 292 pg/ml) and TNFalpha (15.5 +/- 1.32 pg/ml) concentrations did not show differences throughout the normal menstrual cycle group. Cytokine variability and pre-ovulatory values were similar in OHSS compared to controlled ovarian hyperstimulation (COH) patients. However, average follicular phase serum IL-6 concentrations were higher in OHSS (8.71 +/- 0.41 pg/ml) and COH (7.66 +/- 0.38 pg/ml) patients than in normally menstruating women (4.34 +/- 0.99 pg/ml) (P < 0.0001). Pre-ovulatory serum IL-6 concentrations were also higher in OHSS (9 +/- 0.94 pg/ml) and COH (7.3 +/- 0.97 pg/ml) patients than in controls (4.57 +/- 1.1 pg/ml) (P < 0.01 and P < 0.04 respectively). All IL-1RA and TNFalpha concentrations were comparable in all the groups. This study suggests that cytokine measurements cannot be used to predict the occurrence of OHSS prior to the administration of human chorionic gonadotrophin.

Objective: To examine the production and immunolocalization of interleukin-6 (IL-6) in patients with the ovarian hyperstimulation syndrome., Methods: The study group consisted of patients with ovarian hyperstimulation syndrome (n = 9) from whom serum and ascites samples were obtained. The control samples used were serum (n = 10) and peritoneal (n = 16) and follicular fluids (n = 8) from healthy individuals. Follicular fluid (n = 40) and serial serum samples were also obtained from patients undergoing menotropin stimulation for in vitro fertilization (IVF) before (n = 10) and after ovulation (n = 34). Interleukin-6 measurements were performed with a sensitive immunoassay and confirmed with a bioassay. Immunohistochemical localization of IL-6 was performed with a mouse monoclonal antibody in normal premenopausal (n = 5) and postmenopausal ovaries (n = 5), as well as with cells from stimulated follicular fluid aspirates (n = 3)., Results: We found significantly higher serum and ascites IL-6 levels in ovarian hyperstimulation syndrome (mean 18.8 +/- 1.1 and 810.8 +/- 60.7 pg/mL, respectively) compared with postovulatory serum and peritoneal fluid from normal controls (mean 4.4 +/- .69 and 44.7 +/- 7.5 pg/mL, respectively) (P < .001) or serum after menotropin stimulation (13.1 +/- 1.1 pg/mL) (P < .001). At the time of ovulation, follicular fluid IL-6 levels (normal controls, mean 9 +/- 2.1 pg/mL; menotropin stimulation, mean 10.1 +/- 4 pg/mL) were higher than in preovulatory serum (normal controls, mean 4.5 +/- .8 pg/mL; menotropin stimulation, mean 6.3 +/- 1.4 pg/mL) (P < .001). Immunohistochemical localization of IL-6 revealed intense staining in corpora lutea and theca cells from large antral follicles and luteinized granulosa cells in follicular aspirates after menotropin stimulation., Conclusion: Interleukin-6 levels are markedly elevated in the ovarian hyperstimulation syndrome when compared with controls. The higher follicular fluid IL-6 levels seen suggest local secretion of this cytokine. Immunohistochemical correlation demonstrated IL-6 within ovarian theca cells. These findings suggest a local role for IL-6 both in normal and stimulated ovarian function. Whether IL-6 is directly responsible for the clinical manifestations of this syndrome is unclear. However, when produced in massive amounts, the pro-inflammatory effects of IL-6 may contribute to its pathogenesis and perhaps serve as a marker for the disease.

Objective: Our objective was to evaluate the efficacy of Synthetic Serum Substitute (Irvine Scientific--Materials Section, Santa Ana, CA), a globulin-enriched protein preparation containing human serum albumin for supplementation of IVF culture media., Design: We retrospectively analyzed IVF cycles performed at MacDonald Womens Hospital between January 1992 and November 1994. IVF cycles were reviewed and classified according to the nature of protein supplementation used in the embryo culture medium. Three protein supplements utilized during this time period were compared: Synthetic Serum Substitute (SSS), Plasmanate (PL), and maternal serum (MS)., Results: Although clinical pregnancy rates among the three treatment groups were not statistically different, there was a definite trend toward a higher pregnancy rate with SSS supplementation (SSS, 38.2%; MS, 28.0%; and PL, 24.9%). Embryos grown in SSS-supplemented culture media had a significantly higher implantation rate (17.8 vs 10.4 and 10.3%, respectively, for MS and PL). Preliminary data also suggest that human embryo development and blastulation in vitro were enhanced by this protein supplement., Conclusions: The higher implantation rate with SSS suggests that it may be superior to both maternal serum and Plasmanate in supporting human embryo development in vitro. Whether blastocysts derived from PL- and SSS-supplemented media are able to implant and give rise to clinical pregnancies remains to be seen.

