Lynda Gotlieb

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.

ObjectiveTo 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. DesignA 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). ResultsBone 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. ConclusionsLong-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.

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.

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.

Seminal hyperviscosity is associated with poor outcome of in vitro fertilization and embryo transfer: a prospective study

OBJECTIVE To investigate the effect of increased seminal viscosity on fertilization, implantation, and pregnancy outcome in patients undergoing in vitro fertilization/ intracytoplasmic sperm injection (ICSI). DESIGN Prospective study. SETTING University-affiliated infertility center. PATIENT(S) One hundred fifty-eight infertile couples (168 cycles) with increased seminal viscosity and 129 infertile couples (138 cycles) with normal seminal viscosity as controls. INTERVENTION(S) In vitro fertilization using conventional insemination or ICSI. MAIN OUTCOME MEASURE(S) Fertilization, embryo quality, implantation, and pregnancy rates (PR) were evaluated. RESULT(S) Patient age and the cause of infertility were similar between the two groups. Sperm count (36.9 +/- 34.0 vs. 28.1 +/- 25.6) and motility (41.5 +/- 19.2 vs. 37.0 +/- 20.5) was higher in the control group compared to the study group. Fertilization rate after IVF (50.4% vs. 64.6%), clinical PR (28% vs. 39.9%), and the implantation rates (10.5% vs. 16.5%) were significantly lower in patients with hyperviscosity compared to the control group. CONCLUSION(S) The lower implantation rate and clinical PR in couples with seminal hyperviscosity may be attributed to biophysical alterations or chemical changes of the ejaculate that could impact sperm DNA despite the presence of apparently normal motile sperm for the IVF/ICSI procedure.

Ongoing twin pregnancy after rescue intracytoplasmic sperm injection of unfertilized abnormal oocytes

OBJECTIVE To report a case of an ongoing twin pregnancy resulting from rescue intracytoplasmic sperm injection (ICSI) after failed fertilization of morphologically abnormal oocytes. DESIGN Case report. SETTING Tertiary center for assisted reproductive technology (ART). PATIENT(S) A 28-year-old woman with primary infertility due to tubal obstruction. INTERVENTION(S) Rescue ICSI after failed IVF insemination. MAIN OUTCOME MEASURE(S) Clinical pregnancy. RESULT(S) Successful ongoing twin pregnancy. CONCLUSION(S) With failed fertilization of oocytes with abnormal morphology after IVF, early rescue ICSI may increase the fertilization rates and result in an ongoing pregnancy.

Intracytoplasmic Sperm Injection After Follicle Stimulation with Highly Purified Human Follicle-Stimulating Hormone Compared with Human Menopausal Gonadotropin

Purpose:Our purpose was to compare oocyte nuclear maturation and embryo quality after pituitary down-regulation and ovarian stimulation with highly purified follicle-stimulating hormone (FSH) or human menopausal gonadotropin (HMG).Methods:Fifty-five patients 37 years of age or younger who were undergoing in vitro fertilization (IVF)–intracytoplasmic sperm injection (ICSI) were evaluated retrospectively. In all cases, male factor was the only indication for treatment, with no female-related factors identified. Following pituitary down-regulation, patients were stimulated with hMG (n = 20) or highly purified FSH (n = 35). Main outcome measures included ovarian response to stimulation, oocyte maturity, and ICSI fertilization results. Secondary outcome measures included pregnancy rates and outcome.Results:The ovarian response to stimulation was similar for the two groups, as were the percentage of metaphase II oocytes, fertilization and cleavage rates, and number and quality of transferred and cryopreserved embryos. Cycle outcome was comparable.Conclusions:In normogonadotropic subjects, monocomponent therapy with highly purified FSH is as effective as hMG in stimulating ovarian follicular development, synchronization of oocyte maturation, and IVF-ICSI outcome. Our findings support the conclusion that the luteinizing hormone component in the stimulation protocol is unnecessary.

Monozygotic twins in infertile patients with advanced maternal age: case reports and review of the literature

OBJECTIVE To report two cases of successful monozygotic twin pregnancies in women undergoing infertility treatment and to review possible etiologic factors. DESIGN Case report and review of the literature. SETTING University of Toronto-affiliated infertility clinic. PATIENT(S) A 43-year-old woman and a 44-year-old woman with history of secondary infertility. INTERVENTION(S) In vitro fertilization and ET. MAIN OUTCOME MEASURE(S) Monozygotic twin pregnancy. RESULT(S) Delivery of two sets of monozygotic twins. CONCLUSION(S) The only identified potential risk factors for monozygotic twins are maternal age and assisted reproductive technologies. Both patients reported here were aged >40 years and underwent assisted reproduction procedures, including high-dose gonadotropin stimulation, embryo culture, and, in case 2, intracytoplasmic sperm injection plus assisted hatching.

Don't judge a book by its cover; a quintuplet pregnancy following transfer of five poor-quality embryos

OBJECTIVE To report a case of a quintuplet pregnancy following transfer of five poor-quality cellular-stage embryos. DESIGN Case report. SETTING University of Toronto-affiliated infertility clinic. PATIENT(S) A 35-year-old female with a 2-year history of secondary infertility. INTERVENTION(S) Intracytoplasmic sperm injection and embryo transfer. MAIN OUTCOME MEASURE(S) Clinical pregnancy. RESULT(S) Quintuplet implantation with five fetal hearts. CONCLUSION(S) Because the transfer of five poor embryos resulted in a quintuplet implantation, we recommend that embryos with significant morphologic abnormalities, especially in younger patients, be considered as viable embryos with implantation potential.