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To assess the involvement of ovarian-derived regulatory proteins in FSH modulation, we compared FSH, inhibin A, inhibin B, activin A, and follistatin (FS) in 79 women from the following five groups: young cycling, older cycling, perimenopause (PERI), spontaneous menopause (PM), and surgical menopause receiving estrogen (OVX+ET). Although inhibin B varied as expected by ovarian function, no group differences were observed in activin A, barring a tendency for an increase in PERI, while FS 288 was lower in the PERI, PM, and OVX+ET groups and negatively correlated with advancing age.

Objective: To increase understanding of the clinical significance of atypical glandular cells of undetermined significance (AGUS) on cervical cytology and to suggest a management plan., Study Design: All Pap smears classified as AGUS over a period of five years at the University of Michigan Medical Center were reviewed and the diagnosis confirmed. The charts of these patients were reviewed for demographics, significant previous medical history, symptoms, diagnostic studies performed and final histologic diagnoses., Results: In 1993-1998, a total of 208,041 Pap smears were read. Two hundred seven smears from 189 patients were classified as AGUS, for an incidence of 0.1%. There were 136 patients with follow-up information and 114 patients with histologic diagnoses. In 55 of the 114 patients (48%), significant histologic abnormalities were observed, including 11 endometrial cancers, 1 invasive adenocarcinoma of the cervix, 3 adenocarcinomas in situ of the cervix, 18 CIN 3 lesions and 5 CIN 2 lesions. Among 20 patients with Pap smears subclassified as "atypical glandular cells of undetermined significance, favor benign process," there were two CIN 2, five CIN 3 and one adenocarcinoma in situ of the cervix., Conclusion: A diagnosis of AGUS requires an aggressive workup because of the high rate of cancer and precancerous lesions. The evaluation, at the very least, should include colposcopy with directed biopsies and endocervical curettage. Postmenopausal patients, those with irregular bleeding and those with high risk characteristics should also undergo endometrial biopsy.

In the next decade many women will turn to the medical community for advice on maintaining or improving health after menopause. Estrogen replacement therapy, with or without progestins, alleviates menopausal symptoms, prevents or manages osteoporosis, and reduces the increased cardiovascular disease risk that results from estrogen deficiency caused by ovarian decline. Although several estrogen replacement products are available, the pharmacokinetics and efficacy of these products may vary depending on either the estrogen formulation or the route of administration, or both. For example, oral estrogens, which elicit a marked hepatic response, induce greater beneficial effects on serum lipoproteins than transdermal estrogens, which circumvent first-pass liver metabolism. Oral conjugated estrogens and transdermal estradiol increase bone density and prevent bone loss. This article summarizes the studies comparing estrogen formulations and discusses the differential effects of various estrogen products that promote postmenopausal health.

Objective: To determine if pregnancy rates (PRs) for clomiphene citrate (CC)-stimulated IVF-ET can be increased by luteal support with E2 and P., Design: Prospective randomized crossover clinical study., Setting: Infertile women volunteers in an academic research environment., Patients: Ninety-three infertile women underwent a total of 143 IVF-ET cycle using CC for ovulation induction., Interventions: Each woman received either no luteal support (control group) or luteal support with both oral E2 (2 mg three times daily) starting on the day of retrieval and vaginal P suppositories (100 mg twice daily) starting on the day of ET., Main Outcome Measure: Clinical PR., Results: In 79 of 143 (55%) of the cycles, at least one embryo was transferred. Compared with the control group (n = 35 cycles), the luteal support group (n = 44 cycles) had a significantly higher PR per retrieval (control: 2% versus luteal support: 16%) and were older (control: 33 +/- 4 versus luteal support: 35 +/- 4 years; mean +/- SEM). They did not differ in terms of E2 or P levels, endometrial thickness on the day of hCG, number of follicles > 16 mm in diameter, mature oocytes retrieved, or embryos transferred., Conclusions: Luteal support with both E2 and P significantly increase the clinical PRs for CC-stimulated IVF-ET.

