Impact of the "physician factor" on pregnancy rates in a large assisted reproductive technology program: do too many cooks spoil the broth?

OBJECTIVE: To determine whether in one program with unified treatment protocols, patients can expect varying treatment outcomes with different physicians. DESIGN: Retrospective data analysis. SETTING: University-affiliated infertility center with 14 physicians. PATIENT(S): One thousand eight hundred fifty IVF cycles performed consecutively between August 1995 and June 1997. INTERVENTION(S): The pregnancy rate and implantation rate per ET were evaluated for individual physicians between August 1995 and June 1996 (phase I). Physicians with lower success rates underwent strict supervision from July 1996 to June 1997 (phase II). MAIN OUTCOME MEASURE(S): Variations in success rates between physicians. RESULT(S): The pregnancy rate varied among the physicians from 13.2%-37.4%, and the implantation rate varied from 4.4%-14%. Some physicians' outcomes improved between phase I and phase II of the study, whereas others' did not. The pregnancy and implantation rates varied significantly for some physicians, depending on whether they were responsible for the choice of stimulation protocol, supervision of cycle monitoring, or ET in their own or other physicians' patients. CONCLUSION(S): Outcomes of IVF vary depending on the treating physician. Lower than expected pregnancy and implantation rates usually are not caused by poor ET techniques alone, but appear to be disproportionately the consequences of poor cycle stimulation.

Resection of uterine septum using gynaecoradiological techniques.

This paper presents further refinements in our technique for the resection of uterine septum. Fourteen patients [infertility (n = 9) and recurrent miscarriages (n = 5)] underwent in-office resection of a uterine septum under fluoroscopic control. The main outcome measure was complete resection of uterine septum. Resections were carried out using either hysteroscopic scissors in combination with a specially designed uterine balloon catheter, or microlaparoscopy scissors in conjunction with a cervical cannula. In all patients the septum was successfully resected without any intra-operative complications. We conclude that ambulatory gynaecoradiological resection of uterine septa is a safe and simple procedure. It avoids utilization of expensive operating room time, general anaesthesia, and some complications associated with hysteroscopic resection, such as fluid retention and electrolyte imbalance.

Octreotide is not useful for clomiphene citrate resistance in patients with polycystic ovary syndrome but may reduce the likelihood of ovarian hyperstimulation syndrome.

OBJECTIVE: To determine whether octreotide is effective for ovulation induction in patients with polycystic ovary syndrome (PCOS) and clomiphene citrate resistance or for reduction of the risk of ovarian hyperstimulation syndrome (OHSS) with gonadotropin therapy. DESIGN: Prospective, double-blind, placebo-controlled, crossover trial. SETTING: Private infertility practice. PATIENT(S): Twelve patients with PCOS undergoing therapy for infertility. INTERVENTION(S): The patients were assigned randomly to receive either octreotide or placebo. Those with clomiphene citrate-resistant PCOS received clomiphene citrate, 150 mg. Patients at risk for the development of OHSS received urinary FSH for ovulation induction. MAIN OUTCOME MEASURE(S): Ovulation, pregnancy, the development of OHSS, and levels of fasting insulin, insulin-like growth factor 1, insulin-like growth factor binding proteins 1 and 3, testosterone, androstenedione, DHEAS, E2, LH, and FSH. RESULT(S): Octreotide significantly reduced levels of fasting insulin, insulin-like growth factor 1, and LH in both clomiphene citrate- and urinary FSH-stimulated cycles. Levels of insulin-like growth factor binding protein 3 were increased. Two of six clomiphene citrate-stimulated cycles reached ovulation with the use of either octreotide or placebo. In urinary FSH-stimulated cycles, patients who received octreotide had significantly lower E2 levels at the time of hCG administration and fewer mature follicles. No cases of OHSS occurred in either group. One pregnancy occurred in each group. CONCLUSION(S): Octreotide was no more effective than placebo for clomiphene citrate resistance in patients with PCOS, but it did reduce E2 levels and follicle numbers when combined with urinary FSH. Thus, octreotide may reduce the incidence of OHSS in patients with PCOS.

Prospective randomized trial comparing the outcome and cost of in vitro fertilization with that of a traditional treatment algorithm as first-line therapy for couples with infertility.

