Sex differences in quadriceps strength in OA.

The purposes of this study were to determine 1) whether sex differences in quadriceps torque and isotonic power persist when controlling for muscle volume (i. e., torque/muscle volume and power/muscle volume) in participants with knee osteoarthritis (OA) and 2) the factors responsible for potential sex differences. Isometric torque, isotonic power (the product of torque and velocity, measured at 10, 20, 30, 40 and 50% maximal voluntary contraction; MVC) and maximal unloaded velocity were assessed in men (n=16, mean age=62.1 ± 7.2) and women (n=17, mean age=60.4 ± 4.3) with knee OA. Torque and power were normalized to muscle volume. The interpolated twitch technique was used to measure voluntary activation (VA) and evoked twitch and torque-frequency characteristics were measured to obtain information about muscle fibre distribution. Torque and power at all loads were significantly lower in women (p<0.05). Sex differences in power were reduced by 50% when controlling for muscle volume but were still significant at 10-40% MVC (p<0.05). No differences in VA, torque-frequency properties or time-to-peak tension of the evoked twitch were observed (p>0.05). These results suggest that only minor sex differences in torque and power persist when controlling for muscle volume. As VA and contractile property differences were not observed, other factors seem to be responsible.

Effect of sequential and daily continuous hormone replacement therapy on indexes of mineral metabolism.

BACKGROUND: Continuous regimens of estrogen-progesterone have recently been favored over sequential regimens because of a lower incidence of withdrawal bleeding. To determine whether the beneficial effects of sequential hormonal therapy on bone metabolism are preserved with the newer continuous regimens, we studied indexes of skeletal metabolism and changes in bone mineral density during a 1-year prospective trial. METHODS: Our subjects were randomized to one of three treatment groups: those in group C-2.5 were treated with 0.625 mg of conjugated estrogen with 2.5 mg of micronized medroxyprogesterone acetate daily continuously; group C-5 received 0.625 mg of conjugated estrogen and 5.0 mg of micronized medroxyprogesterone acetate daily continuously; and group S-5 received 0.625 mg of conjugated estrogen on days 1 through 25 and 5 mg of micronized medroxyprogesterone acetate on days 14 through 25. RESULTS: At 1 year, all groups demonstrated a significant decrease in indexes of bone formation turnover, including decrements in alkaline phosphatase levels of 11% to 30% and in osteocalcin levels of 45% to 60%. Intact parathyroid hormone levels rose 10% to 20%, with a concomitant near-significant decrement in ionized calcium levels at 12 months. In addition, there were significant decrements in the 24-hour urinary calcium-creatinine ratios and hydroxyproline-creatinine ratios of 13% to 28%, measures of bone resorption. Linear regression analyses showed that the subjects with the high bone resorption achieved the greatest increment in bone mineral density in response to hormone therapy. CONCLUSION: The daily continuous estrogen-progesterone regimens are as efficacious as sequential hormonal therapy in decreasing indexes of bone turnover and stabilizing bone mineral density of the spine and proximal femur.

Lymphocyte dysfunction in autoimmune oophoritis. Resumption of menses with corticosteroids.

In a 32-year-old woman with secondary amenorrhea and biopsy-proven oophoritis, the circulating T lymphocytes were examined utilizing monoclonal antibody L243 to the nonpolymorphic region of the Ia antigen. The percentage of peripheral T cells expressing the Ia "immune-associated' antigen was 5.6 percent (normal 3 percent or less). With corticosteroid therapy, the percentage decreased to 2 percent and menses resumed after secondary amenorrhea of two years' duration. Following cessation of steroid administration, the percentage of Ia-positive T cells rose to 7.0 percent and secondary amenorrhea redeveloped in the patient. After corticosteroid therapy was reinstituted, menses resumed and the percentage of Ia-positive T cells fell to normal. This report represents additional new evidence of immune dysfunction in patients with "autoimmune" oophoritis.

Impaired reproductive performance in DES-exposed women.

