Intrauterine insemination with husband's washed sperm.

Methods used for artificial insemination with the husband's semen (AIH) have undergone continuous revision in the hope of increasing the pregnancy rates obtained. We report our methodology using technology developed for in vitro fertilization to prepare sperm for intrauterine insemination. Our overall pregnancy rate is 30%. In this preliminary study several parameters are compared with the pregnancy rates achieved.

In vitro fertilization. The Scripps Clinic experience.

The in vitro fertilization (IVF) program at Scripps Clinic and Research Foundation, La Jolla, California, was started in 1983. In vitro fertilization is now an accepted type of infertility treatment for many couples with a disorder of tubal origin, endometriosis, male-factor infertility, or idiopathic infertility. Successful outcome has depended on the woman's age, the cause of infertility, and the number of embryos transferred. The highest pregnancy rate has been achieved in women under age 35 with tubal-factor infertility and transfer of three or more embryos. During the first year, the program's overall pregnancy rate was 13% (5 pregnancies/38 embryo transfers) and the pregnancy rate for women under age 35 with tubal-factor infertility was 28%. The functioning of an IVF program depends on the availability of a clinical laboratory for daily hormone measurements, ultrasonography for monitoring follicle growth, an operating room that is available any time day or night, and a laboratory equipped for fertilization of retrieved ova and monitoring of embryo development. Clearly, a carefully integrated team of medical care providers is necessary for a program that draws on so many different clinical resources.

Increased luteinizing hormone sensitivity to dopamine inhibition in polycystic ovary syndrome.

The elevated LH secretion in 8 patients with the polycystic ovarian syndrome (PCO) was promptly suppressed by the infusion of dopamine (DA; 4 microgram/kg.min for 4 h). Compared to normal women studied during the early follicular phase, the maximal LH suppression due to DA infusion was significantly greater in PCO patients when expressed as either the net or percent decrease. This enhanced LH sensitivity to DA inhibition in PCO patients with chronically elevated estrogens, suggests that the inappropriately elevated LH release and the exaggerated LH pulses may be causally related, in part, to a reduction of endogenous DA inhibition of LH secretory activity.

Prevalence of hyperprolactinemia in anovulatory women.

To determine the prevalence of hyperprolactinemia in an ovulatory patients presenting to a general gynecology clinic, a 1-year prospective study (1978) was instituted. A total of 119 patients with at least 3 months of anovulation were screened with serum prolactin determinations. Those patients demonstrating hyperprolactinemia were further evaluated with a serum TSH level and hypocycloidal polytomography of the pituitary sella. In patients with anovulation with or without galactorrhea, a hyperprolactinemia prevalence rate of 15% was established. Anovulatory patients with galactorrhea had a hyperprolactinemia prevalence rate of 43%. This was compared to the 9% prevalence of hyperprolactinemia in patients with nongalactorrheic anovulation (P less than .001). Twenty-two percent of the patients with nongalactorrheic anovulation (2 of 9) were found to have a prolactin-secreting pituitary adenoma. In patients with hyperprolactinemia, galactorrhea, and anovulation, 67% (6 of 9) of patients had a prolactin-secreting pituitary adenoma. The authors therefore conclude that the 15% prevalence rate of hyperprolactinemia in all anovulatory women is sufficiently high to warrant continued screening of serum prolactin determinations in all anovulatory women.

Changes in pituitary hormones during and following transsphenoidal removal of prolactinomas.

Prolactin (PRL) and other pituitary hormones (luteinizing hormone, follicle-stimulating hormone, growth hormone [GH], thyrotropin stimulating hormone) were measured before, during, and after transphenoidal pituitary adenomectomy in 16 patients with hyperprolactinemia. The diagnosis of prolactinoma was made in three of the 16 patients by the absence of PRL response to thyrotropin-releasing factor (TRF) and a dopamine receptor antagonist, metoclopramide, without radiologic evidence of an adenoma. Contrary to findings in subjects with normal PRL values, the PRL rise in response to anesthesia and operation was absent. Other pituitary hormones, with the exception of GH, which increased during anesthesia and operation, exhibited no acute changes. In 11 of 16 cases, complete tumor removal was achieved as determined by the rapid decline of PRL levels to normal values within 24 to 48 hours after operation and by subsequent clinical follow-up. This finding documents that the adenoma is the main source of excessive PRL secretion. The circulating half time of immunoreactive PRL determined by frequent sampling in these patients was variable, ranging from 74 to 190 minutes, significantly longer than the previously reported value of 15 minutes determined by bioassay. Although a transient decline was evident, serum PRL levels remained elevated in those patients with incomplete tumor removal. These findings suggest that a single measurement of serum PRL within 24 to 48 following transphenoidal adenomectomy is a reliable indicator of the success or failure of the procedure.

