John R. Brumsted

A randomized, controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility or surgically corrected endometriosis

This study was initiated to test the hypothesis that treatment with clomiphene citrate (CC) and intrauterine insemination (IUI) results in increased fecundity when compared with periovulatory intercourse in couples with either unexplained infertility or surgically corrected endometriosis. Sixty-seven couples entered a randomized, prospective trial comparing CC/IUI with observation. During the study, there were 14 pregnancies in 148 treated cycles (fecundity = 0.095) compared with 5 pregnancies in 150 untreated cycles (fecundity = 0.033). Using life-table analysis and the log-rank test, the difference in fecundities was statistically significant. Pregnancy outcome was not significantly different between the two groups. When comparing conception with nonconception cycles during treatment, no differences between the size of the lead follicle or the number of dominant follicles was detected. We conclude that treatment with CC/IUI improves fecundity in couples with unexplained infertility or surgically corrected endometriosis.

Efficacy and safety of single-dose systemic methotrexate in the treatment of ectopic pregnancy

OBJECTIVE To evaluate the safety and efficacy of single-dose systemic methotrexate (MTX) in the treatment of ectopic pregnancy (EP). DESIGN A database was started and continued prospectively for 35 patients meeting criteria for MTX therapy from June 1991 to October 1993. Follow-up was performed retrospectively on all patients with EPs (n = 82) by evaluating hospital and clinic records and by contacting affiliated physicians and individual patients. SETTING The University of Vermont Reproductive Endocrinology Service. INTERVENTIONS Methotrexate 50 mg/m2 was administered IM; blood samples were collected on days 0, 4, and 7 of MTX therapy and weekly thereafter until hCG titers became < 4 mIU/mL. RESULTS Thirty-five of 82 (42.7%) patients diagnosed with EP were treated with MTX. The mean hCG concentration on day of treatment was 1388.1 +/- 463.5 (+/- SE) mIU/mL, and mean time to complete resolution of hCG was 23.1 +/- 2.9 days. Thirty of 35 (85.7%) were successfully treated with a single dose of MTX. Five of 35 (14.3%) failed therapy and required laparoscopic surgery. Twelve of 35 (34.3%) experienced mild side effects that resolved spontaneously. Ten of 13 (76.9%) demonstrated tubal patency at follow-up hysterosalpingogram. Of the 15 patients seeking pregnancy, 3 of 15 (20.0%) conceived, resulting in 3 term deliveries and 2 spontaneous abortions. CONCLUSIONS Our results support the use of single-dose systemic MTX for the treatment of unruptured EP in carefully selected patients.

Septate uterus with cervical duplication: a rare malformation

This previously unreported case of complete uterine septum, cervical duplication, and a longitudinal vaginal septum is best explained by the theory of Muller et al. (5), not by classically held views of unidirectional müllerian development. According to their theory, this anomaly could develop from failure of fusion of the most caudad müllerian ducts, resulting in a normal uterine fundus, with a complete septum, cervical duplication, and a longitudinal vaginal septum. This anomaly was accurately characterized using an endoscopic approach.

Color flow pulsed Doppler ultrasound in diagnosing luteal phase defect.

OBJECTIVE To determine whether color flow pulsed Doppler analysis of corpus luteum blood flow in normal cycles differs from cycles with a luteal phase defect. DESIGN A prospective study of natural ovarian cycles. SETTING The University of Vermont Reproductive Endocrinology and Infertility Service. PATIENTS Ten women with regular menstrual cycles and at risk for luteal phase defect (LPD) four with unexplained infertility, two with recurrent abortion, and four with age > 35 years. INTERVENTIONS All women were examined by transvaginal color flow pulsed Doppler during the early follicular, late follicular, early luteal, midluteal, and late luteal phase of the menstrual cycle. Venous blood for P concentration was drawn on each day of Doppler exam. Urine testing for LH surge and endometrial biopsy during the late luteal phase were performed on each patient. MAIN OUTCOME MEASURES Lowest resistance index associated with the highest amplitude signal from intraovarian vessels of each ovary, dated endometrial biopsies, serum P. RESULTS Mean resistance indexes in LPD patients (n = 3) were significantly higher compared with normal women (n = 6) throughout the follicular and luteal phases. One patient remained anovulatory and was excluded from statistical analysis. Although systolic and diastolic velocities generally were observed to be lower in LPD patients compared with normal women, these differences were not statistically significant. High correlations were observed between P and resistance index within each luteal time point, achieving its highest value during the midluteal phase. CONCLUSIONS This initial study provides evidence that color flow pulsed Doppler analysis of blood flow impedance to the corpus luteum may aid in assessing luteal phase adequacy.

