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Biomedical subjects

M D Hornstein

Publications and source records attributed to M D Hornstein.

At least 37 records · Page 2Linked to original sources
PubMed1998

Basal hormone levels in women who use acetaminophen for menstrual pain.

OBJECTIVE: To compare basal gonadotropin and estradiol levels between women using acetaminophen versus those using no or other types of analgesics. DESIGN: Observational study. SETTING: Three IVF clinics in greater Boston. PATIENT(S): Three hundred eighty-six women accepted for their first IVF treatment who completed questionnaires recording medical history, including analgesic use for menstrual pain, and who had blood drawn during the menstrual phase of a cycle before treatment. MAIN OUTCOME MEASURE(S): Basal FSH, LH, and estradiol. RESULT(S): Basal hormone levels, especially LH, were lower for women who regularly used acetaminophen compared with women who used no medication or other types of analgesics. Lower hormone levels in acetaminophen users were consistently observed when women were subdivided by age, body mass index, smoking history, and degree of menstrual pain-features that might have influenced analgesic use or hormone levels. CONCLUSION(S): This study provides preliminary evidence that acetaminophen may lower gonadotropin and estradiol levels and offers a biologic basis for the epidemiologic observation that acetaminophen use may reduce the risk of ovarian cancer.

Acetaminophen↗
PubMed1998

Leuprolide acetate depot and hormonal add-back in endometriosis: a 12-month study. Lupron Add-Back Study Group.

OBJECTIVE: To evaluate the efficacy and safety of a GnRH agonist, leuprolide acetate depot, alone and in combination with three hormonal add-back regimens in the management of endometriosis-associated pelvic pain. METHODS: Two hundred and one patients were enrolled in this multicenter, randomized, double-blind, 1-year trial. All patients were given an intramuscular injection of leuprolide acetate depot 3.75 mg every 4 weeks. Patients were assigned to one of four treatment groups: Group A received placebos for progestin and estrogen, group B received norethindrone acetate 5 mg daily and placebo for estrogen, group C received norethindrone acetate 5 mg and conjugated equine estrogens 0.625 mg daily, and group D received norethindrone acetate 5 mg and conjugated equine estrogens 1.25 mg daily. Pelvic pain scores were assessed monthly, and bone density was measured after 24 and 52 weeks. RESULTS: By week 8, all four groups showed significant improvement in pelvic pain scores compared with baseline levels. A higher proportion of group D patients terminated the study prematurely due to a lack of improvement in symptoms. Group A experienced a 6.3 +/- 2.3% (P < or = .001) loss in bone density after 52 weeks of treatment, whereas bone density was preserved in all three add-back groups. CONCLUSION: The use of leuprolide acetate depot in combination with norethindrone acetate 5 mg alone, or with norethindrone acetate and conjugated equine estrogens 0.625 mg, provides effective suppression of pelvic pain symptoms associated with endometriosis while protecting against bone loss.

Adult↗
PubMed1998

Effects of endometriomas on ooccyte quality, embryo quality, and pregnancy rates in in vitro fertilization cycles: a prospective, case-controlled study.

PURPOSE: The effect of endometriomas on oocyte quality, embryo quality, and pregnancy rates in in vitro fertilization (IVF) cycles was evaluated. METHODS: Forty-five women had "chocolate" cysts aspirated at the time of oocyte retrieval, and cyst fluid CA 125 levels were measured to ascertain presence of "true" endometriomas. Fifty-seven women without any complex cysts at the time of oocyte retrieval served as controls. IVF cycle outcome parameters were compared between the two groups. RESULTS: Women with endometriomas experienced a significantly higher rate of early pregnancy loss compared to controls (47 vs 14%). There was also a trend toward fewer oocytes retrieved and fewer embryos reaching at least the four-cell stage 48 hr after retrieval in patients with true endometriomas vs controls. CONCLUSIONS: The presence of endometriomas at the time of oocyte retrieval is associated with increased rates of early pregnancy losses. The number of oocytes retrieved and the embryo quality may also be affected adversely in the presence of endometriomas.

