Orthopedic Surgeons


Pontiac
Pontiac Osteopathic
50 N Perry St
Pontiac, MI 48342
248-338-5392
Locations and availability (2)

Education ?

Medical School Score
University of New England
  • Currently 2 of 4 apples

Awards & Distinctions ?

Associations
American Society for Reproductive Medicine

Publications & Research

Dr. Tucker has contributed to 64 publications.
Title Maternal Smokeless Tobacco Use in Alaska Native Women and Singleton Infant Birth Size.
Date February 2012
Journal Acta Obstetricia Et Gynecologica Scandinavica
Excerpt

To examine the effects of maternal prenatal smokeless tobacco use on infant birth size.

Title Assessing Patient Recall of Discharge Instructions for Acute Myocardial Infarction.
Date December 2009
Journal Journal for Healthcare Quality : Official Publication of the National Association for Healthcare Quality
Excerpt

Guidelines for acute myocardial infarction (AMI) include secondary prevention (SP) strategies, but little is known about patients' recall of instructions following hospital discharge. We conducted telephone interviews to assess recall of risk-reduction information among patients discharged with AMI. Results indicated similar proportions of documented and patient recall of discharge instructions. However, lifestyle recommendations were documented and recalled less frequently than pharmacologic therapy. Many patients were unable to name their diagnosis or link known risk factors as contributing causes, which may contribute to low adherence to SP therapies. Quality improvement strategies are needed to guide more effective provider-patient communication.

Title No Advantage of Laser-assisted over Conventional Intracytoplasmic Sperm Injection: a Randomized Controlled Trial [nct00114725].
Date July 2007
Journal Journal of Experimental & Clinical Assisted Reproduction
Excerpt

BACKGROUND: Intracytoplasmic sperm injection (ICSI) is a component of infertility treatment often employed when conventional in vitro fertilization is unlikely to be successful. Despite good clinical results with ICSI, the procedure is typically associated with degeneration of a significant percentage (approximately 10%) of the treated oocytes. The cause of this degeneration remains unclear. Speculation that damage caused by oocyte compression during the injection procedure may be responsible has led to the development of a novel technique known as laser-assisted ICSI. This procedure involves drilling a small hole through the zona pellucida with a laser prior to sperm injection. Preliminary studies have suggested that laser-assisted ICSI may dramatically reduce oocyte degeneration rates. The objective of this study was to examine whether the reported benefits of laser-assisted ICSI could be verified on a larger, less-selected group of patients. METHODS: Oocytes retrieved from 59 patients scheduled for ICSI were randomly divided into equal treatment and control groups. Oocytes in the treatment group were inseminated by laser-assisted ICSI, while oocytes in the control group were inseminated by conventional ICSI. Outcome variables (oocyte fertilization and degeneration, embryo cell numbers and fragmentation on days 2 and 3, and compaction and blastocyst formation rates) were compared between treatment and control groups by paired-sample t-test. Subgroup analysis was performed according to zona pellucida and oolemma breakage patterns. RESULTS: No significant differences between treatment and control groups were observed for any of the measured outcome variables. However, fragile zonae pellucidae were associated with significantly poorer embryo quality, and fragile oolemmas that broke easily upon insertion of the injection needle were associated with a significantly higher oocyte degeneration rate. Nevertheless, there were also no between-treatment differences in clinical outcomes within these patient subpopulations. CONCLUSION: Contrary to previous reports based on smaller sample sizes, the results of this study suggest that there is no benefit of laser-assisted ICSI, either for the general population of ICSI patients, or for patients prone to zona pellucida or oolemma fragility.

Title Sulfamethoxazole and Its Metabolite Nitroso Sulfamethoxazole Stimulate Dendritic Cell Costimulatory Signaling.
Date June 2007
Journal Journal of Immunology (baltimore, Md. : 1950)
Excerpt

Different signals in addition to the antigenic signal are required to initiate an immunological reaction. In the context of sulfamethoxazole allergy, the Ag is thought to be derived from its toxic nitroso metabolite, but little is known about the costimulatory signals, including those associated with dendritic cell maturation. In this study, we demonstrate increased CD40 expression, but not CD80, CD83, or CD86, with dendritic cell surfaces exposed to sulfamethoxazole (250-500 microM) and the protein-reactive metabolite nitroso sulfamethoxazole (1-10 microM). Increased CD40 expression was not associated with apoptosis or necrosis, or glutathione depletion. Covalently modified intracellular proteins were detected when sulfamethoxazole was incubated with dendritic cells. Importantly, the enzyme inhibitor 1-aminobenzotriazole prevented the increase in CD40 expression with sulfamethoxazole, but not with nitroso sulfamethoxazole or LPS. The enzymes CYP2C9, CYP2C8, and myeloperoxidase catalyzed the conversion of sulfamethoxazole to sulfamethoxazole hydroxylamine. Myeloperoxidase was expressed at high levels in dendritic cells. Nitroso sulfamethoxazole immunogenicity was inhibited in mice with a blocking anti-CD40L Ab. In addition, when a primary nitroso sulfamethoxazole-specific T cell response using drug-naive human cells was generated, the magnitude of the response was enhanced when cultures were exposed to a stimulatory anti-CD40 Ab. Finally, increased CD40 expression was 5-fold higher on nitroso sulfamethoxazole-treated dendritic cells from an HIV-positive allergic patient compared with volunteers. These data provide evidence of a link between localized metabolism, dendritic cell activation, and drug immunogenicity.

Title Laser Assisted Hatching in Good Prognosis Patients Undergoing in Vitro Fertilization-embryo Transfer: a Randomized Controlled Trial.
Date February 2007
Journal Fertility and Sterility
Excerpt

OBJECTIVE: To evaluate whether assisted hatching improves clinical outcomes of embryo transfers to good prognosis patients, defined as patients < or =39 years with normal follicle-stimulating hormone (FSH) and E(2) levels, no more than one previous unsuccessful cycle of in vitro fertilization (IVF)-embryo transfer, and good embryo quality. DESIGN: Prospective randomized controlled trial. SETTING: Private assisted reproductive technology (ART) center. PATIENT(S): One hundred ninety-nine good prognosis patients undergoing IVF-embryo transfer. INTERVENTION(S): In vitro fertilization followed by embryo transfer on day 3 after oocyte retrieval with or without assisted hatching using a 1,480-nm wavelength infrared laser. MAIN OUTCOME MEASURE(S): Clinical intrauterine pregnancy, spontaneous pregnancy loss, and live birth. RESULT(S): Rates of clinical intrauterine pregnancy with fetal cardiac activity (53% vs. 54% per cycle), spontaneous pregnancy loss (13% vs. 16% per pregnancy), and live birth (47% vs. 46% per cycle) were very similar between treatment cycles with laser-assisted hatching and control cycles in which embryos were transferred without assisted hatching. There were no significant differences between treatment and control groups in any measured clinical outcome parameters. CONCLUSION(S): Assisted hatching does not improve clinical outcomes among good prognosis patients.

Title The Black-white Disparity in Pregnancy-related Mortality from 5 Conditions: Differences in Prevalence and Case-fatality Rates.
Date January 2007
Journal American Journal of Public Health
Excerpt

We sought to determine whether differences in the prevalences of 5 specific pregnancy complications or differences in case fatality rates for those complications explained the disproportionate risk of pregnancy-related mortality for Black women compared with White women in the United States.

Title Cryopreserved Embryo Transfers Suggest That Endometrial Receptivity May Contribute to Reduced Success Rates of Later Developing Embryos.
Date November 2006
Journal Fertility and Sterility
Excerpt

OBJECTIVE: To evaluate viability and implantation potential of cryopreserved blastocysts according to the day of blastocyst expansion and cryopreservation. DESIGN: Retrospective study. SETTING: Private ART center. PATIENT(S): Three hundred and seventy-five patients undergoing embryo transfer with cryopreserved blastocysts. INTERVENTION(S): Blastocyst cryopreservation on day 5, 6, or 7 after oocyte retrieval according to the day of blastocyst expansion and subsequent embryo transfer. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (PR) per embryo transfer. RESULT(S): Clinical PRs were similar between blastocysts cryopreserved on day 5 and blastocysts cryopreserved on day 6 (32% vs. 28%). The clinical PR was lower for blastocysts cryopreserved on day 7 (15%), but this difference was not statistically significant after accounting for the number of embryos per transfer (P=.15). CONCLUSION(S): Viability and implantation potential are similar for day 5 and day 6 blastocyst cryopreservation. Viability may be reduced for blastocysts cryopreserved on day 7, but not to the extent suggested by reports of fresh transfers. These results suggest that reduced success rates associated with fresh transfers of later developing blastocysts may be the result of asynchrony with endometrial receptivity instead of poorer embryo quality.

Title Increased Adverse Drug Reactions to Antimicrobials and Anticonvulsants in Patients with Hiv Infection.
Date October 2006
Journal The Annals of Pharmacotherapy
Excerpt

OBJECTIVE: To review the incidence, signs, symptoms, and mechanisms of adverse drug reactions (ADRs) to sulfonamides, anticonvulsants, and antimycobacterial medications among people with HIV. DATA SOURCES: Searches of MEDLINE/PubMed (1980-November 2005) and National Library of Medicine Meeting Abstracts (1989-November 2005), as well as hand searches of journals and abstracts, were conducted to identify primary literature. Reference lists were reviewed to identify additional relevant reports. STUDY SELECTION AND DATA EXTRACTION: Relevant articles and abstracts, particularly of in vitro experiments and clinical studies, were compiled and reviewed. DATA SYNTHESIS: ADRs, especially in HIV-infected patients, are a cause for concern. Sulfonamides, anticonvulsants, and antimycobacterial drugs are commonly used to prevent and treat complications of HIV, including seizures and opportunistic infections. Patients with HIV have a much greater rate of ADRs to these drug classes, including severe and life-threatening hypersensitivity reactions. Several mechanisms of these ADRs have been postulated. Sulfamethoxazole and anticonvulsant hypersensitivity may involve the increased formation and decreased detoxification of reactive metabolites. The mechanisms for the marked increase in hypersensitivity ADRs to antimycobacterial drugs may be related to an altered immune profile in patients infected with both tuberculosis and HIV. CONCLUSIONS: ADRs to antimicrobial and anticonvulsant therapy cause markedly increased morbidity and mortality in HIV-positive patients. Further research involving the interaction between HIV and the increased ADRs to these drugs is required.