The reproductive history of 69 women with demonstrated diethylstilbestrol (DES)-related cervical-vaginal abnormalities is reviewed. All of the patients were sexually active non-contraceptive users who were studied over an 8-year period. Forty-six patients conceived, for an uncorrected fertility rate of 66.7%. Fourteen patients elected therapeutic abortion. The 32 remaining patients had 62 pregnancies which resulted in 26 living children, for a success rate of 41.9%. However, cervical cerclage was required for continuation of 8 of these successful pregnancies. The 36 pregnancy failures consisted of 19 first- and 11 second-trimester spontaneous abortions, 3 third-trimester losses due to permaturity, and 3 tubal pregnancies. Uterine abnormalities were found in all of the 25 patients who underwent hysterosalpingograms. Although other reproductive diseases unrelated to DES exposure in utero were also present in this select group of patients, it is probable that the high rate of infertility and pregnancy wastage is related to the uterine structural abnormalities encountered.

Successful use of gamete intrafallopian transfer does not reverse the decline in fertility in women over 40 years of age.

To assess the impact of assisted reproductive technologies on the potential fertility of older women, we report our experience with gamete intrafallopian transfer (GIFT) in a large number of women 40 years of age and older. One hundred twenty-two GIFT cycles were initiated in 59 women over 18 months. Seventy-three tubal transfers were performed, resulting in seven clinical pregnancies, a rate of 9.6% per transfer. This contrasts with a 27.3% clinical pregnancy rate per transfer in women under 40. Thus, older patients require thorough counseling regarding the decreased likelihood of success despite the use of assisted reproductive technologies.

Diagnostic value of androgen measurements in polycystic ovary syndrome.

A group of 51 women with a diagnosis of polycystic ovary syndrome (PCO) were investigated. They were further classified into PCO Type I and PCO Type II based on clinical and laboratory investigations. Serum levels of unbound (free) and total testosterone, testosterone binding globulin (TBG), and androstenedione were measured in these women and compared with values in normal women. Mean levels of all these steroids were elevated in women with PCO. No difference in adrogen levels was found between women with PCO Type I and PCO Type II. Serum unbound testosterone concentrations correlated better with the presence and severity of hirsutism than did the total testosterone.

Clinical aspects of the polycystic ovary syndrome.

One hundred and one patients with polycystic ovary syndrome (PCO) were treated during an 11-year interval. Sixty-seven cases were classified as typical PCO with enlarged ovaries of probable ovarian origin (Type I) and 34 as atypical PCO of probable adrenal origin (Type II). Fifty-five patients were treated for anovulatory infertility with clomiphene citrate or other endocrine therapy as indicated. There was a 91% ovulatory response and 51% conception rate from therapy in cases of Type I PCO. In Type II PCO, adrenal suppressive therapy resulted in a 55% ovulatory response. Our data support the concept that anovulation of ovarian origin as seen in PCO Type I responds to clomiphene therapy, while anovulation secondary to adrenal hyperandrogenization should be treated by adrenal suppressive therapy.

Disappearance of human chorionic gonadotropin following removal of ectopic pregnancy.

A study was undertaken to determine the length of time serum beta-subunit of human chorionic gonadotropin (beta-hCG) could be detected following removal of ectopic pregnancy. Seven patients underwent complete removal of trophoblastic tissue by either salpingectomy or partial resection of the involved fallopian tube. Nine other patients had conservative surgical treatment by either linear salpingostomy or fimbrial expression of the fallopian tube. Serum beta-hCG levels were determined serially in all these patients. The results demonstrate that the initial titer of hCG is a significant factor in determining the length of time that it can be detected in the serum postoperatively. In addition, decreasing titers, conforming to the disappearance curve of hCG, as constructed in this study, are a helpful aid in avoiding further surgery in the group of patients who had a conservative removal of the trophoblastic tissue. Finally, the serum clearance of hCG by radioimmunoassay may take at least up to 24 days after surgery.

