The number of embryos available for transfer predicts successful pregnancy outcome in women over 39 years with normal ovarian hormonal reserve testing.

PURPOSE: The purpose was to determine whether the number of embryos available for transfer following IVF in women over age 39 predicted a successful pregnancy outcome. METHODS: Retrospective analysis of 455 consecutive IVF cycles in women > or = 40 years of age. RESULTS: Few cycles were canceled (29/455, 6.4%) or produced no embryos (5/455, 1.1%). Women 40-43 years of age with normal ovarian reserve had a significantly greater delivery rate when > or = 4 embryos were available for transfer than when < 4 embryos were available (17.8% versus 2.4%, P = 0.002). Subsequent IVF cycles, from women with normal FSH whose first cycle produced < 4 embryos, produced delivery rates of 13.0% when > or = 4 embryos were available. Women with abnormal ovarian reserve or age > or = 44 years had very low delivery rates (1.2% and 1.4% respectively). CONCLUSIONS: The number of embryos available for transfer significantly predicts delivery from IVF-ET among reproductively older women. Many women age 40-43 with normal ovarian reserve can achieve pregnancy through IVF.

Screening for hypothyroidism in infertile women.

OBJECTIVE: To determine the frequency of an elevated thyroid-stimulating hormone (TSH) level in 704 patients seeking treatment for infertility. STUDY DESIGN: Sera from 704 women evaluated for infertility were assayed for TSH levels using radioimmunoassay (normal, 0.45-4.09 mIU/mL). All women had at least one year of infertility. Women with a known history of thyroid disease were excluded from the review. RESULTS: Sixteen of 704 patients (2.3%) had elevated TSH levels and were treated with levothyroxine to normalize TSH. None of these women had overt clinical signs or symptoms of hypothyroidism. Of these women, 11 of 16, or 69%, had ovulatory dysfunction, and 7 (64%) later became pregnant while on thyroid replacement. Five of 704 (0.7%) women with infertility who presented without a history of ovulatory dysfunction had elevated TSH levels, and none became pregnant with treatment. CONCLUSION: The prevalence of elevated TSH in 704 women with at least one year of infertility was 2.3%. The majority of women diagnosed with hypothyroidism (11 of 16, or 69%) had ovulatory dysfunction. With treatment for hypothyroidism, successful pregnancies resulted in 7 of 11 (64%) of patients. Women with infertility and ovulatory dysfunction should be screened for hypothyroidism. Screening for hypothyroidism as part of a routine infertility workup in women with normal ovulatory function will yield few abnormal tests.

A randomized, double-blinded trial of preemptive analgesia in laparoscopy.

OBJECTIVE: We tested the hypothesis that local anesthetic administered before skin incision, an example of preemptive analgesia, reduces postoperative pain for women undergoing laparoscopy, as compared with postincisional local anesthetic or placebo. METHODS: Patients undergoing diagnostic laparoscopy were randomized to one of three blinded treatment groups. Treatment group A patients received local infiltration of 0.5% bupivacaine at the surgical site before incision and a saline placebo infiltration before incision closure. Treatment group B received the saline placebo before skin incision and bupivacaine after laparoscopy but before closure of the skin incisions. For treatment group C patients, saline was infiltrated as a placebo before and after laparoscopy. All patients underwent a standardized general anesthetic induction and maintenance. Postoperative pain was evaluated using the modified McGill Present Pain Intensity scale. Pain and supplementary analgesic use was compared among the three treatment groups. RESULTS: A total of 57 patients completed the study for analysis. Age, weight, height, race, indication, and operating time did not vary significantly between the three groups. By 24 hours after surgery, patients in treatment group A reported significantly lower pain scores (McGill Present Pain Intensity Scale: 0.5+/-0.9) than either treatment group B (1.6+/-1.3) or C (1.3+/-1.2). Group A patients also could tolerate a significantly longer time delay to their first analgesic medication than patients who received postincisional bupivacaine or than control patients who received no bupivacaine. CONCLUSION: The preemptive administration of bupivacaine before laparoscopy results in decreased postoperative pain and should allow a more rapid return to normal activities. The popular practice of infiltrating bupivacaine at time of incision closure does not offer any benefit in the control of pain after laparoscopy.

Extended clomiphene citrate (CC) and prednisone for the treatment of chronic anovulation resistant to CC alone.

