Biomedical subjects
Publications and source records attributed to K S Moghissi.
Hormone replacement therapy in postmenopausal women offers important benefits for preventing chronic disabling diseases, including prevention of osteoporosis and decreased risk of colon cancer. Although such therapy also carries various possible increased risks, most women will benefit from this therapy.
Gonadotropin-releasing hormone (GnRH) and its analogues have been extensively used in clinical medicine since they were identified and synthesized in 1971. Native GnRH stimulates gonadotrophs of the anterior pituitary and has been used for induction of ovulation. The GnRH agonists, which have greater potency and a longer half-life than native GnRH, produce an initial stimulation of pituitary gonadotrophs that results in secretion of follicle-stimulating hormone and luteinizing hormone and the expected gonadal response. This response is followed by downregulation and inhibition of the pituitary-gonadal axis. The GnRH antagonists promptly suppress pituitary gonadotropin by GnRH-receptor competition, thereby avoiding the initial stimulatory phase of the agonists. Discontinuation of GnRH antagonist treatment leads to a rapid and predictable recovery of the pituitary-gonadal axis. The GnRH analogues are potent therapeutic agents that are considerably useful in a variety of clinical indications. These indications include management of endometriosis, uterine leiomyomas, hirsutism, dysfunctional uterine bleeding, premenstrual syndrome, assisted reproduction, and some hormone-dependent tumors.
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OBJECTIVE: To determine whether hormone replacement therapy (HRT) plus goserelin (Zoladex) is as effective as goserelin alone for the relief of pelvic symptoms of endometriosis and to determine whether it reduces both the loss of bone mineral density (BMD) and the physiologic side effects associated with goserelin therapy. DESIGN: Prospective, placebo-controlled study, open label for goserelin therapy and double-blind for HRT. SETTING: Forty-two teaching or community hospitals. PATIENT(S): Premenopausal women with symptomatic endometriosis. RESULT(S): Statistically significant mean decreases from baseline in the total pelvic symptom score and total subjective score were observed by week 24 for all three groups. There were no statistically significant treatment differences for change in total symptom score. Some degree of BMD loss occurred in the three groups; however, the percentage loss was consistently greater in the HRT0 group than in the HRT1 or HRT2 groups. When analyzed separately, no overall age effect on BMD change was seen in women >30 years of age versus women < or = 30 years. The HRT1 and HRT2 groups had fewer occurrences of hot flushes and vaginal dryness than did the HRT0 group. CONCLUSION(S): Goserelin plus HRT is as effective as goserelin alone in relieving pelvic symptoms of endometriosis and attenuates both the loss of BMD and the physiologic side effects of hot flushes and vaginal dryness associated with goserelin therapy.
OBJECTIVE: To determine hormone levels across the menstrual cycle in women with rigorously defined unexplained infertility. DESIGN: Prospective study. SETTING: National Center for Infertility Research at Michigan. PATIENT(S): Evaluation of 1,885 women with infertility identified 12 women who met the following rigorously defined criteria for unexplained infertility: [1] infertility of > or = 24 months' duration, with no male factor, anatomic or functional disorders of the reproductive tract, or immunologic infertility; [2] normal body mass index (BMI); (3) ovulatory cycles ranging from 26 to 32 days; [4] normal luteal phase determined by endometrial biopsy; and [5] normal baseline hormonal profile. Controls (n = 12) were healthy, parous women with normal ovulatory cycles and normal hormonal screens, and were matched for age and BMI with patients. MAIN OUTCOME MEASURE(S): Daily gonadotropin and steroid hormone levels across the menstrual cycle. RESULT(S): Basal FSH and LH levels in the early, middle and late follicular phases were increased significantly in the group with unexplained fertility compared with the normal controls. The mean (+/-SD) early follicular FSH levels were 7.0 +/- 0.57 mIU/mL in the unexplained-infertility group and 4.7 +/- 0.37 mIU/mL (conversion factor to SI units, 1.00) in the normal controls, respectively. There was no difference between groups over the periovulatory or luteal phase. Midluteal mean (+/-SD) P levels were lower in the unexplained-infertility group than in the normal controls (13.7 +/- 1.6 versus 24.0 +/- 3.2 ng/mL [conversion factor to SI units, 3.180]). Mean E2 concentrations were elevated in the group with unexplained infertility versus normal controls in the early through the late follicular phase but reached significance only in the midfollicular phase. Mean prolactin levels were elevated consistently across the menstrual cycle in the unexplained-infertility group compared with those in normal controls but reached significance only in the early and late follicular and midluteal phases of the cycle. Cortisol concentrations were similar between the two groups. CONCLUSION(S): These data indicate that there are subtle alterations in various hormones measured across the menstrual cycle in women with unexplained infertility compared with those in normal controls, suggesting a diminished ovarian reserve.
