Marinko M Biljan

Effects of pretreatment with an oral contraceptive on the time required to achieve pituitary suppression with gonadotropin-releasing hormone analogues and on subsequent implantation and pregnancy rates

OBJECTIVE To assess the effect of pretreatment with an oral contraceptive (OC) on ovarian cyst formation during pituitary suppression with buserelin acetate. DESIGN Prospective randomized trial. SETTING Academic medical center. PATIENT(S) Eighty-three patients who were undergoing IVF-ET treatment. INTERVENTION(S) Patients in the study group were pretreated with an OC for 14 days starting on the first day of menstruation. The administration of SC buserelin acetate was initiated on the last day of OC administration. Patients in the control group began to receive buserelin acetate on day 2 of menstruation. Hormonal assays and ultrasound scans were performed on the first day of menstruation, and 7, 11, and 14 days after the commencement of buserelin acetate administration. Thereafter, these tests were performed weekly until pituitary suppression was achieved. MAIN OUTCOME MEASURE(S) Incidence of cyst formation. RESULT(S) A cyst developed in 27 patients in the control group (52.9%) and no patients in the study group (odds ratio [OR]=115; 95% confidence interval [CI]=10-617). Patients in the study group achieved pituitary suppression faster (median difference [MD]=7 days; 95% CI=4-14) and required fewer ampules of gonadotropin (MD=10; 95% CI=6-14). They recruited more follicles (MD=3; 95% CI=0-5) and had higher pregnancy rates (37.2% versus 33.3%). CONCLUSION(S) Pretreatment with an OC abolishes ovarian cyst formation, shortens the time required to achieve pituitary suppression, and decreases gonadotropin requirements without having a negative effect on pregnancy rates.

Impact of reducing the number of embryos transferred from three to two in women under the age of 35 who produced three or more high-quality embryos

OBJECTIVE To investigate the effect of a reduction in the number of good-quality embryos transferred in patients <35 years of age on pregnancy and multiple pregnancy rate. DESIGN Prospective observational study with historical controls. SETTING Academic tertiary referral unit. PATIENT(S) Three hundred eight patients <35 years of age undergoing IVF-ET. INTERVENTION(S) For patients who had three or more good quality embryos available for transfer, those in group 1 were given the option to have either two or three embryos replaced, whereas those in group 2 were allowed a maximum of two embryos transferred. In both groups, patients who had less than three good-quality embryos had the option to have three embryos transferred. MAIN OUTCOME MEASURE(S) Pregnancy and multiple pregnancy rates. RESULT(S) Patients in group 1, compared with those in group 2, had significantly more embryos (3 vs. 2) of significantly higher cumulative embryo score (31 vs. 24) transferred. This resulted in significantly higher multiple (57.8% vs. 30.8%) and triplet (15.6% vs. 1.4%) pregnancy rates in group 1. However, no difference in overall clinical pregnancy rate (37.2% vs. 41.2%) or live birth rate (28.1% vs. 29.4%) was observed between group 1 and 2. CONCLUSION(S) In women <35 years of age, who have three or more good-quality embryos available for transfer, a maximum of two embryos should generally be transferred.

Prospective randomized double-blind trial of the correlation between time of administration and antiestrogenic effects of clomiphene citrate on reproductive end organs

OBJECTIVE To investigate whether the timing of administration of clomiphene citrate (CC) affects hormone levels, follicular recruitment, reproductive end organs, and pregnancy rates. DESIGN Prospective, randomized, double-blind trial. SETTING Academic center. PATIENT(S) Twenty-three patients with unexplained infertility. INTERVENTION(S) Twenty-three patients with unexplained infertility underwent 45 cycles of CC and IUI. For each cycle, patients were randomized either to receive 100 mg of CC on days 1-5 and placebo on days 5-9 (study group), or placebo on days 1-5 and CC on days 5-9 (control group). MAIN OUTCOME MEASURE(S) The difference in uterine artery PI, number of follicles, endometrial thickness, and pregnancy rates. RESULT(S) Gonadotropins and E2 levels, as well as uterine artery pulsatility index, were significantly higher in the study group on day 5. In addition, in the study group, a longer time interval existed between finishing CC and IUI (8 versus 6 days; MD = 2 days; 95% CI = 1-3) and the pregnancy rate was higher than in the control group (6 versus 0; OR = 15.1; 95% CI = 1.1-72.4). CONCLUSION(S) Clomiphene citrate commenced on day 1 of the menstrual cycle, rather than day 5, results in more rapid follicular growth, a longer CC-free period before IUI, and higher pregnancy rates. Although methodologically sound, our results should be taken with some degree of caution because they are based on a relatively small number of patients.