OBJECTIVE: To evaluate effectiveness and safety of a regimen of extended clomiphene citrate (CC) and prednisone for patients who fail treatment with CC alone. DESIGN: Retrospective observational analysis. SETTING: University-based tertiary infertility center. PATIENT(S): Twenty-four anovulatory patients who failed to ovulate after CC 150 mg administered for 5 days. INTERVENTION(S): Treatment consisted of CC given on cycle days 3 through 9 (extended) at a starting dose of 100 to 150 mg/d. Additionally, patients were given prednisone 5 mg orally each night throughout the cycle. MAIN OUTCOME MEASURE(S): Ovulation was confirmed by luteal serum P. Pregnancy was confirmed by rising hCG levels and transvaginal ultrasound. RESULT(S): A total of 60 cycles were available for review. Forty-four of these cycles were ovulatory (73%) and 11 patients (46%) conceived on this therapy. Logistic (two-parameter) pregnancy occurrence over time (cycles) revealed a maximum pregnancy probability of 0.66 and a cycle fecundity of 0.36. No complications of therapy were noted. CONCLUSION(S): Clomiphene citrate-resistant anovulatory patients have high rates of ovulation and pregnancy after treatment with extended CC and prednisone. This therapy offers a potential reduction in cost and risk and should be considered in this group of patients before gonadotropin stimulation or surgery.

Maternal serum creatine kinase does not predict tubal pregnancy.

PURPOSE: Our purpose was to validate prospectively the predictive value of maternal serum creatine kinase in the evaluation of ectopic pregnancy. METHODS: Fifty-one consecutive pregnant first-trimester patients who presented for suspected abnormal pregnancy were enrolled. Maternal serum samples were obtained and assayed for creatine kinase. Patients were subsequently evaluated for abnormal pregnancy by serial quantitative hCG levels, transvaginal ultrasonography, and surgery when appropriate. A receiver operating characteristic (ROC) curve was generated comparing intrauterine to extrauterine (ectopic) pregnancy. RESULTS: Of 51 patients, 18 had an ectopic pregnancy, 16 had a spontaneous abortion, and 17 had an ongoing intrauterine pregnancy. The ROC curve revealed that maternal serum creatine kinase had no ability to predict ectopic pregnancy. CONCLUSIONS: Maternal serum creatine kinase is not a reliable predictor of tubal pregnancy.

Luteal phase consequences of low-dose gonadotropin-releasing hormone agonist therapy in nonluteal-supported in vitro fertilization cycles.

OBJECTIVE: To determine the follicular and luteal phase impact of low-dose GnRH agonist (GnRH-a) treatment during follicular stimulation for IVF. DESIGN: A randomized prospective study compared patients receiving low-dose GnRH-a and hMG therapy to clomiphene citrate (CC) and hMG cycles. SETTING: Patients were treated through a university-based IVF-ET program. PATIENTS: Thirty-six patients underwent follicular stimulation with low-dose GnRH-a and hMG and were compared with 34 patients undergoing ovulation induction with CC and hMG. RESULTS: Significantly shorter luteal phase length occurred with GnRH-a and hMG therapy; however, there was no statistically significant difference in luteal P levels. Follicular parameters were the same (peak E2, number of follicles, and number of oocytes), suggesting that folliculogenesis was not altered. There were no statistical differences in pregnancy rates. CONCLUSIONS: Sustained low-dose GnRH-a therapy during follicular stimulation does not have a clinical effect on luteal function.

A prospective study on the association between red hair color and endometriosis in infertile patients.

OBJECTIVE: To determine if red-haired infertile women have an increased prevalence of endometriosis. DESIGN: Prospective, nonblinded. SETTING: Large, metropolitan, private hospital, associated with a university. Subspeciality care provided by reproductive endocrinologists. PATIENTS: One hundred forty-three consecutive women undergoing laparoscopy or laparotomy for infertility. INTERVENTIONS: Laser ablation of any endometriosis present. MAIN OUTCOME MEASURE: Presence of endometriosis. RESULTS: Of 143 women entered into the study, 12 had natural red hair. The ages of these women ranged between 23 and 41 years. Ten of 12 (83%) of the red-haired women were found to have endometriosis compared with 55 of 131 (42%) of nonredheads. By statistical analysis, the 95% confidence intervals for the presence of endometriosis in redheads was 55% to 100% versus 34% to 51% for nonredheads. CONCLUSION: The results suggest an association between the occurrence of natural red hair and those factors that lead to the development of endometriosis.

Elevated luteinizing hormone on the day of human chorionic gonadotropin administration does not reduce cycle fecundity in a low-dose flare-up in vitro fertilization protocol.

