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Biomedical subjects

P R Gindoff

Publications and source records attributed to P R Gindoff.

17 recordsLinked to original sources

Ovarian suppression with leuprolide acetate: comparison of luteal, follicular, and flare-up administration in controlled ovarian hyperstimulation for oocyte retrieval.

Adjunct use of leuprolide (LA) in patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins (hMG) was evaluated by three protocols: Group F (n = 24) began LA on day 2 of the cycle and Group L (n = 38) began LA on day 23 of the cycle until ovarian suppression, at which time hMG was added. Group FL (n = 17) began LA on day 1 and hMG on day 3. Compared to FL, more ova were collected, more ova fertilized, and more pregnancies resulted per initiated cycle in groups achieving suppression before hMG stimulation. Fewer days were necessary to attain suppression for L vs F. After achieving suppression, patients were maintained on either 0.5 mg LA or 0.25 mg LA daily during hMG coadministration with similar results. Lower maintenance doses of LA during hMG did not decrease the amount of hMG needed but retained the benefits of LA. We recommend luteal initiation of LA to achieve suppression before hMG.

Adult

Efficacy of assisted reproductive technology during diagnostic and operative infertility laparoscopy.

Women being evaluated for infertility were offered assisted reproductive technology at the time of diagnostic laparoscopy. Oocyte retrieval was performed after ovulation induction in 33 women, of whom 19 had concurrent operative laparoscopy. Gamete intrafallopian transfer (GIFT) or in vitro fertilization (IVF) and embryo transfer were performed subsequently depending on laparoscopic assessment of pelvic architecture, oocyte maturity, and semen parameters. The clinical pregnancy rate was 24% per cycle and 28% per gamete or embryo transfer (four pregnancies after GIFT and four after IVF/embryo transfer). The clinical pregnancy rate per transfer did not differ significantly between the 19 women who had therapeutic operations in conjunction with laparoscopy (lysis of adhesions and/or fulguration of endometriosis) and the 13 who did not (25 versus 30%; P greater than .05). Assisted reproductive technology can be performed successfully during diagnostic infertility laparoscopy. Operative endoscopic manipulation did not adversely influence pregnancy outcome.

Adult

Dexamethasone treatment prevents the inhibitory effect of corticotropin-releasing hormone on gonadotropin release in the primate.

Corticotropin-releasing hormone (CRH) has been shown to inhibit gonadotropin secretion and this effect is mediated by endogenous opioid peptides, presumably stimulated by CRH. Since glucocorticoids are known to block the CRH-induced ACTH response, it can be hypothesized that by concurrently preventing endogenous opioid peptide release, they would also prevent the inhibitory action of CRH on gonadotropin secretion. We tested this hypothesis in 4 ovariectomized rhesus monkeys, pretreated with dexamethasone (DEX; 1.5 mg b.i.d. for 5 days). In experiment 1, the effects of a 5 h i.v. hCRH infusion with or without DEX pretreatment and of physiological saline were compared. Blood samples were taken at 15-min intervals during a 3 hour preinfusion control and throughout the infusion. Sera were assayed for luteinizing hormone (LH), follicle-stimulating hormone (FSH) and cortisol by RIA. In the absence of DEX pretreatment, LH and FSH levels were progressively decreased during the CRH infusion: by hour 5, LH and FSH areas under the curve were 34.1 ( +/- 7.6) and 65.3% ( +/- 2.5) (mean % of preinfusion control values; + SE), respectively (p less than 0.01 vs. saline). In contrast, DEX pretreatment prevented the CRH-induced gonadotropin decrease: by hour 5, LH and FSH areas under the curve were 91.9 ( +/- 9.0) and 99.0% ( +/- 5.7) (n.s. vs. saline). In experiment 2, we tested whether DEX-treated monkeys would remain responsive to the gonadotropin inhibitory action of an opiate agonist. After a 3 hour preinfusion control baseline, morphine (9 mg i.v.) was given as a bolus injection to the same 4 animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Induction of ovulation--past, present and future.

