Sequential clomiphene citrate and human menopausal gonadotrophin with intrauterine insemination: the effect of patient age on clinical outcome.

The purpose of this investigation was to examine the influence of female and male patient age on pregnancy rates with sequential clomiphene citrate (CC) and human menopausal gonadotrophin (HMG) ovulation induction with intrauterine insemination (IUI) therapy after previous CC and IUI treatment failure. A total of 208 patients previously unable to conceive with CC/IUI therapy underwent 416 treatment cycles of sequential CC/HMG with IUI at a university fertility centre between May, 1991 and August, 1995. Clinical pregnancy rates, live birth rates, and the effect of female and male partner chronological age were retrospectively examined. Treatment with sequential CC/HMG with IUI resulted in clinical pregnancy rates ranging from 5.9 to 23.1% despite previous CC/IUI treatment failure. Clinical pregnancy rates, live birth rates, and cumulative pregnancy rates declined significantly in female patients > or = 35 years of age compared to those < 35 years of age. A statistically significant decline in clinical pregnancy rates could not be demonstrated as a function of increasing male partner age. Pregnancy rates in patients undergoing ovulation induction with sequential CC/HMG with IUI decline significantly with increasing female partner age.

Aromatase mRNA expression in individual follicles from polycystic ovaries.

Polycystic ovary syndrome (PCOS) is a common reproductive disorder characterized by arrested follicular development prior to selection of a dominant follicle. Dominant follicles produce large amounts of oestradiol but PCOS follicles do not. With several potential aromatase (P450AROM) inhibitors in follicular fluid, the question arises whether P450AROM is expressed in PCOS granulosa cells, but the activity is inhibited, or whether P450AROM is not expressed in PCOS. The purpose of the present study was to determine whether P450AROM mRNA expression is altered in PCOS and to correlate P450AROM mRNA expression in individual follicles with aromatase stimulatory bioactivity and oestradiol in the follicular microenvironments. P450AROM mRNA was measured in individual follicles from 16 PCOS and 48 regularly cycling control women by quantitative polymerase chain reaction (PCR) and correlated with follicular fluid oestradiol concentrations and aromatase stimulating bioactivity measured by the rat granulosa cells aromatase bioassay. Follicular fluid oestradiol was low in all control follicles <7 mm in diameter. Some follicles > or = 7 mm contained elevated oestradiol values (P < 0.01) and all had an androstenedione:oestradiol ratio of <4. Only in granulosa cells from follicles > or = 7 mm with an androstenedione:oestradiol ratio of <4 were P450AROM mRNA levels increased (P < 0.05). These same follicles also contained increased levels of aromatase stimulating bioactivity whereas follicles <7 mm or with androstenedione:oestradiol ratio of >4 contained little or no bioactivity. All PCOS follicles contained low levels of oestradiol, P450AROM mRNA and aromatase stimulating bioactivity similar to size-matched control follicles. These data indicate that P450AROM mRNA expression and oestradiol production begin in developing follicles when they reach approximately 7 mm in diameter. Oestradiol production is low in PCOS follicles because there is insufficient aromatase stimulating bioactivity to increase P450AROM mRNA expression.

Basal estradiol and follicle-stimulating hormone predict fecundity in women of advanced reproductive age undergoing ovulation induction therapy.

OBJECTIVE: To determine the prognostic value of single basal E2 and FSH levels as predictors of fecundity in women of advanced reproductive age who are undergoing ovulation induction with IUI therapy. DESIGN: Prospective, observational. SETTING: Fertility service of university medical center. PATIENT(S): Infertile couples in which the female partner was > or = 38 years old. INTERVENTION(S): Single assessment of basal E2 and FSH levels and ovulation induction with IUI. MAIN OUTCOME MEASURE(S): Cumulative and clinical pregnancy rates and live birth rates. RESULT(S): All live births occurred in patients with a basal E2 < or = 80 pg/mL (conversion factor to SI unit, 3.671), a basal FSH < or = 13 mIU/mL (conversion factor to SI unit, 1.00), and a chronological age < or = 42 years. In women 38 to 42 years of age, 10.3% had elevated basal E2 (> 80 pg/mL) in combination with normal basal FSH (< or = 13 mIU/mL), and no live births occurred in these couples. The cumulative live birth rate after four treatment cycles in women 38 to 42 years of age with both normal basal E2 (< or = 80 pg/mL) and FSH levels (< or = 13 mIU/mL) was 43.9%. CONCLUSION(S): Basal E2 improves the ability to predict fertility potential compared with basal FSH and chronological age alone. Basal E2, in combination with basal FSH and chronological age, has useful prognostic value in prospectively counseling patients of advanced reproductive age who are considering ovulation induction and IUI therapy.

Female and male partner age and menotrophin requirements influence pregnancy rates with human menopausal gonadotrophin therapy in combination with intrauterine insemination.

