Explicit memory in pregnant women.

OBJECTIVE: The study was conducted to systematically investigate previous anecdotal reports of memory decline during pregnancy. STUDY DESIGN: We used a longitudinal design to investigate memory in women throughout pregnancy and in the postpartum period. Closely matched, nonpregnant women were similarly studied at equivalent intervals. We also assessed degree of depression and anxiety. RESULTS: There was a significant time-by-group interaction (P < .01) for both immediate and delayed recall of paragraph length material. Contrasts showed a significant decline in memory for the pregnant group from the second to the third trimester (P < .01). No significant changes in memory were noted for the control group. The pregnant women scored higher on both depression and anxiety scales; however, somatic rather than cognitive items accounted for the elevated scores. Fluctuations in mood and memory did not coincide. CONCLUSION: There is a pregnancy-related decline in memory, which is limited to the third trimester. The decline is not attributable to depression, anxiety, sleep deprivation, or other physical changes associated with pregnancy.

Intensive hormone monitoring in women with unexplained infertility: evidence for subtle abnormalities suggestive of diminished ovarian reserve.

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.

Vaginal-associated immunity in women with recurrent vulvovaginal candidiasis: evidence for vaginal Th1-type responses following intravaginal challenge with Candida antigen.

Studies from women with recurrent vulvovaginal candidiasis (RVVC) and from an animal model of experimental vaginitis suggest that deficiencies in immune function should be examined at the local rather than systemic level. Evidence of vaginal cell-mediated immunity (CMI) was evaluated for the first time in cervicovaginal lavage (CVL) fluid from RVVC patients. Results showed that although constitutive Th1- and Th2-type cytokine expression was detectable in CVL fluid from normal women, and differences in cytokines were observed in RVVC patients, limitations in experimental design of such de novo analyses urged caution in interpretation. Alternatively, attempts were made to establish conditions in control subjects whereby vaginal immunity could be detected after intravaginal challenge with Candida antigen. Preliminary results showed that Th1-type cytokines (interleukin-2 and -12, interferon-gamma) and histamine were increased 16-18 h after intravaginal introduction of Candida skin test antigen. Intravaginal antigenic challenge represents a novel approach for studying Candida-specific vaginal CMI.

Midcycle increase of prolactin seen in normal women is absent in subjects with unexplained infertility.

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.

Unexplained infertility: evaluation of the luteal phase; results of the National Center for Infertility Research at Michigan.

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.

Potential effects of midcycle cervical mucus on mediators of immune reactivity.

OBJECTIVE: To examine the effect of cervical mucus (CM) on immune mediators in cervicovaginal lavage fluid. DESIGN: The stability of cytokines and immunoglobulins (Ig) within cervicovaginal lavage fluid was determined during 18-hour contact with unsolubilized midcycle CM in vitro. SETTING: In vitro experiment. PATIENT(S): Healthy female volunteers from whom cervicovaginal lavage fluid and periovulatory CM were obtained. INTERVENTION(S): Changes in cytokine and Ig concentration in cervicovaginal lavage fluid after incubation with CM. MAIN OUTCOME MEASURE(S): Interleukin (IL)-4, IgA, and IgG concentrations were determined by ELISA. Interleukin-2 concentration was determined by bioassay using the IL-2-dependent cytotoxic T-lymphocyte cell line and ELISA. Results were expressed as percent antibody or cytokine recovery remaining after mucus contact, with differences over time evaluated by analysis of variance. RESULT(S): During 18-hour mucus contact, significant changes were detected for IL-4, IgA, and IgG concentration. Interleukin-2 was stable in mucus-associated cervicovaginal lavage fluid as determined by functional bioassay and ELISA. CONCLUSION(S): Immunoglobulins and cytokines differ in their recovery from aqueous media after CM contact, suggesting that midcycle CM could alter immune reactivity within the reproductive tract by modifying the availability or function of immunomodulatory substances.

Ectopic pregnancy. A recent five-year study and review of the last 50 years' literature.