Gonadotropin levels and secretory patterns in patients with typical and atypical polycystic ovarian disease.

Gonadotropin levels and secretory patterns were studied in 28 oligomenorrheic patients with various types of polycystic ovary disease (PCO). On the basis of ovarian morphology and histology, the patients PCOuld be separated into two distinct categories arbitarily designated "typical" (type I) and "atypical" (type II) PCO. Although no differences were noted in symptomatology or 17-ketosteroid, testosterone, or follicle-stimulating hormone levels, the 12 type I patients demonstrated widely fluctuating, but markedly elevated, luteinizing hormone (LH) levels, while the 16 type II patients demonstrated lower and less fluctuating LH levels which were comparable to those found during the normal follicular phase. It is likely that type I PCO is a distinct entity similar to that described by Stein and Leventhal, while type II co represents a heterogenous spectrum of disorders, many of which remain obscure.

Cytologic features of oocytes in the adult human ovary.

A broad survey of the cytologic features of follicular oocytes from sections of adult ovaries from donors with normal menstrual cycles, from patients with polycystic ovarian disease, and from patients treated with estrogen and progesterone for gynecologic disorders with no apparent ovarian pathology has been made in this study. On the basis of light microscopic observations, four basic types of oocytes could be recognized: (1) oocytes with nuclei containing diffused or filamentous chromatin, (2) oocytes with metaphase I chromosomes or an extruded polar body, (3) oocytes with nuclei possessing massive clumps of chromatin frequently associated with the nucleolus, and (4) degenerating oocytes with no distinguishing cytologic features. The numbers of oocytes in these different groups varied with the reproductive state of the donors: 34 to 35% were type 1 during proliferative and secretory phases; mature oocytes type 2 were 3.3%, and were found only during the late proliferative phase; and 41 to 46% were type 3 during both phases of the menstrucal cycle. Large numbers of oocytes from polycystic ovaries (77%) and from ovaries of patients treated with steroids (86%) were degenerating and frequently contained massive clumps of chromatin material associated with the nucleolus.

Safety of a freestanding surgical unit for the assisted reproductive technologies.

OBJECTIVE: To determine the safety of a freestanding surgical unit for assisted reproductive technology (ART), using the rate of unplanned admissions to a hospital within 24 hours of surgery. DESIGN: Prospective. SETTING: A freestanding surgical unit within a medical office building. PATIENTS: A mixture of private and university-referred patients undergoing 6,776 ART surgical procedures. MAIN OUTCOME MEASURES: Patients admitted during the first 24 hours of surgery were recorded and hospital progress was monitored for invasive procedures, treatments, time of discharge, and residual complications. Variables tabulated included age, fertility diagnosis, ART procedure, E2 level, number of follicles by ultrasound, previous surgery, and type of anesthesia. RESULTS: There were 11 hospital admissions (0.16%). Four patients required surgery: one laparoscopy and three laparotomies. Admissions after vaginal oocyte retrieval were no different from those after GIFT via laparoscopy, 0.16% versus 0.18%, respectively. The number of admissions after monitored anesthesia care was higher than expected compared with general anesthesia. Profiles of hospitalized patients showed no apparent differences from the nonhospitalized patients. CONCLUSIONS: Surgical procedures for ART performed in a freestanding surgical unit can be performed safely with a low hospitalization rate and minimal morbidity.

Gamete intrafallopian transfer: assessment of the optimal number of oocytes to transfer.

The optimum number of oocytes that should be transferred at the time of gamete intrafallopian transfer (GIFT) is important information. Nonessential oocytes can be inseminated and frozen for later use or the extra oocytes can be donated to another women. In this preliminary study, the results of 399 consecutive GIFT procedures were evaluated retrospectively as a function of the number of oocytes transferred. Women who received four or more oocytes were three times more likely to achieve a clinical pregnancy than those who received three or less. There was no statistically significant difference in pregnancy rates between patients who received five, six, seven, or eight oocytes. Oocytes in excess of five may be more effectively used if they are fertilized and frozen as embryos for later transfer rather than replacing them all at the time of GIFT.