OBJECTIVE: To determine whether IVF or a standard infertility treatment algorithm results in better outcome and/or lower cost when used as first-line therapy for couples with infertility. DESIGN: Prospective, randomized clinical study. SETTING: University-affiliated infertility clinic. PATIENT(S): Couples with newly diagnosed infertility and no prior treatment. INTERVENTION(S): Couples were randomized to undergo either IVF (group 1, n = 46) or a standard infertility treatment algorithm (group 2, n = 50) as initial therapy for infertility. MAIN OUTCOME MEASURE(S): Pregnancy rates and costs per couple, per month of treatment, and per pregnancy. RESULT(S): Pregnancy rates were higher in group 2 than in group 1. Costs per couple were not statistically different, although a trend toward higher costs was apparent in group 1, reflected by a higher median cost per clinical pregnancy established and a higher cost per month of treatment. Whereas cost differences between the groups diminished over time, pregnancy rates remained the same. CONCLUSION(S): In vitro fertilization currently does not represent an appropriate first-line treatment option for couples with infertility. The use of a standard infertility treatment algorithm results in a higher pregnancy rate and lower cost and therefore should be the preferred treatment approach.

What is the radiation exposure to patients during a gynecoradiologic procedure?

OBJECTIVE: To evaluate the risk of radiation exposure to infertility patients during a gynecoradiologic procedure. DESIGN: Retrospective clinical study. SETTING: Medical school-affiliated infertility center. PATIENT(S): Three hundred thirty-two consecutive infertility patients undergoing a gynecoradiologic procedure. INTERVENTION(S): Patients underwent a gynecoradiologic procedure as part of their infertility workup and the fluoroscopic exposure time was analyzed. MAIN OUTCOME MEASURE(S): The fluoroscopic exposure (rad time) during gynecoradiologic procedures, including hysterosalpingogram (HSG), selective salpingography, tubal catheterization, and others. RESULT(S): The rad time (mean +/- SD) was 63 +/- 54 seconds for normal HSG (n = 94, range 17 to 404 seconds), 100 +/- 61 seconds for abnormal HSG (n = 53, range 28 to 272 seconds), 111 +/- 57 seconds for unilateral selective salpingography (n = 36, range 31 to 324 seconds), 142 +/- 74 seconds for bilateral selective salpingography (n = 87, range 40 to 430 seconds), 176 +/- 77 seconds for unilateral tubal catheterization (n = 27, range 70 to 342 seconds), and 239 +/- 82 seconds for bilateral tubal catheterization (n = 30, range 110 to 381 seconds). Five patients had other procedures, such as lysis of intrauterine adhesions (n = 2) and resection of an uterine septum (n = 3), for which the rad time was in a range of 180 to 300 seconds. CONCLUSION(S): The radiation exposure of patients during a gynecoradiologic procedure, using previously described standard techniques, is well within established margins of safety.

Elevated tubal perfusion pressures during selective salpingography are highly suggestive of tubal endometriosis.

OBJECTIVE: To investigate the possible etiologies of elevated tubal perfusion pressures. DESIGN: Analysis of 48 consecutive female patients with infertility who underwent laparoscopy and a gynecoradiological investigation as part of their infertility work-up. SETTING: Academically affiliated infertility center. INTERVENTIONS: A gynecoradiological investigation was performed using a previously reported standardized contrast injection system. Laparoscopy was performed routinely. RESULTS: Patients who demonstrated by laparoscopy to have endometriosis showed a significantly increased incidence of tubal blockage during initial hysterosalpingography (HSG) (12/26, 46.1%) compared with controls (2/14, 14.3%). Patients with endometriosis also demonstrated significantly more frequently elevated tubal perfusion pressures (22/26; 84.6%) than women without disease (2/14, 14.3%) and significantly higher mean tubal perfusion pressures than women with normal pelvises (576 +/- 264 versus 450 +/- 268 mm Hg). CONCLUSION: Tubal blockage during initial HSG and elevated tubal perfusion pressures during selective salpingography are highly suggestive of tubal endometriosis. These data are the first evidence that tubal involvement with endometriosis may be more frequent than previously suspected. They also suggest that the performance of a gynecoradiological investigation, inclusive of selective salpingography, can greatly contribute to a presumptive diagnosis of endometriosis.

A randomized prospective comparison between intrauterine insemination and fallopian sperm perfusion for the treatment of infertility.

