A one-year experience with a capitated health care plan for infertility.

OBJECTIVE: To report on a one-year experience participating in a capitated healthcare plan for infertility. DESIGN: Prospective study. SETTING: University population. PATIENT(S): Reproductive-age women 15 to 50 years. INTERVENTION(S): The first-generation Lewin infertility algorithm and CATHI software were used to negotiate infertility services under a capitated arrangement for $0.50 per member per month. The following reports our experience for the fiscal year 1997. MAIN OUTCOME MEASURE(S): Infertility services rendered, pregnancy rate, cost of services, collection rates. RESULT(S): Five thousand forty-six women representing 39,689 member months generated 39 new and 198 return visits. Thirty-two percent of the patients required three visits or less; six patients generated 22% of the visits. Fifty-one percent listed infertility as one of their chief complaints; 31% had mixed diagnoses. Eight (7.6%) patients required surgery, 11 (10.5%) patients underwent either IVF or GIFT cycles. Total charges submitted were $176,636; the amount assigned to specialty care was $135,277, and to IVF/GIFT, $33,433. Total capitated payments, including copayments, was $126,256 under the reproductive medicine agreement and $32,891 under the infertility rider. This resulted in a 71% gross collections rate. CONCLUSION(S): This study indicates that entering into a capitated health care plan to provide an infertility benefit can produce a successful result.

Sperm morphology, motility, and concentration in fertile and infertile men.

BACKGROUND: Although semen analysis is routinely used to evaluate the male partner in infertile couples, sperm measurements that discriminate between fertile and infertile men are not well defined. METHODS: We evaluated two semen specimens from each of the male partners in 765 infertile couples and 696 fertile couples at nine sites. The female partners in the infertile couples had normal results on fertility evaluation. The sperm concentration and motility were determined at the sites; semen smears were stained at the sites and shipped to a central laboratory for an assessment of morphologic features of sperm with the use of strict criteria. We used classification-and-regression-tree analysis to estimate threshold values for subfertility and fertility with respect to the sperm concentration, motility, and morphology. We also used an analysis of receiver-operating-characteristic curves to assess the relative value of these sperm measurements in discriminating between fertile and infertile men. RESULTS: The subfertile ranges were a sperm concentration of less than 13.5 x 10(6) per milliliter, less than 32 percent of sperm with motility, and less than 9 percent with normal morphologic features. The fertile ranges were a concentration of more than 48.0 x 10(6) per milliliter, greater than 63 percent motility, and greater than 12 percent normal morphologic features. Values between these ranges indicated indeterminate fertility. There was extensive overlap between the fertile and the infertile men within both the subfertile and the fertile ranges for all three measurements. Although each of the sperm measurements helped to distinguish between fertile and infertile men, none was a powerful discriminator. The percentage of sperm with normal morphologic features had the greatest discriminatory power. CONCLUSIONS: Threshold values for sperm concentration, motility, and morphology can be used to classify men as subfertile, of indeterminate fertility, or fertile. None of the measures, however, are diagnostic of infertility.

Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network.

BACKGROUND: Induction of superovulation with gonadotropins and intrauterine insemination are frequently used to treat infertility. We conducted a large, randomized, controlled clinical trial of these treatments. METHODS: We studied 932 couples in which the woman had no identifiable infertility factor and the man had motile sperm. The couples were randomly assigned to receive intracervical insemination, intrauterine insemination, superovulation and intracervical insemination, or superovulation and intrauterine insemination. Treatment continued for four cycles unless pregnancy was achieved. RESULTS: The 231 couples in the group treated with superovulation and intrauterine insemination had a higher rate of pregnancy (33 percent) than the 234 couples in the intrauterine-insemination group (18 percent), the 234 couples in the group treated with superovulation and intracervical insemination (19 percent), or the 233 couples in the intracervical-insemination group (10 percent). Stratified, discrete-time Cox proportional-hazards analysis showed that the couples in the group treated with superovulation and intrauterine insemination were 3.2 times as likely to become pregnant as those in the intracervical-insemination group (95 percent confidence interval, 2.0 to 5.3) and 1.7 times as likely as those in the intrauterine-insemination group (95 percent confidence interval, 1.2 to 2.6). The couples in the intrauterine-insemination group and in the group treated with superovulation and intracervical insemination were nearly twice as likely to conceive as those in the intracervical-insemination group. CONCLUSIONS: Among infertile couples, treatment with induction of superovulation and intrauterine insemination is three times as likely to result in pregnancy as is intracervical insemination and twice as likely to result in pregnancy as is treatment with either superovulation and intracervical insemination or intrauterine insemination alone.