This case report describes the use of GIFT to achieve pregnancy for a man with Kallmann's syndrome who obtained only marginal sperm counts with both the pulsatile GnRH infusion pump and gonadotropin injections. Failure of this man to achieve a pregnancy with hormonal therapy alone and in combination with IUI suggests that assisted reproductive technologies should be considered in male patients with Kallmann's syndrome when suboptimal sperm concentrations are achieved despite exogenous hormonal stimulation.

Objective: To compare the efficacy of intracervical insemination (ICI), intrauterine insemination (IUI), and a combination of intratubal and intrauterine insemination (ITI/IUI) for donor insemination., Design: Prospective randomized clinical trial., Setting: The University of Michigan donor insemination program., Patients, Participants: Forty-one women undergoing donor insemination with cryopreserved sperm for either isolated male factor or male factor plus ovulatory dysfunction corrected by clomiphene citrate., Intervention: Each patient was randomly assigned to receive each of the three insemination techniques in consecutive cycles until pregnancy occurred or the patient dropped from the study., Main Outcome Measures: Cycle fecundity rates were compared using the chi 2 test, and cumulative pregnancy rates (PRs) determined by life table analysis were compared using a log-rank test., Results: Cycle fecundity rate was significantly higher for IUI (18.3%) than for ICI (3.9%) or ITI/IUI (7.3%). By life table analysis, the cumulative PR for IUI was significantly higher than for ICI, but the PR for ITI/IUI was not., Conclusion: For donor insemination with cryopreserved sperm, IUI increases cycle fecundity compared with ICI. The addition of ITI to IUI, however, interferes with the apparent beneficial effect of IUI alone.

Transcervical tubal cannulation using tactile guidance has a similar rate of successful cannulation compared with that with US guidance (78% versus 73%) but takes less time to perform (2.3 +/- 1.8 minutes versus 8.7 +/- 6.2 minutes, mean +/- SD) and is associated with less pain and bleeding. This appears to be because of the design of the Labotect tubal cannulation set that uses a special speculum and tenaculum to straighten the uterus before insertion of the guide cannula and a less traumatic ball-tipped guide catheter.

Two cases are reported in which hypersensitivity reactions occurred after intrauterine placement of spermatozoa or embryos. Because the cells were processed and transferred in antibiotic-containing media, these reactions were suspected to be because of penicillin allergy. One patient had no prior penicillin allergy but was found to be penicillin allergic by skin testing. The other had a history of allergy to oral penicillin. In both cases, the allergy symptoms did not occur during subsequent cycles when antibiotics were removed from the transfer media. These reports suggest that in patients known to be penicillin sensitive, penicillin should not be used during transfer of gametes and embryos for assisted reproductive procedures. In addition, the routine use of antibiotics in these procedures should be scientifically evaluated.

Current Food and Drug Administration guidelines for assessing the differences in bioavailability between generic oral contraceptives and brand-name products are inadequate to ensure therapeutic equivalence. The guidelines do not take into account those women who may have blood levels of active ingredients well outside the range of acceptability. Due to the narrow therapeutic range of steroids, these women may become pregnant or experience an increased incidence of breakthrough bleeding. Furthermore, oral contraceptive packaging is unique to each manufacturer, and any change in brands (and therefore packaging) can easily negate the sequential administration of the appropriate tablet. These are among the reasons proposed for placing oral contraceptives in the critical drug category, in which generic substitution and interchangeability of products should not be allowed.

Two patients had elevated beta-human chorionic gonadotropin levels and normal abdominal ultrasound examinations. In both instances transvaginal ultrasonography demonstrated a persistent nodule of trophoblastic disease confirmed at the time of hysterectomy. This new imaging modality can assist in the diagnosis of persistent trophoblastic disease in the uterus.