CA-125 Antigen↗
PubMed1997

Use of nafarelin versus placebo after reductive laparoscopic surgery for endometriosis.

OBJECTIVE: To evaluate the efficacy of the GnRH agonist (GnRH-a) nafarelin compared with placebo administered for 6 months after reductive laparoscopic surgery for symptomatic endometriosis. DESIGN: Randomized, prospective, placebo-controlled, multicenter clinical trial. SETTING: Thirteen clinics including private practice and university centers. PATIENT(S): One hundred nine women aged 18-47 with laparoscopically proven endometriosis and pelvic pain who had undergone reductive laparoscopic surgery for endometriosis. INTERVENTION(S): Patients were randomized to receive either the GnRH-a nafarelin (200 micrograms twice daily) or placebo for 6 months. MAIN OUTCOME MEASURE(S): Time to initiation of alternative treatment (the length of time from beginning study medication to receiving alternative therapy or to deeming that the study drug was ineffective) and patient-reported and physician-assessed pelvic pain scores. RESULT(S): The median time to initiation of alternative treatment was > 24 months in the nafarelin group versus 11.7 months in the placebo group. Fifteen (31%) of 49 nafarelin-treated patients required alternative therapy, compared with 25 (57%) of 44 placebo-treated patients. The patients' pelvic pain scores dropped significantly in the nafarelin and placebo groups after 6 months of treatment. Physician summary ratings showed significant improvement in the nafarelin group and no significant changes in the placebo group after 6 months of treatment. CONCLUSION(S): Compared with placebo, nafarelin administered after reductive laparoscopic surgery for endometriosis significantly delays the return of endometriosis symptoms requiring further treatment.

Adolescent↗
PubMed1997

Exogenous gonadotropin stimulation is associated with increases in serum androgen levels in in-vitro fertilization-embryo transfer cycles.

OBJECTIVE: To examine serum androgen profiles in women undergoing ovarian stimulation with exogenous gonadotropins in the setting of IVF-ET. DESIGN: Prospective study. SETTING: University hospital IVF-ET program. PATIENT(S): Seventeen ovulatory women undergoing IVF-ET for endometriosis, male factor infertility, or tubal disease. INTERVENTION(S): A standard long protocol of GnRH agonist (GnRH-a) pretreatment (1 mg of leuprolide acetate SC for 10 days) was administered before ovulation induction with a urinary gonadotropin preparation. MAIN OUTCOME MEASURE(S): After 10 days of GnRH-a treatment and on the day of hCG administration, serum concentrations of LH, T, androstenedione (A), sex hormone-binding globulin (SHBG), and DHEAS; the free androgen index (T/SHBG); and the number of follicles, oocytes, and embryos were assessed. RESULT(S): Serum samples after 10 days of GnRH-a treatment showed incomplete LH suppression. While continuing the agonist during ovarian stimulation, LH values were suppressed further. However, serum T and A concentrations and the free androgen index showed a significant increase (samples drawn just before hCG administration). Serum T levels after 10 days of GnRH-a (before the administration of exogenous gonadotropins) were correlated negatively with the subsequent number of embryos. CONCLUSION(S): Serum LH suppression with a conventional regimen of GnRH-a is incomplete in this heterogeneous group of ovulatory women. Exogenous gonadotropin stimulation results in a marked increase in ovarian androgen secretion.

Adult↗
PubMed1997

Practice patterns among reproductive endocrinologists: the infertility evaluation.

