Biomedical subjects

Lynda Gotlieb

Publications and source records attributed to Lynda Gotlieb.

9 recordsLinked to original sources

PubMed2007

Expression of glycodelin and cyclooxygenase-2 in human endometrial tissue following three-dimensional culture.

PROBLEM: Our previous study showed that in vitro culture of human endometrial tissue in a three-dimensional (3D) fibrin matrix could mimic the early stages of endometriosis with invasion, gland and stroma formation and sprouting of new vessels. The objective of the present study was to evaluate the expression of glycodelin (Gd) and cyclooxygenase-2 (COX-2), two angiogenic factors, to further validate the 3D culture model of endometriosis. METHOD OF STUDY: Human endometrial fragments were obtained from endometrial biopsies and placed in a 3D fibrin matrix culture. Immunohistochemistry with specific antibodies to Gd and COX-2 was used to examine endometrial epithelium and blood vessels, and 4, 6-diamidino-2-phenylindole staining was used for nuclear identification. RESULTS: Three-dimensional culture of human endometrial tissue in the fibrin matrix resulted in the proliferation of endometrial stromal cells, glandular epithelium and angiogenesis. Gd positive glandular epithelium was seen in 85% of wells with developing endometrial glands and COX-2 positive new vessels were seen in 80% of wells with angiogenesis-like structures after 4 weeks of culture. CONCLUSION: Our findings confirm that angiogenesis occurs following the culture of endometrial tissue in the 3D fibrin matrix, and suggests that Gd and COX-2 might play important roles in promoting neovascularization and cell proliferation in the establishment of endometriosis.

Adult↗

PubMed2006

Effect of a statin on an in vitro model of endometriosis.

OBJECTIVE: To determine the inhibitory effect of a statin on angiogenesis in a three-dimensional (3-D) culture of human endometrial fragments in vitro. Angiogenesis has been proposed as an important mechanism in the pathogenesis of endometriosis, and statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) have been shown to have anti-inflammatory and anti-angiogenic activity. DESIGN: Experimental in vitro study of human endometrial biopsies and 3-D culture in fibrin matrix. SETTING: Research laboratory at a university-affiliated infertility center. PATIENT(S): Forty-six normal ovulating women undergoing infertility treatment. INTERVENTION(S): Endometrial samples obtained from the fundus of the uterine cavity were minced, and the fragments were placed in a three-dimensional fibrin matrix culture system. MAIN OUTCOME MEASURE(S): Presence or absence of proliferation of stromal cells and invasion of the fibrin matrix, presence or absence of vessel sprouting, and immunohistochemical characterization of cellular components. RESULT(S): During the 1st week of culture, invasion of stromal cells into the fibrin matrix occurred in the control group and in some wells outgrowths were observed. After 2 weeks, endometrial glands were observed in the outgrowths at a distance from the main tissue and were growing in conjunction with new vessel formation until the end of culture period. A concentration-dependent effect of lovostatin was seen on cell growth and angiogenesis in the experimental groups. In the presence of 5 and 10 microM of statin, angiogenesis was abolished, and cell proliferation was inhibited. In the presence of 1 microM of lovastatin, angiogenesis was reduced, but cell proliferation was not affected. CONCLUSION(S): The statins were shown to be effective in inhibiting the mechanisms of cell proliferation and angiogenesis in an experimental model for the development of endometriosis-like tissue.

Adult↗

PubMed2006

Brown oocytes: implications for assisted reproductive technology.

Fertilization, embryo development, and successful pregnancy can be achieved after transfer of embryos derived from brown oocytes at the same rate as embryos from morphologically normal oocytes. Therefore, brown oocytes are probably normal and this morphological criterion does not seem to be indicative of any adverse outcome in IVF.

Adult↗

PubMed2005

Live birth of healthy triplets after in vitro fertilization and embryo transfer in an acromegalic woman with elevated growth hormone.

