Deficient 17 beta-hydroxysteroid oxidoreductase activity in testes from a male pseudohermaphrodite.

17beta-Hydroxysteroid oxidoreductase (17 beta-HOR) activity in testicular tissue from a male pseudohermaphrodite (MP) who had elevated plasma LH and androstenedione (A) levels, and normal dehydroepiandrosterone (DHA) levels was compared by in vitro studies to that of testicular tissue from a normal man. The 17 beta-HOR activity from the MP was localized predominantly in the microsomal fraction, as it is in normal testicular tissue. With DHA, A, and estrone as substrates, the 17 beta-HOR activity of the MP was decreased in the presence of NADPH, but not NADH, in comparison with the normal. NADPH was the preferred co-factor for 17 beta-HOR from the normal testes, while 17 beta-HOR activity from the MP testes was less with NADPH than with NADH as cofactor. These results indicate that the inefficient testosterone production in the MP testes may be accounted for by a deficiency of NADPH-dependent 17 beta-HOR activity. Further studies suggested that 3 beta-hydroxysteroid oxidoreductase-isomerase (3 beta-HOR) was increased in the MP testes and was much greater than 17 beta-HOR activity with DHA as substrate. These findings largely explain the elevated plasma A levels with normal DHA levels, and suggest that DHA leads to A leads to testosterone was the major route of testosterone biosynthesis in the MP testes.

Human ovarian 17 beta-hydroxysteroid oxidoreductase activity: a comparison of normal and polycystic ovarian tissues.

Ovarian tissue and ovarian venous blood were obtained from women undergoing wedge resection, and ovarian tissue was obtained from normally menstruating women who had an oophorectomy for medical reasons. A morphological evaluation was made of the wedged tissue. 17 beta-Hydroxysteroid oxidoreductase levels were determined as the 17-ketoreductase (17-KR) and 17 beta-dehydrogenase activities in both normal and wedged tissue. Plasma androstenedione (A) and testosterone (T) levels were measured in the ovarian venous blood. Low, but measurable, 17 beta-hydroxysteroid oxidoreductase activity was found in the mitochondria, microsomes, and cytosol. With whole, cell-free homogenates, mean 17-KR activity was not significantly different in normal tissues and polycystic tissues; mean 17-KR activity of corpora lutea was significantly greater than that of the other tissues. Mean 17 beta-dehydrogenase activity was not significantly different from 17-KR activity in the tissues studied. Ovarian venous A levels were higher than the reported mean ovarian venous A levels of normal women with only one exception; approximately half of the ovarian venous T levels were higher than reported mean ovarian venous T levels of normal women. The morphology of the wedge sections did not correlate well with the biochemical data.

Appendectomy in the surgical treatment of endometriosis.

To address the question of when to perform an appendectomy in the surgical treatment of endometriosis, a series of 500 consecutive appendectomies was reviewed. In 104 patients with pelvic endometriosis who were undergoing appendectomy, the appendix was a relatively common (13%) extragenital site of endometriosis. Gross inspection of the appendix is not sufficient to exclude endometriosis, as 38% of appendices with histologic evidence of endometriosis had a normal appearance. Patient age and the severity of endometriosis do not appear to be risk factors for appendiceal involvement. No increased postoperative morbidity was demonstrated in 65 patients who had an appendectomy when compared with a similar group of 60 patients who did not have an appendectomy. The study supports 1) removal of the appendix in patients undergoing noninfertility surgery for endometriosis, as a high prevalence of occult endometriosis was observed in this group; and 2) excision of an abnormal appendix in patients with endometriosis during infertility surgery although appendectomy for occult involvement is not supported in this group.

Familial male pseudohermaphroditism with incomplete virilization.

