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Biomedical subjects

Mark V Sauer

Publications and source records attributed to Mark V Sauer.

At least 19 recordsLinked to original sources

Elevated serum müllerian-inhibiting substance may be a marker for ovarian hyperstimulation syndrome in normal women undergoing in vitro fertilization.

We identified patients who experienced ovarian hyperstimulation syndrome (OHSS) (n = 16) and compared their baseline pretreatment levels of müllerian-inhibiting substance (MIS) to age- and weight-matched patients with normal responses to gonadotropins (n = 14). Baseline serum MIS in patients with OHSS were sixfold higher than those seen in normal controls (3.62 +/- 0.87 vs. 0.63 +/- 0.09 ng/mL; P=.0036), indicating that MIS could potentially serve as a useful marker for identifying patients at risk for OHSS.

Adult↗

Family members serving the gestational carrier needs of women lacking a uterus: a report of two cases.

CASE REPORT: In two instances, a designated relative served as a gestational carrier for a woman who no longer had a uterus. In the first case, a 38-year-old woman underwent an emergency cesarean hysterectomy due to worsening fatty degeneration of the liver in the third trimester, culminating in massive hemorrhage, consumptive coagulopathy and the loss of twins at 28 weeks gestation following successful in vitro fertilization. In the second case, a 28-year-old had congenital absence of the uterus and vagina. Both surrogates volunteered for service and were carefully screened medically, reproductively, and psychosocially prior to proceeding. All parties were required to execute informed consent and contracts with private attorneys before entry. Both gestational carriers conceived following the initial embryo transfer; one as the result of previously cryopreserved embryos, the other from embryos obtained following the synchronized in vitro fertilization of newly aspirated oocytes. Gestational carriers were prescribed oral estradiol and vaginal progesterone to prepare the uterus for implantation, and maintained this regimen throughout the first trimester of pregnancy. The pregnancies proceeded uneventfully and resulted in the delivery of singleton births at term. Both infants were formally adopted after delivery by the genetic parents in compliance with the advice of counsel under New York State law. CONCLUSION: Family members serving as gestational carriers provide women with functional ovaries but no uterus, the opportunity to have genetic offspring, while avoiding much of the high cost and social uncertainty of commercial surrogates.

Adult↗

American physicians remain slow to embrace the reproductive needs of human immunodeficiency virus-infected patients.

Nearly 1 million Americans are infected with HIV. Most are living well and enjoying productive lives. Yet few programs in the United States permit unrestricted access to assisted reproduction for HIV-seropositive patients. Some of these individuals have conventional problems causing infertility. Many others are attempting to minimize viral transmission to their spouse or offspring. European centers remain far ahead of those in the United States in advancing techniques and offering services to safeguard the uninfected while providing effective, affordable care to the HIV-seropositive patient.

HIV Infections↗

Oocyte and embryo donation 2006: reviewing two decades of innovation and controversy.

For over 21 years, oocyte and embryo donation have been used to treat infertility caused by a variety of conditions affecting the ovary. Many disorders, including premature ovarian failure, advanced reproductive age, unexplained recurrent implantation failure and inherited conditions, are amenable to gamete donation, with high pregnancy rates and good obstetrical outcomes observed in recipients. Protocols for the medical screening of recipients and donors, as well as infectious disease and genetic testing, have become relatively uniform and well accepted. Established guidelines allow synchronization of the menstrual cycles of both women to ensure that embryos are transferred to a receptive endometrium. The high demand for donor services has led to escalating costs and long waiting lists. American programmes bid against each other to secure the participation of young women often motivated as much by financial reward as altruism. In the United States, where the majority of oocyte donation is practised, more than 100,000 treatment cycles have occurred. However, to date no meaningful longitudinal studies detailing the long term effects of treatment on donors, recipients, children born, or families created have been published. Throughout its history, oocyte and embryo donation has proven to be both efficacious and clinically innovative, yet remains highly controversial.

Embryo Transfer↗

Italian Law 40/2004: a view from the 'Wild West'.

The passage of Law 40/2004 in Italy dramatically affected the manner in which assisted reproduction is conducted there. A recent attempt to modify this highly restrictive legislation failed to gain popular support and was defeated in a 2005 referendum. The public's desire to regulate the field of IVF is probably a result of growing concern over the use and misuse of the technology as portrayed in the popular press and media. Practitioners using this technology throughout the world should take note of the impact legislation brings upon the delivery and accessibility of care, and be appreciative of the social sensitivity of the general population regarding the safe guarding of human embryos.

