Vector-apodizing phase plate coronagraph: design, current performance, and future development [Invited].

Over the last decade, the vector-apodizing phase plate (vAPP) coronagraph has been developed from concept to on-sky application in many high-contrast imaging systems on 8 m class telescopes. The vAPP is a geometric-phase patterned coronagraph that is inherently broadband, and its manufacturing is enabled only by direct-write technology for liquid-crystal patterns. The vAPP generates two coronagraphic point spread functions (PSFs) that cancel starlight on opposite sides of the PSF and have opposite circular polarization states. The efficiency, that is, the amount of light in these PSFs, depends on the retardance offset from a half-wave of the liquid-crystal retarder. Using different liquid-crystal recipes to tune the retardance, different vAPPs operate with high efficiencies (${\gt}96\%$) in the visible and thermal infrared (0.55 µm to 5 µm). Since 2015, seven vAPPs have been installed in a total of six different instruments, including Magellan/MagAO, Magellan/MagAO-X, Subaru/SCExAO, and LBT/LMIRcam. Using two integral field spectrographs installed on the latter two instruments, these vAPPs can provide low-resolution spectra (${\rm{R}} \sim 30$) between 1 µm and 5 µm. We review the design process, development, commissioning, on-sky performance, and first scientific results of all commissioned vAPPs. We report on the lessons learned and conclude with perspectives for future developments and applications.

Effects of clomiphene citrate and leuprolide acetate on luteal-phase hyperprolactinemia during ovarian stimulation with menopausal gonadotropins.

Hyperprolactinemia, a known modulator of reproductive function, occurs commonly in women undergoing ovarian stimulation with human menopausal gonadotropins (hMG). Clomiphene citrate (CC) and gonadotropin releasing hormone analogues (GnRHa), when administered during the luteal phase, attenuate the hyperprolactinemic response to hMG. We asked whether follicular-phase administration of CC and GnRHa, as employed clinically in women undergoing ovarian stimulation for in vitro fertilization or gamete intrafallopian transfer, would alter the incidence and severity of hMG-induced luteal-phase hyperprolactinemia. Seventy-five percent of all patients had at least one luteal prolactin level greater than 25 ng/ml, and 40% had mean luteal-phase prolactin levels greater than 25 ng/ml. The incidence of hyperprolactinemia was similar in pregnant and nonpregnant cycles. The incidence of hyperprolactinemia was similar for both the GnRH agonist-treated group and those given clomiphene citrate. The increase in mean luteal prolactin levels over the follicular-phase baseline level was significantly greater in the CC-treated group (P = 0.03). This was due to the significant suppression of follicular-phase baseline prolactin levels in patients receiving CC. We conclude that neither CC nor GnRHa administration in the follicular phase prevents luteal-phase hyperprolactinemia in women undergoing ovarian stimulation with hMG.

Follicular size at the time of human chorionic gonadotropin administration predicts ovulation outcome in human menopausal gonadotropin-stimulated cycles.

OBJECTIVE: The objectives of this study were: (1) to correlate follicle size by transvaginal sonography with ovulation outcome in cycles of controlled ovarian hyperstimulation with human menopausal gonadotropins; (2) to determine if follicular size on the day of human chorionic gonadotropin (hCG) administration predicts the incidence of ovulation; and, if so, (3) to derive a mathematical model that predicts the number of expected ovulations in any given cycle of controlled ovarian hyperstimulation. DESIGN: A retrospective analysis. PARTICIPANTS: Forty-nine consecutive patients undergoing 122 cycles of controlled ovarian hyperstimulation were studied in a tertiary care setting. MAIN OUTCOME MEASURES: Follicular size and evidence of ovulation were determined sonographically. The main outcome measure was the rate of ovulation per follicle size. RESULTS: The percentages of follicles measuring less than or equal to 14 mm, 15 to 16 mm, 17 to 18 mm, 19 to 20 mm, and greater than 20 mm on the day of hCG administration that subsequently ovulated were 0.5%, 37.4%, 72.5%, 81.2%, and 95.5%, respectively. CONCLUSIONS: (1) Follicular size on the day of hCG administration correlates with the incidence of ovulation. (2) The expected number of ovulations in any given controlled ovarian hyperstimulation cycle can be predicted with 95% confidence using the accompanying equation.

Effects of tamoxifen on corpus luteum function and luteal phase length in cynomolgus monkeys.