The use of propofol, nitrous oxide, or isoflurane does not affect the reproductive success rate following gamete intrafallopian transfer (GIFT): a multicenter pilot trial/survey.

BACKGROUND: Whether anesthetic agents administered during gamete intrafallopian transfer (GIFT) affect reproductive outcome is controversial. This multicenter pilot trial and survey had two purposes: to evaluate the effect of propofol, nitrous oxide, midazolam, and isoflurane on pregnancy outcome after GIFT, and to determine if a larger prospective, randomized study is warranted. METHODS: A written invitation was mailed to all 50 fertility programs in the United States that are members of the Society for Assisted Reproductive Technology and perform more than 30 GIFT procedures per year. They were invited to contribute information from the medical records of women who underwent GIFT during the calendar years 1993 and 1994. They were asked to document whether propofol, nitrous oxide, midazolam, a potent inhaled anesthetic agent was used during the GIFT procedure; if the woman became pregnant; and if she delivered at least one live neonate. RESULTS: Seven medical centers participated and contributed data from 455 women. The clinical pregnancy rate (number of pregnancies/total number of GIFT procedures) and the delivery rate (number of women who delivered at least one live baby/total number of GIFT procedures) were 35% and 32%, respectively. A statistically significant difference could not be found in the clinical pregnancy or delivery rates between those women who received propofol, nitrous oxide, midazolam, or isoflurane during GIFT and those who did not. CONCLUSIONS: No agent-related differences in pregnancy rates were found when propofol, nitrous oxide, isoflurane, or midazolam was used as part of the anesthetic technique for GIFT. Therefore, a more extensive prospective trial does not appear to be warranted.

Efficacy of treatment for unexplained infertility.

OBJECTIVE: To analyze the efficacy and cost-effectiveness of alternative treatments for unexplained infertility. DESIGN: Retrospective analysis of 45 published reports. SETTING: Clinical practices. PATIENT(S): Couples who met criteria for unexplained infertility. Women with Stage I or Stage II endometriosis were included. INTERVENTION(S): Observation; clomiphene citrate (CC); gonadotropins (hMG); IUI; and GIFT and IVF. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate. RESULT(S): Combined pregnancy rates per initiated cycle, adjusted for study quality, were as follows: no treatment = 1.3%-4.1%; IUI = 3.8%; CC = 5.6%; CC + IUI = 8.3%; hMG = 7.7%; hMG + IUI = 17.1%; IVF = 20.7%; GIFT = 27.0%. The estimated cost per pregnancy was $10,000 for CC + IUI, $17,000 for hMG + IUI, and $50,000 for IVF. CONCLUSION(S): Clomiphene citrate + IUI is a cost-effective treatment for unexplained infertility. If this treatment fails, hMG + IUI and assisted reproduction are efficacious therapeutic options.

Identification of early pregnancy landmarks by transvaginal sonography: analysis by logistic regression.