OBJECTIVE: To compare the past and current clinical and pathologic factors that are responsible for ectopic pregnancy (EP). STUDY DESIGN: We performed a retrospective chart and histopathologic specimen review of 740 cases of EP during a recent, five-year period. Products of conception, as well as 240 cases of concomitant endometrial biopsies, were examined. RESULTS: The mean age at presentation, proportion of patients with a history of pelvic inflammatory disease, voluntary interruption of pregnancy (VIP), previous surgery and laterality (right side) of the tubal EP were similar to rates reported in previous studies. Ninety-four percent of the EPs were tubal, and 90% of the tubes exhibited some pathologic changes, including chronic salpingitis (49.5%) and follicular salpingitis (10%), among others. Gestational endometrial patterns were seen in 44% of cases. The corpus luteum of pregnancy was contralateral in 30% of cases in which an ovarian biopsy was performed. CONCLUSION: The factors classically associated with EP remained similar over a period of about 50 years, although the association with VIP still appears to be controversial. Endometrial curettage alone cannot be used to exclude an EP. Ovum transmigration may play a role in the genesis of EP.

Flare-up of endometriosis induced by gonadotropin-releasing hormone agonist leading to bowel obstruction.

OBJECTIVE: To report a case of intestinal obstruction that developed shortly after preoperative administration of a GnRH analogue (GnRH-a) that caused flare-up and rapid progression of enteric endometriosis. DESIGN: Case report. SETTING: University tertiary reproductive endocrinology practice. PATIENT: A 34-year-old nulligravid female with progressive severe symptomatic endometriosis. INTERVENTIONS: Planned preoperative administration of GnRH-a for 3 months followed by extirpative surgery and hormone replacement therapy. Instead, total abdominal hysterectomy, bilateral salpingoophorectomy, resection of the obstructed ileocecal junction, and side-to-side ileo-ascending enterocolostomy was performed. RESULTS: Preoperative GnRH-a administered in the midfollicular phase resulted in flare-up of preexisting ileocecal endometriosis that rapidly progressed, resulting in partial small bowel obstruction. CONCLUSION: Gonadotropin-releasing hormone agonist should be used with caution when there is known or suspected enteric endometriosis. Consideration should be given to blocking the agonistic effect of GnRH-a in this setting by the prior or concomitant use of progestins or danazol.

Hormonal contraception and platelet function.

PIP: 73 healthy women (29 controls, 25 using OCs, and 19 using Norplant) were selected from the clinic population at North Oakland Medical Center for inclusion in this study after obtaining informed consent. Age, race, height, weight, blood pressure, and cigarette smoking were recorded for each subject. 12 patients were on monophasic OCs while 13 were on triphasic preparations. Both hormonal contraceptive groups had used their particular contraceptive for at least 3 months prior to blood drawing. Platelet tests were performed within 2 hours of sample collection: platelet counts (PLC) and mean platelet volume (MPV) were determined on an Automated Platelet Counter (Baker 810 Platelet Analyzer). Whole blood aggregation was performed on a platelet aggregometer (Chrono-Log, Model 550) using both ADP (ADP, 5 mM) and collagen (COLL, 2 mcg/ml) as inducing agents. Demographic differences were not significant (p 0.05) among the 3 treatment groups, whose average age was 25.3-25.8 years old. Furthermore, no significant differences (p 0.05) in platelet function were detected among controls or subjects receiving either oral contraceptives or Norplant, compared to control patients. The mean platelet counts (X 10/9/L) were 223 for OC users, 231 for Norplant users, and 232 for controls. The respective platelet aggregation (ADP, ohms) values were 12.5, 18.0, and 19.2 as well as (COLL, ohms) 35.6, 40.7, and 39.0. These results demonstrated that there is no evidence for altered platelet function, with the testing methods employed, in women using either Norplant or combination low dose oral contraceptives. To date, several studies have examined this issue, with contradictory reports about the effects of hormonal contraceptives in platelet function. After controlling for differences between various steroid preparations and other such confounding variables, some of these conflicting conclusions could be the result of a lack of uniformity among the methods used to evaluate platelet aggregation. The ability to draw conclusions regarding altered in vivo thrombotic potential from these studies is thus questionable.^ieng

The effects of in vitro cocaine exposure on human sperm motility, intracellular calcium, and oocyte penetration.