Attempts to induce ovulation have been made since the early 1920s, but the major breakthrough came in the early 1960s with the introduction of clomiphene citrate and the gonadotropins. Additional progress was made in the early 1970s with the introduction of bromocriptine and in the early 1980s with the introduction of pulsatile GnRH. At the present, 'pure' FSH and GnRH agonists are being evaluated as adjuncts to HMG for induction of ovulation. As more insight is gained in the neuroendocrine control of the ovulating cycle, we may soon be able to induce ovulation by direct manipulation of the central nervous system.

Chorionic Gonadotropin

Sustained effects of opioid antagonism during the normal human luteal phase.

The luteal phase of the menstrual cycle is characterized by a progressive decrease in LH pulse frequency. Short term administration of opiate receptor antagonists during the luteal phase increases the release of both LH and PRL. However, the effects of prolonged opioid antagonism throughout the luteal phase are unknown and, hence, the precise role of endogenous opioid peptides in the reproductive cycle remains to be elucidated. In this study, we examine the ability of longer term opioid antagonism during the luteal phase to alter pulsatile LH and PRL release. Naltrexone (NTX), a long-acting oral opioid antagonist, at a dose of 50 mg, was administered daily for 7 days during the luteal phase in five women. Blood samples were obtained at intervals of 10 min starting at 0800 h for 11-12 h on matched days of the luteal phase of both a control and the experimental cycle. LH and PRL pulse frequencies were significantly increased at the end of the 7-day NTX administration period compared to those in the control cycle [LH, 0.22 +/- 0.04 (+/- SE) vs. 0.07 +/- 0.03 pulse/h (P less than 0.01); PRL, 0.20 +/- 0.02 vs. 0.13 +/- 0.02 pulse/h (P less than 0.05)]. The concordance between LH and PRL pulses increased from 50% in the control cycle to 70% in the NTX cycle, and there was a significant positive correlation between the amplitudes of the concomitant LH and PRL pulses (r = 0.72; P = 0.01). In conclusion, prolonged oral opioid antagonism increased pulsatile LH and PRL secretion during the luteal phase in normal women. The results underscore the important role of endogenous opioid peptides in controlling LH pulse frequency during the luteal phase of the cycle.

Adult

Endogenous opioid peptides modulate the effect of corticotropin-releasing factor on gonadotropin release in the primate.

Stress can induce endocrine abnormalities and menstrual dysfunction in the primate. Here, we examine the effects that CRF, the principal neurohormone in control of the hypothalamic-pituitary-adrenal axis, exerts on pulsatile gonadotropin secretion and the role that the endogenous opioid peptides may play in this phenomenon. Ovariectomized rhesus monkeys were given a 5-h continuous iv infusion of physiological saline (2 ml/h), human CRF (100 micrograms/2 ml . h), or hCRF plus the opiate receptor antagonist naloxone (2 mg/2 ml/h; 5 mg in two experiments; n = 7 experiments/group). LH and FSH concentrations were measured at 15-min intervals for a 3-h preinfusion baseline control, during the 5-h infusion, and during a 2-h postinfusion observation period, while cortisol concentrations were measured at frequent intervals during the entire experiment. CRF infusion produced a progressive and significant decrease in both LH and FSH. Mean areas (+/- SE) under the LH and FSH curves during the 5-h CRF infusion, expressed as a percentage of preinfusion baseline, were 59.9 +/- 4.6% and 83.0 +/- 3.1% (+/- SE), respectively (P less than 0.001 and P less than 0.01 vs. saline controls). Large amplitude LH pulses were abolished during the CRF infusion. However, after cessation of CRF infusion, there was a rapid resumption of LH pulsatile release in four of the seven experiments. Addition of naloxone to CRF prevented the CRF-mediated suppression of LH and FSH release. Mean areas for LH and FSH during the 5-h combined infusion were 100.3 +/- 6.6% and 99.6 +/- 4.3% of the preinfusion baseline, respectively (P less than 0.001 and P less than 0.05 vs. CRH alone; NS vs. saline), and pulsatile LH secretion was maintained. Regardless of whether naloxone was administered, CRF increased cortisol levels significantly. Mean cortisol levels at the end of the CRF and CRF plus naloxone infusions were 48.2 +/- 10.4 and 52.9 +/- 7.4 micrograms/dl (+/- SE), respectively, compared to 21.0 +/- 3.0 with saline (P less than 0.05). These results demonstrate that in the ovariectomized rhesus monkey, CRF suppresses the secretion of both LH and FSH, and this effect can be sustained. They also indicate that the CRF inhibitory action on gonadotropin is primarily mediated by endogenous opioid peptides, independent of glucocorticoid levels.