OBJECTIVE: To evaluate the luteal phase in women with rigorously defined unexplained infertility. DESIGN: Prospective study. SETTING: National Center for Infertility Research at Michigan. PATIENT(S): Evaluation of 1,885 women with infertility identified 12 women who met the rigorously defined criteria for unexplained infertility: [1] infertility of > or = 24 months duration, with no male factor, anatomic-functional disorders of the reproductive tract, or immunologic infertility; [2] normal body mass index (BMI); [3] ovulatory cycles ranging from 26 to 32 days; [4] normal luteal phase determined by endometrial biopsy; and [5] normal baseline hormonal profile. Controls (n = 12) were healthy, parous women with normal ovulatory cycles, normal hormonal screen, and were matched for age and BMI to patients. MAIN OUTCOME MEASURE(S): Pattern of follicular growth rate and luteal phase hormonal profile. RESULT(S): Women with unexplained infertility did not differ in menstrual cycle characteristics, follicular growth rate or mean preovulatory follicle diameter, or endometrial biopsy dating. The mean levels of P tended to be lower in the unexplained infertility group throughout the luteal phase, but only the midluteal interval reached statistical significance. Luteal phase mean integrated P or urinary PDG levels of unexplained infertility women did not differ from those of fertile controls. The ratio of integrated E2:P also was significantly greater in women with unexplained infertility than in fertile controls. CONCLUSION(S): Women with rigorously defined unexplained infertility have subtle hormonal anomalies during the luteal phase when compared with fertile controls.
OBJECTIVE: To compare the bioactive and immunoactive PRL in normal and unexplained infertility subjects. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology, Wayne State University and The University of Michigan. PATIENT(S): Twelve normal, fertile women compared with 12 patients with unexplained infertility. INTERVENTION(S): Serum samples were obtained across the menstrual cycle and for each subject, 5 pools were prepared by combining serum aliquots from the early follicular, late follicular, midcycle, and midluteal and late luteal phases of the cycle. MAIN OUTCOME MEASURE(S): Niobium lymphoma cell bioassay and an immunoradiometric assay were used to quantitate PRL. RESULT(S): A midcycle increase in PRL was seen in controls by both assays and these levels were greater compared with other cycle stages. Comparison of midcycle PRL between groups showed differences only between bioactive PRL (34.2 +/- 8.3 versus 19.2 +/- 3.4 ng/mL [conversion factor to SI unit, 1.00]). The ratios between bioactive and immunoactive PRL were comparable. Significant correlation between bioactive and immunoactive PRL was seen for both control (r = 0.616) and unexplained infertility (r = 0.660) groups. CONCLUSION(S): The midcycle elevations of bioactive and immunoactive PRL seen in normal women were absent in women with unexplained infertility. This alteration in PRL dynamics may be a part of subtle differences in the reproductive hormone profile of women with unexplained infertility compared with their fertile counterparts.
OBJECTIVE: To determine the effects of elevated endogenous E2 levels on in vitro platelet function in patients undergoing controlled ovarian hyperstimulation (COH). DESIGN: Women with normal ovulatory cycles and patients undergoing COH on cycle day 3 and near ovulation (preovulatory follicles were at least 16 mm in diameter) were studied. Serum E2, Thrombostat 4000, (V. d. Goltz, Seeon, Germany), von Willebrand factor antigen (vWF-Ag), and platelet aggregation and adenosine triphosphate (ATP) release to adenosine diphosphate (ADP), collagen (COL), and arachidonic acid (AA) were measured. SETTING: University-based outpatient infertility clinic. PATIENT(S): Twenty-two consenting infertile women undergoing COH cycles and 14 women with documented ovulatory cycles. MAIN OUTCOME MEASURE(S): Whole blood platelet aggregation with ADP, COL, AA, and Thrombostat 4000. RESULTS(S): Estradiol levels rose significantly at peak times (P = 0.011). No changes were noted in in vitro platelet function measured by the Thrombostat 4000 and by whole blood platelet aggregation with ADP and AA and in ATP release with ADP, COL, or AA. Aggregation with collagen was increased because of likely elevations in vWF-Ag levels. CONCLUSION(S): No significant changes in in vitro platelet function were noted in 19 women undergoing COH with E2 levels two to three times that observed in oral contraceptive or hormone replacement therapy users, suggesting no increased risk for arterial thromboembolism.