Objective: To estimate the cost per woman delivered of pregnancies from an in vitro fertilization (IVF) program, and to assess what factors contribute to the cost., Methods: The cost during 2 years' experience of a single IVF program was analyzed retrospectively. Cost analysis included cost of the IVF procedure itself as well as costs incurred because of maternal and neonatal complications., Results: The major contributor to the total cost of IVF was high-order multiple pregnancies. The cost per woman delivered of singleton or twin pregnancies was approximately $39,000, whereas the cost per woman delivered of triplet and quadruplet pregnancies was approximately $340,000., Conclusion: In vitro fertilization can be cost-effective if steps are taken to minimize high-order multiple (triplet or more) pregnancies.

Background: Heterotopic pregnancy occurs in about 1% of pregnancies achieved with assisted reproductive technologies. The incidence of cornual pregnancy is approximately 1% of all ectopics., Cases: Two patients became pregnant after treatment with IVF-ET. Both presented during the first trimester with evidence of an acute abdomen and ultrasonographic suspicion for cornual heterotopic pregnancies. The diagnoses were confirmed by laparoscopy, and treatment was undertaken with laparotomy with cornual resection. Both delivered viable infants by cesarean section; the first patient delivered a twin gestation at 28 weeks and the second a singleton pregnancy at 37 weeks. All infants were doing well two months after delivery., Conclusion: Abnormal pregnancies can be detected after IVF-ET with careful follow-up, transvaginal ultrasound studies, serial hCG measurements and pelvic examinations. Cornual heterotopic pregnancies can be successfully treated with cornual resection, especially in cases presenting during the second trimester or when there is clinical evidence of an acute abdomen. All deliveries should be performed by cesarean section at term prior to labor or when tocolysis for premature labor has failed.

Objective: To examine the role of pro-inflammatory cytokines in ovarian hyperstimulation syndrome (OHSS)., Design: In vitro laboratory study of serum, peritoneal cells isolated and fluid obtained from ascites removed in the therapeutic management of four patients with OHSS., Setting: Tertiary care referral teaching hospital., Patients: Four patients with OHSS comprised the study population. Five healthy women at the time of elective laparoscopic tubal ligation served as controls. Control serum was also obtained from healthy adult volunteers, and control peritoneal fluid (PF) was obtained from patients on peritoneal dialysis., Interventions: Therapeutic paracentesis was performed on four patients with OHSS., Results: Peritoneal cells were isolated and fluid obtained from ascites removed in the therapeutic management of the women with OHSS. Peritoneal cells were obtained by intraoperative lavage from the control women. The cells were incubated with various concentrations of Escherichia coli lipopolysaccharide (LPS) for 20 and 48 hours. Interleukin-1 beta (IL-1 beta), tumor necrosis factor (TNF), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) were assayed in the incubation supernatants. The release of the three cytokines and PGE2 in response to LPS by peritoneal cells from women with OHSS was not different from the controls. However, both serum and ascitic fluid from women with OHSS contained significantly greater levels of IL-6 than control serum and PF. No significant differences in TNF levels in serum, ascitic fluid, or PF could be found by ELISA or bioassay., Conclusions: Increased production of IL-6, released into the peritoneal cavity and the circulation, may mediate OHSS.

This report documents the medical details and 3-year follow-up evaluation of the infertile and surrogate couples involved in the first successful in vitro fertilization gestational surrogate pregnancy and summarizes clinical experience and outcome of all patients treated to date. Results of the first 28 couples treated are presented. The pregnancy rate for 39 cycles reaching attempts at oocyte retrieval is 18%. The procedural aspects, ethical issues, legal issues, and subsequent program development are summarized. Recommendations are of a similar program. There are numerous potential pitfalls and traps for the unwary, but our experience has thus far been gratifyingly positive, and we endorse the further provision, observation, and documentation of this controversial approach to the care of the infertile couple.

A case is presented of a woman with severe chronic renal disease who developed evidence of salt wasting during pregnancy. Restoration of renal function and a successful pregnancy outcome were achieved through the use of large quantities of oral and intravenous salt supplementation, together with oral bicarbonate.