Clomiphene citrate ovulation induction in combination with a timed intrauterine insemination: the value of urinary luteinizing hormone versus human chorionic gonadotropin timing.

OBJECTIVE: To evaluate the clinical pregnancy rates (PRs) in anovulatory, male factor, and unexplained infertility using clomiphene citrate (CC) with an IUI and to evaluate the difference in PRs between urinary LH testing and hCG administration for timing of the IUI. DESIGN: Retrospective clinical study. SETTING: Academic, tertiary care fertility center. PATIENT(S): One hundred thirty-eight couples (432 cycles) undergoing IUI with CC ovulation induction as a treatment for unexplained, anovulatory, or male factor infertility were selected. INTERVENTION(S): All women with unexplained or male factor infertility received CC at a dose of 50 mg/d, and those with anovulation received CC at a dose ranging from 50 to 200 mg/d. All women in the study received a single IUI either the morning after a urinary LH surge or 36 to 38 hours after an evening hCG injection. MAIN OUTCOME MEASURE(S): Clinical PR. RESULT(S): There were no differences in the clinical PRs between LH testing or hCG administration in any of the three groups. Clinical PRs were extremely low in the male factor infertility group regardless of the timing used. CONCLUSION(S): These data suggest that the success of IUI with CC is not dependent on the method used to establish the timing for the IUI. In couples undergoing IUI with CC, the use of urinary LH testing may result in lower costs by reducing patient visits and the midcycle ultrasound.

Evaluation of serum CA 125 concentrations as predictors of pregnancy with human in vitro fertilization.

OBJECTIVE: To determine if CA 125, a product of human endometrium, may be an indicator of early endometrial function. To test this hypothesis we examined CA 125 concentrations before oocyte retrieval in IVF cycles. DESIGN: Retrospective data analysis of 111 consecutive IVF cycles. SETTING: Tertiary care academic medical center. PATIENTS: All women who received luteal leuprolide acetate (LA) suppression followed by hMG for IVF and had sera available for analyses were entered into the study. MAIN OUTCOME MEASURE: Serum CA 125 was measured in the previous luteal cycle, day 7 of hMG, day before, and day of hCG administration. Twelve other variables were analyzed. RESULTS: Fifty-six cycles (47 women) qualified for evaluation and included 25 pregnant cycles (45%) and 31 nonpregnant cycles. Higher serum CA 125 concentrations were associated with pregnancy in both endometriosis and nonendometriosis subgroups. CA 125 values on the day of hCG administration were the best predictors of pregnancy, with levels > or = 16 U/mL having a sensitivity of 72%, specificity of 97%, and a positive predictive value of 95% for pregnancy. The other variables were not predictive of pregnancy. CONCLUSIONS: With a LA and hMG stimulation protocol, increased CA 125 concentrations before retrieval are associated with very high pregnancy rates. The source(s) of the serum CA 125, although as yet undertermined, may be of endometrial origin. The study supports further evaluation of CA 125 concentrations in IVF as a preretrieval predictor of pregnancy.

The effect of serum from infertile women with endometriosis on fertilization and early embryonic development in a murine in vitro fertilization model.

OBJECTIVE: To evaluate the effect of serum from infertile women with endometriosis on fertilization and embryonic development in a murine IVF model. DESIGN: Pretreatment and post-treatment comparison of murine oocyte fertilization and early embryonic development with the addition of serum supplements from infertile women with endometriosis. SETTING: Tertiary care academic medical center. PATIENTS: Sera from 10 fertile women without endometriosis and 28 infertile women with endometriosis both before and after laser laparoscopy. RESULTS: When compared with serum from fertile women, serum from infertile women with endometriosis inhibited fertilization rates (51% versus 81%) and subsequent embryonic development rates (46% versus 79%). The inhibitory effect was greater as the stage of endometriosis increased. Treatment of endometriosis by laser laparoscopy improved both fertilization (51% versus 56%) and early embryonic development rates (46% versus 58%). CONCLUSIONS: Serum from infertile women with endometriosis inhibits both fertilization and early embryonic development in the murine IVF model. Inhibition of fertilization and early embryonic development rates increases as the stage of endometriosis increases. Improved fertilization and early embryonic development rates are observed after treatment of endometriosis by laser laparoscopy.

Clinical evaluation of CA-125 concentrations as a prognostic factor for pregnancy in infertile women with surgically treated endometriosis.