OBJECTIVE: To assess the feasibility of logistic regression analysis for determining the gestational ages at which detection of early pregnancy landmarks first can be observed. DESIGN: Retrospective analysis. SETTING: University-based tertiary care clinic. PATIENT(S): Eighty-two women with viable singleton pregnancies in whom ovulation had been achieved by an injection of hCG. INTERVENTION(S): Two hundred fifteen transvaginal sonographic scans. MAIN OUTCOME MEASURE(S): Logistic regression was used to estimate the probability of detection of sonographic findings as a function of gestational age. RESULT(S): We found that the likelihood of visualization of a gestational sac or fetal heart motion could be represented accurately by logistic equations. Gestational age at which there was 95% probability of visualization was 35.5 days for the gestational sac and 44.5 days for fetal cardiac activity. The probability of detecting fetal cardiac activity was 95% when the mean gestational sac diameter was 1.6 cm and was 99% at 1.9 cm. CONCLUSION(S): The sonographic appearances of developmental landmarks in early pregnancy occurs within well-defined gestational time periods, and the probabilities for visualization can be closely approximated using a logistic model. Our results suggest that the number of sonographic examinations required to document infertility treatment success can be minimized by surveillance at standardized gestational ages.

The effect of routine breast examination on serum prolactin levels.

OBJECTIVE: To evaluate the effect of a routine breast examination on serum PRL levels. DESIGN: Prospective clinical study. SETTING: University-based reproductive endocrinology unit. PATIENTS: Eleven nonlactating, euprolactinemic women of reproductive age with a history of regular menstrual cycles and currently taking no medications. INTERVENTIONS: Breast examination using standard technique. MAIN OUTCOME MEASURE: Changes in serum PRL levels after breast examination. RESULTS: Baseline PRL levels ranged from 3.64 to 19.23 ng/mL (mean 7.17 ng/mL; conversion factor to SI unit, 1.00). There were no significant increases in PRL levels after breast examination, with mean PRL levels after 15, 30, and 45 minutes of 6.59, 6.84, and 6.45 ng/mL, respectively. CONCLUSION: Routine breast examination does not alter acutely serum PRL levels in normal women.

Multifetal reduction of high-order multiple pregnancy: comparison of obstetrical outcome with nonreduced twin gestations.

OBJECTIVE: To compare the obstetric outcomes of twin pregnancies obtained as a result of multifetal pregnancy reduction to those in which pregnancy reduction had not been used. DESIGN: Retrospective analysis. SETTING: University-based tertiary care infertility clinic. PATIENTS: Seventy-four twin pregnancies continuing beyond 10 weeks. Of these, 32 gestations had undergone reduction to twins at 10 weeks. MAIN OUTCOME MEASURES: Gestational age at delivery, birth weights, pregnancy complications. RESULTS: All pregnancies advanced beyond 20 weeks gestation. The mean gestational age at delivery of the reduction group was 33.8 versus 35.7 weeks in the nonreduced group; only 25% of reduced pregnancies reached 37 weeks compared with 57.9% of nonreduced twins. The mean fetal birth weights of the two groups differed significantly (reduced: 2,038 g, nonreduced: 2512 g). The gestational age at delivery in patients reduced from triplets was significantly greater than in pregnancies reduced from quadruplets or higher. Multiple regression analysis revealed that for a given gestational age at delivery, a history of pregnancy reduction was associated with decreased birth weight. CONCLUSION: These data suggest that multifetal pregnancy reduction does not reverse completely the decreased gestational age and impaired fetal growth associated with high-order multiple pregnancy. Furthermore, fetal growth of reduced pregnancies seems to be impaired independent of the gestational age at which delivery occurs.

Successful delivery of mature twins after a ruptured interstitial heterotopic pregnancy. A case report.

A 31-year-old primigravida had a combined pregnancy consisting of intrauterine twins and an interstitial ectopic after in vitro fertilization/embryo transfer. The patient underwent repair of the ectopic pregnancy at 15 weeks of gestation, with subsequent delivery of mature twins close to term.

Pituitary-ovarian interactions during follicular maturation and ovulation.