This study analyses the influence of female and male patient age and human menopausal gonadotrophin (HMG) requirements on clinical pregnancy rates and live birth rates with ovulation stimulation using HMG in combination with intrauterine insemination (IUI). In this study, 363 consecutive HMG/IUI treatment cycles in 184 patients carried out at a university fertility centre were analysed in a retrospective fashion. The main outcomes measured were clinical pregnancy rates and live birth rates. Increased female partner age (> or = 35) and male partner age (> or = 40) were found to negatively influence pregnancy rates with HMG/ IUI therapy. In addition, this study demonstrated a critical threshold of HMG requirements beyond which pregnancy did not occur. No pregnancies occurred in treatment cycles requiring > 25 ampoules (1875 IU) of menotrophins to achieve follicular maturity, irrespective of patient age. In conclusion, female partner age, male partner age, and HMG requirements all significantly influence pregnancy rates with HMG/IUI therapy.

Serum immunoreactive leptin concentrations in women with polycystic ovary syndrome.

Recent data in the mouse demonstrate that leptin, a protein hormone produced by fat cells, is required for fertility. In the absence of leptin the mice become obese, diabetic and infertile. Polycystic ovary syndrome (PCOS), a common cause of infertility in women, is associated with obesity and insulin resistance. Because of the increased frequency of PCOS in obese women we tested the hypothesis that alterations in serum leptin concentrations might be associated with PCOS. Immunoreactive leptin concentrations were measured in 58 women with PCOS and 70 regularly menstruating (control) women. As has previously been shown there was a positive correlation between leptin levels and body mass index (BMI). Although the leptin levels in the majority of women with PCOS fell within the control range, 29% of PCOS women had leptin levels above the 99% prediction interval for their BMI and none had low leptin levels. There were also positive correlations of leptin levels with free testosterone and insulin sensitivity in control women. In women with PCOS, 13% and 9.5% exhibited higher than expected leptin concentrations with respect to free testosterone and insulin sensitivity, respectively. Insulin resistant PCOS women had higher leptin levels than controls. The data demonstrate that a substantial proportion of women with PCOS have leptin levels that are higher than expected for their BMI, free testosterone and insulin sensitivity. These results suggest that abnormalities in leptin signaling to the reproductive system may be involved in certain cases of PCOS.

Laparoscopic surgical staging of stage I primary squamous cell carcinoma of the vagina.

Vaginal carcinoma is an uncommon malignancy and one of the few gynecologic malignancies that is still clinically staged. Clinical staging, which can be difficult in some instances, is potentially inaccurate, as it has been shown to be in early endometrial and ovarian carcinoma. In addition, clinical staging can result in over- or undertreatment of the disease. The lack of standardization of treatment further compounds the issue, particularly for patients with small-volume disease. We report three patients with grade 2 or 3 small-volume primary squamous cell carcinoma of the vagina who underwent pelvic lymph node sampling for staging purposes. Each patient had lesions small enough to be considered for brachytherapy only. An average of 12 lymph nodes were removed with an average operative time of 72 minutes. All procedures were performed on an outpatient basis, and there were no intraoperative or postoperative complications. In one patient, teletherapy was added to the brachytherapy because a microscopic focus of squamous cell carcinoma was discovered in an obturator lymph node. Our initial experience indicates that laparoscopic sampling of lymph nodes in patients with early vaginal carcinoma may be helpful in preventing undertreatment of these women. Individualization of treatment can be accomplished quickly and safely on an outpatient basis, and initiation of treatment is not delayed. We believe further evaluation of laparoscopic staging of primary vaginal carcinoma is indicated.

Laparoscopically assisted surgical staging (LASS) of endometrial cancer.

We report 59 patients who were considered candidates for laparoscopically assisted surgical staging (LASS) to manage their clinical stage I adenocarcinoma of the endometrium. Their ages ranged from 40 to 85 years, with a mean of 69; their weights ranged from 102 to 267 pounds, with a mean of 153 pounds. Patients with intraperitoneal disease were taken off study. Laparoscopic pelvic and para-aortic lymphadenectomies were performed based on the grade of the tumor and the depth of myometrial invasion. Six patients were discovered to have intraperitoneal disease. Of the remaining 53 patients, 29 underwent lymphadenectomy, 1 of whom had positive para-aortic nodes. Of the 24 patients who did not have laparoscopic lymphadenectomy, 2 should have, according to the study criteria; however, obesity precluded this from being performed. Eight patients had grade 3 lesions; of these, 4 lesions had metastasized. The remaining 3 patients with metastatic disease had grade 2 lesions. Complications were related to the laparoscopically assisted vaginal hysterectomy and resulted in two laparotomies: one for a transected ureter and the other for a cystotomy. Estimated blood loss was < 200 cc and the average hospital stay was 2.9 days. We feel that LASS is an attractive alternative to the traditional surgical approach in patients with stage I endometrial carcinoma.

Laparoscopy using the left upper quadrant as the primary trocar site.

Laparoscopic surgery was performed on 41 patients who were at high risk for subumbilical adhesions because of either previous midline incisions through the umbilicus or umbilical hernias. Insufflation was performed using a Veress needle placed in the left upper quadrant in the 9th intercostal space. The primary trocar was placed in the left upper quadrant adjacent to the subcostal margin. Sixty-eight percent (28/41) of patients had subumbilical adhesions. One patient required laparotomy because of an enterotomy created when an 11-mm trocar was used. There were no complications in the remaining 40 patients, in whom smaller primary trocars were used. This is a safe location for primary trocar placement in patients at high risk for subumbilical adhesions, provided certain guidelines are followed.