Title Cryopreservation in Assisted Reproductive Technology: New Trends.
Date January 2006
Journal Seminars in Reproductive Medicine
Excerpt

During the last few years, cryopreservation has become a relevant addition to therapeutic concepts in reproductive medicine. New data and publications have made it difficult to maintain an overview of all of the new developments and their results. The focus of interest more recently, especially with the cryopreservation of human oocytes and human ovarian tissue, has been vitrification as an interesting alternative to slow freezing methods. Even though studies investigating the slow freezing of human mature oocytes have resulted in very different survival rates, it could be an option for donor oocyte programs, in the case of threatened ovarian loss or when there is an objection to embryo freezing. An optimal freezing protocol and later use of thawed human ovarian tissue is still a point of discussion. There are encouraging results regarding different kinds of autotransplantation, and recently the first birth after orthotopic autotransplantation of cryopreserved/thawed human ovarian tissue was described in the literature. Independent of any objections to cryopreservation in general, vitrification is a potential and effective alternative to conventional slow cryopreservation, especially for oocytes and embryos. Vitrification might be also be an option for human ovarian tissue; however this is only in its infancy and requires much additional investigation. Our article discusses new trends and results of actual studies regarding these issues.

Title Hypersensitivity of Hiv-1-infected Cells to Reactive Sulfonamide Metabolites Correlated to Expression of the Hiv-1 Viral Protein Tat.
Date October 2005
Journal The Journal of Pharmacology and Experimental Therapeutics
Excerpt

Impairment of human immunodeficiency virus (HIV)-infected cells to deal with reactive drug metabolites may be a mechanism for the increased rate of adverse drug reactions seen in AIDS. HIV Tat protein expression may be associated with increased oxidative stress within HIV-infected cells. To determine the relationship between expression of HIV Tat and sensitivity to reactive drug metabolites, we studied toxicity of sulfamethoxazole (SMX) and its reactive hydroxylamine intermediate (SMX-HA) in lymphocytes transfected with the HIV tat gene. Over a concentration range from 0 to 400 microM SMX-HA, there was a significant concentration-dependent increase in cell death in transfected cell lines expressing Tat compared with controls. Jurkat T cells transfected with a dose-dependent inducible tat gene showed increased toxicity in response to SMX-HA as more Tat expression was induced. Enhanced sensitivity to SMX-HA was accompanied by significantly lower concentrations of total intracellular glutathione compared with controls (P < 0.05). Sensitivity to reactive drug metabolites in HIV-infected cells seems to be mediated by the viral protein Tat.

Title Microstructural Observations of Villous and Membrane Histology in Monochorionic Triplet Placenta After in Vitro Fertilization.
Date March 2005
Journal Histology and Histopathology
Excerpt

The frequency of triplet gestation is low in humans, estimated at 1:6400 deliveries. Monochorionic gestations represent a subpopulation of approximately 10% of these triplet pregnancies. Hypertensive complications are known to occur with greater frequency in the context of multiple gestation. In this report we describe microscopic placental changes associated with pre-eclampsia and proteinuria in the setting of an uncommon monochorionic-triamniotic triplet pregnancy achieved via in vitro fertilization. Histologic features observed in this case include placental stromal fibrosis and increased syncytial nodularity (Tenney-Parker change). In this triplet delivery resulting from two consecutive fissions of a single embryo, chorion and amnion configuration are also characterized with a review of the literature discussing the potential relationship between in vitro culture conditions and monozygotic multiple gestation.

Title Genetic and Epigenetic Modifications Associated with Human Ooplasm Donation and Mitochondrial Heteroplasmy - Considerations for Interpreting Studies of Heritability and Reproductive Outcome.
Date December 2004
Journal Medical Hypotheses
Excerpt

The mitochondrial heteroplasmy present in offspring from IVF and human ooplasm donation is troublesome and merits further exploration in a debate that is already complex and controversial. Improving the understanding of mitochondrial genomics in this context is important because mitochondriopathies can impact crucial cellular processes in renal, cardiovascular, central nervous, and endocrine systems. Relevant epigenetic consequences of mitochondrial heteroplasmy include associated abnormalities in mitochondrial translation products. Furthermore, as transmission and inheritance patterns of mtDNA are species-specific, it remains to be proven if findings derived from animal studies are applicable to human offspring. As an alternative to gamete research and proteomics based on animal experimentation, continued molecular characterization of the de novo human mitochondriopathies is posed to offer further insights regarding mitochondrial heteroplasmy. In this context, because knowledge of human mitochondrial genetics remains limited and the risks associated with ooplasm donation cannot be quantified, we do not favor its use for our patients at present. However, the small number of infants already conceived from this experimental approach warrant careful longitudinal evaluation. In particular, observational study of the few children born after ooplasm donation could provide opportunities to assess human mtDNA transmission and inheritance. Such findings could help identify features distinguishing natural mtDNA heteroplasmy from heteroplasmy observed after ooplasm donation. Future investigations should also quantify the degree any such heteroplasmy can exist innocuously. Disclosure of mtDNA mutations potentially affecting children conceived from IVF and ooplasm donation must be included during patient education at centers contemplating such treatment.

Title Gender Differences in Indices of Opioid Dependency and Medical Comorbidity in a Population of Hospitalized Hiv-infected African-americans.
Date October 2004
Journal The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions
Excerpt

We examined gender differences in drug use patterns and in medical presentation among 520 hospitalized, HIV-infected African-Americans. Substance abuse history was self-reported, and medical data were obtained by chart review. Overall, 321 (65%) reported ever having used heroin, with equivalent rates in men and women. Women were more likely to report current use, to have sought treatment, and tended to feel more dependent on heroin than men. Among heroin users, women were more likely to be admitted for conditions related to drug use, rather than AIDS, and to have CD4 counts > 200/mm3. These gender differences in opioid dependency and medical comorbidity may indicate a need for alternative treatment approaches for men and women.

Title Medical and Psychological Management of Recurrent Abortion, History of Postneonatal Death, Ectopic Pregnancy and Infertility: Successful Implementation of Ivf for Multifactorial Reproductive Dysfunction. A Case Report.
Date August 2004
Journal Clinical and Experimental Obstetrics & Gynecology
Excerpt

The medical and psychological treatment for a 37-year-old Caucasian G6 P1051 woman who presented for evaluation of secondary infertility and recurrent pregnancy loss is described. Although one living child had been conceived without medical assistance, that delivery preceded the present evaluation by ten years and involved a different partner. With the current husband, the patient had two miscarriages and a left ectopic pregnancy. The couple had attempted controlled ovarian hyperstimulation and in vitro fertilization (IVF) elsewhere, but the cycle was cancelled due to poor follicular response. About one year before consultation at our institution, the couple established a pregnancy although the infant was born at 24 weeks with a cardiac anomaly, living only 40 days. Additionally, a persistent cervical lesion required cone biopsy before any fertility treatment could resume. Andrology evaluation found the husband's sperm DNA fragmentation index to be 48.6%. This constellation of stressors represented substantial emotional issues and psychological therapy/counseling was recommended. After obtaining psychological clearance, the couple underwent IVF and 16 oocytes were retrieved. Four embryos were transferred, and a healthy male infant was delivered at term. Although multifactorial infertility can be associated with very poor reproductive outcomes, the advanced reproductive technologies merit consideration during management of complex clinical challenges. Standard IVF strategies can be optimized by inclusion of thorough psychological assessment and counseling.

Title Laparoscopic Approach to an Uncommon Adnexal Neoplasm Associated with Infertility: Serous Cystadenofibroma of the Fallopian Tube.
Date April 2004
Journal The Journal of the American Association of Gynecologic Laparoscopists
Excerpt

A rare case of serous cystadenofibroma of the fallopian tube was discovered during evaluation for in vitro fertilization-embryo transfer. Bilateral tubal occlusion was noted on hysterosalpingogram, and a right adnexal cyst, initially thought to be of ovarian origin, was identified by office transvaginal sonography. Laparoscopy revealed a 5.5-cm, fluid-filled mass involving the distal aspect of the right fallopian tube. Both ovaries and uterine exterior appeared grossly normal. The cyst was decompressed and removed intact without incident through a 5-mm laparoscopic cannula. The mass showed histologic features consistent with benign serous cystadenofibroma. The patient had an uncomplicated postoperative convalescence and continued to do well 3 months after surgery.

Title Chromatin Fluorescence Characteristics and Standard Semen Analysis Parameters: Correlations Observed in Andrology Testing Among 136 Males Referred for Infertility Evaluation.
Date March 2004
Journal Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology
Excerpt

This paper aims to describe the relation between standard semen analysis parameters (concentration, motility and morphology) and sperm chromatin structure assay (SCSA) results among patients referred for infertility evaluation. Healthy males (n=136) seeking infertility consultation were evaluated prospectively by semen analysis and sperm chromatin structure assay (SCSA). Significant inverse correlations were observed between high sperm concentration and DNA fragmentation index (DFI) and high DNA stainability (HDS) (r=- 0.45; P<0.001, and r=- 0.40; P<0.001, respectively). Both progressive motility and normal morphology were also strongly inversely correlated with DFI and HDS. However, in stratified analysis the correlation between concentration < or =20 M/ml and DFI, and concentration < or =20 M/ml and HDS were not significant (P=0.31 and 0.38, respectively). For men with sperm motility < or =40% the correlation between motility and HDS was not significant (P=0.22), but between motility and DFI the correlation remained significant (P=0.04). Although strong correlations between DFI, HDS and semen analysis findings were noted in the overall study population, when oligozoospermic and asthenozoospermic patients were analysed separately the correlation between concentration and sperm chromatin fragmentation was not significant. For such men, SCSA appears to be a diagnostic variable independent of the semen analysis, providing information about nuclear abnormalities not readily apparent from standard semen analysis alone. Additionally, SCSA data may offer explanations for previous miscarriage, providing closure for some couples contemplating future use of anonymous donor sperm.