OBJECTIVE: To determine if the pregnancy rates (PRs) in infertile women could be improved with fallopian sperm perfusion in comparison with IUI. DESIGN: Randomized prospective analysis. SETTING: Academically affiliated infertility center. PATIENTS: Consecutive patients undergoing controlled ovarian hyperstimulation (COH). INTERVENTIONS: After hCG administration, patients were randomized to either IUI or fallopian sperm perfusion. MAIN OUTCOME MEASURES: Pregnancy rates with the two treatment modalities. RESULTS: Of 240 COH cycles, those randomized to IUI included 44 clomiphene citrate (CC) (group I) and 76 gonadotropin (group III) cycles. Patients receiving fallopian sperm perfusion included 44 cycles of CC (group II) and 76 cycles of gonadotropin (group IV) treatment. The overall PRs per cycle (10.8% versus 10.8%) were similar for IUI and fallopian sperm perfusion, respectively. The PRs were also similar when compared for ovulation induction with CC (6.8% versus 9.1%) and gonadotropins (13.2% versus 11.8%). CONCLUSION: We conclude that fallopian sperm perfusion offers no advantage over IUI. Because the process of fallopian sperm perfusion is more time consuming and more costly (because of increased media usage), fallopian sperm perfusion does not seem indicated as a routine infertility therapy and should not replace IUI.

The limited value of hysterosalpingography in assessing tubal status and fertility potential.

DESIGN: To determine whether the diagnostic accuracy and prognostic value of hysterosalpingography (HSG) could be improved if routine spot films were replaced by an on-line recorded gynecoradiologic study. SETTING: Medical school-affiliated private infertility center. PATIENTS: In 1992, a review of 152 infertile women with infertility who demonstrated a normal HSG, by standard criteria of spot film evaluation, in 117 (77%). They were further investigated by gynecoradiologic study if the HSG revealed asymmetrical tubal filling, an increased perfusion pressure, and/or evidence for abnormal tubal spill. In 1993, 47 women with normal HSG by spot film criteria underwent bilateral selective salpingography and were subdivided into those with normal (group I, n = 23) and abnormal (group II, n = 24) tubal perfusion pressures. INTERVENTION: Patients in both study groups then were treated for their infertility independently of pressure perfusion measurements. MAIN OUTCOME MEASURE: Clinical pregnancy rates (PRs) over the ensuing 6 to 10 months. RESULTS: Among 117 women with apparently normal spot film HSG, 64 (55%) demonstrated asymmetrical tubal filling, 32 (27%) demonstrated abnormal spillage into the peritoneal cavity, and 55 (47%) demonstrated abnormally elevated injection pressures. Among 98 women who underwent bilateral selective salpingography, 43 (44%) demonstrated bilaterally normal tubal perfusion pressures and 55 (56%) showed an abnormally elevated pressure in at least one oviduct. Of 47 women that were followed prospectively in 1993, patients with normal perfusion pressure (group I) demonstrated a significantly higher PR than women with elevated tubal pressure (group II) from 2 months and on after the procedure. CONCLUSIONS: Routine spot film HSG is of limited value in assessing tubal status beyond the determination of tubal patency. Especially with regard to fertility potential, HSG should be replaced by gynecoradiologic study.

Analysis of ectopic pregnancies resulting from in-vitro fertilization and embryo transfer.

The purpose of this study was to analyse the risk factors, stimulation characteristics, site and outcome of pregnancy and future fecundity of patients who develop ectopic pregnancies after in-vitro fertilization (IVF). Of 3145 transfer cycles between January 1981 and July 1989, 27 (3.3%) of the resulting 825 pregnancies were ectopic. There was a significantly greater incidence of a prior ectopic pregnancy in the study group compared to the controls. Compared to matched controls with intrauterine pregnancies, the study group had significantly higher peak oestradiol levels. Twenty-one ectopic pregnancies were ampullary, two were interstitial, one was abdominal, one was cervical and two were heterotopic. Sixteen of the patients subsequently underwent 40 IVF attempts with a pregnancy rate of 28% per transfer. We conclude that patients with a prior ectopic pregnancy are at risk for an IVF ectopic pregnancy. The subsequent IVF outcome of those who develop ectopic pregnancies after IVF is encouraging.

The relationship between serum estradiol-17 beta concentrations and induced pituitary luteinizing hormone surges in postmenopausal women.