A 21-year-old 46 XY individual with familial male pseudohermaphroditism was investigated. Phenotype consisted of pseudovaginal perineoscrotal hypospadias with bilateral inguinal gonads and a masculine habitus without gynecomastia. Plasma testosterone, cortisol, follicle stimulating hormone, urinary 17-ketosteroids, and 17-ketogenic steroids were within the normal male range. Plasma dihydrotestosterone was at the lower limit of the normal male range. Plasma luteinizing hormone was three times and plasma estradiol was about one and a half times the upper limit of normal for men. These results are consistent with a partial defect in the mechanism of action of testosterone. The differential diagnosis of various forms of male pseudohermaphroditism is discussed.

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.

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.

Evaluation of early pregnancy by serial chorionic gonadotropin determinations: a comparison of methods by receiver operating characteristic curve analysis.

Two methods of evaluating early pregnancies by serial human chorionic gonadotropin (hCG) determinations were evaluated by receiver operating characteristic (ROC) curve analysis. The first method used normal values (mean and upper confidence limits) of the hCG doubling time (DT) determined by a linear regression analysis of hCG concentrations from 35 normal pregnancies during the first 42 postmenstrual days. In the second method, normal values were determined at multiple sampling ranges of hCG concentrations from 49 normal pregnancies. In the evaluation of 91 pregnancies of which 58 progressed to viability, 25 spontaneously aborted, and 8 were ectopic gestations, the ROC curves demonstrated that for any given false-positive rate, the use of multiple normal values of DT was more sensitive than the use of a single mean DT determined by linear regression analysis. The study indicates that a more precise definition of the normal values of the hCG-DT results in improved early detection of abnormal pregnancies.

The use of CA-125 in the diagnosis and management of endometriosis.

CA-125, a cell-surface antigen, was measured by a radioimmunoassay in the serum of 414 women to determine its potential usefulness in the diagnosis and management of endometriosis. In women with minimal, mild, moderate, and severe endometriosis, the mean levels (+/- standard deviation) were 13.6 +/- 6.8, 22.8 +/- 15.5, 27 +/- 17, and 50 +/- 28 U/ml, respectively, and were significantly higher than mean levels (7.8 +/- 4.1) in 46 women with a normal laparoscopic examination. Higher mean CA-125 values also were observed in acute pelvic inflammatory disease, unexplained fertility, and pregnancy and during menstruation. The mean CA-125 value in women with treated endometriosis and a negative second-look laparoscopy was significantly lower than in women with untreated endometriosis. With the use of the 95% upper limit of 16 U/ml, the test had a sensitivity of 53% and specificity of 93%. The frequencies of elevated levels in minimal, mild, moderate, and severe endometriosis were 27%, 68%, 73%, and 100%, respectively. Changes in the CA-125 levels correlated with the clinical course of endometriosis in 37 of 44 (84%) women (P less than 0.001). The determination of CA-125 levels may assist in the evaluation and treatment of women with endometriosis.

Evaluation of the exponential rise of serum estradiol concentrations in human menopausal gonadotropin-induced cycles.

To determine whether the rate of the exponential rise of estradiol (RER-E2) may be useful in monitoring gonadotropin-induced cycles and have prognostic value with respect to pregnancy, the RER-E2 was evaluated in 70 ovulatory cycles of 25 women. Semilogarithmic plots of E2 concentrations (picograms per milliliter) versus time (days) were linear, with slopes (RER-E2) ranging from 0.18 to 0.74. The mean RER-E2 in the 14 cycles of conception (0.49 +/- 0.03; +/- standard error) was not significantly different from the mean (0.47 +/- 0.02) in 56 cycles in which pregnancy did not occur. The mean of the RER-E2 of three twin pregnancies (P less than 0.02) and of three pregnancy losses (P less than 0.01) were significantly higher than the mean of nine singleton pregnancies. There was a lower pregnancy rate at the lower range of RER-E2 and a higher frequency of twin pregnancies and pregnancy losses at the upper range, but these trends were not statistically significant. By a graphic method, subsequent E2 values were predicted in 25 of 28 cycles within the 95% confidence limits and a clinically acceptable range of actual E2 values. The semilogarithmic plots appear to be useful adjuncts in the monitoring of gonadotropin-induced cycles. Although the data suggest that the RER-E2 may have prognostic value, further study is needed to confirm these observations.

