Arthur Wisot

Routine pituitary suppression with leuprolide before ovarian stimulation for oocyte retrieval

Pituitary suppression with leuprolide acetate (LA) was used before and during ovarian stimulation with human menopausal gonadotropins in 45 consecutive women having their first cycle of in vitro fertilization embryo transfer (IVF-ET). As anticipated, a low rate of cycle cancellation (6.7%) was necessary for poor responses. Follicles were allowed to develop to a larger diameter than with our prior protocol without LA. On the day of human chorionic gonadotropin (hCG), 11.5 + 0.7 follicles of at least 1.0 cm were visualized; 11.7 + 0.9 oocytes were retrieved; 67.5% fertilized and 6.7 + 0.6 normal embryos were available for transfer. Of the 3.4 + 0.1 embryos transferred per patient, 24.6% implanted. The rates of clinical pregnancy per retrieval and per stimulation were 54% and 47%, respectively, of which 23.8% aborted. Routine use of LA resulted in a highly efficient level of ongoing pregnancy per initiated cycle, and therefore may produce a superior first cycle for IVF-ET.

Role of vascular endothelial cell growth factor in Ovarian Hyperstimulation Syndrome.

Controlled ovarian hyperstimulation with gonadotropins is followed by Ovarian Hyperstimulation Syndrome (OHSS) in some women. An unidentified capillary permeability factor from the ovary has been implicated, and vascular endothelial cell growth/permeability factor (VEGF) is a candidate protein. Follicular fluids (FF) from 80 women who received hormonal induction for infertility were studied. FFs were grouped according to oocyte production, from group I (0-7 oocytes) through group IV (23-31 oocytes). Group IV was comprised of four women with the most severe symptoms of OHSS. Endothelial cell (EC) permeability induced by the individual FF was highly correlated to oocytes produced (r2 = 0.73, P < 0.001). Group IV FF stimulated a 63+/-4% greater permeability than FF from group I patients (P < 0. 01), reversed 98% by anti-VEGF antibody. Group IV fluids contained the VEGF165 isoform and significantly greater concentrations of VEGF as compared with group I (1,105+/-87 pg/ml vs. 353+/-28 pg/ml, P < 0. 05). Significant cytoskeletal rearrangement of F-actin into stress fibers and a destruction of ZO-1 tight junction protein alignment was caused by group IV FF, mediated in part by nitric oxide. These mechanisms, which lead to increased EC permeability, were reversed by the VEGF antibody. Our results indicate that VEGF is the FF factor responsible for increased vascular permeability, thereby contributing to the pathogenesis of OHSS.

Timing of initiation and dose schedule of leuprolide influence the time course of ovarian suppression

The time course of suppression of ovarian estrogen production and follicular development with leuprolide was examined in 40 normal women before ovarian stimulation for in vitro fertilization (IVF). Initiation of leuprolide during the midluteal phase caused a significantly more prompt suppression than when treatment was started during the early follicular phase (day 1). Injection of the same total amount of leuprolide in two divided doses also caused a significantly more prompt suppression. These two methods were consistent enough to make routine use of leuprolide practical before ovarian stimulation for IVF.

Assisted hatching reduces the age-related decline in IVF outcome in women younger than age 43 without increasing miscarriage or monozygotic twinning

PurposeOur purpose was to examine the benefits of assisted hatching in our program and to determine whether the procedure increases the implantation of nonviable embryos or monozygotic twinning.MethodsConsecutive in vitro fertilization cycles using assisted hatching were compared with historical controls. The impact of assisted hatching was analyzed according to the woman’s age. Outcome measures were clinical pregnancy, implantation rate, delivery rate, multiple pregnancy, spontaneous abortion, and incidence of monozygotic twins.ResultsThe implantation rate was increased in women aged 35–39 and markedly increased in women aged 40–42. There was no change in spontaneous abortions and no increase in monozygotic twins.ConclusionsAssisted hatching is a safe and highly effective adjunct to in vitro fertilization for women aged 35–42 and did not increase spontaneous abortion or monozygotic twinning.

Cornual pregnancies in patients with prior salpingectomy undergoing in vitro fertilization and embryo transfer

OBJECTIVE To examine the frequency of cornual pregnancy in patients with prior salpingectomy undergoing IVF. DESIGN Review. SETTING Private fertility practice. PATIENTS Women undergoing IVF. MAIN OUTCOME MEASURE Cornual ectopic pregnancy. RESULTS Of 26 ectopic pregnancies detected after ET during a 7-year period, 7 were located in the cornu or tubal stump after prior salpingectomy. CONCLUSIONS Patients with prior salpingectomy undergoing IVF are at particular risk for cornual pregnancy.

Artificial agonadism and hormone replacement for oocyte donation

Use of donor oocytes appears to enhance the success of in vitro fertilization (IVF) and embryo transfer (ET) by avoiding the adverse effects of ovarian stimulation on the recipient endometrium. In a donor egg recipient with menstrual function, we created an agonadal state with leuprolide acetate followed by hormonal replacement to allow precise synchronization with the donor. Her second transfer cycle resulted in a triplet pregnancy

Successful pregnancies with unstimulated cycle oocyte donation using an antagonist of gonadotropin-releasing hormone *

We achieved two ongoing pregnancies in five older recipients with natural cycle oocyte donation from five young donors using a GnRH antagonist, with hMG and hCG to complete oocyte maturation. This provides a new alternative to ovarian stimulation for both oocyte donation and routine IVF.

Leuprolide acetate elevates prolactin during ovarian stimulation with gonadotropins.

ObjectiveThe purpose of this study was to determine whether gonadotropin-releasing hormone agonist further increases the prolactin rise accompanying ovarian stimulation.DesignSerum prolactin concentrations were compared between cycles with and cycles without the use of leuprolide acetate (LA) matched for estradiol levels. Relationships of prolactin levels to cycle outcomes were examined.SettingThe study took place at a private fertility center.PatientsPatients were women receiving stimulation for oocyte retrieval using human menopausal gonadotropins.InterventionsNo interventions were used.Main Outcome MeasuresSerum prolactin level, fertilization rate, embryo quality, and pregnancy were the main outcome measures.ResultsHigher serum prolactin was associated with both higher estradiol levels and use of LA but did not have any effects on fertilization rate, embryo quality, or occurrence of pregnancy.ConclusionLA stimulates prolactin release during ovarian stimulation but without apparent consequence.