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.

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.

The outcome of IVF-embryo transfer treatment in patients who develop three follicles or less.

Among 828 patients undergoing IVF-embryo transfer treatment, the implantation and pregnancy rates of patients who developed < or = 3 follicles were compared prospectively with those patients who had a normal response. Patients who developed 1 to 3 follicles during ovarian stimulation elected to proceed with oocyte collection, have intrauterine insemination if appropriate, or to have their cycle cancelled. In the group of patients who developed < or = 3 follicles and who were aged <40 years, despite a significantly lower number of oocytes collected [2 versus 7; median difference (MD) = 9; confidence interval (CI) = 7-11, and lower number of embryos developed and transferred (1 versus 3; MD = 2; CI = 1-2), no difference in either implantation rate [27.8 versus 20.4%; odds ratio (OR) = 1.58; CI = 0.46-4.54] or pregnancy rate (27.8 versus 36.7%; OR = 0.7; CI = 0.2-2.0) was noted when compared with similarly aged patients who developed >3 follicles. However, in patients aged >40 years who developed < or = 3 follicles, a moderate, albeit non-significant decrease in implantation rate (3.8 versus 7.8%; OR = 1.91; CI = 0.4-57.0) and pregnancy rate (4.2 versus 18.3%; OR = 1.92; CI = 0.38-57.0) was observed when compared with patients of a similar age who developed >3 follicles. Patients aged <40 years, unlike older patients, maintain good implantation and pregnancy rates despite a poor response to ovarian stimulation. This study indicates that for this group of women, continuation of IVF treatment is a better option than cancellation.

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.

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.

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.

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 suppression 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 micrograms of ethinyl estradiol and 150 micrograms 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 suppression 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.

PIP: A retrospective case-controlled study was undertaken to assess the effects of pretreatment with oral contraceptive (OC) on the formation of functional ovarian cysts during pituitary suppression with gonadotropin-releasing hormone (GnRH) agonists, subsequently follicular development, and pregnancy rates. In the period between January 1997 and December 1997, 31 in vitro fertilizations, all of which in a previous cycle, had commenced the long protocol of GnRH agonists in the early follicular phase and were pretreated in a subsequent cycle with an OC containing 30 mcg ethinyl estradiol and 150 mcg desogestrel for 2 weeks prior GnRH agonist administration and then weekly until pituitary suppression was achieved. After data collection and analysis, findings revealed that functional ovarian cysts were detected in 16 (51.6%) of 31 patients not pretreated with an OC and in 0 (0%) of 31 patients pretreated with an OC. Satisfactory pituitary suppression was achieved more rapidly with patients pretreated with an OC. Further, comparable gonadotroph requirements and pregnancy rates were detected among patients pretreated with an OC. In conclusion, pretreating patients with an OC 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 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.

PIP: Administration of a gonadotropin-releasing hormone analog (GnRH-a) before ovarian stimulation with gonadotropins in women undergoing in vitro fertilization (IVF) treatment produces higher pregnancy and live birth rates, but also results in formation of ovarian cysts that must be treated before stimulation can commence. The effect of pretreatment with an oral contraceptive (OC) on ovarian cyst formation during pituitary suppression with the GnRH-a buserelin acetate was investigated in a prospective randomized trial of women undergoing IVF at Royal Victoria Hospital (Montreal, Quebec, Canada). 51 women were pretreated with an OC for 14 days, starting on the first day of menstruation, and began buserelin acetate (500 mcg/day) on the last day of OC administration. The 51 women in the control group were treated with the standard protocol of 500 mcg/day of buserelin acetate starting on the second day of menstruation. A cyst developed in 27 controls (52.9%) but in no women pretreated with OCs (odds ratio, 115; 95% confidence interval, 10.7-617.5). 49 pretreated women (96.1%) compared with 22 controls (43.1%) achieved pituitary suppression after 7 days of GnRH-a administration. Pretreated women also required a median of 10 fewer ampules of gonadotropin than controls, recruited a median of 3 more follicles than their non-pretreated counterparts, and had higher pregnancy rates (37.2% and 33.3%, respectively). OCs are assumed to prevent the formation of ovarian cysts during GnRH-a administration through a dual effect of pituitary suppression and ovarian protection. OC pretreatment enables a significant simplification of the long standard protocol of GnRH-a administration.