Previous data in nonhuman primates have demonstrated that tamoxifen prolongs the luteal phase without altering reproductive hormone levels. A small study in humans found no effect on menstrual cycle length, but an increase in luteal ovarian steroid levels. In view of these conflicting results, we studied the effect of tamoxifen on corpus luteum (CL) function in monkeys (n = 20). Blood was obtained daily beginning cycle day 8, and sera assayed for estradiol (E2), progesterone (P), luteinizing hormone, and follicle-stimulating hormone. Four days after the midcycle E2 peak, laparoscopy confirmed CL formation, and the animals were administered (1) lactose (n = 7), (2) tamoxifen, 0.5 mg.kg-1.d-1 (n = 6), or (3) tamoxifen, 3.0 mg.kg-1.d-1 (n = 7) for 12 consecutive days. Serum collection continued until cycle day 50 or menses, whichever came first. Results indicate a biphasic response among tamoxifen-treated animals, with 7 of 13 developing prolonged luteal phases. There was, however, no significant difference in luteal phase length among the three groups, although when the two groups given tamoxifen were combined, the difference in luteal phase length versus controls approached significance. No differences were found among peak P levels, mean luteal phase P levels, or mean luteal phase gonadotropin levels. No variables were found to correlate significantly with luteal phase length. These results suggest that luteal phase administration of the antiestrogen tamoxifen does not alter pituitary gonadotropin secretion or CL function. However, tamoxifen does prolong luteal phase length in a subset of monkeys, perhaps via a direct effect on the endometrium.

Hysterosalpingography in the preoperative evaluation of tubal anastomosis candidates.

The value of the hysterosalpingogram (HSG) in the investigation of women requesting reversal of tubal sterilization has never been established. Accordingly, we reviewed the preoperative HSGs performed on 54 women and the surgical findings of these and 27 additional patients who underwent laparoscopy and/or laparotomy for tubal anastomosis. The observation of interstitial, isthmic, and ampullary obstruction by HSG correctly correlated with surgical findings in 12%, 94%, and 69% of cases, respectively. The decision to perform an anastomosis was made in 14 of 17 (82.4%) tubes with interstitial obstruction, 45 of 51 (88.2%) tubes with isthmic occlusion, and 26 of 36 (72.2%) tubes with ampullary occlusion. When distal tubal occlusion was demonstrated by HSG (36/104 tubes, 34.6%), 10 had no repairable ampullary segments. The site of tubal occlusion on HSG was not predictive of a repairable tube. We conclude that the routine HSG is not warranted in the preoperative evaluation of candidates for tubal anastomosis.

Effects of gonadotropin-releasing hormone agonist and clomiphene citrate on estrogen/progesterone-induced hyperprolactinemia in monkeys.

The effects of follicular phase clomiphene citrate (CC) and two regimens of leuprolide acetate on estrogen-progesterone-induced hyperprolactinemia in nonhuman primates were studied. All groups received estradiol (E2) benzoate (12.5 micrograms intramuscularly on cycle days 2 to 33) and progesterone (P) (silastic implant for cycle days 14 to 33). A gonadotropin-releasing hormone agonist (GnRH-a) (Lupron 0.5 mg daily, TAP Pharmaceuticals, Chicago, IL) was administered from cycle day 2 to 14 in group II and from day 20 of the previous cycle until cycle day 14 in group III. Oral CC was given on cycle days 3 through 7 in group IV. No significant differences of mean E2 and P concentrations were noted between groups. Neither GnRH-a nor CC had an overall effect on E2/P-induced hyperprolactinemia. However, for the 5-day interval at the onset of the P treatment there was a significant increase in prolactin (PRL) secretion for group II (130.4 +/- 30.6) versus group I (53.9 +/- 3.3), group III (64.4 +/- 11.1), and group IV (68.8 +/- 14.3). This suggests that leuprolide may exert a delayed stimulatory effect on PRL secretion, or that complete suppression of the putative paracrine regulation of PRL stimulation may require more than 13 days of GnRH-a administration.

Gamete intrafallopian transfer vs superovulation with intrauterine insemination for the treatment of infertility.