OBJECTIVE: To determine if cocaine exposure affects human sperm motility, intracellular calcium level, and fertilizing capability. DESIGN AND METHODS: Human semen samples were treated with 1 to 1,000 microM cocaine hydrochloride for up to 2 hours in vitro. Sperm motion kinematics were measured by computer-assisted semen analysis (CASA). Spermatozoan intracellular calcium was determined by laser cytometry. The sperm fertilizing capability was assessed using the zona-free hamster oocyte penetration test. RESULTS: After a short exposure (15 minutes) to cocaine, the sperm motion kinematic parameters, straight line velocity and linearity, were decreased in the high concentration groups. However, after a longer exposure (2 hours) to cocaine, the differences were no longer significant. Cocaine treatment did not alter spermatozoa intracellular calcium levels. Most importantly, human sperm treated with cocaine at a high concentration were fully capable of penetrating zona-free hamster oocytes. CONCLUSION: Human spermatozoa acutely exposed to high concentrations of cocaine initially demonstrate a decrease in two motion kinematics, straight line velocity and linearity. However, overall, cocaine exposure had no significant effects on sperm motility and fertilizing capability.

Stimulation of cryopreserved epididymal spermatozoa of the domestic cat using the motility stimulants caffeine, pentoxifylline, and 2'-deoxyadenosine.

We have investigated the effects of caffeine, pentoxifylline, and 2'-deoxyadenosine on the motion characteristics and longevity of domestic cat spermatozoa. Freshly collected or cryopreserved domestic cat epididymal sperm were incubated with 0.01-20 mM caffeine, pentoxifylline, or 2'-deoxyadenosine for 15 minutes at 23 degrees C. The percent motility (MOT), curvilinear velocity (VCL), linearity (LIN), straight line velocity (VSL), and amplitude of lateral head displacement (ALH) were determined for each group using computer-assisted semen analysis. Freshly collected domestic cat sperm exhibited a strong forward progressive movement, and treatment with caffeine, pentoxifylline, or 2'-deoxyadenosine did not consistently alter sperm motion. Following cryopreservation, spermatozoa exhibited decreased (P < 0.05) MOT, VCL, VSL, and ALH. Caffeine and pentoxifylline increased (P < 0.05) the MOT, VSL, VCL, and ALH of cryopreserved sperm at 0.01-20 mM, in a dose-dependent manner. 2'-Deoxyadenosine also increased (P < 0.05) both VSL and VCL at 1.0 mM, and MOT, VSL, VCL, and ALH at 10 mM. All treatments shifted the percentage of nonhyperactive sperm to either a transitional or hyperactivated state. The motility indices of cryopreserved samples were examined during a 6-hour incubation to assess the effects of caffeine, pentoxifylline, and 2'-deoxyadenosine on sperm longevity. Compared to untreated control samples, the longevity of stimulated cryopreserved sperm was not reduced. These results indicate that motility stimulants may prove useful for enhancing the fertility of cryopreserved cat sperm by increasing their motility and producing hyperactivated motion.

Fibrinolytic parameters in women undergoing ovulation induction.

OBJECTIVE: The purpose of this study was to evaluate the effect of elevated levels of circulating estradiol on the clotting and fibrinolytic system in patients undergoing controlled ovarian hyperstimulation. STUDY DESIGN: Fifty-two patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins or urofollotropin were asked to participate. Blood for hemostasis parameters was obtained on the days that patients returned for estradiol sampling. Sample days were identified as cycle days 1 to 5 (baseline), 6 to 9, and 10 to 14. Each factor was analyzed by repeated-measures analysis of variance and correlation analysis. RESULTS: A significant decline was observed for tissue plasminogen activator antigen and plasminogen activator inhibitor type 1 activity from baseline to cycle days 10 to 14. As serum estradiol levels increased throughout each phase (maximum mean estradiol 739.8 pg/ml), a significant linear decrease was observed for both tissue plasminogen activator antigen and plasminogen activator inhibitor type 1 activity, whereas thrombin-antithrombin III complexes did not change significantly. A significant positive correlation was also observed for plasminogen activator inhibitor activity and tissue plasminogen activator antigen level over all cycle days examined. CONCLUSION: Down-regulation of the fibrinolytic system was observed as estradiol levels increased. However, thrombin formation did not change, thus suggesting that elevated circulating estradiol alone does not predispose to a thromboembolic event.

Thrombosis and hormone replacement therapy in postmenopausal women.

