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Biomedical subjects

Mark V Sauer

Publications and source records attributed to Mark V Sauer.

At least 37 records · Page 2Linked to original sources
PubMed2004

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↗
PubMed2004

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↗
PubMed2004

Gender selection: pressure from patients and industry should not alter our adherence to ethical guidelines.

Patients who undergo assisted reproduction occasionally request that physicians intervene with techniques that help to determine the gender of their offspring. Conventionally, all of these methods require an invasive procedure that places both the mother and pregnancy at risk. However, for sex-linked disorders, the risk/benefit ratio is favorable; therefore, in such cases, gender selection is warranted. The recent introduction of noninvasive techniques for X- and Y-chromosome-bearing sperm sorting now provides another option for couples. However, the method is not absolute in its ability to sort sperm correctly; in many cases, the offspring are not of the desired sex. Sperm sorting has been marketed increasingly as a means for "family balancing," which is contrary to recommendations that are offered by ethics committees of several professional societies. More studies are needed with respect to the impact of gender selection on families before this method is introduced into routine practice.

Ethics, Medical↗
PubMed2004

Comparative efficacy and safety of cetrorelix with or without mid-cycle recombinant LH and leuprolide acetate for inhibition of premature LH surges in assisted reproduction.

An open label, randomized, multi-centre study was performed to compare cetrorelix and leuprolide acetate for prevention of premature LH surge and to assess whether patients treated with cetrorelix benefit from addition of recombinant human (r-h)LH. Normo-ovulatory women (n = 74) undergoing ovarian stimulation prior to intracytoplasmic sperm injection were treated with leuprolide acetate (n = 25) before ovarian stimulation with recombinant human FSH (r-hFSH) or with cetrorelix 3 mg on stimulation day 7 (with (n = 25) or without (n = 24) r-hLH 150 IU on days 7-10). The main outcome measures were the number of metaphase II (MII) oocytes retrieved; secondary efficacy end-points; adverse events (AE) and other safety measures. There were no significant differences between groups for MII oocytes retrieved, duration of stimulation, total r-hFSH dose and pregnancy rates. The group treated with cetrorelix alone had a significantly lower concentration of oestradiol per follicle compared with the other groups. The majority of AE were mild to moderate in severity. Cetrorelix and leuprolide acetate appear to have comparable efficacy and safety, although cetrorelix has the advantage of typically requiring only one injection.

Adolescent↗
PubMed2003

Complications of in vitro fertilization with intracytoplasmic sperm injection in human immunodeficiency virus serodiscordant couples.

INTRODUCTION: Our experience with complications related to in vitro fertilization (IVF), particularly ovarian hyperstimulation syndrome (OHSS) and higher-order multiple gestations, in human immunodeficiency virus (HIV) serodiscordant couples undergoing IVF with intracytoplasmic sperm injection (ICSI) is presented. METHODS: We retrospectively evaluated 132 consecutive IVF-ICSI cycles and the ensuing 43 pregnancies in 74 HIV-seropositive male discordant couples. The diagnosis of moderate and severe OHSS was based on clinical criteria. Higher-order multiple gestations were defined as viable triplets or greater by the end of the first trimester verified by ultrasonography. RESULTS: The incidence of moderate and severe OHSS was 4.5% of initiated IVF cycles. Seven of the 43 (16.3%) pregnancies were higher-order multiple gestations (1 quadruplet and 6 triplet pregnancies), resulting in the delivery of 3 sets of triplets and 3 sets of twins, with an ongoing twin pregnancy. Four patients had undergone multifetal pregnancy reduction to twins. There were no seroconversions in the women and the infants. CONCLUSION: HIV serodiscordant couples undergoing fertility treatment with IVF-ICSI should be made particularly aware of the risks of higher-order multiple gestations and OHSS.

Adult↗
PubMed2003

Preliminary experience offering oocyte donation to human immunodeficiency virus-1 serodiscordant couples.

CASE REPORT: Our preliminary experience on the use of donor oocytes in human immunodeficiency virus-1 (HIV-1) serodiscordant couples who have previously failed conventional in vitro fertilization (IVF) therapy is presented. Five HIV-1 serodiscordant couples in which the male is infected and the female is seronegative underwent IVF with intracytoplasmic sperm injection (ICSI) utilizing donor oocytes with day 3 embryo transfer and cryopreservation. Six oocyte donation cycles in the five couples yielded 16.8 +/- 9.5 (mean +/- SD) (range 11-34) oocytes; 3.8 +/- 0.4 (range 3-4) transferred embryos; and 1.8 +/- 2.2 (range 0-5) cryopreserved embryos per attempt. The fertilization rate from ICSI was 0.60 +/- 0.16 (range 0.40-0.88). Three of five couples conceived; two from one attempt (one singleton pregnancy and one twin pregnancy); and another after a failed fresh cycle using cryopreserved embryos. All female recipients tested remained seronegative 3 and 6 months post-embryo transfer. All babies (n=4) were seronegative at birth and 3 months postpartum. CONCLUSION: Oocyte donation may be considered as an alternative for childbearing in HIV serodiscordant couples in whom conventional IVF has failed due to factors inherent to the female partner.