Comparison of intermediate-dose purified urinary follicle-stimulating hormone with and without human chorionic gonadotropin for ovulation induction in polycystic ovarian disease.

Urinary FSH is capable of inducing ovulation in PCOD. The duration of treatment can be reduced by administering an intermediate dose. However, it appears that prospective monitoring with E2 assays and ultrasound, combined with hCG, is required to optimize outcome and minimize complications. Studies comparing urinary FSH with similar doses of hMG with and without hCG are needed to determine the most effective form of gonadotropin therapy in PCOD.

Laparoscopic recovery of mature human oocytes.

This report provides a detailed description of a method by which mature or maturing human oocytes can safely be recovered by follicular aspiration during laparoscopy. By combining gonadotropin administration with laparoscopic recovery, oocytes which have resumed or completed meiotic division can be obtained for study without subjecting the patient to more hazardous surgical procedures. Fifteen oocytes were obtained from sixteen patients. On electron microscopic examination, four were found to have extruded polar bodies and were therefore classified as mature. Daily rather than intermittent administration of HMG, larger HMG dose, longer HCG aspiration intervals, and controlled aspiration pressures appeared to be the factors which produced the best yield of mature oocytes.

The effectivenss of danazol on subsequent fertility in minimal endometriosis.

Sixty-five patients with minimal endometriosis were studied for the purpose of prospectively comparing conservative medical management in the form of danazol with no therapy in the treatment of this disease. After completion of the basic infertility evaluation and correction of additional factors affecting fertility, a diagnostic laparoscopy, dilatation and curettage (D and C), and tubal lavage were performed. A randomly selected cord determined whether the patient received no treatment for 6 months or danazol for 6 months followed by no treatment for 6 months. The dosage of danazol was 800 mg daily for the first 2 months, 600 mg daily for the next 2 months, and 400 mg daily for the final 2 months. The mean age of both the danazol-treated group and the group that received no danazol was 31 years. Conception occurred in 30% of the danazol-treated patients and 50% of the untreated patients. These results suggest that infertile patients with minimal endometriosis should be given an opportunity to conceive after laparoscopy, D and C, and tubal lavage. This would seem particularly true in older patients where a 6-month delay in permitting attempts at conception represents a significant interval of time.

PIP: 65 patients with minimal endometriosis were studied for the purpose of prospectively comparing conservative medical management in the form of danazol with no therapy in the treatment of this disease. After completion of the basic infertility evaluation and correction of additional factors affecting fertility, a diagnostic laparoscopy, dilatation and curettage (D and C), and tubal lavage were performed. A randomly selected card determined whether the patient received no treatment for 6 months or danazol for 6 months followed by no treatment for 6 months. The dosage of danazol was 800 mg daily for the 1st 2 months, 600 mg daily for the next 2, and 400 mg daily for the final 2 months. The mean of both the danazol-treated group and the group receiving no danazol was 31 years. Conception occurred in 30% of the danazol-treated patients and 50% of the untreated patients. These results suggest that infertile patients with minimal endometriosis should be given an opportunity to conceive after laparoscopy, D and C, and tubal lavage. This would seem particularly true in older patients, where a 6-month delay in permitting attempts at conception represents a significant interval time.

Reversal of persistent anovulation in polycystic ovarian disease by administration of chronic low-dose follicle-stimulating hormone.

Low doses of follicle-stimulating hormone (FSH) were administered once daily to two consecutive patients with polycystic ovarian disease (PCOD) for therapy of infertility. Serial blood samples were obtained for gonadotropins and ovarian steroid determinations during the period of FSH administration. Exogenous FSH resulted in an initial and concomitant decrease in serum androstenedione (A), estrone (E1), and luteinizing hormone (LH), with an increase in estradiol (E2) and FSH. Subsequent changes in the above-mentioned hormonal levels were typical of a normal ovulatory cycle, with the exception of FSH, which continued to rise in the second half of the follicular phase. This was attributed to the exogenous administration of FSH. Both patients became pregnant in their first induced ovulatory cycle by administration of chronic low-dose FSH. These preliminary data demonstrate (1) a correction of the biochemical imbalance characteristic of PCOD, (2) successful ovulation induction, and (3) restoration of fertility in PCOD treated with chronic low-dose FSH.