A randomized study of the effect of 10 minutes of bed rest after intrauterine insemination

OBJECTIVE To evaluate the effects of 10 minutes of bed rest after intrauterine insemination (IUI) on the pregnancy rate. DESIGN Prospective randomized study. SETTING University teaching hospital. PATIENT(S) One hundred sixteen couples with unexplained infertility. INTERVENTION(S) Patients were prospectively randomized either to immediate mobilization after IUI (group I) or to remain in a supine position for 10 minutes after the procedure (group II). MAIN OUTCOME MEASURE(S) Cumulative pregnancy rate. RESULT(S) Ninety-five couples were included in the analysis. Group I consisted of 40 couples (90 cycles), and group II consisted of 55 couples (120 cycles). The pregnancy rate per couple in group I (4 of 40 [10%]) was significantly lower than in group II (16 of 55 [29%]). The pregnancy rate per cycle in group I (4.4%) was also lower than in group II (13. 3%). With use of life-table analysis, the cumulative probability of pregnancy in group II was significantly higher than in group I. CONCLUSION(S) A 10-minute interval of bed rest after IUI has a positive effect on the pregnancy rate. We recommend that mandatory bed rest for 10 minutes after IUI should be adopted into a standard practice.

Pretreatment with an Oral Contraceptive Is Effective in Reducing the Incidence of Functional Ovarian Cyst Formation During Pituitary Suppression by Gonadotropin-Releasing Hormone Analogues

Purpose:Our purpose was to assess the effect of pretreatment with oral contraceptives (OCs) on the formation of functional ovarian cysts during pituitary supression with gonadotropin-releasing hormone (GnRH) agonists, subsequent follicular development, and pregnancy rates.Methods:A retrospective case-controlled study of 31 in vitro fertilization (IVF) patients, all of whom in a previous cycle had commenced the long protocol of GnRH-agonist (Buserelin) in the early follicular phase and were pretreated in a subsequent cycle with 2 weeks of an OC containing 30 μg of ethinyl estradiol and 150 μg of desogestrel prior to GnRH-agonist administration, was undertaken. Follow-up visits were arranged after a minimum of 11 days of GnRH-agonist administration and weekly thereafter until pituitary suppresion was achieved.Results:Cysts were detected in 16 (51.6%) of the 31 patients not pretreated with OCs, and in 0 (0%) of the 31 patients pretreated with OCs (odds ratio = 67.1; 95% confidence interval = 5.6–350.7). Patients pretreated with OCs achieved pituitary suppression more rapidly (median difference = 4 days; 95% confidence interval = 2–7) and had comparable gonadotropin requirements and pregnancy rates.Conclusions:Pretreatment with OCs prior to pituitary suppression in the early follicular phase decreases ovarian cyst formation, without an apparent effect on subsequent follicular recruitment or pregnancy rates.

Effects of functional ovarian cysts detected on the 7th day of gonadotropin-releasing hormone analog administration on the outcome of IVF treatment

OBJECTIVE To investigate the impact of functional ovarian cysts on the time required to achieve pituitary suppression, follicular development, embryo quality, and pregnancy rates during IVF treatment. DESIGN Prospective observational study. INTERVENTION(S) Daily treatment with buserelin (sc 500 microg) was initiated on day 2 of menstruation. Ultrasound and hormonal tests were performed on days 1, 7, 11, 14, and weekly thereafter until pituitary suppression was achieved. RESULT(S) 48 patients underwent 51 cycles of IVF treatment. A functional cyst was detected in three cycles (5.8%) with baseline ultrasound scan and in 27 cycles (52.9%) on day 7 of buserelin administration. Patients who developed a cyst required a significantly longer time to achieve pituitary suppression (21 vs. 7 days), had a significantly lower FSH level at the time of initiation of gonadotropins, required more ampules of gonadotropin (45 vs. 41 ampules), developed less follicles (13 vs. 17.5), and had lower embryo quality. However, there were no differences in the implantation (23.5% vs. 17.2%) and pregnancy rates (37.2% vs. 29.2%) between two groups. CONCLUSION(S) Functional cysts prolong the period to achieving pituitary suppression, increase gonadotropin requirements, and decrease follicular recruitment and embryo quality. They have, however, no negative effect on pregnancy rates.