Adult↗
PubMed2003

Assessing the clinical utility of in vitro fertilization with intracytoplasmic sperm injection in human immunodeficiency virus type 1 serodiscordant couples: report of 113 consecutive cycles.

OBJECTIVE: To assess the utility and safety of in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) in human immunodeficiency virus-1 (HIV-1) serodiscordant couples. DESIGN: Retrospective study. SETTING: University-based practice. PATIENT(S): HIV-1 seropositive men and seronegative women undergoing IVF-ICSI.IVF-ICSI, HIV testing of female partner and infants. MAIN OUTCOME MEASURE(S): IVF performance, pregnancy rates, and HIV-1 seroconversion rate. RESULT(S): We initiated 113 IVF cycles in 61 serodiscordant couples. Due to poor ovarian response, 11.5% of cycles were canceled. The number of oocytes collected per retrieval was 17.11 +/- 9.52 (2 to 47), yielding 13.90 +/- 8.12 (1 to 42) mature oocytes suitable for ICSI, and 9.34 +/- 5.45 (0 to 24) normal fertilized oocytes. We transferred 3.54 +/- 1.09 (1 to 6) embryos. The overall clinical pregnancy rate was 44.8% per embryo transfer (ET); ongoing/delivered pregnancy rate was 36.5% per ET, with a 57.1% multiple gestation rate. Cumulatively, 50.8% of couples achieved a successful pregnancy through IVF-ICSI, 54.1% when including frozen ET cycles. There were no HIV-1 seroconversions in patients or delivered babies. CONCLUSION(S): HIV-1 serodiscordant couples who undergo IVF-ICSI to avoid disease transmission experience high rates of success, but also encounter complications from assisted reproductive technology similar to traditional patients. The best candidates appear to be younger women without strong risk factors for ovarian hyperstimulation syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Reversible azoospermia: anabolic steroids may profoundly affect human immunodeficiency virus-seropositive men undergoing assisted reproduction.

BACKGROUND: In vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) has recently been offered to human immunodeficiency virus (HIV)-serodiscordant couples where the man is seropositive and the woman seronegative to achieve pregnancy while minimizing the risk of HIV transmission. Anabolic steroids are commonly prescribed medications for adjunctive treatment of HIV disease to prevent muscle wasting. CASE: An HIV-serodiscordant couple presented for fertility care and evaluation. The man was found to be azoospermic. Further evaluation attributed his azoospermia to his treatment with testosterone and oxandrolone. After these agents were discontinued, his azoospermia resolved within 3 months. Normal sperm were then cryopreserved for future use, and his medications were resumed. Later the couple conceived by IVF-ICSI using the cryopreserved sperm. CONCLUSION: The popular use of anabolic steroids in HIV-infected men may predispose them to abnormal sperm production.

Adult↗
PubMed2003

Understanding the motivations, concerns, and desires of human immunodeficiency virus 1-serodiscordant couples wishing to have children through assisted reproduction.

OBJECTIVE: To survey the attitudes of human immunodeficiency virus (HIV)-serodiscordant couples interested in assisted reproduction and better characterize their motivations for reproducing. METHODS: A prospectively designed questionnaire and open-ended interview of 50 consecutive HIV-serodiscordant couples interested in undergoing assisted reproduction to avoid transmission of virus were studied. Demographic characteristics and attitudes regarding beginning a family were obtained. By design, males were HIV seropositive (age, 38.0 +/- 5.4 years, range 26-51 years) and healthy. Women were HIV seronegative (age, 34.5 +/- 5.1 years, range 24-45 years). Most couples were married (44 of 50) and in long-term relationships (duration of relationship, 8.9 +/- 4.9 years, range 1-20 years). RESULTS: Before presentation, nine of 50 couples had conceived and delivered a child (three of nine instances with knowledge of paternal HIV status). Previous timed intercourse occurred in 8% of couples (four of 50). Six individuals stated they would proceed with timed intercourse if no other alternatives existed. Forty-eight percent said they would prefer artificial insemination with donor sperm in lieu, if assisted reproduction failed or were unavailable. Forty-three percent of respondents would pursue "posthumous conception" if cryopreserved sperm or embryos were available in the event of the partner's death. Most couples discussed the possibility of single parenting (45 of 50; 90%) or the possibility for adoptive parenting (29 of 50; 58%). Couples were aware of risk, and 92% (46 of 50) understood that their child might contract HIV. CONCLUSION: Human immunodeficiency virus-serodiscordant couples are actively seeking reproductive assistance and often consider or practice unsafe measures to achieve pregnancy. Reproductive issues and concerns unique to these couples need to be addressed before treatment.