Title Opioid Detoxification with Buprenorphine, Clonidine, or Methadone in Hospitalized Heroin-dependent Patients with Hiv Infection.
Date October 2003
Journal Drug and Alcohol Dependence
Excerpt

With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.

Title Absence of Profound Hyperinsulinism in Polycystic Ovary Syndrome is Associated with Subtle Elevations in the Plasminogen Activator Inhibitor System.
Date October 2003
Journal Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology
Excerpt

In order to describe potential hypofibrinolytic tendencies in young (< 35 years) polycystic ovary syndrome (PCOS) patients, we studied plasminogen activator inhibitor (PAI-1) system components in women without laboratory evidence of hyperinsulinism or hyperandrogenism. The study was a prospective, observational comparison and took place in a major urban infertility referral center. Age, body mass index, ovulatory status, selected androgen levels, fasting insulin and plasma lipids were measured in subjects with PCOS (n = 39) and normal control subjects (n = 20). Women with PCOS had higher mean serum total testosterone and androstenedione levels compared with controls (56.4 versus 40.3 ng/dl, p = 0.03, and 179 versus 133 microg/ml, p = 0.03, respectively). Mean fasting insulin levels were higher among PCOS women (p < 0.01) and were strongly correlated with PAI-1 antigen (Ag) (r = 0.46), PAI-1 activity (r = 0.43), and tissue plasminogen activator (t-PA) (r = 0.5). Correlations were evident in both PCOS and control subjects. Mean PAI-1 Ag, PAI-1 activity, and t-PA levels were significantly elevated (p = 0.003, 0.001, and 0.001, respectively) in PCOS. ANOVA was performed to control for insulin effect; a trend toward elevated PAI-1 in PCOS persisted but was no longer statistically significant (p = 0.24). PAI-1 activity elevation remained in PCOS women with mean fasting insulin levels < 10 mIU/ml (p = 0.02), yet the difference became less significant when insulin was controlled (p = 0.38). Although these data confirm known associations between insulin and PAI-1 derangements, this is the first study to quantify discrete PAI-1 elevations that persist in the setting of PCOS even with normal or low ambient insulin levels. Additional prospective studies are needed to determine whether this altered PAI-1 state is associated with a clinically important hypofibrinolytic condition and subsequent poor reproductive outcome.

Title Laser-assisted Human Embryo Biopsy on the Third Day of Development for Preimplantation Genetic Diagnosis: Two Successful Case Reports.
Date September 2003
Journal Fertility and Sterility
Excerpt

OBJECTIVE: To perform preimplantation genetic diagnosis (PGD) with 1.48-microm infrared diode laser assistance during embryo biopsy for two patients undergoing IVF. DESIGN: Case reports. SETTING: Private ART laboratory.Two couples undergoing IVF for infertility therapy, both of whom had previously delivered offspring afflicted with spinal muscular atrophy (type 1) after IVF therapy, and who underwent subsequent cycles of IVF coupled with PGD to screen for this disorder. INTERVENTION(S): Two individual IVF cases involving intracytoplasmic sperm injection (ICSI), embryo biopsy with laser assistance, and PGD.The ease and apparent safety of human embryo biopsy using a 1.48-microm infrared laser for partial zona pellucida (ZP) dissection to assist with embryo blastomere biopsy was evaluated. RESULT(S): Both couples were deemed to have some unafflicted embryos for transfer on the fifth day of development after blastomere biopsy in conjunction with PGD. Patient A had a singleton pregnancy and delivered a healthy normal singleton male. Patient B had a twin pregnancy; however, one twin was spontaneously lost at 10 weeks but she ultimately delivered a healthy normal singleton male. CONCLUSION(S): These successful outcomes help to demonstrate the efficacy and safety of laser-assisted embryo biopsy to facilitate PGD screening.

Title Monozygotic Twin Delivery Following Reduction from Quadramniotic-dichorionic Gestation Established After Icsi and Embryo Transfer: Case Report.
Date August 2003
Journal Human Reproduction (oxford, England)
Excerpt

We report the delivery of healthy monozygous (MZ) twins in a 31 year-old nulligravida following gonadotrophin ovulation induction, ICSI, assisted hatching and fresh embryo transfer. Although a sonogram on day 35 confirmed that two of four transferred embryos had implanted, a second transvaginal sonogram 1 week later showed each gestational sac had two conceptuses-all four were associated with distinct amniotic compartments. Cardiac activity was observed in all four embryos. At 12 weeks and 5 days gestation, chorionic villus sampling was performed on fetuses 1 and 2 which were euploid for chromosomes 13, 18, 21, X and Y via fluorescence in-situ hybridization analysis. Subsequent KCl injection into sacs 3 and 4 resulted in asystole for these fetuses, while cardiac activity in sacs 1 and 2 remained unchanged after reduction. A twin vaginal delivery occurred at 36 weeks gestation, resulting in the birth of two male infants and one placenta. This case represents the first known report of human quadruplet pregnancy consisting of two MZ twin sets conceived by assisted reproductive techniques. Our report reviews proposed mechanisms for explaining twinning, with special emphasis on zona pellucida micromanipulation and subsequent MZ twin induction.

Title Dizygotic Twin Delivery Following in Vitro Fertilization and Transfer of Thawed Blastocysts Cryopreserved at Day 6 and 7.
Date April 2003
Journal Fertility and Sterility
Excerpt

OBJECTIVE: To report the first conception and delivery following transfer of thawed human blastocysts maintained in extended in vitro culture with cryopreservation at day 6 and 7. DESIGN: Case report. SETTING: Major urban infertility referral center. PATIENT(S): A 26-year-old woman with pelvic endometriosis and two prior unsuccessful in vitro fertilization/embryo transfer (IVF-ET) attempts. INTERVENTION(S): The patient underwent controlled ovarian hyperstimulation using a combined FSH + hMG protocol, and 24 oocytes were retrieved. MAIN OUTCOME MEASURE(S): Dizygotic twin delivery after IVF and intracytoplasmic sperm injection (ICSI), assisted embryo hatching, and ultrasound-guided transfer of cryopreserved blastocysts. RESULT(S): After three embryos were subjected to assisted hatching, they were transferred fresh on day 3, but no implantation occurred. All nontransferred embryos (n = 11) were observed during extended in vitro culture and three blastocysts were selected for cryopreservation on day 6 and 7; thaw and transfer occurred the following month and a pregnancy was achieved. Dizygotic twins (female/female) were delivered by cesarean in the early third trimester. CONCLUSION(S): Substantial advancements have been made in the field of embryo cryogenics and in vitro fertilization, but controversy remains regarding the value of freezing late-developing human blastocysts. Here we describe the first reported live births with IVF after extended in vitro culture and cryopreservation at day 6 and 7 after fertilization.

Title Uncomplicated Pregnancy and Normal Singleton Delivery After Surgical Excision of Heterotopic (cornual) Pregnancy Following in Vitro Fertilization/embryo Transfer.
Date March 2003
Journal Archives of Gynecology and Obstetrics
Excerpt

A 39 year-old woman with previous salpingectomy developed a symptomatic heterotopic right cornual pregnancy identified by transvaginal ultrasonography at six weeks' gestation. The patient had previously undergone an ipsilateral partial salpingectomy, and the conception was established four months later after one cycle of controlled ovarian hyperstimulation, in vitro fertilization (IVF) and embryo transfer. We performed immediate surgical excision of the ectopic implantation with conservation of the intrauterine pregnancy. Progesterone was administered as 200 mg/d lozenge (troche) plus 200 mg/d rectal suppository, maintained from day of embryo transfer through the perioperative period and until 11th gestational week. Following an uneventful obstetrical course, a healthy male infant was delivered by cesarean at term. In this report, we review the incidence and significance of heterotopic gestation in the context of IVF/embryo transfer. Risk factors for complex intra- and extra-uterine pregnancies are also outlined. Additionally, the clinical management of heterotopic pregnancy, including a novel approach to progesterone supplementation, is discussed.

Title Blastocyst Development After Vitrification of Multipronuclear Zygotes Using the Flexipet Denuding Pipette.
Date December 2002
Journal Reproductive Biomedicine Online
Excerpt

The purpose of this study was to demonstrate the safety and efficacy of vitrification of human pronuclear stage (PN) embryos in the human assisted reproduction laboratory. Using single pronucleate (1PN) and three pronucleate (3PN) zygotes, the impact of vitrification in the Flexipet denuding pipette (FDP) as a carrier was assessed in terms of survival, embryonic development and blastocyst formation when compared according to the PN number, and unvitrified controls. A total of 65 1PN and 152 3PN zygotes were vitrified; after warming 82% (53/65) of 1PN and 90% (137/152) of 3PN survived. The overall percentage of warmed zygotes (1PN and 3PN) that cleaved and reached 2-cell stage did not differ (chi(2); P = 0.32) from the control groups (77%; 147/190 versus 85%; 115/136). In addition, when the cleavage behaviour was examined on day 3 for >or=4-cell stage, no significant differences (chi(2); P = 0.95) were observed between the vitrified group and the unvitrified control groups (74%; 109/147 versus 77%; 89/115). Comparing the developmental potential up to cavitation and blastocyst formation on day 5, the overall outcome of the vitrified PN was 31% compared with 33% for the controls (chi(2); P = 0.76). The simple vitrification protocol used in this study, and these data highlight the usefulness of vitrification using FDP as a consistent and effective cryopreservation method for pronuclear zygotes, and a suitable alternative to slow cryopreservation protocols.