Cummulative pregnancy and live birth rates after assisted conception.

Within the last 15 years in vitro fertilization (IVF) has become an established treatment modality. Its results compare favorably with that of spontaneous conception in the natural menstrual cycle in fertile women. The possibility of a success for any couple undergoing treatment will, however, depend on their characteristics. Over the past several years, the importance of these individual factors has been subjected to an extensive research. Our group has performed a number of studies that relate the cumulative conception rate (CCR) and cumulative live birth rate (CLR) with the age of the patient, the cause of infertility, and the type of ovarian stimulation used. We have also analyzed the effect of previously successful in vitro fertilization treatment upon the results of a subsequent treatment course, and the obstetric outcome of in vitro fertilization pregnancies when compared to those that are naturally conceived. In this review article, the importance of the above mentioned factors will be discussed in view of our research results and other recently available evidence.

The effect of progestagens on the carotid artery pulsatility index in postmenopausal women on oestrogen replacement therapy.

Part of the cardioprotective effect of postmenopausal oestrogen replacement therapy has been attributed to arterial vasodilation. This effect is partially reversed in the uterine artery by the addition of a progestagen. This study was designed to compare the effects of the C21 progestagen, dydrogesterone and the C19 testosterone derivative, norethisterone on the carotid artery pulsatility index (PI) (thought to represent distal impedance to flow) using a randomized double blind cross-over trial. The addition of progestagen resulted in a significant increase in the carotid artery PI from a median value of 1.67 during the oestrogen only phase to 1.77 (P = 0.02) during the combined phase. This trend was seen with both dydrogesterone and norethisterone, but there was no significant difference in the size of the effect caused by either progestagen. The addition of cyclical progestagen to ERT partially antagonizes the reduction in the carotid artery PI.

Effects of acute changes in oestrogen on muscle function of the first dorsal interosseus muscle in humans.

1. To investigate the effect of the female reproductive hormones on muscle function, patients undergoing in vitro fertilization were tested during two phases of treatment. The first was following the downregulation of pituitary gonadotrophin releasing hormone (GnRH) receptors and the second after 9 days of gonadotrophin injections. 2. Maximal strength and fatiguability of the first dorsal interosseus muscle were assessed when oestrogen and progesterone were low, and less than 2 weeks later when oestrogen production reached supraphysiological levels. 3. There were no significant changes in either strength or fatigue resistance during acute, massive fluctuations in oestrogen. These results occurred at a time when progesterone levels remained relatively low. 4. Contrary to previous work, the present results suggest that oestrogen does not affect muscle strength.

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.

Effects of sperm activity on zinc and fructose concentrations in seminal plasma.

Attempts to correlate zinc and fructose concentrations in seminal plasma with andrological parameters have produced inconsistent results. To assess further this relationship, a prospective study was performed measuring zinc and fructose concentrations in seminal plasma in 1178 patients referred for fertility treatment. Seminal analysis was performed with biochemical measurements of seminal zinc and fructose. The main outcome measures were the correlation between motile sperm concentration and seminal zinc and fructose concentrations. Zinc concentrations were not influenced by the motile sperm concentration (r = 0.039). Fructose concentrations were found to be negatively correlated with motile sperm concentration (r = 0.062). We conclude that seminal plasma zinc is an unreliable marker of spermatogenic activity. While there does appear to be a negative correlation between seminal plasma fructose concentrations and motile sperm concentration this relationship is far from linear. Due to the biochemical complexity of seminal fluid attempts to perform such simple correlations between seminal plasma components and andrological parameters are likely to produce inconsistent results and their role in the assessment of sperm function must therefore be called into question.

Effect of abnormal hypo-osmotic swelling test on fertilization rate and pregnancy outcome in in vitro fertilization cycles.