OBJECTIVE: To extend and confirm earlier observations that serial CA-125 determinations appear to have prognostic value in some infertile women with surgically treated endometriosis using a new automated enzyme immunoassay. DESIGN: A prospective consecutive case series. SETTING: A university-based tertiary practice. PATIENTS: Of 342 women having a laparoscopy for infertility, 123 (36%) had endometriosis. Fifty-six of 123 (45%) infertile women with endometriosis had preoperative CA-125 values > or = 16 U/mL and were followed for 12 months with serial CA-125 determinations. MAIN OUTCOME MEASURE: Proportion of women achieving a pregnancy within 12 months from surgery. RESULTS: Mean preoperative CA-125 concentrations were not statistically different for women conceiving, but mean postoperative CA-125 values were significantly lower for women achieving a pregnancy. Univariate analyses indicated that preoperative CA-125 values between 16-25 U/mL and postoperative CA-125 values < 16 U/mL were associated with significantly higher pregnancy rates. Multivariate analyses of 10 covariables indicated only postoperative CA-125 concentrations to be associated with pregnancy even after controlling for all covariables. CONCLUSION: Using a newly developed assay for CA-125, the study confirms and extends earlier observation that CA-125 concentrations have prognostic value for pregnancy in infertile women with surgically treated endometriosis. The findings provide additional support for the clinical use of CA-125 concentrations in selected women with endometriosis.

Laparoscopic adnexectomy: a comparison with laparotomy.

OBJECTIVE: Our purpose was to compare the newer technique of laparoscopic adnexal excision with conventional laparotomy. DESIGN: With the same entry criteria, a retrospective, consecutive series of 26 women who underwent adnexectomy by laparotomy was compared with a later prospective consecutive series of 64 women who had laparoscopic adnexectomy in a university referral practice. The two groups were similar in all characteristics examined. The ages of the women ranged from 18 to 70 years, but only two women were postmenopausal. Pelvic pain with or without an ovarian cystic mass was the surgical indication in 91% to 92% of the women. Seven women had a persistent adnexal cystic mass and one woman had a unilateral androgen-secreting ovary. Bipolar coagulation was the laparoscopic method used. RESULTS: Median operating time (88 vs 107 minutes), blood loss (72 vs 222 ml), days in the hospital (1 day vs 3 days), total costs ($4573 vs $6044), and recovery time (1 week vs 4 weeks) were significantly less with laparoscopic adnexectomy. There were no differences between the two techniques in major complications (one in each group), blood transfusions, adhesion formation, or the proportion of women noting improvement of pain symptoms. CONCLUSION: In this preliminary assessment of laparoscopic adnexectomy, this surgical procedure offers significant advantages to laparotomy in selected patients when performed by a laparoscopist experienced in advanced techniques.

PIP: In Winston-Salem, North Carolina, researchers compared prospective data on 64 consecutive women (18-70 years old, only 2 of whom were postmenopausal) who experienced laparoscopic adnexectomy between January, 1991, and March, 1993, with retrospective data on 26 consecutive women (21-44 years old) who experienced adnexectomy by laparotomy between January, 1989, and December, 1991. The indication for adnexectomy for most women was pelvic pain (91% for laparoscopy patients and 92% for laparotomy patients). The reasons for the pelvic pain included chronic pelvic inflammatory disease, recurrent ovarian cyst, endometrioma, cyclic ovarian pain, and periovarian adhesions. Among women with no pelvic pain, 7 women had a chronic adnexal cyst, and 1 woman had an ovary secreting an androgen. The median operative time for laparoscopy was significantly shorter than for laparotomy (88 vs. 107 minutes; p = .04). Even though the estimated blood loss was significantly less among laparoscopy patients than laparotomy patients (72 vs. 222 ml; p = .01), the change in hematocrit in both groups was not significant (3.9 vs. 5.2), and no one needed a blood transfusion. Women in the laparoscopy group were in the hospital for a significantly shorter period (1 vs. 3 days; p = .0001) and recovered more rapidly (1 vs. 4 weeks; p = .001) than did those in the laparotomy group. The total cost was lower for laparoscopic adnexectomy than for adnexectomy by laparotomy ($4573 vs. $6044; p = .02). Women in both groups noted improvement in pelvic pain. Just 1 woman from each group had a major complication. These findings suggest that experienced laparoscopic surgeons can quickly, safely, and effectively perform adnexectomy using laparoscopy.

Effectiveness of laparoscopic varicocelectomy.