Attempted transcervical occlusion of the fallopian tube with the Nd:YAG laser

A prospective multi-center trial was initiated to test the efficacy and safety of transcervical occlusion of the fallopian tube with the Nd:YAG laser. A multi-center approach was deemed necessary because of the large sample size required to test adequately the effectiveness of sterilization procedures. However, efforts to continue the study as designed were abandoned because, of the 17 subjects completing the study, only four (24%) had bilateral tubal occlusion at the site of laser treatment. We conclude that the hysteroscopic method, as tested, is inadequate to provide permanent sterilization. Modification of the technique or alterations in patient preparation may improve the outcome.

Transvaginal ultrasonographic assessment of Hyskon or lactated Ringer's solution instillation after laparoscopy: randomized, controlled study.

We sought to evaluate two common fluids placed in the pelvis after pelvic surgery for their ability to remain in the pelvis for a time thought adequate for prevention of adhesions. Thirteen patients undergoing operative laparoscopy were randomized to receive 250 ml 32% dextran 70 (Hyskon), 250 ml lactated Ringers solution, or no fluid (control) at the end of surgery. Serial transvaginal ultrasonograms were obtained at 1 hr, 3 hr, 6 hr, 24 hr, 96 hr (4 days), and 168 hr (7 days) after surgery. Patients were asked about side effects of fluid instillation. The volume of lactated Ringers solution declined rapidly after instillation, with no significant difference from control at 24 hr (12 ml versus 7 ml). The volume of Hyskon did not decline rapidly by 24 hr and remained higher than the volume in controls or those receiving lactated Ringers solution (188 ml, P = 0.003). Although the volume of Hyskon remained higher than that of lactated Ringers solution or fluid volume in control patients by days 4 and 7, this difference did not reach statistical significance (45 ml versus 7 ml and 14 ml respectively, P = 0.39, on day 4). Patients in all groups noted abdominal pain. One patient who received Hyskon developed severe vulvar edema and another developed dyspnea. We conclude that the volume of Hyskon in the peritoneal cavity after laparoscopy does not decline as rapidly as does that of lactated Ringers solution; however, significant side effects may limit its usefulness. Transvaginal ultrasonography is useful in monitoring fluids placed in the pelvis for prevention of adhesions.

The association of intrauterine filling defects on hysterosalpingogram with endometriosis

OBJECTIVE To determine whether there is a significant association between the presence of polyps or polypoid endometrium on hysterosalpingogram (HSG) with the presence of pelvic or peritoneal endometriosis. DESIGN Retrospective chart review. SETTING Department of Reproductive Endocrinology and Infertility at the University of Vermont, College of Medicine. PATIENTS One hundred twenty patients, all of whom had a HSG, hysteroscopy, and laparoscopy by a member of our department between 1989 and 1993. MAIN OUTCOME MEASURE Hysterosalpingograms were assessed for the presence of hypertrophic or polypoid endometrium. The presence of endometriosis was documented laparoscopically and scored according to The American Fertility Society classification and HSG findings were documented by hysteroscopy. RESULTS Endometriosis was found in 27 of 32 women with polyps or polypoid endometrium but in only 19 of 88 women without. chi 2 analysis revealed a significant association between the demonstration of polyps or polypoid endometrium on HSG and the presence of endometriosis, chi 2(1) = 33.97. The predictive value of a positive test was 84% and the negative predictive value was 75%. CONCLUSION The presence of polyps or polypoid endometrium on HSG is significantly associated with the presence of pelvic or peritoneal endometriosis.