OBJECTIVE: To assess the value of the hypo-osmotic swelling test in predicting fertilization, pregnancy, implantation, miscarriage, and live birth rates in IVF-ET cycles. DESIGN: Prospective study. SETTING: Academic tertiary referral center for fertility treatment. PATIENTS: Three hundred twenty-six couples having IVF-ET for tubal damage or male factor infertility with the female partner < 38 years of age. INTERVENTIONS: Each male had a hypo-osmotic swelling test performed between 4 and 8 weeks before IVF-ET. MAIN OUTCOME MEASURES: Fertilization, implantation, miscarriage, and live birth rates. RESULTS: Eighty of 326 men had abnormal hypo-osmotic swelling tests. An abnormal test was not associated with lower fertilization rates (odds ratio [OR] = 1.14; 95% confidence interval [CI] = 0.97 to 1.14) or pregnancy rate (OR = 0.98; CI = 0.50 to 1.96). However, although couples with a normal test had a miscarriage rate of 26.9% (14/52), in the group with an abnormal test the miscarriage rate was 50.0% (7/14) (OR = 0.37; CI = 0.09 to 1.49). This resulted in a reduction in the live birth rate from 14.1% in the group with a normal test to 11.8% in patients with an abnormal test (OR = 1.23; CI = 0.45 to 3.87). CONCLUSIONS: The hypo-osmotic swelling test has little value in predicting fertilization in IVF-ET procedures. However, an abnormal test may help predict adverse outcome if pregnancy is achieved.

Successful pregnancy following oocyte donation in a patient with Diamond-Blackfan syndrome and premature ovarian failure.

Diamond-Blackfan anaemia (DBA) is a rare congenital condition characterized by profound anaemia associated with an absence of red cell precursors on bone marrow examination. This report represents the first case of pregnancy following egg donation in a patient with DBA and premature ovarian failure. The patient was a 24 year old woman who had been diagnosed with DBA when aged 6 months. Shortly after menarche, the patient became amenorrhoeic and was diagnosed as suffering from premature ovarian failure. She was entered onto an assisted conception programme and conceived after one cycle of egg donation. The pregnancy was characterized by a gradual decline in haemoglobin concentration, reaching a low of 8.1 g/dl, necessitating a single blood transfusion at 29 weeks of gestation. The patient suffered preterm rupture of the membranes at 29 weeks gestation and was delivered by emergency Caesarean section at 30 weeks of gestation because of chorioamnionitis and breech presentation. Comparing this case with other reports of pregnancy in patients with DBA, our patient suffered a less dramatic fall in haemoglobin concentration and required only a single blood transfusion. It is suggested that because the pregnancy arose from donated genetic material, this may have conferred some protective effect.

Exaggerated effects of progestogen on uterine artery pulsatility index in Turner's syndrome patients receiving hormone replacement therapy.

OBJECTIVE: To investigate the effect of estrogen and progestogen on the resistance to blood flow in the uterine arteries of Turner's syndrome patients. DESIGN: Prospective clinical study. SETTING: A tertiary infertility clinic. PATIENTS: Five Turner's syndrome patients, six patients who had surgical castration, and five patients with idiopathic primary ovarian failure. INTERVENTIONS: The patients were treated with 2 mg E2 valerate to which 500 micrograms norgesterel was added for 10 days in a 28-day cycle. Transvaginal color Doppler was used to measure pulsatility index in the uterine arteries at eight regular intervals during a single cycle. MAIN OUTCOME MEASURE: Pulsatility index of the uterine arteries. RESULTS: The administration of norgesterel to Turner's syndrome patients resulted in an increase in pulsatility index that was significantly higher than in patients who had surgical castration (confidence interval = 0.17 to 2.42). CONCLUSION: The uterine arteries of Turner's syndrome patients are more sensitive to the tonic effect of progestogen. If manifest in cardiac arteries also this phenomenon may be partly responsible for the increased incidence of cardiovascular disease and shorter life expectancy in Turner's syndrome patients. To achieve optimal protection from cardiovascular disease, Turner's syndrome patients may benefit from hormone replacement treatment containing altered doses of estrogen and progestogen.

Trizygotic quadruplet pregnancy following in-vitro fertilization: an additional factor against replacement of three embryos in young patients?

A study of a 25 year old woman with a previous history of tubal damage, ectopic pregnancy and unsuccessful tubal surgery is reported. Following in-vitro fertilization (IVF) treatment, four viable fetuses were revealed by ultrasound scan at 10 weeks gestation. Two shared the same gestational sac, thus establishing a trizygotic quadruplet pregnancy. The implications of monozygotic twinning in humans are discussed. It is concluded that embryo splitting and its consequences should be seriously considered when multiple embryo transfer in young patients is contemplated.