OBJECTIVE: To determine if elevated LH at the time of hCG administration occurs and adversely affects success in a low-dose gonadotropin-releasing hormone analogue (GnRH-a) flare-up protocol in hMG-stimulated IVF cycles. DESIGN: Pearson correlation matrix analysis of hormonal, gamete, and clinical data derived from 203 consecutive IVF cycles was performed. All patients were treated with low-dose GnRH-a (250 micrograms SC leuprolide acetate) and hMG. In 203 consecutive IVF cases, serum was obtained on the day of hCG administration and assayed for E2, LH, and P. These data were correlated with peak E2, number of follicles, oocytes, embryos, and conceptions. Additionally, patients with elevated LH were compared with the nonelevated LH group. RESULTS: Twenty six women had LH > 35 mIU/mL (mean +/- SEM; 51.1 +/- 1.9) and five pregnancies (cycle fecundity 19.2% per retrieval). One hundred seventy-seven patients had LH < 35 mIU/mL (16.3 +/- 0.5) and 25 pregnancies (cycle fecundity 14.1%). There were no differences in the mean P (1.0 +/- 0.1 ng/mL, conversion factor to SI unit, 3.81) and E2 (1,672 +/- 144 pg/mL, conversion factor to SI unit, 3.671) of the former group compared with the P (1.1 +/- 0.07 ng/mL) and E2 (1,456 +/- 69 pg/mL) of the latter group. There was no correlation with the number of follicles, oocytes, embryos, pregnancies, E2, or P to LH concentration (rmax = 0.132). CONCLUSION: In a low-dose, GnRH-suppression, IVF induction protocol, elevated LH occurs in a small subset (13%) of women at the time of hCG administration. This event does not appear to alter cycle fecundity nor induce premature luteinization.

Progesterone concentration as a predictor of pregnancy normalcy is the most useful when hCG levels are less than 2000 mIU/mL.

OBJECTIVE: Measurements of serum progesterone to predict early gestational normalcy have been found to be as predictive as serial hCG titers. Since ultrasound would be the diagnostic tool of choice if hCG was > 2000 mIU/ml, the purpose of the present study was to determine the best predictive value of a single progesterone measurement when hCG levels were < 2000 mIU/ml. DESIGN: Relative operating characteristic analysis of progesterone level as a predictor of early gestational normalcy when hCG is < 2000 mIU/ml. MATERIALS AND METHODS: Ninety-three pregnant patients that conceived spontaneously were evaluated with progesterone measurements when the patient's hCG was < 2000 mIU/ml. Two-by-two contingency tables were constructed that compared pregnancy outcome with multiple discriminatory serum progesterone concentrations between 0 and 38 ng/mL. From these tables, a relative operating characteristic (ROC) curve was generated to compare the sensitivity and false-positive rates. RESULTS: Of a total of 93 pregnancies, 27 had a normal outcome and 66 had an abnormal outcome. The ROC curve indicated that a serum progesterone concentration of 12 ng/ml had the highest sensitivity associated with the lowest false-positive rate. The area under the curve was equal to 0.941 +/- 0.024. This observation was compared to our previously reported data of progesterone levels that included hCG levels > 2000 mIU/ml, yielding an area under the curve of 0.772 +/- 0.053. Calculation of the critical ratio z revealed that there is a significant improvement in the predictive value of progesterone when hCG is < 2000 mIU/ml (P < 0.005). CONCLUSION: A single serum progesterone level has a better predictive value of pregnancy normalcy when hCG measurements are < 2000 mIU/ml.

One artificial insemination per cycle with donor sperm is as efficacious as two inseminations.

PURPOSE: To compare pregnancy rates per treatment cycle of artificial inseminations with donor sperm in patients receiving one versus two inseminations. METHODS: Retrospective cross-sectioned analysis of 167 patients who underwent 869 cycles receiving one or two donor inseminations were reviewed from 1987 through 1993 at our institution. RESULTS: A total of 256 cycles with one donor insemination per cycle resulted in 21 pregnancies and a cycle of fecundity of 8.2%, and 613 cycles with two donor inseminations resulted in 35 pregnancies and a cycle fecundity of 5.7%. Life table and logistic cumulative probability analysis of pregnancy occurrence showed no difference between treatment groups. CONCLUSIONS: These data suggest there are no important clinical differences of cycle fecundity or cure rate in one versus two inseminations with donor sperm. Economic costs of two inseminations may not be justified.

Expression of functional human chorionic gonadotropin/human luteinizing hormone receptor gene in human uterine arteries.

The present study investigated 1) whether extra- and intramyometrial arteries contain hCG/human LH receptor messenger ribonucleic acid (mRNA) and receptor protein, 2) whether hCG can bind to its vascular receptors and regulate the formation of vasoactive eicosanoids, and 3) whether hCG administration for ovulation induction can affect the vascular resistance in uterine arteries. The uterine arteries contain multiple hCG/LH receptor mRNA transcripts in endothelial and smooth muscle cells. The uterine arteries also contain an 80-kilodalton immunoreactive receptor protein in endothelial and smooth muscle cells. The extra- and intramyometrial arteries and an 80-kilodalton receptor protein bind [125I]hCG, which is inhibited by excess unlabeled hCG. The receptor mRNA, receptor protein, and ligand binding are higher in smaller intramyometrial arteries than in larger extramyometrial arteries. Incubation of uterine arteries with highly purified hCG resulted in a dose-dependent increase in immunoreactive cyclooxygenase-1, cyclooxygenase-2, prostacyclin synthase, and 6-keto-prostaglandin-F1 alpha and a decrease in prostaglandin-E2, thromboxane-A2 synthase, and thromboxane-B2. There was a significant decrease in the resistance index in uterine arteries, but not in common carotid arteries, by 16 h after the administration of 10,000 IU hCG for ovulation induction in women. This decrease is positively correlated with serum hCG levels, but not with progesterone or estradiol levels. In summary, these data, demonstrating the expression of functional hCG/LH receptors in human uterine arteries, are novel and may have important implications for physiological uterine blood flow regulation, reproductive failure, and obstetrical hemorrhage.