Attitude to Health↗

HIV seroconversion in a woman preparing for assisted reproduction: an inherent risk in caring for HIV-serodiscordant couples.

A woman preparing to undergo IVF and intracytoplasmic sperm injection to avoid horizontal viral transmission of HIV from her seropositive husband was discovered to be HIV seropositive, presumably secondary to a condom break or unprotected intercourse. Had this event occurred after treatment, the sperm-washing technique used to avoid infection would have undoubtedly been called into question. Nearly all HIV-serodiscordant couples are sexually active and therefore at risk for transmitting infection, either due to improper condom use or unprotected intercourse. Physicians willing to treat HIV-serodiscordant couples must accept the inevitability of viral transmission in occasional individuals. Furthermore, it should not be presumed that all patients who experience seroconversions after either intrauterine insemination or IVF procedures do so as a result of inadequacies in the sperm preparation technique.

Adult↗

Fertility sparing therapy for ovarian cancer has inherent risks and benefits.

INTRODUCTION: Fertility sparing therapy for epithelial ovarian cancer has been suggested for well-selected patients with early stage disease. The overall recurrence rate of 10% and 5-year disease free survival greater than 90% is similar in conservative and traditional surgical management of epithelial ovarian cancer. Thus, conservative approaches may be considered in young women diagnosed with FIGO stage I cancer who wish to preserve reproductive function. Subsequent use of assisted reproductive technologies (ART) may facilitate production of biologic offspring in these cancer survivors. However, each candidate requires unique consideration by subspecialists to avoid potentially fatal management errors. CASE REPORT: We present two cases in which fertility sparing therapy for early stage epithelial ovarian cancer was considered. The first case delineates the comprehensive work-up required to identify candidates for this therapy, while the second case illustrates the successful application of a fertility sparing approach. DISCUSSION: The conservative management of early epithelial ovarian cancer and use of ART to obtain offspring are reviewed.

Adult↗

Rectus sheath hematoma after transvaginal follicle aspiration: a rare complication of in vitro fertilization.

OBJECTIVE: To discuss the diagnosis and management of rectus sheath hematomas after transvaginal follicle aspiration. DESIGN: Case report. SETTING: A single healthy patient in an academic IVF center. PATIENT(S): A healthy patient undergoing routine transvaginal follicle aspiration for IVF. INTERVENTION(S): CT scan, serial phlebotomy, IV fluid, in-patient observation. MAIN OUTCOME MEASURE(S): Condition at discharge. RESULT(S): Patient was successfully managed with conservative measures. After the initial decline, serial hematocrits were stable over 24 hours without any operative interventions. CONCLUSION(S): Rectus sheath hematomas are rare complications of IVF and can be managed conservatively.

Adult↗

Surviving the shifting focus from basic research to clinical activities in reproductive endocrinology and infertility.

Important members of our clinical and scientific community are defecting to the private sector as frustration with academic medical centers grows intolerable. Departments need to rethink traditional paradigms for assigning research, teaching, and clinical care duties to allow faculty the time to do these activities with the care and attention they deserve.

Academic Medical Centers↗

Assessing the treatment efficacy of IVF with intracytoplasmic sperm injection in human immunodeficiency virus-1 (HIV-1) serodiscordant couples.

The purpose of this study was to evaluate the treatment efficacy of using IVF-intracytoplasmic sperm injection (ICSI) in HIV serodiscordant couples interested in having children while minimizing the risk of viral transmission. This study reviews the cases of HIV serodiscordant couples (n = 142) seeking fertility treatment at an assisted reproductive centre. The main outcome measures were successful pregnancy rate and HIV seroconversion rate. In calculating crude pregnancy rates, only patients who were actually treated were taken into account. To compensate for cancelled patients, and patient drop-out, lifetable analysis was performed. Life-table analysis demonstrated that 37.0 +/- 5.0% of couples attain a successful pregnancy after one completed IVF-ICSI with embryo transfer (IVF-embryo transfer) cycle. Following two and three IVF-embryo transfer cycles, the pregnancy rates rose to 56.8 +/- 6.0 and 73.4 +/- 6.9% respectively. Overall pregnancy rates were inversely related to age. There were no HIV seroconversions in treated patients or in delivered babies. It is concluded that the use of IVF-ICSI to avoid disease transmission in HIV-1 serodiscordant couples desiring children appears to be safe and yields high rates of pregnancy. However, success is influenced by the woman's age.

Adult↗

Sperm washing techniques address the fertility needs of HIV-seropositive men: a clinical review.