In vitro fertilization and intracytoplasmic sperm injection pregnancies after successful transport of oocytes by airplane.

OBJECTIVE To determine the feasibility of a transport IVF program involving air transportation of oocytes. DESIGN Prospective cohort study. SETTING Regional hospital (Hôpital de Chicoutimi) and University Infertility Center (McGill Reproductive Center, Montreal). PATIENT(S) The first series of patients referred for IVF or IVF and ICSI, for a variety of indications, who opted for inclusion in the transport IVF program. INTERVENTION(S) The IVF-ET with ovarian stimulation and oocyte collection at the peripheral unit and transport of the oocytes by airplane to the McGill Reproductive Center where IVF or ICSI was performed. MAIN OUTCOME MEASURE(S) Clinical pregnancy. RESULT(S) Seven couples, in the first series, underwent nine cycles of transport IVF treatment. Two also underwent ICSI. There were two clinical pregnancies. CONCLUSION(S) Transport IVF using air travel is possible and opens the possibility for this type of program to be implemented in large countries with scattered populations, such as the United States, Canada, and Australia.

An ectopic pregnancy masked by follicular initiation of gonadotropin-releasing hormone agonist for pituitary desensitization prior to in vitro fertilization.

Pituitary suppression by gonadotropin-releasing hormone (GnRH) agonists starting in either the midluteal or the early follicular phase has become a routine pretreatment before controlled ovarian hyperstimulation for in vitro fertilization (IVF). The administration of this long protocol of GnRH agonist increases the cumulative birth rate after IVF (1) and simplifies treatment by reducing the amount of monitoring necessary during ovarian stimulation (2). One of the disadvantages of commencing the administration of GnRH agonists in the luteal phase is interference with an unexpected pregnancy. At least 75 pregnancies and 49 deliveries following initiation of GnRH agonists in the luteal phase have been described in the literature (3). This risk cannot be eliminated, as serum p-hCG levels at the time of initiation of GnRH agonist administration in the midluteal phase are not sufficiently high to be detected by currently available hormone assays. In CASE REPORT

Prospective randomized trial of the effect of two flushing media on oocyte collection and fertilization rates after in vitro fertilization

OBJECTIVE To assess the value of heparinized saline as a flushing medium for oocyte recovery. DESIGN Prospective randomized study. SETTING Academic tertiary referral center for fertility treatment. PATIENT(S) Thirty-five patients, with both ovaries intact having IVF-ET. INTERVENTION(S) Patients were randomized either to have the follicles of the left or right ovary flushed with heparinized normal saline at the time of oocyte recovery for IVF-ET. The contralateral ovary was flushed with heparinized culture medium. Oocytes obtained from each side were cultured separately and assessed for fertilization 18-21 hours after insemination. MAIN OUTCOME MEASURE(S) Collection and fertilization rates. RESULT(S) A total of 481 follicles were aspirated yielding 366 oocytes. Of these, 240 fertilized. From the side flushed with saline 185 oocytes were collected from 237 follicles, which was not significantly different from 181 oocytes collected from 244 follicles on the side flushed with culture medium (odds ratio = 1.23; 95% confidence interval = 0.79-1.92). Similarly, there was no significant difference observed in fertilization rates between oocytes obtained after saline (median 71.4%) and culture medium flush (median 75.0%) (odds ratio = 1.08; 95% confidence interval = 0.68-1.72). CONCLUSION(S) Heparinized normal saline is an equally good but cheaper and more convenient medium than standard heparinized culture medium and could replace it for flushing follicles during oocyte recovery for IVF-ET procedures.

The first pregnancy in a transport-intracytoplasmic sperm injection (T-ICSI) scheme

in ascites during severe ovarian hyperstimulation syndrome: Implications for pathophysiotogy and clinical management. Fertil Steril 1994;62:731-737 8. Pride SM. Ho Yuen B, Moon YS: Clinical. endocrinological and intraovarian prostaglandin-F response to H-I receptor blockade in the ovarian hyperstimulation syndrome. Am l Obstet Gynecol 1984;148:670-674 9. Aboulghar MA, Mansour RT, Serour GI. Sattar MA. Amin YM, Elattar I: Management of severe ovarian hyperstimulation syndrome by ascitic fluid aspiration and intensive intravenous fluid therapy. Obstet Gynaecol 1993;81:108-111 10. Schenker JG: Prevention and treatment of ovarian hyperstimulation. Hum Reprod 1993;8:653-659