Adult↗
PubMed2003

Obstetric outcomes of human immunodeficiency virus-1-serodiscordant couples following in vitro fertilization with intracytoplasmic sperm injection.

The objective of this article is to report obstetric outcomes of human immunodeficiency virus-1 (HIV-1)-serodiscordant couples who underwent in vitro fertilization and embryo transfer (IVF-ET) with intracytoplasmic sperm injection (ICSI) at a tertiary care center. We reviewed the outcomes of seronegative women after IVF-ET with ICSI from January 1, 1997 to June 1, 2002. Serodiscordant couples (n = 25) successfully conceived 27 pregnancies delivering 40 neonates (16 singletons, 9 twins, and 2 triplets). The mean gestational age at delivery was 37 0/7 weeks +/- 3 6/7 weeks (range 26 0/7 to 41 2/7 weeks). The mean birth weight was 2646 g +/- 952 g (range 678 to 4396 g). The cesarean section rate was 70%. Preterm delivery (<37 weeks) occurred in 7 pregnancies, and low birth weight (<2500 g) was observed in 8 pregnancies. There were no HIV-1 seroconversions detected at delivery. One hundred percent of the mothers and offspring were beyond 3 months postpartum and remained seronegative. IVF-ET with ICSI seems safe and effective for serodiscordant couples. Obstetric outcomes are favorable, and HIV-1 infection risk is limited.

AIDS Serodiagnosis↗
PubMed2003

Vascular endothelial growth factor receptor 2-mediated angiogenesis is essential for gonadotropin-dependent follicle development.

Gonadotropins induce ovarian follicle growth that is coincident with increased follicular vasculature, suggesting a role of angiogenesis in follicle development. Functional studies performed in nonhuman primates show that administration of substances that inactivate VEGF block the development and function of preovulatory follicles as demonstrated by histological analysis or hormone measurements. Blockage of function of VEGF receptor 2 (VEGFR-2) alters follicular hormone secretion, suggesting that the intraovarian effect of VEGF might be mediated by this receptor. The specific mechanism by which follicular development was blocked in these previous studies remains unclear, however. Here we characterize the intraovarian role of VEGFR-2 activity on follicular development by choosing a model in which active feedback is absent, the prepuberally hypophysectomized mouse. Hypophysectomy prevents advanced follicle growth and maturation; however, follicle development to the preovulatory stage can be stimulated by administration of gonadotropins. We report that exogenously administered gonadotropins are unable to drive follicle development to the preovulatory stage in the presence of antiangiogenic agent, VEGFR-2-neutralizing Ab's. This inhibition of follicular development is caused by arrests to both angiogenesis and antrum formation. We conclude that the intraovarian VEGF/VEGFR-2 pathway is critical for gonadotropin-dependent angiogenesis and follicular development.

Animals↗
PubMed2003

The role of factor V Leiden mutation in recurrent pregnancy loss.

Although recurrent pregnancy loss is rare, it is a major health problem. Fewer than 50% of cases have definitive causes. Thrombophilias such as factor V Leiden mutation may be responsible for a portion of the unexplained cases. In recent years, a number of studies have reached conflicting conclusions about the role of factor V Leiden in recurrent pregnancy loss. This article reviews the current literature. It appears that factor V Leiden mutation may be associated with stillbirth as well as with some poor pregnancy outcomes. The mutation may also be linked to first-trimester loss. Prospective case-controlled studies to better answer many of the questions concerning the role of this mutation in recurrent pregnancy loss and to determine optimal treatment may not be feasible because it is so rare. At this point, treatment involves anticoagulation and is based on observational studies and expert opinion.

Abortion, Habitual↗
PubMed2002

Predictors of ovulatory failure in women with epilepsy.

