Frederick K. Chapler

Endocrine consequences of continuous antiestrogen therapy with Tamoxifen in premenopausal women.

Daily administration of estrogen antagonists to premenopausal women has been incorporated into the adjuvant treatment of breast cancer. We have studied the changes in reproductive hormones, pituitary responses to hypothalamic-releasing hormones, and endometrial histology during treatment with the antiestrogen tamoxifen in five healthy, premenopausal women. These studies were carried out during one menstrual cycle before and during two cycles of antiestrogen treatment. All subjects continued to have regular menses with biphasic basal body temperature records. During treatment, estradiol (E2) levels were increased but followed the usual pattern reflecting follicular maturation and corpus luteum formation. The mean E2 concentration at the midcycle peak and during the luteal phase was twice that observed during the non-treatment cycle. By contrast, the concentrations and secretory patterns of luteinizing hormone and follicle-stimulating hormone were not greatly changed, and the gonadotropin responses to gonadotropin-releasing hormone were not suppressed. Endometrial biopsies obtained during the follicular phase of control and tamoxifen treatment cycles showed no differences whereas biopsies obtained during the luteal phase of tamoxifen cycles uniformly showed a lack of changes attributed to progesterone action with no progression of histologic changes beyond those expected on day 7-8 of the luteal phase. These observations are consistent with maturation of multiple ovarian follicles, a surprising finding considering the normal gonadotropin concentrations. The retarded development of the endometrium in the presence of supranormal serum E2 and progesterone concentrations is a morphologic demonstration of the antiprogestational effect of antiestrogens. The lack of gonadotropin suppression in the presence of hyperestrogenemia suggests a major antiestrogen action on the hypothalmus and pituitary gland.

Cost-effectiveness of infertility treatments: a cohort study

OBJECTIVE To determine the cost-effectiveness of infertility treatments. DESIGN Retrospective cohort study. SETTING Academic medical center infertility practice. PATIENT(S) All patients treated for infertility in a 1-year time span. INTERVENTION(S) Intrauterine inseminations, clomiphene citrate and IUI (CC-IUI), hMG and IUI (hMG-IUI), assisted reproductive techniques (ART), and neosalpingostomy by laparotomy. MAIN OUTCOME MEASURE(S) All medical charges and pregnancy outcomes associated with the treatments were obtained. Cost-effectiveness ratios defined as cost per delivery were determined for each procedure. The effects of a womans age and the number of spermatozoa inseminated on cost-effectiveness of the procedures was also determined. RESULT(S) Intrauterine inseminations, CC-IUI, and hMG-IUI have a similar cost per delivery of between

Early diagnosis of ovarian torsion by color Doppler ultrasonography.

7,800 and

Danazol: Endocrine consequences in healthy women***

10,300. All of these were more cost-effective than ART, which had a cost per delivery of

Effects of danazol on plasma lipid and lipoprotein levels in healthy women and in women with endometriosis

37,000. Assisted reproductive techniques in women with blocked fallopian tubes was more cost-effective than tubal surgery performed by laparotomy, which had a cost per delivery of

Tubal versus uterine transfer of cryopreserved embryos: a prospective randomized trial

76,000. Increasing age in women and lower numbers of spermatozoa inseminated were factors leading to higher costs per delivery for IUI, CC-IUI, hMG-IUI, and ART. Use of donor oocytes reduced the cost per delivery of older women to the range seen in younger women with ART. CONCLUSION(S) Our analysis supports, in general, the use of IUI, CC-IUI, and hMG-IUI before ART in women with open fallopian tubes. For women with blocked fallopian tubes, IVF-ET appears to be the best treatment from a cost-effectiveness standpoint.

The effectiveness of sublingual progesterone administration during cryopreserved embryo transfer cycles: Results of a matched follow-up study

Ovarian torsion is often difficult to diagnose because of the nonspecific nature of the clinical findings. We report on the use of color Doppler ultrasonography in diagnosing early ovarian torsion. This technique provides a highly specific finding, the absence of blood flow to the ovary, that greatly facilitates the diagnosis of ovarian torsion.

The effect of an antihistamine and/or a glucocorticoid on the prolactin response to surgical procedures☆☆☆

We studied the effects of danazol on pituitary and gonadal function in seven normal women who volunteered to take danazol, 400 mg twice daily, for 2 months. We measured circulating levels of sex steroids, gonadotropins, and prolactin on alternate days throughout a control menstrual cycle and during treatment. Danazol inhibited ovulation in all subjects. The amenorrheic state induced by danazol was characterized by normal basal levels of gonadotropins, prolactin, and estrogen. Serum androgen levels were significantly increased as was the urinary excretion of 17-ketosteroids. The LH and FSH responses to gonadotropin-releasing hormone were enhanced during treatment, and there was a normal LH rise following administration of estradiol valerate, indicative of intact positive feedback. These observations fail to support the contention that danazol suppresses pituitary gonadotropin secretion or directly inhibits steroidogenesis. The results suggest that danazol may have a primary site of action at the ovary by suppressing the normal, orderly process of follicular maturation.

Spontaneous Pregnancy in Women with a Prolactin-Producing Pituitary Adenoma*

Previous studies of the effects of danazol on lipid and lipoprotein levels have been conflicting and limited to women with endometriosis. In the present study, plasma levels of lipids and lipoprotein-cholesterol and triglycerides were determined in 25 infertile women with endometriosis and in eight normal women before, during, and after treatment with danazol at daily doses of 200 to 800 mg for 2 to 6 months. Pretreatment values of cholesterol, triglycerides, and lipoprotein were within the normal range in all subjects except three (one with type III and two with type IV hyperlipoproteinemia). During treatment, the mean levels of total cholesterol and triglycerides decreased slightly, while no significant changes in low-density and very low-density lipoproteins were seen. However, a marked (40%) reduction in the mean levels of high-density lipoprotein cholesterol and triglycerides occurred (P less than 0.001) within 4 weeks of therapy in all subjects, which persisted for the duration of the treatment. Patients with pretreatment hyperlipoproteinemia experienced a substantial fall in plasma lipids and lipoprotein and had normal lipoprotein profiles during treatment. Within 4 weeks after danazol was discontinued, all changes in plasma lipid and lipoprotein levels returned to pretreatment levels. These findings have important implications for the atherogenic potential of danazol, a new treatment for hyperlipidemia, and the relationship between gonadal hormones and lipoprotein levels.

The Treatment of Hyperprolactinemia with a New Ergot Derivative, Lergotrile Mesylate*

OBJECTIVE To compare pregnancy rates after fallopian tubal and uterine transfer of cryopreserved embryos. DESIGN Prospective randomized trial with assignment to treatment groups by a random number table. SETTING University of Iowa Hospitals and Clinics, a tertiary care academic institution. PATIENTS Forty patients with patent fallopian tubes and at least three cryopreserved embryos. INTERVENTIONS Cryopreserved embryos were thawed and transferred to the fallopian tube by laparoscopy or to the uterus by a transcervical catheter. MAIN OUTCOME MEASURES Clinical and ongoing pregnancy rates. RESULTS Tubal transfer of cryopreserved embryos resulted in statistically higher clinical (68% versus 24%) and ongoing pregnancy rates (58% versus 19%) when compared with uterine transfer. CONCLUSIONS Tubal transfer of cryopreserved embryos is highly effective and offers an improved pregnancy rate when compared with uterine transfer of embryos. This method of transfer should be considered in patients with patent fallopian tubes and at least three cryopreserved embryos.