It is estimated that nearly 40 million people worldwide are infected with HIV. HIV/AIDS prevalence among young people is high, with youth under age 25 years accounting for approximately half of all new infections. Nearly 1 million Americans are HIV-seropositive. Today, HIV-seropositive individuals live active and productive lives despite their illness, largely a result of prescribed highly active antiretroviral therapy (HAART). Most individuals are of reproductive age, and many desire to have children. Various assisted reproductive techniques have been used to reduce or eliminate infectious elements known to be present in semen so that isolated spermatozoa can be safely inseminated or used for intracytoplasmic sperm injection into oocytes. Presently, several European centres and a few US groups offer assistance to HIV seropositive men and their seronegative partners by performing either intrauterine insemination (IUI) or IVF. Since 1987, more than 3600 published attempts have been reported in which processed spermatozoa from HIV-seropositive men were used to establish pregnancy in HIV-seronegative women. Although the data remain observational, sperm washing techniques appear to be relatively safe and effective, offering HIV-serodiscordant couples an opportunity to have children.

Fertilization in Vitro↗

Addressing the growing problem of multiple gestations created by assisted reproductive therapies.

Iatrogenic multiple pregnancy is the most significant complication of assisted reproductive technology (ART). Approximately half of all children born subsequent to ART result from a plural gestation. Furthermore, the majority of triplets and higher order births are the product of ART. The risks for multiple pregnancy vary with practice patterns and the techniques used to achieve pregnancy. Recognizing the potential for serious morbidity associated with multiple pregnancies, infertility specialists have developed strategies to reduce the complication of multiple pregnancies while maintaining acceptable pregnancy rates. Implementation of these refined practices has led to a reduction in the incidence of higher order multiple births, although the incidence of twins has yet to be minimized. Further reduction in the incidence of multiple births after ART necessitates a redefinition of success to emphasize the healthy singleton birth rate, rather than crude pregnancy rates.

Female↗

Deaths of HIV-positive men in the context of assisted reproduction: five case studies from a single center.

Provision of reproductive services to individuals infected with HIV-1 is gaining popular acceptance and is generally endorsed by specialists in reproductive medicine. In the situation in which the male is HIV positive and the female partner is not infected, a large body of evidence has demonstrated that the use of assisted reproductive technology is effective for achieving pregnancy, while eliminating the risk of viral transmission to the mother and fetus. No reports have documented the well-being of the HIV-infected partners subsequent to seeking fertility services. In the current report, we document the cases of five HIV-positive men who died secondary to complications of HIV infection shortly after participating in the assisted reproduction program for HIV-1-serodiscordant couples at Columbia University. Three of these couples successfully achieved pregnancy and live birth, including one set of triplets, and one case of posthumous conception; the fourth case resulted in the cryopreservation of all embryos after the sudden death of the male before the time of embryo transfer; the fifth couple failed to conceive. None of the deaths, which occurred within a few months to 2 years from initial consultation, were related to infertility treatment. The demographic and social statuses of these patients were not different from the general population of men seeking assisted reproduction in our clinic. Regarding the HIV infection status of these cases, three patients had a longer duration of infection compared to the general population of men in our cohort, and one had a significantly lower CD4 cell count. All five men had stable HIV viral loads, and were determined by their primary care providers to be clinically healthy at the time of entry into the program for assisted reproduction. The untimely deaths of these patients underscores the importance of the thoughtful consideration of the complex issues involved in family planning for these individuals, including advanced directives for the use of cryopreserved gametes and embryos, and the social, emotional, and practical issues for the children and surviving partners subsequent to the death of the HIV-positive parent.

Adult↗

Further HFEA restrictions on egg donation in the UK: two strikes and you're out!

The UK and Europe have lagged far behind the USA in the number of egg donation cycles performed over the past two decades. This disparity has been largely attributed to governmental restraints placed on the method within these locales, combined with the lack of regulation in the USA. Severely limiting donor compensation and requiring donors to be identified 18 years or more after their participation will undoubtedly lead to the demise of egg donation as the UK now knows it. Throwing more money at the problem, in the form of increased donor compensation, is unlikely to fix the shortage of participants that is to come. As already witnessed, increasing numbers of women and couples will probably seek treatment outside their native borders to escape the unreasonable demands placed upon their personal liberties by government. Regulation will promote 'reproductive tourism' as patients seek care in areas of the world where self-determination is protected by law.

Disclosure↗

The vascular endothelial growth factor (VEGF)/VEGF receptor 2 pathway is critical for blood vessel survival in corpora lutea of pregnancy in the rodent.

The vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR-2) pathway regulates proliferation, survival, and permeability of vasculature. This pathway is active during the formation of a corpus luteum, a highly vascularized, endocrine organ with a short life span during the nonpregnant state. In the pregnant state, the life span of corpora lutea is much longer because they play a critical role in supporting pregnancy development. We hypothesized that the VEGF/VEGFR-2 pathway plays a critical role in regulating angiogenic events in the corpora lutea of pregnancy. Injection of the neutralizing anti-VEGFR-2 antibody DC101 (ImClone Systems, Inc., New York, NY) on embryonic d 3.5 (preimplantation) or 6.5 (postimplantation) disrupts function of the corpora lutea of pregnancy in CD1 mice, as evidenced by a decrease in organ size, regression of luteal vessels, and a fall in progesterone secretion within 24 h postinjection. Inhibition of the VEGFR-2 caused removal of endothelial cells, mostly through endothelial cell detachment from the vascular basement membrane. Luteal steroid-producing epithelial cells were eliminated through apoptosis secondary to vasculature becoming dysfunctional. Disruption of luteal function caused arrest of embryonic development. The effect of antibody is specific to the ovary, because pregnancy progresses normally in ovariectomized, progesterone-replaced animals treated with anti-VEGFR-2 antibody. Embryonic blood vessels were not affected directly by the antibody, because it did not reach the embryo. Administration of an antibody against VE-cadherin (E4G10), which specifically blocks endothelial proliferation, did not disrupt luteal function and pregnancy development. Thus, VEGFR-2-mediated endothelial cell signals are critical to maintain functionality of luteal blood vessels during pregnancy. Potential clinical applications of inhibitors of the VEGF/VEGFR-2 pathway include emergency contraception and medical treatment of ectopic and abnormal intrauterine pregnancies.

Animals↗

Inhibition of the vascular endothelial cell (VE)-specific adhesion molecule VE-cadherin blocks gonadotropin-dependent folliculogenesis and corpus luteum formation and angiogenesis.

Although it has been previously demonstrated that administration of anti-vascular endothelial growth factor (VEGF) receptor-2 antibodies to hypophysectomized (Hx) mice during gonadotropin-stimulated folliculogenesis and luteogenesis inhibits angiogenesis in the developing follicle and corpus luteum (CL), it is unclear which of the many components of VEGF inhibition are important for the inhibitory effects on ovarian angiogenesis. To examine whether ovarian angiogenesis can be more specifically targeted, we administered an antibody to VE-cadherin (VE-C), an interendothelial adhesion molecule, to Hx mice during gonadotropin stimulation. In tumor models and in vivo and in vitro assays, the anti-VE-C antibody E4G10 has been shown to specifically inhibit angiogenesis, but VE-C has yet to be inhibited in the context of ovarian angiogenesis. In addition to studying the effect on neovascularization in the follicular and luteal phases, we also examined the effect of E4G10 on established vessels of the CL of pregnancy. The results demonstrate that E4G10 specifically blocks neovascularization in the follicular and luteal phases, causing an inhibition of preovulatory follicle and CL development, a decrease in the vascular area, and an inhibition of function demonstrated by reduced hormone levels. However, when administered during pregnancy, unlike anti-VEGF receptor-2 antibody, E4G10 is unable to cause disruption of the established vessels of the mature CL. These data demonstrate that E4G10 causes a specific inhibition of neovascularization in the ovary without destabilizing preexisting vasculature.

Animals↗

Vaginal administration of oral micronized estradiol results in successful twin pregnancy in a functionally agonadal woman.

CASE REPORT: A 31-year-old nulligravid woman seeking fertility treatment with in vitro fertilization and intracytoplasmic sperm injection failed to achieve pregnancy. Supernumerary embryos were cryopreserved for future use. In preparation for the transfer of the frozen embryos, the patient was prescribed hormones, which included pituitary down-regulation with leuprolide acetate, followed by oral micronized estradiol (E2) and vaginal progesterone (P4) suppositories. At the time of embryo transfer (ET) it was noted that the patient had misunderstood her instructions and was administering both her estrogen and progesterone vaginally. Ultrasound examination revealed a well-developed endometrium adequate for ET so the procedure was performed, and at that point she was instructed to use E2 orally as originally prescribed. Two weeks later, her beta-hCG was elevated, and subsequent ultrasound examinations revealed a twin gestation. The pregnancy progressed normally. CONCLUSION: This patient's hormones were adequately replaced despite vaginal placement of oral medication. Although not commonly prescribed, oral E2 tablets may be administered vaginally in functionally agonadal women preparing for ET, and may serve as an alternative route for women who experience difficulties with oral formulations.

Administration, Intravaginal↗