During the past decade, research on hypothalamic-pituitary-ovarian relationships in ovulation has explored the contributions of ovarian steroids and other possible ovarian-derived endocrine factors, such as inhibin, follistatin, and activin. Follistatin and activin probably have a significant intraovarian and intrapituitary function but are not likely to have critical endocrine roles during the follicular phase. Studies carried out with both recombinant and highly purified forms of follicle-stimulating hormone in humans and monkeys indicate that this hormone is the primary stimulant of follicular growth and development. Studies on animals may have led to incorrect emphasis on the local role of estradiol in primate follicular growth. It appears that estradiol is not a critical folliculotropin in humans, although it may have some important direct effects on the oocyte.

An evaluation of the effect of gonadotropin-releasing hormone analogs and medroxyprogesterone acetate on uterine leiomyomata volume by magnetic resonance imaging: a prospective, randomized, double blind, placebo-controlled, crossover trial.

The purpose of this study was to prospectively compare the effectiveness of administering medroxyprogesterone acetate (MPA; 20 mg/day) in either the first (protocol A) or last (protocol B) 12-week period along with a 6-month course of the GnRH analog (GnRH-a; leuprolide acetate; 1 mg/day, sc) on uterine and leiomyomata volumes and hormone (estradiol, LH, and FSH) and serum lipid (total cholesterol, triglycerides, and high and low density lipoprotein) levels. Sixteen women were randomized into protocol A or B, received either MPA or placebo along with GnRH-a, respectively, and were then crossed over at 12 weeks to placebo or MPA, respectively, for the final 12-week interval of GnRH-a therapy. Total, myoma, and nonmyoma uterine volumes were determined by magnetic resonance imaging, and serum studies were performed at the beginning of the study and at 12 and 24 weeks. In both protocols, LH and estradiol levels declined by 80-90% (P < 0.03) and 55-72% (P < 0.02) of the baseline, respectively, at 12 weeks and remained at this level at 24 weeks. There were no significant changes in the other laboratory tests between protocols or longitudinally over time. Total uterine volume decreased to 73% of the baseline at 12 weeks in protocol B (P < 0.04), but did not change in protocol A. After crossover at 12 weeks, the total uterine volume of women in protocol A decreased to 74% of the baseline (P < 0.02) at 24 weeks. Between-protocol comparisons demonstrated a greater decline in total uterine volume in protocol B than A at 12 weeks, but after cross-over, MPA addition was associated with a significant increase in total uterine volume (protocol B) compared to a decrease in protocol A at 24 weeks (P < 0.005). In contrast, although myoma volume declined in both protocols, no significant changes in myoma volume were detected within or between groups over the treatment period. Nonmyoma volume changes in protocols A and B roughly paralleled total uterine volume changes, with MPA coadministration showing a correlation with a reversal in the GnRH-a-associated decrease in nonmyomatous tissue volume.(ABSTRACT TRUNCATED AT 400 WORDS)

Detection of free peritoneal fluid by transvaginal sonography.

The recognition of peritoneal fluid is of considerable clinical importance; however, the sensitivity of modern techniques for the detection of this finding has not been determined. The purpose of this study was to assess the utility of transvaginal sonography for the detection of free peritoneal fluid. Nineteen infertile women scheduled to undergo diagnostic laparoscopy were scanned with a 5-MHz transvaginal probe just before the surgical procedure. Peritoneal fluid was then aspirated laparoscopically, and the volume and location was compared to the sonographic findings. The volume of fluid obtained at laparoscopy ranged from 0 mL to 45 mL (median 8 mL). All patients with fluid volumes > or = 0.8 mL had free fluid identified sonographically. The location of fluid observed sonographically corresponded to that noted at laparoscopy in all cases. Free peritoneal fluid was visualized in 8 (73%) of 11 patients with regular menstrual cycles who were in the follicular phase at the time of the study. We conclude that transvaginal sonography is a sensitive and reliable method for the detection of free peritoneal fluid in anatomically normal women. This finding should not necessarily be considered abnormal, at least in women of reproductive age, nor should it be considered diagnostic of oocyte release.

A simplified approach to in vitro fertilization.