OBJECTIVE: To report a case of successful triplet pregnancy in an acromegaly patient with IVF and embryo transfer. DESIGN: Case report. SETTING: Tertiary center for assisted reproductive technologies. PATIENT(S): A 33-year-old woman with acromegaly and primary infertility. INTERVENTION(S): Controlled ovulation hyperstimulation and IVF/embryo-transfer treatment using gonadotropins. MAIN OUTCOME MEASURE(S): Uncomplicated pregnancy course and successful take-home triplet infant girls. RESULT(S): Successful ovarian stimulation and IVF is possible in acromegalic patients. CONCLUSION(S): There may be an effect of elevated growth hormone resulting in increased ovarian response to gonadotropin, inducing hyperstimulation and high-order multiple pregnancies in these patients.

Acromegaly↗

PubMed2005

Successful pregnancy following transfer of embryos from oocytes with abnormal zona pellucida and cytoplasm morphology.

The failed or impaired fertilization in an IVF cycle may be a result of undetected abnormalities in sperm function, poor oocyte quality, or impaired spermatozoon-oocyte interaction. Whether oocyte dysmorphisms have an impact on intracytoplasmic sperm injection (ICSI) outcome, fertilization, and implantation is controversial. A 33-year-old nulligravida female with a 2-year history of primary infertility was referred to the Toronto Centre for Advanced Reproductive Technology for infertility management. The patient underwent several cycles of ovulation induction followed by timed intercourse or intrauterine insemination without a resulting pregnancy. Following the failed insemination cycles, she proceeded to IVF. Six morphologically abnormal oocytes (including three that were cucumber-shaped) were retrieved and all injected with a single spermatozoon. Four oocytes showed normal fertilization and developed to day-3 embryos with abnormal morphology and were transferred. Two weeks after the embryo transfer, the patient had a positive beta-human chorionic gonadotrophin (beta-HCG). The pregnancy was uneventful, and a healthy baby boy was delivered at 41 weeks of age by Caesarean section. Since fertilization, embryo development, and successful pregnancy was achieved in this case, it is recommend that oocytes with extreme morphological abnormalities should not be discarded as ICSI may overcome the barriers to fertilization and cleavage.

Adult↗

PubMedDate not supplied

Prevention of bone loss and hypoestrogenic symptoms by estrogen and interrupted progestogen add-back in long-term GnRH-agonist down-regulated patients with endometriosis and premenstrual syndrome.

OBJECTIVE: To examine the utility of a low-dose estrogen and pulsed progestogen hormone replacement therapy (HRT) regimen for add-back during long-term gonadotropin-releasing hormone-agonist (GnRH-agonist) therapy. DESIGN: A pilot clinical trial conducted at a tertiary referral, academic, reproductive sciences center. The study included 15 patients with endometriosis and 5 patients with severe premenstrual syndrome (PMS). Patients with endometriosis received leuprolide acetate depot 3.75 mg IM monthly until their symptoms had resolved (2-3 months), at which time HRT was initiated along with the GnRH-agonist. Patients with severe PMS received the same treatment with the addition of HRT after 1 month. The HRT regimen consisted of 1 mg oral micronized estradiol daily and 0.35 mg norethindrone daily for 2 days alternating with 2 days without norethindrone. The main outcome measure included bone density assessment in the lumbar spine and femoral neck by dual-energy x-ray absorptiometry at 6- to 12-month intervals. The mean follow-up duration +/- SD while on GnRH-agonist treatment was 31.2 +/- 17 months (for endometriosis patients) and 37.7 +/- 8.4 months (for patients with severe PMS). RESULTS: Bone mineral density was stable after initiation of HRT for the entire follow-up period. No patient had return of pelvic pain or resumption of mood swings after HRT add-back. After the first 3 months of HRT, all women remained amenorrheic. CONCLUSIONS: Long-term GnRH-agonist down-regulation is safe and effective when combined with HRT add-back. Furthermore, on the basis of this small study, the low-dose pulsed progestogen, continuous estrogen HRT regimen seems to be safe for use as add-back therapy in terms of bone health.

Administration, Oral↗

PubMedDate not supplied

Gestational carrier is an optimal method for pregnancy in patients with vaginal agenesis (Rokitansky syndrome).