The role of ultrasound in ovulation induction: a critical appraisal.

Twenty-five cycles induced by human menopausal gonadotropin (hMG) were serially studied by ultrasound. The developing follicles were observed up to and beyond human chorionic gonadotropin (hCG) administration. Ovulation as determined by subsequent pregnancy or a sustained elevation of basal temperature was seen in 18 of these cycles. Among these patients the follicular size ranged between 24 and 13 millimeters. No pregnancies occurred where the follicular size was below 15 mm. A shortened luteal phase was noted in three cycles where the follicular size was either 13 or 14 mm. Multiple follicles greater than 10 mm were observed in 14 of the ovulating cycles, but in no case did a multiple pregnancy occur. Fifteen millimeters is therefore suggested as a minimum size for satisfactory ovulation, but it does not appear that an optimum size exists. We conclude that ultrasound can play an important role in the monitoring of ovulation induction but does not replace the present methods.

The use of gonadotropins for the induction of ovulation in women with polycystic ovarian disease.

Ten infertile patients with polycystic ovarian disease were treated with 18 cycles of "pure" human pituitary follicle-stimulating hormone (HP-FSH) and 10 cycles of human menopausal gonadotropin (HMG) consisting of FSH and luteinizing hormone (LH) in a 1:1 ratio. Human chorionic gonadotropin was used to trigger ovulation when optimal follicular development was achieved as judged by urinary estrogen determinations. Of the 18 cycles utilizing HP-FSH, 14 were presumptively ovulatory, 2 were conceptual, and in 5 cycles ovarian enlargement was noted. Of the 10 HMG cycles, none was ovulatory, no conceptions resulted, and 6 instances of hyperstimulation were noted. Pretreatment serum LH levels were significantly higher than normal follicular phase values. These observations suggest that endogenous LH levels in patients with polycystic ovaries are quite adequate for follicular development so that the administration of exogenous LH is unwarranted. Furthermore, the data suggest that HP-FSH or low-LH-containing HMG may prove to be an additional safe and effective nonsurgical treatment modality for patients who are anovulatory because of polycystic ovaries.

The association between smoking and female infertility as influenced by cause of the infertility.

Smoking histories were compared in 901 women with infertility of different types and 1264 women admitted for delivery at seven collaborating hospitals. The relative risk for infertility associated with cigarette smoking prior to the infertility diagnosis for nulliparous cases or first live birth for controls was calculated using a multivariate logistic-regression model to control for potential confounding factors, including center, age, religion, education, number of sexual partners, and contraceptive use. The adjusted risk for infertility attributed primarily to cervical factor (n = 96) was 1.7 (P = 0.04), to tubal disease unrelated to endometriosis (n = 225) was 1.6 (P = 0.009), to ovulatory factor (n = 389) was 1.0 (not significant [NS]), and to endometriosis (n = 191) was 0.9 (NS). The authors conclude that cigarette smoking is significantly associated only with certain types of primary female infertility.

Intractable primary infertility in women exposed to diethylstilbestrol in utero.

Fertility factors were examined in 50 women with primary infertility and presumed in utero diethylstilbestrol (DES) exposure and in 50 age-matched controls. Uterine deformities and endometriosis were more frequent in the DES-exposed women than the controls. When managed from one to four years, only 4% of DES-exposed women with primary infertility conceived (with no conceptions resulting in a viable fetus) as compared to 44% of controls. Primary infertility of one to two years' duration with uterine deformities characteristic of DES exposure seems to signal a poor prognosis for pregnancy despite treatment of identifiable fertility factors.