Superovulation with intrauterine insemination (SO-IUI) has been suggested as an alternative to gamete intrafallopian transfer (GIFT), despite the absence of controlled or comparative trials. We retrospectively analyzed all GIFT and SO-IUI cycles performed concurrently from January 1985 to August of 1987 at a single university center. Pregnancy rates were significantly better for GIFT than SO-IUI (P less than 0.001), with an odds ratio of 3.25 (P = 0.001). Stepwise multiple logistic regression identified factors that correlate with pregnancy: absence of endometriosis (P = 0.05), infertility less than 3 years' duration (P = 0.002), TMS greater than or equal to 30 X 10(6) (P = 0.005), and treatment with GIFT rather than SO-IUI (P = 0.001). These data give a first approximation of the increased efficacy of GIFT versus SO-IUI and provide valuable insight into significant confounding variables to be considered when planning a randomized, prospective trial to evaluate these techniques.

Relationship of age and pubertal development to ovulation in adolescent girls.

A random sample of adolescent girls, 13 to 16 years of age, were surveyed with multiple serum progesterone determinations. The presence of ovulation was correlated with various indexes of pubertal development, including a pubertal developmental index that was devised using a summation of developmental factors. There was a significant correlation of ovulation with breast development, pubic hair development, and with the developmental index.

Salpingitis isthmica nodosa: radiologic and clinical correlates.

Salpingitis isthmica nodosa (SIN) is thought to be an inflammatory condition of the fallopian tubes and is strongly associated with infertility and an increased risk of ectopic pregnancy. The diagnosis is best made radiographically at hysterosalpingography (HSG), where the characteristic finding consists of multiple nodular diverticular spaces in close approximation to the true tubal lumen. We reviewed 1,194 HSGs performed over a five year period and identified 45 patients who had SIN (4%). There was a high rate of primary infertility (37.5%) and ectopic pregnancy (9.4%). Of 70 involved tubes, 62 (89%) had evidence of associated inflammation on historic, radiologic, surgical, or histologic grounds. We conclude that SIN is a disorder most likely acquired during the fertile years, and that the lesion is either a direct consequence of infection or that--once present--it predisposes the patient to subsequent infections.

Serum androgenic hormones motivate sexual behavior in adolescent boys.

In order to separate hormonal from social effects on adolescent male sexual behavior, serum hormone assays were performed and questionnaire data on sexual motivation and behavior were collected on a representative sample of 102 boys in grades 8, 9, and 10 of a public school system. Free testosterone was a strong predictor of sexual motivation and behavior, with no additional contribution of other hormones. Including measures of pubertal development and age (indexing the effects of social processes) indicated no additional effects. Free testosterone, therefore, appears to affect sexual motivation directly and does not work through the social interpretation of the accompanying pubertal development.

Effects of neutralization of luteinizing hormone on corpus luteum function and cyclicity in Macaca fascicularis.

The primate corpus luteum (including the human) is thought to require continuous exposure to LH for normal progesterone production and menstrual cyclicity. Recently, normal luteal function was reported in rhesus monkeys after postovulatory hypophysectomy or treatment with an antagonist to GnRH. We studied the effects of neutralization of LH by specific antiserum in the fascicularis monkey. A potent antiserum to ovine LH, which cross-reacted with monkey pituitary extract, was produced in rabbits; this antiserum was administered daily to cycling monkeys during the midluteal phase. The pretreatment cycle duration was 32.4 +/- 1.7 (+/- SE) days, and luteal length was 16.5 +/- 0.8 days, with a midluteal progestin peak of 15.28 +/- 2.23 ng/ml. LH antiserum treatment resulted in a precipitous fall in serum progestin within 24 h, which remained low for the remainder of the cycle. All treated monkeys had premature menstrual bleeding, with mean cycle length shortened to 22.8 +/- 1.6 days (P less than 0.0005). These results confirm that the continuous presence of LH is essential for maintenance of corpus luteum function in this species of primate.

Amenorrhea-galactorrhea, hyperprolactinemia, and suprasellar pituitary enlargement as presenting features of primary hypothyroidism.

Two women who presented with amenorrhea-galactorrhea and hyperprolactinemia associated with x-ray evidence of pituitary enlargement and suprasellar extension were found to have primary hypothyroidism. Resolution of the pituitary enlargement and galactorrhea occurred after thyroid hormone replacement. Both women spontaneously ovulated and conceived, and normal pregnancies resulted. Amenorrhea, galactorrhea, and/or pituitary enlargement may be the principal manifestations of primary hypothyroidism. In such patients, it is imperative that primary hypothyroidism be excluded before drug or surgical therapy for presumed prolactinoma is undertaken. When these findings are due to primary hypothyroidism, thyroid hormone replacement alone is adequate therapy.