Serum progesterone predicts abnormal gestations in clomiphene citrate conception cycles as well as in spontaneous conception cycles.

OBJECTIVE: To determine if a "discriminatory" P concentration could be established that predicted abnormal early pregnancies in clomiphene citrate (CC)-conceived cycles. DESIGN: Progesterone concentrations of gestations between 28 and 49 days from last menstrual period in both spontaneously conceived and CC-stimulated cycles were analyzed using a relative-operating characteristic (ROC) curve. INTERVENTIONS: Serum P concentrations were measured in 222 pregnant patients from the first 49 days of gestation. One hundred sixteen patients conceived in a spontaneous cycle and 106 patients conceived in CC-treated cycles. Two by two contingency tables were used to calculate the true-positive (sensitivity) and false-positive rates at 20 specific P at 20 specific P concentrations. A ROC curve was then generated by plotting the sensitivity of the test against the percent of normal patients incorrectly classified (false positive) at each P level. The best discriminatory value was estimated in each curve at a point of high sensitivity associated with a minimal false-positive value. The areas under the curve and SE were calculated for each group and compared by the critical ratio z-test. RESULTS: The best discriminatory P concentration was 10 ng/mL (32 nmol/L) for spontaneously conceived pregnancies and 30 ng/mL (95 nmol/L) for CC-treated pregnancies. The area under each ROC curve was significantly predictive. Comparison of the two curves indicated that the ability of P measurements to predict gestational complications was independent of follicular stimulation. CONCLUSIONS: Follicular stimulation with CC increases the discriminatory P value that predicts gestational normalcy but does not alter the clinical utility of the test.

Increased expression of human chorionic gonadotropin/human luteinizing hormone receptors in adenomyosis.

Adenomyosis is a benign disease in women in which myometrium is invaded by endometrial glands and stroma. Our laboratory recently demonstrated that normal human endometrial glands and stroma express the hCG/LH receptor gene. This prompted us to investigate whether invading glands and stroma in adenomyosis also express this receptor gene. Fifteen hysterectomy specimens with confirmed histological diagnosis of adenomyosis were examined for hCG/LH receptors by in situ hybridization and immunocytochemistry. The results showed that invading glands contained more receptor mRNA and receptor protein than noninvading glands in the same endometrium. However, the degree of difference between invading and noninvading glands varied among the patients. The higher receptor expression in invading glands is specific because the invading and noninvading stroma showed similar receptor expression, invading and noninvading glands showed similar expression of cadherin, a cell adhesion receptor, and ectopic and eutopic endometrial glands from endometriosis showed similar hCG/LH receptor expression. In summary, the present results demonstrate that invading endometrial glands in adenomyosis selectively express more hCG/LH receptor mRNA and immunoreactive receptor protein than noninvading glands. Whether this increased receptor expression is the cause or a consequence of myometrial invasion of glands in unknown.

The expression of human chorionic gonadotropin/human luteinizing hormone receptors in ectopic human endometrial implants.

Our laboratory previously demonstrated that normal human endometrium contains hCG/human LH receptors. Since ectopic endometrial implants in endometriosis arise directly at least in part from uterine endometrium, we investigated whether the implants continue the expression of these receptors. The presence of hCG/LH receptor mRNA and/or immunoreactive receptor protein in ectopic endometrial implants on pelvic peritoneum, uterine endometrium, and unaffected or normal peritoneum from patients with (n = 12) and without (n = 14) clinically apparent endometriosis was examined by in situ hybridization and immunocytochemistry analyses. The results showed that the peritoneal biopsies with visible or microscopic endometrial implants contain receptor mRNA and receptor protein. The glands contain more receptor mRNA and receptor protein than stromal cells in implants similar to uterine endometrium from patients with or without endometriosis. However, there is no consistent difference in the expression of receptors in implants compared to uterine endometria from patients with or without endometriosis. Contrary to ectopic endometrial implants, unaffected or normal peritoneum contain neither receptor mRNA nor receptor protein. In summary, we conclude that ectopic endometrial implants contain hCG/LH receptor mRNA and receptor protein, which suggests new possibilities in the medical treatment of endometriosis.