Women with epilepsy (WWE) are at increased risk for reproductive disorders. This study was designed to evaluate whether WWE are more likely to have anovulatory cycles and to assess the relative association of the epilepsy syndrome category and antiepileptic drugs (AEDs) to ovulatory dysfunction. Subjects included women aged 18 to 40 years not receiving hormones. Women without epilepsy (23 controls) and women with localization-related epilepsy (LRE, n = 59) or idiopathic (primary) generalized epilepsy (IGE, n = 35) receiving either a cytochrome P450 enzyme (cP450) inducing AED (carbamazepine, phenytoin, and phenobarbital), a cP450 inhibiting AED (valproate), or an AED that does not alter cP450 enzymes (lamotrigine and gabapentin) in monotherapy for 6 months or more were followed for three menstrual cycles. A transvaginal ovarian ultrasound was obtained. Endocrine and metabolic variables were measured and luteinizing hormone sampled over 8 hours on days 2 to 5 of one cycle. Anovulatory cycles occurred in 10.9% of cycles in controls, 14.3% of cycles with LRE, and 27.1% of cycles with IGE. Of women using valproate currently or within the preceding 3 years, 38.1% had at least one anovulatory cycle in contrast with 10.7% of women not using valproate within the preceding 3 years. Predictors of ovulatory failure included IGE syndrome, use of valproate currently or within 3 years, high free testosterone, and fewer numbers of luteinizing hormone pulses, but not polycystic-appearing ovaries. WWE are more likely to experience anovulatory menstrual cycles and the effects of epilepsy syndrome, and AED therapy may be additive. Women with IGE receiving valproate were at highest risk for anovulatory cycles, polycystic-appearing ovaries, elevated body mass index, and hyperandrogynism. WWE with anovulatory cycles may have no other signs of reproductive dysfunction. Therefore, clinicians must be alert to this potential complication of epilepsy.

Adolescent↗
PubMed2002

Successive pregnancies with delivery of two healthy infants in a couple who was discordant for human immunodeficiency virus infection.

OBJECTIVE: To describe two successive pregnancies resulting in two healthy infants in an HIV-discordant couple who underwent IVF-ICSI. DESIGN: Case report. SETTING: University-based infertility clinic. PATIENT(S): A couple seeking fertility treatment in which the male partner was seropositive for HIV-1. INTERVENTION(S): Controlled ovarian hyperstimulation and IVF-ET with ICSI. MAIN OUTCOME MEASURE(S): Pregnancy outcome and HIV-1 seroconversion. RESULT(S): The couple delivered two healthy infants on successive pregnancies with use of IVF-ET with ICSI. CONCLUSION(S): For HIV-discordant couples in which the male partner is seropositive for HIV-1, IVF with ICSI is a viable option.

Adult↗
PubMed2002

Severe hypertriglyceridemia and pancreatitis following hormone replacement prior to cryothaw transfer.

PURPOSE: A case of acute pancreatitis with severe hypertriglyceridemia occurred following use of intramuscular estradiol valerate during endometrial preparation for cryopreserved embryos. METHODS: A 30-year-old woman with primary infertility and a past history of well-controlled hypothyroidism, underwent endometrial development with intramuscular estradiol valerate in preparation for the transfer of cryopreservred embryos. RESULTS: Initial hospitalization, discontinuation of all estrogens, aggressive intravenous fluid hydration, and initiation of low-fat diet with additional gemfibrozil treatment resulted in complete resolution of all symptoms related to the pancreatitis including the hyperlipidemia. A subsequent cryothaw cycle using oral estradiol resulted in a viable pregnancy with only mild increases in the patient's triglyceride and cholesterol levels noted throughout her 38-week gestation. CONCLUSION(S): Estradiol valerate, a commonly used form of estrogen for endometrial preparation during cryothaw cycles, may cause severe hypertriglyceridemia and acute pancreatitis in certain predisposed individuals. Oral and transdermal estrogens should be the preferred method of endometrial preparation in patients at high risk for lipid metabolism disorders, such as patients with polycystic ovarian syndrome and familial hypertriglyceridemia. These estrogens are more rapidly metabolized and have a shorter half life compared to that of estradiol valerate.

Cryopreservation↗
PubMed2002

Oocyte donation.

Oocyte donation affords women with ovarian failure, advanced reproductive age, heritable conditions or recurrent implantation failure the ability to conceive. Recipients must be medically screened carefully prior to attempting pregnancy. Egg donors should also be healthy and pose no infectious or genetic risk to the recipient or offspring. Donor and recipient menstrual cycles are synchronized so that embryos are transferred to a receptive endometrium. Donors are prescribed injectible gonadotrophins to achieve multifollicular growth. Recipient endometrial priming begins with 2 weeks (or more) of oestradiol, with progesterone added to the regimen 3-4 days prior to the transfer of embryos. Pregnancy rates following egg donation are among the highest observed following assisted reproduction. Despite advanced reproductive age, perinatal and obstetric outcomes are generally good. Techniques (i.e. germinal vesicle transfer, donor ooplasm, and ovarian cryopreservation and transplantation techniques) may permit the recipient to provide some genetic contribution to offspring and are currently under investigation.

Adult↗