Title Comparison of Centrifugation- and Noncentrifugation-based Techniques for Recovery of Motile Human Sperm in Assisted Reproduction.
Date September 2002
Journal Archives of Andrology
Excerpt

To compare standard density gradient centrifugation sperm preparation with a novel non-centrifugation-based dual-chamber capillary dish in efficiency for motile human sperm separation, approximately 3 mL fresh ejaculate specimens was obtained from 21 men (median age = 32 years. range 26-42 years) undergoing infertility evaluation. For each specimen, half of the sample was processed with a standard 45%/90% density gradient preparation (PureSperm. Nidacon International, Gothenburg, Sweden) followed by semen analysis. The other half was incubated in the Zech glass capillary dish (Astromedtec, Salzburg, Austria) consisting of 2 concentric wells overlaid by a U-ring and coverglass. After approximately 3 h, a 1-mL sample was taken from the central chamber and analyzed. Percentage motile sperm recovery, absolute (motile) cell number, and path velocities were compared for spermatozoa obtained from both methods. Both techniques reduced overall sperm concentration while enriching specimens with more motile spermatozoa. A trend towards higher % recovery of motile spermatozoa (p = .264) was observed with the Zech device, but at a cost of fewer absolute numbers of higher velocity cells (p = .004). The Zech device, therefore, localized a very small population of motile sperm without exposure to centrifugation stress, which has been considered potentially harmful to spermatozoa. This technique could theoretically improve efficiency by reducing time required to identify motile cells in in vitro fertilization where intracytoplasmic sperm injection is planned. However, refinements in incubation interval and suspension volumes are needed before this technique can be considered comparable to the density gradient method in recovering sperm for use in intrauterine insemination.

Title Healthy Twin Delivery After Day 7 Blastocyst Transfer Coupled with Assisted Hatching.
Date April 2002
Journal Fertility and Sterility
Excerpt

OBJECTIVE: To report a normal twin delivery after transfer of two fresh day 7 blastocysts. DESIGN: Case report. SETTING: Private infertility clinic. PATIENT(S): A 35-year-old woman with a 6-year history of primary infertility with significant pelvic adhesions. INTERVENTION(S): Review of individual IVF-ET therapy cycle. MAIN OUTCOME MEASURE(S): Full-term delivery after day 7 blastocyst transfer. RESULT(S): During the patient's first IVF-ET cycle, the decision was made to undertake blastocyst transfer after extended culture. No blastocysts had formed until late on day 6, by which time the patient had been hospitalized with a renal stone. Subsequently, on day 7, the patient was asymptomatic and presented for embryo transfer, and after assisted hatching, two expanded blastocysts were transferred to her uterus under ultrasound guidance. After confirmation of implantation of a viable twin, pregnancy was uneventful with no obstetrical complications, and a dizygotic twin was delivered vaginally at 38 weeks of gestation. CONCLUSION(S): Few reports have been made regarding viability of more slowly developing blastocysts; however, this case indicates that blastocysts that did not fully expand until day 7 of extended in vitro culture are still able to implant after superovulation and IVF-ET therapy. Assisted hatching of these embryos may have been beneficial in achieving this successful outcome by hastening the blastocyst hatching, allowing more rapid contact with the endometrium.

Title Successful Ovulation Induction, Conception, and Normal Delivery After Chronic Therapy with Etanercept: a Recombinant Fusion Anti-cytokine Treatment for Rheumatoid Arthritis.
Date April 2002
Journal American Journal of Reproductive Immunology (new York, N.y. : 1989)
Excerpt

Etanercept (Enbrel; Wyeth-Ayerst/Immunex Inc, Seattle, WA, USA) is a subcutaneously administered novel fusion protein consisting of the extracellular ligand-binding domain of the 75 kD receptor for tumor necrosis factor-alpha (anti-TNFalpha) and the Fc portion of human IgG1. The agent is synthesized by plasmid transfection of a Chinese hamster ovary cell line, utilizing recombinant DNA technology. Etanercept was approved by the US FDA for treatment of multi-drug resistant rheumatoid arthritis in 1998, but no human data exist regarding the impact of anti-TNFalpha therapy on human reproductive function or its use before ovulation induction. As TNFalpha potentiates collagenolysis via matrix metalloproteinase gene expression (thereby facilitating ovulation), there exists a theoretical risk that TNFalpha-inhibition could exert an undesirable effect on ovulation and pregnancy. In this report, we describe the first case of ovulation induction, intrauterine insemination, normal pregnancy and singleton delivery of a healthy infant following chronic ( > 1 year) pre-ovulatory TNFalpha-inhibitor therapy for rheumatoid arthritis. Reproductive endocrinologists and obstetrician-gynecologists should be familiar with etanercept therapy in the context of severe rheumatic disease, and offer appropriate reassurance regarding its safe use for infertility patients planning ovulation induction.

Title Characterization of a Novel Receptor Mutation A-->t at Exon 4 in Complete Androgen Insensitivity Syndrome and a Carrier Sibling Via Bidirectional Polymorphism Sequence Analysis.
Date March 2002
Journal International Journal of Molecular Medicine
Excerpt

The complete androgen insensitivity syndrome (AIS) is a sub-type of X-linked male pseudohermaphroditism resulting from total dysfunction of the androgen receptor. Affected patients are phenotypically female despite a 46,XY genotype; gonadal tissue displays a classic Sertoli cell-only pattern on microscopic examination. We describe the diagnosis and management of a 19(1/2)-year-old patient who presented for primary amenorrhea and absent cervix, identified incidentally during a routine Pap test. Serum total testosterone was elevated (725 ng/dl) and the karyotype was 46,XY. Molecular investigation for specific gene defect(s) causing disruption and functional incapacity of the androgen receptor was undertaken for the proband and her only sibling. From this we discovered a previously unknown hemizygous mutation (A-->T) in exon 4 of the androgen receptor gene, associated with replacement of asparagine (AAT) with tyrosine (TAT) in the resultant androgen receptor protein [N705Y]. Bidirectional, non-isotopic sequence analysis of exon 4 was next undertaken for the proband's sister who was found to be heterozygous for this mutation. Psychological and genetic counseling was provided to both individuals; the patient underwent an outpatient laparoscopic orchiectomy without complication. She continues to receive oral hormone replacement therapy following an oral contraceptive model. In this report, the clinical approach to AIS is outlined from a reproductive endocrinology perspective with special emphasis on psychological counseling and laboratory methods employed to confirm the diagnosis at the molecular level. We also outline other recently described mutations of the androgen receptor gene (Xq11-12) which have been associated with AIS.

Title Plasma Homocysteine, Fasting Insulin, and Androgen Patterns Among Women with Polycystic Ovaries and Infertility.
Date October 2001
Journal The Journal of Obstetrics and Gynaecology Research
Excerpt

OBJECTIVE: To measure plasma homocysteine, androgen, and insulin concentrations in women with normal and polycystic-appearing ovaries in an infertility setting. METHODS: Among women referred for infertility evaluation (n = 54), homocysteine, androstenedione, DHEAS, total testosterone, fasting insulin/glucose and methyltetrahydrofolate reductase (MTHFR) polymorphism status (C677T mutation) were studied. Ovaries were examined via transvaginal sonogram by one observer and scored as either normal (n = 18) or polycystic (n = 36). RESULTS: When polycystic ovaries were identified, mean total testosterone was significantly higher than when non-polycystic ovaries were present (p = 0.01), although no measured androgen was outside the normal reference range in either group. Average BMI was higher in the polycystic group, but the difference was not significant (p = 0.10). We observed a trend toward higher mean fasting insulin levels in women with polycystic ovaries, but this increase did not reach statistical significance (p = 0.07). Median plasma homocysteine was identical (7.0 mmol/l) in both populations, and no study subject exceeded the current recommended maximum reference value. CONCLUSIONS: In this population, the presence of polycystic ovaries was associated with higher serum androgens (especially total testosterone) although none of the measured androgens were above the normal range. While fasting insulin levels were also higher in this group, median plasma homocysteine levels were similar irrespective of ovarian morphology. Concomitant plasma homocysteine derangements in this population of young, lean patients with polycystic-appearing ovaries seem unlikely. Further studies are needed to clarify the role(s) of homocysteine in human reproductive physiology.

Title Periovulatory Serum Human Chorionic Gonadotropin (hcg) Concentrations Following Subcutaneous and Intramuscular Nonrecombinant Hcg Use During Ovulation Induction: a Prospective, Randomized Trial.
Date August 2001
Journal Fertility and Sterility
Excerpt

OBJECTIVE: To describe serum levels of human chorionic gonadotropin (hCG) as a function of hCG injection method (subcutaneous vs. intramuscular) among infertile women undergoing ovulation induction. DESIGN: Prospective, randomized clinical trial. SETTING: Major urban infertility referral center. PATIENT(S): Women presenting for infertility evaluation and ovulation induction. INTERVENTION(S): Controlled ovarian hyperstimulation was followed by 5,000 IU urinary (nonrecombinant) hCG injection, given intramuscularly (i.m.) or subcutaneously (s.c.). MAIN OUTCOME MEASURE(S): Serum hCG levels measured 24 hours after administration of hCG, and patient tolerability of injected hCG. RESULT(S): There were no statistically significant differences in age or body mass index (BMI) among patients receiving hCG s.c. (n = 13) or i.m. (n = 15). Mean [IQR (25; 75)] serum hCG levels in the s.c. and i.m. groups were 171.7 [27.0; 207.0] and 142.2 [102.5; 157.5] mIU/mL, respectively. No adverse events were registered by any patient receiving hCG by either injection method. In this non-IVF population, two pregnancies were established in each subgroup (4 of 28, or approximately 14% pregnancy rate). CONCLUSION(S): The s.c. administration of 5,000 IU hCG (reconstituted in vol. = 0.5 mL) was well tolerated by all women in this study and was associated with postinjection serum hCG levels similar to those observed after administration of an equivalent i.m. hCG dose. This investigation suggests that clinical use of s.c. hCG is suitable for lean women (e.g., BMI <30) undergoing ovulation induction, but additional data are needed to study the appropriateness of s.c. hCG administration in heavier patients.