OBJECTIVE: To determine how board-certified reproductive endocrinologists vary in their approach to the clinical tests performed on the infertile couple. DESIGN: A cross-sectional study to assess differences in the approach to evaluating the infertile couple. SETTING: A population-based national survey. PARTICIPANT(S): United States board-certified reproductive endocrinologists. MAIN OUTCOME MEASURE(S): The frequency of clinical tests and evaluation procedures by physician age, sex, size and setting of practice, institutional affiliation, and geographic location. RESULT(S): The overall response rate was 84%. Although the majority of practitioners routinely order a semen analysis (99.9%), an assessment of ovulation (98%), a hysterosalpingogram, (HSG; 96%), laparoscopy (89%), and a postcoital test (PCT, 79%), there was less agreement regarding hormonal testing (range, 22% [LH] to 66% [PRL]), use of pelvic ultrasounds (55%), hysteroscopy (53%), cervical cultures (range, 24% to 54%), and antisperm antibody testing (24%). Compared with male colleagues, female physicians order two to three times more cervical cultures and endometrial biopsies. Serum hormonal testing was two to three times more commonly ordered by younger (< 40 years) compared with older physicians, and physicians in private practice twice as frequently ordered hormonal testing, cervical cultures, PCTs, and antisperm antibody studies compared with their academic-affiliated colleagues. Western U.S. physicians order hormonal tests and cervical cultures 50% less often than their midwest and eastern counterparts. CONCLUSION(S): Trained specialists rely heavily on five "traditional" infertility tests: semen analysis, an assessment of ovulation, HSG, laparoscopy, and PCT. With regard to additional modes of testing, there is marked variability by physician sex, age, type of practice, and geographic location.

Adult↗
PubMed1997

Retreatment with nafarelin for recurrent endometriosis symptoms: efficacy, safety, and bone mineral density.

OBJECTIVE: To assess the efficacy, safety, and effect on bone mineral density of a 3-month course of retreatment with intranasal nafarelin acetate for recurrent symptoms of endometriosis. DESIGN: Multicenter, open-label, nonrandomized clinical trial. SETTING: Eleven hospital-based and private practices. PATIENT(S): Thirty-six women with endometriosis symptoms recurring after 3 or 6 months of treatment with nafarelin. INTERVENTION(S): Nasal nafarelin 200 micrograms twice daily for 3 months. MAIN OUTCOME MEASURE(S): Assessments for dysmenorrhea, dyspareunia, pelvic pain, tenderness, and induration. Measurement of bone mineral density of the lumbar spine. RESULT(S): Improvements from admission to the end of retreatment were significant for dysmenorrhea, pelvic pain, tenderness, induration, and dyspareunia. Three months after retreatment ended, mean symptom scores for dysmenorrhea and pelvic tenderness, although worse than at the end of retreatment, were still significantly better than scores at admission. Mean bone mineral density 3 months after retreatment was 0.56% lower than before retreatment and 1.94% lower than before initial treatment. CONCLUSION(S): Three-month nafarelin retreatment for recurrent endometriosis symptoms was effective and safe.

Administration, Intranasal↗
PubMed1997

The role of GnRH agonists plus add-back therapy in the treatment of endometriosis.

Agonistic analogs of GnRH have emerged as effective drugs in the treatment of pelvic pain associated with endometriosis. Iatrogenic hypoestrogenism is the fundamental mechanism through which GnRH agonists induce regression of the exquisitely estrogen-dependent endometriotic lesions. The decrease in bone mass consistently observed in women on long-term GnRH agonist treatment has prompted regulatory agencies such as the FDA to approve the use of these drugs for a maximum of six months in the treatment of endometriosis. The very high recurrence rate of pelvic symptomatology after the interruption of medical therapy underlines the importance of strategies aiming at improving the safety of effective long-term treatments. Data has recently become available suggesting the existence of an ideal range of circulating estradiol levels which would maintain a normal bone metabolism and still cause atrophy of endometriotic lesions. Add-back regimens including estrogen preparations have been therefore studied with variable results. In strict analogy, as oral progestins have been shown to improve bone mass in postmenopausal women, regimens employing progestin add-back have been proposed. Our review describes most of the currently published studies employing these and other substances in association with the commonly used GnRH agonists in patients with symptomatic endometriosis.

Bone Resorption↗
PubMed1997

Association between endometriosis, dysplastic naevi and history of melanoma in women of reproductive age.