Laparoscopic varicocelectomy is a new technique which has been described in a limited number of clinical reports. We reviewed the results of 46 patients undergoing laparoscopic repair of 75 varicoceles over a two-year period to assess the effectiveness of this operative technique. The internal spermatic artery was preserved in 80 percent of the varicoceles and two arteries were present in 5 percent. Our ability to preserve the internal spermatic artery improved significantly with the use of the intraoperative Doppler probe after the first six months of performing this operation (p < 0.01). Nineteen infertile patients had a minimum follow-up of twelve months with seminal improvement in 68 percent and a pregnancy rate of 26 percent. Complications occurred in 2 patients (4%), inferior epigastric vessel bleeding in one, and genitofemoral nerve injury in the other. There was one persistent varicocele (1%). Our results with laparoscopic varicocelectomy are comparable with those reported with standard open surgical approaches.

Effects of hemodialysis on prostate-specific antigen.

We undertook a prospective study to evaluate the effects of hemodialysis on serum prostate-specific antigen (PSA) in 26 male patients with end-stage renal disease as a clinical model for assessing the role of the kidney in PSA clearance. Patients ranging in age from fifty-one to eighty-three years (mean 64.8 years) underwent phlebotomy immediately before and after outpatient hemodialysis on a Monday/Wednesday/Friday or Tuesday/Thursday/Saturday schedule, with serum PSA values determined by the Abbott IMX Microparticle Enzyme Immunoassay. The mean +/- standard deviation for all post-dialysis PSA levels, 2.43 +/- 3.74, was significantly greater than that for pre-dialysis levels, 2.11 +/- 3.19 (p = 0.04). However, no statistically significant differences were found on comparing the combined pre- and post-dialysis PSA values over the course of the study (p = 0.2733) or when sequential pre-dialysis (p = 0.28) and post-dialysis (p = 0.92) levels were analyzed separately. We conclude that PSA is not eliminated by hemodialysis, and our results infer that it is not cleared by renal mechanisms.

The use of serial CA 125 concentrations to monitor endometriosis in infertile women.

To evaluate the potential use of CA 125 concentrations in monitoring women with endometriosis, serial determinations were correlated with the clinical course of the disease and pregnancy rates. Preoperative CA 125 concentrations were obtained in 134 consecutive infertile women with endometriosis. Seventy-six (57%) women had values greater than or equal to 16 U/ml and were followed up for 18 months. At the 6-, 12-, and 18-month intervals, pregnancies occurred in 18 of 45 (30%), 14 of 24 (58%), and 5 of 12 (42%) women in the good prognosis group, respectively; pregnancy rates in the poor prognosis group were 1 of 31 (3%), 2 of 33 (6%), and 0 of 26 (0%) women (p less than 0.001). Changes in the CA 125 values correlated with the surgical findings in 24 of the 26 women (92%) who had a second-look operative procedure. The study supports the use of serial CA 125 concentrations to assist in the management of women with endometriosis.

CA-125 in women with endometriosis.

The serum CA-125 level is elevated in most women with endometriosis. Although tests are readily available to measure the marker, simple modifications of the present assays are required to improve and standardize the quality of the measurements. The serum test has low sensitivity and would not be appropriate for general screening purposes, but in clinical situations that have a relatively high prevalence of endometriosis, CA-125 determinations have acceptable sensitivities and very high specificities. The concentrations of CA-125 correlate with both the severity and the clinical course of the disease. In women with diagnosed endometriosis, use of serial CA-125 determinations to monitor the course of the disease shows much promise in early studies. The changes in the CA-125 levels can offer additional information to the clinician about the status of the endometriosis, but how much this information will assist in the management and improve the outcome of treatment must await the results of prospective studies.

Assay characteristics of the immunoradiometric method for CA-125.

A nonlinear standard curve for the immunoradiometric method for determining CA-125 may result in an overestimation of values below 20 U/ml. Since the modification of the assay as described in the report eliminates the problem, we propose the use of this simple modification when using CA-125 determinations for evaluating women with endometriosis.

Serum CA-125 in women with endometriosis and chronic pelvic pain.