Title Assisted Reproductive Technologies and Monozygous Twins: Implications for Future Study and Clinical Practice.
Date August 2001
Journal Twin Research : the Official Journal of the International Society for Twin Studies
Excerpt

That the zona pellucida (ZP) plays a prominent role in the physiology of some human twinning is an attractive, albeit incompletely proven, medical hypothesis. Indeed, an association has been proposed between manipulation of the ZP and/or native ZP microarchitecture and monozygotic (MZ) twins. Ovulation induction also has been theoretically linked to in vivo ZP alterations facilitating MZ twin development. In vitro fertilization (IVF) relies on necessary (and, in some cases extended) embryo culture techniques potentially creating subtle ZP changes and subsequent MZ twinning. With growing experience in the assisted reproductive technologies and particularly IVF, some preliminary reports have noted an increased frequency of MZ twins after procedures that artificially breach the ZP (i.e., intracytoplasmic sperm injection [ICSI], or 'assisted hatching'). Such ZP manipulations ostensibly enhance oocyte fertilization or facilitate blastocyst hatching, thus improving pregnancy rates for couples undergoing fertility treatment. Evidence exists both to challenge and support the connection between these phenomena and MZ twins. This report outlines the fundamental embryological processes believed responsible for these conflicting observations; the current literature on the subject of human ZP micro-manipulation and MZ twins is also discussed.

Title The Development of Methods for Assessing the in Vivo Oestrogen-like Effects of Xenobiotics in Cd-1 Mice.
Date July 2000
Journal Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
Excerpt

The increasing awareness and concern about the potential health risks posed to the ecosystem and to man by endocrine disrupting chemicals with oestrogen-like activity in the environment has focused attention on the need for developing sensitive and specific methods for identifying these xenobiotics and to evaluate their degrees of toxic effects. We have conducted dose response studies in immature (21 days old) CD-1 female mice treated with four compounds, diethylstilboestrol (DES) (0.1 microg to 25 mg/kg body weight), alpha-zearalanol (0.5 mg to 25 mg/kg body weight), methoxychlor (0.5 mg to 500 mg/kg body weight) and bisphenol A (10 microg to 100 mg/kg body weight) administered subcutaneously daily for 3 days, and measured a number of uterine markers in treated and control (vehicle treated) mice. These were, in addition to the commonly measured changes in relative uterus weight and histopathological examination of uterine tissue, three other markers indicative of uterotrophic effects, namely, uterine luminal epithelium BrdU labelling index over the last 24 hr, peroxidase activity and lactoferrin expression. All of these markers showed clear dose-related increases in DES- and methoxychlor-treated animals. In the case of alpha-zearalanol treatment, relative uterine weight, peroxidase activity and lactoferrin expression showed dose-related increases at all the doses investigated. BrdU incorporation (an index of cell proliferation) also progressively increased at dose levels ranging from 0.1 mg to 5.0 mg/kg body weight, but apparently decreased at 25 mg/kg body weight. In contrast to these findings, bisphenol-A treatment showed no consistent changes in any of the four markers at the dose levels investigated. Additionally, studies were also conducted on a number of chemicals in CD-1 mice at one dose level. The chemicals investigated were: bisphenol A (1 g/kg body weight/day), naringenin (1 g/kg body weight/day) o,p'-DDT (500 mg/kg body weight/day), genistein (1 g/kg/day), coumestrol (0.5 mg/kg/day) and chlordecone (20 mg/kg/day) administered subcutaneously daily for 3 days. There was some variability in response of the markers perhaps indicating that the chemicals did not all act in the same way. The findings of our exploratory in vivo studies in CD-1 mice suggest that the measurement of a range of uterine markers, in addition to organ weight and histopathology, would provide useful information on the potential oestrogenicity of chemicals.

Title Tamoxifen Induces Endometrial and Vaginal Cancer in Rats in the Absence of Endometrial Hyperplasia.
Date May 2000
Journal Carcinogenesis
Excerpt

Tamoxifen was administered orally to neonatal rats on days 2-5 after birth and the subsequent effects on the uterus were characterized, morphometrically, over the following 12 months. Tamoxifen inhibited development of the uterus and glands in the endometrium, indicating a classical oestrogen antagonist action. Between 24 and 35 months after tamoxifen treatment there was a significant increase in the incidence (26%) of uterine adenocarcinomas and a 9% incidence of squamous cell carcinomas of the vagina/cervix in the absence of any oestrogen agonist effect in the uterus. This demonstrates that an oestrogen agonist effect is not an absolute requirement for the carcinogenic effect of tamoxifen in the reproductive tract of the rat. The unopposed oestrogen agonist effect of tamoxifen on the endometrium may not be the only factor involved in the development of endometrial cancers. It is possible that tamoxifen causes these tumours via a genotoxic mechanism similar to that seen in rat liver. However, using (32)P-post-labelling we failed to find evidence of tamoxifen-induced DNA adducts in the uterus. Tamoxifen may affect hormonal imprinting of oestrogen receptor responses in stem cells of the uterus, causing reproductive tract cancers to arise at a later time, in the same way as has been proposed for diethylstilbestrol. If these rodent data extrapolate to humans, then women who are taking tamoxifen as a chemopreventative may have an increased risk of vaginal/cervical cancer, as well as endometrial cancer.

Title Compartmentalized Uterotrophic Effects of Tamoxifen, Toremifene, and Estradiol in the Ovariectomized Wistar (han) Rat.
Date August 1999
Journal Toxicological Sciences : an Official Journal of the Society of Toxicology
Excerpt

The comparative uterotrophic responses of ovariectomized Wistar (Han) rats to tamoxifen, toremifene, and 17beta-estradiol have been determined over a period of 72 h. Uterine wet weight; luminal epithelial cell hypertrophy; and BrdU labeling index in the different tissue compartments of the uterus, and the immunohistochemical expression of nuclear estrogen receptor alpha (nERalpha), and nuclear progesterone receptor (nPR) were examined. Luminal epithelial cell hypertrophy was produced by all three compounds to a similar degree. 17beta-Estradiol produced an increase in uterine wet weight due to fluid imbibition over the 3-day period, and an increase in DNA synthesis in the endometrial stromal and myometrial compartments of the uterus, as measured by increased BrdU incorporation. Estradiol increased the expression of nERalpha and nPR in the myometrium with time and decreased nERalpha levels from the overexpressed levels in control ovariectomized rat luminal epithelial cells. Tamoxifen and toremifene caused a smaller increase in uterine weight and the BrdU labeling index in the endometrial stroma and myometrium than did estradiol, and they increased the expression of nERalpha and nPR in the myometrium. Tamoxifen and toremifene differed from estradiol in that they did not decrease the expression of nERalpha in the luminal epithelial cells of the uterus. The response of PR expression was the same for tamoxifen, toremifene, and estradiol, and was therefore considered to be the most reliable indication of an estrogen-agonist effect in this study. The ability to distinguish differential, compartmentalized effects for agonists of estrogen action in the uterus will allow a better risk assessment for new pharmaceuticals that are used as breast cancer chemotherapeutic agents, especially where their use may also be associated with an increased risk of uterine cancers, in particular.

Title Micromanipulation in Assisted Reproduction: a Review of Current Technology.
Date August 1998
Journal Current Opinion in Obstetrics & Gynecology
Title Caprine Blastocyst Formation Following Intracytoplasmic Sperm Injection and Defined Culture.
Date April 1998
Journal Zygote (cambridge, England)
Excerpt

Experiments were undertaken to develop intracytoplasmic sperm injection (ICSI) to produce caprine embryos out of the normal breeding season. Oocytes were obtained from 2-6 mm ovarian follicles at slaughter. Selected oocytes with two to four layers of cumulus cells were incubated in 1 ml of H-TCM199 supplemented with 10 micrograms each of oFSH and bLH (NHPP, NIDDK, NICHD, USDA) and 20% fetal bovine serum (FBS) in a thermos (38.5 degrees C) for 4.5 h during transportation. Then, oocytes were transferred into 75 microliters of freshly prepared maturation medium under paraffin oil and a mixture of 5% O2, 5% CO2 and 90% N2. Approximately 26 h after recovery oocytes were denuded by incubation with hyaluronidase (100 IU/ml) and pipetting and held at 38.5 degrees C for 90 min. Spermatozoa frozen in egg yolk extender were thawed in a 37 degrees C water bath for 15 s. Motile fractions were selected by swim-up, then incubated for 90 min in TALP with 10 micrograms heparin/ml. Each oocyte was positioned with its first polar body at 6 or 12 o'clock by a holding pipette. Sperm (1 microliter) were added to 10 microliters medium containing 10% polyvinylpyrrolidone. A sperm cell was aspirated into a pipette, and then injected head-first into the cytoplasm of an oocyte maintained in H-TCM199 + 20% FBS at 37 degrees C. Injected oocytes were transferred to HM and, after 90 min, cultured in 50 microliters of BSA-free synthetic oviduct fluid plus polyvinyl alcohol, citrate and non-essential amino acids. Results demonstrate that caprine blastocysts can be produced outside the breeding season by the use of frozen-thawed semen and injection of sperm cells with broken tails into ova followed by culture in defined medium.