Women with melanoma and its precursor lesions, dysplastic naevi, have a higher prevalence of reproductive disorders than women without melanotic lesions. This association appears strongest among young women with dysplastic naevi and endometriosis. The purpose of this study was to evaluate patients with laparoscopy-confirmed endometriosis for the presence of dysplastic naevi. A total of 66 endometriosis patients and 35 controls completed a detailed questionnaire and underwent an extensive dermatological examination for the presence of dysplastic naevi. In all, 41% of patients aged < or = 32 years had dysplastic naevi, compared with 8% of controls (P = 0.038). In addition, 29% of patients with endometriosis reported a family history of melanoma compared with 10% of controls (P = 0.039). This study demonstrated an association between endometriosis and dysplastic naevi in younger women of reproductive age and found an associated family history of melanoma among endometriosis patients. These observations may be useful in the evaluation and care of young women by both gynaecologists and dermatologists.

Adult↗
PubMed1997

Estrogen-induced changes in protein binding of bupivacaine during in vitro fertilization.

BACKGROUND: Patients having in vitro fertilization (IVF) procedures that use gonadotropin-releasing hormone agonist down-regulation undergo hormonal manipulation of estrogen concentrations to induce oocyte maturation. After achieving minimal estrogen concentrations (baseline), stimulation increases estrogen concentrations to supraphysiologic levels, leading to egg retrieval. The isolated effect of estrogen on protein binding has not previously been reported. This study was conducted to measure the effect of estrogen concentrations on protein binding of two concentrations of bupivacaine, 1 microg/ml and 5 microg/ml, corresponding, respectively, to systemic concentrations expected after administration of epidural anesthesia and associated with bupivacaine toxicity. Serum proteins were measured to address the mechanism. METHODS: Twenty-nine healthy women undergoing IVF procedures were enrolled and venous samples were drawn at times of minimal and maximal estrogen concentrations. The percentage of free bupivacaine was determined at fixed concentrations of 1 and 5 microg/ml. Serum albumin and alpha1-acid glycoprotein concentrations were measured at baseline and at retrieval in a group of 24 women. RESULTS: The percentage of free bupivacaine increased between times of minimal and maximal serum estrogen concentrations, corresponding to decreased protein binding. Concentrations of serum albumin and alpha1-acid glycoprotein decreased between baseline and retrieval times. CONCLUSIONS: Patients undergoing IVF procedures demonstrate a decrease in protein binding of bupivacaine from baseline concentrations. These changes may be explained by a decrease in albumin and alpha1-acid glycoprotein. During anesthesia for egg retrieval, clinicians should consider the implications of increased free fraction of drug, especially for highly protein-bound agents.

Anesthetics, Local↗
PubMed1997

Early singleton pregnancy outcome: effects of maternal age and mode of conception.

PURPOSE: To assess the effect of prognostic factors on the outcome of singleton pregnancies. MATERIALS AND METHODS: First-trimester ultrasonographic (US) scans that demonstrated a living fetus in 4,156 consecutive singleton pregnancies were studied. The relationship between outcome and maternal age, mode of conception, maternal symptoms, and US findings was evaluated. RESULTS: Spontaneous abortion occurred in 371 of 4,156 (8.9%) cases. Higher pregnancy-loss rates were associated with older maternal age (P < 10(-5)), assisted mode of conception (P < 10(-8)), maternal symptoms of pain and/or bleeding (P < .001), and abnormal US findings (P < 10(-8)). US abnormalities were more frequent in older women than in younger women (P < 10(-5)) and in assisted conceptions than in natural conceptions (P < 10(-8)). At stepwise logistic regression, with gestational age as a covariate, US abnormalities and maternal symptoms independently affected pregnancy outcome. Maternal age and mode of conception had no further statistically significant effect on pregnancy outcome. CONCLUSION: The prognosis for older mothers and for those with assisted conception is not statistically significantly different from that for younger mothers and for those with natural conception if maternal symptoms, US findings, and gestational age are the same.

Abortion, Spontaneous↗
PubMed1996

The effect of elevated serum progesterone during ovulation induction in in vitro fertilization-embryo transfer.