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.

Ovarian surgery in an infertility patient as an indication for a short-interval second-look laparoscopy: a preliminary study.

The usefulness of a short-interval second-look laparoscopy (SLL) after ovarian surgery was examined. In 23 infertile women who had either bilateral wedge resection (BWR) of polycystic ovaries, an oophorocystectomy (OC), or resection of endometriomata (RE), adhesions were graded before and after surgery and before and after laparoscopic lysis for each ovary. At SLL, periovarian adhesions involving at least one ovary were observed in all women. Of the 22 women who wanted to become pregnant, 3 of 3 with BWR, 1 of 3 with OC, and 6 of 16 with RE conceived. In the women with residual adhesive disease in both or the only remaining adnexa after SLL, there were no pregnancies; whereas 67% of the women with at least one adnexa free of disease became pregnant (P = 0.005). This preliminary study indicates that ovarian surgery does result in significant adhesion formation and that SLL offers an opportunity to reassess the pelvis, to lyse adhesions, and to establish a postoperative prognosis.

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 role of laparoscopic adhesiolysis in an in vitro fertilization program.

Adhesiolysis was evaluated in 82 women who had 129 laparoscopies for in vitro fertilization and embryo transfer (IVF-ET). Fifty-five women (67%) had lysis during the first laparoscopic attempt, and 20 of the 129 laparoscopies (16%) required lysis for identification and aspiration of follicles. In 11 women who had a second laparoscopy, 69% of the ovaries had improved access. With the use of laparoscopic lysis, only 3 of 82 women (4%) had insufficient ovarian access, preventing recovery of at least one oocyte. The findings support the efficacy of laparoscopic adhesiolysis and indicate that it has an important role in a program of IVF-ET in assuring initial access for oocyte recovery and in improving access for subsequent attempts.

Spironolactone in combination drug therapy for unresponsive hirsutism.

Clinical and laboratory evaluations of nine hirsute women were performed for determination the efficacy of combination drug therapy. Each patient had previously failed to respond to single drug therapy with oral contraceptives (OC), dexamethasone (DEX), or spironolactone (S) and received S (100 to 150 mg) and either an OC (mestranol, 0.05 to 0.08 mg, and norethindrone, 1 mg) or DEX (0.5 mg) daily. Total testosterone, dehydroepiandrosterone sulfate, free testosterone, and sex-hormone-binding globulin were measured before therapy and 4 to 6 weeks after initiation of therapy and were compared with the responses to OC (n = 7), DEX (n = 8), and S (n = 6). A satisfactory clinical response in the rate of hair growth was defined as at least a doubling of the time interval between adjunctive therapies (electrolysis, shaving, or bleaching) and patient satisfaction with treatment. The responses of the androgenic parameters were not statistically different between combination and single drug therapy. Although all patients noted a subjective improvement in hair growth, eight of nine fulfilled the criteria for a clinical response (P less than 0.001). Transient diuresis was the only side effect noted. The study suggests that combination drug therapy is an efficacious and well-tolerated approach to the management of unresponsive hirsutism.

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.

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.

A comparison of the CO2 laser and electrocautery on postoperative intraperitoneal adhesion formation in rabbits.

The effect of the CO2 laser and microelectrocautery on postoperative intraperitoneal adhesions was examined in 31 female rabbits. Standard injuries were performed and/or repaired with each technique on the uterine peritoneum, the right uterine horn, and the left ovary. The animals were sacrificed 5 weeks later, and the adhesions were graded at each site. No significant differences were found between the two techniques for each site or all sites collectively (P greater than 0.05). The ovary had more extensive adhesions than the other soft tissue site (P less than 0.01) with both techniques. The present study suggests that there is no apparent difference between CO2 laser and conventional microelectrocautery on adhesion formation, and that the ovary seems particularly prone to adhesion formation with either technique.