Title Pregnancy-associated Hospitalizations in the United States in 1991 and 1992: a Comprehensive View of Maternal Morbidity.
Date March 1998
Journal American Journal of Obstetrics and Gynecology
Excerpt

OBJECTIVE: Our purpose was to update the national estimate of severe pregnancy complications and describe associated maternal characteristics of hospitalizations during pregnancy, applying an expanded definition of maternal morbidity. STUDY DESIGN: From 1991 and 1992 National Hospital Discharge Survey data, we estimated ratios of hospitalizations per 100 deliveries and compared relative ratios by maternal characteristics. We computed standard errors with the SUDAAN program and estimated 95% confidence intervals for relative ratios. RESULTS: The likelihood of hospitalization for pregnancy complications appeared to decline between the period 1986 and 1987 and the period 1991 and 1992, although primarily for pregnancy loss hospitalizations. In 1991 and 1992 there were 18.0 total pregnancy-associated hospitalizations/100 births (17.2 for whites, 28.1 for blacks). Component ratios were 12.3 for obstetric hospitalizations, 4.4 for pregnancy loss hospitalizations, and 1.4 for nonobstetric hospitalizations; all ratios were higher for blacks than for whites. CONCLUSIONS: Maternal hospitalization remains a substantial component of prenatal care. Because of underreporting and changes in medical practice, recent declines in maternal hospitalization may not represent true reductions in maternal morbidity.

Title Reinsemination by Intracytoplasmic Sperm Injection of 1-day-old Oocytes After Complete Conventional Fertilization Failure.
Date October 1997
Journal Fertility and Sterility
Excerpt

OBJECTIVE: To analyze the efficacy of intracytoplasmic sperm injection (ICSI) for "rescue" of failed conventional insemination cycles. DESIGN: Retrospective clinical study. SETTING: Private infertility clinic. PATIENT(S): Fifty-four couples with non-male factor infertility undergoing routine IVF within our clinic. INTERVENTION(S): Twenty- to 24-hour-old unfertilized mature oocytes from conventional IVF cycles in which fertilization failure was complete were reinseminated by ICSI to attempt late fertilization and rescue of the otherwise failed IVF cycle. MAIN OUTCOME MEASURE(S): Late fertilization, pregnancy, and embryonic implantation. RESULT(S): Intracytoplasmic sperm injection reinsemination of 489 unfertilized mature oocytes caused degeneration in 50 (10.2%) oocytes, gave rise to normal fertilization in 215 (44.0%) of the injected oocytes, and allowed ET in 48 of the 54 cycles in which initial complete fertilization failure had occurred. One hundred sixty-four (76.3%) of 215 late-fertilized oocytes either were used for fresh transfer or were frozen-stored. Eight viable pregnancies resulted, yielding a 14.8% pregnancy rate per initiated cycle. CONCLUSION(S): Barring potential concerns regarding the chromosomal normality of embryos arising from reinsemination, our results suggest that ICSI is a relatively successful means of rescuing conventional IVF cycles in which fertilization fails completely.

Title Multiple Pregnancy Rate and Embryo Number Transferred During in Vitro Fertilization.
Date September 1997
Journal American Journal of Obstetrics and Gynecology
Excerpt

Our goal was to achieve a good pregnancy rate after in vitro fertilization; more than one embryo, if available, is transferred to the uterine cavity. This is a recognition of the low implantation rates of embryos from in vitro fertilization. A consequence of this can be high-order multiple implantation with obstetric complications.

Title Failure of Oocyte Activation After Intracytoplasmic Sperm Injection Using Round-headed Sperm.
Date July 1997
Journal Fertility and Sterility
Excerpt

OBJECTIVE: To examine the outcome of intracytoplasmic sperm injection (ICSI) with round-headed sperm (globozoospermia). DESIGN: Retrospective analysis. SETTING: In vitro fertilization laboratory with extensive ICSI experience. PATIENT(S): A patient couple with infertility because of globozoospermia seeking ICSI treatment. MAIN OUTCOME MEASURE(S): Fertilization, cleavage, and pregnancy rates. INTERVENTION(S): Intracytoplasmic sperm injection and calcium ionophore. RESULT(S): This couple experienced only 7% fertilization after ICSI in their first cycle. Treatment of the unfertilized oocytes with calcium ionophore 20 hours after ICSI-induced fertilization and cleavage of 70% of the oocytes. Embryo quality was fair to good. On the second cycle, 8 of the injected oocytes were treated with ionophore immediately after ICSI and the remaining 20 oocytes were untreated. Normal fertilization was achieved in 75% of the treated and 10% of the untreated oocytes. Treatment of these unfertilized oocytes with ionophore 20 hours after ICSI resulted in fertilization in 73%. Pregnancy was not achieved after either ICSI cycle. Ultrastructural analysis indicated multiple structural abnormalities in the sperm. CONCLUSION(S): These results indicate that the round-headed sperm from this patient were incapable of oocyte activation after ICSI. This may be the reason for the frequent ICSI fertilization failure seen with this condition. Current ICSI procedures may not always overcome the infertility associated with globozoospermia, and further study of the etiology of this condition is needed.

Title Enhancement of Outcome from Intracytoplasmic Sperm Injection: Does Co-culture or Assisted Hatching Improve Implantation Rates?
Date March 1997
Journal Human Reproduction (oxford, England)
Excerpt

In two separate prospectively randomized trials, intracytoplasmic sperm injection (ICSI) cycles were studied in a controlled manner to monitor the effects of either bovine oviductal epithelial cell co-culture (n = 119) or assisted hatching by zona drilling (n = 100). In the first study, immediately following ICSI, all eggs were placed directly either onto partial monolayers of bovine oviductal cells or into regular culture medium. Although the embryo developmental rate was apparently compromised in part by the presence of the co-culture cells, ultimately there were no significant differences in either the viable pregnancy rate (31.6% co-culture versus 29.0% control) or the embryonic implantation rate (11.4% co-culture versus 13.6% control). Assisted hatching also had no significant impact on ICSI cycle outcome in terms of either the viable pregnancy rate (30.0% assisted hatching versus 32.0% control) or the embryonic implantation rate (8.5% assisted hatching versus 13.5% control). However, in female patients aged > or = 35 years, assisted hatching appeared to convey a marginally significant benefit in terms of both the viable pregnancy rate (35.5% assisted hatching versus 11.1% control) and the embryonic implantation rate (10.3% assisted hatching versus 3.1% control). It seems that the overall improvement of ICSI cycle outcome cannot be achieved by the general application of either co-culture or assisted hatching. Nevertheless, it is possible that there remain specific patient groups that might benefit from selected use of either of these modalities.

Title The Development and Use of the Concept of a Sexually Transmitted Disease Core.
Date November 1996
Journal The Journal of Infectious Diseases
Excerpt

A small proportion of people experiencing a sexually transmitted disease (STD), who are frequently infected or often transmit the infection, has been referred to as the "core." Though a prominent paradigm in the epidemiology of STDs, there is confusion about the meaning of the core. The term has been used to refer variously to people who are infected a large proportion of the time, infect more than one other person, are repeatedly infected, or are prostitutes or their clients and to geographic areas with large numbers of cases. Three perspectives that have contributed to the development of the concept of an STD core were identified: mathematical, clinical-epidemiologic, and sociocultural. These different perspectives share the common aim of identifying strategic points of intervention to reduce STDs. The value of the concept of an STD core will ultimately derive from its utility in lowering STD rates.

Title Effects of Cyproterone Acetate in C57b1/10j Mice.
Date October 1996
Journal Human & Experimental Toxicology
Excerpt

Male and female C57BL/10J mice were fed 0 or 800 ppm cyproterone acetate (CPA) in the diet for 13 weeks. 1. Body weight was reduced (P > 0.001 at 13 weeks) by approximately 33%. 2. Seminal vesicle weights were reduced (P > 0.001) and showed histological atrophy, changes consistent with the anti-androgenic activity of the compound. 3. Liver weights were increased (P > 0.001) by +90% of control mean weights; hepatocyte hypertrophy and increased fat and glycogen were seen by light microscopy, and hyperplasia of smooth endoplasmic reticulin by transmission electron microscopy. 4. Assessment of liver mixed function oxidase activity demonstrated induction of cytochrome P450 enzymes, and increased isozyme 2B1/2 in males and 3A1 in both sexes was confirmed by immunohistochemical staining of liver sections. 5. An increase in bromodeoxyuridine (BrdU) labelling index of the liver was seen in females only. 6. This study is the first in a programme of work with CPA designed to investigate the effects of the compound in mice. It demonstrates that the hepatic effects of the compound which have been described in the rat also occur in mice.

Title Effect of Coculture on Subsequent Survival and Implantation of Cryopreserved Human Embryos.
Date June 1996
Journal Journal of Assisted Reproduction and Genetics
Excerpt

PURPOSE: This retrospective analysis was designed to assess the performance of human embryos following cryopreservation based on whether they were originally developed in standard culture medium (65 cycles, 223 embryos) or cocultured on partial monolayers of bovine oviductal epithelial cells (63 cycles, 198 embryos). Embryo cryosurvival and implantation were compared between the study group and the contemporaneously match controls. RESULTS: During a 2-year period when no factors of the cryopreservation program were altered, 63 transfers of 159 surviving thawed control cleavage-stage embryos (71.3% survival) that were 54% intact gave rise to 11 viable pregnancies (17.5%/ET), to yield an implantation rate of 6.9% per embryo. Sixty-three transfers of 147 thawed cocultured embryos (74.2% survival) that were 61% intact gave an implantation rate of 13.6% per embryo that was significantly higher than the control group (P < 0.05). CONCLUSION: Coculture of embryos prior to cryopreservation does not appear to improve cryosurvival; however, it does improve implantation postthaw compared with embryos following standard culture prior to cryopreservation.