OBJECTIVE: The effects of postmenopausal hormone replacement therapy on thrombosis remain controversial. We tested the hypothesis that estrogen or progesterone has no significant effect on thrombosis by means of newly developed markers of blood clotting, specifically prothrombin fragment 1 + 2, a marker of factor Xa generation, and thrombin-antithrombin III complex, a marker of thrombin generation. STUDY DESIGN: A prospective study that included 106 women, 68 postmenopausal women on hormone replacement therapy and 38 postmenopausal controls, was performed. Plasma levels of prothrombin fragment 1 + 2 and thrombin-antithrombin III complex were measured by enzyme-linked immunosorbent assay. Multivariate analysis of the covariance was used for statistical analysis, controlling for patient's age because the hormone replacement therapy group was older. RESULTS: There were no statistically significant differences between the hormone replacement therapy and control groups in either of the clotting parameters measured. A comparison of the levels of prothrombin fragment 1 + 2 and thrombin-antithrombin III complex in patients receiving estrogen alone or estrogen plus progestin also revealed no differences. CONCLUSIONS: Current doses of postmenopausal hormone replacement therapy do not appear to enhance in vivo clotting. Thromboembolic complications among postmenopausal women receiving hormone replacement therapy may therefore be secondary to congenital or other acquired coagulation defects.

Pregnancy after medical therapy of adenomyosis with a gonadotropin-releasing hormone agonist.

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.

Computer-assisted semen analysis (CASA) of epididymal sperm from the domestic cat.

Motion characteristics of epididymal sperm from domestic cats exhibiting a high (> 60%; normozoospermic; n = 21) or low (< 40%; teratozoospermic; n = 6) occurrence of structurally normal spermatozoa were correlated with morphology (MOR) using computer-assisted semen analysis (CASA). Mean values and standard errors for percent motility (MOT), curvilinear velocity (VCL), linearity (LIN), straight line velocity (VSL), and amplitude of lateral head displacement (ALH) were recorded for 3 hours. Average values for percent normal spermatozoa, MOT, VCL, VSL, and ALH were higher (P < 0.01) in samples from normozoospermic cats than from teratozoospermic cats at 0 hours, and there was no difference in motion parameters over the 3-hour incubation period in either group. Strong correlations (P < 0.01) existed between MOR and VCL, VSL, ALH, or MOT, but not LIN, upon regression analysis. We conclude that (1) motion parameters of domestic cat sperm are significantly correlated with morphology and (2) abnormal motion parameters associated with low fertility potential in other species are prevalent in samples from teratozoospermic cats. The correlation between morphology and altered sperm movement found in this study suggests that motion analysis of spermatozoa by CASA may be useful in evaluating fertilization potential in felids.

Luteal phase defect. Etiology, diagnosis, and management.

Luteal phase defect is an ovulatory disorder of considerable clinical importance that is implicated in infertility and recurrent spontaneous abortion. As a subtle disruption of ovulatory or luteal function, it may be the most common ovulatory disorder in women. Pathophysiologic alterations of the complex reproductive process that lead to delayed endometrial maturation characteristic of LPD include disordered folliculogenesis, defective corpus luteum function, and abnormal luteal rescue by the early pregnancy. A variety of clinical conditions, such as hyperprolactinemia, hyperandrogenic states, weight loss, stress, and athletic training may result not in overt oligo- or anovulation, but rather may be manifest as LPD. Reasonable consensus exists regarding the use of endometrial biopsy for diagnosis of LPD, although issues regarding timing, number of samples needed, method of interpretation, and the adjunctive use of hormone assay and ultrasonography are still not settled. Other tests, including assay of progesterone-associated endometrial protein, analysis of decidual steroid receptors, or determination of decidual prolactin production, may in the future contribute to the accurate diagnosis of this condition. In the absence of an identifiable correctable underlying cause of LPD, progesterone replacement and clomiphene citrate are the usual treatment options for consideration. Combination therapy, gonadotropins, and other treatments are reserved for refractory cases. No data at present suggest a difference in efficacy between progesterone and clomiphene. When abnormal luteal endometrial biopsy is corrected, conception and live birth rates are high.

Cervical dysplasia in the postmenopausal female: diagnosis and treatment.

Thirty-two postmenopausal women, age 50 years or older, were colposcoped for abnormal Papanicolaou (PAP) smears. Sixteen had mild to moderate dysplasia, six severe dysplasia and the remainder had no dysplasia. Treatment included observation, topical estrogen, cryotherapy, conization or hysterectomy. Based upon our observations, satisfactory colposcopy can be performed in the majority of postmenopausal women. Oral or topical estrogen is a valuable adjunct in the initial evaluation and treatment of abnormal PAP smears in postmenopausal women. Criteria for adequate colposcopy in postmenopausal women are discussed and a management scheme is proposed.