A simplified protocol for in vitro fertilization treatment was developed using low-dose clomiphene for ovarian stimulation, timing of human chorionic gonadotropin administration based solely on sonographic criteria, in-office egg retrieval and use of a simplified culture medium for embryo culture. Twenty-six infertile women underwent 39 treatment cycles, with 33 egg retrievals resulting in 29 embryo transfers. Clinical pregnancy was obtained in six patients (20.7% per embryo transfer), for a rate comparable to that achieved with conventional in vitro fertilization treatment in an age-matched control group. This simplification of in vitro fertilization treatment protocols can lead to decreased patient stress and costs without a substantially lower success rate.

Inhibition of preimplantation mouse embryo development by isoflurane.

OBJECTIVE: Preimplantation mouse embryos were exposed to a commonly used inhalational anesthetic agent, isoflurane, to determine its effects on embryo development. STUDY DESIGN: Two-cell embryos were exposed at various intervals (5 to 6 hours, 3 to 4 hours, and 0 to 1 hour) before the onset of their first cleavage in vitro. In addition, the effects of 5% isoflurane on four-cell embryos exposed about 2 hours after the first cleavage and morula stage embryos also were examined. RESULTS: Development to the blastocyst stage was inhibited by 3% and 5% isoflurane (p less than 0.005) but not by 1.5% isoflurane when two-cell embryos were exposed 3 to 4 hours or 0 to 1 hour before the onset of cleavage. Most of the affected embryos completed cell division and came to a halt at the three- to four-cell stage. The development of embryos exposed to isoflurane at the four-cell or morula stage was unaffected. CONCLUSIONS: Isoflurane adversely affects subsequent preimplantation development when two-cell mouse embryos are exposed just before the onset of their first cleavage in vitro.

Visualization of free peritoneal fluid with transvaginal sonography. A preliminary study.

Visualization of free peritoneal fluid during sonographic examination is often of considerable clinical importance. To determine the sensitivity of transvaginal sonography in the detection of this finding, measured amounts of isotonic saline were instilled into the abdominal cavities of 15 women undergoing diagnostic laparoscopy while a 5-MHz transvaginal probe was employed to view the pelvic contents. Small amounts of free fluid could be visualized easily in all the patients (mean +/- SD, 25.8 +/- 6.4 mL). Fluid was first seen in the cul-de-sac in 10 patients and in the adnexal region in 5. When fluid instillation was continued to a total volume of 200 mL, the pelvic viscera were distinctly outlined in all the patients, markedly enhancing visualization of the uterus, tubes and ovaries. Transvaginal sonography seems to be a sensitive and reliable method of detecting free peritoneal fluid. Instillation of fluid into the peritoneal cavity may be a clinically useful technique for enhancing the sonographic visualization of pelvic structures.

Effect of estrogen/progestin administration on the ovarian response to gonadotropins: a randomized, prospective study.

The findings of our study indicate that women pretreated with E/progestin demonstrate increased gonadotropin requirements when undergoing ovulation induction. Whether this treatment has a significant effect on the outcome of ovulation induction in patients receiving gonadotropins remains to be established.

Hormonal treatment of functional ovarian cysts: a randomized, prospective study.

Estrogen (E)/progestin therapy for functional ovarian cysts is widely used in clinical practice, but the efficacy of this treatment has not been determined in controlled trials. In this study, we examined the effect of E/progestin administration in a group of infertility patients enrolled in a program of ovulation induction who had cysts identified by transvaginal sonography. Patients were randomized to receive either norethindrone 1 mg/mestranol 0.05 mg/d (group A, n = 24) or no treatment (group B, n = 24) for up to 6 weeks. Patients were re-evaluated by sonography at 3, 6, and 9 weeks after entry into the protocol. The ages, mean cyst diameters, and proportions of patients having received gonadotropins in the previous menstrual cycle were not significantly different among the two groups. All patients who had a sonographic abnormality persisting for 9 weeks were surgically explored and found to have pathological cysts. The rate of disappearance of functional ovarian cysts was not affected by E/progestin treatment.