Title Factors Affecting Success with Intracytoplasmic Sperm Injection.
Date December 1995
Journal Reproduction, Fertility, and Development
Excerpt

In this study, 141 couples underwent 163 cycles of in vitro fertilization (IVF) and embryo transfer in which the eggs were inseminated by intracytoplasmic sperm injection (ICSI). Overall, 41% of the injected eggs were normally fertilized and 81% of the resulting embryos were suitable for cryopreservation (91 embryos) or uterine transfer. From 153 fresh embryo transfers, 45 ongoing or delivered pregnancies (27.6% per cycle) were achieved, and of the 507 embryos transferred, 54 successfully implanted giving an implantation rate per embryo of 10.7%. Five additional pregnancies did not yield a viable fetus or underwent a spontaneous abortion, giving a miscarriage rate of 10% (5/50). Increased maternal age or a prior diagnosis of failed fertilization after conventional IVF had a significantly negative impact on success. Sperm from the testis and epididymis, those retrieved by electro-ejaculation, and completely immotile ejaculated sperm all gave rise to pregnancies. ICSI reinsemination was used with limited success to rescue failed fertilization cycles, although the implantation rate per embryo was poor (5%). ICSI has greatly improved the ability to use IVF for treating couples with a poor fertilization potential.

Title A Live Birth from Intracytoplasmic Injection of a Spermatozoon Retrieved from Testicular Parenchyma.
Date September 1995
Journal The Journal of Urology
Title Minimal Stimulation with Simplified Monitoring for in Vitro Fertilization.
Date July 1995
Journal Journal of Assisted Reproduction and Genetics
Excerpt

PURPOSE: This retrospective, descriptive study was designed to determine the effectiveness of using clomiphene citrate in relatively high daily doses (100, 150, and 200 mg) with simplified monitoring for in vitro fertilization in a private office and surgical center. The self-selected study population comprised 109 women who were 25-42 years old, including 26 women whose husbands had mild male-factor infertility. RESULTS: During January 1992 through December 1993, 165 stimulation cycles resulted in 137 egg retrievals, 24 clinical pregnancies (17.5%), and 20 viable pregnancies (14.5%). Cycles that could not be completed (28/165 or 16.9% of all cycles) involved luteinizing hormone surges, insufficient follicles, or low estradiol levels. There were no pregnancies in patients who were 40 years or older or who received 200 mg daily doses of clomiphene citrate. The viable pregnancy rate among patients with male factor infertility was 7.7% (2/26). For non-male-factor infertility patients who were younger than 40, the viable pregnancy rate was 17.6% (18/102). CONCLUSION: The simplified monitoring method did not appear to compromise the results.

Title Intracytoplasmic Injection of Testicular and Epididymal Spermatozoa for Treatment of Obstructive Azoospermia.
Date July 1995
Journal Human Reproduction (oxford, England)
Title Practical Evolution and Application of Direct Intracytoplasmic Sperm Injection for Male Factor and Idiopathic Fertilization Failure Infertilities.
Date April 1995
Journal Fertility and Sterility
Excerpt

OBJECTIVE: To analyze the introduction of a new assisted fertilization technique for the treatment of severe male factor and idiopathic fertilization failure infertilities. DESIGN: Retrospective analysis of 16-month clinical application of IVF-ET where insemination was performed solely by direct intracytoplasmic sperm injection. SETTING: Clinical IVF-ET program. PATIENTS: Ninety-two couples undergoing 105 cycles of sperm injection. RESULTS: One hundred embryo transfers yielded 28 viable pregnancies (28%) from which eight normal deliveries have occurred to date. Complete cleavage arrest or fertilization failure occurred in four cycles, and one couple had all embryos cryopreserved. One thousand one hundred forty-three eggs were injected of which 173 (15%) degenerated. Four hundred seventy-nine of the surviving 970 eggs became normally fertilized (49%), and 381 of these zygotes (79.5%) developed suitably for cryopreservation or for transfer. Thirty-four of 310 embryos transferred implanted, yielding an implantation rate of 11%. Both testicular and epididymal sperm were used successfully to achieve fertilization and pregnancies, as was sperm retrieved by electroejaculation. Older women and couples suffering from prior idiopathic fertilization failure had a markedly poorer outcome. CONCLUSIONS: These results confirm that the intracytoplasmic sperm injection technique is a successful form of assisted fertilization that can be applied to a wide range of couples at significant risk from fertilization failure.

Title "the Best of Us".
Date October 1994
Journal Fertility and Sterility
Title Treatment of Male Infertility and Idiopathic Failure to Fertilize in Vitro with Under Zona Insemination and Direct Egg Injection.
Date September 1993
Journal American Journal of Obstetrics and Gynecology
Excerpt

Failure to fertilize eggs in vitro may be countered by micromanipulation of gametes to place selected spermatozoa underneath the zona pellucida of the egg or directly into the egg, thereby improving chances of fertilization and production of viable embryos. Analysis of our clinical data for assisted fertilization was undertaken to assess those factors of relevance in this therapy, and a description of our procedures are given.

Title Repeated Sperm Injection Under the Zona Following Initial Fertilization Failure.
Date May 1993
Journal Human Reproduction (oxford, England)
Excerpt

When fertilization fails following micromanipulative under-zona insemination, it is possible to repeat the procedure adding more spermatozoa to achieve fertilization, embryonic development and pregnancy. We report on 18 human in-vitro fertilization cycles where this approach was used. In nine cycles only late-fertilized embryos were available for transfer, and these gave rise to two viable pregnancies (22.2% per transfer). In six cycles, where a mixture of late- and timely fertilized embryos were available for transfer, two viable pregnancies arose (33.3% per transfer). In three cycles no fertilization was achieved even after reinsemination by repeated under-zona insemination.

Title Electroejaculation in Combination with in Vitro Fertilization and Gamete Micromanipulation for Treatment of Anejaculatory Male Infertility.
Date September 1992
Journal American Journal of Obstetrics and Gynecology
Excerpt

OBJECTIVE: Failure to ejaculate may be overcome by use of electroejaculation. However, such semen samples are often unsuitable for therapies like intrauterine insemination. The combination of electroejaculation with in vitro fertilization, including gamete micromanipulation, should improve chances of fertilization and pregnancy in such cases. STUDY DESIGN: Within a private infertility clinic electroejaculation in combination with intrauterine insemination was carried out in 18 cycles (10 couples). Four couples went on to receive therapy by electroejaculation plus in vitro fertilization, along with six other couples (15 cycles total) with semen too poor for intrauterine insemination. RESULTS: One term pregnancy arose in the electroejaculation-intrauterine insemination group, and one term pregnancy plus one continuing pregnancy arose from two couples (three cycles) who underwent in vitro fertilization with conventional insemination after electroejaculation. Six couples (nine cycles) had embryos arising only from gamete micromanipulation transferred, and this yielded two term pregnancies, one spontaneous abortion, and a biochemical pregnancy. Two couples (three cycles) failed to achieve fertilization even with micromanipulation; however, donor-inseminated eggs gave rise to two term pregnancies and one continuing pregnancy in these patients. CONCLUSIONS: This report confirms the feasibility of in vitro fertilization in conjunction with electroejaculation and extends the therapy to incorporate gamete micromanipulation.

Title How Many Ivf Embryos to Transfer?
Date July 1991
Journal Lancet
Title Routine Gamete Intrafallopian Transfer (gift): a Highly Successful Option for Treatment of Non-tubal Infertility.
Date January 1990
Journal Asia-oceania Journal of Obstetrics and Gynaecology / Aofog
Excerpt

Gamete intrafallopian transfer (GIFT) is increasingly accepted as a realistic alternative to in vitro fertilization (IVF), or intrauterine insemination (IUI) for treatment of non-tubal infertility. The lack of information on fertilization capacity of the gametes, the greater cost relative to IUI, and the partly unsubstantiated claims of higher success rates, caused us some concern with the readiness with which GIFT had been accepted as a standard infertility treatment. So we undertook a provisional GIFT programme with these considerations in mind, and we report on the first 91 GIFT cycles performed in our clinic. Sixty of the patients (62 cycles) treated suffered from idiopathic infertility, 12 from minimal endometriosis, 9 from male factor infertility, and 8 from ovulatory dysfunction. An initial clinical pregnancy rate of 41% (38/91) was achieved; pregnancy loss was 23% (9/38), giving a continuing pregnancy rate of 32% (29/91). Given this undeniably encouraging result, and the potential for diagnostic IVF, embryo freezing, and ovum donation with surplus oocytes collected from this GIFT programme, we now have adopted GIFT permanently as a treatment to complement our IVF and IUI programmes.

Title Fallopian Replacement of Eggs with Delayed Intrauterine Insemination (fredi): an Alternative to Gamete Intrafallopian Transfer (gift).
Date November 1989
Journal Journal of in Vitro Fertilization and Embryo Transfer : Ivf
Excerpt

This report contains details of what is the first group of patients with nontubal infertility to undergo fallopian replacement of eggs with delayed intrauterine insemination (FREDI). Twenty-three patients suffering from idiopathic or immune infertility, polycystic ovarian disease (PCOD), or mild endometriosis underwent follicular stimulation with human menopausal gonadotropin and/or pure follicle-stimulating hormone plus human chorionic gonadotropin prior to laparoscopic pickup of eggs of varying maturity. Eggs without spermatozoa were transferred at the time of laparoscopy. Subsequent high intrauterine insemination (IUI) of washed spermatozoa at a time when egg maturation within the tubes was judged to be complete enabled a cohort of fully capacitated spermatozoa to meet fully mature eggs in a totally physiological manner. Eight clinical pregnancies arose from this group, one healthy, male infant has been delivered, and four pregnancies remain ongoing. Although based on a small population of patients, it does seem that in vivo egg maturation following replacement in the fallopian tube is an effective alternative to in vitro maturation and, with the increased control over timing of egg insemination, leads us to propose FREDI as a flexible new therapeutic approach for the treatment of nontubal infertility.