The present study was designed to evaluate the effect of different serum concentrations of estradiol-17 beta (E2) on pituitary luteinizing hormone (LH) release in postmenopausal women. Serum E2 levels were evaluated in healthy postmenopausal women while they wore two, four, and six transdermal E2 delivery systems. The mean serum E2 levels at 48 hours after application of the devices were 185.5, 338.9, and 520.5 pg/mL, respectively, which were significantly different from each other. Serum E2 levels were stable throughout the first 48 hours of patch application but declined by a mean of 54% between 48 and 72 hours. Pituitary LH surges were induced with all three serum concentrations of E2 but were present more often with the higher serum values. There were no significant differences between the mean interval of device utilization and initiation, height, or duration of the induced pituitary LH surge at any of the three serum E2 concentrations studied.

Are implantation and pregnancy outcome impaired in diethylstilbestrol-exposed women after in vitro fertilization and embryo transfer?

Forty-six infertile women with a history of diethylstilbestrol (DES) exposure in utero underwent 149 stimulation attempts for in vitro fertilization (IVF). The mean (+/- SE) number of preovulatory oocytes harvested at retrieval and transferred was 3.9 +/- 3.3 (536/138) and 2.6 +/- 1.4 (328/124). When compared with patients with tubal factor infertility and less than or equal to 4 pre-embryos transferred, the clinical pregnancy rate (15.3% versus 22%) was not statistically different. However, the term/ongoing pregnancy rate was significantly lower in the study group (8% versus 16%). Comparison of the IVF outcome with different uterine anomalies as detected by hysterosalpingogram (n = 29) showed a trend for a worse prognosis in women with constrictions and a combination of T-shape and constrictions. It is concluded that implantation and pregnancy outcome are impaired in DES-exposed women after IVF.

Non-functional ovarian cysts do not affect ipsilateral or contralateral ovarian performance during in-vitro fertilization.

Reports on the significance of ovarian cystic structures during in-vitro fertilization (IVF) have been conflicting. This study examined the effect of such structures on ovarian performance during IVF. Twenty-one patients with one or more cystic structures of 20-50 mm in diameter, detected on day 6 of the menstrual cycle, were compared to 35 non-cystic controls. Differences (cyst versus non-cyst) included basal oestradiol (E2) levels (40 +/- 4.8 versus 29 +/- 2.0 pg/ml; P less than 0.01), ampoules of gonadotrophins administered (24 +/- 2 versus 16 +/- 1; P less than 0.001) and peak E2 concentrations (415 +/- 45 versus 744 +/- 88 pg/ml; P less than 0.05). There were no differences in the number of follicles aspirated or oocytes retrieved. In 19 patients with unilateral structures, the ipsilateral ovary produced fewer follicles (2.5 +/- 0.5 versus 3.9 +/- 0.6; P less than 0.05); however, there were no differences in the number or maturity of oocytes recovered. Since the numbers of oocytes recovered were equivalent in the presence or absence of ovarian cystic structures, their presence is not an indication to cancel an IVF cycle.

Correlation between clinical, endocrinologic and nuclear magnetic resonance findings in women with suspected pituitary adenomas.

Twenty-nine women with suspected pituitary adenomas were evaluated with nuclear magnetic resonance (NMR). Twenty-six had prolactin levels less than 100 ng/mL, and three had levels greater than 100. We tried to correlate the clinical findings with the prolactin levels and NMR findings. Pituitary adenomas were detected on NMR even with prolactin levels less than 100 ng/mL.

High-dose follicle-stimulating hormone stimulation at the onset of the menstrual cycle does not improve the in vitro fertilization outcome in low-responder patients.

In an attempt to improve their outcome with in vitro fertilization (IVF), 34 low-responder patients were stimulated with six ampules of follicle-stimulating hormone (FSH) daily starting on day 1 (n = 17) or day 2 (n = 17) of their menstrual cycles. The stimulated cycles showed a mean peak estradiol of 443 +/- 173 pg/mL, mean days of human chorionic gonadotropin of 7.6 +/- 1.4, 2.67 +/- 1.5 preovulatory oocytes per retrieval, and 2.56 +/- 1.3 oocytes per transfer. Three clinical pregnancies resulted after 25 embryo transfer cycles (12%). With paired analysis, we compared 8 patient cycles with prior six ampules of FSH stimulation starting on day 3; all parameters examined showed no significant differences. In a comparison of 22 patient cycles with prior 4 ampules of FSH stimulation on cycle day 3, no significant differences in any parameters were observed except in the higher number of ampules used in the present study. We conclude that high-dose FSH stimulation at the onset of the menstrual cycle does not improve the IVF outcome in low-responder patients.