OBJECTIVE: Our purpose was to determine whether elevated progesterone (P) during ovulation induction in IVF-ET cycles is a poor prognostic factor for achieving pregnancy. DESIGN: We retrospectively reviewed 672 consecutive IVF-ET cycles in which ovulation was performed using luteal LA downregulation and hMG. SETTING: The ART program at the Brigham & Women's Hospital, a tertiary care institution, was the study setting. MAIN OUTCOME MEASURES: Patients were divided into groups by serum P levels at baseline, on stimulation day 5, on the day of hCG injection, and, on the day after hCG injection and the following parameters were compared: duration of luteal LA treatment, number of ampoules of hMG used, estradiol (E2) levels, number of follicles > or = 12 mm, number of follicles > or = 15 mm, number of oocytes, number of normal embryos, number of polyspermic embryos, fertilization rate, implantation rate, and clinical and ongoing/live birth pregnancy rates. RESULTS: Based on serum P level, patients were divided into three groups: Group I, < or = 0.31 ng/ml (conversion factor to SIU, 3.180); Group II, and > 0.3 and < 1.0 ng/ml and Group III, > or = 1.0 ng/ml. Measureable P at baseline was associated with a higher cancellation rate, but no difference in other cycle outcome parameters. Progesterone > 0.31 ng/ml on stimulation day 5 was associated with a higher fertilization rate in Groups II and III, but there was no difference in the clinical pregnancy or ongoing/live birth rates among the three groups. Based on P on the day of hCG administration, Groups II and III had significantly more oocytes and higher fertilization rates than did Group I, however, clinical pregnancy and ongoing/live birth rates were not significantly different. On the day after hCG, there was a trend toward a higher clinical pregnancy rate in Group III, which had younger patients, better follicular recruitment, and more embryos than Groups I or II, but these differences did not reach statistical significance. CONCLUSIONS: Serum P > 0.31 ng/ml during ovulation induction reflects good follicular recruitment, and is not a predictor of IVF outcome.

Adult↗
PubMed1996

A randomized clinical trial to evaluate the clinical effects of split- versus single-dose human menopausal gonadotropins in an assisted reproductive technology program.

OBJECTIVE: To compare the effect of twice (split) versus once (single) daily administration of hMG on assisted reproductive technology (ART) cycle parameters. DESIGN: A randomized clinical trial. SETTING: Hospital-based academic ART program. PATIENTS: A total of 171 patients undergoing their initial ART cycle were enrolled. All patients received one of two hMG regimens and were excluded from the study if they were receiving medications other than leuprolide acetate (LA) and hMG for ovulation induction. INTERVENTIONS: Subjects were randomized to receive an initial dose of 300 IU/d of hMG in either split-dose (i.e., 150 IU twice daily) or single-dose fashion for four successive days after down-regulation with LA. Thereafter, their daily dose was individualized, maintaining a split-or single-dose schedule. All cycles were managed in accordance with our standard ART protocols. MAIN OUTCOME MEASURES: Cancellation rate, total hMG requirements, number of days treated with hMG, E2 and P responses, oocyte yield and maturity, fertilization rate, total number of embryos, embryo quality, number of embryos transferred, implantation rate, clinical and ongoing-delivered pregnancy rates. RESULTS: Split-dose hMG administration resulted in a significantly higher implantation rate, but significantly lower normal and polyspermic fertilization rates than single-dose hMG administration. No significant differences were noted between the two dosage protocols with respect to the other outcome measures. CONCLUSIONS: Split-dose hMG administration may be associated with significantly higher implantation rates; single-dose hMG with significantly higher fertilization rates. Although our data also demonstrate a trend toward higher clinical and ongoing-delivered pregnancy rates with split-dose therapy, demonstration of a significant difference would require a multicenter trial. Based on our data, clinicians may want to consider split-dose therapy for patients with repeated implantation failures.

Adult↗
PubMed1996

Endometriosis associated with the N314D mutation of galactose-1-phosphate uridyl transferase (GALT).