Title Pregnancies from Fallopian Replacement of Immature Eggs with Delayed Intrauterine Insemination.
Date June 1989
Journal Human Reproduction (oxford, England)
Excerpt

Gamete intrafallopian transfer requires that a woman should not only have patent tubes but should also have had mature eggs collected for replacement. Eggs must be collected as close to ovulation as possible, to give them a good chance of fertilizing upon replacing them directly into the tubes with the spermatozoa. Preliminary results from three patients who received Fallopian replacement of immature eggs followed by delayed intrauterine insemination indicate that maturation of eggs can occur in vivo in the Fallopian tubes. Intrauterine insemination at a later time when the eggs were judged to be mature has given rise to two pregnancies from the three patients with whom this procedure was adopted.

Title Comparative Study of Combined Gift and Ivf-et with Gift Alone.
Date December 1988
Journal Human Reproduction (oxford, England)
Excerpt

Twenty-eight couples with unexplained infertility, or with suboptimal spermatozoa were divided into two groups. One group underwent gamete intra-Fallopian transfer (GIFT), and the other had combined GIFT and in-vitro fertilization--embryo transfer (IVF-ET) (GET). There was a marked difference in pregnancy rates between the two groups, with the pregnancy rate surprisingly being less in the combined GET group; 10% for GET, as compared with 39% for GIFT alone. The results suggest that GIFT and IVF-ET are incompatible. Differences in the pregnancy rates may be explained by limitations in implantation, whereby the embryo-endometrium interaction that allows for implantation and continued embryonic development has a 'single event capacity', and once this interaction is initiated, the 'implantation window' is closed to other embryos that may arrive later in the uterus.

Title Is Embryonic Mortality Increased in Normal Female Rats Mated to Subfertile Males?
Date June 1988
Journal Journal of Reproduction and Fertility
Excerpt

Normal female rats were mated to control males or males which were subjected to unilateral testicular heating (43 degrees C for 30 min), irradiation (500 R), efferent duct ligation, arterial ligation or castration; in all males, the contralateral ductus deferens was ligated. All treatments caused reduced fertility and eventually infertility, as judged by the percentage of females becoming pregnant; the infertility was temporary after heating and irradiation. During the periods of reduced fertility, the numbers of fetuses per pregnant female and the fetus/corpus luteum ratios were reduced. In subsequent experiments, after heating of the testis, there was not only failure of fertilization despite the presence of normal numbers of spermatozoa in the uterus, but also an increased rate of embryonic degeneration in normal females. These results provide evidence that the male, while still fertile, can affect the fecundity of the female and the rate of embryo mortality.

Title Is Delayed Capacitation a Complicating Factor in the Treatment of Idiopathic Infertility by Intrauterine Insemination?
Date October 1987
Journal Journal of in Vitro Fertilization and Embryo Transfer : Ivf
Title Cryopreservation of Human Spermatozoa: an Assessment of Methodology Using Rhodamine 123.
Date August 1987
Journal Archives of Andrology
Excerpt

Rhodamine 123 fluorescent labeling of the human spermatozoal midpiece was used as a means of monitoring spermatozoal viability. This simple procedure was used in three separate studies to establish differential spermatozoal survival. Twenty ejaculates of reasonable quality were taken from men attending the Cromwell Hospital IVF Clinic. These were split three ways: cultured fresh at 37 degrees C as for IVF, or frozen/thawed and then cultured at 37 degrees C after freezing in either an egg yolk-free glycerol cryoprotectant or an egg yolk citrate medium. An expected overall difference in viability between fresh and frozen/thawed spermatozoa was observed, with no significant difference between the cryoprotective abilities of the two cryoprotectants studied. Four ejaculates were either frozen/thawed in the egg yolk-free cryoprotectant or cultured fresh, and both were subsequently stored at room temperature. Fall-off in frozen/thawed spermatozoal viability was more rapid than for the fresh cultured spermatozoa, although all spermatozoa survived longer at room temperature than at 37 degrees C. Five ejaculates were split to culture their spermatozoa at 37 degrees C in media containing either human or bovine serum albumin, or human fetal cord serum. BSA proved to be the least successful of protein supplements in maintaining spermatozoal viability, with HSA and cord serum giving rise to comparable viability of spermatozoa cultured in each. RH 123 is recommended as an alternative means of assessing human spermatozoal viability, and the results arising from the use of this technique here are discussed with their particular relevance to semen freezing and preparation in IVF centers.

Title Mycoplasmas and in Vitro Fertilization.
Date May 1987
Journal Fertility and Sterility
Excerpt

Semen samples taken from 135 patients attending an in vitro fertilization clinic were shown to be colonized, 53 with Ureaplasma urealyticum (39%) and 16 with Mycoplasma hominis (12%). An unidentified mycoplasma species was isolated from the sperm of two patients. M. hominis was recovered from all the washed sperm samples taken from colonized semen, whereas washing the sperm eradicated U. urealyticum from 71% of colonized semen. The presence of mycoplasmas in semen made no significant difference to the sperm count, sperm motility, sperm abnormalities, or fertilization of eggs.

Title Diagnostic and Treatment Characteristics of Polycystic Ovary Syndrome: Descriptive Measurements of Patient Perception and Awareness from 657 Confidential Self-reports.
Date
Journal Bmc Women's Health
Excerpt

BACKGROUND: This investigation was undertaken to describe patient perception and awareness of the polycystic ovary syndrome (PCOS), the most common cause of anovulation/oligoovulation among women of reproductive age. METHODS: Fifteen parameters were evaluated by a computer-based research instrument accessed by a large, unscreened population. Incomplete questionnaires were not entered, and responses were electronically tabulated to block duplicate submissions. RESULTS: From 657 participants, the majority (63%) were between 26-34 years old; mean BMI was 30.4 kg/m2. 343 of 657 had at least one pregnancy and 61% of the study group had taken fertility medicine (any type) at least once. Physicians were the most common provider of PCOS information for all study participants, irrespective of age. Patient emotions associated with the diagnosis of PCOS included "frustration" (67%), "anxiety" (16%), "sadness" (10%), and "indifference" (2%). Self-reported patient aptitude regarding PCOS was scored as high or "very aware" in >60% of women. Respondents were also asked: "If your PCOS could be safely and effectively helped by something else besides fertility drugs or birth control pills, would that interest you?" Interest in alternative PCOS treatments was expressed by 99% of the sample (n = 648). CONCLUSIONS: In our study population, most women associated negative emotions with PCOS although the self-reported knowledge level for the disorder was high. While these women regarded their obstetrician-gynecologist as integral to their PCOS education, traditional PCOS therapies based on oral contraceptives or ovulation induction agents were regarded as unsatisfactory by most women.

Title Monochorionic-triamniotic Triplet Pregnancy After Intracytoplasmic Sperm Injection, Assisted Hatching, and Two-embryo Transfer: First Reported Case Following Ivf.
Date
Journal Bmc Pregnancy and Childbirth
Excerpt

BACKGROUND: We present a case of monochorionic-triamniotic pregnancy that developed after embryo transfer following in vitro fertilization (IVF). METHODS: After controlled ovarian hyperstimulation and transvaginal retrieval of 22 metaphase II oocytes, fertilization was accomplished with intracytoplasmic sperm injection (ICSI). Assisted embryo hatching was performed, and two embryos were transferred in utero. One non-transferred blastocyst was cryopreserved. RESULTS: Fourteen days post-transfer, serum hCG level was 423 mIU/ml and subsequent transvaginal ultrasound revealed a single intrauterine gestational sac with three separate amnion compartments. Three distinct foci of cardiac motion were detected and the diagnosis was revised to monochorionic-triamniotic triplet pregnancy. Antenatal management included cerclage placement at 19 weeks gestation and hospital admission at 28 weeks gestation due to mild preeclampsia. Three viable female infants were delivered via cesarean at 30 5/7 weeks gestation. CONCLUSIONS: The incidence of triplet delivery in humans is approximately 1:6400, and such pregnancies are classified as high-risk for reasons described in this report. We also outline an obstetric management strategy designed to optimize outcomes. The roles of IVF, ICSI, assisted embryo hatching and associated laboratory culture conditions on the subsequent development of monozygotic/monochorionic pregnancy remain controversial. As demonstrated here, even when two-embryo transfer is employed after IVF the statistical probability of monozygotic multiple gestation cannot be reduced to zero. We encourage discussion of this possibility during informed consent for the advanced reproductive technologies.

Title First Successful Case of in Vitro Fertilization-embryo Transfer with Venom Immunotherapy for Hymenoptera Sting Allergy.
Date
Journal Clinical and Molecular Allergy : Cma
Excerpt

BACKGROUND: To describe immune and endocrine responses in severe hymenoptera hypersensitivity requiring venom immunotherapy (VIT) during in vitro fertilization (IVF). CASE PRESENTATION: A 39-year old patient was referred for history of multiple miscarriage and a history of insect sting allergy. Four years earlier, she began subcutaneous injection of 100 mcg mixed vespid hymenoptera venom/venom protein every 5-6 weeks. The patient had one livebirth and three first trimester miscarriages. Allergy treatment was maintained for all pregnancies ending in miscarriage, although allergy therapy was discontinued for the pregnancy that resulted in delivery. At our institution ovulation induction incorporated venom immunotherapy (VIT) during IVF, with a reduced VIT dose when pregnancy was first identified. Serum IgE was monitored with estradiol during ovulation induction and early pregnancy. Response to controlled ovarian hyperstimulation was favorable while VIT was continued, with retrieval of 12 oocytes. Serum RAST (yellow jacket) IgE levels fluctuated in a nonlinear fashion (range 36-54%) during gonadotropin therapy and declined after hCG administration. A healthy female infant was delivered at 35 weeks gestation. The patient experienced no untoward effects from any medications during therapy. CONCLUSION: Our case confirms the safety of VIT in pregnancy, and demonstrates RAST IgE can remain <60% during IVF. With proper monitoring, VIT during IVF can be safe and appropriate for selected patients and does not appear to adversely affect blastocyst implantation, early embryo development or perinatal outcome. Further studies will be needed to develop VIT guidelines specifically applicable to IVF.


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