OBJECTIVE: To evaluate the results of successful pregnancy for patients with Mayer-Rokitansky-Kuster-Hauser syndrome using a gestational carrier. METHODS: All gestational carrier patients who attended our infertility clinic between 1995 and 2002 were reviewed for this study. Of the patients, 6 women with MRKH syndrome had 12 ovarian stimulation cycles, which resulted in 12 fresh and 5 frozen embryo transfers into six gestational carriers. RESULTS: The mean number (+/-SD) of embryos obtained per cycle was 4.8 (+/-2.9). Either two (n = 15) or three (n = 2) embryos were transferred to the gestational carrier. Three pregnancies were achieved following fresh embryo transfer, which included one clinical pregnancy that ended in spontaneous abortion, a singleton, and a set of twins. The pregnancy rate for fresh embryo transfer was 25% per retrieval and 50% per patient. No pregnancy was achieved following frozen embryo transfer. CONCLUSION: Gestational carrier is shown to be an effective treatment for patients with Mayer-Rokitansky-Kuster-Hauser syndrome.

Adult↗

PubMedDate not supplied

Complete failed fertilization after intracytoplasmic sperm injection--analysis of 10 years' data.

OBJECTIVE: To investigate incidence and causes of complete failed fertilization after intracytoplasmic sperm injection (ICSI) in a tertiary care facility. METHODS: A total of 1,779 cycles between February 1994 and December 2003 were analyzed. Study parameters were female age, infertility diagnosis, ovarian stimulation protocol, estradiol level on day of hCG administration, number of follicles, number of oocytes retrieved, number of oocytes injected, and semen parameters. RESULTS: Complete failed fertilization occurred in 23 cycles (1.29%) involving a total of 85 oocytes injected. Infertility causes among patients with failed fertilization included unexplained (43.6%), male factor (26%), presence of more than one factor (17.4%), hysterectomy (4.4%), premature ovarian failure (4.3%), and advanced age (4.3%). In 12 cycles (52%), fewer than 5 follicles were present. In three (13%) cycles, no mature (MII) oocyte was available and in 61% (14/23) fewer than 3 MII oocytes were available for ICSI. Immotile sperm was used for ICSI in 5 cycles (21.7%). The source of sperm in 17 (74%) cycles was from ejaculate, in 4 cycles from testicular aspiration (TESA), one from percutaneous epididymal sperm aspiration (PESA) and one from retrograde ejaculation. CONCLUSIONS: Our data indicate that major contributing factors to failed fertilization after intracytoplasmic sperm injection are number of MII oocytes retrieved and availability of viable sperm for injection. Although the incidence of complete failed fertilization is not remarkable, it may increase with increasing patient age and a lower number of follicles.

Adult↗

PubMedDate not supplied

Seminal hyperviscosity is associated with poor outcome of controlled ovarian stimulation and intrauterine insemination: a prospective study.

OBJECTIVE: To determine the relationship between seminal hyperviscosity and pregnancy outcome in patients undergoing ovarian hyperstimulation and intrauterine insemination (IUI). METHODS: Patients were enrolled in the study between October 2002 and December 2003 at the Toronto Centre for Advanced Reproductive Technology. This was a prospective trial that included 37 infertile couples with abnormal seminal viscosity who underwent 57 insemination cycles as treatment for infertility (group I) and 37 couples undergoing 51 IUI cycles during the same time period, with normal semen viscosity, who served as controls (group II). Cycles were stimulated using either gonadotropin (FSH) only or FSH combined with an aromatase inhibitor, and raw semen processed for intrauterine insemination using swim-up or density gradient. Results-The mean number (+/-SD) of IUI cycles was 1.93 +/- 1.42 per patient (range 1 to 7 cycles) in group I and 2.4 +/- 1.05 (range 1 to 4) in group II. The overall pregnancy rate (PR) was 14% (8/57) and 11.8% (6/51) per cycle, and 21.6% (8/37) and 16.2% (6/37) per patient in group I and in group II, respectively. Among patients where the male had seminal hyperviscosity, five (62.5%) pregnancies miscarried in the first trimester; there was no miscarriage in the control group. CONCLUSION: The high miscarriage rate in couples with semen hyperviscosity may be attributed to biophysical alterations or chemical changes of the ejaculate that could impact sperm quality despite normal sperm parameters on semen analysis.

Adult↗