To explore a possible connection between endometriosis, Müllerian anomalies, and possession of the N314D allele of the gene for galactose-1-phosphate uridyl transferase (GALT), we studied 33 women with endometriosis attending a fertility clinic. Patients completed questionnaires and had DNA tested for the N314D mutation of GALT. A previously completed general population survey of 111 women which obtained the same information was available for comparison. Women with endometriosis were more likely to carry at least one N314D allele (30% compared with 14%) and more likely to report a medical history of scoliosis (21% compared with 2%) compared to general population controls: two features we have described in women with vaginal agenesis. Compared with endometriosis cases without the N314D allele, those cases with the allele tended to have more advanced disease and a family history of endometriosis. We speculate that endometriosis may arise due to defects of canalization of the cervix leading to cervical stenosis and retrograde menstruation. The relevance of the N314D mutation, via this model, may derive from an association between abnormalities of galactose metabolism and vaginal agenesis which represents a canalization defect of the vaginal plate of the Müllerian tubercle, the same structure which gives rise to the cervix.

Contraceptives, Postcoital, Synthetic↗
PubMed1996

Use of a second-generation CA125 assay in gynecologic patients.

OBJECTIVE: To determine the correlation between the widely used CA125 assay and a second-generation assay, CA125 II, in a large population of women to determine the utility of measuring CA125 levels in the diagnosis of benign gynecologic disease. METHODS: A total of 822 patients who presented to a gynecology clinic completed a medical questionnaire and underwent a physical examination. Blood samples were obtained to determine serum CA125 levels. Hospital charts were reviewed, and diagnoses were correlated with serum CA125 levels as measured by the CA125 and CA125 II assays. RESULTS: CA125 and CA125 II assay values were highly correlated within four subject categories: age, ethnicity, smoking history, and menstrual category. Mean values decreased with increasing age but were unchanged across ethnic groups and cigarette-smoking status. When means were compared for results of the second-generation and current assays, little difference was found in the age, ethnicity, and smoking categories. Mean serum CA125 values on the CA125 II assay exceeded those on the CA125 assay when obtained during the menstrual and follicular/luteal phases of the menstrual cycle, but they did not differ in anovulatory, pregnant, and menopausal women or in those patients taking hormonal medications. CA125 levels were elevated on both assays in women with fibroids and were higher on the CA125 II assay than on the CA125 assay in women with benign ovarian cysts. CONCLUSIONS: Serum CA125 levels obtained using the CA125 II assay are closely correlated with those obtained using the more familiar CA125 assay. In the diagnosis of benign gynecologic disease, the usefulness of a single serum level measured with the newer CA125 II assay was the same as that of a single CA125 assay level.

Biomarkers↗
PubMed1996

Dexamethasone during ovulation induction for in-vitro fertilization: a pilot study.

The purpose of the present study was to determine whether adrenal androgen suppression with dexamethasone (DEX) during ovulation induction improves the outcome of in-vitro fertilization (IVF) cycles. A total of 25 patients with serum dehydroepiandrosterone sulphate (DHEAS) concentrations > 2.5 micrograms/ml were randomized to receive either 0.5 mg DEX daily or placebo during ovulation induction with leuprolide acetate down-regulation plus human menopausal gonadotrophins (HMG). Nine patients undergoing a subsequent IVF cycle were crossed over to the other treatment group. Ovarian responsiveness and IVF outcome variables analysed included number of follicles > 12 mm in diameter, serum oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration, number of ampoules of HMG administered, number of oocytes retrieved, percentage of oocytes fertilized, number of embryos transferred, implantation rate and numbers of clinical pregnancies and live birth pregnancies. The 31 randomized IVF cycles revealed a trend towards a higher implantation rate for the placebo-treated group compared to the DEX-treated group (24 versus 10%; P = 0.07). The remainder of the IVF cycle variables revealed no statistically significant differences. In conclusion, the suppression of adrenal androgens with DEX in women with DHEAS concentrations > 2.5 micrograms/ml appears to have no beneficial effects on ovarian responsiveness or clinical or live birth pregnancy rates.

Adult↗