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OBJECTIVE: Our purpose was to assess the changes in multifetal pregnancy generation as a function of utilization of ovulation stimulation and assisted reproductive techniques and to document the relative control of hyperstimulation between the methods. STUDY DESIGN: The methods of infertility treatment, number of fetuses, and outcomes of 220 patients referred for multifetal pregnancy reduction were compared over three time periods (1986 to 1989, 1991 to 1992, and 1992 to 1993). Clomiphene, human menopausal gonadotropin, and ovulation stimulation with urofollitropin were compared against gamete intrafallopian transfer, zygote intrafallopian transfer, and in vitro fertilization (assisted reproductive techniques). RESULTS: The proportion of multifetal pregnancies generated by assisted reproductive techniques has steadily risen from 26% in the first two time periods to nearly half in the last 2 years. However, the number and proportion of quintuplet and greater pregnancies from assisted reproductive techniques have steadily fallen while for ovulation stimulation the proportion has remained about one third. CONCLUSION: Despite considerably increased use and proportionate generation of triplet and quadruplet pregnancies, the incidence of quintuplets has fallen for assisted reproductive techniques while there has been no improvement for ovulation stimulation. Continued, greater vigilance, particularly in the use of human menopausal gonadotropin and urofollitropin, must be emphasized.
To study why suckling-induced plasma prolactin levels decline in magnitude with advancing lactation, we examined prolactin release in lactating rats following suckling and pharmacologic manipulations during early, mid- and late lactation. On day 2 of lactation, litters were adjusted to 8 pups. On day 3, dams were implanted with an atrial catheter and experiments were conducted on lactation days 5, 11 and 17. To examine suckling-induced prolactin release, pups were removed at 0800 h, an extension was attached to the catheter at 1100 h, and pups returned to dams at 1200 h. Blood samples were obtained before, and at 10, 30, 60, 90 and 120 min after suckling started. Prolactin responses to sulpiride and thyrotropin releasing hormone (TRH) administration were studied in lactating rats separated from their litters for 4 hours. Blood samples were obtained before, and at 10, 30, 60 and 90 min after sulpiride (10 or 40 micrograms/kg BW) and 5, 10, 20 and 30 min after TRH (1 or 4 micrograms/kg BW) in rats pretreated with sulpiride. Prolactin release in response to suckling, administration of sulpiride or sulpiride and TRH diminished as lactation advanced. From these results, we conclude that refractoriness in anterior pituitary lactrotropes to prolactin-releasing stimuli is at least partially responsible for the decline in suckling-induced prolactin release with advancing lactation.
A patient with long-standing secondary infertility was explored for myomectomy, at which time severe adenomyosis was found. A 6-month course of nafarelin acetate resulted in resolution of dysmenorrhea and uterine enlargement. The patient conceived quickly. Although the patient spontaneously aborted, this report presents the first in which medical therapy of adenomyosis is associated with successful treatment of infertility.
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OBJECTIVES: To determine if Poloxamer 407 (poloxamer, Pluronic F-127; BASF Wyandotte Corp., Parsippany, NJ) is as effective as Interceed(TC7) (Ethicon, a Johnson and Johnson company, Sommerville, NJ) in preventing postoperative adhesion formation using the rat uterine horn model and to determine if the presence of blood or lactated Ringer's solution affects the effectiveness of Poloxamer 407. DESIGN, SETTING, PARTICIPANTS: Sprague-Dawley white rats, weighing 225 to 250 g in a conventional laboratory setting. The left or right sidewall was randomly assigned to receive no treatment (control), Interceed(TC7), or poloxamer. INTERVENTIONS: Each uterine horn and ipsilateral sidewall was subjected to a standardized lesion of denudation. To evaluate the barrier agents in the presence of blood, a sidewall vessel was ligated and a thrombus allowed to form. To evaluate the effectiveness of lactated Ringer's solution, 10 mL was injected intraperitoneally after abdominal closure. MAIN OUTCOME MEASURES: Degree of adhesion formation was evaluated 14 days after surgery. RESULTS: The adhesion score for the poloxamer-treated animals was significantly lower than its control. Interceed(TC7) did not reduce adhesion formation as compared with its control. In animals that received both poloxamer and Interceed(TC7) on either side, the poloxamer-treated sides had a significantly lower adhesion score than Interceed(TC7)-treated sides. The presence of blood and lactated Ringer's reduced the adhesion-reducing properties of poloxamer. CONCLUSION: In this model, poloxamer is more effective than Interceed(TC7) in the prevention of postoperative adhesion formation. These findings also suggest that the presence of blood compromises the effectiveness of poloxamer to prevent postoperative adhesion formation, therefore requiring complete hemostasis before poloxamer's application. Lactated Ringer's instillation was ineffective in reducing adhesion formation on the control or poloxamer-treated sidewall.