Animals

Polycystic ovarian disease.

Polycystic ovarian disease has a variety of biochemical and clinical features with great individual variation. In our clinical experience, oligo-ovulation, manifested as oligomenorrhea or frank amenorrhea, associated with an acyclic estrogen milieu, is a consistent finding. This may be associated with hyperandrogenemia, hirsutism, inappropriate gonadotropin levels, hyperprolactinemia, obesity, insulin resistance, and ultrasound evidence of multicystic enlarged ovaries. A common presentation is infertility or irregular menstruation secondary to oligo-ovulation and hirsutism secondary to altered androgen metabolism. A challenge in diagnosis is to differentiate polycystic ovarian disease from latent cases of congenital adrenal hyperplasia. Although the precise mechanism in the pathogenesis of polycystic ovarian disease remains undefined, altered function of the hypothalamic-pituitary-ovarian and adrenal axes is both involved and integrated. Results from clinical trials of ovulation induction using different agents have implicated one site or another as the major progenitor of the "vicious cycle" but with no definitive pathway established. Restoring fertility to these patients can be challenging in that not all patients with polycystic ovarian disease respond to clomiphene or do so satisfactorily. The use of glucocorticoid suppression, pituitary suppression with GnRH analogues, or the use of FSH alone may be of benefit in clomiphene treatment failures.

Female

Ileal resection in the operative treatment of endometriosis.

Endometriosis is a common gynecologic condition in which the small intestine is often involved. Anatomic involvement of the appendix and ileum can be catastrophic, leading, respectively, to intussusception and obstruction with potential perforation. We present a case of subclinical ileal endometriosis and recommend careful examination of the ileocecal region during laparotomy when endometriosis is present. Operative treatment is discussed.

Adult

Reproductive potential in the older woman.

There is a definite increase in the number of women bearing children in the 30- and 40-year-old age groups. The total number of women who are 35 to 40 years of age in the United States is projected to increase 42% and the percent births to this age group is projected to increase 37%. This is apparently because of a trend to postpone childbearing and first birth due to women's career priorities, advanced education, control over fertility, financial concerns, late and second marriages, and infertility. Associated with this is an increase in visits to the infertility specialist for older women who have an intrinsic decrease in fecundity with advancing age. Although, on the average, a woman will not experience menopause until about 50 years of age, her effective childbearing period may stop almost a decade earlier. A woman in her late 30s and, especially, early 40s is at some disadvantage in terms of conception delay, ability to carry a chromosomally normal fetus until term, and risk of trisomic conception. Certain endocrinologic parameters have been identified for the woman entering the transition to menopause. Biologic aging of the hypothalamic-pituitary-ovarian axis is intertwined with changes in the endocrine milieu of the perimenopause and preperimenopause. Despite a clear association of decreased fecundity in older women due to multiple biologic and social influences, so long as the individual has regular cycles and essentially normal endocrine parameters, she should be a candidate for an expedited infertility workup and ovulation induction, if not more aggressive treatment. Her obstetric profile is much improved, except for an increase in congenital anomalies and chromosomal defects. Chorionic villus biopsy study or amniocentesis is advised in all cases, regardless of therapy.

Abortion, Spontaneous

The vanishing sac syndrome. Ultrasound evidence of pregnancy failure in multiple gestations, induced and spontaneous.

During a five-year period an ultrasound diagnosis of multiple gestations was made in 162 women. Four cases evidenced an empty gestational sac or sacs associated with viable, normal-appearing gestations. Three of the four patients had ovulation-induced pregnancies. Resorption of these empty sacs was documented. First- and early-second-trimester vaginal bleeding occurred frequently in these pregnancies and was a warning of the possible loss of one or more of the sacs.

Female