Since serum CA-125 concentrations are increased in women with endometriosis, the authors evaluated CA-125 levels to determine whether this serum test would be useful in differentiating between pelvic pain due to endometriosis and other causes. During a 30-month period, 163 women who had had pelvic pain for at least 3 months had a CA-125 level obtained prior to surgery. Serum CA-125 was measured by an immunoradiometric assay. Of the 82 women with endometriosis, 66 (80%) had CA-125 concentrations greater than or equal to 16 U/ml (95% upper limit). The frequencies of elevated levels in minimal, mild, moderate, and severe endometriosis were 52, 86, 100, and 100%, respectively. Of the 81 women without endometriosis, 5 (6%) had elevated concentrations. With the use of serum CA-125 determinations for the detection of endometriosis, the sensitivity was 80%, the specificity was 94%, and the accuracy was 93% when the prevalence of endometriosis was 50%. The authors conclude that determination of CA-125 levels may assist in the evaluation and treatment of women with chronic pelvic pain.

Spontaneous abortions in women with endometriosis.

Pregnancy outcomes were evaluated retrospectively in 350 women to investigate the relationship between endometriosis and spontaneous abortions. The frequency of spontaneous abortions in women with endometriosis was significantly higher than in both a fertile nonendometriosis group and an infertile group with tubal disease. There was no correlation between the severity of the endometriosis and the frequency of spontaneous abortions. After treatment, the frequency of spontaneous abortions was significantly decreased in both the endometriosis and the tubal disease group, but these values were not significantly different from each other. We conclude that high spontaneous abortion rates are a characteristic of other subgroups of women with secondary infertility and not just in women with endometriosis, and that the majority of spontaneous abortions associated with endometriosis are not caused by the condition.

Preclinical abortions and endometriosis.

A single human chorionic gonadotropin determination was performed in 786 infertile women during the late luteal phase to determine the frequencies of preclinical abortions and whether the frequency was increased in women with endometriosis. Thirty-seven pregnancies (4.7% of cycles) were identified, of which six were classified as preclinical abortions (0.8%). In women with endometriosis, the frequency of preclinical abortions was 0.9% and was not statistically different from other infertile subgroups. This study suggests that preclinical abortions are not cause of infertility in either an infertile population as a whole or in the subgroup of women with endometriosis.

Correlation of an enzyme immunoassay with the radioimmunoassay for CA-125.

Serum CA-125 concentrations from 60 women were determined by radioimmunoassay and an enzyme immunoassay. Correlation of the CA-125 values obtained by the two methods indicated a linear relationship between 13 and 73 U/ml, lower values in the enzyme immunoassay, and a lower sensitivity of the enzyme immunoassay as compared with the radioimmunoassay.

Serum CA-125 in the evaluation of benign adnexal cysts.

Because serum CA-125 concentrations are increased in women with endometriosis, our objective was to determine whether CA-125 levels could be used to differentiate endometriotic from nonendometriotic benign cysts. During a 2-year period, all women who had an endometrioma (n = 33) or a nonendometriotic cyst (n = 27) that was greater than or equal to 4 cm were included. Serum CA-125 levels were measured by an immunoradiometric assay, and the mean concentrations in women with an endometriotic cyst increased as the diameter of the cyst increased. The mean CA-125 concentrations in women with cysts greater than or equal to 4 cm were 53 +/- 2 U/ml in 19 women with an endometriotic cyst, 11 +/- 1 U/ml in 20 women with a nonendometriotic cyst, and 15 +/- 1 U/ml in 7 women with a nonendometriotic cyst and endometriosis. In the fluid of 10 endometriomas, the mean CA-125 concentration was 290 +/- 94 X 10(3) U/ml (range 10 to 900 X 10(3) U/ml). With cysts diameters greater than or equal to 4 cm, 19 of 19 women with endometriotic cysts, zero of seven women with nonendometriotic cysts and endometriosis, and zero of 20 women with nonendometriotic cysts had CA-125 concentrations greater than or equal to 20 U/ml (99% upper normal limit). We conclude that serum CA-125 determinations offer an excellent method to differentiate endometriotic from nonendometriotic benign cysts.

Serum CA-125 antigen levels increase during menses.

Serum CA-125 antigen levels were measured by radioimmunoassay before and during menses in women with and without endometriosis. Mean CA-125 levels were significantly increased in both groups during menses. Samples obtained during menses represent a potential source of elevated levels and false positive results.

Ureteral abnormalities in women with endometriosis.

High-volume intravenous urography was performed in 63 women with surgically proven endometriosis. Subtle abnormalities were found in 15.9% of these women. No patient had urologic symptoms, and there was no evidence of hydroureter or ureteral obstruction on the IVP. Long-term follow-up study will be required to determine whether or not these lesions will progress and cause ureteral obstruction.