Diagnosis treatment of cornual obstruction using a flexible tip guidewire

Proximal tubal obstruction, either unilateral or bilateral, is a frequent finding on hysterosalpingogram (HSG). Approximately two-thirds of the fallopian tubes resected for proximal tubal obstruction reveal an absence of luminal occlusion. The distinction between true pathologic occlusion and either spasm or plugging is crucial in determining therapy. We combined hysteroscopic cannulation of the proximal fallopian tube with laparoscopy in 11 patients with proximal tubal obstruction diagnosed by HSG and confirmed at laparoscopy. Hysteroscopic cannulation was able to be performed in 72% of the fallopian tubes attempted, and there was a postcannulation patency rate by HSG of 73%. Six of the 11 patients became pregnant after tubal cannulation and adjunctive distal tubal surgery. Hysteroscopic cannulation of the fallopian tube is a safe diagnostic procedure that can be used to identify those patients with true proximal occlusion, and may also serve as a therapeutic procedure in some of these patients.

Reproductive outcome after tubal reversal in women 40 years of age or older

OBJECTIVE To determine the reproductive outcome of women who received a microsurgical tubal anastomosis operation at age 40 years or older. DESIGN Multicenter retrospective cohort study. SETTING Four university teaching hospitals. PATIENTS Fifty-two women having undergone tubal sterilization reversal at age > or = 40 years. MAIN OUTCOME MEASURES Pregnancy and live birth rate. RESULTS Of the 52 women, 10 were lost to follow-up. Of those traced, 18 of 42 (42.8 percent) conceived. Of those 18, 6 patients had a live birth, 10 patients had a first trimester spontaneous abortion, 1 patient had an ectopic pregnancy, and 1 patient had an elective termination. Overall, the live birth rate was 14.3 percent, spontaneous abortion rate was 23.8 percent, and ectopic pregnancy rate was 2.4 percent. CONCLUSIONS Microsurgical tubal anastomosis is a justifiable alternative to IVF-ET in women age 40 years or older.

Angiotensinogen genotype and plasma volume in nulligravid women

Objective To determine if nonpregnant plasma volume is altered in women who are homozygous for the T 235 coding angiotensinogen allele, which predisposes women to an increased risk of preeclampsia. Methods We measured plasma volume by Evans blue dilution and analyzed it as a function of angiotensinogen genotype in 15 nulligravid women during midfollicular phase of 26 menstrual cycles. Eleven women were evaluated during two cycles, and four women were evaluated in one cycle. Fourteen women were white, and one was Asian. No subjects had illnesses or were taking medication. The range of body mass index (BMI [kg/m2]) was 20.2-31.0. Plasma volume (mL) was reported as plasma volume divided by BMI to control for variations in body sizes. Statistical analysis was performed by analysis of variance with post hoc testing using Fisher least significant difference test for multiple comparisons (P < .05 accepted for significance) Results Angiotensinogen genotype analysis showed five women homozygous for M 235, three women homozygous for T 235, and seven women who were heterozygous (MT 235). T 235 homozygotes had significantly lower plasma volume divided by BMI compared with women who were homozygous for M 235 and women who were heterozygous for MT 235 (mean 1 standard deviation [SD] [71.2 + 8.8, 86.6 + 5.2, 95.8 + 15.6, respectively, P < .05]). There was a tendency toward higher plasma volume in heterozygote MT 235 compared with homozygote M 235 carriers, but it was not statistically significant. Conclusion We conclude that the homozygous T 235 coding angiotensinogen genotype is associated with reduced plasma volume in nulligravid women during the follicular phase of the menstrual cycle compared with M 235 homozygotes and heterozygotes. This association of the T 235 coding genotype might contribute to fetal growth restriction in preeclampsia.