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The effect on fertilization and development of local anesthetics routinely used during ultrasound-guided oocyte retrieval in women undergoing in vitro fertilization was examined in a mouse in vitro fertilization system. Mouse oocytes were exposed in vitro to lidocaine, chloroprocaine, and bupivacaine at concentrations of 0 (control), 0.01, 0.1, 1.0, 10.0, 100.0 micrograms/mL for 30 min, washed, and then inseminated. In vitro oocyte fertilization at 24 and 48 h and embryo development at 72 h were determined. Bupivacaine adversely affected mouse in vitro fertilization and embryo development only at the highest exposure concentration, 100 micrograms/mL, while lidocaine and chloroprocaine produced adverse effects at concentrations as low as 1.0 and 0.1 microgram/mL, respectively. Furthermore, an adverse dose-related effect on fertilization and embryo development was shown for lidocaine and chloroprocaine, but not for bupivacaine. These data demonstrate that the local anesthetics, lidocaine (L), chloroprocaine (C), and bupivacaine (B), adversely affect mouse in vitro fertilization and embryo development in the order of C greater than L greater than B.
OBJECTIVE: To assess the fertility after varicocelectomy in men with subclinical varicocele. DESIGN: We define subclinical varicocele as the varicocele detected by Doppler examination of the scrotum, in which no varicocele was found on clinical examination. Varicocelectomy was performed on subclinical varicocele, and fertility was assessed. SETTING: We reviewed the records of 54 men who underwent unilateral varicocelectomy at the Department of Urology, Wayne State University, between 1986 and 1987. PATIENTS: Records of 54 men were analyzed. Thirty-eight (70%) of the varicocele were diagnosed clinically (confirmed by Doppler examination) in group 1. In 16 (30%) men, the varicocele was diagnosed by Doppler examination only, with no varicocele detectable clinically, subclinical varicocele (group 2). RESULTS: Spermiograms improved in 76% of the patients in group 1 and in 81% of the patients in group 2. Fertility was assessed after 2 years of varicocelectomy. Eighteen (47%) of 38 patients in group 1 and 8 (50%) of 16 men in group 2 managed to impregnate their partners. Statistical analysis by chi 2 shows similar improvement in fertility potential between the two groups (P = 0.86). Multivariate repeated measure analysis showed significant improvement in sperm density (P = 0.0006) and sperm morphology (P = 0.0016) after varicocelectomy. CONCLUSIONS: These data suggest that varicocelectomy, in infertile men with subclinical varicocele, leads to fertility in 50% of the patient population as compared with 47% in clinical varicocele group. We suggest that the use of sophisticated, noninvasive techniques such as Doppler may have a place in the management of male infertility to detect subclinical varicocele.
The effects of cocaine on ovulation and corpus luteum function were investigated in New Zealand White rabbits. Forty females were randomly assigned to control and cocaine-treated groups. Controls were given vehicle s.c. daily for 5 days and cocaine-treated rabbits received 40 mg/kg cocaine hydrochloride s.c. daily for 5 days. One hour after the last cocaine dose, half the control and half of the cocaine-treated groups were mated with fertile males and the other half of each group received hCG i.v. Serial blood samples were obtained over 4 h on the day of mating or hCG treatment (Day 0), and then at intervals from Days 1-18. No mated, cocaine-treated rabbits ovulated, vs. 6 of 10 controls (chi-square: p = 0.01). In contrast, all animals given hCG had comparable numbers of corpora lutea (control: 7.1 +/- 0.8; cocaine: 5.7 +/- 0.8). Peak levels of benzoylecgonine (the major cocaine metabolite) occurred between 180 and 240 min after cocaine administration. In cocaine-treated animals that were mated, Day 0 serum LH (repeated measures MANOVA, p less than 0.01) and FSH (p less than 0.03) concentrations were lower than those in pregnant controls. Serum LH and FSH levels for all hCG recipients (cocaine-treated and control) did not differ. Serum prolactin concentrations in mated, pregnant rabbits were higher than in all other groups; cocaine treatment did not affect this hormone.(ABSTRACT TRUNCATED AT 250 WORDS)