Correlations between seminal radioimmunoreactive prolactin, sperm count, and sperm motility in prevasectomy and infertility clinic patients.

Semen samples were collected from 50 prevasectomy patients and 43 infertility clinic patients. Various parameters were measured, including semen radioimmunoreactive prolactin (rPRL) levels. Linear correlations were tested between the measured parameters, and a significant correlation was found between semen rPRL concentration and sperm count for both the prevasectomy (r = 0.73, P less than 0.00002) and the clinic patients (r = 0.72, P less than 0.00002). For the clinic patients a correlation was also found between the amount of ejaculate rPRL and sperm motility (r = 0.46, P less than 0.002) and between ejaculate volume and motility (r = 0.36, P less than 0.02).

Progesterone induced acute release of prolactin in estrogen primed ovariectomized women.

Progesterone (10 mg) administered intramuscularly induces a concurrent release of prolactin as well as gonadotropin in estrogen-primed women. The time course of pituitary release of all three of these hormones appears to include a latent phase of 4 hrs and is maintained for at least 5 hrs. It is considered that this effect of progesterone may be mediated through a reduction of hypothalamic dopamine.

Inhibition of gonadotropin and prolactin release by dopamine: effect of endogenous estradiol levels.

The influence of endogenous estradiol (E2) levels on gonadotropin and PRL sensitivity to dopamine (DA) infusion (4 micrograms/kg/min) was assessed at different stages of the follicular phase of the menstrual cycle. Basal LH and FSH levels were comparable in day 2 and day 12 subjects, and despite a 4-fold increase in E2 concentration, the inhibition of LH by DA was small and quantitatively similar and there was no discernible effect on FSH in either group. In marked contrast, day 14 subjects with an elevated basal LH level exhibited a dramatic increase in the sensitivity of LH and FSH to DA inhibition. Further, a remarkable rebound release for LH but not FSH occurred on the termination of DA infusion. There was a significant correlation between basal LH and response to DA (r = 0.979). This unique increase in response to DA at a time when hypothalamic LRF secretion is assumed to be elevated suggests that DA may exert its effect by inhibiting LRF release. The inhibition of PRL release by DA is correlated with endogenous E2 levels (r equal 0.685) as well as basal PRL levels (r = 0.878). Rebound release of PRL occurs in all three groups of women on termination of the DA infusion, but the magnitude was greatest in Day 14 subjects with the highest endogenous E2 levels. These data suggest that while E2 seems to augment the sensitivity of PRL inhibition by DA, its does not seem to directly influence gonadotropin sensitivity to DA inhibition. The selective hypersensitivity of both LH and FSH to DA observed on the day before midcycle LH peak is consistent with a reduction in LRF neuronal inhibition by tuberoinfundibular DA neurons at this time.

The impairment of progesterone-induced pituitary release of prolactin and gonadotropin in patients with hypothalamic chronic anovulation.

Sequential administrations of progessively increasing amounts of estradiol benzoate (EB) for five days followed by 10 mg. of progesterone (P) elicited a prompt pituitary release of luteinizing hormone, follicle-stimulating hormone, and prolactin in normal women during the early follicular phase but not in women with normogonadotropic hypothalamic chronic anovulation with or without associated hyperprolactinemia. Since hypothalamic dopamine functions as an inhibitor for the secretion of both prolactin and gonadotropin, we postulate that sequential EB-P stimulation for simultaneous release of gonadotropin and prolactin may be mediated by a reduction of hypothalamic dopamine in response to progesterone. The failure of patients with hypothalamic chronic anovulation to respond to this sequential ovarian steroid feedback demonstrated in this study may indicate the presence of dopaminergic dysfunction and that this test may prove to be useful in delineating hypothalamic function in amenorrhea patients.

Correlation of the effects of dexamethasone administration on urinary 17-ketosteroid and serum androgen levels in patients with hirsutism.

Total 24 hour urinary 17-ketosteroid and serum testosterone (T), androstenedione (delta), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DS), and cortisol levels were measured before and during four days of dexamethasone administration in 28 hirsute patients and 10 women with normal ovulatory cycles. Both the base-line urinary 17-ketosteroids and serum androgen levels were significantly higher (p less than 0.05) in hirsute than in normal subjects. Cortisol levels were similar in the two groups. Dexamethasone administration resulted in a significant suppression (p less than 0.05) of all the urinary and serum androgen and cortisol levels in both groups. At the end of suppression the serum DHEA, DS and cortisol levels were similar, while the urinary 17-ketosteroids and serum T and delta levels were still significantly higher (p less than 0.05) in the hirsute than in normal women. There was poor correlation between total urinary 17-ketosteroid and serum androgen results. These finding suggest there is a dual abnormality of androgen production in hirsute patients. The adrenal glands appear to secrete increased quatities of DHEA and DA, while the ovaries appear to produce elevated amounts of T and delta.